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Home , Cardiorenal syndrome, Organ dysfunction

Outline

Cardiorenal Syndromes: New ° Definitions Insights into Combined Heart and ° Complex, bidirectional pathogenesis ° Novel diagnostic targets Peter A. McCullough, MD, MPH ° Therapy FACC, FACP, FAHA, FCCP, FNKF ° Putting it all together

History Outline

•1913: Sir Thomas Lewis gave a clinical lecture on paroxysmal dyspnoea in cardiocardio--renalrenal patients with special reference to “cardiac” and “uremic” asthma •1951: the term cardiorenal syndromes (CRS) was coined by Ledoux [i] •1997 to present: Schrier in multiple papers summarized the impact of salt and ° Definitions water retention combined with neurohormonal activation in the pathogenesis of CRS. [ii] [iii] [iv] ° Complex, bidirectional pathogenesis •2003: Brammah and colleagues pointed out that treatment of bilateral renal arterial disease could result in improvement of both heart and kidney function. [v] •2005: Braam demonstrated in animals that in one system ° Novel diagnostic targets influences that in the other. [vi] •2008: Ronco and colleagues proposed five distinct CRS according to the temporal sequence of organ injury and failure as well as the clinical context. [vii] ° Therapy •2008: Dialysis Quality Initiative (ADQI) involving , critical care, cardiac surgery, and cardiology was convened. [viii] ° Putting it all together •2011: Karger launches “Cardiorenal Medicine” James Sowers, MD, Editor •2012: ADQI conducted a second consensus conference to review the spectrum of pathophysiologic mechanisms involved in CRS [i] University College Hospital, London, November 12th, 1913. BMJ 2: 1417–1420. Ledoux P. []. Avenir Med. 1951 Oct;48(8):149-53. [ii] Blair JE, Manuchehry A, Chana A, Rossi J, Schrier RW, Burnett JC, Gheorghiade M. Prognostic markers in -congestion, neurohormones, and the cardiorenal syndrome. Acute Card Care. 2007;9(4):207-13. [iii] Sarraf M, Masoumi A, Schrier RW. Cardiorenal syndrome in acute decompensated heart failure. Clin J Am Soc Nephrol. 2009 Dec;4(12):2013-26. [iv] Sarraf M, Schrier RW. Cardiorenal syndrome in acute heart failure syndromes. Int J Nephrol. 2011 [v] Brammah A, Robertson S, Tait G, Isles C. Bilateral renovascular disease causing cardiorenal failure. BMJ. 2003 Mar 1;326(7387):489-91. [vi] Bongartz LG, Cramer MJ, Doevendans PA, Joles JA, Braam B. The severe cardiorenal syndrome: 'Guyton revisited'. Eur Heart J. 2005 Jan;26(1):11-7. [vii] Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008 Nov 4;52(19):1527-39. [viii] Ronco C, McCullough PA, Anker SD, Anand I, Aspromonte N, Bagshaw SM, Bellomo R, Berl T, Bobek I, Cruz DN, Daliento L, Davenport A, Haapio M, Hillege H, House A, Katz NM, Maisel A, Mankad S, Zanco P, Mebazaa A, Palazzuoli A, Ronco F, Shaw A, Sheinfeld G, Soni S, Vescovo G, Zamperetti N, Ponikowski P; Acute Dialysis Quality Initiative (ADQI) consensus group. Cardiorenal syndromes: an executive summary from the consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2010;165:54-67.

1 Five Cardiorenal Syndromes Recognition of Cardiorenal Cardiorenal Syndrome (CRS) General Definition: Syndrome A pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ

CRS Type I (Acute Cardiorenal Syndrome) Abrupt worsening of cardiac function (acutely decompensated congestive heart failure) leading to CRS Type II ( Chronic Cardiorenal Syndrome) Chronic abnormalities in cardiac function (chronic congestive heart failure) causing progressive and permanent chronic CRS Type III (Acute Renocardiac Syndrome) Abrupt worsening of renal function (acute kidney ischaemia or tubular injury) causing acute cardiac disorder (new or decompensated heart failure) CRS Type IV (Chronic Renocardiac Syndrome) (diabetic nephropathy) contributing to decreased cardiac function, cardiac hypertrophy and/or increased risk of adverse cardiovascular events CRS Type V (Secondary Cardiorenal Syndrome) Systemic condition (e.g. ) causing both cardiac and renal dysfunction

Ronco C, McCullough PA, Anker SD, et al; Acute Dialysis Quality Initiative (ADQI) consensus group. Cardiorenal syndromes: an executive summary from the consensus conference of the Acute Dialysis Quality Initiative (ADQI). Contrib Nephrol. 2010;165:54 -67.

Definition of Acute Kidney Injury (KDIGO Guidelines 2012)

2 Risk of Worsening Renal Function (WRF) by Number of Risk Factors

Characteristics Adjusted OR 6.0 Women 1.41 HTN 1.64 53% 5.0 Rales>Bases 1.28 HR >100 bpm 1.34 38% 4.0 SCr ≥1.5 mg/dL 1.77 SBP >200 mm Hg 1.63 29% 3.0 (%) 24% 2.0 Risk of WRF Risk 16% 1.0

0.0 ≤ 1 2 3 4≥ 5 No. of Risk Factors N=1,681, WRF, defined as a rise in serum creatinine of >0.3 mg/dl (26.5 µmol/l). Krumholz HM et al. Am J Cardiol . 2000;85:1110.

Outline

° Definitions ° Complex, bidirectional pathogenesis ° Novel diagnostic targets ° Therapy ° Putting it all together

3 High Central Venous Pressure and Cardiorenal Syndrome

JACC Vol. 53, No. 7, 2009

Cardio-Renal Syndrome Pathophysiology Venous Congestion and Glomerular CKD-Associated Myocardial Changes Systolic or Diastolic Dysfunction or Both Myocyte hypertrophy Myocyte dysfunction Altered Intra-renal Hemodynamics Filtration ↑↑Intersal Fibrosis ↓Capillary density ↑↑LV Mass Elevated serum levels Increased CKD-Associated Vascular Changes Decreased Perfusion venous Accelerated atherosclerosis pressure Renal ↑Vascular sffness Congestion ↓Smooth muscle density Precipitators Osteoblastic VSMC transformation Vasodilators Intra-and extracellular calcification Procedures Toxicity Vascocostriction Acute on Acute on Chonic Chronic Cardiac Acute Neurohoromonal Activation Kidney Disease SNS+RAS+Aldosterone+ Endothelin+ADH+, renal Injury Chronic Neurohormonal vasoconstriction (adenosine)+prostaglandin DM+HTN + other CKD ↑SNS, RAS, Aldosterone dysregulation Renal hypoperfusion ↓Vitamin D Decreased GFR ↑PTH Resistence to diuretics ↑PO4 LV Failure Resistance to ANP/BNP Mechanisms Hypotestesteronism Na + H 2O retention • Pressure overload ANP/ Blocked ↓EPO • Volume overload BNP Natruretic Peptides Natriuresis Necrosis / apoptosis ↓Fe ulizaon • Fibrosis ↓Na-K ATPase Humoral Anemia/Relave ↓Epo/Fe transport blocked Cytokine Biomarkers signalling Inciting Events secretion ↑BNP/NT-proBNP ↓Medical compliance ↑ N-GAL IL-1, TNF- ↓Tubulo- ↑Sodium intake ↑ KIM-1 Alpha Glomerular Leukocyte Function ↑IL-18 Endothelial (AF) Activation Catalytic iron Dysfunction OSAS ↑Cystan-C

↑Cytokines, ↑Adhesion Molecules, ↑Enzymac Acvaon, ↑Oxidave Stress ↑Creanine Added Insults Urine albumin NSAIDS, TZDs Many others McCullough PA, Diez J, KDIGO 2010 Workshopt, Adapted, Courtesy Ronco, C 2009

4 Tubular Recovery and Renal Reserve in AKI ~30% of In-hospital AKI results in permanent loss in eGFR (~5% ESRD) Outline ~70% must have had tubular recovery or compensation by the remaining nephrons ° Definitions ° Complex, bidirectional pathogenesis ° Novel diagnostic targets ° Therapy ° Putting it all together

Adapted fromThadhani et al., N Engl J Med 1996

BOLD MRI History of Urine in Western Medicine

Power Doppler ° Ancient Babylonian and Sumerian physicians Clinical Evaluation first inscribed their And Biomarkers evaluations of urine into clay tablets as early as Positron Emission Tomography 4,000 B.C.

Figure: People showing for a diagnose a sample of their urine to the physician Constantine the African.

Advanced Imaging Yoquinto, My Health Daily News, Aug 15 2011

5 Blood and Urine Biomarkers of Acute Kidney Injury

G1 cell cycle arrest markers ([TIMP-2].[IGFBP7])

NGAL, IL-18, KIM-1, L-FABP

Tubular Enzymuria GGT, AlkPhos, LDH Cr, Cystatin-C NAG, α/πGST,

Adapted from Geraghty et al. Am J Physiol Renal Physiol. 1992; 263: 958-962, Westhuyzen, et al, NDT 2003, Endre Z, 2008, Kashani Crit Care 2013

Predicted AKI Detection Multimarker Panel Approach Diagnostic value of biomarker Single Combination Liangos et al., Biomarkers 2008 0.50-0.66 0.78 Han et al., Clin JASN 2009 0.59-0.68 0.80-0.84 Kashani K et al, Crit Care 2013 0.76-0.79 0.80 Inducers of G1 cell cycle arrest (Urine [TIMP-2].[IGFBP7]) AKI Cystatin C Creatinine KIMKIM--11 IL 1818IL NGALNGAL

0 h 4 h 8 h 12 h 24 h 48 h

Adapted Courtesy Herget-Rosenthal 2010 24

6 Baseline Samples and Prediction of AKI NEPHRO CHECK ® Test System: (TIMP-2 x IGFBP-7 Product in Spot Urine): Sapphire Study the Astute Medical NEPHRO CHECK ® Test System has received 510(k) clearance through FDA’s de novo classification process. On 9/5/14 FDA: “Current laboratory tests can only assess whether a patient may already have AKI; often, the patient has progressed to moderate to severe AKI before the test results confirm the clinical diagnosis. NephroCheck detects the presence of insulin-like growth-factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases (TIMP-2) in the urine, which are associated with acute kidney injury. Within 20 minutes, the test provides a score based on the amount of the proteins present that correlates to the patient’s risk of developing AKI within 12 hours of the test being performed. No other tests currently on the market are FDA- approved or cleared to assess the risk of developing AKI in at-risk patients.”

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Urinary [TIMP-2]•[IGFBP7] Discriminates Patients With AKI From Those Without AKI (Topaz Study)

Bihorac et al, AJRCCM 2014

7 NEPHRO CHECK ® AKIRisk™ NGAL is an endogenous bacteriostatic protein by Case #1 Positive Test Performed Score = 2.6 reducing available catalytic iron

Day 1 Day 2 Day 3 Day 4 Day 5

Therapies Cardiac Surgery: 6 hrs. NGAL E. coli Pump time: 1.5 hrs. Siderophore No Transfusion

Serum Creatinine (SCr, mg/dL) 3x SCr Baseline 1.3 SCr Baseline Iron X Urine Output AKI (UO, mL/h) <0.5ml/kg/h for ≥12h 0.5 ml/kg/h bacterial without NGAL growth Fluid Balance +6.4L +9.5L +11.2L +12.5L (Cumulative) curves with NGAL Hours 0 12 24 36 48 60 72 84 96 108 Goetz et al. 12 hrs. after Mol Cell 2002 NEPHRO CHECK ® Test

Neutrophil Gelatinase-Associated Lipocalin (NGAL) ACS – a specific biomarker of acute kidney injury

Siderophore Labile Iron NGAL

Haber Weiss · - O 2 O 2 Control NGAL NGAL

3+ Fe Fe 2+ - H2O OH Siderophore + · + OH H 2 O 2 AKI Fenton Iron Oxidative Stress Reactions Ferric Iron = Fe + ; Ferrous iron= Fe + ; hydrogen peroxide = H O ; Goetz et al. 3 2 2 2 Mol Cell 2002 Hydroxyl radical = OH . ; Hydroxide anion = OH - ; oxygen = O superoxide anion = . O - 2 ; 2

8 NGAL for the Diagnosis of AKI in the Meta-Analysis: Emergency Department Accuracy of NGAL in AKI NGAL Serum Creatinine ° Meta-analysis of 19 Diagnostic and Prognostic Accuracy of NGAL 1500 20.00 N=635 adults admitted to hospital, diagnostic studies Diagnostic 32% of NGAL > mean age 60, Setting Specificity AUC-ROC Odds Ratio 130 µg/g required 18.00 30 (4.7%) developed AKI: (2538 patients) 1250 dialysis * •Cardiogenic (40%) AKI across settings 85.1 0.815 18.6 16.00 •Urinary obstruction (16.7%) ° NGAL was a valuable •Multiple myeloma (10%) and early predictor of 14.00 •sepsis (6.7%) AKI after cardiac surgery 75.1 0.775 13.1 1000 AKI, both overall and

g/g •HTN emergency (6.7%)

µ * 12.00 •NSAIDS (6.7%) across a diverse range * •SLE (3.3%) of clinical settings 750 10.00 •Interstitial nephritis(3.3%) AKI in critically ill patients 75.5 0.728 10.0 • (3.3%) * •Rhabdomyolysis (3.3%) ° The cutoff NGAL value 8.00 * for optimum sensitivity Urine NGAL, Urine 500 * and specificity across 6.00 * AKI after contrast infusion 96.3 0.894 92.0 * * all settings was >100 4.00 * 250 * ng/mL

Presenting SerumPresenting Creatinine, mg/dL AKI prediction using 2.00 * 86.6 0.775 17.9 * * * ° A more consistent cutoff serum NGAL 0 0.00 value of >150 ng/mL AKI Prerenal CKD Normal AKI Prerenal CKD Normal was identified when AKI prediction using Azotemia Kidney Azotemia Kidney 84.3 0.837 18.6 Function Function using standardized urine NGAL platforms N = 635

33 Nickolas TL, et al. Ann Intern Med. 2008;148:810-819. Haase M, et al. Am J Kidney Dis. 2009;54:1012-1024.

Event=30 day HF rehospitalization or death

9 New Spectrum of AKI based on Combination of Functional and Damage Biomarkers Outline

Based on NGAL NO DAMAGE DAMAGE PRESENT ° Definitions Based on Serum Creatinine No functional Damage without ° Complex, bidirectional pathogenesis NO FUNCTIONAL changes or loss of function CHANGE damage ° Novel diagnostic targets ° Therapy

FUNCTIONAL Loss of function Damage with ° Putting it all together CHANGE without damage loss of function

New Criteria for AKI Diagnosis and Staging Using Biomarkers Pharmacologic Therapy and CRT for HF

Post-MI Mild Moderate Severe LV Dysfunction HF HF HF

AIRE/SAVE SOLVD Treatment CONSENSUS (ramipril/captopril) (enalapril) (enalapril) Based on VALIANT CHARM Val-HeFT Serum Based on (valsartan) (candesartan) (valsartan) Creatinine Nephroheck® CAPRICORN US Carvedilol/MERIT COPERNICUS and Urine , NGAL, L- (carvedilol) (carvedilol/metoprolol) (carvedilol) Output FABP EPHESUS/EMPHASIS-HF CHARM/Val-HeFT RALES (eplerenone) (candesartan/valsartan) (spironolactone) A-HeFT Long-acting nitrate/hydralazine

CRT and/or ICD

10 Treatment Patterns and Mortality in Advanced HF

1.0 Group dose ACE inhibitor dose A High…………………………… Low n=240 B High…………………………… High n=160 0.8 C Low……….…………………… Low n=526 D Low……………………………. High n=224

A 0.6 B C 0.4 D Total Mortality Total

0.2 Chi-square=33.83 P = .0001

0.0 0 6 12 18 24 30 36 Months from Randomization Neuberg GW et al. Am Heart J. 2002;144:31-38.

Prevention of Type I Cardiorenal Risk of Developing Renal Insufficiency Syndrome: Lessons Learned from on ACEI Therapy: Results From SOLVD Clinical Trials and Registries

° Programmatic use of PA catheter (Nohria JACC 2008) Enalapril Placebo ° Programmatic use of inotropes/indodilators (ACC/AHA Guidelines) Clinical Variable RR (95% CI) RR (95% CI) ° High-dose loop diuretics (DOSE Trial 2011) Age (per 10 yrs) 1.42 (1.32-1.52) 1.18 (1.12-1.25) Drug/Strategy ° Beta-blocker withdrawal (Fonarow, JACC 2008) Baseline EF Ineffective/Harmful 0.93 (0.91-0.96) 0.93 (0.91-0.96) (per 5% increment) ° ACEI/ARB withdrawal (Shukla, CIRC, 2008) OR ° Digoxin withdrawal (Packer, NEJM, 1993) Diuretics 1.89 (1.70-2.08) 1.35 (1.09-1.66) Have not identified ° Rolophylline (PROTECT, ESC, 2009) 1.33 (1.13-1.53) 1.96 (1.57-2.44) the ideal patient ° Endothelin receptor antagonists (Forbes KI 2001) subset for benefit ß Blockers 0.70 (0.57-0.85) 0.70 (0.57-0.85) ° Argnine vasopressin receptor antagonists (Konstam JAMA 2007)

° (Yancy, ASCEND HF, 2011, ROSE-HF 2014) EF, ejection fraction; SOLVD, Studies of Left Ventricular Dysfunction. Knight EL et al. Am Heart J. 1999;138:849-855. ° Ultrafiltration after AKI (Pavlesky, CARRESS 2013)

11 Acute Kidney Injury (AKI) in DOSE Trial

P = 0.04 AKI Cr Rise > 0.3 mg/dl 0.3 >Cr Rise AKI

Diuretic Strategy

N Engl J Med. 2011 Mar 3;364(9):797-805.

Continuous versus Bolus Intermittent Loop Diuretic Infusion in DOSE Trial: Study Design Acutely Decompensated Heart Failure: A Prospective Randomized Trial Alberto Palazzuoli MD PhD*, Marco Pellegrini MD*, Gaetano Ruocco MD*, Giuseppe Martini MD*, Beatrice Franci PhD*, Maria Stella Campagna PhD*, Marilyn Gilleman MD*, Peter A. McCullough, MD, MPH,† Claudio Ronco MD ♦, Ranuccio Nuti MD*. Acute Heart Failure (1 symptom AND 1 sign) <24 hours after admission Continuous Infusion Bolus P value

2x2 factorial randomization

Acute kidney injury 22% 15% 0,30 Low Dose (1 x oral) Low Dose (1 x oral) High Dose (2.5 x oral) High Dose (2.5 x oral) Na ↓ use of hypepertonic saline 33% 18% 0,01 Q12 IV bolus Continuous infusion Q12 IV bolus Continuous infusion Inotrope Infusion 35% 23% 0,02 Length of hospital stay (days) 14 + 5 11 + 5 <0,03 Death or rehospitalization 58% 23% 0,001 48 hours 1) Change to oral diuretics 2) continue current strategy 3) 50% increase in dose

72 hours Co-primary endpoints 60 days Clinical endpoints Manuscript accepted 2014 N Engl J Med. 2011 Mar 3;364(9):797-805.

12 Physical Exam Findings at Admission Effects of Ultrafiltration vs IV and Discharge Furosemide

70% Admission Discharge Neurohormones 60% Norepinephrine Plasma Renin Activity Aldosterone 50% + 80 – + 170 – + 80 – 40% + 40 – + 80 – + 40 – + 40 – % 0 – % 0 – % 0 – 30% -140 – -140 – - 40 - 20% d 0 1d 2d 3d 4d 5d 3m d 0 1d 2d 3d 4d 5d 3m d 0 1d 2d 3d 4d 5d 3m 10% Triangles = Ultrafiltration Squares = Furosemide 0% JVD Rales Edema

JVD=jugular venous distention. Agostoni et al. Am J Med. 1994;96:191-199. The OPTIMIZE-HF Registry [database]. Final Data Report. Duke Clinical Research Institute. July 2005.

Fluid Removal by Ultrafiltration UNLOAD Trial: N=200, RCT UF Started before AKI Develops, Freedom From Heart Failure Rehospitalization Within 90 Days After Discharge

100 • In theory removes fluid from the Ultrafiltration Arm (16 Events) Ultrafiltrate Interstitial blood at the same rate that fluid can Space (edema) be naturally recruited from the tissue 80 Na P • Transient removal of blood illicits H2O compensatory mechanisms, termed 60 Standard Care Arm (28 Events) Na K plasma or intravascular refill 1,2 K • Ultrafiltrate is isotonic with plasma, PR 40 • Removes more sodium than diuretic

therapy Rehospitalization P

% Patients% Free From 20 • Decreases ECF volume more than a comparable volume of diuretic- P = 0.037 Na Vascular induced fluid loss without Space 0 neurohormonal activation Vascular Na 0 10 20 30 40 50 60 70 80 90 Space

1. Lauer et al. Arch Intern Med . 1983;99:455-460. 2. Marenzi et al. J Am Coll Cardiol . 2001;38:4. Costanzo, M. et al., J Am Coll Cardiol 2007;49:675-83.

13 Mean Changes from Baseline Serum Creatinine Levels at A B Various Time Points in Ultrafiltration/Standard Care Group Characteristic Pharmacologic Therapy Ultrafiltration Outcome Pharmacologic Ultrafiltration P-value (N=94) (N=94) Therapy (N=94) Age (yrs) (N=94) Ultrafiltration Arm Standard Care Arm -Median 66 69 Death 13 (14%) 16 (17%) 0.55 -Interquartile range 57-78 61-78 1.0 Ejection fraction Hospitalization P > 0.05 at all time points -Median 35% 30% -All cause 24 (26%) 23 (26%) 0.97 0.9 -Interquartile range 25-55% 20-52% -Heart failure 37 (40%) 46 (51%) 0.12 Baseline creatinine (mg/dL) Unscheduled emergency 13 (14%) 19 (21%) 0.21 0.8 -Median 2.09 1.90 department or clinic -Interquartile range 1.71-2.65 1.57-2.37 visits 0.7 Increase in creatinine (mg/dL) -Median 0.46 0.43 0.6 -Interquartile range 0.37-0.70 0.35-0.60 0.5 C D 0.4 0.3 0.2 0.1 Serum Creatinine Change (mg/dl) ChangeCreatinine Serum 0.0 8 hrs 24 hrs 48 hrs 72 hrs Discharge 10 30 90 days days days Costanzo, M. et al., J Am Coll Cardiol 2007;49:675-83.

Volume Depletion Fluid Balance Volume Overload Diuretics Liberal Intake Ultrafiltration Positive Balance

Diseased At-Risk Heart Kidneys Hypotension Peripheral Edema Shock Impaired Oxygenation Organ Hypoperfusion Management Organ Congestion * Oliguria Window Normal Normal Heart Kidneys

Volume Depletion Acute Arterial Underfilling Optimal Status Decompensation

Low Blood Pressure High Risk of Cardiorenal Syndrome Cardiorenal of Risk *Trial of UF after AKI has developed

14 Selective Cardiac Myosin Activator: Omecamtiv Mecarbil Clinical Actions for Acute Kidney Injury

Science 18 March 2011: Vol. 331 no. 6023 pp. 1439-1443

Novel Therapies in Trials Acutely Decompensated Heart Failure Omecamtiv mecarbil

Serelaxin (RLX030) (recombinant form of human relaxin-2) Serelaxin is a recombinant form of human relaxin-2, a Ularitide (modified natriuretic peptide) naturally occurring peptide pregnancy hormone Caperitide (atrial natriuretic peptide) Cinaciguat (activates soluble guanylate cyclase (sGC)) Istaroxime (stimulates SERCA)

Acute Kidney Injury ABT-719 (alpha MSH receptor analogue) THR-184 (agonist for renal BMP receptors (ALK2, 3, and BMPR-II) AC607 (stem cells) BCT197 (anti-inflammatory) Serelaxin IV for up to 48 h, started within 16 h of CMX-2043 (small molecule adduct of lipoic acid) presentation, with placebo in patients hospitalized for AHF Ezekowitz Current Cardiol Rep 2013, Courtesy Shaw A, ADQI 2013

15 Outline

Baptist Health ° Definitions Continuing Medical Education ° Complex, bidirectional pathogenesis 8900 N. Kendall Drive ° Novel diagnostic targets Miami, Florida Phone ■ 786-596-2398 Fax ■ 786-533-9821 ° Therapy [email protected] ° Putting it all together BaptistHealth.net/CME

Heart Failure Goals

Stage D Stage C Stage B Stage A Revised Staging System Early Recognition and Treatment

Pharmaceuticals and Devices Preserve Renal Function Adapted from: Hunt SA et al. ACC/AHA 2005 CHF Guideline Update. Circulation 2005;112:e154-235.

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