PracticeUpdate Cardiology June 2019

VOL. 4 • NO. 2 • 2019

OUR EXPERTS. YOUR PRACTICE.

ISSN 2206-4672

Contemporary Treatment of Atrial Fibrillation in 2019

Expert Opinion My Approach to Syncope

in the Adult Interviewwith Paul D. ThompsonMD

American College of Cardiology Annual Scientific Session & Expo 2019

JOURNAL SCANS A Fully Magnetically Levitated Left Ventricular Assist Device—Final Report

Stress Related Disorders and Risk of Cardiovascular Disease: Population Based, Sibling Controlled Cohort Study

Association of Influenza-Like Illness Activity With Hospitalizations for Heart Failure: The Atherosclerosis Risk in Communities Study

Before prescribing, please review full Product Information available from www.novartis.com.au/products/healthcare-professionals PBS Information: Authority required (STREAMLINED) for chronic heart failure. Patients must be NYHA Class II–IV, have LVEF ≤40% and be receiving optimal standard chronic heart failure treatment. Refer to PBS Schedule for full Authority Information.

MINIMUM PRODUCT INFORMATION ENTRESTO ® (sacubitril/valsartan). Indication: Treatment of chronic heart failure (NYHA Class II-IV) with reduced ejection fraction. Contraindications: Hypersensitivity to sacubitril, valsartan, or excipients. ACE inhibitors (ACEi). Do not administer within 36 hours of switching from or to an ACEi. Angioedema related to previous ACEi or ARB therapy. Use with aliskiren in Type 2 diabetes (T2D). Severe hepatic impairment, biliary cirrhosis and cholestasis. Pregnancy. Precautions: Caution in switching from ACEi or T2D (see Contraindications). Caution is required while co-administering with aliskiren. Should not be co-administered with an ARB. May cause symptomatic hypotension, especially in those ≥75 years old, renal disease and systolic BP <112 mmHg. Initiation not recommended in systolic BP <100 mmHg. Monitor BP when initiating therapy or during dose titration. Patients with an activated RAAS, such as volume- and/or salt-depleted patients, are at greater risk. If hypotension occurs, dose adjustment of diuretics, antihypertensives, and treatment of other causes of hypotension should be considered initially. If hypotension persists, consider dose reduction or temporary interruption. Sodium and/or volume depletion should be corrected before starting treatment. Caution, may be associated with decreased renal function. Assess renal function before initiation and during treatment. Closely monitor serum creatinine, and down-titrate or interrupt if a clinically significant decrease in renal function develops. May increase blood urea and serum creatinine levels in patients with bilateral or unilateral renal artery stenosis. Not recommended with end-stage renal disease. Should not be initiated and consider discontinuation

She’s lived life WHOLE-HEARTEDLY. Treat her that way. † 1

† Replace an ACEI or ARB with an ARNI to decrease mortality and hospitalisation in suitable HF-rEF patients ‡1

if the serum potassium level is >5.4 mmol/l. Hyperkalaemia may occur. Monitor serum potassium periodically and treat appropriately, especially with risk factors such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Dosage reduction or interruption may be required. Caution with medications known to raise potassium levels. If clinically significant hyperkalaemia occurs, consider adjusting the dose of concomitant medications. If angioedema occurs, immediately discontinue, and appropriate therapy and monitoring should be provided until complete and sustained resolution of signs and symptoms. Patients with a prior history of angioedema may be at higher risk, caution is recommended. Black patients may have increased susceptibility to develop angioedema. Caution in NYHA Class IV. Caution in moderate hepatic impairment or with AST/ALT >2X upper limit of the normal range, exposure may be increased. Do not use in severe hepatic impairment, biliary cirrhosis or cholestasis. Use in lactation is not recommended. Use contraception during treatment and for 1 week after last dose. Interactions: Aliskiren in T2D, ACEi/ARB. Caution with statins, sildenafil, lithium, potassium-sparing diuretics including mineralocorticoid antagonists, potassium supplements, or salt substitutes containing potassium, NSAIDs including selective COX-2 Inhibitors, frusemide, inhibitors of OATP1B1, OATP1B3, OAT3 or MPR2 and metformin. Dosage: Target dose one oral tablet of 97 mg/103 mg twice daily. Starting dose is one tablet of 49 mg/51 mg twice daily. Starting dose one tablet of 24 mg/26 mg taken twice daily is recommended for ACEi/ARB naive patients, those with severe renal impairment, moderate hepatic impairment, and in those ≥75 years old. Also consider risk factors for hypotension and low systolic BP ≥100 to 110 mmHg. Double every 2-4 weeks to the target dose. Adverse effects: Very common: Cardiac failure, hyperkalaemia, renal impairment and hypotension. Common: Anaemia, angina pectoris, atrial fibrillation, congestive or chronic cardiac failure, ventricular tachycardia, constipation, diarrhoea, nausea, asthenia, cardiac death, fatigue, non-cardiac chest pain, oedema peripheral, bronchitis, influenza, nasopharyngitis, pneumonia, upper respiratory tract infection, urinary tract infection, diabetes mellitus, gout, hyperuricaemia, hypokalaemia, arthralgia, back pain, pain in extremity, dizziness, headache, syncope, insomnia, renal failure, chronic obstructive pulmonary disease, cough, dyspnoea and hypertension. (ent081117m). ® Registered trademark. Novartis Pharmaceuticals Pty Limited. 54 Waterloo Road, Macquarie Park NSW 2113. Ph (02) 9805 3555. For medical enquiries please contact 1800 671 203 (phone) or medinfo.phauno@novartis.com (email).

‡ HF-rEF (with LVEF ≤40%) despite maximally tolerated or target doses of ACEI (or ARB) and beta-blocker (unless contraindicated), with or without an MRA. 1 Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor; HF-rEF, heart

failure with reduced ejection fraction; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist. Reference: 1. Atherton JJ et al. Heart Lung Circ 2018; 27: 1123–1208. AU-9024. McCann Health NOEN15957M. May 2019.

PRACTICEUPDATE CARDIOLOGY BOARD PracticeUpdate is guided by a world-renowned Editorial and Advisory Board that represents community practitioners and academic specialists with cross-disciplinary expertise. Editor-in-Chief Douglas Zipes MD Distinguished Associate Editors Joerg Herrmann MD Associate Professor

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ABOUT For a complete listing of disclosures for each board member and editorial contributor, please refer to their profile on PracticeUpdate.com PracticeUpdate ’s mission is to help medical professionals navigate the vast array of available literature and focus on the most critical information for their patients and practice. All journal articles selected for PracticeUpdate receive a Take-Home Message designed to quickly summarize the key findings and explain the importance of that research within the specialty area. The most critical articles also receive Expert Commentaries from experts who are handpicked by the PracticeUpdate Editorial Board, providing additional context on that research for the reader. Expert Opinion pieces give special highlights to important topics and Conference Coverage captures relevant takeaways from a vast array of medical meetings throughout the year. PracticeUpdate Cardiology provides coverage of key research from leading international conferences, and a collection of top journal articles and accompanying expert commentaries in a convenient print periodical. These and more are also available online at PracticeUpdate.com PracticeUpdate and PracticeUpdate Cardiology are commercially supported by advertising, sponsorship, and educational grants. Individual access to PracticeUpdate.com is free. Premium content is available to any user who registers with the site. While PracticeUpdate is a commercially-sponsored product, it maintains the highest level of academic rigour, objectivity, and fair balance associated with all Elsevier products. No editorial content is influenced in any way by commercial sponsors or content contributors. DISCLAIMER PracticeUpdate Cardiology has been developed for specialist medical professionals. The ideas and opinions expressed in this publication do not necessarily reflect those of the Publisher. Elsevier will not assume responsibility for damages, loss, or claims of any kind arising from or related to the information contained in this publication, including any claims related to the products, drugs, or services mentioned herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. Please consult the full current Product Information before prescribing any medication mentioned in this publication. Althoughalladvertisingmaterial isexpected toconform toethical (medical)stand- ards, inclusion in thispublicationdoesnotconstituteaguaranteeorendorsement of the quality or value of such product or of the claims made of it by its manu- facturer. The printing and distribution of this publication has been made possible through paid advertising. The editorial content herein is independently produced by Elsevier with no involvement by the advertiser. It contains content published in accordancewiththeeditorialpoliciesofElsevier’sPracticeUpdate.com.Allcontent printed in this publication can be found on PracticeUpdate.com. CONTENT Abstracts are available when the publisher grants permission to MEDLINE/ PubMed, a database of the US National Library of Medicine. • NLM data are produced by a US Government agency and include works of the United States Government that are not protected by US copyright law but may be protected by non-US copyright law, as well as abstracts originating from publications that may be protected by US copyright law. • NLM assumes no responsibility or liability associated with use of copyrighted material, including transmitting, reproducing, redistributing, or making commercial use of the data. NLM does not provide legal advice regarding copyright, fair use, or other aspects of intellectual property rights. Persons contemplating any type of transmission or reproduction of copyrighted material such as abstracts are advised to consult legal counsel. SALES Matthew Buttsworth m.buttsworth@elsevier.com PRODUCTION Content was originally published on PracticeUpdate.com Editorial Manager A nne Neilson anne.neilson@elsevier.com Editorial Project Manager Carolyn Ng Designer Jana Sokolovskaja Cover: Human heart surrounded by waves, beats and pulses/gettyimages.com PracticeUpdate Cardiology is published by Elsevier Australia ISSN 2206-4672 (Print) ISSN 2208-0228 (Online)

Benjamin Scirica MD Cardiologist and Director, Innovation, Cardiovascular Division, Brigham and Women’s

Professor, Professor Emeritus of Medicine,

of Medicine, Mayo Graduate School of Medicine, Rochester, Minnesota

Pharmacology and Toxicology; Emeritus Director, Division of Cardiology and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana

Hospital; Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts

Advisory Board

Deepak Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC Professor of Medicine, Harvard Medical School; Executive Director, Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center; Senior Physician, Brigham and Women’s Hospital, Boston, Massachusetts Peter Libby MD Mallinckrodt Professor of Medicine, Harvard Medical School, Boston, Massachusetts J WilliamMcEvoy MB BCh BAO, MEHP, MHS, FRCPI Professor of Preventive Cardiology, National University of Ireland; Medical and Research Director, National Institute for Preventive Cardiology, Ireland; Adjunct Faculty Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins, Baltimore, Maryland

Paul Thompson MD Physician Co-Director, Hartford Healthcare Cardiovascular Institute, Hartford, Connecticut; Professor of Medicine, University of Connecticut, Storrs, Connecticut James Udelson MD Chief, Division of Cardiology; Director, Nuclear Cardiology Laboratory; Professor, Medicine and Radiology, Tufts University School of Medicine, Boston, Editor-in-Chief, ChiP Network and ACHD Learning Center; Consultant, Cincinnati Adult Congenital Heart Program; Emeritus Professor, Department of Pediatrics, University of Cincinnati, Ohio Clyde Yancy MD, MSc, MACC, FAHA, MACP, FHFSA Chief of Cardiology, Northwestern University, Feinberg School of Medicine; Associate Director, Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago, Illinois Massachusetts Gary Webb MD

Editorial Contributors

Ashish Aggarwal MD Staff Physician, Interventional Cardiology, Providence Holy Cross Medical Center, Mission Hills, California

Samer Ajam MD Clinical Cardiac Electrophysiologist, Community Care Network Inc, Munster, Indiana

Jason Garlie MD Staff Cardiologist; Electrophysiologist, Metropolitan Heart and Vascular Institute, Minneapolis, Minnesota

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CONGENITAL HEART DISEASE FACULTY Editor-in-Chief Gary Webb MD

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CONTENTS 5

RESEARCH 6 A Fully Magnetically Levitated Left Ventricular Assist Device Comment by Clyde W. Yancy MD, MSc, MACC and Jayson R. Baman MD

COVER 14 Contemporary Treatment of Atrial Fibrillation in 2019 Interview with Douglas P. Zipes MD by Aman Shah MD

EXPERT OPINION 16 My Approach to Syncope in the Adult Interview with Paul D. Thompson MD by Aman Shah MD

7 TAVR With a Balloon-Expandable Valve in Low-Risk Patients 8 Stress-Related Disorders Associated With Risk of Cardiovascular Disease Comment by Viola Vaccarino MD, PhD 9 Improved Survival With Catheter Ablation of Refractory Ventricular Fibrillation Storm After Myocardial Infarction Comment by Sana M. Al-Khatib MD, MHS 10 Association of Influenza-Like Illness Activity With Hospitalizations for Heart Failure Comment by Jonathan Temte MD, PhD

CONFERENCE 18 American College of Cardiology Annual Scientific Session & Expo 2019

11 Early or Delayed Cardioversion in Recent- Onset Atrial Fibrillation 12 Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI Comment by Paul M. Ridker MD 13 Identification of Imaging Markers of Coronary Plaque Vulnerability Using Radiomic Analysis of Coronary CTA Comment by James E. Udelson MD

18 Dual Antiplatelet Therapy After PCI With Drug-Eluting Stents Interview with Deepak L. Bhatt MD, MPH, FACC by Aman Shah MD 19 Anticoagulation for AFib After Percutaneous Coronary Intervention Interview with Deepak L. Bhatt MD, MPH, FACC by Aman Shah MD

20 2019 ASCVD Guidelines: General Approaches

Interview with J. William McEvoy MB BCh BAO by Aman Shah MD 22 Updated Guidelines for the Management of Heart Failure: New Medications Interview with Clyde W. Yancy MD, MSc, MACC by Aman Shah MD

VOL. 4 • NO. 2 • 2019

EDITOR’S PICKS 6

A Fully Magnetically Levitated Left Ventricular Assist Device The New England Journal of Medicine Take-home message • Patients with advanced heart failure were randomized to receive a fully magnetically levitated centrifugal-flow left ventricular assist device or a mechanical-bearing axial-flow left ventricular assist device as either a bridge to transplantation or destination therapy. At 2 years, 76.9% of patients in the centrifugal-flow pump group were alive and free from disabling stroke or reoperation compared with 64.8% in the axial-flow pump group (P < .001 for superiority). In addition, patients in the centrifugal-flow pump group had a lower rate of pump replacement at 2 years compared with patients in the axial-flow pump group. • The use of a fully magnetically levitated centrifugal-flow left ventricular assist device in patients with advanced heart failure was associated with improved survival outcomes and less need for pump replacement than an axial-flow device. COMMENT By Clyde W. Yancy MD, MSc, MACC, FAHA, MACP, FHFSA and Jayson R. Baman MD " Our evolving expectation of a less complicated application of mechanical circulatory support brings this technology to more patients and offers hope to the desperately ill patient with advanced heart failure. "

Abstract BACKGROUND In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated cen- trifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondis- abling stroke than were patients treated with

F or 50 years, cardiovascular investigators have been in pur- suit of capable means of mechanical circulatory support (ie, left ventricular assist device, or LVAD therapy) for the failing heart. The dire outcomes associated with heart failure in the early years fueled the rush to invention, whereas the ongoing need for mechanical support strategies for NYHA class IV heart fail- ure in the contemporary era (despite effective, evidence-based medical therapy) has sustained the need for iterative product development. LVADs have been historically bioengineered as axial-flow devices, but adverse events, particularly pump thrombosis, drive line infection, gastrointestinal bleeding due to mechanical disruptions in coagulation profiles, and stroke, have been significant and costly challenges. These events, especially pump thrombosis, have proven to carry grave prognoses. Yet, the need remains acute, and, when all goes well, the remarkable stabilization of the heart failure syndrome and subsequent evi- dence-based improvement in morbidity and mortality compared with medical therapy has positioned LVAD therapy as a realistic but imperfect treatment option for heart failure. The technology has evolved from large-format, pulsatile, mechanical devices that limited portability to smaller, electronic, non-pulsatile devices that were more patient friendly but abruptly challenged our understanding of physiology. Is there a true need for pulsatile blood flow? The most recent iteration of LVAD technology incorporates a magnetically levitated, friction-free pump with no blood-pump interface and a pump that restores (modest) circulatory pulsatility. The MOMENTUM 3 trial tested this latest third-generation pump against second-generation pumps. The early 6-month and then later 2-year data were heralded as breakthrough findings. We now

have the final report. The authors report superiority of the Heart- Mate 3 device with regard to the primary endpoint of survival free of disabling stroke and reoperation (HR, 0.84; P < .001) and the secondary endpoint of the necessity of pump replacement within 2 years (HR, 0.21; P < .001). Remarkably, the HeartMate 3 device was associated with a 90% reduction in cases of pump thrombosis (70 cases vs 7 cases; HR, 0.08; P < .001). This was in conjunction with reduced rates of cerebrovascular events (HR, 0.42; P < .001) and bleeding events (HR, 0.64; P < .001). We are now able to arguably assert that optimal use of these third-generation pumps has eradicated the most compelling complication of pump thrombosis and has largely reduced the worrisome risk of stroke. There is a need for more research. The authors report the still high rates of drive line infections, there remains a need for devel- opment of best-quality practices, and easier pumps to implant are needed. However, we have reached a pause moment in the care of patients with advanced heart failure. Our evolving expectation of a less complicated application of mechanical circulatory support brings this technology to more patients and offers hope to the desperately ill patient with advanced heart failure. For those of us who provide care for these patients, this technology reliably answers questions raised 50 years ago. The journey continues, but it has been nicely rewarded.

Dr. Baman is an Internal Medicine Resident at Northwestern University in Chicago, Illinois.

PRACTICEUPDATE CARDIOLOGY

EDITOR’S PICKS 7

TAVR With a Balloon-Expandable Valve in Low-Risk Patients

The New England Journal of Medicine

Take-home message • Patients with severe aortic stenosis and at low surgical risk were randomized to undergo transcatheter aortic valve replacement (TAVR) with transfemoral placement of a balloon-expandable valve or surgical aortic-valve replacement to compare outcomes. The rate of the composite primary outcome of death, stroke, and rehospitalization at 1 year was significantly lower in the TAVR group compared with the surgical group. In addition, TAVR was associated with lower rates of stroke, death, and new-onset atrial fibrillation at 30 days compared with surgery. The length of hospital stay was shorter in the TAVR group than in the surgery group. • Among low-risk patients with severe aortic stenosis, TAVR is associated with better outcomes compared with surgical aortic valve replacement. Abstract

a mechanical-bearing axial-flow left ventricular assist device. METHODS We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axi- al-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (rel- ative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replace- ment was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The num- bers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS Among patients with advanced heart failure, a fully magnetically levitated cen- trifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. A Fully Magnetically Levitated Left Ventricular Assist Device—Final Report. N Engl J Med 2019 Apr 25;380(17)1618-1627, MR Mehra, N Uriel, Y Naka, et al. www.practiceupdate.com/c/82954

BACKGROUND Among patients with aortic ste- nosis who are at intermediate or high risk for death with surgery, major outcomes are simi- lar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk. " Among low-risk patients with severe aortic stenosis, TAVR is associated with better outcomes compared with surgical aortic valve replacement. " METHODS We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemo- ral placement of a balloon-expandable valve or surgery. The primary end point was a com- posite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population. RESULTS At 71 centers, 1000 patients under- went randomization. The mean age of the patients was 73 years, and the mean Soci- ety of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan-Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, -6.6 percentage points; 95% con- fidence interval [CI], -10.8 to -2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P =0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P=0.02) and in lower rates of

death or stroke (P=0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treat- ment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascu- lar complications, new permanent pacemaker insertions, or moderate or severe paravalvu- lar regurgitation. CONCLUSIONS Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. Transcatheter Aortic-Valve Replacement With a Balloon-Expandable Valve in Low- Risk Patients. N Engl J Med 2019 Mar 17;[EPub Ahead of Print], MJ Mack, MB Leon, VH Thou- rani, et al. www.practiceupdate.com/c/81206

VOL. 4 • NO. 2 • 2019

EDITOR’S PICKS 8

Stress-Related Disorders Associated With Risk of Cardiovascular Disease

COMMENT By Viola Vaccarino MD, PhD T he link between depression and risk of cardiovascular disease (CVD) has been established by numerous stud- ies, but prospective data on posttraumatic stress disorder (PTSD) and other psychiatric conditions remain limited. In this large, Swedish population study, investigators examined the association between a diagnosis of a “stress-related disorder,” including PTSD, acute stress reaction, or adjustment disor- der, and a subsequent diagnosis of CVD over a follow-up of almost 30 years. The authors utilized data from the Swedish National Patient Register linked to other national databases. Using an elegant design, they compared approximately 130,000 individuals with such psychiatric diagnoses in the database (over about 25 years) with siblings without these disorders, as well as with unrelated people from the general population. In both types of comparisons, they found a consistent association between having a stress-related disorder and future CVD events of var- ious subtypes, with an increase in risk between 30% and 70%. The associations were strongest in the first year after a diag- nosis of a stress-induced psychiatric disorder, especially in the first few months. Associations were also stronger in those who were young at baseline (particularly if <30 years old), and those with early-onset CVD (occurring before age 50). The controlled design in a population-based sample is an important strength of this study, and its large size allowed the authors to examine relatively rare psychiatric diagnoses in relation to specific subtypes of CVD. However, reliance on diag- nostic codes in clinical databases for the definition of health conditions can be problematic, especially for psychiatric dis- orders, which tend to be systematically underdiagnosed. This problem, and the fact that the association with CVD occurred mostly within a short time after the psychiatric diagnosis, raises the potential for reverse causation, such that the acute stress disorder could be a consequence of cardiac problems rather than a cause, especially since the exact time of onset was not known. In addition, CVD diagnostic codes could have been overused in persons with stress-induced disorders, such as PTSD, who tend to report more physical symptoms. Such concern should be less, however, for acute severe cardiac conditions, such as myocardial infarction and cardiac arrest. Nonetheless, these data are an important addition to our understanding of the link between psychological stress and CVD. This study suggests that the time immediately after the diagnosis of a psychiatric disorder induced by acute stress or trauma is a vulnerable time for CVD risk. It also highlights an observation largely overlooked before, which is that stress may affect CVD risk primarily in younger people and may affect development of early-onset CVD. Studies that have focused on older populations and that have used long-term follow-up durations may have missed important early risks associated with stress-related psychiatric disorders.

British Medical Journal Take-home message

• Data from the SwedishNational Patient Register were analyzed to evaluate the association between stress-related disorders and the risk of cardiovascular disease. Data of individuals affected by post-traumatic stress disorder, acute stress reac- tion, adjustment disorder, and other stress reactions and their unaffected siblings were analyzed. The hazard ratio for any cardiovascular disease in the affected individual compared with the sibling was 1.64 in the first year after diagnosis of the stress-related disorder, and the hazard ratio for heart failure in this time period was 6.95. After the first year, the hazard ratios in the affected individual compared with the sibling ranged from 1.12 for arrhythmia to 2.02 for artery thrombosis/embolus. • Stress-related disorders have a significant association with many types of cardiovascular disease. Abstract OBJECTIVE To assess the association between stress related disorders and subsequent risk of cardiovascular disease. DESIGN Population based, sibling controlled cohort study. SETTING Population of Sweden. PARTICIPANTS 136637 patients in the Swedish National Patient Register with stress related disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reac- tions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366370 matched unexposed people from the general population. MAIN OUTCOME MEASURES Primary diagnosis of incident cardiovascular dis- ease—any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhyth- mia/conduction disorder, and fatal cardiovascular disease)—and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders. RESULTS During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age <50) than later onset ones (1.24 (1.18 to 1.30) for attained age ≥50; P for difference=0.002). Except for fatal cardio- vascular diseases, these associations were not modified by the presence of psychiatric comorbidity. Analyses within the population matched cohort yielded similar results (hazard ratio 1.71 (1.59 to 1.83) for any cardiovascular disease during the first year of follow-up and 1.36 (1.33 to 1.39) thereafter). CONCLUSION Stress related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, his- tory of somatic/psychiatric diseases, and psychiatric comorbidity. Stress Related Disorders and Risk of Cardiovascular Disease: Population Based, Sibling Controlled Cohort Study. BMJ 2019 Apr 10;365(xx)l1255, H Song, F Fang, FK Arnberg, et al. www.practiceupdate.com/c/82357

Dr. Vaccarino is the Wilton Looney Chair of Cardiovascular Research and Professor and Chair of the Department of Epidemiology at the Rollins School of Public Health, Emory University in Atlanta, Georgia.

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EDITOR’S PICKS 9

Improved Survival With Catheter Ablation of Refractory Ventricular Fibrillation Storm After Myocardial Infarction Circulation

COMMENT By Sana M. Al-Khatib MD, MHS T his multicenter, retrospective, observational study reports on the outcomes of 110 patients with post-MI refractory VF storm not preceded by monomorphic VT who underwent catheter ablation of Purkinje- related ventricular extrasystoles triggering VF. Between the ablation and hospital discharge, VF storm subsided in the vast majority of patients; however, 30 patients (27%) died before discharge. After hospital discharge, although the rate of VF storm recurrence was very low (only 1 patient), 29 additional patients (36%) died within a median follow-up of 2.2 years. Although it is important to keep in mind the retrospective design of this study and acknowledge that a randomized clinical trial is the best study design to address the questions at hand, this study has some important implications for clinical practice. First, the success rate of VF storm ablation is notable. Sec- ond, the high rate of in-hospital mortality after ablation for VF storm should be shared with patients (if conscious), their families, and the primary teams taking care of them to ensure that everyone has realistic expectations regarding the impact of VF ablation on in-hospital mortality. Third, the decision regarding whether or not to proceed with ablation has to be made quickly, as this study suggests that a 1-day delay in ablation may be associated with a 10% increase in mortality. Fourth, the rate of mortality within 2.2 years of follow-up is high, with heart failure being a major cause. This underscores the importance of optimiz- ing heart failure management in these patients.

Take-home message • This multicenter, retrospective observational study examined the use of catheter ablation to treat patients who experienced a ventricular fibrillation (VF) storm after myocardial infarction (MI). In the 110 included patients, VF storm occurred close to MI onset in 39% of patients, over 1 week after MI in 44% of patients, and over 6 weeks after MI in 17% of patients. In 80% of patients, the focal triggers originated from the zone bordering the scar. Although the VF storm subsided in 84% of patients during their hospital stay following ablation, 27% died in the hospital. There was an association between greater delay between VF occurrence and catheter ablation and greater in-hospital mortality. Although only 1 patient developed recurrent VF storm after discharge, 36% of patients died during follow-up. • This study suggests that catheter ablation of culprit triggers improves outcomes and is associated with low recurrence in patients who experience VF storm after MI. Abstract

BACKGROUND Ventricular fibrillation (VF) storm after myocardial infarction (MI) is a life-threat- ening condition that necessitates multiple defibrillations. Catheter ablation is a potentially effective treatment strategy for VF storm refrac- tory to optimal medical treatment. However, its impact on patient survival has not been verified in a large population. METHODS We conducted amulticenter, retrospec- tive observational study involving consecutive patients who underwent catheter ablation of post-MI refractory VF storm without preceding monomorphic ventricular tachycardia. The target of ablation was the Purkinje-related ventricular extrasystoles triggering VF. The primary out- come was in-hospital and long-term mortalities. Univariate logistic regression and Cox propor- tional-hazards analysis were used to evaluate clinical characteristics associated with in-hospi- tal and long-term mortalities, respectively. RESULTS One-hundred ten patients were enrolled (65±11years; 92 men; left ventricu- lar ejection fraction [LVEF] 31±10%). VF storm occurred at acute phase of MI (4.5±2.5 days after the MI onset during index hospitaliza- tion for MI) in 43 (39%) patients, subacute (>1 week) in 48 (44%), and remote (>6 months) in 19 (17%). The focal triggers were found to orig- inate from the scar border zone in 88 (80%) patients. During in-hospital stay after ablation, VF storm subsided in 92 (84%) patients. Over- all, 30 (27%) in-hospital deaths occurred. The duration from the VF occurrence to the ablation procedure was associated with in-hospital mor- tality (odds ratio for each one-day increase: 1.11; 95% confidence interval [CI]: 1.03-1.20; p=0.008). During follow-up after discharge from hospital, only one patient developed recurrent VF storm. However, 29 (36%) patients died with a median survival time of 2.2 years (interquartile range: 1.2- 5.5 years). Long-term mortality was associated with LVEF<30% (hazard ratio [HR]: 2.54; 95%CI:

1.21-5.32; p=0.014), New York Heart Association class ≥III (HR: 2.68; 95%CI: 1.16-6.19; p=0.021), a history of atrial fibrillation (HR: 3.89; 95%CI: 1.42- 10.67; p=0.008), and chronic kidney disease (HR: 2.74; 95%CI: 1.15-6.49; p=0.023). CONCLUSIONS In patients with MI presenting with focally-triggered VF storm, catheter ablation of culprit triggers is life-saving and appears to be associated with short- and long-term freedom from recurrent VF storm. Mortality over long- term follow-up is associated with the severity of underlying cardiovascular disease and comor- bidities in this specific patient population. Catheter Ablation of Refractory Ventricular Fibrillation Storm After Myocardial Infarction: A Multicenter Study. Circulation 2019 Apr 01;[EPub Ahead of Print], Y Komatsu, M Hocini, A Nogami, et al. www.practiceupdate.com/c/82025

Dr. Al-Khatib is Professor of Medicine at Duke University Medical Center in Durham, North Carolina.

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Association of Influenza-Like Illness Activity With Hospitalizations for Heart Failure JAMA Cardiology

Take-home message • The authors evaluated the association between influenza activity and hospitaliza- tions for heart failure (HF) or myocardial infarction (MI) between 2010 and 2014. A 5% increase in influenza activity was associated with a 24% increase in the rate of HF hospitalizations. The same association was not seen for MI hospitalizations. • Influenza activity may contribute to the risk of HF hospitalization among community- dwelling adults. COMMENT By Jonathan Temte MD, PhD Congestive Heart Failure Hospitalization and Influenza-Like Illnesses S o far this year, 1 of every 600, or nearly 80,000, individuals aged 65 years or older has been hospitalized due for heart failure (HF). Influenza infection may increase metabolic demands, acti- vate the sympathetic nervous system, trigger proinflammatory cytokines, or cause volume overload – all factors that could contribute to exacerbations of HF. A recent study links ILI prevalence in pri- mary care to HF hospitalizations.

Abstract IMPORTANCE Influenza is associated with an increased risk of cardiovascular events, but to our knowledge, few studies have explored the temporal association between influenza activity and hospitalizations, especially those caused by heart failure (HF). OBJECTIVE To explore the temporal association between influenza activity and hospitalizations due to HF and myocardial infarction (MI). We

HF and myocardial infarction (MI) in four communities with the monthly ILI across four influenza seasons (2010–2014). Analyses were adjusted for outside tem- perature, sex of patient, race, age, and region. A very large and significant 24% increase in HF was associated with a 5% absolute rise in ILI (eg, from 1% to 6%). Overall, the adjusted incidence rate ratio was 1.24 (95% CI, 1.11–1.38) for the pooled anal- ysis. On the other hand, no increased risk for MI was noted (aIRR, 1.02; 95% CI, 0.90–1.17). In this study, the authors were not able to assess any association with vaccination status. Moreover, there was no direct assessment of influenza in the patients, leaving the possibility that other infections, such as respiratory syncytial virus or human metapneumovirus, could also contribute to this effect. This study adds to existing evidence by showing that increases in prevalence of influenza, as indicated by increases in ILI, are associated with increases in cardio- vascular hospitalization. Moreover, efforts to reduce the spread of influenza may result in reduced morbidity, hospitaliza- tion, and mortality. Reference 1. FluView. 2018-2019 Influenza Season Week 12 ending March 23, 2019. Available at: www.cdc. gov/flu/weekly. Accessed April 3, 2019.

to influenza. We are in the midst of our seasonal influenza outbreak, but the nation- wide prevalence of influenza-like illness (ILI) is declining. 1 ILI – defined as a fever of 100°F (37.8°C) or higher, along with cough and/or sore throat – is a useful construct in primary care-based influenza surveillance. In gen- eral, the prevalence of ILI correlates well with the prevalence of influenza. Although there is much known about the association between cardiovascular mortality and influenza, far less is known about the extent to which influenza contributes to cardiovascular hospitali- zation, and, in particular, hospitalization

The US Outpatient Influenza-like Illness Surveillance Network (ILINet) is run by the CDC, with ample assistance from state and local public health departments. 1 Each week, primary care clinicians report the total number of patients seen and the number of patients with ILI (Figure). Researchers from the Atherosclerosis Risk in Communities study compared the monthly frequency of hospitalization for

Percentage of visits for influenza-like-illness (ILI) reported by the US Outpatient Influenza-like-Illness Surveillance Network (ILINet), Weekly National Summary, 2018–2019 and selected previous seasons.

Dr. Temte is Professor at the University of Wisconsin School of Medicine and Public Health, Department of Family Medicine and

Community Health in Madison, Wisconsin.

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Early or Delayed Cardioversion in Recent- Onset Atrial Fibrillation

The New England Journal of Medicine Take-home message

• Patients in the emergency department (ED) with hemody- namically stable, recent-onset symptomatic atrial fibrillation were randomized to early cardioversion or a wait-and-see approach with delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The rate of sinus rhythm at 4 weeks was similar in the two groups, confirming the noninferiority of the wait-and-see approach. Conversion to sinus rhythm was seen in 69% of the delayed-cardiover- sion group within 48 hours and in a further 28% following delayed cardioversion. The rate of recurrence of atrial fibril- lationwithin 4weekswas 30% in the delayed-cardioversion group and 29% in the early-cardioversion group. • A wait-and-see approach was noninferior to early car- dioversion for the outcomes of return to sinus rhythm at 4 weeks among ED attendees with recent-onset, symptomatic atrial fibrillation. Abstract BACKGROUND Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously. METHODS In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (<36 hours), symptomatic atrial fibrillation in the emer- gency department to be treated with a wait-and-see approach (delayed-cardioversion group) or early cardioversion. The wait-and- see approach involved initial treatment with rate-control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The primary end point was the presence of sinus rhythm at 4 weeks. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10. RESULTS The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P=0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recur- rence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-car- dioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively. CONCLUSIONS In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation. N Engl J Med 2019 Mar 18;[EPub Ahead of Print], NAHA Pluymaekers, EAMP Dudink, JGLM Luermans, et al. www.practiceupdate.com/c/81402

hypothesized that increased influenza activity would be associated with an increase in hospitalizations for HF and MI among adults in the community. DESIGN, SETTING, AND PARTICIPANTS As part of the community surveillance component of the Atherosclerosis Risk in Communities (ARIC) study, a pop- ulation-based study with hospitalizations sampled from 4 US communities, data were collected from 451 588 adults aged 35 to 84 years residing in the ARIC communities from annual cross-sectional stratified random sam- ples of hospitalizations during October 2010 to September 2014. EXPOSURES Monthly influenza activity, defined as the percentage of patient visits to sentinel clinicians for influenza-like illness by state, as reported by the Centers for Disease Control and Prevention Surveillance Network. MAIN OUTCOMES AND MEASURES The monthly frequency of MI hospital- izations (n = 3541) and HF hospitalizations (n = 4321), collected through community surveillance and adjudicated as part of the ARIC Study. RESULTS Between October 2010 and September 2014, 2042 (47.3%) and 1599 (45.1%) of the sampled patients who were hospitalized for HF and MI, respectively, were women and 2391 (53.3%) and 2013 (57.4%) were white, respectively. A 5% monthly absolute increase in influenza activity was associated with a 24% increase in HF hospitalization rates, standard- ized to the total population in each community, within the same month after adjusting for region, season, race/ethnicity, sex, age, and number of MI/HF hospitalizations from the month before (incidence rate ratio, 1.24; 95% CI, 1.11-1.38; P< .001), while overall influenza activity was not signifi- cantly associated with MI hospitalizations (incidence rate ratio, 1.02; 95% CI, 0.90-1.17; P= .72). Influenza activity in the months before hospitaliza- tion was not associated with either outcome. Our model suggests that in a month with high influenza activity, approximately 19% of HF hospitaliza- tions (95% CI, 10%-28%) could be attributable to influenza. CONCLUSIONS AND RELEVANCE Influenza activity was temporally associated with an increase in HF hospitalizations across 4 influenza seasons. These data suggest that influenza may contribute to the risk of HF hospitaliza- tion in the general population. Association of Influenza-Like Illness Activity With Hospitalizations for Heart Failure: The Atherosclerosis Risk in Communities Study. JAMA Cardiol 2019 Mar 27;[EPub Ahead of Print], S Kytömaa, S Hegde, B Clag- gett, et al. www.practiceupdate.com/c/81652

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