Advanced Heart Failureto Contraindications

This articleisprotected bycopyright.Allrightsreserved. Accepted Article evidence-based treatment algorithms to algorithms to prolong lif treatment evidence-based studies is lacking for mosttherapies for advanced he prospective from evidence Robust be should emphasized. life of quality and improve symptoms reduce patients,who are often elderlywith multiple co-morbidities,management of advanced heart failureto contraindications. Some will patients notbe candidates for advanced heart failure therapies. For these as destination therapy.Heart tran or transplantation to a bridge either for support circulatory mechanical long-term and shock cardiogenic of management immediate for devices support circulatory mechanical short-term with occurred onits used palliativeown, when measure becaus patients. Inot inthese insufficient preserved ejection fraction are included in this upda in areincluded this fraction ejection preserved 2016 ESC the guidelines co-morbidities,and arrhythmias, failurecentres. heart advanced patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to these for options treatment and diagnostic new describes and failure heart advanced of classification This article updates the Heart Failure Association of the European Societyof Cardiology (ESC) 2007 CIBERCV, UDC, La Coruña, Spain; Spain; Coruña, La UDC, CIBERCV, Cardiology, Karolinska Institute, Stockholm, Sweden; [email protected] Email: A Coruña(CHUAC), CIBERCV, Coruña, 981 LaSpain. 15006 +34 178304, 178299, +34 981 Tel: Fax Universitario Hospitalario Complexo Program, Transplant Heart and Failure Heart author. *Corresponding failure:HFA heart positionstatementAdvanced M.G. Crespo-Leiro Running head 11 8 1 Hannover, Germany; Germany; Hannover, Bologna University Hospital, Bologna, Italy; Zedek Medical Center, Jerusalem, Israel; Israel; Jerusalem, Center, Medical Zedek Center Zagreb, UniversityZagreb,Zagreb, of Croatia; Received4 May2018; revised 17May 2018; accepted21May 2018 Austria; Utrecht, Utrecht, The Netherlands; Netherlands; The Utrecht, Utrecht, Belgrade, Serbia; and Serbia; Belgrade, Center, Medical University Belgrade Center, Failure Heart and Medicine of School University Belgrade Medicine, University Hospital Attikon, Athens, Greece; Greece; Athens, Attikon, Hospital University Transplant Unit, Royal Papworth Hospital, Cambridge, UK; UK; Cambridge, Hospital, Papworth Royal Unit, Transplant (INIBIC), ACoruña de Biomédica de Investigación Instituto (CHUAC), ACoruña Universitario Hospitalario Complexo Advanced heart failure: aposition failure: Advanced heart Gerasimos Filippatos Nalbantgil Department of Cardiology, Beirut Cardiac Institute, Beirut, Lebanon; Lebanon; Beirut, Institute, Cardiac Beirut of Cardiology, Department Maria G.Crespo-Leiro

Jonge 14 article as d differencesbetween version lead to this may been through the copyediting, typesetting, pagination andproofreading process, which This article hasbeen accepted for publication andundergone full peer review but has not Department of Cardiology, Ege University Hospital, Izmir, Turkey; Turkey; Izmir, Hospital, University Ege Cardiology, of Department 14 Association oftheEuropean 9 , Luciano Potena , Luciano , Maria Frigerio , Maria et al et 17 oi: 10.1111/e 19 Department of Cardiology, King’s College Hospital, London, UK; UK; London, Hospital, College King’s Cardiology, of Department University Heart Center, University Hospital Zurich, Zurich, Switzerland Switzerland Zurich, Zurich, Hospital University Center, Heart University . 6 , Finn Gustafsson 1 *, MarcoMetra 2 10 10 Cardiology, University of Brescia,Brescia, Italy; Transplant Center and De Gasperis Cardio Center, Niguarda Hospital, Milan, Italy; Italy; Milan, Niguarda Hospital, Center, Cardio De and Gasperis Center Transplant 15 , Righab Hamdan , Righab jhf.1236 Unplanned visits for heart failure decompensation, malignant malignant decompensation, failure heart for visits Unplanned , Johann Bauersachs Johann , ropic therapy may be used as a bridge strategy, but it is only a isonlya it but strategy, as abridge maybe used ropic therapy splantation remains thetreatment of choicepatients for without 13 Department ofInternal Medicine II, MedicalUniversity of Vienna,Vienna, 16 7 and Frank Ruschitzka Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; Denmark; Copenhagen, Rigshospitalet, ofCardiology, Department Department ofCardiology andAngiology, MedicalSchool Hannover, 2 7 , Lars H. Lund Lars , , Steven Tsui 4 5 Department forCardiovascular Diseases, University Hospital Advocate Heart Institute, Naperville, IL, USA; USA; IL, Naperville, Institute, Heart Advocate e of the lack of outcomes data. Major progress has has progress Major data. outcomes of lack the e of 11

9 ted definition. tr Standard e whenpossible andin accordance with patient Department of Cardiology, University Medical Center Center Medical University Cardiology, of Department , TalHasin statementof the HeartFailure

art failure. There is an urgent need to develop need an urgent is There failure. art and the Versionof Record. Please cite this 16 Society ofCardiology criteria for the diagnosis of heart failure with with failure heart of diagnosis the for criteria , Theresa McDonagh 8 3 , EduardoBarge-Caballero , , Davor Milicic , Davor 12 19 19 Jesselson Integrated Heart Center, Shaare Shaare Center, Heart Integrated Jesselson 12 , MartinHülsmann 15 Heart and Lung Transplant Program, Program, Transplant Lung and Heart 3 Department of Medicine, Unit of 4 , Maria Rosa Costanzo 18 Department of Internal ofInternal Department eatment is,eatment by definition, 17 , Petar Seferovic Petar , 13 1 , Sanem , Sanem 6 , Nicolaas De , Nicolaas Athens Athens 5 18 , , This articleisprotected bycopyright.Allrightsreserved. Accepted Article advanced heart failure comprise an estimated 1% anestimated failurecomprise heart advanced based therapies, ultimately, they still progress toan advanced stage ofthe disease. Patients with im heartfailurehave chronic with patients Although Introduction heart failure failure heart chronic advanced for statement position Association Failure Heart the2007 of Limitations (HFpEF).fraction of advanced heartfailure canapplied be also pa to heart failure with reducedejection fraction (HFrEF), co haemodynamic and symptoms on based implantation the INTERMACS profiles were developed to classify pa Prior definitions for patients with failure heart advanced of Definition in care. transitions through nurses and physicians, care primary internists, as such patients these of care the in involved professionals other and cardiologists failure heart cardiologists, general guide to intended is article practice standards, and expert opinions on the manage evidence, available best the summarizes statement position This teams. care end-of-life including care symptom-focused or palliative failure, heart advanced between collaboration (v)ensure and centres, physicians to recognize the optimal time and processe these patientsin order to improve their candidacy for heart transplantation or MCS,(iv) enable an advancedstageofdisease,physiciaeducate (iii) patientswith advanced heart failure,(ii) informphysicians about markers ofpoor prognosis thatindicate context, theHFA has prepared this positiondocument to (i) describe the clinical characteristics of Inthis (ESC). Cardiology of Society European the (HFA)of Association Failure Heart the of mission burdenofsymptomatic advanced heart the lessen to strategies management optimize ofand care, goals changing about discussions noteligible patients whoareclearly needsof the time optimal the for recognize referral. Ofequal impo th patients toidentify equipped beappropriately to need clinicians Thus, care. in steps next navigate patients helping and resources (MCS)devices. support appropriate application of treatment such as heart transplantation or long-term mechanicalcirculatory treatment and survival. A thorough definition of advanced heart failure is mandatory to facilitate with failure and due ofheart better their prevalenceto thenumber patients the growing is increasing Circulatory (INTERMACS)Support prof Assisted Mechanically for Registry The Interagency therapies. failure heart advanced for evaluated fa heart ‘end-stage’ and ‘refractory’, the pu for patients; these describe to used be can end-of-l or volume, control to dialysis peritoneal or therapies (e.g. cardiac transplantation, MCS) or palliative therapies (e.g.inotropic infusions, ultrafiltration advanced and symptoms, patient’s the control to insufficient are surgery) conventional devices, drugs, wh astage identified statement position HFA 2007 the Heart failure Heart Keywords population. increase andreduce preferences, thequality, life bu characteristics consistent with a need for advanced therapies ( therapies advanced aneedfor with consistent characteristics The management of patients with ofpatientsfailure management heart to The often is aIt general cardiologistwho is responsible fordirecting patients to advancedfailureheart

●

Heart transplantation transplantation Heart advanced heartfailure are shown in at might be candidates for advanc for candidates be might at ● ilure interchangeable terms, all reflecting patients who should be Heart-assist devices devices Heart-assist failure and improve quality of life. iles are also useful to further

ife comfort care) are needed. Overlapping terminology terminology Overlapping are needed. care) ife comfort to 10% of the overall heart failurepopulation, ns onoptimal short-term managementstrategies for whereas our classification and, in general, the term term the general, in and, classification our whereas proved outcomeswith impl tients to being considered for long-term MCS device MCS device long-term for considered to being tients ere conventional treatments (i.e. guideline-directed (i.e.guideline-directed treatments conventional ere rposeofthis document, we consider ‘advanced’, for advanced heartfailureengage therapies, in tients withheart failure preserved with ejection rden of hospitalizationvulnerablein this patient rtance, physicians shouldbe prepared to address ment of patients with advanced heart failure. This failure. This heart advanced with ofpatients ment s for referring patients to advanced heart failure improve their quality of life and longevity is a mpromise and, moreimportant, is specific for ● Extracorporeal membrane oxygenation Table 2 Table ). Table 1 ed heart failuretherapiesto and ed heart 7–9 describe clinicalparameters describe and However, it mustbe noted that . 3–6 The criteria suggested in in suggested criteria The ementation of evidence- 1–3 and This articleisprotected bycopyright.Allrightsreserved. Accepted Article can be consequences of advanced heart failure. terminal pro-BNP (NT-proBNP) levels independently of LVEFvalues. of independently levels (NT-proBNP) pro-BNP terminal provision todiagnose advanced heart failure on the basis ofhigh B-type natriureticpeptide (BNP) N- or (unless contraindicated) before advanced therapies considered. are therapies advanced before contraindicated) (unless heart failure,and patientsmust be treatedaccording to the best availablemedical and device therapies ther such optimize needto failure. The heart advanced ivabradine andsacubitril/valsartan, although date,to no trial has specifically addressed patients with as such drugs, new of availability the (CRT) and therapy resynchronization cardiac for indications for therapy. fraction, but on the patient’s symptoms, prognostic markers, presenceof end-organ damage,and goals ad that is raiseawareness needs. It important to practice clinical current meet to sufficiently emphasized not were HFpEF of setting in the symptoms criteria for the identification of patients patients of identification the for criteria the definition to update an areas, these address To failure heart ofadvanced Updated definition be difficult to distinguish primary and secondary dysfunction or to predict reversibility. pulmonary hypertension,may be aconsequence ofacute congestionand/or low-outputstate, itbut may • clinical practice. Second, recurrent malignant arrhyt malignant recurrent Second, clinical practice. forthe di criteria amongst considered must be failure advanced heart failure therapy, but but therapy, failure heart advanced (NYHA) class IV. The first HFA posi HFA IV. Thefirst class (NYHA) with advanced heart failure who remain ambulatory vent left of regardless management guideline-directed wh patients encompasses failure heart Advanced application of advanced therapies. transplantation,although it should berecognized in that some cases co-morbidities mayimprove after of patients withadvanced heart failure, and sometimesinfluence candidacy for MCS or heart failure. are medications vasoactive other and/or diuretics therapies), toproperly conv centre cent (i.e. those appropriate an referral to Accurate prognostication is especiallyimportant in advanced heartfailure to identify the ideal time for stratification Prognostic • with the former HFA definition of advanced heart strategies.

The treatment armamentariumThe hastreatment improved for HF outlined in the definition are present. are present. in thedefinition outlined patientsmaypreserved LVEF, these and alsobeco LVEF.least ofHowever, patientsreduced at have 50% a hospitalizedheart failure foracute have a cardiomyopathy, LVEF.a With fewexceptions, such as patients with hypertrophic cardiomyopathy or restrictive of independent failure, heart with patients all to importance same the gives dysfunction cardiac for ch that criteria other by accompanied when failure heart advanced of definition the for be used can they and dysfunction, cardiac define to sufficient are Further criteria must also be considered. First, outpatient visits with intravenous administration of loop of administration intravenous with visits outpatient First, considered. also be must criteria Further and resourceand utilization. course clinical the of instability the on placed emphasis with treatment, of independent failure, heart or visit(s) unplanned one ormore added asbeen amajor causeof ac added and given the same value as a heart failure hospitalization. failure aheart valueas same and given the added Criterion 3now includesheart failure hospitalization.Unplanned visits forheart failure have been Criterionnow isbased completely 2 recentthe mostfailure ESC on heart guidelines. 11 Thus, both unplanned outpatient both unplanned Thus, 24,25 However,detailed prognostication is complex and difficult. It is required for selection for 19 the vastmajority of patientswith anindication for heart transplantation orMCS

ey expectationsey topatients and famili 15–18 tion statement acknowledged the acknowledged im statement tion it is not required for referral to an advanced heart failure centre. failurecentre. heart advanced an to referral for not required it is hospitalization(s) within 12 mont 12 within hospitalization(s) ute events. Criterion 3 acknowledges that acute events leading to leading acute events acknowledges that 3 Criterion events. ute End-organ damage, in particular kidney or liver dysfunction and and dysfunction kidney orliver damage,in particular End-organ with advanced heart failure are outlined in in failure are outlined heart with advanced visits and hospitalizations for worsening symptoms of heart heart of symptoms worsening for hospitalizations and visits 12–14 failure, we have updated the following criteria: criteria: following the updated have we failure, Third, co-morbidities can complicate theevaluation of advanced heart of advancedfailureis warranted. Ourupdated vanced heart failuredoes not dependon ejection hmias are now well recogniz well now are hmias o remain severely symptomatic despite optimal optimal despite symptomatic severely o remain agnosisof advanced heartfailure toreflect evolving res capableof providing advanced heart failure apies should be reflected in definitions of advanced but are essentially New York Heart Association Association Heart York New essentially are but aracterize patient severity. Using the ESC criteria ricular ejection fr ejection ricular increasingly replacing hospitalizations for heart heart for hospitalizations replacing increasingly rEF since the 2007 HFA document, with clearer nsidered advanced provided the other criteria criteria other the provided advanced nsidered es, and to plan treatment planfollow-up to and es, and 9,10 4 Despitethis recognition, advanced

portance of HFpEF and included portanceand a ofHFpEF 20–23 hs are the hallmarkof advanced action (LVEF), including patients Malignant arrhythmias have have arrhythmias Malignant ed contributors to and contributors ed Table 3 9 The ESC criteria criteria ESC The . Compared . Compared This articleisprotected bycopyright.Allrightsreserved. Accepted Article Kidney Indexes (MECKI) score, (MECKI) Indexes Kidney Seattle Heart FailureSeattle Heart Model (SHFM), managementof patients with advanced heart failure, heart failure interventions, including selection for cardiac transplantation. cardiac for selection including interventions, failure heart performed by the heart failure team, areuseful for prog (MAGGIC) actual outcome), and reclassification (how well addition of information correctly reclassifies events). ofdisc score understanding requires poor prognosis. Finally, appropriate clinical use of and do not improve outcome, although interventions targeting haemodynamics, which do not targeting a riskmarker will not automatically im increased serum bilirubin, respectively. bilirubin, serum increased and ALT) (AST, levels transaminase increased are state low-output and/or congestive due to damage liver chronic and acute of indices common most The insufficiency. renal than investigated extensively less been has failure heart ofadvanced in the setting dysfunction Liver failure. heart to secondary or intrinsic be may (CKD) disease kidney chronic as such dysfunction End-organ MCS. or transplantation cannot modifiedbe heartfailureby therapy and pr withoutcomes interventions (contraindications). Contra adverse for potential the and (indication) therapy without prognosis both consider should physicians markersimportant prognostic failure.heart inIn patients with advanced heart failure who are able in work-up the of component critical a is it and factors, psychological and peripheral pulmonary, cardiac, by are impacted that parameters integrated of a set provides (CPET) test exercise cardiopulmonary of patientsin critical conditions, e.g. cardiogenic shock, not respondingto standardtreatment. The inform decisions. to assessments risk comprehensive at arriving in team failure heart the assist can scores multiparametric These tools. online interactive as available are and validated, derived, been have risk scores composite of thepresence advanced only Referral requires markers from multiple pathophysiological domains ( domains pathophysiological multiple from markers function. ventricular right of assessment the to adds and gradient, transpulmonary resistance, vascular pulmonary pressure, wedge capillary pulmonary the as such parameters, important of estimate accurate an allows critical component of the work-up for potential heart transplantation or long-term MCS recipients. It accura the doesnot improve assessment haemodynamic gradually taking place the of rightheart catheterization, though with some limitations. management, patient guide to also but prognostication for only serve not they may and modalities, critical. An expanding spectrum of parameters areavailable from echocardiographyand other imaging physi the and hospitalizations, failure heart recurrent Other co-morbidities, such as disordered iron metabolism, must be systematically investigated be systematically must metabolism, iron disordered as such co-morbidities, Other heart failurethe teamtoassesswhether such damage treatment may improve quality of life and symptoms. cohorts, while providing very different prognostic estimates when applied individuals. to applied when estimates prognostic very different providing while cohorts, it must bekept mind in that differentprognostic mort expected particular a to corresponds that NT-proBNP of value particular no is there because poorly calibrates it but risk), very discriminates NT-proBNP example, advanced but non-hospitalized heart failure in failure heart non-hospitalized but advanced been derived and for acute validated both heart failur have scores Numerous calibration. and discrimination of terms in both markers individual outperform failure specific death or hospitalization. death specific failure heart or cardiovascular for well less but mortality well for perform scores and markers risk Third, cohorts. failure heart advanced derivedfrom not were prognosis estimating for tools available of the most Second, centres and may notbe generalizable ‘real-world’to heart failure populations or individual patients. overlooked when applying thes Nevertheless, objective risk markers and scores, especially as part of a comprehensive assessment assessment acomprehensive of part as especially scores, and risk markers objective Nevertheless, No single variable can account for all prognostic dimensions. Multivariable prognostic scores scores prognostic Multivariable dimensions. prognostic all for account can variable No single First, many prognostic tools were derived and validated in selected clinical trial populations or at single single at or populations trial clinical in selected validated and derived were tools prognostic many First, 25,130,131 105 ( Table 5 Table Invasive haemodynamic monitoringis haemodynamic Invasive 9 However, are there several important cons ). The SHFM been has shown tounderestimate therisk of decompensation and ality rateor thatcan be used tolist a patient for cardiac transplantation. Finally, e tools in clinical settings and in clinical trial design. 134–136 rimination (between event and non- and event (between rimination 109 and Meta-Analysis and the Global Groupin Chronic Heart Failure an impaired haemodynamic profile is a very powerful indicator of 16 well (i.e. valueshigher accurately greaterpredict heartfailure the Metabolic Exercise test data combined with Cardiac and and Cardiac with combined data test Exercise Metabolic the 9,26–28 End-organ damage outcomes, impacts and it is important for Fourth, not all risk markers are also risk factors. Thus, Thus, factors. risk also are riskmarkers all not Fourth, clude the Heart Failure Survival Score (HFSS), Score Survival HeartFailure the clude prove outcomes. Oneexampl prove outcomes. any prognostic variable multiparametric (biomarker) or scores may perform more or less equally in patient patient in equally less or more perform may scores to perform the test. Co-morbidities are common and 9 edispose patients to adverse outcomes afterheart heart failure.Numerous single riskmarkers and 132 selecting advanced heartfailure interventions,

cian’s impression from the patient from encounter are impression cian’s e and outpatients. Selected prognostic scores for for scores prognostic Selected outpatients. e and indications are often related to co-morbidities that nostication, prioritization, and triage for advanced Table 4 but it is useful for the evaluation and and treatment it isthe but forevaluation useful correct theunderlyingaetiology failure ofheart is likely reversible after transplantation or MCS. MCS. or transplantation after reversible likely is cy heart failure of prognostication,but it is a not routinely recommended for in-hospital forin-hospital recommended routinely not iderations andlimitations that areoften ). 8,25,27,28,30–127 event), calibration (predicted vs. vs. (predicted calibration event), 25 It is useful to consider risk risk consider to is useful It Clinical history such as e includes pharmacologic pharmacologic e includes 29

128,129 Invasive Invasive 133 24 the 9 For For as This articleisprotected bycopyright.Allrightsreserved. Accepted Article particularly in those patients reporting a dispro a reporting patients those in particularly work-up for elective patients with advanced heart patients with potential indications for heart transplantation or long-term MCS and should be part of the advanced heart failure. heart advanced represents a significant risk marker and potential co asindicated describedabove. Inaddition, the6MWT patiobjective in evidence offunctional impairment the the procedure as well as meticulous interpretation. failure in some, in failure consumption (pVO consumption instance by ensuring a respiratory exchange rate >1.05. In addition to pVO to Inaddition >1.05. rate exchange a respiratory byensuring instance indication for left ventricular assist device (LVAD) in patients with advanced heart failure. heart advanced with patients in (LVAD) device assist ventricular for left indication functional capacity as assessed pVO by assessed as capacity functional while the 6MWT is performed at submaximal exercise levels. Thus, the 6MWT does not accurately reflect arterioven the and output cardiac maximal expresses CPET during uptake Peak oxygen measures. 6MWTareverydifferent CPETand that emphasized It is well known that inotropes may improve ha improve may inotropes that well known is It Intravenous vasoactivedrugs short-term management strategy. ce (i.e. hub failurecentre heart advanced specialized overal and patient the of Discussion list. transplant be can MCS until beneeded may therapies short-term situations where patient’s the clinical condition de Advanced heartfailuretherapies long-ter referto failure heart advanced of management Short-term Management strategiesheart withfor failure advanced patients those with a submaximal CPET, have a poor prognosis, and V and prognosis, poor a have CPET, a submaximal with those Additionally, patients with aventilation equivalent of carbon dioxide (V failure heart inadvanced treatment referral and interv advanced for screening active of The concept interventions remains difficult, and patientsare often referred toadvanced heart failurecentres toolate. parameters,predicting ab bothin the outcomes prognostic of set extensive an of availability the Despite outcomes. with associated strongly also are up, in Thesefor referral. arelisted allows for somesuggested clinical, laboratory, echocardiography and criteriamay that serve as triggers hear forreferraltoadvanced criteria as beused can cut-offs and variables which indicate that studies validated no are there Although this riskTherefore, score should beusedcaut blocker intolerant). blocker heart failure failure (<300 heart evaluation. achieving a pVO help informthe evaluation of hear Guidelines elective listing pati for they wereco if failure heart with advanced patients ambulatory of of evaluation the part been CPET has Traditionally, prognosis. and reserve cardiovascular Cardiopulmonaryexercisereproducib testing is Exercise testing The 6-min walk test (6MWT) is easy to perform andwidely used in heartfailure. Itshould be Finally, non-patient-related factors, such as organization of care and access to treatment and follow- and treatment to access and care of organization as such factors, non-patient-related Finally, 25 Performing high quality CPET is not a simple task and reliable results require staff skilled in in skilled staff require results reliable and task simple a not is CPET quality high Performing 127 2

butnotall studies. 2 25

≤ ) m) andalso as anendpoint in clinical trials. Use ofthe 6MWT is encouraged to give Importantly, confirmation thatpeak valu 50% of predicted may be appropriate to ≤ 99,146 12 mL/kg/min is a potential indication for heart transplantation (

Table 6 ents for hearttransplantation still t transplantation candidacy. In women or patients <50 years of age, age, of years <50 patients or women In candidacy. transplantation t t failuret centres,thetotality of dataon heart failureprognostication . 143–145 2 , 127 The 6MWT has been used as a screening tool in advanced toolin advanced screening The a usedas 6MWT hasbeen butit is correlated to pVO iously inthe setting of advanced heart failure. portion between symptoms andportion objective betweensymptoms parameters. 139,140 emodynamics and helpreverse end-organ worsening 141 nsidered for heart transplantation or long-term MCS. MCS. long-term or fortransplantation heart nsidered ents with advanced heart failure where CPET where is CPET failure not heart ents with advanced teriorates, orend-organ function is compromised, ( le and provides important information about failure in arefailure in whom these treatments considered, l plan for advancedl planfor failure heart therapieswith a However, CPET remains highly valuable to identify ntre) canbe helpful to select the most appropriate sence and presence of advanced heart failure failure sence heart andpresenceofadvanced ention has been proposed to improve to beenproposed appropriateention has m MCS orcardiac transplantation. However, in ous oxygen difference during maximal exhaustion, exhaustion, maximal during difference oxygen ous Figure 1 Figure ntraindication to non-pharmacologic strategies in implanted orwhilethe patient is waiting on the can be a useful tool to assess frailty, which which frailty, assess to tool auseful be can E ). es have been achieved ismandatory, for /V determine heart transplantreferral. heart determine CO2 slope may beapplied patientin the state that a peak exercise oxygen state oxygen that apeakexercise

2 and predicts survival in heart E /V CO2 2 , other CPET findings may , otherCPET findings ) slope >35, particularly particularly >35, ) slope ≤ 14 if beta- 110,137,138 142

This articleisprotected bycopyright.Allrightsreserved. Accepted Article dischargewith inotropes for patients waiting fortr Lo decongestion. during forinstance dysfunction, alsoasbe used short-term patients therapy in lo MCS, temporary to bridge a as patients selected in failure heart in refractory necessary be may support inotropic that opinion expert is there However, patients should probably be considered for long-term MCS if MCSif feasible. long-term for be considered probably should patients 12–24 a after days >7 for last may effect haemodynamic the since levosimendan, of use especially popularity, planned. diuretic’s tubular site of action. regarding this controversial topic comes from a Swiss observational study, observational Swiss a from comes topic controversial this regarding expected waiting time for transplantation. In the risks ofsu expected the balancing transplantationstill isa of decimatter debate.This approach may beuseful for patients with contra weeks for 12 weeks. for 12 weeks to placebo. Adverse events were similar between groups. between weresimilar placebo.Adverse events to experience or failure heart for hospitalized be to likely comparedlevosimendan group tothegroup. Pa placebo Most of heartfailurethe hospitalizations ar ofcongestion Management 69 patients69 with advanced heartfailure placebo to or levosimendan 0.2 µg/kg/minover 6 demonstrated inasingle, adequately sized, prospective study. The LION-HEART study pilot randomized observational studies, options. inotropes maybe acceptable asa palliativemeasure for patientswithout other advanced treatment regardinginotropic therapyMCS or forpatients awaiting transplantation should beassessed. Continuous effect onsurvival positive a suggested have strategy infusion repeated of a trials small heterogeneous several of analyses prognosis. worsened studies, some in have, and outcomes, improved with beenassociated not generally heartfailure( in advanced function purpose. effective alte less invasive as aand emerged potential waiting list time fortransplantation ofmont only 8 forIC wasobserved benefit survival inflammation,oxidative nephrotoxic stress, and drugs. reabsorption, sodium tubular excessive activation, neurohormonal haemodynamics, abnormal (cardiorenalsyndrome) and by diuretic resistance. The clinicalcourse ofpatientsadvanced with heart further their and failure treatment for heart guidelines congestion in patientsthe with heart failure. Diure diuret Loop outcomes. patients’ worsens congestion pressurereversibleconsidered is a condition or defi blood low the if only and goals, clinical desired the obtains that dose lowest the at shock) (cardiogenic hypoperfusion organ of evidence and pressure blood systolic low with patients for reserved be Increased uremic anions anduremic proteinuriaIncreased alsoimpair andto nephron ofthe sites other of hyperfunction seriesof renal adaptations after diuretic use (‘braking phenomenon’) including hypertrophy and outcomes compared compared outcomes to placebo in Ultrafiltration (UF)mightanalternative be toloop practice. this guide to exists trials clinical from evidence no However, phenomenon. braking the Intermittent use of inodilators for long-term sy Whether or not to implant an implantable cardioverter Vasopressors (dopamine, norepineph (dopamine, Vasopressors Concomitant administrationof thiazide diureticsor me

h infusion because of the pharmacologically active metabolite with a long half-life. long a with metabolite active pharmacologically the of because infusion h 160

147–149

Hence, inotropes have no place ro the in have place no Hence, inotropes 156 and a reduction inhospitalizations, 158 152 NT-proBNP time,theprimary wassignificantly endpoint, over lower inthe andlow-dose dopamine does not improve congestionor cardiovascular 161

Table 7 Table acute decompensated heartfailure. decompensated acute dden death and device-related complications, and considering the considering and complications, and device-related death dden D carriers,D asprimaryorsecondary both prevention, with amedian rine, epinephrine) are broadly associated with worse outcomes in in outcomes worse with associated broadly are epinephrine) rine, ). However, inotropes studied in randomized clinical trials have have trials clinical randomized in studied inotropes ). However, e due to signs and symptoms of fluid overload. indications totransplantationlong-term or MCS. ng-term MCS, or heart transplantation. Inotropes may transplantation. heart MCS, or ng-term with low cardiac output and evidence of end-organ end-organ of evidence and output cardiac low with ansplantation, is notrout nitive therapy (long-term MC (long-term therapy nitive ng-term (i.e. months) or chronic treatment aftertreatment orchronic months) (i.e. ng-term failure is often characterized by kidney dysfunction The first may have multiple mechanisms including including mechanisms multiple have may The first tic therapy is thoroughly described in the current diuretic administration. It removes isotonic fluid fluid isotonic removes It administration. diuretic mptomatic improvement or mptomatic achievement of therapeuti achievement absence of randomized trials, the best evidence evidence best the trials, randomized of absence a decline in health-related quality of life compared rnative to conventional implantable devices for this increased renin secretion in the maculasecretiondensa. inthe renin increased ics remain the cornerstone for the treatment of thetreatment for the cornerstone ics remain hs. Inrecentyears, wearabledefibrillators have sion is usually made on anindividualized basis, 161 tients randomized tolevosimendanwere also less discussion goesbeyond the aims of this article. tolazone with loop diuret loop with tolazone 158 Loop diuretic resistanceisgenerally due to a -defibrillator(ICD)in patients listedfor heart More studies are needed to determine ifthis to needed are Morestudies utine treatmentheartfailure. ofadvanced 157 such a survival effect has not been 150,151 153,154 However, patient preferences preferences patient However, Hence, these agents should should agents these Hence, inely recommended. These These recommended. inely 159 c concentrations at the at the c concentrations inwhich asignificant S transplantation) or is ics is usedto overcome palliation has gained 155 161 While meta- While

Recurrent Recurrent h every 2 This articleisprotected bycopyright.Allrightsreserved. Accepted Article The initial dose of the intravenous intravenous the of dose initial The receive intravenous diuretics starting with anintraven from the interstitium decreases as fluid is removed. is fluid as decreases interstitium the from catheter) and the blood. the and catheter) solute moleculesexchanged can between be the dialys which through filter as the used is peritoneum The overload. fluid and syndrome cardiorenal failure, heart patients in diuretics intravenous including therapy guideline-directed to compared days 90 at deaths cardiovascular and events failure heart fewer in result diuretics intravenous low-dose with combined UF peripheral whether evaluate will (NCT03161158) that preceding that thesigns andsymptomspreceding of congesti low UF with over rates conducted delivered ho several Among patientswith advanced heart failure, short-termMCS maybe indicated in the setting of circulatory support mechanical Short-term peritoneal dialysis is associated with improved survival. diuretics may enhance sodium re sodium enhance may diuretics loop of use concomitant and restriction sodium dietary function, renal residual significant with patients summarized in the online online supplementary in the summarized movement ofsodium continuesdwell and time sufficiently is long. diffusive the as concentration serum the approaches This dialysate. the in sodium of concentration slowlythroughmore the small poresoftheperitoneal of aquaporin waterfreeacross the rapid transport During the first 60–90 min of intraperitoneal dwell ofdextrose-containing peritoneal dialysis solutions, short follow-up, and insufficient power to detect an effect onmortality. more research more research in th technology pulmonary and arterypressure sensorsall electromagnetic spectroscopy, bioimpedance analysis, vector Bioimpedance volume. intravascular the haematocri therapy when resume (e.g. 7%) and 5% to set exceedsa threshold haematocrit the removal if fluid stop to programmed haematocrit sensors permit continuous estimation removal with automated peritoneal dialysis. peritoneal automated with removal UF. dialysis solutions with icodextrin, ahighmolecular weight glucosewhich polymer induces transcapillary requiring specialized technicians or acute care settings. care acute or technicians specialized requiring exceed capillaryaccess toUF refill. st Greater without direct activation oftherenin–angiotensin–aldosterone system, fluid if removal rates donot failure hospitalizations andincrease inLVEF. have shownthis modality is associated with weightloss, improved quality of life,reduction in and heart V). Stage ofStudies peritoneal dialysis in heart failure patients CKD with and refractory fluid overload (CKD choice of therapy replacement renal the is dialysis peritoneal whom in disease renal end-stage used is dialysis peritoneal whom IV/V)in (Stages CKD blood. Peritoneal dialysis has a role in patients wi of the osmoticpressure gradient between the hypertonic dialysate and the hypotonic peritoneal capillary onlytolerate lowUF rates(50to100 mL/h). Patients with right-sided heartfail antagonists. Only if these measur Persistent congestion can be then treated by adding th high-dose diuretic treatment. investigatio additional for need the UF underscore early fluid-overloaded patients with heart failure. ambulatory peritoneal dialysis may be preferred when sodium removal is the primary target, as it is in decongestion and fewer heartfailur Peritoneal dialysisa is home-based therapeutic modali Practice guidelinessuggest that patients with anin Once an initial UF rate is chosen, it should be ei shouldbe it ischosen,rate UF initial Once an The adjustment ofUF ratesto patients’vital si The PeripheralUltrafiltration for the Relieffr 171 Another strategy is to decrease the number of nocturnal cycles to increase the dwell time. For For time. dwell the increase to cycles nocturnal of number the decrease isto strategy Another is areaneeded. 166 With peritoneal dialysis, removal of sodium and water byUFoccurs because 163,164 ure are orHFpEF susceptible to intravascular volume and depletion may es fail can UF be considered. UF be can es fail

moval by peritoneal dialysis. treatment should be increased in case of an inadequate response. inadequate an of case in beincreased should treatment 161 e events than standard ofcare. t valuefallst below pre-specified the level, indicatingan adequate

Table S1 169 167–170 170 Oneapproach is to substitute conventionaldextrose-based 164 Several strategiesallow Extracorporeal fluid removal is better toleratedwhen ems from the developmentems fromthe ofsimplified devices not with heartwith failure hospitalized congestion. for th concomitant heart failure . channels occurs, whereas the solute-rich water moves water solute-rich the whereas channels occurs, However, these studies lack a control group, have a a have group, control lack a studies these However, on and on and used as the for target fluid removal. 165 gns andrenal functionmayprovide moreeffective om Congestion in Heart Failure (PURE-HF) trial trial (PURE-HF) Failure Heart in Congestion om of blood during be volume changes UF andcan adequate response oraldiuretic to treatment should ther maintained or reduced because capillary refill refill capillary because orreduced maintained ther have limitations for estimation of blood volume and urs.Patients’ currentweight can be comparedwith iazide, or thiazide-like,di Rates of UF>250 mL/h are not recommended. 162 ous dosegreater than that of the oral treatment. as an UF strategy and those with heart failure and membrane. This results in an early drop in the in the an earlydrop results in This membrane. ate (delivered to the peritoneal cavity through a a through peritonealcavity the to (delivered ate n of UF in clinicalsettings as an alternative to

ty than can be used in patients withrefractory 6,9 However, favourable results of trials of trials of results favourable However, 172 Future studies should determine if determine should Future studies 166 161 The longer dwells of continuous of continuous dwells Thelonger The results of UF studies are adequate sodium and water water and sodium adequate with and without advanced advanced without and with uretic agents, aldosterone uretic agents,aldosterone 164 Inline Inline 164 6,9

This articleisprotected bycopyright.Allrightsreserved. Accepted Article Its contribution to cardiacbyIts L/minis small, 0.5 outputA some small approximations. merely ( consumption. oxygen reducing thus afterload, reducing and myocardium the to supply oxygen improving balloon duringinflated isdeflated diastole du and fivethan decades. The mechanism of action is based subclavian artery and the renal arteries. Intra-aortic inflated a balloon with catheter implanted a percutaneously of consists (IABP) pump balloon An intra-aortic with gas (usuallyIntra-aortic balloonpump helium, alow-density gas) that ispositioned in the aorta between the left remaining 43%hadfurther clinical stabilization in 57% ofthepatients who re ( study single-centre A small limited. also is practice this for evidence to provide mechanicalsupport to patients withca ventricles. On the arterial side, ECMO delivers 4–6L/min of flow to the aorta resulting in increased both of pressures filling reduces consequently, and, heart, the to preload of reduction a in results the my on consequences detrimental haemodynamic distal limb perfusion. for cannula a of addition routine the despite frequent relatively remains ischaemia limb distal ECMO, mostly related to vascular complications, bleeding, thrombosis, and infections. In the case ofperipheral in the femoral artery andvein. cannulas of insertion for technique Seldinger the using intensivists trained or cardiologists interventional in patientswho failwean to offcardiopulmonary by cannulationand is aorta, ascending pr it ofthe and access surgical requires ECMO Central access. peripheral or central with beconfigured can oxygenation cases ofsevere respiratory insufficiency with preserved cardiac output. Extracorporeal membrane mode provides only respiratory support, i.e. oxygenation of venous blood, and it is used primarily in configurations.veno–arterial The mode provides fu Thus, ECMO provides full systemic circulatory support support. respiratory full provide to oxygenator an as well as flow, of L/min 6 to up provide can that pump longer Extracorporeal transport. useand and memb easier for modified machine bypass cardiopulmonary a is (ECMO) oxygenation membrane Extracorporeal oxygenation membrane Extracorporeal arecurrentlyventricle preferred. frequently and maintained between160–180 maintained and frequently monitored be should time clotting activated heparin; with anticoagulation demands support oxygenation membrane Extracorporeal complications. vascular possible manage to beavailable must surgeons echocardiographyor fluoroscopic guidance advisable is for cannula positioning, and vascularor cardiac transoesophageal initiation; and priming ECMO circuit for are essential technicians Perfusion area. MCS can used as be a bridge-to-decision (BTD short-term way, this In support. of a period after occur not does recovery whencardiac plan a include also should which expertise specific MCSrequires short-term on patients of care the straightforward, and simple relatively is devices short-term most of insertion Although brain. and liver, kidneys, as the such organs other of recovery as well as recovery cardiac allow weeks, to several to up few days, a for used be can which available are devices paracorporeal and percutaneous Several shock. cardiogenic IABP. to respond to more likely patients predict may pressure artery pulmonary higher and indices power scientific evidence for these applications is lacking. heart disease, and for protective support during high-riskpercutaneous coronary intervention,but no single ideal device, their use should be primarily guided by clinical and judgment local experience. implantation. LVAD before IABP support undergoing patients in pressure end-systolic ventricular left and work stroke cardiac in 20% of increase amedian reported study Although ECMOAlthough fullfor provides support pati the Implantation and management of ECMO demands ade or veno–venous veno–arterial be in can used either membrane oxygenation Extracorporeal 178 In general, newer devicesthat generate greater 175 Currently, IABP are primarily used for cardiogenic shock in the setting of acute ischaemic ischaemic acute of setting in the shock cardiogenic for used IABP are primarily Currently, clinical deterioration. clinical ) for long-term heart transplantation. MCS or ) forlong-term

s. Complications of ECMO support are frequent and are and are frequent are ECMOsupport of s. Complications 178 176,177 ceived IABP prior LVAD to edominantly used for postcardiotomy short-term MCS MCS short-term postcardiotomy for used edominantly rdiogenic shock prior to LV to prior shock rdiogenic pass.Conversely, peripheral ECMO can be placedby Higher right ventricular and left ventricular cardiac ventricular left and ventricular right Higher ll cardiopulmonary support, while the veno–venous veno–venous the while support, cardiopulmonary ll balloon pumps have been have been pumps balloon rane oxygenationdevices have acentrifugal blood and can restore be to end-organ useful perfusion. ring systole, thus facilitating coronary flow and and flow coronary facilitating thus systole, ring ent, it may have non-physiologic and sometimes sometimes and non-physiologic have may it ent, index and significantindex and reductionsventricularin left on the principle of diastolic augmentation, i.e. the ocardium. Draining blood from the venous side venous fromthe blood Draining ocardium. Intra-aortic balloon pumps are sometimes used used sometimes are pumps balloon Intra-aortic support andunloadingsupport of provide left better the dicated team with expertise in this specific n =56) reported that IABP provided IABP =56) reportedthat implantation, whereas the the whereas implantation, AD implantation, but the used formore used clinically 173 As there is is Asthere n =10) 174

This articleisprotected bycopyright.Allrightsreserved. Accepted Article RVAD). (TandemHeart system support ventricular right a to configured be easily can TandemHeart ventricle. left the to preload on depends atrium the left of out blood pumping Furthermore, atrium. right the to back or position suboptimal a to migration cannula frequently, most or perforation, as such complications, passage intotheleft ventricle. However, positioning ofthecannulain atrium left the carries risk a of decrease in left ventricular filling pressures,volumes and oxygen demand and that it does not require devices. implanted percutaneously short-term other to compared as longer and complex more procedure implant the makes This use. its in proficiency 6 for approval (FDA) Administration Drug and Food has TandemHeart support. respiratory provide to circuit in significant right-to-left shunting providers must secure the inflowcannula since movement thromboembolic incidents. The major disadvantage is which significantly increases the risk of bleeding complications. days (www.tandemlife.com). (www.tandemlife.com). days TandemHeart is adevice that left ventricleexpelling and it theascendingto aorta. deviceThe Impella is asmall axial flow placed pump across theaorticvalve, blood aspirating fromthe Requirements for activated clotting time are even events. thromboembolic of risk high the to due mandatory is therapy Anticoagulation insufficiency. anticoagulation therapy, presence of right or left atrial thrombi, ventricular septal defect, or severe aortic IABP. The same effect was not observed when effectwasnotobserved TheIABP. same consists of a21 of consists short- to-medium-termsurgic ventricle[e.g. IABP, Impella Ventricular Support Systems (Abiomed Inc., Danvers,MA, USA), or other left the unload to device asecond adding or ECMO), peripheral with apex(e.g. ventricular left the or such as insertinga left atrial ventfor unloading th function. respiratory compromise and oedema pulmonary to lead may congestion venous pulmonary The resulting le femoro–femoral ECMOperipheral mayeven increase depending on the severity of myocardial dysfunction and heart, the decompress necessarily not does itself in ECMO Therefore, ventricle. left the to afterload 19 extracorpo left atrium),the continuous acentrifugal TandemHeart pulmonary oedema. also been reported method asto unload a theleft heart in ECMO-supported patients with refractory cardiogenic shock in which ECMO is is considered. ECMO which in shock cardiogenic as used canbe SAVE score(www.save-score.com) The hypoxic blood perfusing the brainand the well-oxygenat studies performed to date. to performed studies in beenestablished not has survival on effect positive a However, pressure. wedge capillary pulmonary Impella used. cardiac arrest patients when treated with ECMO in comparison to controls inwhom ECMO was not heart failure asashort-termheart bridge-to-transplant chronic byend-stage caused shock cardiogenic in beused readily ECMOcan treatment. heparin adequate in may evenresult output cardiac native of Absence

h ofand alsoCEmark, supporth whichincludes appr

Fr, inserted in iliofemoralthe artery).A membra The main advantages of this device are thedirect are device ofthis advantages The main Other importantcomplications Other TandemHeartof vascular support are complications, site infections,and The need for trans-septal puncture and positioning of Other contraindications include significant peripheral vascular disease, general contraindications for for contraindications general disease, vascular peripheral significant include contraindications Other TandemHeart improves haemodynamics by adding upto 4 A recent meta-analysis of cohort studies suggested studies suggested meta-analysis ofcohort recent A 184 188 ® Furthermore, ECMO provided better survival in patients in cardiogenic shock when compared to to compared when shock cardiogenic in patients in survival better provided ECMO Furthermore, 179 ventricular support systems (Abiomed Inc., Danvers, MA, USA) MA,USA) Danvers, Inc., (Abiomed systems support ventricular

In these cases, a few modifications in the ECMO circuit can be performed to optimize support, support, optimize to be performed can ECMOcircuit in the afew modifications cases, In these ® percutaneous ventricular assist device (Cardiac Assist, Inc., Pittsburgh, PA, USA) PA,USA) Pittsburgh, Inc., Assist, (Cardiac device assist ventricular percutaneous

Fr inflow cannula (inserted via the femoral vein to the right atrium and trans-septally into 182 Native cardiac output and ECMO flow should be carefully balanced to prevent prevent to balanced becarefully should ECMOflow and output cardiac Native 189,190 ally implanted MCS device]. MCS implanted ally connects left atrium the with the iliofemoral artery.

with catastrophic desaturation. ECMO was comparedto Impella orTandemHeart. 183 ECMO foruse hasbeenregistered up to 30days. e pulmonary veins/left atrium (e.g. with central ECMO) ation (BTT), BTD, or bridge-to-candidacy (BTC). (BTT),bridge-to-candidacy ation BTD,or higher than forand should ECMO, be around 300 real pump,blood and an outflow arterial cannula (15- ne oxygenator can be added can ne oxygenator to be the TandemHeart In this way, it unloads the left ventricle, improving improving ventricle, left the unloads it way, this In oval for Protec Duo veno–venous cannula up to 30 up cannula Duo veno–venous oval forProtec ft ventricular end-diastolic pressures and volumes. pressuresand ventricular end-diastolic ft better survival rates and ratesand ne survival better unloading of the leftatrium which results ina the immobility of the supported patient; carepatient; of immobility thesupported the complete clotting of left the ventricle despite and presence of aortic or mitraland presenceregurgitation, or ofaortic the inflow cannula into the left into the atrium cannula demands theinflow ed blood mainly perfusing the rest of the body. of ed bloodthe mainly rest perfusing the 180,181 of the tip from the left to right atriumresults a to tool survivalpredict inpatients with Percutaneous left atrial septostomy has has atrial septostomy left Percutaneous

L/mincardiac oflowering and output urological outcomes inurological outcomes 186,187 TandemHeart TandemHeart 185

180,181

This articleisprotected bycopyright.Allrightsreserved. Accepted Article transaxillary approach has beenreported. approach transaxillary prohibitive surgical risk due to co-morbidities but with projected survival >1 year after aortic valve of the degree irrespective of (AVR) is recommended unloading duringECMO. Impella has been shown alsoasan option for acute right ventricularsupport or for leftventricular are associatedwith vascularthro injury, bleeding, use Impella of complications Major reason. any for patients anticoagulate to inability the as well as use, its to contraindication a is disease artery peripheral devices, percutaneous all peripheral with As days. 5 recommended for such patients with left with patients forsuch recommended using an Impella device. Impella an using intervention coronary risk, surgical high unacceptably Surgical Treatment for Ischemic Heart Failure (STICH) trial. the in follow-up of years 10 over alone therapy medical to compared hospitalization cardiovascular or death all-cause and death cardiovascular of outcomes secondary the and death, all-cause of grafting inaddition me to bypass coronary artery For patients with an LVEF Conventional cardiac surgery patients. fo and therapies, failure heart advanced considering described herein, physicians should re not are failure heart chronic for therapies device and medical guideline-directed on details Although be adequately longer no can symptoms that such andoptimized inthe asappropriate been implemented whengu indicated are therapies failure heart Advanced failure heart advanced of management Long-term and femoral venous cannulation as inflows andrigh three three versions: 2.5device (12 implanted mechanical aortic valve, orexistence ofle severe include aortic Contraindications artery flow. coronary increasing and pressure, wedge capillary pulmonary decreasing with combined haemodynamics 10 is flow Maximal unloading. cardiac complete and support circulatory full in results but sternotomy supp biventricular and ventricular, right ventricular, left for used be can which pump centrifugal paracorporeal levitated a magnetically is CentriMag The USA) MN, Minneapolis, circulatoryJude, (St. acute system support CentriMag reported. supportintegratedCentriMag withECMO invasive such cases. such could not be demonstrated, and itisgenerally advised ventricular cavity and reduces suction events. Survival benefit with 2.5 the device in cardiogenic shock and 5.0 device (21 device 5.0 and surgical procedure to insert a 21 a insert to procedure surgical Also, the possibility of right ventricular support can be an advantage. bean can support ventricular right of possibility the Also, those patients who need a longer duration of support than is feasible by the previous mentioned devices. anticoagulation with intravenous heparin. This device cardiogenic shock and isolated left ventricular failure, ventricular left isolated and shock cardiogenic rates. may be associatedwith improvedoutcomes and lowerthan previously reported or predicted mortality

L/minfor is up intended of andduration support In severe symptomatic aortic valve stenosis with mean gradient >40 mmHg, aortic valve replacement replacement valve aortic mmHg, >40 gradient mean with stenosis valve aortic symptomatic severe In The Impelladevice is FDA approved for partial support of up 6 to days,and ithas a CE mark for up to The distal tip of the catheter is designed as apigtai isdesigned catheter ofthe tip The distal 193

197 192 The Ec-VAD circuit is configured with left ve left with configured is circuit TheEc-VAD Recent results suggest that whenused as part of a standardized protocol in patientswith

Fr, maximum Fr, maximum flow 5 181,194 201

≤

35% and35% coronary artery disease amenableto surgicalrevascularization,

Fr, maximum flow Fr, maximum 2.5

Fr catheter in the femoral arterycatheter in Fr the femoral fer to existing guideline fer to documents existing guideline 191

L/min). Impella 5.0 is not fully percutaneous and requires a requires and percutaneous fully is not 5.0 Impella L/min). main stenosis or mainleft equivalent.

dical therapy significantly t axillary artery cannulation as anoutflow. mbosis, haemolysis, and devicembosis, haemolysis, andmigration.Recently,

managed or end-organ functionis compromised. L/min), CP device CPdevice (14 L/min), early active haemodynamic early (Ec-VAD) not requiring not (Ec-VAD) asternotomybeen has r guidance onthe management continued of these ft ventricular thrombus. Impella is manufactured in is manufactured Impella thrombus. ventricular ft valve disease (both stenosis and regurgitation), stenosisand (both disease valve can beused as abridge-to-recoveryor as aBTD for is an option and maybefacilitated under protection ort. It requires bywayof implantation ort. surgical It ideline-directed medical and device therapies have therapies device and medical ideline-directed

l catheter which contributes to stability in the left left the in stability to contributes which catheter l individualpatient but heartfailure has progressed to 30 days,30 longer requiresto but possible. is It ntricular apicalcannulat ntricular to use either the CP device or the 5.0 device in the5.0 to use or CPdevice either the left ventricular dysfunction. In patients with with Inpatients dysfunction. ventricular left 198,199 Coronaryartery bypass graft surgery is . Preliminary experiencewith the 195,196 9 to ensure optimization prior to

Fr, maximum flow maximum 2–4 Fr, reduced the primaryreduced theoutcome A new approach, minimally minimally approach, A new ion via mini-thoracotomy ion viamini-thoracotomy support support with Impella CP 200 For patients with

L/min), L/min), This articleisprotected bycopyright.Allrightsreserved. Accepted Article malignancy,renal dysfunction,hypertension, diabetes mellitus). dysfunction, graft late vasculopathy, allograft cardiac rejection, antibody-mediated infections, (e.g. therapy immunosuppressive of complications and effectiveness limited both of consequences HFSS, surgical and/or post-transplant outcomesor require special management. for heart transplant applied locally. locally. applied transplant heart for contraindications and indications impact may Availability country. by substantially vary can which hearts, as asymptomatic patients with LVEF LVEF with patients asymptomatic as well as patients symptomatic all in recommended AVRis regurgitation, aortic severe In scarring. to due is dysfunction is due toexcessive afterload;however, outcomeis less certain ifleftventricular dysfunction considered with revascularization.’ with considered tocoronarydue artery disease,evidencebut with of myocardial viability,valve mitral be surgeryshould behavioural factors that may cause difficulties during the waiting period, convalescence, and long-term long-term and convalescence, period, waiting the during difficulties cause may that factors behavioural during candidates transplant heart all of evaluation the (ISHLT) Registry shows 1-year survival of around 90% and median survival of 12.2 years. 12.2 of survival median and 90% around of survival 1-year shows Registry (ISHLT) refractoryheart failure. Datafrom the latestInternational Society for Heart andLung Transplantation infectious complications. Thus, hearttransplantatio because of developments inrecipient and donorse gradient severe aortic stenosis aortic severe gradient aortic transcatheter intervention, characteristics.’ ventricularevaluation a for assist device hearttransplant or accordingindividual to patient HeartTeam mayconsiderapercutaneous the edge-t optimal medical (including management CRTand ifindicated) who havenooption for revascularization, despite symptomatic remain who <30% LVEF and regurgitation mitral secondary severe with patients that contraindicate aspecificdonor. assessmentrecommended; is however,cono is there Blood compatibility group indicated. antibody patients.is transplant heart adult mandatoryfor HLA clinically as addressed and status) vaccination (e.g. beperformed should assessments maintenance of assess the used three thesecomponents to <35 mL/m <35 [e.g. complete medical history, physical examination, CPET, examination, physical history, medical complete [e.g. transplant. patients with a high mortality riskwithout heart transplant that also havea good expected survival post- in achieved is benefit survival The greatest beestimated. should prognosis Second, need. greatest re to and transplant cardiac for candidacy patient’s aetiologies oralternative explanations for advanced presencerefractory of failur heart Karnofsky score 80–100%) is 90%. asphysician-rated (defined activity of normal capable survivors of the proportion transplant, post-cardiac years 3 to At 1 life. of quality and status functional also but survival improves only not Transplantation function (lung, liver and kidney), screening for neoplasms or active infections], active or neoplasms for screening kidney), and liver (lung, function peripheral vascular disease, assessme The ongoing COAPT (CardiovascularThe ongoingCOAPT repair less amitral the likelythat stage, failure heart are applied( conventional with work compared return of lifeto and signif transplantation heart that community cardiology heartstage failure. Although controlled trials have end- or advanced with patients selected carefully for choice of the treatment is transplantation Heart Heart transplantation hospitalization. MitraClip system in 610 patients with heart fail Failure PatientsHeart with Functional Mitral Regurgit Since thefirst case hearttransplantof human in 1967, The patient evaluation before listing for transplant involves four main considerations. First, the 133 SHFM, 2 205 ), with a depressed LVEF, left ventricular function usually improves after AVR if left ventricular Third, co-morbidities should be evaluated to detect conditions that may negatively affect affect may negatively that conditions detect to beevaluated should co-morbidities Third, Table 8 202 109 Additionally, ‘in patients with LVEF <30% and severe functional mitral regurgitation IMPACT ). 9,25 The main limitation of heart transplantation is the limited supply of donor 207 ), and other studies as indicated based on co-morbidities ( 202 (valve area <1 202 e should be confirmed to ensure that there are no other treatable treatable other ensurethere e that areno to should beconfirmed valve implantation should be considered. In ‘true’ low-flow, low- low-flow, ‘true’ In considered. be should implantation valve 214 However, there is a legitimate concern that the more advanced the moreadvancedthe that the concern legitimate a there is However, Outcomes Assessment of the Mitr the of Assessment Outcomes Finally, a complete psychosocial evaluation should beincluded in ≤ 204 nt of frailty and nutritional status, nutritional and frailty of nt 50%. The main challenges after heart transplantation are the arethe transplantation heart after challenges Themain 202 According to the most recent valvular guidelines, ‘in guidelines, recentvalvular to most the According

cm never been conducted, there is consensus within the within there isconsensus never beenconducted, n is now considered the gold standard therapy for therapy for goldstandard the considered n isnow ation, NCT01626079) will evaluate safety the the of ure and its effects on death and heartfailure and effectsondeath ure its and 2 symptoms. This step is important to guarantee the to guarantee is important step This symptoms. operation or clip procedure can benefit the patient. the benefit can procedure orclip operation , mean gradient <40 mmHg, stroke volume index lection, immunosuppression, and management of and immunosuppression, lection, icantly improves survival, exercise capacity, quality nsensuslevel regarding the andtypeantibodiesof serve scarce donororgansfor patientswith the pre-cardiac transplant evaluation. Otherhealth evaluation. transplant pre-cardiac treatment, provided that proper selection criteria theinitialsocial processto identify screening and o-edge procedure or valve surgery after careful careful after surgery valve or procedure o-edge 25,88 203 204 right heart catheteriz post-transplant survival has improved improved has survival post-transplant

aClip Percutaneous Therapy for 25,204 206 Diagnostic and other tests determination of organ 25 prognostic scores (e.g. ation, evaluation of of evaluation ation, Table 9 ) 208–213 are 19

This articleisprotected bycopyright.Allrightsreserved. Accepted Article virus, hepatitis C, andhepatitis B). MCS devices are also an option for these patients. patients. these for option an are also MCS devices Long-term BTD. a as devices assist short-term orpercutaneous paracorporeal use either to prefer centres profile 2indicatesINTERMACS prog Similarly, intervention. and decision for time limited very with shock cardiogenic critical indicates willing to make long-term commitments for the patient’s welfare) is also a critical component. acritical also is welfare) patient’s the for commitments long-term make to willing that the patient has adequatesocial support (i.e. family or friends ableto givesupport and who are actually improve patient survival. may centres experience, gaining by and approach, Team Heart multidisciplinary a requires MCS term heart failureheart treated with an LVAD, but 2-year survivalwas not statistically different. showedimproved 1-year survival ininotrope-depen Evaluation of MechanicalAssistance forthe Treatmen amyloidosis. transthyretin gene, oran autologous stem cell transplantation may be indicated for light chain required may be transplant ahepatic transplantation, to heart addition in Forexample, diseases. these by impacted systems organ other manage to necessary failure symptoms may be for candidates cardiac transplantation. Collaboration with specialties other is resuscitation). evaluationbrain of ofcandidacy extent damage orother end-organ (e.g.determine injury post- an permit and perfusion end-organ and haemodynamics stabilize may MCS short-term cases, these In patients initially ineligible fortransplantation, such expected mortality whileawaiting asuitable donor MCSheart. Short-term canalso serveas abridge in ahigh- have and ill extremely who are transplantation to patients selected bridge can systems support circulatory Mechanical allocation. organ for countries some in criterion priority bea also can instability clinical however, outcomes; post-transplant early of predictor strong a is stability clinical Pre-operative Unstable patients recipients that harbour chronicin that recipients follow-up, particularly regarding substance abus hospital mortality following heart transplantation. treatment with inotropes) had the highest risk of primary graft failure, dialysis requirement, and in- despite decline clinical (progressive criteria 2 profile and shock) (cardiogenic criteria 1 profile INTERMACS Transp Heart National Spanish in the transplant appropriateness of this strategy isnow being deba The INTERMACS profiles can help identify potential candidates for MCS Patient for selection long-term durable support mechanical circulatory impr and continuous failure patients, heart of advanced technology of LVAD and conserva ofLVAD and technology dependent patientsor in patients withcontraindications for heart transplantation. survival benefits andimpr support Long-term with durable MCS devices like LV support circulatory mechanical Long-term MCS as aBTD might constitute amorereasonable initial strategy thananurgent transplant. transplant eligibility, as described elsewhere. described as eligibility, transplant infiltrativecardiomyopathies) require specificapproaches diagnosis, to prognosis, determination of and and heart disease, congenital complex dysplasia, ventricular right arrhythmogenic cardiomyopathy, follow-up. monitoring and yet needheart transplant andshoulda either notbe important aspect of the pre-transplant transplants is increasing. transplants transplantation, the proportion of long-term MCS devicesimplanted for destination therapy (DT) to heart Some aetiologies of advanced heart failure (e.g. hypertrophic cardiomyopathy, restrictive restrictive cardiomyopathy, (e.g. hypertrophic failure heart advanced of aetiologies Some Originallyonly considered as alifesaving ther 25 Special considerations are n considerations Special 9,173 Although urgent cardiac transplant listing is possible in many countries, the the countries, many in possible is listing transplant cardiac urgent Although 220 This growth is toa due growing shorta oves quality of life compared with 219 fections (e.g. Chagas disease,tu Chagas (e.g. fections tive management have improved. 25

ressive decline despite inotropic cardiacevaluationis the identification whothose ofpatients donot 25 eeded for eeded for patients withcongenital heart in disease and Patients with restrictive cardiomyopathy and severe heart severe and heart restrictive cardiomyopathy with Patients e, totherapy and adherence follow-up visits. 216 as those in cardiogenic shock with end-organ damage. end-organ with shock cardiogenic in those as Therefore, in these critical these Therefore, in INTERMACS 3 patients are those who are stable on on arestable arethosewho INTERMACS 3patients for familial amyloidosisrelatedto mutations inthe lant Registrylant database, recipientsmeeting the apyfor patients who were ineligible forheart dent, transplant-ineligible patients with advanced t of Congestive HeartFailure (REMATCH) trial first ted. Among patients list ovements in MCSovements in andsurvival technologies rates. AD in patients with patients advancedADfailure in has heart listed or removed if alreadylisted with close ge of donor hearts, increasing numbers ofdonornumbers ge hearts, increasing conventional treatments ininotrope- berculosis, human human immunodeficiency berculosis, 217,218 221 support. In these patients, many Inthese support. ( Managingpatients long- with Table 2 ed for emergent cardiaced foremergent ly ill patients, short-term ). INTERMACS profile 1 ). INTERMACSprofile 9 The Randomized Randomized The 217 213 Since then, Sincethen, Assessing Assessing 215 An An This articleisprotected bycopyright.Allrightsreserved. Accepted Article events and hospitalizations, compared to receivingthose optimal medical management. for12 survived months had and improvement in 6-min wa optimalwith medical showed management that greater a proportion of patients treated with LVAD appropriateness of long-term MCS. long-term of appropriateness treatments.Shared conventional despite optimal medicaltreatment plus CRT if needed, toNYHA classpatients IV who are refractory to a wide spectrum of patients ranging from housebound timing andassure best the outcomesboth for transp infections, VAD-relatedinfections,infections, non-VAD and infections. (VAD)-specific device assist ventricular differentiate to infections MCS for definitions standardized transplantation, but renal or liver function may improve after MCS, after may improve function liver or renal but transplantation, heart for contraindication a is insufficiency Severerenal support. mechanical biventricular or ventricular heart failure and need for concomitant cardiac surgery. cardiac concomitant for need and failure heart implantation include renaldysfunction, contraindications for heart transpla heart for contraindications chronic driveline infection, bleeding, or thrombosis. implanting an LVAD asBTT a usually becomes DT, unless pump-related complications occur such as function (bridge torecovery). In however, context, this heart of recovery a to lead may therapy LVAD circumstances, rare In DT. and BTC BTT, strategies: implanted. Basedthis onconcept, LVADs may be centre transplant bythe out ruled are transplant to indications/contraindications possibility to offer transplant opportunity tothe patient, andit would beadvisable that the of light in projected be should therapy LVAD of use the standard, gold the still is transplantation dysfunction aortic insufficiency, ascites, and cach mechanicalissues, malposition. or cannula ventri Right general wound appearance. into superficial and deep according to surgical/histolo MCS. events exchangein for potentially longer survival and better functional status can consideredbe for adverse of a risk accept to willing who are patients 4–7 INTERMACS selected carefully Furthermore, MCS. INTERMACS selected data available major complications of MCS and contribute to readmission and death. and readmission to contribute MCSand of complications major remain therapies these to secondary events bleeding and events ischaemic embolic Both thrombosis. resistance. 4–7). profiles (INTERMACS III patients NYHAclass advanced or patients IV NYHAclass dependent non-inotrope in even better were rates survival that showed studies retrospective selected from Data complications. patients categorizedINTERMACS as or1 and 2, the potential for benefit overwhelms therisksof optimalinotropes and candidates are forMC implantable for listing the patient for urgent heart transp complicated driveline infections (i.e. ascending drivel and Resistant suspected. is infection driveline when obligatory are cultures blood and swabs site Exit trials), clinical randomized Drivelinesiteexit infection is acommon complication,in 20–25% occurring of patients (data from main infections of the pump, cannula, anastomoses, po anastomoses, pump,infections of cannula, the MCS-specificinfections mayon thehardware itselfbe Adverse events andmorbidities related will develop contraindications for transplantation over time. MCS with patients some However, DT. than rather BTC as considered be primarily should MCS transplant, High pulmonary vascular resistance or transpulmonary gradient, or a recently treated cancer are cancer treated arecently or gradient, transpulmonary or resistance vascular pulmonary High Other complications include heart failure symptoms on MCS, which may be attributed to device failure, failure, device to attributed be may which MCS, on symptoms failure heart include complications Other Although INTERMACS profiles alone are insufficient to Patient selection for MCS overlaps with indications for heart transplantation. heart for indications with MCS overlaps for selection Patient Treatment withTreatment anticoagulation andantiplatelet agen In general, early referral of patients with advanc with of early patients referral In general, 104,151,224 151,222,223 230 228 Thus, with the exception of advanced age the Thus, age ofadvanced exception with In addition to INTERMACS profiles 1–2, risk factors for early mortality after MCS system MCSsystem after mortality early for risk factors 1–2, INTERMACS profiles to Inaddition A prospective, non-randomized, observationa non-randomized, A prospective, is a contraindication for LVAD, because there are still no good long-term solutions for right right for solutions long-term good no still are there because LVAD, for contraindication a is 234,235 but the majority remain superficial and can be managed by antibiotics. 232 ntation but not for MCS. On the ot On notforMCS. but ntation decision making is an important component of determining the 1–2 patients and1–2 all INTERMACSpatients 3 shouldbe considered for exia are also important considerations.

elevated bilirubin, advanced age, advanced bilirubin, elevated to mechanical circulatory support lantation if thereare no contraindications. lantation or long-term MCS. Early referral applies to to applies referral Early MCS. long-term or lantation ed heart failure to transplant and MCS centres can and MCScentres to transplant failure ed heart or the body surfacesthat cket, or the percutaneous ortunnel. cket, or driveline the ine or pump pocket infection) can be an indication indication bean can infection) pocket pump or ine implanted according to three major treatment treatment major tothree according implanted 225–227 NYHA class IV patients with poor exercise capacity capacity exercise poor with patients IV NYHA class in countries with low or declining transplant rates, rates, transplant declining or low with countries in cular dysfunction, new onset of right heart failure, failure, heart right of onset new dysfunction, cular gy, microbiology, clinicaland criteria asas well evaluate anindividual patient for MCS, on based S, as their outcomes S, astheiroutcomes are ts are mandatory to minimizethe riskts aremandatory forpump lk distance, along with a higher rate of adverse adverse of rate a higher with along distance, lk 231 233 l, propensity-adjusted study comparingLVAD

Driveline infection can be further classified further can be Driveline infection or other irreversible contraindications for contraindications irreversible or other her hand, severe right ventricular right hand,severe her 237 female presence of right gender, 229 Continuous flow Continuous devices have as may pulmonary vascular vascular pulmonary may as 224

contain them and include include containthem and significantly better than 25 However,as heart before 151

224 a device is is device a TheISHLT 233 236

This articleisprotected bycopyright.Allrightsreserved. Accepted Article transplantation or long-term MCS have failed. have MCS long-term or transplantation of-life decision making is even more challenging fo transmission). energy transcutaneous with pumps implantable (e.g.fully future the in expected are breakthroughs patient is different. Stocker Stocker is different. patient demonstrated ahalvingof stroke years rates at2 compared to HeartMatedevice.the II existswith stroke at2years),HVAD deviceespecially HeartMate3 rates, the the with has and (29% and the specialized advanced heart failure service, according to the resources of each centre. each of resources the to according service, failure heart advanced specialized the and their caregivers should beable toeasily communicate with primary care, specialist palliative care services life. of quality maximize and suffering patient reduce sufficiently may not approach) journey. the patient during appropriate whenever Optimal care of patients with advanced heart failure in failure heart advanced patients with of care Palliative artificial heart can ensure a satisfactory quality of life and acceptable adverseevent profile. biventricularneed, asne an unmet failure remain the incidence of other adverse events is events adverse of incidence other the although strokes, disabling device, and malfunctioning a or removal replacement to reoperation of rates magnetically-levitated HeartMate 3 potentially almost eliminating pump thrombosis) has reduced the of 83%). The incidenceadverse of eventswith recent that approaching rates survival mid-term 3, HeartMate of device-related morbidity, improved functional ca treated with MCS for DT. Living will and advance dire end-of life preferencesfor and goals Whenever possible, therapies. failure heart advanced for period evaluation and assessment the during ideally, caregivers, and their patients with be discussed should complications potential and MCS or transplant heart despite obvious deterioration in disease stage and ne andmaintenance, management onday-to-day focus prefer to and disease a terminal of heart as failure wellbeing comparedwithusualalone. care in patients resulted failure heart advanced in intervention care palliative interdisciplinary that showed patients, 150 of study single-centre raised important considerations for haemocompatibility. for considerations important raised be confirmed by means of an echocardiographic ramp test. may thrombosis pump of diagnosis the suspicion, clinical of case In thrombosis. pump of detection early thrombosis.In HeartWare HVAD carr of pump detection early for areuseful markers haemolysis as dehydrogenase lactate and haemoglobin regarding goals ofcare. regarding palliative care intervention enhancesprognostic lif their overestimate from heartfailure frequently Intervention inHigh-riskPatients wi complicate heart management failure heart complicate Aging, co-morbid conditions, end-or incisional length, and still require an open sternotomy if the right ventricle fails. ventricle right the if sternotomy open an require still and length, incisional theyalso have a greate need for open sternotomy, investigation of te these structured methods implantation VAD invasive 10 3( HeartMate and oftenHeartMate II,HeartWareHVAD, most arethe used MCS devices three the Currently, dramatically. changed has MCS in options potential of landscape the years, 15 last the in Thus, MCSdevices. implantable first-generation pulsatile over superiority significant have shown flowimplantabl Continuous MCS. long-term and term considerab a and vendors areseveral there Currently, Device selection ). Communication with advanced is heartfailurepatients Communication Successful palliative care must involve shared care through a multidisciplinary approach. Patients and and Patients approach. amultidisciplinary through care shared involve must care palliative Successful 151,223,234,235,239–258 258 Importantly, appropriate long-term solutions for cases of severe right heart or heart right severe of cases for solutions long-term appropriate Importantly, Thesedevices gooddurability,have shown 264

et al . 265 greater benefits in benefitsgreater quality life, anxiety,spiritual of and depression chniques is needed. Although minima needed. Although is chniques showed that the majority of patients with heart failure reject the idea gan damage, cognitive impairment, fr damage, cognitive impairment, gan th Heart Failure)th trialshowed that patients highrisk at formortality , and palliative care should addr , and palliative care should iers, routinelog-file reviewhas demonstrated itsusefulness forthe willthe overall benefit hopefully further ofpatients, outcome but similar between newer and older devices. and older newer similarbetween 263 262 The SWAP-HF (Social Worker-Aided Palliative Care Care Palliative (SocialWorker-Aided TheSWAP-HF understanding and patient–physician communication communication patient–physician and understanding The PAL-HF(Palliative CareinHeart Failure) trial, a ither biventricular support with VADs or the total total the or VADs with support biventricular ither eds over time. Common expectations pre- and post- pre-and expectations overtime. eds Common r patients with advanced heart failure when heart heartfailurewhen heart with advanced r patients ctive preferences are ctive useful e expectancy and a structured social worker-led e expectancysocial worker-led astructured and pacity in implanted patients, and in the case of technologicalimprovements (e.g.as with thefully e MCS devices of the second and third generation generation third and second the of e MCSdevices cludes palliative care at at care palliative cludes r potential for malposition, the same cumulative cumulative same the malposition, for r potential Conventional therapy (cardiologic therapeutic therapeutic (cardiologic therapy Conventional of post-transplant survival (overall 2-year survival survivalof post-transplant survival 2-year (overall le number of devices that are used for medium- for areused that devices of le number issuesshould bediscussed, especially in patients complex. In heart failure, the trajectory of each 238

237 Routine monitoring monitoring of plasma-free Routine reasonable but still relatively high rates rates high relatively still but reasonable ess each of these components. End- ess eachofthese components. lly invasive techniques avoid the avoid techniques lly invasive ailty and limited social support support social limited and ailty their end-of-life period and period end-of-life their , and patients should be 259 258 New technological Particular concern 258 Minimally 9,131,260,261 Table Table

This articleisprotected bycopyright.Allrightsreserved. Accepted Article from thetertiary hubcentre retrieveto the patient. and heartand failure. intensivedied inthe care unit.The main causes of 88% these, of and hospitalized, were died who patients the of 78% that showed patients MCS long-term The broad spectrum of heart failure network Organizational issues forpatient referral to patientthe and psychological support to family the and care team. adequately trained tocorrectlydeactivate devices an be should involved personnel care health and Nurses resources. local and feasibility, preferences, family decisions.Support can be discontinuedin thehospital, in hospice, orat home depending on patient and their convey to independently isunable patient the if committee ethics hospital or family, caregiver, patient’s the or possible, whenever the patient’s be should decision This treatment). immunosuppressive concerns should also be addressed. spiritual and Psychosocial insomnia). and constipation, anorexia, depression, anxiety, pain, symptoms, transplantation and revisited during the course of care. of course the during revisited and transplantation patient the necessary toprepare documents. A co encouraged should be available. This plan of care sh considerations resource and availability each at spoke, geographical account into taking individualized, be must protocol This failure. heart deteriorating chronic, bedeveloped availablemust and ateachtertiary hubcentre, bothfor between the transfer hospitals. inpatient two an orrequires basis outpatient an on done be can theconsultation whether agree jointly should teams andspoke hub iscentre a the Once patient referredforevaluation, ifnecessary. urgently, including ensure that spoke centres know how to communicat support circulatory mechanical or afterhearttransplantation shared care of Principles spoke centres. with experience their patient. of the management successful the is for key centres hub and spoke between communication Two-way decisions. therapeutic implementing and condition patient’s the monitoring in role key a has physician centre spoke the However, hub. tertiary the at team failure heart advanced by the guided be must care patient, in relation to his/her individual characteristics and needs. and characteristics individual his/her to relation in patient, referring for pathways regarding centres hub tertiary ( appropriate time at the and adherence toguideline-directedtherapy ensuring th managed within this ‘hub and spoke’continuum of care ( wo astrong to develop centre hub tertiary a with therapies ( identification of patients with advancedheart fail in the aid to proposed been has mnemonic A useful dialysis). peritoneal UF, (e.g. centres specialized therapiesforsymptom advanced need forthe other on need eligibility (i.e.indication) and (i.e.absence of be based must MCS, and transplantation heart for capabilities with those i.e. centre, hub tertiary failure follow-up to detect progression of symptoms and disease.The criteria for referral to an advanced heart requir and advanced stages managed by primary carephysicians and secondarycare cardiologists,to those who progress tomore Patients with MCS as DT are particularly complex. A study at the Mayo ClinicarePatientsparticularlywithend-of-lifecomplex. theMayo MCS care Aon DT as at study in An important aspect is deciding when to discontinue advanced therapies (e.g.MCS, ICD,or A protocol for the immediate management and safe transfer of unstable patients in cardiogenic shock shock cardiogenic in patients unstable of transfer safe and management immediate the for A protocol While the patient is on the waiting list for heart for list waiting the on is patient the While Each country should define the standards and organizational structures for advanced heart failure failure heart advanced for structures organizational and standards define the should country Each Ideally, secondary care centres without advanced he 260

Tertiary hub centres must provide education education provide must centres hub Tertiary Table 11 Table 266 ). Goals of palliative care include management of physical symptoms (e.g. heart failure failure (e.g. heart symptoms of physical management include care of palliative Goals 267,268 Figure 1

e specialized tertiary care.All failure heart patients regularshould undergo ). ranges from patients in ranges ea the advanced heart failurecentres: huband spoke ure and timely referral for consideration of advanced of advanced timely consideration ure and for referral 277,278 ould beforebe defined MCS implantation or heart death were multiorgan were fail death d associated alarms andto provide comfort care to rking relationship. Heartfailure patients are then transplantation, decisions regarding cardiovascular cardiovascular regarding decisions transplantation, patients,which should be made availableto every 262 contraindications) for those therapies, as well as as well as therapies, those for contraindications) 272–276 management that maybe unavailable atnon- e in an agile way (telephones, email address) address) email way e agile (telephones, in an at patientsarereferredto the centre hub tertiary

art failure therapies (spokeshould liaise centre)

mprehensive end-of life plan of care for each each care for of life plan end-of mprehensive on advanced heart failure therapies and share share and heart failure on advanced therapies Figure 2 Figure including in some cases a team dispatched dispatched team a cases some in including 260,269–271 ). Spoke centres areresponsible for rly stagesof the disease largely de novo The tertiary hub centre should hub The should centre tertiary ure, haemorrhagic stroke, stroke, haemorrhagic ure, patients and those with patients with andthose

This articleisprotected bycopyright.Allrightsreserved. Accepted Article advanced heart Inotropic agents heart advanced failure therapies. have frequentlyas intermittent beenused intravenous management th guideline-directed Once new methods. robust data are lacking from prospective, controlled trials demonstrating the clinical usefulness of these However, progression. disease of mechanisms of assessment the and stratification prognostic better criteria definitionoriginal ofadvanced forthe hear have made treatment failure ofheart clinical practice Advanced heartfailure remains amajor clinical chal Conclusion therapies. of needs the address and care shared to approach ce tertiary Highlyexperienced care asappropriate. on therapies. co-morbiditiesDepending complicatio and practitioner should also beapart general and psychiatrist, psychologist, physiotherapist, nutritionist, a Ideally, problem. surgical Fo complications. case surgical of in beincluded also patientthe and caregivers, aswellas coordinate he cardiologist and MCS device specialist, a dedicated transplant/MCS device nurse is important to educate needs complex meet the to approach interdisciplinary mo rejection therapies, other and immunosuppressive driveline exit site. the of care onproper educated regularly be should Patients encouraged. be should self-monitoring available at bedirected should attention Special distance). functi possible, If intervals. regular at obtained be the interventricular opening septum, of the aortic valve, need for device optimization, e.g. increasing or decr as mmHg.Regularechocardiographic ideally<85 and mmHg, <90 be maintained should pressure arterial Mean HVAD. the like devices some for pressure blood to related closely is stroke of risk the since important is control pressure Blood indicated. if lowered and pulsatility) low with patients in device ultrasonic a Doppler with assisted (preferably measured be should pressure Blood integrity. their ensure to be examined should components system MCS other and site, MCS,thedriveline shouldexit meticulously site be potentialinfection, thepatient’s thrombosis,andgeneralcondition. bleeding, apatient long-term with For breath, of shortness congestion, of signs pressure, blood to attention special with performed, be should markers) infection and renal, liver, anaemia, haemolysis, (e.g. assessment laboratory and examination outpatient clinic. At each appointment for patients with long-term MCS, patient history and physical ventricle, while balancing the preload provided to the right ventricle. speed of device pump the andadjustingmedicalth the setting includes which optimization, device as well as evaluation allograft cardiac of part integral tamponade, hypovolaemia, post-operative (e.g. period allows for early detectionthe ofsomepotentia of imaging, echocardiographic with along monitoring, Haemodynamic therapy. vasodilator or inotropic of monitoringis of grea haemodynamic phase, early the In cardiologists. and surgeons intensivists, among beshared should care implantation, immediate post-operative periodand long-termfollow-up. In the immediate post-transplant orpost-MCS care. shared for own pathways their develop should centre andspoke hub Each issue. this regarding beenreached hasnot consensus MCS, although and offerboth transplantation that centres within ad These MCS implantations. more long-term for need As the numbers receiving of patients Shared care with referral cardiologists and primary care physicians is needed. is physicians care primary and cardiologists referral with care Shared treatment. comprehensive require that co-morbidities and neoplasia, including complications potential other and effects, side immunosuppression vasculopathy, allograft cardiac and/or disease artery coronary Post-transplant patients shouldundergo a pre-defined regimenof graft biopsies,titration of Long-term follow-up of patients with advanced he Follow-up patientsof after heart transplantation or implantation of MCS devices consists of both Treatment and follow-up of patients patients arepost-car who of follow-up and Treatment of the team taking careof patients t importancet for both therapies,for allowing moreaccurate titration heart transplants are plateauing or declining, there is an increasing increasing an is there declining, or areplateauing transplants heart t failure.t New biomarkers and imaging tools may allow onal should testing performed(e.g.6-min be walking l adverse events that mightoccur intheimmediate easing the device speed, depending on the position of on the position devicedepending speed, the easing maintaining adequate anticoagulation status, andif r patients with MCS, driveline isinfection primarily a ntres arerequiredto providentres this multidisciplinary inspected for potential infection. The driveline, exit exit driveline, The infection. potential for inspected alth care team members.A cardiac surgeon should it necessary to develop the present update of of the update present the develop to necessary it lenge. Changes in the clinical characteristics and characteristics clinical the in Changes lenge. vanced therapies should preferably be should established therapies vanced heart failure patientsmanaged with advanced erapy is insufficient, the the insufficient, is erapy art failure therapies is ideally done through the donethrough isideally failure therapies art sessment should be performed, determining the acute right heart failure). Echocardiography is is an heart failure). Echocardiography right acute erapy to achieve optimal achieveoptimal erapy to or size of the left ventricle. Alarm history should should history Alarm ventricle. left the of size or ns, specialists other should participate inshared of these patients. In addition to the transplant addition transplant In to the patients. of these nitoring, assessment for nitoring, assessment diac transplant or MCSrecipients requires an treated with advanced heartfailure advanced with treated patient may benefit from unloading oftheleft unloading infections, transplant transplant infections, This articleisprotected bycopyright.Allrightsreserved. Accepted Article 3. 2. 1. References disclose. to interest of conflicts no have authors other The Abbott. Bayer, Roche, Vifor, Fresenius, Pfizer, Servier, Medical, Jude St. from member) committee grants from St. Jude Medical, Novartis; personal fees (lectures, advisory board meetings, steering CVRx Zoll, from support research Medtronic/Heartware; Novartis, Pfizer, Vifor, Bayer, Servier, Orion, GlaxoSmithKline; non-financial support from Abbott. J. fees board,for Amgen;personal (advisoryspeaker Madrilena. T.H.: personal f academic grant from Abbott Vascular (PCHF Course MSD; Servier, Vascular, Abbott Rovi, Novartis, from board) advisory fees, lecture grants, (travel Corvia, andS.T.: Novartis. advisorMedtronic, He to speaker/ad Novartis; and Corvia, CARMAT, Abbott, from investigator an as support research F.G.: Medtronic. and Servier, Novartis, by Bayer, sponsored steering G.F.: Technologies. Axon CHF Solutions, Pharma, AstraZeneca.M.R.C.: personal fees (consultin AstraZeneca; personal fees (consulting) fromNova AFFIRM-AHF). L.H.L.: research grants from Novartis, Boehringer Ingelheim, Vifor Pharma, and member committee (executive Vifor and Bayer, co-chairman), (RELAX-AHF Novartis from committees) MSD Servier.and M.M.: personal (consulting feeshonoraria for advisory board and clinical trial executive personal (travel fees lecture fees grants, andadviso Conflict ofinterest: contributions to the manuscript. bythe Sciences),supported Health PharmD Stough, Gattis Wendy acknowledge The authors (KFO 311)‘(Pre-)terminal heart and lung failur Deutsche Fo by the was supported Johann Bauersachs Acknowledgements Table S1. Additional Supporting Information may be foun Supplementary Information vulnerable patientpopulation. treatment algorithms to prolong life, increaselife qual is basedon reliable prospective and ther studies, Fi progressesto end-of-life. patient ineligible for advanced failure heart therapies or treatment in patients with advanced heart failure. Lastly, palliative care is indicated when patients are medical to alternative valid a and them make indications their broaden will MCSdevices of characteristics the in improvement Recent DT. as or BTT a as used be MCScan Long-term immunosuppression. quality of life, butit is limited by organavai of choice thetreatment is considered transplantation Heart shock. cardiogenic of treatment immediate the for available devices are four least At MCS devices. with made been has progress Impressive conditions. unstable in orstabilization treatment symptomatic only provide agents these Thus, mortality. increased with association an shown have studies infusions, nodefinitivebut outcom

Fang JC, Ewald GA, Allen LA, Butler J, Westlake Canary CA, Colvin-Adams M, Dickinson MG, Levy P, Stough WG, WG, Stough P, Levy MG, Dickinson M, Colvin-Adams CA, Canary Westlake J, Butler LA, Allen GA, Ewald JC, Fang trials. in clinical used criteria of review a systematic failure: heart advanced Defining AP. Kalogeropoulos J, Butler VV, KK,Georgiopoulou Alton JB, Bjork community. inthe stages failure heart of prognosis and correlates, neurohormonal Prevalence, RS. Vasan GF, Mitchell TJ, S,Wang Cheng EJ, Benjamin J, Aragam D, JL, Levy Januzzi KC, Wollert MG, Larson DM, V, Enserro Xanthakis Ultrafiltration clinical trials: overview of study designs and key findings. keyfindings. and designs study of overview trials: clinical Ultrafiltration

JACC Heart Fail

M.G.C.L.: Research support from Novartis, Vifor Pharma, and FEDER Funds; Funds; FEDER and Pharma, Vifor Novartis, from support Research M.G.C.L.: ees (lecture) from Novaris, Boehringer Novaris,Boehringer from ees (lecture) 2016; 4 :808–815. nally, it isnally,note important it thatno to therapyadvancedfailure in heart e datafromprospective, randomized trials areavailable some and Heart Failure Association of the Eu J CardFail e: Unloading and repair’ (DFG;TP1, BA 1742/9-1). 2016; d in the online version of this article: article: this of version online d in the CVRx, Abiomed, Abbott/St. Abiomed, CVRx, after advanced therapiesperformed and have been 22 ry boards) from Novartis, Abbott Vascular, Astellas, Astellas, Vascular, Abbott Novartis, from ry boards) visor for Abbott, CARMAT, ORION Pharma, Bayer, Bayer, Pharma, ORION CARMAT, Abbott, for visor of ESC); the research grant from Fundacion Mutua bureau)from Medtronic, Bayer, Actelion, Novartis, e is an urgent need to develop evidence-based needtodevelopevidence-based urgent is an e rschungsgemeinschaft, Clinical Research Group 311 311 Group Research Clinical rschungsgemeinschaft, lability, graft dysfunction, and side effects of effects side and dysfunction, graft lability, ity,the reduceburden and ofhospitalizationinthis artWare,CorWave, E.B.C.: and3R.personal fees Zoll, AstraZeneca, Sanofi, Novartis, Amgen, BMS, BMS, Amgen, Novartis, Sanofi, AstraZeneca, Zoll, rtis, Merck, Boehringer Merck, rtis, Boehringer :569–577. g) from Respicardia (study principal investigator), investigator), principal (study Respicardia from g) for eligible patientseligible survival withand for excellent committee forclinical member trials/registries , Bayer, Vifor,Abiomed, Medtronic. F.R.: research B.: honoraria for lectures and/or consulting from consulting and/or lectures for honoraria B.: (Campbell University College of Pharmacy and Ingelheim. S.N.:investigator research ropean Society of Cardiology for for Cardiology of Society ropean JudeMedical/Thoratec, Ingelheim, Sanofi, Vifor Vifor Sanofi, Ingelheim,

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. 19. 18. 17. 16. 15. 14.

SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). Trial). Failure in Heart Death Cardiac (Sudden SCD-HeFT in the outcomes to relationship interrogation: cardioverter-defibrillator implantable on found tachycardia ventricular nonsustained Rapid-rate JE. Poole GH, Bardy KL, Lee DB, Mark J, Anderson AS, Hellkamp G, J,Johnson Chen therapeutic approaches. and outcomes, epidemiology, shocks: cardioverter-defibrillator Implantable FA. Masoudi PD, Varosy RT, Borne assessment. efficacy and design trial in clinical advances failure: heart chronic for products medicinal New P. Graeff De C, Boulton F, Zannad B, Tyl K, Swedberg WG, Pfeffer MA, Pocock SJ, Ponikowski P, Prasad K, Richard-LordereauI, Roessig L, Rosano GM, Sherman W, Stough S, Perez Figueroa M, Metra JJ, McMurray FI, AR, Malik Lyon J, Lopez-Sendon M, Lefkowitz I, Laws D, Lautsch Cronin M, Doevendans PA, El-GazayerlyA, Gimpelewicz C, Honarpour N, Janmohamed S, Janssen H, AM,Kim K, Slot Bruins M, Borentain DM, A,Bloomfield Baczynska SD, Anker ML, Garcia Alonso GS, Filippatos MR, Cowie Cardiol America. of Society Failure Heart the and Guidelines Practice Clinical on Force Task Association Heart Cardiology/American of College American the of report a failure: heart of management the for Guideline ACCF/AHA ACC/AHA/HFSA Focused update on new pharmacological therapy for heart failure: an update of the 2013 MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2016 Givertz GC, G,Fonarow Filippatos MH, Drazner MM, Colvin DE Jr, Casey J, B, Butler Bozkurt M, CW,Jessup Yancy ESC. ofthe (HFA) Association Failure the Heart of contribution thespecial with Developed (ESC). ofCardiology Society theEuropean of failure heart chronic and acute of treatment and diagnosis for the Force Task The failure: heart RuschitzkaRutten F, FH, van der MeerP.2016 ESCGuidelines forthe diagnosis and treatmentof acute and chronic LM, Ruilope GM, Rosano JP, B,Riley Pieske JT, P, Parissis C, Nihoyannopoulos Linde JessupM, EA, Jankowska VP, Harjola JR, V,Gonzalez-Juanatey AJ, Falk Coats JG, Cleland H, Bueno SD, Anker AA, Voors P, Ponikowski 2009; Kirklin JK.INTERMACS profilesof advanced heart failure: the current picture. P, Desvigne-Nickens K, Ulisney DC, Naftel RL, Kormos L, M,Miller Jessup JB, Young Pagani FD, LW, Stevenson for durable devices for circulatory support: first annual report. report. annual first support: circulatory for devices for durable database JB.INTERMACS K, Young Ulisney MA, Miller FD, Pagani RL, Kormos LW, Stevenson DC, Naftel JK, Kirklin guidelines. onpractice Force Task Association Heart Foundation/American of Cardiology of College a report the American summary: executive ofheart failure: management the for guideline ACCF/AHA 2013 BL. Wilkoff EJ, Tsai TangWH, LW, Stevenson Sam F, B, Riegel PN, Peterson JE, Mitchell JJ, McMurray PE, McBride FA, Masoudi WC, Levy EK, Kasper MR, Johnson JL, T,Januzzi Horwich SA, Geraci GC, Fonarow MH, Drazner DE Jr, Casey J, B,Butler Bozkurt M, Jessup CW, Yancy with the International Society for Heart and Lung Transplantation. Transplantation. Lung and Heart for Society International the with in collaboration developed Guidelines Practice Force on Task Association Heart Foundation/American Cardiology 2005Guidelines forthe diagnosis and managementofheart failurein adults: areportof the American College of ACC/AHA the into incorporated update Focused 2009 CW. LW, Yancy Stevenson MA, Silver PS, Rahko JA, Oates K, Michl DM, Mancini MA, M,Konstam Jessup TG, Ganiats GS, Francis AM, Feldman MH, WT,Chin Abraham SA, Hunt Eur J Heart Fail Heart J Eur Cardiology. of Society theEuropean of Association Failure ofthe Heart Failure Heart onAdvanced Group Study the from statement a position failure: heart chronic Advanced M. Komajda D, Brutsaert H, S, Dargie Anker Bohm M, P, Mohacsi A, T,Pitsis AG, Jaarsma CH,Fraser Bergh A, JJ, Gavazzi K, McMurray Dickstein P, Ponikowski M, Metra Adult Heart Transplantation Report–2017; Focus Theme: Allograft ischemic time. time. ischemic Allograft Theme: Focus Report–2017; Transplantation Heart Adult Thirty-fourth LungTransplantation: and Heart for Society oftheInternational Registry The J. Stehlik RD, Yusen DC, Chambers JW, Rossano B, Meiser BJ, Levvey AY, Kucheryavaya S, Goldfarb WS, Cherikh KK, Khush Lund LH, assist devicesand the kidney. ventricular Left KD. Jhaveri M, Merzkani HA, Fernandez S, Jauhar DT, Majure R, Wanchoo GR, Stevens DW, Ross support. with in patients function inend-organ Changes K. Takeda Y, P,Naka Kurlansky J, Han VK, Topkara AR, Garan M, Yuzefpolskaya PC, Colombo H, Takayama D, Yoshioka (ESC). Cardiology of Society European the of (HFA) Association Failure Heart ofthe Committee Failure Heart Acute the of behalf on review A management. and todiagnosis pathophysiology from failure: heart in acute failure and injury dysfunction, Organ A. Mebazaa MB, Yilmaz H, Skouri PM, Seferovic A, F, Schafer Ruschitzka A, Rudiger E, Platz J, Z, Parissis C, Papp J, Mueller M, Masip J,Legrand Lassus M, V, Lainscak AJ, Fuhrmann Flammer GS, Filippatos W, Doehner SP, Collins O, Chioncel HP, Rocca J,Brunner-La Bauersachs M, Banaszewski W, Mullens VP, Harjola failure. in heart ofco-morbidities significance and association the Reframing G. Filippatos J, Butler J, Skoularigis H, Boudoulas RC, Starling J, Parissis G, Giamouzis F, Triposkiadis Card Fail Card Committee. Guidelines America of Society Failure Heart the from astatement failure: heart D) (stage Advanced MM. Givertz AR, JG, Vest Rogers JE, S,Rodgers Moore SD, Katz RE, Hershberger AF, DL, Hernandez Dries MC, Chan PE, Carson MR, Bonnell Walsh MN, MW, Rich R, Krishnamani NM, Albert DJ, Whellan JR, NK,Teerlink Sweitzer defibrillator patients. patients. defibrillator cardioverter implantable in survival predict shocks inappropriate not but therapy Appropriate F. Hintringer F, Duru LM, Haegeli O, Pachinger A, Strasak K, Spuller Berger T, M, S,Stuhlinger U,Brullmann T,Paoli Wolber W, Dichtl Eur J Heart Fail 28 2016; Eur JHeart Fail :535–541. 2015; Ann Thorac Surg Ann Thorac 68 2007; 21 :1476–1488. :519–534. 2016; Clin Cardiol Clin 9 2017; :684–694. JAMA Intern Med 2017; 18 19 Circulation :891–975. Clin J Am Soc Nephrol J Clin Am Soc :821–836. 103 2011; :717–724. 34 2013; 2013; :433–436. 128 173 :1810–1852. :859–865. 2018; EurHeart J Fail J Am CollCardiol 13 prolonged continuous-flow left ventricular assist device device assist leftventricular continuous-flow prolonged :348–355. J Heart Lung Transplant Lung J Heart Eur J Heart Fail Heart J Eur J Am Coll Cardiol Coll Am J 2017; 2013; 19 61 2016; :718–727. 2009; :2161–2168. 2008; 18 J Heart Lung Transplant Lung J Heart J Heart Lung Transplant Lung Heart J 53 :744–758. :e1–e90. 27 :1065–1072. J Am Coll J Am J

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 30. 31. 29. 28. 27. 26. 25. 24. 23. 22. 42. 41. 40. 21. 39. 37. 36. 35. 38. 20. 34. 33. 32.

CB. Predictors of mortality and morbidity in patients with chronic heart failure. failure. heart chronic with inpatients morbidity and mortality of CB. Predictors KS, Granger Pieper EL, Michelson J, Ostergren KB, Swedberg JJ, S, McMurray Yusuf MA, Pfeffer D, SJ, Wang Pocock Stevenson LW, Davis RB. Model building as an educational hobby. hobby. educational asan building RB. Model Davis LW, Stevenson Risk prediction in patientswith heart failure: a systematicreview and analysis. S. MacMahon J, A, McMurray Patel M, J,Woodward Dwight J, Basu TM, N, Williams D, Conrad Bennett K, Rahimi mortality and/or heart failure hospitalization in patients with heart failure. failure. heart with inpatients hospitalization failure heart and/or mortality predicting for ofmodels power the predictive influencing Factors AH. Zwinderman AA, Voors W, Ouwerkerk (VERITAS). Studies failure heart inAcute Tezosentan with Inhibition Receptor Endothelin of Value the of An analysis information? prognostic useful add it failure–does heart with in patients admission after shortly peptides natriuretic and troponin of Measurement JJ. McMurray DJ, Veldhuisen G,van Torre-Amione CM, O’Connor H, G, Krum Jondeau JD, RC, Parker G, Bourge Cotter O, S, Milo M,Senger A, Metra Shoaib Davison BA, JR, Teerlink JG, Cleland listing criteria for heart transplantation: a 10-year update. update. a 10-year transplantation: heart for criteria listing Transplantation Lung Heart for Society International 2016 The Council. Transplantation and Failure Heart (ISHLT) Transplantation (ISHLT) Pediatric Transplantation Council; International Society for HeartLung Transplantation Lung Heart for Society International Council; Diseases Infectious (ISHLT) Transplantation Lung Heart for Society International A; Zuckermann EA, Verschuuren DO, Taylor HJ, Ross L, LH, Potena Lund SS, Kushwaha KirkR, JK, L, Kirklin Danziger-Isakov DA, Baran PA, Uber MJ, Semigran MM, CE, Hannan Canter MR, Mehra LungTransplant Heart J utility. clinical and accuracy topredictive journey a failure: heart in biomarkers and scores Risk J. Stehlik LH, Lund 2018; Greene SJ, Mentz RJ, Felker GM. Outpatient worsening (PARADIGM-HF). Trial Failure Heart in Morbidity and Mortality Global on Impact Determine to ACEI With ARNI of Comparison Prospective the from evidence setting: outpatient in the treated failure heart of worsening ofclinical Importance JJ. McMurray M, Packer SD, Solomon MR, K, Zile Swedberg VC, Shi JL, Rouleau AR, Rizkala MP, Lefkowitz J, Gong PS, Jhund N, Okumura fraction: findings from the Swedish Heart Failure Registry. Registry. Failure Heart Swedish from the findings fraction: ejection reduced and failure heart with in patients rhythm sinus and fibrillation atrial in of beta-blockers use and rate heart resting of significance Prognostic M. M,Fu Petzold M, Adiels U, Dahlstrom LH, Lund U, Sartipy SJ, Li meta-analysis. patient individual MAGGIC the from results fraction: ejection preserved or reduced with failure heart with in patients pressure ofpulse value prognostic Differing JJ. McMurray RN, Doughty SJ, Pocock G, Whalley N, Earle KK, Poppe CA, Ariti J, Dobson C, Tribouilloy A, Bayes-Genis AM, B,Richards Andersson K, Swedberg IB, L,Squire AP, Kober D, Maggioni Castagno CE, Jackson dysfunction. dysfunction. ventricular left with patients in pressure arterial mean and pressure pulse determined sphygmomanometrically by provided information prognostic Independent MA. Pfeffer B, Pitt DV, Exner JE, Norman GF, Mitchell MJ, Domanski 842. trial: MADIT-CRT. MADIT-CRT. trial: clinical failure heart in a event failure heart outpatient and inpatient offirst therapy to response and Prognosis SD. Solomon MA, AJ, Pfeffer Moss S, E, McNitt Lichstein M, R, Kukin Krone M, R,Haigney EM,Goldstein Dwyer H, Skali value of long-term blood pressure changes in patients with chronic heart failure. failure. heart chronic with in patients changes pressure blood long-term of value F. Prognostic Enseleit F, TF,Ruschitzka Luscher GM, Frohlich R, Huang B, Seifert P, O, Keller Schlager FA, Schmid theCooperative North Scandinavian Enalapril Survival Study (CONSENSUS). of Results failure. heart congestive in severe mortality on ofenalapril Effects Group. Study Trial CONSENSUS The patientswith reducedleft ventricular ejection fractions. in asymptomatic failure heart of development the and mortality on ofenalapril Effect Investigators. SOLVD The heart failure. and congestive fractions ejection ventricular left reduced with in patients survival on ofenalapril Effect Investigators. SOLVD The 2011; failure. failure. Lee TT,Chen J, CohenDJ, Tsao L. The associationbetween bloodpressure and mortalityin patients withheart heart failure shifted from the hospital to the emergency department and outpatient clinics? clinics? andoutpatient department emergency the to hospital the from shifted failure heart of diagnosis incident has the care: failure inheart Trends FA. H, McAlister JA,Quan P, Bakal Kaul JA, Ezekowitz resychronization therapy. therapy. resychronization cardiac for implications fraction: ejection reduced with heart in failure survival and QRS duration, class, functional U, Association Lund LH. New Heart York Dahlstrom M, C,F, Linde L,Stahlberg Braunschweig Benson fraction. ejection left ventricular reduced and failure heart worsening with hospitalized in patients duration QRS of implications Clinical M. C, Gheorghiade Orlandi C, B,Zimmer Traver T, Cook JE, Udelson K, Swedberg L, Grinfeld Jr, JC Burnett HB, Krasa F, Zannad MA, Konstam AP, Maggioni NC, Wang 2017; 2013; fraction. ejection preserved and withreduced failure in heart prolongation QRS of significance prognostic and correlates, Prevalence, U. Alehagen C, Linde U, Dahlstrom L, Benson M, Edner J, Jurga LH, Lund therapy. resynchronization cardiac after than men prognosis term long- better have Women LH. C,Lund Linde J, Hornsten M, Stahlberg F, Braunschweig F, Gadler S, Zabarovskaja 3 13 36 34 :252–259. Am Heart J Heart Am :142–147. :1037–1046. :529–539. Eur JHeart Fail J Am CollJ Am Cardiol Eur J Heart Fail JHeart Eur 2006; 2016; 151 Eur J Heart Fail 2017; N Engl JMed :76–83. 1999; 35 :711–713. 2014; 19 Circulation 33 :739–747. :951–958. 16 2017; 1991; :560–565. 2016; 19 325 :366–376. Eur Heart J :293–302. 133 heart failure as a target for therapy: a review. areview. therapy: for target asa failure heart N Engl J MedN Engl :2254–2262. Circ Heart Fail J Heart Lung Transplant Transplant Lung Heart J 2015; Europace Circ Heart Fail Heart Circ 1992; 36 JAMA :1106–1114. 2015; JACC Heart Fail Heart JACC 2008; 327 2012; N Engl J Med J N Engl Eur Heart J Heart Eur JACC Heart Heart Fail JACC 8 :685–691. 2016; :871–879. 299 14 2016; Eur J Heart Fail J Heart Eur :1148–1155. :2656–2666. 9 :e003457. 35 2014; 1987; 2006; :1–23. 2014; 2 316 27 :429–436. Eur J Heart Fail JHeart Eur :65–75. 2017; :1429–1435. 2 :440–446. JAMA Eur Heart J Eur Heart 19

Cardiol :837–

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 65. 64. 62. 61. 63. 60. 54. 53. 52. 51. 46. 59. 50. 47. 49. 48. 45. 44. 56. 58. 66. 43. 57. 55.

2250. potential adjunct for risk stratification in patients with stable congestive heart failure. failure. heart congestive stable with in patients stratification risk for adjunct potential Bauter S, J,Susen B, Dagorn Hennache F, Mouquet N, Lamblin failure. heart chronic with of patients prognosis short-term predict to levels plasma endothelin big and testing exercise cardiopulmonary of Value R. Pacher G, Maurer W, Woloszczuk Hulsmann M,Stanek B, Frey B, phenotypes. failure Sturm ofheart spectrum in a hormones B, cardiovascular Adaptive LH. Lund L, A, Mellbin Gabrielsen E, JC, Donal C,Daubert C, Linde Hage S, Zabarovskaja Putz D, Kos T, Berger R, Woloszczuk W, Putz D, Kos T, Berger R, Cardiol Cardiol failure. heart withcongestive in patients and mortality for factors morbidity risk independent are failure heart for treatment optimized after interleukin-6 and peptide natriuretic brain plasma of levels High M. Kinoshita T, Matsumoto M, M, Sawaki M, Fujii Ohnishi Tsutsui T, T, Wada N, M, A, Hayashi K, Mabuchi Maeda Tsutamoto (Val-HeFT). (Val-HeFT). Trial Failure Heart Valsartan inthe morbidity and mortality and time over norepinephrine and peptide natriuretic in brain Changes JN. Cohn G, Tognoni RD, Glazer AP, Maggioni S, R, Masson YT,Latini Chiang LD, Fisher IS, Anand events in patients with heart failure: systematic review. review. systematic failure: heart with in patients events Doust JA, PietrzakE, Dobson A, GlasziouP. well How doesB-type natriuretic peptide predict death and cardiac cardiomyopathy are predictive of adverse outcomes. outcomes. adverse of are predictive cardiomyopathy dilated idiopathic with inpatients t troponin cardiac of concentrations serum increased Persistently Y. Takatsu Sato Y, Yamada257. T, Taniguchiin ambulatory patients with chronic heart failure: theimportance of change over time. R, measurements biomarker Serial AS. Jaffe Jr, JC Burnett RJ, Rodeheffer DE, Grill MF, Burritt KA, Hartman Nagai WL, Miller K, Makiyamaenzymeinhibition in patientswith severe chronic heart failure. T, converting- by itsmodification and concentration of sodium serum importance M. Prognostic Okada Lee WH,Packer H, Kataoka device transplantation. and post-heart K, assist ventricular post-left failure, in heart Copeptin Ito LH. Lund L, A, Mellbin Gabrielsen C, S,Hage Zabarovskaja H,Matsumori A,Sasayama S, Kingdom heart failure evaluation and assessment of risk trial (UK-heart). (UK-heart). trial ofrisk assessment and evaluation failure heart Kingdom JM, Fox KA.Prospective study of heartrate variability and mortalityin chronic heart failure: results of the United RJ, Neilson A, Cowley Prescott AD, Flapan M, Baig W, P, Mullen SJ, Brooksby R,Lindsay Andrews PD, Nolan J, Batin failure. failure. heart congestive stable with inpatients stratification risk for information independent provide consumption oxygen de Groote P, Dagorn J, Soudan B, Lamblin N, McFadden E, third heart sound in patients with heart failure. failure. heart with in sound patients heart third Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. cardiomyopathy. dilated idiopathic or ischemic to secondary failure heart congestive of inchronic death predictor an independent as rate variability heart Depressed AJ. Coats K, W, Wrabec M, R, Piepoli Szelemej TP, Chua SD, Anker P, Ponikowski Stevenson LW. Design of therapy for advanced heart failure. failure. heart foradvanced therapy of Design LW. Stevenson 2003; failure. heart with admitted in patients outcomes predict that profiles hemodynamic identifies assessment Clinical LW. Stevenson GH, Mudge JA, Jarcho EF, Lewis JC, SW, Fang Tsang A, Nohria dynamics. rate heart of indices conventional and nonlinear for deriving methods automated of fully byuse subjects control and Ho KK, Moody GB,Peng CK, Mietus JE, Larson MG,Levy D, GoldbergerAL. Predicting survivalin heart failurecase trial. controlled randomised a of analysis subgroup a (BEAUTIFUL): dysfunction systolic left-ventricular and disease artery coronary with patients in factor risk as a prognostic rate R. Heart M, Ferrari Robertson M, Tendera I, K,Ford PG, Steg Fox role for risk stratification in acutely decompensated heart failure. failure. heart decompensated in acutely stratification risk for role complementary peptide: natriuretic pro-B-type andN-terminal T- troponin high-sensitivity ST2, Soluble Januzzi JL. M, Valdes F, Pastor-Perez JC, Bonaque IP, Garrido T, Casas M, Boronat S, Manzano-Fernandez DA, Pascual-Figal 2003; hospital mortality in acute decompensated heart failure. failure. heart decompensated in acute mortality hospital in- and levels peptide natriuretic B-type Admission M. Lopatin MM, Givertz CO, WF,Phillips Peacock GC, Fonarow acute congestive heart failure. failure. heart congestive acute in mortality long-term and Inflammation AP. Perruchoud HP, Rocca A, Brunner-La K,Christ C, Laule-Kilian Mueller Fail meta-analysis. MAGGIC the from Results fibrillation? atrial concomitant and failure heart chronic with patients in marker risk a rate Isheart JJ. McMurray GA, Whalley GD, Gamble FA, McAlister MC, Petrie M, Komajda JA, Ezekowitz B, Andersson M, Richards I, Squire N, Earle KK, Poppe RN, Doughty D, Castagno J, Simpson high-risk patientidentification. for monitoring T troponin cardiac value of failure: heart severe in stable injury myocardial Ongoing A. Barbagelata M, R, Brizuela Obregon EH, AE, Garcia Pitzus JR, Cialzeta JL, Stival N, Augier JP, Canella SM, Macin ER, Perna failure. heart in advanced rates mortality increased and dysfunction, ventricular left progressive hemodynamics, impaired with associated Iis troponin Cardiac GC. WR, Fonarow J,MacLellan TB,Patel Horwich 2015; 41 108 2000; J Am Coll Cardiol J Am Coll :1797–1804. 17 :833–838. Circulation :1182–1191. 36 Circulation Lancet :1587–1593. 2008; 2003; 2004; 1997; 372 107 Am Heart J Heart Am 43 Circulation 96 :817–821. :1278–1283. :1584–1589. :842–848. Heart Lung Circ Lung Heart 2004; 2006; N Engl JMed N 110 151 :2376–2382. :845–850. Circulation Int J Cardiol Int J 2017; BMJ J Cardiol Coll Am J Adamopoulos S, Webb-Peploe K, HarringtonD, Banasiak Bauters C. B-type natriuretic peptide and peak exercise peak exercise and peptide natriuretic C. B-type Bauters 2005; 2001; 26 Eur J Heart Fail Heart J Eur sC, de Groote P. High-sensitivityC-reactive protein: Circulation 2001; :143–149. 2015; Eur J Fail Heart J Am Coll Cardiol J Am Coll 330 345 103 :625. :574–581. 189 Am J Cardiol J Am 2007; 1986; Circulation :369–374. :6–11. :6–11. 2005; 49 73 2011; :1943–1950. 7 :257–267. 1998; 1998; :323–331. 1997; 13 Eur Heart J Heart Eur Circulation :718–725. 32 98 79 :1695–1700. :1510–1516. :1645–1650. J Am Coll Cardiol Coll J Am 2007; 2005; Eur JHeart Circulation 116 26 J AmColl :2245– :249–

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 88. 87. 86. 84. 83. 82. 85. 81. 76. 78. 77. 80. 75. 73. 70. 79. 74. 72. 71. 69. 68. 67.

for optimal timing of cardiac transplantationin ambulatory patientswith heart failure. consumption oxygen exercise peak of Value JR. Wilson Jr, LH R,Edmunds Mull W, Kussmaul H, Eisen DM, Mancini rate variability in patients with chronic heart failure: a prospective study. study. a prospective failure: heart chronic with inpatients variability rate heart and imaging metaiodobenzylguanidine iodine-123 cardiac of value prognostic the of Comparison Hoki N. M, YamadaT, Shimonagata T,Fukunami M,Kumagai K, Ogita H, HirataA, Asai M, MakinoN, Kioka H, Kusuoka H, Hori prognosis. and uptake oxygen peak with relationship failure: heart chronic moderate with in patients uptake metaiodobenzylguanidine Cardiac P. Merlet R, G, Gourgon Dreyfus C, Dubois F, Pessione D, Logeart Y, Esanu A, Cohen-Solal Fail Heart J Eur patients in gradient pressure pulmonary diastolic negative the of implications andprognostic Determinants A. Manouras LH, B,Lund Merkely A, Venkateshvaran AI, Nagy Heart Fail study. follow-up 4-year a failure: heart systolic severe with in patients outcome adverse predicts reserve contractile Multidimensional J. Lekakis G, Makavos V, Stasinos J, Parissis P, Simitsis I, Ikonomidis IA, Paraskevaidis 2015 ESC/ERS guidelines and insights for future changes. changes. future for insights and guidelines 2015 ESC/ERS the of classification thehaemodynamic to according survival of analysis disease: left heart to due hypertension Palazzini M, Dardi F, Manes A, Bacchi Reggiani ML, Gotti E, RinaldiA, Albini A, Monti E, Galie N. Pulmonary 2017; review. asystematic failure: heart chronic and acute in ultrasound lung by congestion pulmonary of value prognostic and changes Dynamic JJ. R, McMurray Campbell A, Vazir PS, AA, Jhund Merz E, Platz 1997; right ventricular ejection fractions onlong-term survivalin idiopathic dilated cardiomyopathy. and left both of value predictive Additional F. Cherrier N, Danchin A, Grentzinger L, G, Feldmann Barbier Y, Juilliere failure. failure. diastolic filling with optimized oral therapy predicts a more favorable prognosisin patients with chronic heart left ventricular restrictive Reversible P. F,Giannuzzi Scapellato E, A, Bosimini Imparato U, Corra PL, Temporelli in heart failure: evidence from the CHARM programme. programme. CHARM the from evidence failure: in heart hypertrophy left ventricular electrocardiographic of implications andprognostic Prevalence FG. Dunn EL, Michelson J, Ostergren SJ, S,Pocock CB, Yusuf K, Granger Swedberg MA, Pfeffer JJ, McMurray Wang D, NM, Hawkins chronic heart failure. with inpatients pressure artery pulmonary and function systolic ventricular ofright value prognostic and additive Independent L. F, Tavazzi E, Recusani Arbustini R, Sebastiani C, Klersy C, C, Inserra Campana A, S, Gavazzi Ghio and prognostic implications. Heart Muscle Disease Study Group. Group. Study Disease Heart Muscle implications. and prognostic correlations hemodynamic and echocardiographic clinical, echocardiography: Doppler by assessed cardiomyopathy indilated pattern filling ventricular left Restrictive F. Camerini G, Sinagra A, Di Lenarda B, Pinamonti patients. failure heart of spectrum inbroad a outcomes oncardiovascular fraction ejection of Influence MA. Pfeffer S, Swedberg JJ, McMurray H, Skali N, Anavekar SD, Solomon patients with chronic heart failure. of stratification risk for levels A, G. Triiodothyronine L’Abbate A, Iervasi Ripoli MC, Taddei P, A, Landi Pingitore of left atrial volume in patients with dilated cardiomyopathy. cardiomyopathy. dilated with inpatients volume leftatrial of value prognostic and M. Determinants Enriquez-Sarano P, Zardini G, Golia R, Sandrini L, Zanolla M, Cicoira A, Rossi (Val-HeFT) echocardiographicdata. Trial Failure Heart Valsartan failure: in heart therapy to response and outcomes defines remodeling ventricular Wong M, Staszewsky L, Latini R, Barlera S, GlazerR,Aknay N, Hester A, AnandI,Cohn JN.Severityleft of Cardiol Dysfunction. Ventricular Left of Studies hypertrophy. ventricular left of significance trials: and registry in SOLVD the enrolled dysfunction ventricular left with in patients outcome ofclinical predictors Echocardiographic DH. Weiner BJ, Shelton DM, Shindler MC, Limacher C, Koilpillai HA, Kopelen BH, Greenberg MA, Quinones 2009; importance. prognostic and prevalence failure: heart in chronic Albuminuria JJ. McMurray S, Yusuf MA, Pfeffer K, Swedberg CB, Granger EL, B,Michelson S, Olofsson Zetterstrand HC, Gerstein SD, Solomon CE, Jackson staging. andhemodynamic functional, inmetabolic, and application validation failure: heart inchronic and survival acid Uric AJ. Coats P, R, Ponikowski F, Hetzer Leyva KJ, Osterziel R, Segal W, Kemp Shamim M, M, CH,Cicoira C, Davos D,Knosalla R, Francis M,Sharma W, Rauchhaus SD, Doehner Anker 2017; peptides. natriuretic cardiac with comparison failure: heart systolic for decompensation following pro-adrenomedullin midregional of potential F.Prognostic Heart Network Competence the INHS, Group CE, Angermann Ertl G, JO, S, Vollert Stork C, S, Feldmann Brenner G, Guder M, A,Kaspar C,Marx Morbach heart failure treated with angiotensin-converting enzyme inhibitors. inhibitors. enzyme angiotensin-converting with treated failure heart with chronic in patients survival and cytokines to inflammatory rate sedimentation erythrocyte the of relationship SD. The AJ,Anker DL, Coats Mann PA, S, Poole-Wilson Varney PP, Ponikowski M, R,Rauchhaus Sharma failure and left ventricular systolic dysfunction. dysfunction. systolic ventricular left and failure heart with in patients parameters tolerance with exercise compared information incremental and independent provides volume atrial Left C. Vassanelli L, Franceschini L, Zanolla G, Golia S, Bonapace M, Cicoira A, Rossi 19 18 374 19 2000; J Am Coll Cardiol J Am Coll :1154–1163. :276–280. :1166–1175. Circulation 2017; :543–550. 35 2017; 19 :1237–1244. :846–861. 2005; J AmCollCardiol 19 J Am J Am Coll Cardiol 1998; :88–97. 112 :3738–3744. 31 :1591–1597. Am J Am Med J Am Coll Cardiol J Am Coll 2001; 1999; 2005; 37 33 Heart :183–188. :759–766. 118 2004; 2007; :132–136. Heart Eur J Heart Fail Heart J Eur with pulmonary hypertension due to left heart disease. toleft due heart hypertension disease. with pulmonary 43 93 K, Yusuf S, Granger CB, Michelson EL, Wang D, Pocock Pocock D, EL, Wang Michelson CB, Granger S, K, Yusuf J Cardiol Am Coll 2007; :2022–2027. :1420–1425. J Am CollJ Am Cardiol 93 J Am J Am Coll Cardiol :59–64. 2018; J Am Coll Cardiol AmColl J 2002; Circulation 20 1993; :248–255. 40 2000; :1425. 22 2003; Circulation 2003; :808–815. 36 :523–528. 107 41 Eur J Heart Fail :1991–1997. Eur J Heart Fail :231–238. 1991; Eur Heart J Eur Heart J Am Coll J Am 83 Lancet :778– Eur J J Eur

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 96. 100. 97. 95. 99. 98. 94. 93. 92. 91. 90. 107. 106. 89. 104. 101. 108. 105. 103. 109. 102. 110.

prevalence, intervention effects, and associations with clinical outcomes. of review a meta-analytic failure heart in Depression PJ. BH,Mills Greenberg SE, Linke VA, Reis T, Rutledge patientswith congestive heart failure. in rehospitalization and ofmortality risk increased to of depression Relationship CM. O’Connor RR, Krishnan RM, Califf C, Davenport MA, Blazing MS, Cuffe LH, Gaulden M, E, Kuchibhatla Christopher J, Jiang W, Alexander heart failure. failure. heart systolic with patients in survival predict levels Albumin GC. Fonarow RW, MacLellan K, Kalantar-Zadeh TB, Horwich systematic review. review. systematic a failure: heart in advanced PJ.Frailty Newton PS, Macdonald PM, Davidson HannuM, LD, Hickman HS, SR,Ha Jha 2007; failure. heart with patients in mortality long-term and symptoms depressive between Relationship CM. O’Connor RR, Krishnan RM, Califf JD, Alexander EJ, Christopher MS, Cuffe GL, Clary M, Kuchibhatla Jiang W, Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program. program. (CHARM) Morbidity and in Mortality Reduction of Assessment Failure: in Heart Candesartan the from data failure: heart chronic with in patients and outcome abnormalities function Liver CB. Granger EL, Michelson S, Yusuf D, K, Wang Swedberg MA, Pfeffer JJ, S, McMurray Pocock GM, Felker LA, Allen [SOLVD]). Dysfunction LeftVentricular Of Studies ofthe analysis (an dysfunction systolic left ventricular and nonischemic ischemic with in patients mortality and count cell blood White MJ. Domanski MA, Waclawiw DV, Exner HA, Cooper Databank. Duke the and Program CHARM the from data failure: heart in marker prognostic novel as a width distribution cell Red CB. Granger EL, Michelson S, D, Yusuf K,Wang Swedberg MA, Pfeffer JJ, McMurray LK, Shaw SJ, Pocock Allen LA, GM, Felker 131. registry. failure heart population-wide a in outcomes and covariates clinical anemia, between the of association assessment Acomprehensive U. Dahlstrom LH, Lund M, Edner AC, A, Hallberg Jonsson meta-analysis. and review systematic failure: in heart outcomes SmithGL, Lichtman JH, BrackenMB,Shlipak MG, Phillips CO,DiCapua P,Krumholz HM. Renalimpairment and 2017; kidney diseasein heart failurewith preserved, mid-range,reduced and ejection fraction. chronic of impact with and prognostic Associations LH. T,Lund U, Jernberg Dahlstrom K, Szummer Lofman I, 786.

program. insights from the Candesartanin Heart failure: Assessment ofReduction in Mortality and morbidity (CHARM) failure: heart chronic with in patients prognosis index and Body mass SD. Solomon JJ, McMurray CB, Granger EL, K,Michelson Swedberg S, MA, Yusuf H, Pfeffer Skali LA, Zornoff PV, Finn SJ, D, Wang Pocock S, Kenchaiah failure. failure. heart with in patients hospitalization and mortality to predict models multivariable of validation and Development AH. Zwinderman SD, Anker JG, Cleland K, Dickstein G, Filippatos P, Harst der van HL, Hillege CC, Lang JM, Maaten Ter M, Metra NgLL, P, Ponikowski NJ, Samani DJ, vanVeldhuisen F, Zannad W, Ouwerkerk AA, Voors failure risk score in 51,043 patients from the Swedish heart failure registry. registry. failure heart Swedish the from patients in51,043 score risk failure heart MAGGIC of the validation failure: inheart survival Predicting LH. Lund M, Edner U, Dahlstrom U, Sartipy Heart Fail Heart failure. heart for hospitalizations after therapy onmedical risk high at patients ambulatory identifies profiling Support) Circulatory Assisted Mechanically for Registry (Interagency LW.INTERMACS Stevenson JJ, Teuteberg RameJE, ME, FL,Guglin MM, Johnson CB, Mountis Patel JA, Cowger PC, Patel MM, Kittleson GC, Stewart observational study. study. observational in chronic heart failure and theeffect of treatment with angiotensin-converting-enzymeinhibitors: an loss ofweight importance S. Prognostic JN,Yusuf Cohn PA, R, Poole-Wilson Afzal AJ, Coats A, Negassa SD, Anker heart failure risk tool: the Barcelona Bio-Heart Failure risk calculator (BCN Bio-HF calculator). calculator). Bio-HF (BCN calculator risk Failure Bio-Heart Barcelona the tool: risk failure heart Lupon J, de Antonio M,Vila J, Penafiel GalanJ, A, Zamora E, Urrutia A,Bayes-GenisA. Development of a novel based on 39 based on Doughty RN; Meta-Analysis Global Group in Chronic Heart Failure. Predicting survival in heart failure: a risk score Sq A, L, Kober Maggioni JJ, CA,McMurray Pocock SJ,Ariti center? failure heart toa referred be should who failure: heart severe to with moderate patients of Triage M,LundLH. U,Edner Dahlstrom M, Stahlberg L, Benson T, Thorvaldsen failure. failure. inheart of survival prediction Model: Failure Heart Seattle M. The Packer DL, Mann PA, Poole-Wilson B, Pitt MD, Sullivan P, A,Burton Maggioni I, Anand AB, Cropp SD, Anker SC, Sutradhar DT, Linker D, Mozaffarian WC, Levy 2014; Fail disorders. different dementia and failure of heart to types inrelation survival dementia: failure and K, Winb Johnell SM, Fereshtehnejad Lund LH, P, Cermakova Ventricular Assist Device and Medical Managementin AmbulatoryHeart FailurePatients). Left of Effectiveness Comparative and Assessment (Risk study theROADMAP from insights patients: failure heart advanced in non-inotrope-dependent Risk Score II HeartMate Model and Failure Heart of Seattle Accuracy RC. Starling DJ, Farrar J, Chuang AJ, Boyle KB, Shah JG, Rogers JD, Estep J, Stehlik WC, Levy DE, Lanfear 2015; 154 19 9 :e85466. :1606–1614. EurHeart J Fail Circulation :102–108. 2016; Am J Cardiol J Am Circulation 17 Am Heart J

372 patients from 30 studies. 30 studies. from patients 372 :612–619. 9 :e003032. Heart Fail Rev Fail Heart 2006; 2007; Lancet 1999; 2017; 2008; 113 116 2003; 84 :1424–1433. 19 155 :627–636. :252–257. 2015; :627–634. J Am CollJ Am Cardiol 361 :883–889. Arch Intern Med Arch Intern :1077–1083. 20 :553–560. Eur Heart J J Heart Eur 2007; 2001; 2013; 50 uire IB, Swedberg K, Dobson J, Poppe KK, Whalley GA, GA, Whalley PoppeKK, J, K,Dobson Swedberg IB, uire :40–47. 161 34 lad B, Dahlstrom U, Eriksdotter M, Religa D. Heart D. Heart Religa M, U, Eriksdotter lad B,Dahlstrom :1404–1413. J Am Coll Cardiol J Am Coll :1849–1856. J Am CollCardiol J Am Coll Cardiol Eur J Heart Fail Eur JHeart Fail 2006; IntCardiol J 47 2014; 2006; :1987–1996. 2014; 2009; 63 48 :661–671. Eur J Heart Fail 2016; 16 :1527–1537. Circ Heart Fail 11 :173–179. Am Heart J Heart Am Eur J Heart Heart J Eur :170–177. PLoS One 211 :124– Circ

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 124. 123. 111. 113. 112. 130. 127. 125. 115. 114. 131. 129. 128. 126. 116. 133. 132. 121. 120. 118. 117. 122. 119.

detection of left ventricular systolic dysfunction, and prediction of death. of death. prediction and dysfunction, systolic ventricular left of detection factors, influencing failure: in heart chronic peptides natriuretic andB-type pro-atrial midregional of Comparison Moertl D, Berger R, Struck J, Gleiss A, Hammer A, 2006; failure. in heart outcome of predictor as anovel precursor, vasopressin the of fragment a Copeptin, R. A, Pacher NG, Bergmann Morgenthaler J, Struck R, Berger M, Hulsmann D, B,Mortl Stoiser 2008; inthetherapy. era device of selection transplantation heart Surviv Failure Heart The D. Mancini LH, A, Lund Goda 2017; Failure Survival Score (HFSS) and the Seattle heart failure model (SHFM). (SHFM). model failure heart Seattle the and (HFSS) Score Survival Failure Heart the of comparison transplantation: heart for patients Selecting LH. Lund D, Mancini P, Williams A, Goda score for selection for cardiac transplantation. transplantation. cardiac for selection for score survival failure heart and consumption oxygen of peak races across Comparison DM. Mancini LH, Lund A, Goda Card Fail Card registry. and trial (SHOCK) Shock Cardiogenic for Coronaries Occluded Revascularize Emergently We Should the of analysis hemodynamic a shock: cardiogenic by complicated infarction myocardial acute in dysfunction ventricular Right NK. Kapur D, Burkhoff JS, Hochman SD, Katz R, Karas K, Morine M, Esposito Xu J, Guo Y, A, Lala Fail Card failure. heart decompensated with acute hospitalized patients African-American in rehospitalization failure heart and mortality all-cause long-term predicts test walk minute Six TD. Stamos S, IN, Napan Mansour MT, Alahdab failure. heart withacute in patients measurements galectin-3 ofserial value Prognostic KM. Akkerhuis HL, E, Hillege Boersma E, Orsel Wajon JG, FW, Asselbergs RA, YM, de Boer D,Pinto I, SJ, Postmus Baart van Vark LC, Lesman-Leegte 1002. failure. with heart age of years >65 in patients survival to predict score survival failure the heart and consumption oxygen exercise of peak Usefulness D. Mancini A, Goda Lund LH, MN, Parikh men. inwomen versus prognosis predicting Score for Survival Failure and the Heart consumption oxygen exercise ofpeak Comparison D. LH,Mancini P,Lund Green 2011; summary. summary. executive support: circulatory mechanical for Guidelines Transplantation Lung and Heart for Society International Eduardo Rame J, Russell SD, Sorensen EN, Sun B, Strueber M, Mangi AA, Petty MG, Rogers J. The 2013 A, KusneS,Loebe M, Massicotte MP, Moazami N,Mohacsi P,Mooney Nelson M, T,PaganiF, Perry W,Potapov EV, R, Kaan John K, Hryniewicz K, Jones KL, DJ,Grady Goldstein T, Elliot A, El-Banayosy ML, Dickstein M, HW, Deng ME, Buchholz F, Bauman Arabia JA, Morgan SA, K, Moore E, Lietz Birks JJ, Teuteberg SV, D, Pamboukian Feldman pressure. filling ventricular ofleft assessment SF. Non-invasive Nagueh measurements. andinvasive echocardiography simultaneous utilizing astudy fraction: ejection and preserved failure heart with patients in pressures pulmonary and ventricular left of estimation Echocardiographic ES. Hoendermis AA, Voors DJ, Veldhuisen S, van Rosenkranz P, Meer der van M, Rienstra K, Damman DF, Fonseca-Munoz CS, Lam LCY, Liu Hummel YM, measurements in patientswith chronicheart failure. T troponin highly-sensitive and factor-15, differentiation growth ST2, soluble serial of comparison head JL Januzzi Head-to- S, Jr. TJ, Wang B, Motiwala A,De Berardinis A, Belcher Bhardwaj J, Szymonifka Gaggin HK, blocker therapy. on beta- failure heart severe with patients in ambulatory survival DM. Predicting Mancini KD, Lund LH, Aaronson 1997; evaluation. transplant cardiac for referred patients ambulatory in survival predict to index clinical a of validation prospective and Development DM. JE, Mancini Goin KL, Wong TM, Chen JS, Schwartz KD, Aaronson pulmonary artery catheterization effectiveness: the ESCAPE trial. trial. ESCAPE the effectiveness: catheterization artery pulmonary and failure heart congestive of study Evaluation Coordinators. Study ESCAPE and Investigators The ESCAPE Lung Transplant use? to clinical leading – pathophysiology failure heart in advanced Biomarkers A. Gabrielsen Lund LH, failure. heart congestive in severe survival long-term of as apredictor strength R. Muscle D,P, Pacher C, Nuhr Moser Mortl M, R, Springer Crevenna R, M,Berger Quittan M, Hulsmann score for advanced heart failure. failure. heart advanced for score risk 4-variable Angeles Los of California, University ofa Assessment LH. Lund DM, Mancini A, Goda U, Sartipy SurvivalScore for serial risk stratification inadvanced heart failure. Failure Heart the and consumption oxygen exercise peak of Validation DM. Mancini KD, Aaronson Lund LH, in patients with chronic heart failure: prediction of death at different stages of the disease. peptide natriuretic pro-B-type amino-terminal and peptide, natriuretic B-type copeptin, of Comparison R. Pacher A, Berger R, D, Moertl NG, Bergmann J, Morgenthaler B, Struck Stoiser G, M,Strunk S, Neuhold Huelsmann international registry. registry. international the QUALIFY fraction: ejection reduced with failure heart with in outpatients prognosis better with associated is adherence guideline Physicians’ GS. Filippatos SD, Anker P, Ponikowski L, Tavazzi MR, Cowie M, Komajda 36 52 10 30 95 :771–778. :266–272. :e003745. 2018; 2009; :1236–1243. :2660–2667. J Heart Lung Transplant J Am Heart Assoc Heart Am J 24 15 2014; Am J Cardiol J Am :148–156. :130–135. Eur J Heart Fail 33 :1213–1214. 2003; 2017; J Am Heart Assoc Heart Am J 2013; 92 2017; 6 :1350–1354. :e003700. 32 :157–187. 19 Am J Cardiol J Am :1414–1423. Eur J Fail Heart 2014; JACC Heart Fail Am J Cardiol J Am Morgenthaler NG, Bergmann A, Huelsmann M, Pacher R. R. Pacher M, Huelsmann A, Bergmann NG, Morgenthaler al Score outperforms the peak oxygen consumption for for consumption oxygen peak the outperforms Score al 3 :e000998. 2010; J Heart Transplant J Heart Lung 2017; 105 JAMA 2007; Am J Cardiol J Am 2014; 19 :1439–1444. EurHeart J Fail 2005; Eur J Heart Fail :1651–1660. 99 J Am Coll Cardiol Coll Am J 2 :399–403. :65–72. 294 2005; :1625–1633. 2011; Am J Cardiol J Am 2004; J Heart Lung Transplant Lung Heart J 2018; 95 2009; :734–741. 30 6 :315–325. 20 :101–107. Eur Clin J Invest J Am Coll Cardiol Am Coll J 53 :38–48. 2009; :1783–1790. Circulation 103 J Heart :998– J J

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 145. 146. 137. 136. 135. 134. 151. 150. 140. 139. 138. 149. 148. 147. 143. 142. 141. 144.

failure and preserved ejection fraction. fraction. ejection preserved and failure heart with in patients walk test tosix-minute in relation haemodynamics and exercise Resting F. Gustafsson Wolsk D, Kaye E, BA,Borlaug D, Burkhoff Kitzman DW frailty and its components in non-dependent elderly patients with heart failure. failure. heart with patients elderly non-dependent in its components and frailty impact of prognostic and H. Prevalence Bueno JA, J, Serra-Rexach Ortiz E, V, Sanchez Blaya-Novakova Vidan MT, outpatient cohort with congestive heart failure. failure. heart congestive with cohort outpatient 714. committee. therapeutics failure heart toanadvanced presented patients ambulatory in Model Failure Heart Seattle ofthe Application RC. Starling E, Hsich WC, Levy CH, Chow EC, Chu EZ, Gorodeski prognosis in heart failure. A validation study. study. A validation failure. inheart prognosis and score (MECKI) Indexes Kidney And Cardiac with combined data test exercise The metabolic E. D, Berton Bertipaglia D, Caputo S, Campanale D, R,Santoro Maria De R, Calabro A, Buono T, Roselli G, Malfatto F, Pietrucci F, Bovis S, E, Farina C, Bertella Segurini L, Antonioli MF, Piepoli P, C, Giannuzzi Passino C, Vassanelli M, Contini P, Palermo S, Paolillo AM, Iorio A, Apostolo R, Ricci A, Lenarda Di D, Scrutinio A, Mezzani F, Veglia M, Giovannardi E, Salvioni M, Cicoira C, Fiorentini D, Magri G, Parati R, Belardinelli M, Guazzi F, Re R, Raimondo G, Limongelli G, Sinagra M, M, AB,Metra Emdin R,Scardovi Gioia E, La G,Battaia A,Cattadori Giordano P, Corra Agostoni U, comparison. comparison. long-term a fraction: ejection reduced with failure heart chronic in scores prognostic Multiparametric PP. A, Filardi C, Passantino S,Lombardi P, Binno Gargiulo G, Marchese F, Clemenza M, Contini P, Palermo A, Apostolo Ricci R, G, E, Pacileo S, Zambon Sciomer C, Passino A, Lenarda R,Di Badagliacca M, Guazzi L, Pastormerlo A, Mezzani Parati G,Caravita S, Re F, Cicoira M, MinaC, Correale D, M, Magri Piepoli M, R, Emdin D, Raimondo Scrutinio V, M,Carubelli AB, Metra Scardovi G, Cattadori G, Sinagra M, Frigerio M, Bussotti M,Oliva F, Battaia G, E,R, Limongelli Lagioia U, Corra A, Belardinelli Bonomi F, Veglia E, Salvioni P, Gentile M, Mapelli S, Paolillo P, Agostoni R, prognosis. failure to heart approach score: a multiparametric the MECKI indexes, kidney and cardiac with combined data test exercise Metabolic C. Passino MF, Piepoli LD, Cas A, Passantino P, Giannuzzi M, Confalonieri M, Contini Ricci R, Bettari L, Di Lenarda D, Scrutinio E, Salvioni A, A, C, Mezzani Fiorentini D, Magri G, Pastormerlo R,Parati Belardinelli M, Guazzi Re F, R, Raimondo LE, Pacileo G, Vaninetti G, G, Limongelli M, Sinagra M,Metra AB, Emdin R, Scardovi F,La Gioia Veglia G, U,Cattadori P,Corra R,Agostoni Apostolo A, Iorio A, Paolillo S, Palermo P, Stehlik J, Kasirajan V, Haas DC, O’Connell JB, Boyle AJ, Farrar DJ, Rogers JG. Risk assessment and comparative comparative and assessment Risk JG. Rogers DJ, Farrar AJ, JB, Boyle O’Connell DC, V, Haas Kasirajan J, Stehlik JW, Long N, M, Moazami KB, Loebe Shah CH, Selzman CA, Milano DA, Horstmanshof RC, Starling Estep JD, Fail Heart failure. heart in advanced therapy inotropic intravenous of outcomes and characteristics Clinical D. Acharya JF, George RY, Loyaga-Rendon SV, JA, Pamboukian Tallaj CJ, Morgan M, Revilla-Martinez K, Sanam T, Hashim 875. Heart Failure treatment (SEE-HF) study. (SEE-HF) treatment Failure Heart advanced for ScrEEning the from results system: assist ventricular left and transplantation heart for Screening Schmitto S, Shaw K, Caliskan B, Meyns JN, Trochu Lund LH, study. study. apilot cardioverter-defibrillator: implantable or therapy resynchronization cardiac with patients by screening therapy failure heart advanced for patients Identifying LH. C, Lund Linde A, Gabrielsen F, Gadler S, Zabarovskaja Cardiol Coll Am failure. heart advanced with in patients Model Failure Heart Seattle ofthe Utility J. Butler WC, Levy D, Vega S, J, Dunbar Puskas S, Laskar S, Waheed SA, Agha AL, Smith G, Giamouzis VV, Georgiopoulou AP, Kalogeropoulos decompensated heart failure. failure. heart decompensated acutely with patients of course clinical short-term onthe levosimendan of Effect T. Sarapohja B, Huang C, Garratt J, Salon L, Delgado-Herrera R, Thakkar RJ, Padley J, Young JR, Teerlink BM, Massie L, Fisher W, Colucci M, Packer J Heart Am (FIRST). Trial Survival Randomized International Flolan the from insights failure: heart advanced with patients K, Gheorghiade M,Califf RM. Continuousintravenous dobutamineis associatedwith anincreased risk of deathin F, Swedberg Zannad WJ, McKenna SH, Grossman SE, McNulty Jr, KF Adams BF, Uretsky WA, Gattis CM, O’Connor randomized controlled trial. trial. controlled randomized Silver MA, Gheorghiade M.Short-term intravenous milrinone for acute exacerbation ofchronic heart failure: a R, I, Pina Quigg CM, O’Connor BM, Massie WS, R,Colucci R, Bourge Jr, KF Benza RM, Adams Califf MS, Cuffe with chronicheart failure: acomparative analysis onclinical and prognosticinsights. in patients testing exercise cardiopulmonary and test walk Six-minute R. Arena M, Vicenzi K, Dickstein M, Guazzi chronic heartfailure. in capacity functional physical assessing for walk test Six-minute RA. J,Clark P,Tongpeth Du H, Wonggom Heart FailureAssociation of the EuropeanSociety Cardiology. of stratificationin heart failure.A position paper from the Committee on Exercise Physiology and Training ofthe in clinical testing exercise Role ofcardiopulmonary MF. PM,Piepoli J,Seferovic Riley P, Ponikowski M, Metra M, LH, Lund L, Hill Lainscak VP, RA, Hairola Boer MG,de Leiro AJS, Crespo Coats SD, Anker PG, U,Agostoni Corra 555. neurohumoral activation, the six-minute walk test and the Minnesota Living with Heart Failure Questionnaire in an Questionnaire Failure Heart with Living andthe Minnesota test walk six-minute the activation, neurohumoral by ofoutcome Prediction R. J, Pacher Bergler-Klein W, Woloszczuk A, B,Bojic Sturm R, Berger M, Hulsmann J Heart Lung Transplant Heart J 2015; Int J Cardiol 1999; Eur JHeart Fail 2009; 8 :880–886. 138 Curr Heart Fail Rep Fail Heart Curr 53 (1 Pt 1):78–86. 2013; :334–342. 2018; JAMA 167 JACC Heart Fail 2013; 2002; :2710–2718. 20 32 :700–710. Eur JHeart Fail 287 :651–654. 2017; Eur JHeart Fail :1541–1547. 2013; Int J Cardiol Int J 14 Eur HeartJ :158–166. 1 :103–111. 2018; 2018; 2016; 2002; , KomtebeddeCS,Lam J, Ponikowski SJ, P, Shah JD, Schibilsky D, Damme L, Heatley J, Gustafsson F. F. J,Gustafsson Heatley L, D,Damme Schibilsky JD, 20 20 :715–722. 203 Eur J Heart Fail Heart J Eur 23 :152–160. :886–891. :1067–1072. 2018; Eur JHeart Fail Circ Heart Fail Heart Circ Circ Heart Fail Heart Circ 20 :3–15. 2016; 2010; 2009; 18 3 2 :706– :869– :549– Circ Circ J This articleisprotected bycopyright.Allrightsreserved. Accepted Article 166. 165. 154. 153. 152. 172. 171. 170. 169. 168. 167. 164. 155. 163. 158. 156. 162. 161. 160. 159. 157.

108. Dialysis eds. TS, Ing PG, Blake JT, Daugirdas In: dialysis. peritoneal of Physiology JT. Daugirdas PG, Blake ultrafiltration. extracorporeal of effects failure: heart in congestive metabolism salt fluid and and hemodynamics, factors, Marenzi G,Grazi S, Giraldi F, Lauri G,Perego G, Guazzi M, SalvioniA, Guazzi MD. Interrelationof humoral diuretics for patients hospitalized for acute decompensated heart failure. failure. heart decompensated foracute hospitalized patients for diuretics intravenous versus Ultrafiltration Investigators. Trial PA; UNLOAD Sobotka MP, Schollmeyer AS, Anderson Haas ED, GJ, JC, Feller Fang BE, Jaski JR, Teerlink BA, Bart ML, Jessup MT, Saltzberg ME, Guglin MR, Costanzo (DAD-HF II) trial. II Failure Heart Decompensated inAcute Dopamine the infusion: dopamine without with or dose furosemide low versus high of dose andsafety Efficacy G. Giamouzis AP, H,Kalogeropoulos G,Karvounis L, Giannakoulas T, Mantziari Tsaknakis C, J, Nastas C, Stefanadis C,Pitsavos Chrysohoou CK, Antoniou J, Skoularigis K, Koutrakis D, C, Rovithis J,Parisis K, Parissis Wolski G, RC,Filippatos G,Starling Karayannis J, Butler FK, Triposkiadis JAMA trial. randomized failure heart acute ROSE the renal dysfunction: with failure heart in acute nesiritide low-dose Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM. Low-dose dopamine or SE, McNulty VG, Davila-Roman DL, Mann EO, Ofili TP, Cappola KB, Margulies RE, CM, Bonita O’Connor GM, A, Felker J, Deswal Butler RC, WH,Starling E, Tang O’Meara JL, Rouleau GS, Huggins Konstam MA, MM, LeWinter J, Stehlik DA, Bull Bart SR, BA, Goldsmith MJ, Semigran LW, Stevenson MM, AnstromKJ, Givertz Chen HH, methods. scoring propensity using registry ALARM-HF global the failure: heart acute with hospitalized patients among treatment by survival Short-term F. Follath JF, Delgado FV, Boas M, Nikolaou E, R, Gayat J, Porcher A, Parissis Mebazaa Study. ROADMAP the from results patients: failure heart in ambulatory management medical and device assist leftventricular of effectiveness of peritoneal dialysis. dialysis. of peritoneal practice the for Implications syndrome: cardiorenal of in management target major asa overload Fluid A. Kazory Frampton JE, Plosker GL. Icodextrin: a review of its use in peritoneal dialysis. dialysis. itsinperitoneal use a review of Icodextrin: GL. Frampton JE,Plosker advanced congestive heart failure. failure. heart congestive advanced LlacerA, Miguel A. Continuous ambulatory peritoneal dialysis as a therapeutic alternative in patientswith P, Merlos P, Palau MJ, Puchades Nunez E, V, Bodi J, R,Sanchis G, Garcia-Ramon Minana M, Gonzalez Nunez J, failure: asystematicreview. heart congestive refractory with in patients dialysis C.Peritoneal Ronco MH, A, Z, Rosner Ni C, Brendolan Crepaldi Lu R, Mucino-Bermejo MJ, Ribeiro LC, Tonini E, Estremadoyro C, SamoniS, Sharma A, Zaragoza Galvan Jde J, 2012; disease. kidney andchronic failure heart refractory with in patients is tolerated and well Koch M, Haastert B, Kohnle M, Rump LC,Kelm M, Trapp R, AkerS. Peritoneal dialysis relieves clinical symptoms the number of hospitalization days in heart failure patients refractory to diuretics. diuretics. to refractory patients failure heart in days hospitalization of number the CourivaudC, KazoryA, Crepin T, Azar R, Bresson-Vautrin C,Chalopin JM, Ducloux D. Peritoneal dialysisreduces and hospitalizations for heart failure. failure. heart for and hospitalizations diuretics intravenous versus Aquapheresis GC. Fonarow MP, NabutJL,Schollmeyer JA, GJ,Watts Haas ED, Adler DB, Chomsky AM, Kaneshige JM, Smelser IS, Anand JT, Heywood BA, Bart BE, D, Jaski Negoianu MR, Costanzo Sweden. in medicine internal and cardiology in failure heart for Thorvaldsen T, Benson L, Hagerman I,Dahlstrom U, Edner M, Lund LH.Planned repetitive use of levosimendan 1309. print] print] trial. randomised multicentre LION-HEART the failure: heart advanced with patients in of levosimendan administration outpatient intravenous intermittent of safety and Efficacy J. Bruguera M, Grau JL, F, Lambert-Rodriguez Gonzalez-Vilchez D, Pascual-Figal Blasco T, A, Sionis MG, Crespo-Leiro L, Almenar JM, Pinilla Garcia J, Delgado J, Segovia-Cubero N, Manito J, Comin-Colet meta-analysis. meta-analysis. an updated failure: heart in advanced treatment levosimendan or intermittent Repeated MS. S, Nieminen Silvetti effects on symptoms, renal function, and prognosis. prognosis. and function, renal onsymptoms, effects therapies: extracorporeal and diuretics with failure heart in congestion of M. Treatment Jessup MR, Costanzo Cardiol ultrafiltration forfluid overloadin heart failure: currentstatus and prospects forfurther research. Extracorporeal AA. Voors JM, Testani WHW, Tang MM, Redfield D, Negoianu W, Mullens G, Marenzi HR, Levin AP, Levin A, Kazory BE, Jaski SS, Gottlieb GC, J,Fonarow Barasch P, Agostoni WT, Abraham C, Ronco MR, Costanzo as a bridge to cardiac transplantation: a national database analysis. analysis. database national a transplantation: cardiac to bridge as a cardioverter-defibrillator Wearable RK. Thakur SJ, Szymkiewicz J, Ahmad N, Salehi V, Singh C, Wan M, Opreanu transplantation. heart awaiting failure heart end-stage with in patients treatment defibrillator cardioverter implantable Prophylactic F. Ruschitzka R, Hetzer TF, Luscher V, Falk J, G, Steffel Noll HB, Lehmkuhl D, B, Hurlimann Seifert F, Enseleit M, S, Wolfrum Hubler M, Hubler J, Holzmeister GM, Frohlich advanced heart failure patients: a meta-analysis of randomized trials. trials. ofrandomized meta-analysis a patients: failure heart advanced in treatment levosimendan intermittent after Rehospitalization P. Pollesello A, Fontana A, Belletti S, Silvetti 2013; 14 2017; . 3rded.. Kluver: Lippincott, Williams, and Wilkins;2001. p281–296. :530–539. 310 69 Am J Med J Am Int J CardiolInt J :2533–2543. :2428–2445. Intensive Care Med IntCardiol J World J Nephrol J World 1993; 2016; Cardiorenal Med Cardiorenal 2014; 94 :49–56. 202 J Am CollCardiol J Am Eur J Heart Fail J Heart Eur 172 2011; JACC Heart Fail 2017; :138–143. :115–121. :115–121. Eur J Heart Fail J Heart Eur 37 6 2015; :168–175. :290–301. 2012; 2015; 5 Heart Fail Rev Fail Heart 2016; :145–156. 14 66 4 20186. Feb doi: 10.1002/ejhf.1145. [Epub ahead of :540–548. :95–105. :1747–1761. Int J Cardiol 2012; ESC HeartFail J Heart Lung Transplant Lung Heart J J Cardiol Am Coll J 17 2014; :313–324. Drugs Heart 175 2003; 2017; Perit Dial Int Dial Perit :55–61. 2013; 2007; 63 4 :595–604. :2079–2105. 99 :1158–1165. 49 Eur JHeart Fail 2015; 2014; :675–683. Handbook of J Am Coll AmColl J 34 34 :1305– :100–

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 174. 187. 175. 173. 188. 186. 185. 184. 181. 179. 178. 177. 176. 189. 183. 182. 180. 191. 190. 193. 192.

2015; Association of Interventional Cardiology-Association Canadienne de Cardiologie d’Intervention. India, andSociedad Latino Americana deCardiologia Intervencion; AffirmationValue of byCanadian the support devices in cardiovascular care: endorsed by the American HeartAssocation, the Cardiological Society of circulatory mechanical percutaneous of use the on statement consensus expert Clinical SCAI/ACC/HFSA/STS 2015 T. Tu V, Dimas JA, Goldstein KN, Garratt M, Kern NK, Kapur JA, Burke WY, Szeto MM, Givertz SS, Naidu CS, Rihal refractory cardiogenic shock. shock. cardiogenic refractory Kar B, GregoricID,Basra SS, IdelchikGM, LoyalkaP. The percutaneous ventricular assist devicein severe pumps in advanced heart failure. failure. heart pumps in advanced counterpulsation balloon ofintra-aortic effects hemodynamic Acute NK. RH, Kapur Karas MS, Kiernan AR, Patel B, Wessler K, R, Morine O’Kelly R, Pedicini C, Breton A, V, Mullin Paruchuri ML, Esposito L, Buiten SK, Annamalai transplantation: a nationwide Spanish registry. registry. Spanish a nationwide transplantation: LeiroMG. Clinical outcomes of temporary mechanical circulatory support as adirect bridge toheart F u e n t e -la De M, Martinez-Selles G D, Rangel-Sousa IP, Garrido-Bravo J, Delgado-Jimenez MA, Castel-Lavilla J, a Cubero l a nL , R a Gonzalez-Vilchez L, Almenar-Bonet E, bBarge-Caballero a g o - J u a n - A r a c i l G , S a n z - J u l v e M , H e r v a s - S o t o m a y o rD , M i r a b e t - P e r e zS , M u n i z J , C r e s p o - devices for acuteright ventricular failure. Kapur NK,Esposito ML, Bader Y,Morine KJ, Kiernan MS,Pham DT, Burkhoff D.Mechanical circulatory support to recovery. recovery. to Kar B, Basra SS, Shah NR, Loyalka P. Percutaneous circulatory support in cardiogenic shock: interventional bridge Butt W,MacLarenExtracorporeal G. membrane oxygenation 2016:an update. meta-analysis. and review asystematic shock: cardiogenic and arrest cardiac during support life Extracorporeal JP. Henriques BA, Mol OuweneelDM, Schotborgh JV, Limpens J,Sjauw KD, Engstrom AE, LagrandCherpanath WK, TG,Driessen AH, de patients with cardiogenic shock. shock. with cardiogenic patients of survival improve may oxygenation membrane extracorporeal veno–arterial of top on ofImpella® implantation Concomitant D. A, Westermann S, Zangrillo H, Blankenberg Reichenspurner F, Wagner Bonis M, De Sydow K, A, Colombo K, Mullerleile R, Lembo T, Greco G, Soeffker R, Contri B, Schrage M, C, Pieri Schulte F, Pappalardo percutaneous extracorporeal membrane oxygenation in adults. for strategies Cannulation J. Bauersachs A, A, Schafer Haverich J, Vogel-Claussen MM, C,Hoeper Napp LC,Kuhn of stabilization. and predictors response clinical shock: and cardiogenic failure heart chronic with in patients counterpulsation balloon Intra-aortic SM. Joseph DL, Mann SC, Silvestry RG, Bach E, Novak KJ, Lavine M, Nassif BR, Lindman M, Gdowski MA, Sintek Engl JMed shock. cardiogenic with infarction myocardial for support balloon Intraaortic IITrial Investigators. IABP-SHOCK K; G,Werdan Schuler S, H,Schneider M, Ebelt J, Bohm R,Fuhrmann I,Hambrecht Eitel S, Desch G, Fuernau HG, Olbrich M, Ferenc FJ, U, Neumann H, Zeymer Thiele Engl JMed shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. cardiogenic by complicated infarction in acute myocardial revascularization Early TH. LeJemtel SM, McKinlay J, Col JN, Slater AK, CE, Jacobs Buller JD, HD, Talley White TA, Sanborn JG, Webb LA, Sleeper JS, Hochman intraaortic balloon pumping for treatment of cardiogenic shock. shock. cardiogenic of treatment for pumping balloon intraaortic with therapy conventional versus device assist ventricular percutaneous theTandemHeart of and efficacy safety the evaluate to study clinical multicenter randomized A WW. O’Neill C, H, Brunckhorst Cohen D, Burkhoff the survival after veno–arterial-ECMO (SAVE)-score. (SAVE)-score. veno–arterial-ECMO after survival the shock: cardiogenic refractory for ECMO after survival Predicting D. V, Pilcher Pellegrino D, Brodie RR, Thiagarajan Schmidt BurrellM, A, Roberts L, Bailey M, Sheldrake J, Rycus PT, Hodgson C, Scheinkestel C, Cooper DJ, Surg oxygenation. membrane extracorporeal veno–arterial with supported shock cardiogenic refractory with in adults decompression atrial left Percutaneous F. V, Rao E, Billia Fan E, H, Ross Horlick M, Osten M, Alhussein support: a review of the current literature. life extracorporeal on unloading ventricle left of effects and R. Modalities J,Lorusso Z, Maessen E, Babar Korver LozekootP, Kats S, Sluijpers N,SchreursR, DelnoijT, Montalti A, Sels vandePollJW, Roekaerts M, P,Poels T, S, G, Heuts Raffa M, Makhoul E, Bidar F, Pappalardo HB, Rocca DM, Johnson E, S, Natour Gelsomino P, Meani print] print] First experience in Spain. transplant. to heart bridge asa device support circulatory mechanical CP of theImpella implantation Transaxillary JJ. Cuenca-Castillo MG, Crespo-Leiro C, Garcia-Velasco M, Solla-Buceta F, D, Estevez-Cid Couto-Mallon support. circulatory mechanical temporary for Options P. Bonde A, Saffarzadeh cardiogenic shock treated with the Impella CP microaxial pump for isolated left ventricular failure. failure. ventricular left isolated for pump microaxial CP Impella the with treated shock cardiogenic Sieweke JT, Berliner D, Tongers J, Napp LC, Flierl U, Zauner F, Bauersachs J, Schafer A. Mortality in patients with care unit experience. experience. unit care intensive Center Medical the Academic shock: cardiogenic and profound with severe presenting patients infarction myocardial ST-elevation for devices 5.0 and 2.5 Impella The JP. JJ, Henriques Piek BA, Mol RJ,de JG, deWinter Tijssen JA, Sloot der van WK, Lagrand JM, de J, Baan MM, Vis KD, Sjauw AH, Driessen R, Cocchieri AE, Engstrom 2017; 65 :e7–e26. 2012; 1999; 32 Circulation :396–401. 367 341 :1287–1296. :625–634. Crit Care Med 2012; Rev Esp Cardiol (Engl Ed) (Engl Cardiol Esp Rev Intensive Care Med J Cardiol Am Coll 125 J Card Fail Eur J Heart Fail Heart J Eur J Card J Card Fail :1809–1817. 2011; 2015; 39 Circulation Eur JHeart Fail 2017; :2072–2079. 2016; 2011; Eur J Fail Heart 21 2017; 23 :868–876. 2017Dec 4.10.1016/j.rec.2017.09.020. doi: [Epubahead of 2017; 42 57 Eur Heart J :606–614. 19 :1922–1934. :688–696. F, Lambert-Rodriguez JL, Gonzalez-Costello J, Segovia- J, Gonzalez-Costello JL, Lambert-Rodriguez F, :404–412. 2017; 136 Hausleiter J, Richardt G, Hennersdorf M, Empen K, M, Empen Hennersdorf G, J, Richardt Hausleiter 2018; :314–326. Clin ResCardiol Clin Am Heart J Heart Am 2015; 19 Suppl 2:84–91. 2:84–91. Suppl 20 36 :178–186. :2246–2256. 2006; F1000Res 2016; J Thorac Dis 152 105 :469.e1–8. 2016; :283–296. 2015; 5 :750. J Am Coll Cardiol J AmColl 7 :2102–2111. Eur Heart J Eur Heart J Card J Card N N

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 195. 194. 212. 211. 210. 209. 208. 207. 205. 206. 196. 197. 198. 200. 199. 201. 202. 203. 204.

of the LevitronixCentriMag ventricular assist system for short-termcirculatory support. trial amulticenter of Outcomes LD. Joyce OH, Frazier AJ, Tector BC, Sun BP, Griffith HT, Massey JW, Long John R, 2015; RP device. ofImpella the study RIGHT RECOVER the prospective failure: heart SilvestryS, Holman WL,Douglas PS, O’Neill W. Benefits a of novel percutaneous ventricularassist device forright JN, Baker J, Garcia A, Bansal NK, Kapur J, Bhama RL, Kormos LD, Morris C, Milano J, Goldstein MB, Anderson Acute Cardiovasc Care Cardiovasc Acute 2017; for Chagas cardiomyopathy. transplantation F.Heart GH, Bacal Oliveira RD, Benatti Transplant Jahangiri B, Haddad H. Cardiac transplantation in HIV-positive patients: are we there yet? disease. advanced with patient an HIV-1-infected in transplantation cardiac Successful R. Zackin J, Jarcho P,HaugM, McCarthy J, Young M, Albrecht LH, Calabrese 2011; vasculopathy. allograft and coronary rejection cellular risk of cardiac and decreases survival excellent an provides transplantation and kidney heart BS.Combined Edwards NL, C, Pereira McGregor MD, Stegall TS, Larson RJ, Rodeheffer AL, Clavell RP, Frantz WK, Kremers RC, Daly SS, E, Kushwaha Raichlin Transplant Lung Heart Registry. Transplantation and Lung forHeart Society International the of analysis management–an transplant post- of personalization for Implications mortality: transplant heart of and causes age ofrecipient Association J. Stehlik LH, Lund JC, Fang CH, Selzman SG, Drakos AG, Kfoury DO, Taylor LB, Edwards O, Wever-Pinzon data. registry international using (IMPACT) Transplantation Cardiac After Prediction Mortality for Index States-derived United the of Validation ES. Weiss JG, Allen A, Kilic Profiles in Transplantation (COCPIT) Study Group. Group. Study (COCPIT) in Transplantation Profiles andClinical Outcome Comparative severity. failure heart by stratified list, on toa waiting entered cohort national ofa analysis transplant: heart a receiving of Effect HH. Scheld J, Heinecke JM, Smits JM, Meester De Deng MC, 2011; (Engl Ed) recipients. transplant in index heart risk nutritional ofthe value MG. Prognostic Crespo-Leiro JM, Vazquez-Rodriguez JJ, Cuenca-Castillo JM, F,Herrera-Norena C,Pita-Gutierrez Velasco-Sierra M, Solla-Buceta MJ, Paniagua-Martin D, Couto-Mallon G, Barge-Caballero R, Marzoa-Rivas F, Garcia-Lopez E, Barge-Caballero ventricular assist device in acute heart failure refractory to medical management. management. tomedical refractory failure heart acute in device assist ventricular Worku B, PakSW, van Patten D, Housman B, Uriel N,Colombo P, Jorde U, Takayama H, Naka Y. The CentriMag support configuration. configuration. support biventricular CentriMag conventional with comparison a patients: shock in cardiogenic oxygenation membrane Takayama H. Minimallyinvasive CentriMag ventricular assist device support integratedwith extracorporeal J, M, Han AR,Ando Garan Takeda K, 2012; dysfunction. dysfunction. ventricular left with in patients surgery bypass Coronary-artery Investigators. JL; STICH Rouleau Jones RH, GR, Rankin RO, Bonow L, She P, Panchavinnin CM, O’Connor MC, P, Petrie H, Ferrazzi Szwed D, Prabhakaran M, Yii WT, S, Abraham Gradinac G, Pohost IS, Ali A, G,Marchenko Sopko A, Jain MA, Deja KL, Lee EJ, Velazquez European Association of Percutaneous Cardiovascular Interventions (EAPCI). (EAPCI). Interventions Cardiovascular Percutaneous of Association European the of contribution special the with Developed (EACTS). Surgery for Cardio-Thoracic Association and the European revascularization: The TaskForce onMyocardial Revascularization of the EuropeanSociety Cardiology of (ESC) Taggart DP,Torracca L,Valgimigli M,Wijns W, Witkowski A. 2014 ESC/EACTS Guidelines on myocardial GG, Stefanini Sousa Uva M, P, Schauerte DJ, Richter FJ, G,Neumann U,Laufer Landmesser A, Knuuti J, Kastrati WindeckerS, Kolh P, Alfonso F, Collet JP,Cremer J,Falk V, Filippatos C, G,Hamm Head SJ, Juni P,Kappetein AP, in surgery with ischemic cardiomyopathy. patients bypass Coronary-artery Investigators. JL;STICHES Rouleau G, Sopko P, Desvigne-Nickens VL, Moore L, JK, She Oh MC, Petrie T, Doenst RO, Bonow RE, Michler JA, Panza JA, Hill HR, Al-Khalidi RH, Jones KL, Lee EJ, Velazquez intervention with microaxial Impella(R) pump: results from the German Impella® registry. registry. Impella® German the from results pump: Impella(R) microaxial with intervention coronary percutaneous ofhigh-risk outcomes clinical short-term and Indication Akin I. T, Becher T, Bauer K, Karatolios A, D,Schafer Westermann JM, F,Sinning R,Al-Rashid K, Westenfeld N, Ibrahim S, Werner Baumann Mar8. 10.1007/s00392–018-1230-6. doi: [Epub ahead ofprint] Document Group. 2017 ESC/EACTS guidelines for the management of valvular heart disease. disease. heart valvular of management the for guidelines ESC/EACTS 2017 Group. Document Scientific JL; ESC Zamorano S, Windecker O, Wendler T, Walther A, Vahanian PT, Mas J, Sjogren R, Rosenhek Baumgartner H,Falk V,J, BaxDe Bonis M, Hamm C, Holm PJ,IungB, Lancellotti P,Lansac E, MunozDR, Groote Schuur Hospital, Cape Town. at performed operation asuccessful report of interim an transplant: cardiac A human operation. The CN. Barnard 2017; Transplant Transplant Prim Theme: Report–2016; Focus Transplantation Adult Heart Thirty-third Transplantation: and Lung Heart for Society International the of J.TheRegistry Stehlik RD, Yusen JW, Rossano B, Meiser BJ, AY, Levvey Kucheryavaya S, Goldfarb AI, Dipchand LB, Edwards Lund LH, 34 36 43 141 31 38 :1549–1560. :597–603. :1871–1876. :611–617. :2739–2791. 2017; :932–939. 2007; 2016; N Engl JMed N 70 26 35 :639–645. :103–107. :1158–1169. 2017; 2018 Feb 1. doi: 10.1177/2048872618757393. [Epub aheadof print] Eur J Cardiothorac Surg J Cardiothorac Eur 2011; 36 :407–417. 364 :1607–1616. S Afr Med J Med Afr S Topkara VK, Kurlansky P, Yuzefpolskaya M, Farr MA, Colombo PC, Naka Y, 2017; 1967; N Engl JMedEngl N BMJ N Engl J Med N Engl J 52 ary diagnostic indications for transplant. for indications diagnostic ary 2000; 41 :1055–1061. :1271–1274. J Heart Lung Transplant Lung J Heart 321 2003; 2016; :540–545. 348 374 :2323–2328. :1511–1520. Eur Heart J Heart Eur 2013; J HeartJ LungTransplant 2014; J Heart Lung Transplant J Heart Lung J Thorac Cardiovasc Surg Cardiovasc Thorac J J Heart Lung Transplant HeartJ Lung 32 Clin Res Cardiol Res Clin :492–498. 35 Transplant Proc :2541–2619. Rev Esp Cardiol Cardiol Esp Rev J Heart Lung J Heart Lung J Heart Lung Eur Heart J 2018 J

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 213. 228. 227. 226. 225. 224. 214. 229. 217. 216. 215. 232. 231. 230. 219. 218. 221. 220. 222. 223.

1504. 1757. 2014; Retransplantation. Report–2014; Focus Theme: Heart Adult Transplant Official Thirty-first Meiser B,Yusen RD,Stehlik J.The registry of the InternationalSociety forHeart and Lung Transplantation: BJ, Levvey SB, F, Goldfarb AI,Dobbels Dipchand JD, C, Christie AY, Benden Kucheryavaya LB, Lund LH, Edwards Cardiology. Cardiology. the WorkingGroup on Pulmonary Circulation and RightVentricular Function ofthe European Society of Contemporarymanagement acuteof right ventricular failure: a statement from theHeart FailureAssociation and S. MB, Konstantinides A, Yilmaz Vieillard-Baron B, Sztrymf P, F,Seferovic Ruschitzka A, G, Rudiger Rosano A, Ristic JP, Riley J, Parissis AV, Nordegraaf R, W,Naeije C, Mullens Mueller J, Masip J, Lassus A, S, Leite-Moreira H, D,Bueno Bettex J, Celutkiene A, Mebazaa VP, Harjola Russell SD, Miller LW, Pagani FD. Advanced heart failure: a call to action. a call toaction. heart failure: Advanced FD. LW, Pagani Miller SD, Russell Cardiol score. risk II HeartMate the devices: assist ventricular left flow continuous receiving in patients survival Cowger J,Sundareswaran K, Rogers JG, ParkSJ, Pagani FD,Bhat G, Jaski B, Farrar DJ,Slaughter MS. Predicting JB. Seventh INTERMACS annual report: 15,000 patients and counting. and counting. patients 15,000 report: annual INTERMACS JB. Seventh Young JT, Baldwin MA, Miller SL, Myers ED, Blume LW, Stevenson RL, FD, Kormos Pagani DC, Naftel JK, Kirklin outcomes. and selection patient failure: heart in advanced therapy device assist ventricular Left Rogers JG. F, Gustafsson antibodies in heart transplantation: An ISHLT consensus document. document. consensus An ISHLT transplantation: in heart antibodies of management A. The S, Zuckermann D,Urschel Tyan RC, Starling H, Ross ER, Rodriguez N, E,Reinsmoen Reed J, Patel J, Parameshwar M, Olymbios JF, Delgado MG, Crespo-Leiro D, Dragun L, Potena M, Colvin J, Kobashigawa flowleft ventricular assist devices. continuous- of implantation after function in renal Changes SS. Kushwaha SJ, Park R, Daly L, NL, Joyce Pereira Hasin T, Topilsky Y,Schirger JA, Li Z, Zhao Y, BoilsonBA, ClavellAL, RodehefferRJ, Frantz RP,Edwards BS, failure. failure. heart end-stage for device assist a left ventricular use of Long-term Group. Study (REMATCH) Heart Failure Congestive of Treatment the for Assistance Mechanical of Evaluation Randomized VL; Poirier MC, Oz P, Nickens Desvigne- OH, Frazier L, Gupta LW, RM, Miller Lazar PA, Shapiro NS, Ronan P, Meier JT, RG,Watson Levitan AR, Tierney DD, Ascheim JW, Long W, Dembitsky LW, Stevenson DF, Heitjan AJ, AC, Moskowitz Gelijns EA, Rose of Registry. National Transplant the Spanish Heart analysis transplantation: heart emergency undergoing patients ill critically in outcomes postoperative determine F i g a lD ,Manito JL, Lambert-Rodriguez F, Perez-Villa E, Lage-Galle F u e n t J, eDelgado-Jimenez A, Villa-Arranz F, Gonzalez-Vilchez L, Almenar-Bonet J, -Segovia-Cubero E, Barge-Caballero G a l a n L candidates–2006. transplant d of cardiac care the for guidelines e L , S a n Transplantation and Lung Heart for Society International transplantation: heart for criteria Listing M. Barr z - J u l v e S,Aaronson K, J, P, Augustine Mohacsi S, R, PA, Uber Parameshwar Russell J, Starling MR, Kobashigawa Mehra M , M u n i z - G a r c i a J , C r e s p o - L e i r o M . P r e o p e r a t i v e I N T E R M A C S p r o f i l e s supporting shared decision making for destination therapy left ventricular assist device: the DECIDE-LVAD DECIDE-LVAD the device: assist ventricular left therapy destination for making decision shared supporting intervention an of Effectiveness DD. Matlock MN, Walsh V, Baldridge C, Phillips Jr., JC, Cleveland RE, Glasgow EC, Allen LA, McIlvennan CK, Thompson JS, Dunlay SM, LaRue SJ, Lewis EF, PatelCB, Blue L, Fairclough DL, Leister American Heart Association. the from statement scientific a selection: andpatient strategies device support: circulatory use ofmechanical O’Connell JB, Pagani FD,Petty M,Ravichandran P, Roge PeuraColvin-Adams JL, Francis M, GS, Grady KL,Hoffman TM, Jessup M,John R, KiernanMS,Mitchell JE, 2011; inrecipients. device assist support left ventricular fixedhypertension pulmonary of Reversibility EV. Potapov R, Hetzer HB, Lehmkuhl M, Dandel A, Loforte T, Krabatsch A, Stepanenko E, Mikus Lund LH, Matthews J, Aaronson K. Patient selection for left ventricular assist devices. devices. assist ventricular left for selection Patient K. Aaronson J, Matthews LH, Lund failure. failure. heart refractory advanced with patients in implantation device assist vs. management conservative of Outcome R. Pacher G, Strunk A, Bojic A, Zuckermann S, Neuhold F, Eskandary WurmR, M, Hulsmann C, Adlbrecht 2010; Stevenson LW, Couper G. On the fledgling field of mechanical circulatory support. support. circulatory mechanical of field fledgling the On G. Couper LW, Stevenson Inst J differently? patients thesame we are treating therapy: destination toward trend Achanging Birks EJ. 2007; classification. classification. INTERMACS pre-operative by stratified patients device assist ventricular left continuous-flow for outcomes Clinical JJ. Teuteberg KN, AC, Hong Y,Gelijns Naka R, John RL, Kormos MJ, Russo DD, Ascheim AJ, Boyle registry (InteragencyRegistry for Mechanically Assisted Circulatory Support). INTERMACS using the study aprospective device: assist ventricular left flow withacontinuous study approval administration and drug post-food therapy destination the of Results SJ. Park DJ, Farrar EJ, Birks MS, Slaughter JJ, Teuteberg RL, Kormos DA, Horstmanshof JW, Long G, Bhat Y, Naka AJ, Tatooles SS, Kushwaha Jorde UP, 2011; 33 40 12 50 2013; N Engl J Med J N Engl EurClin J Invest :996–1008. :971–977. :434–443. :748–751. Eur J Heart Fail Eur J Heart Fail JHeart Eur 38 61 J Heart Lung Transplant Lung J Heart :552–554. :313–321. 2001; 2016; 2017; 345 2016; Circulation 46 :1435–1443. 19 :34–41. :34–41. 18 J AmColl Cardiol :595–602. :226–241. 2011; 2012; 30 126 :402–407. :2648–2667. Circ Heart Fail Heart Circ 2012; rs JG, Semigran MJ, Toole JM. Recommendations for the for Recommendations JM. Toole MJ, Semigran JG, rs Chioncel O, Crespo-Leiro MG, Falk V, Filippatos G, Gibbs G, MG, Falk V, Gibbs O,Crespo-Leiro Chioncel Filippatos -Lorite N, Arizon-Del Prado JM, Brossa-Loidi V, Pascual- JM,Brossa-Loidi Prado Arizon-Del -Lorite N, 59 :26–36. J Heart Lung Transplant Lung J Heart 2013; J Heart Lung Transplant 6 J Heart Lung Transplant Lung J Heart :763–772. Congest Heart Fail Heart Congest J Am Coll Cardiol Am Coll J 2006; Eur J Cardiothorac Surg Cardiothorac J Eur J Heart Lung Transplant Lung Heart J 2018; 2008; 25 J Am Coll Cardiol Coll Am J :1024–1042. Eur JHeart Fail 2014; 2015; 37 14 :537–547. :316–321. 63 34 Tex Heart J Am Coll :1495– :1751–

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 251. 249. 247. 246. 244. 233. 250. 248. 245. 234. 235. 237. 236. 241. 240. 239. 238. 243. 242.

randomized clinical trial. trial. clinical randomized 2014; National Health Service bridge-to-transplant program for patients with heart failure. Kingdom United inthe used devices assist ventricular left II HeartMate versus HeartWare the of cost-effectiveness A.Comparative Clarke NR, H,Banner Maheswaran P, Sutcliffe NB, Kandala M, Connock G, R,Suri Pulikottil-Jacob System (ReVOLVE). Assist Ventricular Left HeartWare the toEvaluate Registry thepost-market of Results S. K,Schueler GM, Najarian Strueber M, Larbalestier R, Jansz P, Zimpfer D, Fiane AE, Tsui S, Simon A, Schmitto JD, Khaghani A, Wieselthaler from the multicenter RESIST study. study. RESIST multicenter from the results 30 feasibility days management: site andexit stabilization through trauma driveline Reduce L. FD, Blue Pagani DJ, Farrar R, Chinn SV, L,Pamboukian Chen P, Blood W, Hallinan S, KS, Fox Sundareswaran M, Stahovich Transplant study. multi-center PREVENT The Management: Clinical II Through Thrombosis Pump HeartMate of PREVENtion I. Gregoric KS, Sundareswaran DJ, Farrar JB, O’Connell N, Uriel J, Stulak R, Adamson 3rd, JW, G, Entwistle Egnaczyk A, Brieke B, Sheridan JN, Katz J, Ransom S, Emani M, Keebler S, A,Nathan Kilic S, Maltais ventricular assist device thrombosis. thrombosis. device assist ventricular inleft increase abrupt Unexpected NG. Smedira BW, Lytle EG, Soltesz MM, L, Mountis J, Thuita Ehrlinger EH, Blackstone MA, Acker JE, Rame CA, Milano JG, G,Rogers Ewald SC, Silvestry N, Moazami RC, Starling Lung Transplant formulation for the standardization of definitions of infections in patientsusing ventricular assist devices. Working ML. Mooney JV, Conte RL, RF,Kormos Padera JG, Montoya K, Gould JM, Herre NG, Mahon SM, Gordon LP, WL, Lawler S, Holman Schueler GR, Corey L, Drew RJ, Danziger-Isakov F, Mattner S, Husain Hannan MM, transplant and continued access protocol trial. trial. protocol access andcontinued transplant to bridge of the results combined totransplant: forbridge system assist ventricular HeartWare Investigators. Trial ADVANCE Transplant to Bridge KD;HeartWare Aaronson KB, Najarian DR, R, Hathaway John MA, SW, Acker Boyce SS, Najjar T, Icenogle FO, Howard I, Gregoric WG, Cotts EJ, Birks EC, McGee FD, Pagani MS, Slaughter intrapericardial left ventricular assist system. system. assist ventricular left intrapericardial Strueber M,O’Driscoll G,Jansz P,Khaghani A, Levy WC, WieselthalerGM. Multicenter evaluation ofan Support data. data. Support Circulatory Assisted Mechanically for Registry Interagency of analysis non-parametric thrombosis: II pump Smedira NG, Blackstone EH,Ehrlinger J, Thuita L,Pierce CD, Moazami N, Starling RC. Currentrisks of HeartMate Med failure. heart advanced for pump circulatory levitated magnetically A fully Investigators. 3 MOMENTUM C; Salerno JW, D,Long Horstmanshof GA, Ewald A, Itoh K, McCants DA, Dean KD, Aaronson FD, Pagani UP, Jorde CB, Patel CA, Milano MN, Walsh PC, Colombo Jr., JC, Cleveland DJ, Goldstein N, Uriel Y, Naka MR, Mehra ventricular assist device for advanced heart failure. failure. heart advanced for device assist ventricular left Intrapericardial CA. Milano OH, Frazier KD, Aaronson K, Leadley H, Mallidi ID, Gregoric AS, Anderson V, SS, Jeevanandam SW, Najjar Boyce EJ, Birks MS, G,Slaughter Bhat AJ, Tatooles FD, Pagani JG, Rogers 201723. Feb doi: 10.1093/eurheartj/ehx036. [Epubprint] ahead of weave. complex a systems: assist ventricular left with haemocompatibility of burden The MR. Mehra continuous-flow ventricular assist device recipients. recipients. device assist ventricular continuous-flow of cohort large in a infection drive-line of impact and Evolution E. N,Blackstone Moazami L, Thuita CE, Koval Circulatory Support). Support). Circulatory Assisted for Mechanically Registry (Interagency theINTERMACS using study a prospective transplantation: toheart as abridge device assist leftventricular flow withacontinuous study Administration-approval Drug and Food post-U.S. ofthe Results FD. Pagani DJ, Farrar DT, D, Pham DeNofrio WG, Cotts EC, Jr., McGee KD, Aaronson JV, Conte SD, U,Russell R,Jorde John G, Gonzalez-Stawinski AJ, Boyle Y, RC, Naka Starling 2009; device. assist left ventricular rotary a continuous-flow with support circulatory mechanical Extended OH. Frazier DJ, Farrar GA, Ewald N, Moazami JM, Aranda CT, Klodell L, Chen HT, Massey D, Mancini Y, TE,Naka MacGillivray RC, JV,Bogaev Conte AJ, Boyle R, John KD, Aaronson SD, Russell LW, Miller Pagani FD, patients awaiting heart transplantation. in device continuous-flow a of Use Investigators. IIClinical HeartMate OH; Frazier DJ, Farrar TE, MacGillivray RM, Delgado D, Mancini Y, Conte Naka JV, KD, Aaronson AJ, R,Boyle SD, John Russell FD, LW, Miller Pagani Columbia ramp study. ramp Columbia study. the devices: assist ventricular left in continuous-flow thrombosis ofdevice diagnosis and optimization speed testfor ramp novel echocardiography ofa Development Jorde UP. Y, Naka PC, Colombo R, H,John Takayama M, Flannery DM, Mancini SW, Restaino F, Latif M, Yuzefpolskaya TS, Kato AR, Garan KA, N, Morrison Uriel ambulatory heart failure patients: the ROADMAP study 2-year results. results. 2-year study ROADMAP the patients: failure heart ambulatory in management medical and device assist ventricular left of effectiveness comparative and assessment Risk Investigators. Study JG;ROADMAP DJ,Rogers Farrar J, Chuang AJ, Boyle DC, V, Haas CH, Kasirajan Selzman JW, S,Long Lee BA, Bruckner KB, Shah J, Stehlik CA, Milano DA, Horstmanshof JD, Estep RC, Starling with continuous-flowleft ventricular assist device. treated failure heart Advanced Investigators. II OH; HeartMate Frazier DJ, W, Farrar Ghumman TC, JW, Wozniak Long 3rd, RM Delgado AJ, Tatooles Sun B, D, Feldman JV, Conte SD, Russell CA, Milano JG, Rogers MS, Slaughter 2017; 33 54 :350–358. :312–321. 2017; 376 J Heart LungTransplant Heart J :440–450. 2011; 36 :1–12. J Heart Lung Transplant Lung J Heart J Am CollCardiol J Am 30 J Am CollCardiol J Am JAMA Intern Med :375–384. ASAIO J N Engl J MedN EnglJ 2015; 2011; 2012; N Engl J MedN Engl J 2018; 2016; 2014; 34 57 J AmColl Cardiol 60 J Heart Lung Transplant Transplant Lung Heart J :1527–1534. :1890–1898. 178 :1764–1775. 2014; N Engl J Med J N Engl 62 33 N Engl J Med J N Engl J Heart Lung Transplant Lung J Heart :520–529. 2007; :240–245. :486–491. 370 357 :33–40. 2011; 2009; :885–896. 2017; 57 361 JACC Heart Fail 376 2013; :1375–1382. :2241–2251. :451–460. 2014; 32 :675–683. 33 :1164–1172. 2017; J Heart Lung Transplant 5 :518–527. J Am CollCardiol J HeartLung Eur Heart J J Heart Eur N EnglJ J Heart J Heart

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 263. 261. 260. 259. 258. 257. 256. 252. 270. 269. 265. 264. 262. 255. 253. 268. 267. 266. 254.

341. trial. clinical controlled randomized, PAL-HF the failure: in heart care Palliative JA. Tulsky CM, O’Connor DB, Mark JL, Kirchner Jr, DH Taylor GC, Dodson KJ, Anstrom H, A,Yang Krishnamoorthy Steinha BB, RJ, Granger Mentz CB, Patel JG, Rogers 2017; of the Heart Failure Association of the European Society of Cardiology. Cardiology. of Society theEuropean of Association Failure Heart of the workshop care the palliative from statement aposition failure: in heart care Palliative J. McMurray F, Strasser L, E, Blue Delacretaz K, Dickstein P, A, Ponikowski Gavazzi SD, Anker A, Pitsis M, C, Leventhal Angermann Ekman I, M, I, Metra T, Bergh SA, Grodzicki Murray P, Mohacsi T, McDonagh FH, Rutten Ryder M, JM, Beattie Jaarsma T, Transplantation Guidelines forthe care of heart transplant recipients. and Lung Heart of Society International The J. Vanhaecke S, Russell H, Ross J, Rogers J, O’Connell C, Lewis A, M, Keogh Johnson J, Hosenpud L, Goldberg H, D,Eisen Delgado G, J,Wolfel D,Towbin Pini J, G, Patel J, Parry K,Kao W, Grady Lamour F, Dobbels R, Delgado M, Crespo-Leiro R, Chinnock C, G, Canter Bhat M, Burch Frigerio M, KfouryA,J, D,Kobashigawa Kim Shullo StehlikM, J, Teuteberg UberZuckermann J, P, A, Hunt S, MartinelliG, P,Gonzales-Stawinski S, Fisher S,Fedson M, Desai A,Chan Anderson R, Starling A, Dipchand MR, Costanzo L, McGiffin Rev Cardiol Curr art. the of state implantation: LVAD D,Minimally-invasive JD. Schmitto A, Haverich M, Avsar SV, Rojas JS, Hanke Smith J, Taylor D, Meiser B, Webber S, Baran D,Carboni M, DenglerT, FeldmanD, Engl JMed failure. inheart pump cardiac levitated amagnetically with outcomes Two-year 3Investigators. Y; MOMENTUM D,Long Gulati JW, G, V,Sayer Horstmanshof Jeevanandam JD, Estep BA, Bruckner UP, AJ, Jorde Tatooles WG, A, Cotts Krishnamoorthy D, Dean A, Itoh GA, Ewald CB, Patel CA, Milano MN, C, Walsh Salerno M, Jr, Yuzefpolskaya JC Cleveland N, Uriel DJ, Goldstein MR, Mehra transplantation. heart awaiting in patients pump centrifugal continuous-flow, intrapericardial, ofan Use Investigators. Trial ADVANCE Transplant to Bridge (HVAD) Device Assist Ventricular HeartWare SW; Boyce DR, Hathaway FD, Pagani RM, Bittman DC, Naftel WC, Levy JJ, Teuteberg RL, Kormos AS, Anderson V, OH, Jeevanandam Frazier P, Loyalka ID, Gregoric ML, MA, Jessup WG,Acker Cotts EC, LW, McGee Miller MS, Slaughter KD, Aaronson Transplant protocol. study clinical exemption device investigational 3) (MOMENTUM 3 HeartMate With Support Therapy Circulatory Mechanical Undergoing in Patients Technology MagLev of Study of theMulticenter rationale and trial design Clinical MR. Mehra D, J,Middlebrook Cleveland N, D, Uriel Goldstein P, Sood G, Heatley 2017; Dunn E,Teuteberg JJ. Leftventricular assist device malfunctions:itis more thanjust the pump. KormosRL, McCall M, Althouse A, Lagazzi L, SchaubR, Kormos MA, Zaldonis JA,Sciortino C, Lockard K, Kuntz N, Aspromonte N, Gulizia MM, Di Lenarda A, Mortara A, Battistoni I, De Maria R, Gabriele M, Iacoviello M, Navazio A, A, Navazio M, Iacoviello M, R,Gabriele Maria De I, Battistoni A, Mortara A, Di Lenarda MM, Gulizia N, Aspromonte Ed) Cardiology. of Society Spanish ofthe consensus scientific units: failure heart of standards Manito Lorite F, Vilchez Gonzalez MG, Leiro Crespo J, Colet R,Comin JL, Freire Bover Rodriguez M, Lambert Sanchez Anguita N, SegoviaCubero J, Ruiz Mateas F, ElolaSomoza FJ, Iniguez Romo A.Classification and quality and its management. and its management. prognosis failure heart of understanding clinicians’ and carers’ patients’, failure heart of study A care? palliative requiring illness terminal as a regarded be failure heart Should APS. Hungin H, Hancock H, Close R, Stocker JAMA Cardiol trial. clinical randomized a pilot (SWAP-HF): Failure Heart With Patients in High-risk Intervention Care Palliative Worker-Aided Social AS. Desai MR, WalshK,Mehra K, DeVoe LW, Stevenson KG, Schaefer AE, O’Donnell Bayoumi E, Sheikh F, Groninger H. Palliative care in cardiac transplantation: an evolving model. model. evolving an transplantation: in cardiac care Palliative H. Groninger F, Sheikh E, Bayoumi heart failure – 1 year results from the CE mark trial. trial. CE mark from the results –1year heart failure advanced of treatment the for device assist left ventricular levitated magnetically 3 fully Y.HeartMate L, Pya Damme S, Marasco F, Beyersdorf M, Morshuis V, Rao J, Garbade D, Zimpfer JD, Schmitto I, T, Netuka Krabatsch versus the Heartmate II. II. Heartmate the versus HVAD HeartWare the with to transplantation bridge undergoing inpatients transplantation heart after orthotopic Survival AS. Shah GJR, Whitman CM, Sciortino SD, Russell RJ, Tedford TC, Crawford JC, Grimm JT, Magruder Pathways. Pathways. Decision Consensus Expert on Force Task Cardiology of College American of the report a fraction: ejection reduced with failure heart about issues pivotal to 10 answers treatment: failure heart of optimization for pathway decision consensus Expert ACC 2017 A. Wasserman MN, Walsh JH, Patterson SR, Motiwala FA, Masoudi TM, Maddox J, Lindenfeld M, Jessup NE, Ibrahim GC, Fonarow LL, Davis J, Butler LA, Allen JL Jr, Januzzi CW, Yancy 2017; failure. heart advanced in referral timely aid to mnemonic Help”–A Need “I J. Baumwol deviceas destination therapy. assist left ventricular with a Dying KM. AJ,Swetz JM, Luckhardt Stulak SE, Wordingham Strand JJ, SM, Dunlay multicenter study. study. multicenter a HF: advanced treating for system assist ventricular left levitated magnetically Fully JD. Schmitto L, Damme F, Beyersdorf S, Marasco M, V, Morshuis Rao J, Garbade T, Krabatsch D, Zimpfer Y, Pya P, I, Sood Netuka 2016; 22 136 36 :605–610. :593–594. 69 :1714–1725. 2016; 2018; J Am Coll Cardiol :940–950. 201811.Apr 10.1001/jamacardio.2018.0589. doi: [Epub aheadofprint] 2015; Circulation 35 378 J Am Coll Cardiol Coll Am J :528–536. :1386–1395. BMJ Support Palliat Care Palliat Support BMJ 11 Ann Thorac Surg Ann Thorac :246–251. 2012; 2018; Circ Heart Fail 125 71 2015; :201–230. :3191–3200. 2017; 66 2016; :2579–2589. 2017; 103 9 :e003096. :1505–1511. J CardiothoracSurg 7 :464–469. user KE, Fiuzat M, Adams PA, Speck A, Johnson KS, A, Speck Johnson Adams PA, M, KE,Fiuzat user S, Skipper ER, O’Connell JB, Heatley G, Sood P, Naka Naka P, Sood G, Heatley JB, O’Connell ER, Skipper S, J Heart Lung Transplant Lung Heart J Eur J Heart Fail Heart J Eur 2017; 12 J Am Coll Cardiol Coll Am J :23. 2009; J Heart Lung Transplant Lung J Heart Rev Esp Cardiol (Engl (Engl Cardiol Esp Rev 11 2010; :433–443. 2017; Heart Fail Rev Fail Heart J Heart Lung J Heart Lung 29 :914–956. Circulation 70 :331– N

This articleisprotected bycopyright.Allrightsreserved. Accepted Article 272. 271. 278. 277. 276. 275. 273.

274.

cardiology networks for outpatient heart failure care. care. failure heart outpatient for networks cardiology Pini D,Di Tano G, MariniM, Ricci RP,Alunni G,Radini D,MetraM, Romeo F. ANMCO/SICConsensus Document: 2017 Jun1. doi: 10.1177/2048872617719652. [Epubprint] ahead of France. Metropolitan Island and Reunion between Cooperation transplantation: heart emergency for oxygenation membrane extracorporeal venoarterial on patients shock cardiogenic of transfer kilometre thousand N. Ten Allou O, Martinet C, E, Brulliard F,Braunberger Nativel B, Bouchet J, C,Allyn Charon Herzinsuffizienz. undchronischen der akuten Behandlung (HF Netzwerken Herzinsuffizienz- von Organisation und Aufbau S, BöhmM. Wv, Welz Scheidt S, Störk PWJ, Raake S, M, Perings Ertl G, Angermann CE, Bekeredjian R, Beyersdorf F,Güder G, Gummert J, Katus HA, Kindermann I,Pauschinger cardiac-RESCUE program). program). cardiac-RESCUE study (the a pilot in institutions: remote patients shock cardiogenic in refractory support circulatory Emergency BeurtheretS, Mordant P, Paoletti X, Marijon E, Celermajer DS, Leger P, PavieA, Combes A, Leprince P. Transplant shock. cardiopulmonary in patients unstable of management and transfer the expedite to concept Jaroszewski DE, Kleisli T, Staley L, Pierce C,Scott R, SteidleyDE, DeValeriaP, Arabia FA. Atraveling team J ASAIO driver. Ikusstationary the with patients ofnonambulatory transports VADinterhospital pediatric EXCOR heart Berlin First PD. S,Wearden B,Winowich E, J,Miller Morelli J, Sanchez-de-Toledo S, Spinnato JR, Dady Woolley airbridge for circulatory support inthe Carribean. Lebreton G,Sanchez B, Hennequin JL, ResiereD, HommelD, Leonard C, Mehdaoui H, Roques F. The French refractory cardiogenic shock. shock. cardiogenic refractory Dini CS, Lazzeri C, Chiostri M, Gensini GF, Valente S. Alocal network for extracorporeal membrane oxygenation in transport. transport. patient LVAS Intercontinental TV. Mussivand G, JP, Lavallee A, Veinot PJ, Kawai Hendry RG, Haddad M,Masters 2013; 2011; Ann Thorac Surg Thorac Ann 59 ‑ 30 :537–541. NETs) und Herzinsuffizienz-Einheiten (“Heart Failure Units”, HFUs) zur Optimierung der der Optimierung zur HFUs) Units”, Failure (“Heart und Herzinsuffizienz-Einheiten NETs) :618–623. 2004; Eur Heart J Acute Card Care Card Acute 78 :1818–1820. 2013; 34 2015; :112–120. Interact Cardiovasc Thorac Surg Thorac Cardiovasc Interact 17 Eur Heart J Suppl Heart J Eur :49–54. Der Kardiologe Der 2017; 2016; 19 10 Eur Heart J Acute Cardiovasc Care Cardiovasc JAcute Heart Eur (Suppl D):D89–D101. 2012; :222–235. 15 :420–425. J Heart Lung

This articleisprotected bycopyright.Allrightsreserved. Accepted Article resynchronization therapy; ICD,implantable cardioverter-defibrillator. cardiac CRT, system. care health ofthe needs local to the tailored be can which concept, ofthe overview directreferral to the tertiary hub bypassing thespecializ circumstances in some but HFunit, aspecialized to referred be will first patients typically (i.e. referral/communication for pathways secondary indicate lines Dashed referral. and communication lines of main reflect lines Solid described. are (red) centres tertiary and (orange), HF specialized (yellow), cardiology general care, for primary Theroles HF. advanced with patients for model ofcare ahubandspoke of the structure for aconcept presents figure 2 Figure RAS, renin–angiotensinsystem; SBP, systolic blood pressure; SCr, serum creatinine. Association; Heart New York NYHA, fraction; ejection left ventricular LVEF, cardioverter-defibrillator; implantable ICD, therapy; resynchronization cardiac CRT, disease; pulmonary obstructive chronic COPD, inhibitor; receptor–neprilysin 1 Figure Conceptual structure of a hub and spoke model of care for patients with advanced heart failure (HF). This This (HF). failure heart with advanced patients for care of model spoke hub and a of structure Conceptual Triage of patients with advanced heart failure (HF) and appropriatetiming of referral. ARNI, angiotensin ed HF centre may be appropriate.) This model depicts an depicts model This beappropriate.) may ed HFcentre 5. 6. Heart Failure Association Failure Heart 6MWT, 6-minute walk test; ACE, angiotensin-converting enzyme; AD enzyme; ACE, angiotensin-converting test; walk 6-minute 6MWT, 4. 1. Table 1 2. 3.

emergency department; HF, heart failure; HFSS, Heart Failure Surviv Failure Heart HFSS, failure; heart HF, department; emergency pro-B-type natriuretic peptide; NYHA, New York Heart Associatio Heart New NYHA, York peptide; natriuretic pro-B-type Failure Score; VO Score; Failure

History of are poorly tolerated or contraindicated, and CRT, when indicated these unless beta-blockers, and system, angiotensin–aldosterone renin– the of inhibitors diuretics, including therapy optimize’ to ‘attempts despite features previous the all of Presence b) a) following: Severe impairment of functional capacity shown by one of the d) with minimal exertion (NYHA functional orclass III IV) Severe symptoms of HF with dyspnoea and/or fatigue at rest or c) at (peripheralrest hypoperfusion) congestion, peripheraloedema) and/or ofreduced cardiacoutput Episodes of fluid retention (pulmonary and/or systemic b) a) least one of the following: byat shown severe dysfunction, cardiac of evidence Objective c)

This article isprotectedby copyright. Allrights reserved. 6MWT distance <300 distance 6MWT cardiac causes non- of absence levels, in the plasma BNP or NT-proBNP High Inability to exercise Inability mean RAP>12 mmHg by pulmonary artery catheterization) and/or mmHg, >16 (mean PCWP pressures filing LV High inflow pattern mitral restrictive or apseudonormal with echocardiography A abnormality severe of functioncardiac on Doppler A low LVEF (<30%) LVEF A low Peak VO Peak Accepted≥ Article 75 years years 75

Prior definitions and indicators of advanced heart failure heart advanced of indicators and definitions Prior ≥ 2 1 HF hospitalization in the past 6 monthspast the in 1 HFhospitalization <12to 14mL/kg/min 2 , oxygenconsumption.,

m or less in females and/or patients aged and/orm or patients infemales less 4 American College of Cardiology/American Heart Association Heart Cardiology/American of College American n; PCWP, pulmonary capillary wedge pressure; RAAS,wedge renin–angiotePCWP, pulmonarypressure; n; capillary al Score; ICD, implantable cardioverter-defibrillator; l implantable LV, Score; ICD, al L, activities of daily living; BNP, B-type natriuretic peptide; BNP,natriuretic B-type living; daily of activities L, 10. 9. 8. 7. 6. 5. 4. 3. 2. 11. 1.

use of supplemental metolazone therapy reaching daily furosemide equiva often status, volume to diuretics needto maintain escalate Recent fatigue to or due walk to ground 1 Inability thelevel dyspnoea on block Persistent dyspnoeawith dressingbathing or requiringrest Frequent systolic blood pressure <90 mmHg orhypotension HF worsening to due beta-blockers to Intolerance renal function worsening and/or hypotension dueto inhibitors ACE to Intolerance Weight loss without othercause (e.g. cardiac cachexia) creatinine) deterioration in Progressive renal Progressive declineProgressive in serum sodium, usually <133 to mEq/L ( Repeated Frequent ICD shocks ≥ 2) hospitalizations or ED visits for HF in the past year year past HFin the for visits ED or hospitalizations 2) lent dose >160 mg/day and/or function (e.g.rise in andBUN eft ventricular; LVEF, left ventricular ej BUN, blood urea nitrogen;CRT, cardiacresynchronization therapy; ED, nsin–aldosterone system; RAP, right atrial pressure; SHFS, Seattle Heart Seattle Heart system; RAP, right SHFS, atrial pressure; nsin–aldosterone 5,6 Heart Failure Society Heart FailureAmerica of • • include: therapies advanced of evaluation for referral sh that therapies and electrical optimal medical of setting the HF in ofadvanced Indicators the HF syndrome. by driven primarily be and mortality. Importantly, the progressive decline should isas poor qualityof lifeand and tolerance, exertional limited severely hospitalization, and devicetherapy. It is gene and symptoms ofHF despite The presence of progressive and/orpersistent severe signs • • • • • • • • • • • • •

Peak VO Peak function end-organ to maintain or relief Need for intravenous inotropic therapy for symptomatic Inability to perform Inability ADL cachexiaCardiac frequentshocks ICD Recurrent refractory ventricular tachyarrhythmias; (serum <134 mEq/L) hyponatraemia sodium Persistent Progressive renal or hepatic end-organ dysfunction HF survival models (e.g.SHFS, HFSS, etc.) Increased 1-year mortality (e.g. 20–25%) predicted by symptoms III–IV functional class NYHA Progressive/persistent blocker therapy beta- or inhibition RAAS to Circulatory–renal limitation function renal worsening with associated refractoriness Diuretic hypertension Worsening right HF and secondary pulmonary months last 12 the in or clinic) ED (e.g. visits unscheduled >2 ≥ 6MWT distance <300 2 HF admissions in the last 12 last monthsthe HF admissions2 in 2 <14 mL/kg/min or <50% of predicted ection fraction; NT-proBNP, N-terminal N-terminal NT-proBNP, fraction; ection

m sociated with high morbidity morbidity high with sociated optimized medical, surgical, rally accompanied by frequent ould trigger consideration of consideration ouldtrigger 3

Reprinted with permission from Stevenson Profile ADL, activities of daily living; ECMO, extracorporeal membrane membrane extracorporeal ECMO, living; daily of activities ADL, usually defibrillator, external contributed substantially toclinical compromise. This Recurrent profile. any can modify A-Arrhythmia INTERMACS devices). Thisincludes IABP,ECMO, TandemHeart, Levitronix, BVS5000 or AB5000, Impella. only modify can TCS-Temporary Support Circulatory 2: decline Profile Progressive 1: Profile Critical cardiogenic shock Circulator Assisted Mechanically for Registry 2 Interagency Table Modifiers for profiles NYHA III 7: class Advanced Profile limited 6: Exertion Profile intolerant 5: Exertion Profile 4: symptoms Profile Resting inotrope-dependent but 3: Stable Profile or hospitalizations for diuretics, fordiuretics, or hospitalizations ultrafiltration design only modify outpatients, Flyer can FF-Frequent Patient with declining function despite intravenous intravenous despite function declining with Patient acid by worsening confirmed often hypoperfusion, organ critical support, inotropic escalating rapidly despite hypotension life-threatening with Patients to mild physical exertion. exertion. physical to mild balance, fluid of unstable recent episodes or current futu in specification precise for more placeholder A wounded.” “Walking impairment. of cardiac severity to confirm monitoring haemodynamic limitation cardiac of careful requires measurement to Attribution any activity. of meaningful minutes first few afterthe fatigues the but home outside activities minor and ADL andwith rest, at is comfortable overload fluid of evidence without Patient intervention. definitive patientsmarginal, are mafunction organ and status underlyingrefractory elevated volume status, ofte but have may symptoms, at congestive rest without are comfortable Patients house. the within Comfortableat rest and with ADL but unableto engage inany other activity,living predominantly and 5. compliance that would compromiseoutcomes with any therapy. Some patients may shuttlebetween 4 strategies and management should be surveillance at restor during ADL.Doses of diuretics genera closeto can be Patient normal volume stabilized st “Dependent stability.” failure to wean from support due to recurrent repeated both),demonstrating but or device support a(or support temporary circulatory inotropic intravenous continuous on symptoms and nutrition, function, organ pressure, blood stable with Patient therapy. inotropic tolerate to unable in patients status declining describes inability to depletion, function,re renal nutritional

This article isprotectedby copyright. Allrights reserved. Accepted Article more than twice weekly. weekly. than twice more et al et , or temporary intravenous vasoactive therapy. . ventricular tachyarrhythmias havethat recently 8 symptomatic hypotension or renal dysfunction. dysfunction. or renal hypotension symptomatic

lly fluctuate at very high levels. More intensive levels. veryhigh at lly fluctuate store volume volume store “Slidingbalance. on inotropes.” Also osis and/or lactate levels. “Crash and burn.” “Crash and lactatelevels. and/or osis n withrenal dysfunction. If underlying nutritional includes frequent ICD shocks or requirement for patients in hospital (other devices would be be would devices (other hospital in patients re, this level includes patients who are without without whoare patients includes this level re, atus but experiences daily symptoms of congestion of symptoms daily experiences but atus inotropic support, may be manifest by worsening peak oxygen consumption, in some cases with considered, which may in some cases reveal poor reveal cases some may in which considered, ating ating a patient frequent requiring visits emergency living living comfortably withmeaningful activity limited y be more at risk than INTERMACS 4,and require oxygenation; IABP, intra-aortic balloon pump; ICD, implantable c balloonoxygenation;intra-aortic implantable pump; ICD, IABP, y Support (INTERMACS) profile descriptions in patients with ad with patients in descriptions profile (INTERMACS) Support y Definitive intervention needed within hours. for frame intervention Time 1, 2,3 in hospital. Transplantation or circulatory support may not currently be indicated. indicated. be currently not may support circulatory or Transplantation level. nu of maintenance upon depends Variable, activity. and function, organ nutrition, of upon maintenance depends urgency, Variable Definitive intervention elective over a period of weeks to few months. Definitive intervention elective over a period of weeks to few months. days. few within needed intervention Definitive Possible profilesmodify to 3 if at home, 4, 5, 6. A Frequent6. A home, 4,5, at if Flyerwould 3 rarelybe profile 7. Any profile. ardioverter-defibrillator; NYHA, New York Heart Association. New Association. York NYHA, Heart ardioverter-defibrillator; vanced heart failure failure vanced heart trition, organ function, and activity activity and trition, organfunction, This articleisprotected bycopyright.Allrightsreserved. Accepted Article Heart Association; pVO leftventricular;LV, leftventricula LVEF,

Heart Failure Association;Heart with heart HFmrEF, failure mid-range ARVC, arrhythmogenic right ventricular cardiomyopathy; BNP, B-type 1. All the following criteria mustbe present despiteoptimal guideline-directed treatment: heart failure advanced defining 3 for Table Updated criteria HFA-ESC 2. 3. 4. evaluation as someone in whom the only disease is cardiac, but the therapeutic options for these patients are usually more limi more usually are patients these for options therapeutic the but cardiac, is disease only the in whom someone as evaluation limited oflifeand quality have still patients These aetiology). to due limitation conditions other severe pulmonary(e.g. disease, who1 dysfun have cardiac Criteria inpatients and 4 met can be typepulmonary 2 hypertension may be present, arebutnot required. In addition to the above, extra-cardiac organ dysfunction due to heart failure (e.g. cardiac cachexia, liver, or kidney dysfunc

Severe and persistentfa symptomsheart of dysfunction dysfunction or LVabnormalities accord structural abnorm orcongenital abnormalities LVEF a reduced by defined dysfunction cardiac Severe output requiring inotropes or vasoactive drugs or malignant arrh Episodes of pulmonary or systemic congesti months. months. Severe impairmentSevere inability capacity ofexercise with or to exercise low6MWTD (<300 ofcardiac origin.be 2 , peak exercise oxygen consumption; RV, right ve right RV, oxygen consumption; exercise peak , alities or persistently high (or increasing) BNP or NT-proBNP values and data of severe diast data severe of and values NT-proBNP BNP or increasing) (or high persistently or alities r ejectionr fraction; NT-proBNP, N-terminal on requiring high-dose high-dose intrav on requiring ilure [NYHA class III (advanced) or IV]. or IV]. (advanced) III class [NYHA ilure ing to the ESC definition of HFpEF and HFmrEF. and HFpEF of ESC the definition ing to ≤ 30%, isolated RV failure (e.g. ARVC) or non-operable severe valve ejectionfraction; HFpEF, heart failure withpreserved ejection survival due to advancedsurvival due diseas non-cardiac cirrhosis, or most commonly by renal disease wit renal disease by commonly or most cirrhosis, non-cardiac ythmias causing >1 unplanned visit or hospitalization in the la ction (as described in criterion criterion in described (as ction natriuretic peptide; ESC, European natriureticof Cardiology; ESC,HF peptide; Society ntricular; 6MWTD, 6-minute distance.test walk enous diuretics (or diuretic combinations) or episodes o pro-B-type natriuretic peptide; NYHA, New

m) or pVOm) or e and warrant the same intensi thesame e and warrant 9 2

#2), #2), but who alsohave substant (<12–14 mL/kg/min), estimated to fraction; ted. ted. h mixed h mixed tion) or st 12 st olic f low York ty of ial A, A, This articleisprotected bycopyright.Allrightsreserved. Accepted Article JVD LV LV Aortic hypertrophy stenosis Higher NYHA class Oedema Left atrial enlargement V Reduced miBG uptake Reduced 6-min walk test 6-min walk Lower Echocardiography LVEF Imaging Copeptin S3 Increased NT-proBNP over time over NT-proBNP Increased Diastolic Diastolic dysfunction Reduced peripheral muscle strength muscle peripheral Reduced Poor quality oflife Low T3 Uric Uric Lower acid LDL ESR Recent /recurrent HF hospitalizations Pulmonary hypertension Poor viability on stress echo and CMR echo on stress Poorviability CMR on fibrosis and Inflammation Mitral Mitral regurgitation ANP Higher BNP and/or NT-proBNP Cardiomyocyte stress Large areas of hypo/akinesis LV dilatation Albuminuria Reduced HRvariability Reduced Age General clinical in 4 Riskmarkers patients Table pVO Cardiopulmonary exercise test Cardiomegaly CRP Inflammation Troponin Cardiomyocyte injury Lower and labile Lower and SBP andlower DBP MAP and Longer HF duration HF Longer MR-proADM Restingdobutamine stress strain ↑ Lower pulse pressure Male sex ST2 fibrosis and stress Oxidative Right ventricular function ↑ Laboratory andbiomarkers Ascites Hepatomegaly Ischaemic heart disease/prior Ischaemic infarction myocardial Cardiovascular Co-morbidity GDF-15 Low sodium LV LV mass Peripheralarterial disease attack/stroke transient ischaemic Prior MR-proANP Rales Galectin-3 Haemodynamic profiles Pulmonary congestion by ultrasound lung by congestion Pulmonary Other imaging

E HR in sinus rhythm butnot in atrial fibrillation QRS duration QRS /V 50 50 30 2

CO2 CO2 59,88 30

slope 56 65,66 67 64 30

31 51, 122, 123

70 126

52 72 69

25,64 53-57

125 32,33

62,124 72–74 127 68 71 74

34–37

30 72,77

45–47

30 48,49 75,76

86,87

72,78,79

80,82

80,81

121

56,58–62 53,63 with advanced heart failure failure heart advanced with 120 83,84 30

30,38–40 85

30,42–44

This articleisprotected bycopyright.Allrightsreserved. Accepted Article HFSS Liver dysfunction and low albumin low and dysfunction Liver Iron deficiency SHFM Cachexia INTERMACS UCLA score Cognitive dysfunction Diabetes Frailty type natriuretic peptide; NYHA, New York Heart Association; pVO Association; YorkHeart NYHA, New natriuretic peptide; type MR-proADM, mid-regionalpro-adrenomedullin; MR-proANP,mid-region pressu mean arterial metaiodobenzylguanidine; Failure;MAP, Heart miBG, Chronic in Group Global Meta-Analysis MAGGIC, fraction; low-de LDL, distention; venous jugular JVD, Support; Circulatory implantable rate;cardioverter-def heart ICD, HR, Survival Score; blood pressure; ESR, erythrocyte sedimentation rate; GDF-15, growth differentiation factor 15;HF, heart failure; HFSS, Heart F natriu BNP,B-type Failure; in Chronic Heart natriuretic atrial peptide;ANP, Bio-HF, BCNBio-Hear Barcelona Chronic suddenarrhythmia, Ventricular cardiac death, ICD shocks Non-cardiovascular kidney disease Atrial fibrillation Composite scores Diuretic resistance Higher red cell distribution width BIOSTAT-CHF Chronic obstructive pulmonary disease Smoking BCN Bio-HF BCN Anaemia Simplified variables Simplified Poor guideline adherence factors organization-related Treatment and relationship. MAGGIC Model; SBP, systolic blood pressure; UCLA, UCLA, pressure; blood systolic SBP, Model; Sleep apnoea and Cheyne–Stokes breathing Depression Higherwhite blood count cell 111–117 109,110 105,106 99

118 108

8,104 91 30 30 30,100,101

107

96–98

103 27,28 30

119 102 89,90

92 94,95

University of California, Los Angeles; V Los Angeles; California, of University retic peptide; CMR, cardiac magnetic resona magnetic cardiac CMR, retic peptide; t Failure; BIOSTAT-CHF,t to Biology ASystems StudyTailored Trea ibrillator; INTERMACS, Interagenc nsity lipoprotein; LV, left ventricular; LVEF, leftventricular ventricular; LVEF, left LV, lipoprotein; nsity 2 , peak exerciseoxygen consumption; SHFM,Seattle Heart Failure al pro-atrial natriuretic peptide;NT-proBNP,al N-terminal pro-B E /V CO2 , minute ventilation–carbon productiondioxide nce; CRP, C-reactive protein; DBP, diast y Registry forMechanically A yRegistry ejection ssisted ssisted tment ailure olic re; -

MAGGIC Metabolic Exercise test data combined with Cardiac and Kidney Indexes; NYHA, New York Heart Association; SHFM, Seattle Heart Fa Heart Seattle SHFM, Association; Heart York New NYHA, Indexes; Kidney and Cardiac with combined data test Exercise Metabolic Chron in Global Group Meta-Analysis MAGGIC, fraction; ejection ventricular left LVEF, defect; conduction intraventricular IVCD, BP, blood pressure; COPD, chronic obstructive pulmonary disease; SHFM HFSS Score Components Table 5 Prognostic scores MECKI relationship; VO 133 This article isprotectedby copyright. Allrights reserved. 109

Accepted 134–136 Article

105

2 , oxygen consumption. consumption. oxygen , HFSS = [(0.0216 = HFSS • • • • • • • www.heartfailurerisk.org • • • • • • • • • • • • • • • • www.seattleheartfailuremodel.org • • • • • • disease)] absence of IVCD) +(0.6931 (–0.047

Peak oxygen uptake oxygen Peak Serum sodium delay conduction intraventricular of Presence/absence arterialMean blood pressure ventricularLeft ejection fraction rate heart Resting Presence/absence coronary artery disease Medications Length of failureheart diagnosis Co-morbidities (e.g. diabetes, COPD) Smoking history class NYHA Serum creatinine Body mass index pressure blood Systolic LVEF Gender Age V eGFR by MDRD LVEF Serum sodium Haemoglobin Devices Devices Laboratory data Medications characteristics Clinical Demographics Percent predicted peak VO peak predicted Percent E /V CO2

slope serum sodium) + (–0.0546+ serum sodium)

resting (–0.0255 HR) +

* 2

presence or absence of ischaemic heart heart ischaemic of absence or presence

peak VO

mean BP) + (–0.0464mean BP) + 2 ) + (0.608 ) + CPET,cardiopulmonary exercisetest; eGFR, estimated glomerula

presence or or presence

LVEF) + LVEF) Generalizable toGeneralizable a broad score model into integer Risk converted Incorporatesdata fromtheCPET Comments estimates of 1, 2, andestimates of1,2, 5-year survival intervention of impact Incorporates High-risk: HFSS Medium-risk: HFSS 7.20 to 8.09 Low risk: coefficients is onScore based a sumofthese variables defined multiplied by ≥ 8.1 8.1 ≤ 7.1 7.1 spectrum of patients spectrum patients of as well as kidneywell function as ic Heart Failure; MDRD, Modification of Diet in Renal Disease; MECKI,Disease; Renal Failure; in MDRD,Diet Heart Modificationic of s (medicaland device) andprovides r filtration r filtration rate; HFSS, Heart Failure Survival Score; HR, heart rate; ilure Model; V Model; ilure E /V CO2 , minute ventilation–carbon dioxide production ventilation–carbon dioxide minute , transplantation listing or left ventricular assist device implan device assist ventricular or left listingtransplantation in patients who do not need referral, but by considering these these considering by but referral, need not do who patients in

*Note that this table reflects many clinically relevant but so but relevant many clinically reflects table this that *Note RV, right artery; pressure;ventricular; SBP,blood SCr, • • • • • • † HeartChronic Failure; MLHFQ, Minnesota withHeartLiving Failure pota vena inferior cava;K, haemoglobin; failure; IVC, HF, heart 6MWT, 6-min walk test; CPET, cardiopulmonar • • • • • Laboratory Clinical 6 SuggestedTable clinical, laboratory,and echocardiographiccriteria trigger to referral* Imaging Risk score data Moderate mitral regurgitation alone is not sufficient, but is one one is but sufficient, not is alone regurgitation Moderate mitral

MLHFQ KCCQ Cachexia, unintentio CRT non-responderclinically 6MWT to CPETperform Inability SBP requirement diuretic Increasing Intolerant of optimal dose of any GDMT HF drug class III–IV NYHA >1 HF hospitalization in lastyear

This article isprotectedby copyright. Allrights reserved. Accepted Article ≤ 90 mmHg nal weight loss loss nal weight yexercise test; CRT, cardiac resynchronization therapy; eGFR, estimated glomerular serum creatinine; SHFM, Seattle Heart FailureModel. Heart creatinine; serum SHFM, Seattle • • • • • • • •

Low albumin test function liver Abnormal NT-proBNP NT-proBNP Hb Hyponatraemia K >5.2or <3.5 mmol/L SCr eGFR <45 mL/min metimes subjective and non-specific criteria. With these criteria these With criteria. non-specific and subjective metimes tation, there are no data to support specific cut-offs for refe for cut-offs specific support to data no are there tation, ≤ ≥ criteria in a comprehensive criteria inathereis assessment, comprehensive lower risk th 120 g/L 160 mmol/L factor suggesting risk of progression and should considere risk be should of progression and suggesting factor ssium; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEF, le LVEF, ssium; KansasCityCardiomyopathy KCCQ, Questionnaire; Questionnaire; NT-proBNP, N-terminal pro-B-type Questionnaire; sodium; n Na, ≥ 1000 pg/mL • • • • • • • •

Moderate area ofakinesis/dyskinesisLarge aneurysm or LVEF IVC dilated or without respiratory variation orwithoutrespiratory dilated IVC Difficult tograde aortic stenosis regurgitation tricuspid Moderate-severe PA pressure RV dysfunction ≤ 30% 30% † -severe mitral regurgitation ≥ 50 mmHg rral to a HF centre. , sensitivity has been prioritized hasbeen sensitivity , over specif d together with other variables. variables. other with together d at high-risk patients may be missed or referred too late. While cut-offs exist for cut-offs While late. too or missed referred may be patients at high-risk ft ventricular ejection fraction; MAGGIC, Meta-Analysis Global Group in in Group Global MAGGIC, Meta-Analysis fraction; ft ejection ventricular atriuretic peptide; NYHA, New York Heart Association; PA, pulmonary filtration filtration rate; GDMT, guideline-directed therapy;medical Hb, • •

SHFM predicted survival survival predicted MAGGIC icity, i.e. many criteria may be present present manycriteria may be i.e. icity, ≤ 80% at 1 year ≤ 80% 1year at Vasopressin V1 and V2 activation activation V2 V1and Vasopressin CO, cardiac output; PDE2, phosphodiesteras Beta-1 activation, slight beta-2 Dobutamine Inodilators Table 7 Inotropes and vasoconstrictors Mlioe PDE2 inhibition Milrinone Lvsmna Calcium sensitization Levosimendan ntoe/aoosrcos Beta-1, al Dopamine Inotropes/vasoconstrictors Arnln Beta-1, alpha-adrenergic, Adrenaline aoosrcos Beta Norepinephrine Vasoconstrictors

This article isprotectedby copyright. Allrights reserved. Accepted Article Mechanism of action Haemodynamic effect Comment Comment effect Haemodynamic vasodilatation action of Mechanism dopaminergic activation moderate beta-2 activation activation beta-2 moderate -1, alpha activation pha-adrenergic, and e-2; SVR, systemicvascular resistance. SVR CO CO CO CO SVR CO ↑ ↑ ↑ ↑ ↑ ,SVR ,SVR ,SVR ,SVR ,SVR ↑ ↑ ,CO ,CO ↔ ↔ ↓ ↓ ↓ ↑ ↑ / / ↓ ↓

Half-life minutes minutes Half-life Half-life 2 Half-life Half-life (metabolite) days (metabolite) Half-life >10 µg/kg/min: alpha, beta-1 2–10 µg/kg/min: beta-1

h BMI, body mass index; HF, heart failure; failure; HF, body index; heart mass BMI, Contraindications 1. 1. consider to Patients Table 8 Indications and contraindications to heart transplantation Adapted from Ponikowski Ponikowski from Adapted

This article isprotectedby copyright. Allrights reserved. Accepted Article 8. 7. 6. 5. 4. 3. 2. 3. 2. 10. 9.

et al

achieve a <35BMI kg/m Pre-transplant BMI >35 kg/m >35 BMI Pre-transplant serious co-morbidity with poor Other prognosis diseaseSystemic withmultiorgan involvement mL/min) Irreversible renal dysfunction (e.g. creatinine clearance <30 stratify each patient as to their risk of tumour recurrence) Cancer (a collaboration withoncology should occur specialists to candidacy) with considered subsequent be Pharmacologic irreversible pulmonary hypertension (LVAD should Severe peripheralarterial infection Active postoperatively Capable of complying with the intensive treatment required informed,and emotionallyMotivated, well stable remaining alternative treatment options no and prognosis, apoor symptoms, severe with HF End-stage achieve compliant in achieve care to insufficient deemed are supports social whom for patient Any Current alcohol or drug abuse abuse drug or alcohol Current . 9 and Mehra Mehra and LVAD, left ventricular assist device. et al . 25

2 the outpatient setting setting outpatient the ) or cerebrovasculardisease 2 (weight loss is recommended to to recommended loss is (weight re-evaluation establish to Psychosocial Complete evaluation evaluation Complete Psychosocial Hepatitis B and C Antibody/antigen testing testing Antibody/antigen Band C Hepatitis Renal impairment Estimated GFR Estimated impairment Renal CD4, cluster of differentiation 4; GFR, gl index mass Body (e.g. damage neuropathy, End-organ nephropathy) Diabetes mellitus Obesity Age Parameters Co-morbidity co-morbidities in assessment of 9 Table Considerations to evaluate

usac bs Tobacco (including environmental or second-hand exposure) HIV Substance abuse disease vascular Cerebral orperipheral Cancer Active malignancy Chagas diseaseChagas 210,211 208 This article isprotectedby copyright. Allrights reserved. Accepted Article Frailty Active or or infections prior opportunistic Active 212 Serology testing for Potential for adherence therapyto adherence for Potential biopsy Liver Serology Viraemia tests function Liver HCV RNAPCR Candidacy for combined heart/kidney transplant heart/kidney forcombined Candidacy Presence of renal arterialdisease Proteinuria estimation Renal ultrasonography haemoglobin Glycated Local organ availability and quality quality and availability organ Local Co-morbidity burden Recreational drugs drugs Recreational Alcohol rehabilitation to limit Potential to work-upseverity clinical Diagnostic asindicated assess Metastatic work-up therapy to response type, tumour Previous for Collaboration withoncologist CD4 count RNA HIV to combination anti-retroviral Adherence therapy omerular filtration rate; HCV, hepatitis C virus; HIV, human immunodeficiency virus; virus; human immunodeficiency virus;C HIV, hepatitis HCV, filtration rate; omerular T. cruzi in patients at risk risk at patients in prior cancer previously treated 213

209

PCR, polymerasePCR, chainreaction;ribonucleic RNA acid. Assessment and Comparative Effectiveness of Left Ventricular ofLeft Assi and Effectiveness Ventricular Comparative Assessment Studyof MagLev Technologyin Patients Undergoing Mechanical Ci System Assist Ventricular theHeartWare of Evaluation De Assist Ventricular Left HeartWare the of Evaluation ADVANCE, studies Ongoing/future Abbott) risks Major trials clinical from major Evidence Medtronic) HeartWare (HeartWare, characteristics Device Abbott) Jude, HeartMate (Thoratec, St. II Device Table 10 Overview of long-term mechanical circulatory support devices

HeartMate 3 (St. Jude,

This article isprotectedby copyright. Allrights reserved. Accepted Article 234,254–256,258 235,248–253,257 151,223,239–247

cannula to ascending aortato ascending cannula ventricular apex, and via outflow connected via inflow cannula to left Implanted in pre-peritoneal pocket, pump Axial flow driveline tocontrollerdriveline pericardialconnectedviawithin space, completely positioned and Implanted Continuous flow centrifugal pump rotor, artificial pulse levitated magnetically bearing-less Continuousflow, centrifugal pump, for Destination Therapyof vice for the Treatment of Advanced Heart Failure; BTT, bridge to Failure;Heart BTT, ofAdvanced bridge Treatment the for vice st Device and Medical Management st Device in Ambulatory Heart FailureP rculatory Support Therapy with HeartMate 3; NYHA, New York Heart BTT strategy (prospective, single-arm, single-arm, (prospective, strategy BTT survival 6 months, 68%survival 6months, survival 12months II, bothBTT and DT, MOMENTUM 3 (randomized, HeartMate 3 vs. HeartMate inferior to axial-flow pump at 6 months;6also superiority at pump axial-flow to inferior ENDURANCE (randomized,open-label, survival at 2 years free from disabling stroke or stroke device survival disabling from at 2 free years non-inferiority of HeartWarevs. devices for other HF ineligible for transplant survival, 73% 3-year survival n established (HR 0.55, 95% CI 0.32–0.95,established (HR0.55,95% CI devices removal; higher rateofstroke,failure,RVsepsis survival devices HeartMate II LVAD HeartMate II LVADs): non-inferior to commercially available ADVANCE (HeartWare vs. commercially available Post-CE mark approval registry ( Single-arm(transplant candidates, NYHA class IV, functional 2years capacity at OMM): associated LVAD with better survival and ‒ 92% 6-month survival; 1-year survival toothersimilar armSingle ( ROADMAP failure fordevice contin pulsatile):improved survival2-year freeofstroke or ‒ MOMENTUM2-year 3 outcomes(

=50): 84% 1-year survival 1-year 84%=50): 0.27–0.84, 95% CI 0.47, (HR 19.2% vs. 10.1% stroke: of Rate CI 0.31–0.69,CI 95% 0.46, HR device: replace/remove to reoperation of free survival or stroke disabling of free Survival 254,255 257 250 Advanced Failure;Heart Advanced ; continued access access protocol 84%; continued 1-year 151,243

=50, BTT and DT):BTT and 98% =50, 30-day survival, P =0.02) (observational, (observational, P <0.001 (superiority) 242 (randomized continuous flowvs. n =294):centrifugal flowpumpnon- uous flow vs. pulsatile pulsatile vs. flow uous , HeartWare vs. HeartMate II): 248 249

n =97 LVAD, =97 LVAD, n =254): 85% 1-year

=366): HF, heart failure; HR, hazard ratio; LVAD, leftventricular assist device; MOMENTUM, Multicenter 258 n n =446 advanced =133): 75%

P =0.04) 239 n =103 =103

235 234

transplant; transplant; confidenceinterval; CI, atients; RV, right ventricular. Device failure Device Infection failure RV Haemorrhagic stroke Ischaemic stroke Driveline infection Driveline thrombosis Pump RV failure RV Bleeding (haemorrhagicstroke) Driveline infection Driveline Ischaemic stroke Pump thrombosis Pump failure Device Driveline infection Driveline Infection Stroke failure RV 10.1% ingroup axial flow MOMENTUM 3 comparedto No pumpthrombosis in Association; Association; optimal management;OMM, medical ROADMAP, Risk 252,253 244–246 247

DT, DT, therapy;destination ENDURANCE, outcomes)

both BTT and DT (long-term DT and (long-term BTT both vs.HeartMate 3 HeartMate II, randomized, 3: MOMENTUM 256

withReprinted from permission Baumwol. Association. Heart York New NYHA, peptide; pro-B-type natriuretic N-terminal BNP, natriureticpeptide B-type inhibitor; angiotensin receptor–neprilysin ARNI, enzyme inhibitor; angiotensin-converting ACEI, N I failure heart advanced of Help’—Markers Need ‘I 11 Table D E E H L E P

This article isprotectedby copyright. Allrights reserved. Accepted Article N I D E E H L E P orps Previous or ongoing requirement for do notropes ow blood pressure Consistently low BP with systolic <90 to 100 mmHg mmHg to 100 <90 systolic with low BP Consistently pressure blood ow eto rcin Verylow ejection fraction <20% liver or renal Worsening jection fraction dysfunction nd-organ dema/escalating diuretics Persisting fluid over fluid Persisting dema/escalating diuretics rognostic medication Inability to up-titrate (or need to decrease/cease) ACEI, beta-blockers, ARNIs, or MRAs MRAs or ARNIs, beta-blockers, ACEI, decrease/cease) to need (or up-titrate to Inability medication rognostic efibrillator shocks Recurrent appropriate Recurrent shocks defibrillator efibrillator shocks ospitalizations More than 1 hospitalization hospitalization More 1 than ospitalizations YHA class/natriuretic peptide Persisting NYHA class III or IV and/or persistently high BNP NT-proBNP or high orpersistently and/or III NYHA IV class Persisting peptide class/natriuretic YHA 271 load and/or increasing diuretic requirement diuretic increasing and/or load dysfunction in the setting of heart failure heart of setting the in dysfunction with heart failure in the last 12 months 12 thelast failure with heart in butamine, milrinone, dopamine, or levosimendan or milrinone, dopamine, butamine, ; BP, bloodpressure; MRA,mineralocorticoid receptor antagonist; NT-proBNP, Figure 1. AcceptedThis articleisprotected bycopyright.Allrightsreserved. Article Figure 2. AcceptedThis articleisprotected bycopyright.Allrightsreserved. Article