STEMI ACCELERATOR-2: Regional Coordination Improves Outcomes

WEDNESDAY, NOVEMBER 15 DailyNewsNovember 11-15 | Anaheim, California

Today’s highlights from 3 the program chair STEMI ACCELERATOR-2: Regional Queen Latifah honored for her 4 work promoting heart failure awareness coordination improves outcomes,

Small case series challenges 6 thinking about fluoropyrimidine- FMC-to-device times in STEMI patients related cardiac toxicity egional training and coor- patients having a cath lab activated within 20 dination interventions that minutes of paramedic arrival. GEMINI-ACS-1: provide timely reperfusion “For the overall project, we increased from for ST-elevation myocardial 67 percent to 74 percent of patients reaching Switching P2Y12 infarction patients improve the national standard of first medical contact inhibitor in ACS outcomes and the interval of to device within 90 minutes. This coordina- patients based on first-medical-contact-to- tion of training was associated with signif- Rdevice time, according to a study present- icant reductions in heart failure and death, pharmacogenomic ed at Scientific Sessions on Tuesday. and demonstrated a marked and statistically testing results uncommon In the study, investigators worked with significant decline in mortality,” Jollis said. leaders, healthcare professionals, paramed- The study is a collaboration of Duke An update of the GEMINI-ACS-1 ics, nurses, emergency medicine physicians and the AHA’s Mission: Lifeline program. James G. Jollis, MD, FACC trial found that switching of P2Y12 in- and cardiologists in 12 major U.S. metropol- hibitors based on the results of pharma- itan regions to develop centralized STEMI ICARE-ACS cogenomics testing and reporting for plans for EMS catheterization lab activation Results of a New Zealand study suggest Patients with Possible Acute Coronary reduced or enhanced function alleles of and rapid transfer from non-PCI hospitals. a national clinical guidance framework Syndromes trial, researchers analyzed data CYP2C19 was not common. Clopido- “At baseline across the 12 regions, 38 that assesses patients presenting to from 11,529 patients before the framework grel carries a black-box warning recom- percent of patients had cath lab activation emergency departments with possible was implemented and 19,803 post- mending testing because patients with within 20 minutes,” said James G. Jollis, acute coronary syndromes is effective and implementation at seven diverse hospitals the reduced function alleles have higher MD, FACC, of the Duke University Clinical safely reduces hospital length of stay. in New Zealand. The primary outcome platelet reactivity and a potentially high- Research Institute in Durham, North Carolina, The findings were presented Tuesday was the proportion of patients successfully er risk of ischemic events, especially who presented the findings of the Regional by Martin Than, MD, of Christchurch discharged within six hours of emergency following PCI. STEMI Systems of Care: Results of the Hospital in New Zealand. department arrival. A successful discharge Results of the update to the P2Y12 Mission: Lifeline STEMI ACCELERATOR-2 In the National Implementation of a was defined as one with no major adverse Inhibitor Switching in Response to Rou- Study. “But with the new process in place, Clinical Guidance Framework for the cardiac event during the following 30 days.

tine Notification of CYP2C19 Clopido- we saw that increase to more than half of Emergency Department Assessment of ACCELERATOR-2 continued on page 14 grel Metabolizer Status Following Acute Coronary Syndromes trial were presented Tuesday by E. Magnus Ohman, MD, professor of medicine and member of Canagliflozin results mixed for primary, secondary the Duke Clinical Research Institute in prevention in diabetes, CANVAS update finds Durham, North Carolina. “GEMINI looked at clinical out- The sodium glucose Sixty-six percent of the — 41 percent reduction for secondary comes for rivaroxaban versus aspirin co-transporter 1 inhibitor 10,142 patients in CANVAS had prevention and 37 percent reduction for with either clopidogrel and ticagrelor,” canagliflozin showed mixed a prior cardiovascular event and primary prevention. Ohman said. “The choice of therapy results for cardiovascular were evaluated for secondary Adverse events included an expected was at the discretion of the clinician. prevention in a study pre- prevention. The 34 percent with increase in genital infections, low-trauma This update looks at switching be- sented Monday afternoon two or more cardiovascular risk fracture and volume depletion events. The tween these two agents.” at Scientific Sessions. factors were evaluated for pri- risk for lower-extremity amputations dou- In the trial, reporting of the The agent improved car- Kenneth W. Mahaffey, MD mary prevention. bled in the secondary prevention group CYP2C19 status was mandatory. diovascular and renal out- As expected, the secondary compared to placebo. A central lab reported CYP2C19 comes, but increased risk for lower extremi- prevention arm had a higher cardiovascu- Larger and longer-term studies already metabolizer status for 99.9 percent ty amputations in patients with diabetes. lar burden. These patients also showed under way will provide additional insight of the 3,037 patients. A total of 34.4 Kenneth W. Mahaffey, MD, professor greater benefit from canagliflozin — an into the effects of canagliflozin and other percent were ultra-metabolizers (UM), and director of the Stanford Center for 18 percent reduction in the risk for car- SGLT2 inhibitors. 37.8 percent extensive metaboliz- Clinical Research at Stanford University diovascular death, nonfatal MI or nonfatal ers (EM), 24.5 percent intermediate in California, presented the update to the stroke. Primary prevention patients had a EXSCEL metabolizers (IM) and 3.2 percent CANVAS (Canagliflozin for Primary and 2 percent reduction. The treatment effects of the GLP-1 recep- reduced metabolizers (RM). The trial Secondary Prevention of Cardiovascular Both groups had a similar benefit for tor agonist exenatide don’t vary based on protocol made no recommendations Events in Type 2 Diabetes) trial. Initial hospitalization for heart failure — 32 per- the patient’s baseline cardiovascular risk, regarding P2Y12 inhibitors or switch- results of CANVAS released earlier this cent reduction for secondary prevention according to an update to the Effect of Ex- ing agents based on CP2C19 status. year showed a 14 percent reduction in and 36 percent reduction for primary pre- enatide Once-Weekly on Clinical Outcomes cardiovascular events. vention. Renal outcomes were also similar GEMINI-ACS-1 continued on page 14 CANVAS continued on page 13

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HIGHLIGHTS FROM THE PROGRAM CHAIR TODAY AT By Eric D. Peterson, MD, MPH, FAHA, Committee on Scientific Sessions Program Chair SESSIONS Don’t miss today’s highlighted presentations and the hottest research in population, It’s the final day of Scientific events. For a complete schedule, download the Sessions! Over the past four days, basic and clinical science that was Mobile Meeting Guide, see the Final Program or we’ve heard exciting reports on presented over the past four days view the online program at scientificsessions.org. important breakthroughs in research. at Scientific Sessions. Each session 9-10:15 a.m. Additionally, we learned about novel offers a unique opportunity to hear Innovative Therapies and Novel Applications advances in clinical care, many of commentary from international Ballroom CD, 3rd Level, Main Building which can immediately impact how leaders. 9-10:15 a.m. we treat our patients. And there is The first of these sessions, “Trending Trending Topics in Population Science more to come today! Topics in Population Science,” begins Ballroom A, 3rd Level, Main Building Today’s program includes the at 9 a.m. in Ballroom A, 3rd Level, 10:45 a.m.-Noon week’s final Late-Breaking Science Main Building. “Trending Topics in Eric D. Peterson, MD, MPH, FAHA Trending Topics in Basic Science Ballroom A, 3rd Level, Main Building session, “Innovative Therapies and Basic Science” and “Trending Topics Novel Applications,” which begins at in Clinical Science” run concurrently 10:45 a.m.-Noon 9 a.m. The session will feature the at 10:45 a.m. in Ballroom A and Trending Topics in Clinical Science Ballroom CD, 3rd Level, Main Building latest results from the REDUCE LAP- Ballroom CD, respectively. maintaining the Scientific Sessions’ HF, TNT-POAF, PROPEL, ALLSTAR Before we adjourn today and head reputation as the world’s premier and HOPE-Duchenne trials. The back to our practices, hospitals, meeting in cardiovascular science HEARTY HUMOR by Jonny Hawkins presentations feature novel findings clinics and labs, I want to thank my and medicine. in the fields of preventive therapies, fellow members of the Committee And finally, I want to thank all of my heart failure, atrial fibrillation, peripheral on Scientific Sessions Program for colleagues and friends who attended artery disease, myocardial infarction putting together an outstanding this year’s meeting. I look forward and Duchenne cardiomyopathy. educational program. I must to seeing all of you again next year The schedule also includes three also thank the AHA staff for their at the 2018 Scientific Sessions in Main Event sessions highlighting dedication and exceptional efforts in Chicago, Nov. 10-14.

Late-Breaking Science VII: Innovative Therapies and Novel Applications LBS.07 | 9-10:15 a.m. Wednesday | Ballroom CD, 3rd Level, Main Building Trial Description REDUCE LAP-HF — Transcatheter InterAtrial Shunt Device for the This trial was designed to evaluate the safety and effectiveness of the Treatment of Heart Failure: Results from the REDUCE LAP-HF I InterAtrial Shunt Device to lower LA pressure in patients with heart failure. Randomized Controlled Trial

TNT-POAF — Temporary Neurotoxin Treatment to Prevent Postoperative This trial was designed to assess the efficacy and safety of epicardial Atrial Fibrillation botulinum toxin injection to prevent atrial fibrillation after cardiac surgery. Claiming CME/CE at PROPEL — Granulocyte Macrophage Colony-Stimulating Factor With and This trial was designed to determine whether granulocyte-macrophage Scientific Sessions Without Supervised Exercise to Improve Walking Performance in Peripheral colony stimulating factor (GM-CSF) combined with supervised treadmill Healthcare professionals attending Scientific Artery Disease exercise improved walking performance more than GM-CSF alone and Sessions can claim and print CME/CE certificates supervised exercise alone in PAD. when they have attended all of the sessions for the meeting. Physicians, nurses and EMS must claim ALLSTAR — 6-Month Results of ALLogeneic Heart STem Cells to This trial evaluated the safety and efficacy of intracoronary allogeneic credit by May 15, 2018. Pharmacists must claim Achieve Myocardial Regeneration Trial: A Randomized, Placebo- cardiac-derived stem cells in post-infarction patients. credit by Dec. 15, 2017. ABIM MOC credit is Controlled, Double-Blind Study available and must be claimed by Dec. 15, 2017. HOPE-Duchenne — Cardiosphere-Derived Cells for the Treatment of The HOPE-Duchenne clinical trial was designed to evaluate the 1. Go to learn.heart.org. Duchenne Cardiomyopathy: Results of the Halt cardiOmyopathy ProgrEssion- safety and efficacy of multivessel intracoronary delivery of allogeneic 2. Click “Activities in Progress” in the left-hand Duchenne Trial cardiosphere-derived cells in patients with cardiomyopathy secondary to navigation. You will be prompted to sign Duchenne muscular dystrophy. in using your American Heart Association username and password. You can create an account if you don’t have one. 3. Review the “Activity Overview and “Activity Material” tabs. WALKING 4. Complete the evaluation. 5. Claim your credit(s). CHALLENGE International attendees can obtain their Congratulations, Walking attendance verification certificate at the Challenge participants. registration center. For a full list of conference You logged millions of accreditation statements and credit hours, visit steps at Scientific Sessions scientificsessions.org. 2017. The top stepper is George Vetrovec, MD, Attendee feedback Scientific Sessions attendees will complete who logged 73,903 steps a survey evaluating Scientific Sessions in the in the annual competition. process of claiming their CME/CE credit. The Miriel Ho finished second American Heart Association uses these attendee with 68,769 steps. surveys for feedback on programming, location, Congratulations to the networking and more. Attendees who are not winners and thanks to all claiming CME/CE credit are invited to fill out a who participated! non-CME survey, which will be emailed following the meeting. Responses are anonymous. 4 SCIENTIFIC SESSIONS DAILY NEWS

Queen Latifah honored for her work promoting heart failure awareness

hen Rita Owens was diagnosed stage, she crossed with heart failure, her family the Anaheim Con- W rallied together. vention Center to MEMBER SPOTLIGHT They attended doctor’s appointments another stage where Jessica Zègre-Hemsey, PhD, RN and learned all they could about the she joined Clyde condition. They took pictures of which Yancy, MD, an AHA pills to take at different times of the day past-president, for a Emergency nursing to use as a visual checklist. Because Facebook Live dis- expert has passion her diet had to change, they changed cussion. theirs, too, as a show of solidarity and a “There are so for Mission: Lifeline step toward prevention. many things we As an emergency cardiovascular Then her daughter was asked to can do now than care researcher and emergency share the family’s story. Having long before,” said department nurse, Jessica Zègre- been in the public eye, the daughter Yancy, a heart Hemsey, PhD, RN, was intrigued and preferred to keep this private. failure expert and inspired by the AHA’s Mission: Lifeline. “But my mother said, ‘I’m all for chief of cardiology So when she was asked last year to anything I can do to prevent someone at Northwestern Queen Latifah was honored with the Woman of Distinction Award at join the cardiovascular system of care from going through what I’ve had to go University Feinberg Scientific Sessions on Sunday. program as a representative from the through,’” entertainer Queen Latifah said. School of Medicine Cardiovascular and Stroke Nursing “My mother is that type of person — she in Evanston, Illinois. “We have more and out of the hospital ever since, with Council, she eagerly accepted. wants to help people. I’m the mini-her, drugs, devices, technologies. We can Latifah and a cousin sharing the duties of “Working with others who are so I’m doing my job.” make a difference.” primary caregiver. Because her career of- passionate about improving patient care Since Owens’ urging more than two More than 6.5 million Americans are ten keeps her on the road, Latifah some- and outcomes for those afflicted with years ago, Latifah has been the face living with HF and more than 308,000 times checks in via FaceTime. She’ll even acute coronary syndrome, stroke and of Rise Above Heart Failure, an AHA people die from it each year. One in five ask to see her mom’s ankles to make sudden cardiac arrest has been, thus awareness campaign. On Sunday, AHA people will have heart failure in their sure she’s not retaining fluid. far, one of the highlights of my career as CEO Nancy Brown honored Latifah’s lifetime with nearly a million new cases “It’s brought us closer as a family,” a nurse-scientist,” said Zègre-Hemsey, work by presenting her the Woman of diagnosed each year. Latifah said. an assistant professor at the University Distinction Award at Scientific Sessions. “What we don’t want is for people to As they discussed strategies for treat- of North Carolina School of Nursing in “She is helping others understand the be hospitalized,” Latifah said. “We want ment and, better yet, prevention, Yancy Chapel Hill. signs and symptoms of the condition people to be home with their family said the focus shouldn’t be on heart failure. Zègre-Hemsey’s AHA membership — and providing support so they can live enjoying life, not in a hospital trying to “It’s about heart success,” he said. especially her work with Mission: Lifeline a full life,” Brown said. “She is truly an fight for it or get it back together, when “I love that!” Latifah said. “Heart success.” — reflects her commitment to advancing inspiration.” so much of this can be prevented.” And as the Facebook Live event cardiovascular health and outcomes. Latifah gave a brief acceptance speech, Owens’ diagnosis came about 12 years ended, she smiled and pumped her arm “I’m passionate about Mission: Lifeline then went right back to spreading the ago after she passed out at the school as she turned the phrase into a chant: and the group’s commitment to its word about heart failure. From the main where she was a teacher. She’s been in “Heart suc-cess! Heart suc-cess!” overarching goals,” said Zègre-Hemsey, who was recently nominated to serve on the Mission: Lifeline Steering Committee. “I hope to continue my work with this dynamic committee, which seeks to advance cardiovascular systems of care EHR and genomic test data can identify FH individuals for time-sensitive conditions and improve patient access to definitive care and ulti- at risk for adverse CV outcomes, study finds mately better patient outcomes. Serving as a representative of the Cardiovascular The results of a population-based study suggest used for multivariate analyses using binary logistic regression and Stroke Nursing Council gives me the that lipid levels and other electronic health record-derived for outcome measures of myocardial infarction, coronary opportunity to bring nursing to the table clinical data points, combined with exome sequencing for interventions and a composite ischemic heart disease burden. of this highly interdisciplinary committee.” familial hypercholesterolemia (FH) variants, can be used to Patel reported that baseline characteristics identified by Zègre-Hemsey, who is also an risk-stratify individuals for adverse cardiovascular outcomes. all hypercholesterolemia phenotype definitions showed that adjunct assistant professor in the Prashant Patel, MD, presented the study’s findings Tuesday each was associated with a high prevalence of the outcome Department of Emergency Medicine at at Scientific Sessions. measures. When compared to mutation-negative individuals the University of North Carolina School “Our goal in this study was to employ a population- with LDL-C ≤ 130mg/dl, there was a stepwise increase in of Medicine, said she joined the AHA based approach using EHR-based algorithms to risk-stratify the odds for outcomes, starting with a simple LDL-C based in 2002 to disseminate her research, hyperlipidemia using available clinical variables,” said Patel, of cutoff (≥190mg/dl) to addition of data elements from EHR and which focuses on non-invasive Geisinger Clinic and Medical Center in Danville, Pennsylvania. finally FH mutation positivity. Subjects with LDL ≥190 and FH monitoring strategies to improve the “In this process, we envisaged identifying the hidden burden mutation-positive status identified the highest risk with an OR diagnosis of acute coronary syndrome of familial hypercholesterolemia and the associated trends of 28.9 (95 percent CI 15.0-55.8, p<0.0001), 26.8 (13.9-51.6, and other time-sensitive conditions. of major adverse cardiovascular events. We also sought to p<0.0001) and 44.3 (23.7-82.9, p<0.0001) for MI, coronary “I value the active engagement with study the role of genomic testing in the prediction of clinical interventions and IHD burden, respectively. colleagues — all of whom share a pas- outcomes.” “These findings suggest an important role for biochemical sion for cardiovascular science, research A Geisinger Health System cohort of 41,649 patients was and genetic phenotype determination,” said Vishal C. Mehra, and strategies to improve patient out- included in the study (57.61 percent female, median age 62 MD, PhD, a senior author of the study. “The ever-increasing comes — that comes with getting in- years). The researchers deployed five phenotyping methods to use of EHR systems may broaden the appeal of well- volved at AHA,” Zègre-Hemsey said. risk-stratify severe hypercholesterolemia in the cohort. These designed, population-based screening to identify high-risk included an LDL-C cutoff, addition of clinical data (family and groups, which can then be preferentially targeted by cascade personal history of heart disease) from the EHR and presence of genetic screening or aggressive, novel therapies to improve FH pathogenic variants. A priori associated confounders were outcomes.” WEDNESDAY, NOVEMBER 15, 2017 5

Plaque regression, LDL lowering important in post-ACS management, study finds laque regression of non-culprit sites on treatment LDL cholesterol (13.7 percent vs. 19.6 percent). analysis showed that those patients who in patients with acute coronary syn- and MACE. All patients were Among those patients with achieved both regression and on-treatment P drome may be associated with better treated with statins. plaque regression, 40.2 percent LDL cholesterol had a 62 percent long-term outcomes, according to data pre- The overall change in PAV achieved on-treatment low LDL decreased risk of MACE (HR=0.38; sented Tuesday at Scientific Sessions. was -1.6 and plaque regres- cholesterol levels. 95 percent CI, 0.14-0.90; P=.03). Data from prospective studies of serial sion, defined as PAV change About 40 percent of “The growing interest in treating vul- intravascular ultrasound (IVUS) showed from baseline <0, occurred patients achieved both plaque nerable plaque has substantially raised that patients who achieved both plaque in 67.6 percent of patients. regression and on-treatment the bar on current treatment approaches regression and lower LDL cholesterol had The rate of MACE was low- low LDL (group 1), 27.2 percent and, if complemented by confirmatory significantly reduced risk for major adverse er in patients with plaque Hirohisa Endo, MD met only plaque regression imaging techniques and markers, can cardiovascular events. regression than in those (group 2) and 32.4 percent had possibly help regress plaque evolution and “The results of this study suggest reach- without regression, but the plaque progression with/without eliminate the possibility of atherosclerosis ing both plaque regression and sufficient difference was not statistically significant LDL cholesterol (group 3). A multivariate altogether,” Endo said. LDL-C lowering is clinically important in post-ACS management,” said Hirohisa PAID ADVERTISEMENT Endo, MD, who presented the study. “In addition, this study shows that plaque regression determined by volumetric IVUS measurement could be a surrogate marker The Medtronic AF Advantage of future cardiovascular events.” According to Endo, of the department of cardiovascular medicine at Juntendo Uni- versity Graduate School of Medicine in To- kyo, Japan, IVUS follow-up in patients with ACS is not routinely performed. Therefore, Endo and colleagues looked at data taken from four prospective clinical trials that included patients with ACS undergoing regular IVUS of non-culprit lesions in the culprit vessel at baseline and six months follow-up. Of all 382 patients, they excluded the patients without available serial IVUS measurements (n=150) and without statin therapy (n=59). They looked at outcomes related to percent atheroma volume (PAV),

BODY FAT IS MAJOR DETECT PLAYER IN CELLULAR REDUCE AND CARDIAC AGING RESPOND TREAT

Stop by our booth to find out how our portfolio During an abstract poster session can help you manage Tuesday, investigators reported that direct measure of body fat, rather atrial fibrillation (AF) in than body-mass index, is associated with telomere length. Telomere length, your patients. a marker of cellular aging, has been linked to cardiovascular disease. In the For information on the benefits study, shorter TL was associated with and risks of these products, diastolic dysfunction in subjects with visit our booth or visit high, but not low, body-fat mass. The results suggest that accumulation of Medtronic.com/AFadvantageISW body fat is both an important mediator of cellular aging and a modulator of the latter’s impact on heart function, the UC201804311 EN ©2017 Medtronic. researchers concluded. Minneapolis, MN. All Rights Reserved. Printed in USA. 10/2017 6 SCIENTIFIC SESSIONS DAILY NEWS

Advances in PAH treatment on the horizon, Small case series says Distinguished Scientist lecturer challenges thinking about fluoropyrimidine- remendous progress in the use of vasodilators, endothelin Marlene Rabinovitch, MD, FAHA related cardiac toxicity T receptor blockers and nitric oxide activators has improved the With the combination of careful cardiac quality of life and the survival of monitoring, calcium channel blockers and long- patients with pulmonary arterial acting oral nitrates, researchers at the Hospital of the hypertension (PAH), but morbidity University of Pennsylvania were able to successfully and mortality remain high, said rechallenge with fluoropyrimidines agents such as 5-FU Marlene Rabinovitch, MD, FAHA, and capecitabine in patients who experienced cardiac during the Distinguished Scientist toxicity related to the chemotherapy. Lecture on Tuesday. Suparna C. Clasen, MD, presented results from the Rabinovitch, the Dwight case series Tuesday in an abstract poster session. and Vera Dunlevie Professor complication, and treatments of “The genetic basis of idiopathic “Fluoropyrimidines are the backbone of standard of Pediatric Cardiology at the scleroderma and liver disease are pulmonary arterial hypertension chemotherapy for gastrointestinal and other Stanford University School of further challenged by the presence has given us important clues to the major solid malignancies,” said Clasen, a fellow Medicine said that at best there’s of this complication.” pathways that are perturbed that at the Hospital of the University of Pennsylvania in a 65 percent five-year survival rate The most insidious presentation not only target the lung vasculature Philadelphia. followed by rapid attrition. of PAH, Rabinovitch said, is the but are also relevant to systemic However, fluoropyrimidines use has been limited “Additionally, there’s an increasing idiopathic form because there is no vascular disease,” she said. by cardiac toxicity, presenting as a spectrum of number of conditions in which underlying condition to provide a Recent studies have shown that asymptomatic and symptomatic manifestations related PAH is recognized as a serious clue to its presence, and the symp- loss of BMPR2 not only induces to coronary vasospasm leading to myocardial ischemia. complication that negatively tomatology is also vague. She not- apoptosis of endothelial cells, but Clasen said experiencing these serious adverse effects impacts survival,” she said. “So, ed that PAH affects females more also can be responsible for their has rightfully made patients and clinicians leery to along with congenital heart disease, than males, frequently in the third transition to smooth muscle-like reintroduce these medications. we now see PAH with heart failure to fifth decade of life, but also in cells. As a consequence, in addition Clasen and colleagues reported a case series of 11 and preserved ejection fraction, as infants and children. Its incidence is to losing their ability to proliferate, consecutive patients with suspected fluoropyrimidine- well as reduced ejection fraction similar to a rare disease, but about they lose their important function as induced coronary vasospasm who were successfully with metabolic syndrome.” 15 percent of cases are familial. a tight barrier, and they take on pro- rechallenged to allow for chemotherapy completion. Rabinovitch discussed her Rabinovitch said research has inflammatory properties. Together with Joseph R. Carver, MD, Clasen research exploring the fundamental identified that a BMPR2 receptor “Loss of BMPR2 recruits developed two algorithms for rechallenge that varied mechanisms responsible for the loss mutation is present in approximately inflammatory cells, such by the type of fluoropyrimidines given, either oral or by and obliteration of blood vessels that 70 percent of familial PAH cases as neutrophils, that release infusion. Patients underwent a full work-up to test for cause PAH. and 20 percent of sporadic PAH increased elastase, degrading underlying coronary artery disease and to try to modify “In addition to lung disease, cases, adding that further studies poorly assembled elastic fibers,” underlying cardiovascular risk factors such as diabetes there’s also increasing recognition identified reduced BMPR2 expres- Rabinovitch said. “Emerging or hypertension. of the adverse impact of PAH in sion in all forms of pulmonary arte- therapies, such as elafin and “We never take it for granted that it is coronary sickle cell disease, and there’s rial hypertension. The challenge for FK506, repress inflammation vasospasm,” Clasen said. “We want to rule out virtually an epidemic of PAH researchers, she said, became one and improve BMPR2 functions. underlying coronary artery disease that is the culprit related to substance abuse,” she of relating the dysfunction of this Induced pluripotent stem cells for the chest pain presentation and, if CAD is present, said. “Worldwide attempts to receptor to the pathological features also may prove to be useful understand how much is underlying burden prior to eradicate HIV and schistosomiasis, of PAH and to what was already in developing patient-specific rechallenge.” for example, still face PAH as a understood from laboratory studies. treatments.” The protocols use a bolus infusion regimen of intravenous 5-FU chemotherapy and oral capecitabine with cardioprotective pretreatment of two calcium blockers and long-acting oral nitrates, which are titrated to the patient’s blood pressure and heart rate. “We pretreat with anti-anginal agents before THANKS TO OUR SUPPORTERS infusion, treat during infusion, and after the infusion for up to 24 hours after the first dose,” Clasen said. “Patients are then closely observed either in The American Heart Association Janssen Pharmaceuticals, Inc. University of Kentucky an inpatient setting if considered high-risk or in an is grateful for the continued McGraw-Hill Education University of Pittsburgh – outpatient setting where they are closely monitored.” support and generosity of the Pittsburgh Heart, Lung and Blood Medtronic All of the patients in the cohort successfully contin- following companies: Vascular Medicine Institute Memorial Healthcare System ued and completed their previously planned first-line Adinstruments WA University & Barnes-Jewish fluoropyrimidine chemotherapy regimen with minimal Millar, Inc. Hospital Amgen therapeutic interruption. There were no cardiac events or National Kidney Foundation Wolters Kluwer Aralez Pharmaceuticals, US, Inc. evidence of recurrent coronary spasm after completion National Lipid Association AstraZeneca Pharmaceuticals The AHA would also like to thank of therapy. Prophylactic medications were discontinued NEJM Group the following companies for their AtriCure, Inc. upon therapy completion. Novartis Pharmaceuticals Corp support of Scientific Sessions In the case series, Clasen and colleagues took all Boehringer Ingelheim/Eli Lilly 2017. This support was provided in comers presenting to the cardio-oncology clinic with Novo Nordisk Inc. the form of educational grants: Boehringer Ingelheim Pharma Inc. suspected fluoropyrimidine-related cardiotoxicity, Partnership for Advanced Cellagis Devices Inc. Cardiovascular Health Aegerion but future research might attempt to identify if there Pharmaceuticals Inc. are certain patients with an underlying genotype that Cleveland Clinic Portola Pharmaceuticals Denka Seiken USA Amgen makes them more susceptible to vasospasm. Sanofi Regeneron “We think this is a protocol that could potentially Eclinicalworks Chiesi Sanofi Regeneron be widely implemented with the inclusion of very Exemplar Genetics Medical Info Merck careful cardiac monitoring,” Clasen said. “This has the GuardaHeart Foundation Theheart.org Pfizer potential to reintroduce a widely used and potentially curative chemotherapy agent for these patients.” WEDNESDAY, NOVEMBER 15, 2017 7

Disparities for NSTEMI angiography and revascularization are narrowing but still present, according to study acial disparities in the management when patients are black. Racial disparities 2005 to 2013, it declined. However, data have been the development of NSTEMI of non ST-segment elevation myo- in angio graphy and revascu- revealed that the proportion guidelines and management algorithms in R cardial infarction (NSTEMI) persist larization would have the po- of patients evaluated by angi- the late 1990s, he said. Greater access to despite narrowing over time, according tential to negatively influence ography was higher for white medical insurance also may have been a to results from The Atherosclerosis Risk mortality outcomes for black than black patients, reaching a factor. in Communities (ARIC) Surveillance Study patients.” peak disparity in 1992. A higher Finally, narrowing racial disparities presented Tuesday at Scientific Sessions. In the study, black pa- proportion of white patients may have resulted from the expansion The study looked at trends in angio- tients were more often was revascularized each year, of cardiac catheterization units over graphic evaluation and revascularization female and younger. From reaching a peak disparity in the past decades, he said. Many of for NSTEMI. Since 1987, the ARIC study 1987 to 2004, the propor- 1990. the black patients were sampled from has conducted hospital surveillance of tion of patients undergoing Sameer Arora, MD Many factors may be influenc- economically depressed regions, acute MI in four U.S. states: Maryland, angiography and revas- ing the trend toward narrowing which may not have had cardiac Minnesota, Missouri and North Carolina. cularization increased for disparities observed in the study, catheterization services available at the Clinical data and procedures were ab- both black and white patients. Then from Arora said. One of the most important may start of the surveillance. stracted from the medical records, and NSTEMI was classified with a validated PAID ADVERTISEMENT algorithm. Study presenter Sameer Arora, MD, and colleagues compared the probabilities of angiography and revascularization for white patients (n=21,721) relative to black patients (n=9,525) with adjustment for age, sex, TIMI risk score and hospital geo- graphic region. “Invasive strategy (angiography with intent to revascularize) has become the guide- line-recommended standard for management of NSTEMI,” said Arora, of the Division of Cardiology at the University of North Car- olina School of Medicine in Chapel Hill. “The efficacy of this strategy has been widely accepted, but it appears to be utilized less

Attend a 2017 Poster Winners Sanoﬁ /Regeneron Early career work is extremely important to Sponsored the American Heart Association. The future Lecture of cardiovascular science is in the hands of these healthcare professionals and scien- tists, and the poster sessions include many examples of the important work being done by this group. Here’s a look at the poster winners from Scientific Sessions 2017 — all of whom are early career professionals:

Basic Science Laurel Grisanti β-Arrestin-Biased β2-Adrenergic Receptor Activation Confers Cardioprotection in Ischemia/Reperfusion Injury

Basic Science Sara Vandenwijngaert Join us at Visit Booth 2522 for an A Low-Frequency Coding Variant in Natriuretic Expert Theater 2467 Expert Lecture Peptide Receptor 1 (NPR1) Increases Systolic Blood Sunday, November 12 Monday, November 13 Pressure by Reducing 11:15 AM – 12:00 PM 10:15 AM – 10:45 AM Guanylate Cyclase Activity PRALUENT® (alirocumab) Injection: PRALUENT® (alirocumab) Injection: Clinical Science Erin Bohula The Time to Treat the Appropriate Modify Your Approach to Your Atherothrombotic Patient Is Now Patients’ Needs Risk Stratification and Magnitude of Benefit of Paul Thompson, MD, FACC Pam R. Taub, MD, FACC Evolocumab in FOURIER Hartford Hospital, Hartford, CT Associate Professor of Medicine, UC San Diego Professor, University of Connecticut, Department Health System of Medicine Population Science Neel Chokshi Loss-framed Financial Incentives and Personalized Goal Setting Increase This event is not part of the offi cial Scientifi c Sessions 2017 as planned by the AHA committee on Scientifi c Sessions Program. Physical Activity in Ischemic Heart Disease Patients © 2017 Sanofi and Regeneron Pharmaceuticals, Inc. 08/2017 SAUS.PRL.17.08.6296 Using Wearable Devices: The ACTIVE REWARD Randomized Clinical Trial 8 SCIENTIFIC SESSIONS DAILY NEWS Scenes from

HEALTH TECH COMPETITION Admetsys, a company that has created a first-of-its-kind artificial pancreas for hospital and surgical care settings, took home the Judge’s Choice Award in the fourth annual Health Tech Competition at Scientific Sessions. Procyrion, a company that has developed a minimally invasive circulatory assist device to treat heart failure, earned the People’s Choice Award. Admetsys CEO and co- founder Jeff Valk (at right in photo at left) and Procyrion Chief Scientific Officer Jace Heuring, PhD (left), accepted the awards. Congratulations to the winners and thanks to all the finalists: Amicomed, Bodyport, MobioSense, Play-it Health, Tasso Inc. and TupeloLife. WEDNESDAY, NOVEMBER 15, 2017 9

CELEBRATING RESEARCH Some of the current and past American Heart Association research awardees gathered for a group photo on Tuesday at Scientific Sessions. The AHA has funded more than $4.1 billion in research into heart disease, stroke and other cardiovascular diseases — more than any organization outside the federal government. The organization has funded 13 Nobel Prize winners and many lifesaving research advances such as the first artificial heart valve, cholesterol-inhibiting drugs, heart transplantation, and CPR techniques and guidelines. 10 SCIENTIFIC SESSIONS DAILY NEWS

Study demonstrates Race and ethnicity influence cardiovascular risk association between skin inflammation, high-risk in patients with history of hypertensive disorders coronary plaque of pregnancy, but does not influence MI, study finds A study examining the effect of esearch presented Tuesday at Scientific Sessions in- psoriasis treatment on high-risk coronary dicates that race and ethnicity modify the association plaque characteristics presented Tuesday R between hypertensive disorders of pregnancy and heart revealed additional evidence that remote failure, but do not modify the association between hyperten- inflammation can modulate coronary sive disorders of pregnancy and myocardial infarction. disease. Presenter Leila Beach, MD, noted that it’s well-established The architect and senior author of the that race and ethnicity play a role in both cardiovascular study, Nehal N. Mehta, MD, MSCE, FAHA, disease outcomes and hypertensive disorders of pregnancy. said in an interview before the meeting But her study is the first to try to determine if race and that the results of the study are a warning ethnicity mediate the increased risk of cardiovascular to physicians not to ignore ongoing, low- disease following hypertensive disorders of pregnancy. The grade sources of inflammation in patients. study reviewed the hospital discharge data of 1.5 million “We know psoriasis is a common, female patients in California. chronic inflammatory skin disease, “What was novel is that we and we know inflammation is critical to found that African-American future heart attack risk, but the results did not indicate that race atherosclerosis,” said Mehta, chief of women who had hypertensive or ethnicity significantly mediated the hazard for MI hospitaliza- inflammation and cardiometabolic diseases disorders in pregnancy were tion. In the study, hazard ratios for future MI ranged from 2.7 for at the National Heart, Lung, and Blood actually at much lower hazard gestational hypertension to 6.0 for chronic hypertension. Institute. “This needs to be taken seriously. of heart failure hospitalization “Why race and ethnicity mediate the hazard for heart We recently showed that patients whose than women in other racial or failure and not for MI is something we don’t have pinned skin disease got worse over time had ethnic groups,” said Beach, down at this point,” she said. “Even without understanding worsening of high-risk coronary plaque. If clinical instructor at the the mechanisms that are driving the difference, I think the we follow the people with high-risk plaques University of California, San implications are significant for the care of women who have for the next decade, we will see a number Leila Beach, MD Francisco, School of Medicine. a history of hypertensive disorders of pregnancy, especially of preventable heart attacks.” “And Asian-American women as medicine becomes more personalized.” The study results were presented in who had hypertensive Beach said the study also confirmed a lot of what is an abstract poster session by Jonathan disorders during pregnancy had a significantly higher hazard generally known in the literature. Chung, MD, a fourth-year medical student of heart failure hospitalization. This is not necessarily what “We found that, indeed, women had a much higher at SUNY Downstate College of Medicine we expected to find because, for the population at large, it’s hazard for heart failure and heart attack hospitalization if they in New York. Chung worked on the study well established that African-Americans are at higher risk for had hypertensive disorders of pregnancy,” she said. “We with Mehta while doing a research year at heart failure and that’s in large part driven by hypertension.” also found that the prevalence of hypertensive disorders of the National Institutes of Health through Beach said it also was interesting that they did not see the pregnancy was highest among black women and lowest in the NIH Medical Research Scholars same results for myocardial infarction. The study showed that Asian-American women. That’s something that has been Program. hypertensive disorders of pregnancy were associated with seen before in other cohorts in other states.” For the study, Mehta’s team used coronary CT angiography to measure the amount of high-risk plaque in patients with psoriasis. Participants were measured Pulmonary autograft associated with improved at baseline and again one year later. The study showed that when the skin long- and short-term outcomes in pediatric AVR condition improves, patients have a Children undergoing aortic autograft, is a more complex surgery; procedure, 84 percent for mechanical decrease in high-risk plaque features. A valve replacement had improved short- it involves replacing the diseased aortic procedure and 77.6 percent for tissue similar investigation by Mehta has shown term and long-term outcomes with valve with the patient’s own pulmonary prosthesis. the converse to also be true. That study, pulmonary autograft (Ross procedure) valve and then placing a pulmonary There was increased long-term presented earlier this year, showed that compared to mechanical or tissue AVR allograft in the right ventricular outflow survival for patients after the Ross when patients with psoriasis were not procedures, according to the results and re-attaching the coronary arteries procedure compared with mechanical effectively treated, their high-risk coronary of a retrospective study presented to the neoaorta. or tissue valve replacement with plaque features increased. Tuesday at Scientific Sessions. Amber In the study, the researchers looked increasing advantage five years after “When the inflammation goes down as Leila Sarvestani, a third-year medical at data from Pediatric Cardiac Care the AVR procedure. A multivariable assessed by their psoriasis skin disease student at the University of Missouri- Consortium, a large multi-institutional, analysis showed that outcomes with severity, the high-risk coronary plaque Kansas City, presented the research. U.S-based registry of interventions for the Ross procedure were still three features go down,” Mehta said. “These Based on the study’s results, congenital heart diseases. The study times better than with the mechanical findings add to the body of literature that clinicians may need to revisit this issue included 1,068 children who had valve. uncontrolled inflammation is a dangerous and give more consideration to the undergone their first AVR after 1991. The results are encouraging, thing, not only for systemic inflammation, Ross procedure, according to senior The median age of the children in Kochilas said, because the Ross but the blood vessels as well.” author Lazaros Kochilas, MD. the study was 12.7 years. The most procedure is associated with improved The study’s cohort included 72 middle- “Even after adjustment for a patient’s common AVR procedure in the study quality of life compared to the other age patients with moderate to severe age, era effect and co-existing condi- cohort was the Ross procedure AVR procedures. psoriasis at baseline. Participants who tions, the Ross procedure still seems to (44 percent) followed by mechanical “An additional benefit to the autograft improved their skin disease had a 68 be holding its place as the more favor- valve replacement (40 percent) and is the low risk for blood clots and, thus, percent decrease in their high-risk plaque able choice compared with any of the then tissue prosthesis (16 percent). no need for anticoagulation, which score. Conversely, those who worsened other choices,” said Kochilas, medical The in-hospital mortality was lowest can have big implications for children’s had a 50 percent increase in their high-risk director of cardiac clinical research at for Ross procedures (3.1 percent), fol- quality of life,” Kochilas said. “With plaque score. Larger studies will need to Children’s Healthcare of Atlanta. lowed by mechanical replacement (4.9 the mechanical valve, children need be conducted to confirm these findings. The study was designed to compare percent). It was highest in patients un- to take blood thinners, which can be “Our findings echo recent data from the long-term, transplant-free survival of dergoing tissue prosthesis (11.9 percent). very demanding as it requires frequent CANTOS trial, which examined whether children undergoing AVR with several Of the 1,037 patients that survived to blood tests and dose adjustment, treatment of residual inflammation in procedures: pulmonary autograft, me- discharge, the transplant-free survival and it imposes dietary restrictions and patients with prior heart attack reduced chanical valve or tissue valve prosthe- up to 15 years was 92.9 percent limits participation in certain physical recurrent heart attack,” Mehta said. sis. The Ross procedure, or pulmonary for those who underwent a Ross activities.” WEDNESDAY, NOVEMBER 15, 2017 11

Diastolic-systolic velocity ratio may be useful in assessing functional stenoses in coronary arteries, study finds n international study has identified “The most important finding is that we sound cannot provide pressure Another potentially useful the diastolic-systolic velocity ratio were able to unravel how the DSVR index data and is less precise than application, he said, might be A (DSVR) as potentially useful in as- works,” de Waard said. “Because micro- direct angiographic measure- in noninvasive follow-up for sessing functional stenoses in coronary vascular resistance is lower during diastole ment. He said there are several patients after CABG or PCI arteries. The technique, which can be per- than during systole, while stenosis resist- situations, though, in which to monitor graft patency and formed either invasively via angiography or ance does not differ for both phases of the a quick, reasonably accurate in-stent restenosis. noninvasively by echocardiography, could cardiac cycle, a stenosis that is functionally substitute may be useful. “I am not recommending be a useful adjunct to clinical practice, ac- significant has a higher impact on diastole The most common that the DSVR index replace cording to Guus de Waard, MD, a cardiolo- than on systole. This results in a decrease of scenario is the patient who any of the clinical tools we gy research fellow at VU University Medical DSVR, which can be measured immediately presents in the emergency Guus de Waard, MD already have in place,” de Center in Amsterdam, the Netherlands. using ultrasonographic echocardiography.” room with chest pain. Waard said. “It should be de Waard presented the findings from However, de Waard noted, DSVR should Electrocardiography may be viewed as an interesting and the study during the Melvin Judkins Young not be viewed as a replacement for cor- inconclusive and a troponin assay may potentially useful tool to add to our current Investigator Award Competition on Sun- onary angiography or FFR because ultra- not be immediately available. armamentarium.” day at Scientific Sessions. “We found a reasonable diagnostic accuracy for DSVR when we compared it to inva- PAID ADVERTISEMENT sive measurements, such as fractional flow reserve (FFR) to determine whether a stenosis is functionally significant,” de Waard said. “Coronary angiography with FFR remains the Learn more at gold standard for assessing the functional Booth importance of stenosis, but DSVR could be In patients with a history o MI 10 a useful adjunct in certain scenarios.” Researchers at four cardiology centers in Great Britain, Spain and the Netherlands THERE’S MORE TO collaborated on the project, which compared the diagnostic accuracy of DSVR and FFR, and explored the physiologic mecha- CONSIDER THAN LDL-C nisms that underlie DSVR. Researchers obtained simultaneous measurements of intracoronary pressure and Doppler flow velocity using coronary angiography in 228 stable patients. Meas- urements also were analyzed after percu- taneous intervention in 39 patients. de Waard reported that DSVR declines with worsening of the FFR, classified into

0.05 unit groups (Ptrend<0.001), and that DSVR shows acceptable diagnostic agree- ment with FFR at an ischemic threshold of 0.75 and a hyperemic stenosis resistance SATURDAY, NOVEMBER 11 index threshold of 0.80 mmHg·cmNovember 11-15 | Anaheim,-1·s. California The optimal cutoffDaily value forNews DSVR is 1.74. Be- cause DSVR has a close inverse correlation with the diastolic-systolic resistance ratio 2 SUNDAY, NOVEMBER 12 (r =0.83, p<0.001), de WaardNovember said 11-15 | Anaheim, the California dis- tribution ofDaily vascular resistanceNews among dias- Even when treated with optimal LDL-C–lowering therapies, tole and systole could be interrogated. The difference between systolic patients remain at risk for recurrent CV events. One of the

MONDAY, NOVEMBER 13 1-3 4 and diastolic stenosis resistanceNovember 11-15 | Anaheim, Californiaas reasons is due to inﬂ ammation —a signiﬁ cant CV risk factor. a percentageDaily of totalNews vascular resistance gradually increases as FFR class worsens (Ptrend<0.001). After PCI, DSVR TUESDAY, NOVEMBER 14 increased from a mean of November1.56 11-15 | Anaheim, to California 1.77 (p<0.01).Daily News

References: 1. Armitage J, Bowman L, Wallendszus K, et al; Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. WEDNESDAY, NOVEMBER 15 November 11-15 | Anaheim, California 2010;376(9753):1658-1669. 2. Sabatine MS, Giugliano RP, Keech AC, et al; FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-1722. 3. Cannon CP, Blazing MA, Giugliano RP, et al; IMPROVE-IT Investigators. Ezetimibe added to statin therapy DailyNews after acute coronary syndromes. N Engl J Med. 2015;372(25):2387-2397. 4. Sabatine MS, Morrow DA, Jablonski KA, et al; PEACE Investigators. Prognostic signifi cance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation. 2007;115(12):1528-1536. The American Heart Association’s Scientific Sessions 2017 Daily News is published by TriStar Publishing, Inc., as a service to American Heart Association Scientific Sessions attendees. All rights reserved. American Heart TriStar Publishing, Inc. Association 7285 W. 132nd Street, 7272 Greenville Avenue Suite 300 Dallas, TX 75231 Overland Park, KS 66213 Phone: (214) 570-5935 Phone: (913) 491-4200 scientificsessions.org tristarpub.com Novartis Pharmaceuticals Corporation Once you’ve read this issue of Daily News, East Hanover, New Jersey 07936-1080 © 2017 Novartis 9/17 XMI-1349216 please share with colleagues or deposit it in an approved paper recycling bin. Thank you. 12 SCIENTIFIC SESSIONS DAILY NEWS

Study: PCSK9 Prophylactic ablation for atrial flutter variation produced low LDL associated reduced onset of new AF, study finds he use of prophylactic pulmonary assigned to either found that patients who did with low risk for CV, vein isolation (PVI) in patients with cavo-tricuspid not undergo prophylactic all-cause death T typical atrial flutter significantly isthmus (CTI) ablation had a much higher reduced new onset of atrial fibrillation ablation alone likelihood of visiting the Having genetically low LDL cholesterol and burden, the associated number (n=25) or CTI hospital or emergency due to proprotein convertase subtilisin/kexin 9 of hospitalizations and repeat ablation with concomitant room, or being hospitalized (PCSK9) was associated with a reduced risk for AF, according to three-year results PVI (n=25). All for cardiovascular causes, for cardiovascular and all-cause mortality in the of the PREVENT AFI study presented patients received which we suspect were general population, according to data presented Tuesday at Scientific Sessions. an implantable loop largely atrial fibrillation.” Tuesday at Scientific Sessions. These results confirmed the benefit recorder and had Specifically, 32 percent “The results suggest that more prolonged of PVI seen after one-year follow-up regular follow-up Jonathan Steinberg, MD of patients in the CTI alone reductions in LDL in the study. Patients were assessed for three years. The group underwent repeat cholesterol with, for using continuous implantable loop primary endpoint of the study was the ablation compared with 8 percent in the example, PCSK9 recorder with a battery life of about occurrence of any atrial tachyarrhythmia PVI plus CTI group (P=.037). The three- inhibitors, might three years that allowed Jonathan including AF or atrial flutter after ablation year AF burden was only 6.2 percent eventually translate Steinberg, MD, and colleagues to with the monthly burden exceeding 0.5 for prophylactic PVI compared with into a reduction in both continue to follow outcomes for an percent on the recorder. 16.8 percent for the CTI alone group cardiovascular and extended period. At three years, 80 percent (P=.038). Finally, about half (48 percent) all-cause mortality,” “Over three years, there was still a of patients who did not have of patients in the CTI alone group were said Marianne Benn, substantial reduction in the incidence prophylactic PVI developed AF or hospitalized during the follow-up period MD, PhD. “However, Marianne Benn, MD, PhD of atrial fibrillation,” said Steinberg, atrial flutter compared with only about compared with 16 percent of patients randomized clinical a cardiologist with the University of half (52 percent) of patients in the CTI who underwent prophylactic ablation intervention trials of Rochester in New York. “Because we plus PVI group (hazard ratio=2.40; 95 (P=.032). PCSK9 inhibitors with long follow-up are needed documented this with the implantable percent CI, 1.18-4.86; P=.015). “We may be moving in a different to document such effects.” loop recorder, we saw a substantial Because the researchers were able direction now when it comes to According to Benn, associate professor and reduction of about two-thirds of to follow patients for this extended applying prophylactic ablation for AF,” chief physician in the Department of Clinical atrial fibrillation burden over time. period they could clinically track other Steinberg said. “In future research, Biochemistry at Rigshospitalet, a function of Prophylactic ablation worked in greatly outcome events, Steinberg said. we may be looking at groups that Copenhagen University Hospital in Denmark, reducing the amount of new onset “We found that one-third of patients have high risk of AF who may be PCSK9 degrades LDL receptors and lowers the atrial fibrillation.” who did not have prophylactic ablation candidates for additional clinical amount of LDL cholesterol that can be removed The study included 50 patients with were referred back for ablation for investigation or for prophylactic by the liver. Genetic variation in the PCSK9 gene documented atrial flutter randomly atrial fibrillation,” he said. “We also ablation procedures.” reducing protein function (similar to PCSK9 inhibition) increases the number of LDL receptors and lowers LDL cholesterol. Study: Cardiosphere-derived cell infusion improved In this study, Benn and colleagues tested whether genetically low LDL due to PCSK9 was several outcomes of functional single ventricle causally associated with reduced cardiovascular ntracoronary autologous cardiosphere-derived cell who underwent stage 2 or stage 3 surgical palliation and all-cause mortality in the general population. (CDC) infusion in patients with functional single ventricle with single-ventricular physiology between January 2011 They genotyped for PCSK9 R46L (rs11591147), I resulted in significant improvements at two years in and March 2015. Forty-one patients were assigned to R237W (rs148195424), I474V (rs562556) and ventricular function, somatic growth, heart failure status receive CDC infusion into coronary arteries four weeks E670G (rs505151) in 109,566 individuals from and event-free survival, according to the results of a study after staged palliation. Sixty patients were treated by the Copenhagen General Population study presented Tuesday by Toshikazu Sano, MD. staged palliation alone. and the Copenhagen City Heart Study. With a “Cardiosphere-derived cell infusion in Compared with stage palliation alone, median follow-up of 8.6 years and more than patients with single-ventricle physiology patients treated with the CDC infusion had 1 million person years, they observed 2,261 was associated with improved cardiac significantly improved cardiac function cardiovascular deaths and 14,651 deaths from function at two years regardless of the (P<.05) and somatic growth (P<.01). In any cause. proceeding stage procedure,” said addition, CDC infusion was associated Results of the study revealed that genetically Sano, of the department of vascular with improved event-free survivals such as low LDL cholesterol due to PCSK9 variation surgery at Okayama University Hospital late failure, adverse events and catheter (corresponding to pharmacologic inhibition in Japan. “These better outcomes may intervention. of PCSK9 by alirocumab or evolocumab) be attributed to decreased incidence Multivariate analyses showed that both was causally associated with low risk of of rehospitalization or repeated cardiac CDC infusion (P<.02) and heart failure status cardiovascular mortality. Specifically, an surgery for recurrent heart failure, as well (P<.03) were significant affecters for adverse increasing number of weighted PCSK9 alleles as reduced the parenting stress during Toshikazu Sano, MD events at two years. were associated with stepwise lower LDL child care for their families.” The researchers also categorized study cholesterol of up to 0.61 mmol/L (P for trend Cardiosphere-derived cells are enriched patients into two subgroups: heart failure <.001), and with lower cardiovascular (P=.0002) with a cardiac progenitor cell population that can give rise with preserved or reduced ejection fraction (cardiac and all-cause mortality (P=.045). to cardiomyocytes, smooth muscle and endothelial cells function <50 percent). CDC infusion improved cardiac “Mortality data on low LDL cholesterol via in vitro and in vivo. Along with these direct-differentiation function at two years in both groups. In patients with PCSK9 has not been reported before,” Benn capabilities toward cardiovascular-lineage specification reduced ejection fraction receiving CDC, the incidence said. “There is only one study which has shown for myocardial repair, recent studies have shown that of all-cause mortality, late failure, adverse events and that lowering LDL cholesterol as primary cardiosphere-derived cells are able to transfer exosomes, unplanned catheter intervention were significantly prevention reduces mortality.” which contain various molecular constituents of their cell reduced compared with those treated by surgical The researchers conducted causal genetic of origin, including proteins and micro RNA, as biologically reconstruction alone. analyses and found a 1 mmol/L lower LDL active cell-derived small vesicles. “In patients with preserved ejection fraction, the functional cholesterol was associated with significantly In this study, Sano and colleagues assessed the benefits brought by cell therapy was neither associated reduced risk for cardiovascular death (risk long-term effects and clinical outcomes of intracoronary with improved mortality nor reduced late complication after ratio=0.33; 95 percent CI, 0.19-0.58; P<.001) infusion of autologous CDCs in patients with single- staged palliation. It may require further studies to investigate and all-cause mortality (risk ratio=0.72; 95 ventricle physiology compared with patients treated by the underlying mechanisms to innovate novel therapy to percent CI, 0.60-0.88; P=.001). staged palliation alone. The study included 101 patients treat these patients,” Sano said. WEDNESDAY, NOVEMBER 15, 2017 13

CANVAS continued from page 1 in Patients with Type 2 Diabetes Mellitus and In EMPA-REG, adding empagliflozin BiomarCaRE University of Hamburg in Germany. “In Cardiovascular Disease (EXSCEL) trial. to standard care for patients with PAD Serum metabolites could become the our cohort of middle-aged individuals, we The primary EXSCEL trial had more than reduced the risk of cardiovascular death next generation of predictors and prog- found four metabolites that are significantly 14,000 participants with Type 2 diabetes from by 43 percent, all-cause mortality by 38 nosticators for coronary heart disease, associated with coronary heart disease.” 35 countries and showed a 15 percent reduc- percent and heart failure hospitalization according to the largest study performed The four metabolites are phosphatidyl- tion in the risk for all-cause mortality compared by 44 percent versus placebo. In patients on serum metabolites. cholines and have an inverse relationship to to placebo. About 70 percent of the trial popu- without PAD, risk reduction was 36 per- Serum Metabolomic Profiles Predict coronary heart disease. Lower metabolite lation had a prior cardiovascular event. cent for cardiovascular death, 30 percent Coronary Heart Disease in the General levels increase risk while higher levels are “The question was whether the magni- for all-cause mortality and 32 percent for Population (BiomarCaRE) used the Bio- protective. The predictive strength of metab- tude of the treatment benefit depends on a heart failure hospitalization. marker for Cardiovascular Risk Assess olite markers is similar to classical risk fac- patient’s baseline risk,” said Robert J. Men- “There’s a profound and precocious in Europe database to create a cohort of tors such as BMI, systolic blood pressure, tz, MD, assistant professor of medicine at separation of curves favoring empagli- 10,741 people that included 2,166 pa- diabetes and total cholesterol, Zeller said. Duke University in Durham, North Carolina. flozin in patients with PAD,” Verma said. tients with coronary heart disease. More research and validation are need- “Our hypothesis was that patients who are “This is reflective of the higher baseline “Metabolites are good candidates be- ed before metabolites are ready for clinical at increased risk for mortality and MACE risk of this population. The substantial cause they reflect genomic changes in use, she said. But the BiomarCaRE study have a relatively greater benefit with exen- risk reductions seen in patients with PAD individuals and indicate changes in phe- indicates the value of metabolomics to atide than those at lower risk.” have important translational implications notypes,” said Tanja Zeller, PhD, professor develop novel biomarkers and improve However, data showed no significant for clinical practice.” for genomics and systems biology at the risk stratification. difference in treatment benefit based on baseline cardiovascular risk. Instead, the PAID ADVERTISEMENT study showed that familiar baseline characteristics — including age, prior cardiovascular events, comorbidity burden and lab values — provide good prognostic value for mortality and MACE.

EMPA-REG OUTCOME Patients with diabetes and peripheral artery disease at baseline benefit more from empagliflozin added to standard care compared to patients with diabetes and other types of cardiovascular disease, according to results from a sub-analysis of the Empagliflozin Reduces Mortality and Hospitalization for Heart Failure in Patients with Type 2 Diabetes and Peripheral Artery Disease (EMPA-REG OUTCOME) trial. Adverse events, including rates of lower limb amputations, were similar in both groups. PAD is among the most common co- morbidities in patients with Type 2 diabetes. Similarly, PAD patients often have diabetes. PAD is a predictor of cardiovascular death and is associated with an increased risk of heart failure. The primary EMPA-REG OUTCOME trial of empagliflozin in patients with Type 2 diabetes and CVD showed good cardiovascular results. The risk of cardiovascular death was reduced by 38 percent, all- cause mortality by 32 percent, heart failure hospitalization by 35 percent and incident or worsening neuropathy by 39 percent compared to placebo. The primary analysis didn’t explore the effect of empagliflozin on the 1,461 patients who had PAD. The trial update compared cardiovascular death, all-cause mortality, MACE, heart failure hospitalization, a composite of heart failure hospitalization or death, neuropathy and adverse events in patients with and without PAD. The biggest difference in the PAD group was an excess of former and current smokers. “That’s not surprising,” said Subodh Verma, MD, PhD, FAHA, Professor and Canada Research Chair in Atherosclerosis at the University of Toronto in Ontario. “In patients with PAD, 70 percent are current or former smokers. The presence of PAD identifies a group at higher risk of cardiovascular events and death.” 14 SCIENTIFIC SESSIONS DAILY NEWS

ACCELERATOR-2 continued from page 1 Than reported that all sites had an outcomes, including a reduction in our understanding of which patient groups de- DECIDE-LVAD increase in proportion of patients discharged primary outcome of the rate of death, rive the most clinical benefit from adherence The findings of another recent trial within six hours (pre-implementation mean recurrent heart attack, stroke and major improvement efforts.” suggest that a shared decision-making 8.3 percent; post-implementation mean bleeding at 30 days — from 6.4 percent intervention for destination therapy 18.4 percent). Researchers found no in the control group to 5.3 percent in the SWEDEHEART left ventricular assist device (DT LVAD) difference in the proportion of patients with a intervention group,” Huffman said. An analysis of data from a national improved patient decision quality based MACE within 30 days of patients discharged myocardial infarction registry in Sweden on patient knowledge and concordance within six hours: pre-implementation STIC2IT shows a dramatic improvement in long-term between stated values and patient- (0.52 percent) compared with post- A novel, technologically enabled, survival and reduction in the risk of new reported treatment preference. implementation (0.44 percent). behaviorally targeted, pharmacist-based ischemic events and heart failure in non-ST- Results from the Effectiveness of a intervention improves adherence to elevation MI patients over the last 20 years. Shared Decision Making Intervention for ACS QUIK medications for chronic diseases and The researchers believe these improve- Patients Offered a Destination Therapy The results of a recent trial conducted across disease control, according to findings from ments in outcomes are attributable to the Left Ventricular Assist Device for End- 63 hospitals in Kerala, India, demonstrated the Results of the Study of a Tele-Pharmacy gradual uptake and widespread use of Stage Heart Failure trial were presented that a quality improvement intervention led to Intervention for Chronic Diseases to Improve in-hospital coronary interventions and evi- Tuesday by Larry A. Allen, MD, of the improvements in in-hospital and discharge Treatment Adherence trial. dence-based medications. University of Colorado-Denver. medications, but not in the rate of 30-day A total of 4,078 patients with diabetes, Findings from the Improved Outcomes in After randomly varying time in usual care, MACE in acute MI patients. hypertension or hyperlipidemia who Patients with Non-ST-Elevation Myocardial LVAD implanting centers were transitioned Findings from the Effect of a Quality were both non-adherent and had poor Infarction During 20 years are Related to an intervention consisting of clinician Improvement Toolkit on Acute Myocardial disease control were randomized in equal to Implementation of Evidence-Based education and use of a DT LVAD pamphlet Infarction in India: The ACS QUIK Cluster numbers to the intervention and usual- Treatments study were presented Tuesday and video patient decision aids. Patients Randomized, Stepped Wedge Trial were care arms. The intervention consisted of by Karolina Szummer, MD, of Karolinska being considered for DT LVAD were enrolled presented Tuesday by Mark D. Huffman, a brief pharmacist-delivered telephone University Hospital in Stockholm. and followed up at one and six months. MD, of Northwestern University in Chicago. consultation, text messaging, mailed Szummer reported that the standard- Allen reported that patient knowledge The researchers evaluated the effect of reports providing patients with updated ized, one-year mortality ratio in NSTEMI (mean test performance) during the a locally adapted, evidence-based quality biometric and adherence information compared to the control population de- decision-making period improved from 59.5 improvement toolkit on process measures and feedback from the pharmacists to creased from 5.53 (5.30-5.77) in 1995-96 percent to 64.9 percent in control versus and outcomes among 21,374 patients patients’ primary care physicians. to 3.03 (2.89.3.19) in 2013-14. After ad- 59.1 percent to 70 percent in intervention. from November 2014-November 2016. “The intervention increased medication justing for differences in baseline charac- Correlation between stated values and The toolkit included audit and feedback, adherence but did not improve measures of teristics, the change of one-year CV-death patient-reported treatment preference at admission and discharge checklists, disease control, including LDL cholesterol, or MI corresponded to a linearly decreas- one month was stronger in intervention than patient education materials and linkage blood pressure and hemoglobin A1C,” said ing trend of 0.930 (95 percent CI: 0.926- control. However, there was no improved to emergency cardiovascular care and Niteesh K. Choudhry, MD, PhD, of Brigham 0.935) per two-year period. This trend correlation between stated values and quality improvement training. and Women’s Hospital and Harvard Medi- was substantially attenuated after adjust- actual treatment received by six months “We saw improvements in process cal School in Boston. “Future work should ing for changes in coronary interventions, for intervention compared to control. There measures, including in-hospital and focus on strategies to increase the uptake and almost eliminated after also adjusting were no differences in decision conflict, discharge medications, and clinical of similar interventions and on improving the for changes in discharge medications. decision regret or preferred control.

GEMINI-ACS-1 continued from page 1 A total of 6.5 percent of patients switched oxaban plus aspirin versus aspirin alone. metal stents or ticagrelor versus clopidogrel. Edmonton. “But 470 patients with prior PCI agents, with 8.5 percent of the ticagrelor The primary trial found a 24 percent The primary trial compared two dabig- were randomized, which give us the opportu- group switching to clopidogrel and 4 percent reduction in the risk for cardiovascular atran doses, 150 mg and 110 mg, plus a nity to look at any potential subgroup effect.” of clopidogrel patients switching to ticagrelor. death, stroke or MI, said Andre Lamy, P2Y12 inhibitor versus warfarin triple-ther- The subgroup analysis found that in pa- CP2C19 status played a small role in MD, associate professor of surgery at apy with a P2y12 inhibitor plus aspirin. tients with prior PCI, those taking aspirin switch decisions, Ohman said. The vast ma- McMaster University in Hamilton, Ontario. Both doses of dabigatran showed non-in- had a 50 percent risk reduction for death jority of patients did not switch, irrespective The trial update examined the potential ferior outcomes vs. warfarin therapy. And or MI compared to placebo. of their metabolizer status. And while patients cost impact in the United States, Canada, while the trial was not powered to show “Among those with prior PCI undergo- with RM status were five times more likely France and Germany based on direct superiority with 2,725 patients, both dab- ing noncardiac surgery, perioperative as- to switch compared to UM patients, only 43 medical and procedural costs for all car- igatran doses showed better efficacy. pirin may be more likely to benefit patients percent of RM patients switched from clopi- diovascular events in the trial. “There were no interactions in the sub- than to harm them,” Graham said. dogrel to ticagrelor because of metabolizer U.S. treatment costs ranged from groups based on ACS, the type of stent status. The other 57 percent switched due to $6,871 for severe limb ischemia to used or the antiplatelet agent,” said Jonas PRAGUE-18 nonbleeding adverse events, recurrent isch- $48,859 for stroke. Costs in the other four Oldgren, MD, professor of medicine at Patients who take prasugrel or ticagrelor emic events, or another reason. countries were lower, particularly for pro- Uppsala University in Sweden. “The bene- following MI and then switch to clopi- Only one patient switched from ticagre- cedures, Lamy said. fits of dabigatran dual therapy were entire- dogrel are not at increased risk for isch- lor to clopidogrel because of metabolizer “We are looking only at direct-care ly consistent with the main results.” emic events, according to findings from status. Other switches were due to non- costs for cardiovascular events and pro- PRAGUE-18, an academic study that bleeding adverse events, recurrent isch- cedures,” he said. “And the 2.5 mg dose POISE-2 PCI examined one-year outcomes comparing emic events or other reasons. of rivaroxaban has not been approved Patients with previous PCI who are taking patients who did and did not switch to “Our findings do not support the utility of anywhere, nor do we know the list price. aspirin probably do not need to interrupt clopidogrel. Because there was no indus- mandatory pharmacogenomics testing for But we saw that rivaroxaban decreases aspirin for noncardiac surgery. For every try support, patients had to pay for anti- P2Y12 inhibitor use because clinicians do not the direct costs of hospitalization, proce- 1,000 patients with prior PCI, periopera- platelet agents after discharge. act on it,” Ohman said. “And we saw no in- dures and other treatments for major car- tive aspirin will prevent 59 MIs and cause “Patients commonly switch to clopi- creased risk of ischemic events or increased diovascular events.” eight major bleeds, according to findings dogrel after discharge for economic rea- bleeding with the RM phenotype, suggesting from a post-hoc analysis of a subgroup of sons,” said co-principal investigator Zu- the information is of little clinical value.” RE-DUAL PCI the 10,010 patients in the POISE-2 study zana Motovska, PhD, professor and head Clinicians should not expect any significant comparing aspirin to placebo in patients of acute cardiology at Charles University COMPASS subgroup differences when using dabiga- undergoing noncardiac surgery. Third Medical Faculty in Prague. Rivaroxaban 2.5 mg bid plus aspirin has tran dual-therapy for patients undergoing “This was not a prespecified analysis “Most patients who switched because the potential to reduce direct care costs an PCI. The results of a subgroup analysis of because the steering committee did not ex- of cost did so immediately after discharge. average of $682 for every patient treated. the RE-DUAL PCI trial found no differences pect to randomize patients with prior PCI,” Whether they switched or not, we saw no The estimate comes from a trial update of between the primary outcome and sub- said Michelle M. Graham, MD, professor of difference in the key endpoint of cardio- COMPASS, which compared cardiovascu- groups with acute coronary syndrome as cardiology at the University of Alberta and vascular death or nonfatal stroke or MI,” lar outcomes for patients treated with rivar- the index event, drug-eluting versus bare the Mazankowski Alberta Heart Institute in Motovska said. PAID ADVERTISEMENT

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