PracticeUpdate Cardiology Best of 2018

Best of 2018

OUR EXPERTS. YOUR PRACTICE.

ISSN 2206-4672

VOL. 3 • NO. 4 • 2018

TOP STORIES 2018 The Best of Sports Cardiology The SCOT-HEART Long-Term Follow-up Study The Benefits of His Bundle Pacing

JOURNAL SCANS Propranolol Versus Metoprolol for Treatment of Electrical Storm in Patients With Implantable Cardioverter-Defibrillator

Safety of Magnetic Resonance Imaging in Patients With Cardiac Devices

Outcomes of Cardiac Screening in Adolescent Soccer Players

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CONTENTS 3

16 My Approach to Triglyceride Levels in Comment by Clare M. C. Tempany-Afdhal MB, BAO, BCh, FISMRM and Minesh P. Mehta MD, FASTRO 10 Supplemental Vitamins and Minerals for CVD Prevention and Treatment Comment by David Rakel MD, FAAFP 11 Efficacy of Self-Monitored Blood Pressure for Titration of Antihypertensive Medication Comment by Ronald G. Victor MD 12 Outcomes of Cardiac Screening in Adolescent Soccer Players Comment by Barry J. Maron MD and Jonathan A. Drezner MD EDITOR’S PICKS 8 Propranolol vs Metoprolol for Treatment of Electrical Storm in Patients With ICDs Comment by Anisiia Doytchinova MD and Peng-Sheng Chen MD 9 MRI Appears Safe in Patients With Cardiac Devices

TOP STORIES 2018 5 The Best of Sports Cardiology By Paul D. Thompson MD

6 The SCOT-HEART Long-Term Follow-up Study By James E. Udelson MD

7 The Benefits of His Bundle Pacing By Douglas P. Zipes MD

EXPERT OPINION 14 MY APPROACH to Evaluating a Patient With Newly Discovered Brugada Syndrome By Josep Brugada MD, PhD, FESC 15 MY APPROACH to the Patient With Ventricular Arrhythmia and No Structural Heart Disease By Ziad F. Issa MD, MMM CONFERENCE 18 American College of Cardiology 67th Annual Scientific Session & Expo 2018 18 Optimal Duration of DAPT Therapy Post PCI in Acute Coronary Syndrome Interview with Deepak L. Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC 19 An Overview of Chemotherapy-Induced Heart Failure Interview with Joerg Herrmann MD by Jennifer N. Caudle DO 20 ECG on an Apple Watch Detects Atrial Fibrillation Accurately By the PracticeUpdate Editorial Team 21 TAVR for Low Risk Patients With Severe Aortic Stenosis Interview with James E. Udelson MD by Jennifer N. Caudle DO

Specific Patient Scenarios Interview with Paul D. Thompson MD by Jennifer N. Caudle DO

22 European Society of Cardiology Congress 2018 By the PracticeUpdate Editorial Team

25 American Heart Association Scientific Sessions 2018 By the PracticeUpdate Editorial Team

22 In Patients With Hypertension, Antihypertensives and Statins Continue to Improve Survival 23 Percutaneous Reduction of Secondary Mitral Regurgitation in Heart Failure Appears Futile 24 Oral Anticoagulants + Antiplatelets Linked to Poor Outcome in Atrial Fibrillation

25 Prescription Omega-3 Fatty Acids Reduce Risk of Major Adverse Cardiac Events 26 Dapagliflozin Reduces Risk of Cardiovascular Death or Hospitalization for Heart Failure in Diabetes 27 Type 2 Diabetes Patients Receiving Empagliflozin Experience Left Ventricle Reverse Remodeling

VOL. 3 • NO. 4 • 2018

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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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

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, Massachusetts Gary Webb MD 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

Professor of Medicine, Harvard Medical School; Executive Director, Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center; Senior Physician at 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 Maurice E. Sarano MD, FACC Professor of Medicine, Mayo Medical School, Rochester, Minnesota

Editorial Contributors

Ashish Aggarwal MD Staff Physician, Interventional Cardiology, Providence Holy Cross Medical

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

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

Center, Mission Hills, California

Minneapolis, Minnesota

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TOP STORIES 2018 5

The Best of Sports Cardiology By Paul D. Thompson MD

D o you want a sure fire way to start an argument? Bring up the topic of sports pre-participation screening using an ECG in a group of cardiologists interested in the cardiac problems of young athletes. Approximately 40% of the group will insist that pre-participation screening with an ECG saves lives by detecting conditions associated with exercise-related sudden cardiac death (SCD) such as hypertrophic cardiomyopathy (HCM), right ventricular cardiomyopathy (RVCM), long QT syndrome (LQTS), and Wolff-Parkinson- White (WPW) syndrome. Another ~ 40% of the group will insist that pre-participation screening with an ECG puts athletes at risk for inappropriate implantable cardiac defibrillator (ICD) insertions, unnecessary ablations, exercise restriction, and general anxiety. The other 20% (all fellows or recent fellowship graduates), will be searching for the correct answer on their smart phones but to no avail because we do not know what approach is best. A central problem in determining the best approach to saving athletes’ lives is that no one knows for sure how big a problem SCD during sports participation is. The inci- dence for high school athletes has generally been estimated at 1 death per year for every 200,000 athletes. 1 The risk is much higher in men than in women, and some estimates of SCD death in young athletes have been as high as 1 death for every 3100 National Collegiate Athletic Association (NCAA) Divi- sion 1 basketball players. 2 So for my Best of Sports Cardiology article in 2018, I selected the article from Sanjay Sharma’s research group in London enti- tled, “ Outcomes of Cardiac Screening In Adolescent Soccer Players ” 3 (see page 12). I selected this article because it demonstrates

no symptoms, is always difficult because the decision can be affected by the ath- lete’s desire to compete and the clinician’s desire to take as little risk as possible. All of the surgical cases and 24 of the WPW pattern cases returned to soccer after their procedure. Most importantly, however, despite this extensive screening, the annual inci- dence of SCD was high at 1 SCD per 14,794 screened athletes. The reason for this high rate is unclear, but raises a troubling addi- tional question. Because SCD seems higher in Division 1 NCAA basketball players and in these elite soccer players, does intense exercise training increase the risk of SCD? This sounds like heresy; however, it is not questioning the widely recognized bene- fits of moderate physical activity, 4 but the benefits of the extreme training required for highly competitive endurance sports. This question has been asked before, 5 and perhaps, should be asked again. References 1. Lawless CE. Minnesota high school athletes 1993- 2012: evidence that American screening strategies and sideline preparedness are associated with very low rates of sudden cardiac deaths. J Am Coll Cardiol. 2013;62(14):1302-1303. 2. Harmon KG, Asif IM, Klossner D, Drezner JA. Incidence of sudden cardiac death in National Collegiate Athletic Association athletes. Circulation 2011;123(15):1594-1600. 3. Malhotra A, Dhutia H, Finocchiaro G, et al. Outcomes of cardiac screening in adolescent soccer players. N Engl J Med 2018;379(6):524-534. 4. Eijsvogels TM, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the extremes: the amount of exercise to reduce cardiovascular events. J Am Coll Cardiol 2016;67(3):316-329. 5. Eijsvogels TM, Fernandez AB, Thompson PD. Are there deleterious cardiac effects of acute and chronic endurance exercise? Physiol Rev 2016;96(1):99-125. www.practiceupdate.com/c/76212

the complexity of the problem and raises an additional troubling question. These authors screened 11,168 adolescent, elite soccer players whose mean age was 14 ±1.2 years (mean ± SD), using medical history, physical examination, ECG, and echocardiography on all athletes. The stud- ies were reviewed by expert cardiologists. Consequently, the study does not directly address the benefit of adding only an ECG to the history and physical examination because they also underwent echocardi- ography. It also does not provide insight into how using non-expert cardiologists would affect the results. Even after this extensive screening and follow-up assessment by expert cardiol- ogists, 830 of the athletes (7%) required additional studies and 409 (4%) required cardiac magnetic resonance imaging. This demonstrates that the medical cost of ECG screening is not simply the cost of the ECG but the cost of subsequent testing. It also reminds us that elite athletes are different and their cardiac findings often mimic dan- gerous medical conditions. A total of 42 athletes (0.38%) were found to have cardiac disorders associated with SCD including HCM in 2 athletes, ARVC in 2, dilated cardiomyopathy in 1, LQTS in 3, anomalous coronary artery in 2, aortic valve disease in 2, and WPW ECG pat- tern in 26. The athletes with anomalous coronary artery and aortic valve disease and 24 of the athletes with WPW pattern underwent corrective surgery or ablation before returning to athletics. These 24 with WPW had evidence of dangerous accessory pathways on electrophysiol- ogy study. Only 2 of these 42 athletes had symptoms. Whether or not to operate on athletes with some of these disorders, and

VOL. 3 • NO. 4 • 2018

TOP STORIES 2018 6

The SCOT-HEART Long- Term Follow-up Study By James E. Udelson MD

I n the earlier days of cardiac imaging tests, initial reports focused on sensitivity and specificity to detect or rule-out disease (such as anatomic CAD by invasive angiography), and subsequent inves- tigations often then focused on assembling large databases to examine the prognostic capabilities of the imaging modality associating the imaging results with outcomes. Virtually every test we use – exercise ECG, stress nuclear/echo/CMR or coronary CT angi- ography (CCTA) – has followed this path. Only more recently has a higher level of rigor been pursued, with randomized trials comparing existing modalities or a new modality with a more standard care testing approach. These trials are often referred to as “pragmatic effectiveness” trials, with the “prag- matic” reflecting the practical nature of the design, and the “effectiveness” referring to the downstream management after the test, which is usually not strictly defined by the trial protocol but left up to the clinicians managing the patient. The outcomes are associated with the randomized initial test strategy assignment, but are also highly influenced by the subsequent medical or invasive management driven by the test results, which may be variable. Examples include the WOMEN trial, 1 which randomized women with suspected CAD and low-intermediate likelihood to exercise ECG or exercise SPECT imaging as the initial test. The results showed similar 2-year out- comes, but with lower costs in the exercise ECG group. More recently, the PROMISE trial randomized just over 10,000 people with suspected CAD and low-intermediate likelihood to either an “anatomic” strategy (CCTA) or a “functional” strategy (mostly stress nuclear or echo) as the initial test. 2 There were no significant outcome differences at ~ 2 years. From a resource utilization standpoint, there were fewer catheterizations with normal coronaries in the initial CCTA group, but a greater number of total catheter- izations and revascularizations in the CCTA group. This latter finding is often seen in CTA studies. In 2015, Newby and colleagues reported the primary results of the SCOT-HEART trial, a very large (>4000 patients) randomized strategy trial. 3 The trial was a randomized comparison of diagnosis and manage- ment based on CCTA usually in addition to exercise ECG results vs standard of care (mostly exercise ECG) alone. Their primary results published in 2015 in The Lancet showed better diagnostic certainty of angina/CAD for the patients randomized to have CCTA. The follow-up reported in that paper (average 1.7 years) showed a trend toward fewer fatal or non- fatal myocardial infarctions in the CCTA group, and a trend in the usual signal of slightly more revascu- larizations in the CCTA group.

My vote for Story of the Year in Cardiac Imaging was for their long-term follow-up study, which was presented in August at the European Society of Car- diology meeting and published simultaneously in the NEJM . 4 In this study, the SCOT-HEART investi- gators reported on the 5-year long-term follow-up outcome data of their trial. With the longer follow-up, the authors reported a 41% reduction in an out- come composite of coronary heart disease death or nonfatal MI, driven entirely by the MI component. Importantly, in contrast to many previous studies, the group randomized to CCTA did not have an excess of catheterizations or revascularizations. This is the first study to show an impact on outcomes (here, non-fatal MI) within the context of a randomized trial of testing strategies and pragmatic effectiveness management. Mechanisms or explanations for observed results such as these can be challenging to discern from randomized comparisons of diagnostic testing. The relative magnitude of reduction in MI is quite large, and in fact the relative risk reduction exceeds that observed in many therapeutic trials. It is unlikely that revascularization played a role, as the incidence was balanced across the groups and in general revascularization does not reduce MI risk in stable out-patients. As discussed in the accompanying editorial, 5 more likely is the better use of medica- tions such as aspirin and statins in the CCTA group, as the presence of CAD – even non-obstructive CAD – would have been more obvious in a greater number of patients following CCTA compared with exercise ECG. But even that explanation falls some- what short. A careful look at the medication use over time in the two groups does show more aspirin and statin use after CCTA imaging, but the differences

PRACTICEUPDATE CARDIOLOGY

TOP STORIES 2018 7

The Benefits of His Bundle Pacing

By Douglas P. Zipes MD T ransvenous cardiac pacing began almost 60 years ago with the observation by Furman and Schwedel that stimula- tion of the right ventricular

(RV) endocardium produced ventricular con- traction. 1 For many years thereafter, RV apical lead placement represented the transvenous pacingmodel of choice. Attempts at His bundle pacing to create normal ventricular electrical systole were fragmentary and largely aban- doned because of lead placement difficulties. When a pacing-induced cardiomyopathy from the resultant LBBB during RV apical pacing became known, high septal and outflow RV pacing was attempted, mostly replaced by cardiac resynchronization therapy (CRT). CRT, although successful, is cumbersome by requir- ing a left ventricular lead, expensive, and has a higher complication rate than simple RV pacing. Fortunately, several groups re-investigated the concept of His bundle pacing, and pre- liminary findings indicate that it is feasible, practical, and beneficial. 2,3,4 The success of His bundle pacing represents the top 2018 story because it restores normal physiologic electrical ventricular depolarization with a sin- gle lead even in the presence of most bundle branch blocks, and it eliminates the need for left ventricular pacing and the potential for a pacing-induced cardiomyopathy. Further lead and electrode development will make His bundle pacing the optimal choice for ven- tricular pacing. I anticipate it will replace CRT. As such, it becomes a therapeutic paradigm shift in the world of pacing. References 1. Furman S, Schwedel JB. An intracardiac pacemaker for Stokes-Adams seizures. N Engl J Med 1959;261:943-948. 2. Huang W, Su L, Wu S, et al. Long-term outcomes of His bundle pacing in patients with heart failure with left bundle branch block. Heart 2018 Aug 9. doi:10.1136/heartjnl-2018-313415. [Epub ahead of print.] 3. Vijayaraman P, Chung MK, Dandamudi G, et al. His bundle pacing. J Am Coll Cardiol 2018;72(8):927-947 4. Ezzeddine FM, Dandamudi G. Updates on His bundle pacing: the road more traveled lately. Trends Cardiovasc Med 2018 Sep 9. doi:10.1016/j. tcm.2018.09.018. [Epub ahead of print.] www.practiceupdate.com/c/74883

are modest. In a therapeutic trial of, say, the new PCSK9-inhibitors, such as the FOURIER trial, 6 where 100% of the inter- vention group is initially on the drug while 0% are on the drug in the control group, a 38% reduction in non-fatal MI was seen. In SCOT-HEART, the abso- lute difference in aspirin and stain use was on the order of ~ 10%, with a larger relative risk reduction in MI than seen in FOURIER. Thus, the mechanism under- lying the striking reduction in MI risk in SCOT-HEART is unclear. The SCOT-HEART data are in contrast to those of the PROMISE trial, where, with over 2 years of follow-up, no difference in outcomes was observed. Although patients in both trials had CCTA-based management as one randomization arm, the difference in the trials was the comparator arm. In SCOT-Heart, the comparator was predominantly exer- cise ECG (only ~ 10% of patients had an imaging stress test, nuclear or echo), whereas in PROMISE, the comparator was predominantly stress imaging (only ~ 10% of patients had exercise ECG). One might interpret the totality of results from these two trials (as well as the more recent CRESCENT–II trial, comparing a “tiered” CT approach to exercise ECG) that there is now little role for exercise ECG in out-patients with suspected CAD, and that stress imaging or CCTA should lead to similar outcomes.

The SCOT-HEART trial joins the pantheon of randomized trials of diagnostic strate- gies for its novel findingof anassociationof initial CCTAwith reducedMI risk. The data reinforce a general message regarding the importance of aggressive preventive measureswhenCAD is suggested (by any test!), so that the testing results can drive management well beyond simply being used for diagnosis of CAD. References electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial. Circulation 2011;124(11):1239–1249. 2. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med 2015;372(14):1291-1300. 3. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet 2015;385(9985):2383-2391. 4. SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med 2018;379(10):924-933. 5. Hoffmann U, Udelson JE. Imaging coronary anatomy and reducing risk of myocardial infarction. N Engl J Med . 2018;379(10):977-978. 6. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376(18):1713-1722. www.practiceupdate.com/c/76418 1. Shaw LJ, Mieres JH, Hendel RH, et al. Comparative effectiveness of exercise

VOL. 3 • NO. 4 • 2018

EDITOR’S PICKS 8

Propranolol vs Metoprolol for Treatment of Electrical Storm in Patients With ICDs Journal of the American College of Cardiology Take-home message • Patients with ICDs and having an electrical storm admitted to the intensive care unit were randomized to receive either oral propranolol or oral metoprolol in conjunction with IV amiodarone. There was a 2.67-times decrease in the incidence of ventricular arrhythmic events and a 2.34-times decreased rate of ICD discharges seen in the propranolol group compared with the metoprolol group. After 24 hours of treatment, 90.0% of the propranolol group was free of arrhythmic events vs 53.3% of the metoprolol group (P = .03). Patients in the metoprolol group were 77.5% less likely than those in the propranolol group to achieve the termination of arrhythmic events (P < .001). Both the time to termination of the arrhythmia and the length of admission were significantly shorter in the propranolol-treated patients compared with the metoprolol-treated patients. • Among patients with an ICD and suffering an electrical storm receiving IV amiodarone, the addition of oral propranolol is superior to the addition of oral metoprolol.

COMMENT

By Anisiia Doytchinova MD and Peng-Sheng Chen MD S ympathetic activation has long been known to promote ventricu- lar arrhythmogenesis. However, except for a few case reports, there have been little data evaluating specific beta-blocker regimens for the treatment of electrical storm. The study by Chatzi- dou et al is a double-blind randomized clinical trial, which compared proprano- lol (40 mg orally every 6 h) vs metoprolol (50 mg orally every 6 h) for the acute treatment of electrical storm in patients who had already received intravenous amiodarone. The results demonstrated that the propranolol group had 2.67 times reduced incidence of ventricu- lar arrhythmias, 2.34 times reduced incidence of implantable cardiovert- er-defibrillator (ICD) discharges, and shorter hospital length of stay. During the 2-month follow up, no electrical storm recurrences or patient deaths were observed in either study arm. The beneficial effects of propranolol may stem from its ß2 effects by prevent- ing epinephrine-induced hypokalemia associated with ß2 receptor activa- tion. In addition, propranolol has been demonstrated to have a direct blocking effect on both the peak and the late (persistent) sodium current, which may also be anti-arrhythmic. Although the authors do not address whether pro- pranolol offers additional benefits over metoprolol beyond the acute treatment phase, this study represents significant advancement in the treatment of elec- trical storm with immediate potential applications to clinical care.

" …this study represents

Abstract BACKGROUND Electrical storm (ES), character- ized by unrelenting recurrences of ventricular arrhythmias, is observed in approximately 30% of patients with implantable cardioverter-de- fibrillators (ICDs) and is associated with high mortality rates. OBJECTIVES Sympathetic blockade with β-block- ers, usually in combination with intravenous (IV) amiodarone, have proved highly effective in the suppression of ES. In this study, we com- pared the efficacy of a nonselective β-blocker (propranolol) versus a β1-selective blocker (metoprolol) in the management of ES. METHODS Between 2011 and 2016, 60 ICD patients (45 men, mean age 65.0 ± 8.5 years) with ES developed within 24 h from admission were randomly assigned to therapy with either propranolol (160 mg/24 h, Group A) or metopr- olol (200 mg/24 h, Group B), combined with IV amiodarone for 48 h. RESULTS Patients under propranolol therapy in comparison with metoprolol-treated individuals presented a 2.67 times decreased incidence rate (incidence rate ratio: 0.375; 95% confidence interval: 0.207 to 0.678; p = 0.001) of ventricular arrhythmic events (tachycardia or fibrillation) and a 2.34 times decreased rate of ICD discharges (inci- dence rate ratio: 0.428; 95% CI: 0.227 to 0.892; p = 0.004) during the intensive care unit (ICU) stay, significant advancement in the treatment of electrical stormwith immediate potential applications to clinical care. "

after adjusting for age, sex, ejection fraction, New York Heart Association functional class, heart fail- ure type, arrhythmia type, and arrhythmic events before ICU admission. At the end of the first 24-h treatment period, 27 of 30 (90.0%) patients in group A, while only 16 of 30 (53.3%) patients in group B were free of arrhythmic events (p = 0.03). The termination of arrhythmic events was 77.5% less likely in Group B compared with Group A (hazard ratio: 0.225; 95% CI: 0.112 to 0.453; p < 0.001). Time to arrhythmia termination and length of hospital stay were significantly shorter in the propranolol group (p < 0.05 for both). CONCLUSIONS The combination of IV amiodar- one and oral propranolol is safe, effective, and superior to the combination of IV amiodarone and oral metoprolol in the management of ES in ICD patients. Propranolol Versus Metoprolol for Treatment of Electrical Storm in Patients With Implanta- ble Cardioverter-Defibrillator. J Am Coll Cardiol 2018 May 01;71(17)1897-1906, S Chatzidou, C Kontogiannis, DI Tsilimigras, et al. www.practiceupdate.com/c/67408

Dr. Dovtchinova is Assistant Professor of Clinical Medicine in the Division of Cardiovascular Health and Disease at the University of Cincinnati in Cincinnati, Ohio. Dr. Chen is Medtronic Zipes Chair in Cardiology, Director at Krannert Institute of Cardiology, and Chief of the Division of Cardiology at Indiana University in Indianapolis, Indiana.

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MRI Appears Safe in Patients With Cardiac Devices The New England Journal of Medicine Take-home message

COMMENT By Clare M. C. Tempany-Afdhal MB, BAO, BCh, FISMRM T his is an important article that prospectively documents the safety of 1.5 Tesla MR scanning in 1509 patients with implanted cardiac legacy devices. All patients were scanned in a single center under very tightly controlled proto- cols and real-time physiological monitoring before, during, and after the MR exams. No long-term adverse events were iden- tified. In the past, all cardiac implanted devices were a major contraindication to MR scanning. However, driven by the recog- nition of the clinical need and value of MRI exams, many device manufacturers have redesigned their implants, which are now classified by the FDA as non-hazardous or “MRI-conditional.” As a word of caution, the careful monitoring of the patients in this study was resource-intensive, unlikely to be generaliza- ble and, importantly, the results are only relevant to 1.5 Telsa imaging. As this readership will know, we generally prefer 3 Tesla for prostate MR examinations. It is likely that these results combined with earlier ones from the MagnaSafe registry will lead to a modification of current safety guidelines for legacy

• Patients with a pacemaker or an ICD not meeting the FDA criteria as suitable for MRI underwent clinically necessary MRI and were followed to evaluate potential adverse effects. There were no reports of any long-term clinically significant adverse events in 1509 patients. Overall, nine devices required a reset to a backup mode; in eight of these cases, the reset was transient and, in a single case, there was insuffi- cient battery life to allow reprogramming and the pacemaker was replaced. Around 1% of patients demonstrated a reduc- tion in P-wave amplitude immediately after MRI. Common long-term changes included decreases in P-wave amplitude from baseline (4%), increases in atrial capture threshold (4%), increases in right ventricular capture threshold (4%), and increases in left ventricular capture threshold (3%), but these changes were not clinically significant. • MRI with the use of a prespecified safety protocol was found to be safe for individuals with a legacy pacemaker or a legacy ICD system. Abstract BACKGROUND Patients who have pacemakers or defibrillators are often denied the opportunity to undergo magnetic resonance imaging (MRI) because of safety concerns, unless the devices meet certain criteria speci- fied by the Food and Drug Administration (termed “MRI-conditional” devices). METHODS We performed a prospective, nonrandomized study to assess the safety of MRI at a magnetic field strength of 1.5 Tesla in 1509 patients who had a pacemaker (58%) or an implantable cardioverter–defibrillator (42%) that was not considered to be MRI-conditional (termed a “legacy” device). Overall, the patients underwent 2103 thoracic and nonthoracic MRI examinations that were deemed to be clinically necessary. The pacing mode was changed to asynchronous mode for pacing-dependent patients and to demand mode for other patients. Tachyarrhythmia functions were disabled. Outcome assessments included adverse events and changes in the variables that indicate lead and generator function and interaction with surrounding tissue (device parameters). RESULTS No long-term clinically significant adverse events were reported. In nine MRI examinations (0.4%; 95% confidence interval, 0.2 to 0.7), the patient’s device reset to a backup mode. The reset was transient in eight of the nine examinations. In one case, a pacemaker with less than 1 month left of battery life reset to ventricular inhibited pacing and could not be reprogrammed; the device was subsequently replaced. The most common notable change in device parameters (>50% change from baseline) imme- diately after MRI was a decrease in P-wave amplitude, which occurred in 1% of the patients. At long-term follow-up (results of which were available for 63% of the patients), the most common notable changes from baseline were decreases in P-wave amplitude (in 4% of the patients), increases in atrial capture threshold (4%), increases in right ventricular capture thresh- old (4%), and increases in left ventricular capture threshold (3%). The observed changes in lead parameters were not clinically significant and did not require device revision or reprogramming. CONCLUSIONS We evaluated the safety of MRI, performed with the use of a prespecified safety protocol, in 1509 patients who had a legacy pacemaker or a legacy implantable cardioverter– defibrillator system. No long-term clinically significant adverse events were reported. Safety of Magnetic Resonance Imaging in Patients With Cardiac Devices. N Engl J Med 2017 Dec 28;377(26)2555-64, S Nazarian, R Hansford, AA Rahsepar, et al. www.practiceupdate.com/c/62465

devices. 1 Reference

1. Russo RJ, Costa HS, Silva PD, et al. Assessing the risks associated with MRI in patients with a pacemaker or defibrillator. N Engl J Med 2017;376(8):755-764.

Dr. Tempany-Afdhal is the Ferenc Jolesz MD Professor of Radiology at Harvard Medical School, Vice-Chair of Radiology Research at Brigham & Women’s Hospital, and Director of the Ferenc Jolesz National Center for Image-Guided Therapy in Boston, Massachusetts.

By Minesh P. Mehta MD, FASTRO People have been concerned about the use of MRI in patients who have cardiac devices, and this has led to some patients actually not having MRI scans performed. This paper in a large number of patients (over 1500) shows that patients with either pacemakers or implanted cardioverter defibrillator systems did not experience any clinically significant adverse events. In a long-term analysis of a large database of patients with cardiac devices, no significant adverse events linked to the perfor- mance of MRI scans were observed, implying that it is safe to proceed with MRI in these patients as clinically necessary and indicated. And this would now allow appropriate use of MRI without undue concern about its toxicity.

Dr. Mehta is Deputy Director and Chief of Radiation Oncology at Miami Cancer Institute in Miami, Florida.

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EDITOR’S PICKS 10

Supplemental Vitamins and Minerals for CVD Prevention and Treatment Journal of the American College of Cardiology Take-home message • In this meta-analysis, the authors evaluated the cardiovascular disease outcomes and all-cause mortality associated with supplemental vitamin and mineral intake. They report moderate- or low-quality evidence that folic acid and B-vitamin supple- mentation improves cardiovascular disease (CVD) or stroke outcomes. They noted no effect with multivitamin, vitamins C and D, β-carotene, calcium, and selenium supplementation. Finally, antioxidant combinations and niacin preparations were associated with increased risk of CVD or stroke. • The authors concluded that, since vitamin supplementation was not associated with a significant reduction in CVD risk, the risk-to-benefit ratio must be strongly considered.

COMMENT By David Rakel MD, FAAFP Meals vs Pills: Benefits of Vitamins and Supplements I t has been estimated that 52% of the population take nutritional supple- ments. But is this helpful compared with a healthy diet?

can deplete potassium, some commonly used medications are known to deplete nutrient levels and strategic replacement can be considered. Here is a list. Medication Nutrient depleted Metformin B12, folate, thiamine (B1) ACE inhibitors Zinc Acetaminophen Glutathione Proton pump inhibitors B-vitamins, calcium, magnesium,

vitamin A as a supplement bypasses this mechanism, causing harm when the body is exposed to too much vitamin A.

What this meta-analysis found Benefit

Why a meal is better than a pill The challenge of getting good nutrition through a pill vs a meal is that you can only pack so much into a capsule. This results in dilution of the amount of nutrients. The length of the ingredient list is inversely proportionate to the dose of each. You would be better off just eating a broccoli floret. Also, when we consume a nutrient in isolation, it is removed from the other chemicals that work synergistically in the plant. Studies suggest that the natural combination of chemicals found in nature is likely more powerful than taking what we think is the most important one in isola- tion. And, finally, when we take a vitamin, it bypasses the self-regulatory mechanisms of the body. For example, when one eats a carrot, the body obtains beta-caro- tene to make vitamin A. The body won’t make vitamin A unless it needs it. Taking

Abstract The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease out- comes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (mul- tivitamins, vitamins C, D, β-carotene, calcium, Eating a healthy, plant-based meal is likely much more beneficial than getting nutri- tion through a pill. But, just as diuretics • Folic acid was associated with a 17% reduction in cardiovascular risk (risk reduction of 0.83) with a number needed to treat of 111. Using folic acid within a B-complex vitamin is being considered for stroke prevention. No benefit • Taking multivitamins, vitamin D, vitamin C, vitamin E, vitamin B6, magnesium, zinc, iron, and calcium had no effect on reducing cardiovascular risk. (overall risk reduction, 0.99). Potential for harm • Long-acting niacin (no flush) and mul- tivitamins were associated with an increase in all-cause mortality.

zinc, chromium, vitamin C, iron

Insulin Statins

Magnesium

Co-enzyme Q10

Dr. Rakel is Professor and Chair of the Department of Family & Community Medicine at the University of New Mexico School of Medicine in Albuquerque, New Mexico.

and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks. Supplemental Vitamins and Minerals for CVD Prevention and Treatment. J Am Coll Cardiol 2018 Jun 05;71(22)2570-2584, DJA Jenkins, JD Spence, EL Giovannucci, et al. www.practiceupdate.com/c/69005

" …when we consume a

nutrient in isolation, it is removed from the other chemicals that work synergistically in the plant. "

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Efficacy of Self- Monitored Blood Pressure for Titration of Antihypertensive Medication The Lancet Take-home message • In this large randomized, controlled trial (n=1182), the authors evaluated the clinical utility of blood pressure (BP) self-moni- toring compared with telemonitoring or clinic blood pressure readings for managing medication titration for high BP. At 12-month follow-up, participants undergoing telemonitoring or performing self-monitoring had lower BP compared with participants monitored by in-clinic measurement. Telemoni- toring and self-monitoring produced similar results in regard to overall high BP control. • The authors concluded that BP self-monitoring is an effective method for monitoring BP for the purposes of medication titration and offers a simple and accurate strategy for moni- toring BP in patients managed by primary care practitioners. Abstract BACKGROUND Studies evaluating titration of antihypertensive medication using self-monitoring give contradictory findings and the precise place of telemonitoring over self-monitoring alone is unclear. The TASMINH4 trial aimed to assess the efficacy of self-monitored blood pressure, with or without telemonitoring, for antihypertensive titration in primary care, compared with usual care. METHODS This study was a parallel randomised controlled trial done in 142 general practices in the UK, and included hypertensive patients older than 35 years, with blood pressure higher than 140/90 mmHg, who were willing to self-monitor their blood pressure. Patients were randomly assigned (1:1:1) to self-monitoring blood pressure (self-montoring group), to self-monitoring blood pressure with telemonitoring (telemonitoring group), or to usual care (clinic blood pressure; usual care group). Randomisationwas by a secureweb- based system. Neither participants nor investigators were masked to group assignment. The primary outcome was clinic measured systolic blood pres- sure at 12months from randomisation. Primary analysis was of available cases. FINDINGS 1182 participants were randomly assigned to the self-monitoring group (n=395), the telemonitoring group (n=393), or the usual care group (n=394), of whom 1003 (85%) were included in the primary analysis. After 12 months, systolic blood pressure was lower in both intervention groups comparedwith usual care (self-monitoring, 137·0 [SD 16·7] mmHg and telemon- itoring, 136·0 [16·1] mmHg vs usual care, 140·4 [16·5]; adjustedmean differences vs usual care: self-monitoring alone, -3·5mmHg [95%CI -5·8 to -1·2]; telemon- itoring, -4·7 mm Hg [-7·0 to -2·4]). No difference between the self-monitoring and telemonitoring groups was recorded (adjusted mean difference -1·2 mm Hg [95% CI -3·5 to 1·2]). Results were similar in sensitivity analyses including multiple imputation. Adverse events were similar between all three groups. INTERPRETATION Self-monitoring, with or without telemonitoring, when used by general practitioners to titrate antihypertensive medication in individ- uals with poorly controlled blood pressure, leads to significantly lower blood pressure than titration guided by clinic readings. With most general practitioners and many patients using self-monitoring, it could become the cornerstone of hypertension management in primary care. Efficacy of Self-Monitored Blood Pressure, With or Without Telemon- itoring, for Titration of Antihypertensive Medication (TASMINH4): An Unmasked Randomised Controlled Trial. Lancet 2018 Feb 27;[EPub Ahead of Print], RJ McManus, J Mant, M Franssen, et al. www.practiceupdate.com/c/64937

COMMENT By Ronald G. Victor MD S elf-monitored home blood pressure – even without tele- monitoring – leads to lower blood pressure in general practice, reports a paper in the recent edition of The Lan- cet . Almost 1200 patients (mean age 67, baseline systolic BP 153 mmHg) from 142 general medical practices in the UK were randomly assigned (1:1:1) to self-monitoring of BP, self-monitor- ing plus telemonitoring, or usual care (office BP readings). After 12 months, the mean systolic BP was lower with both inter- ventions: 137.0 mmHg with self-monitoring and 136.0 mmHg with self-monitoring plus telemonitoring vs 140.6 mmHg with usual care. Thus, after multivariable adjustment, systolic BP was 3.5 mmHg lower with self-monitoring than usual care and 4.7 mmHg lower with self-monitoring plus telemonitoring. The strengths of the study are the rather large sample size and the statistically significant intervention effect(s). There also are major weaknesses. First, the effect size is modest. The final group mean systolic BP levels do not approach the new 2017 ACC/AHA goal of <130/80 mmHg, although the general prac- titioners at the time were targeting higher values. Second, the primary endpoint was office BP. Third, and more importantly, there was only a marginal intervention effect on drug regimen intensification. All 3 groups were under-treated at the end of the study, with <2 drug classes being prescribed per patient. Most hypertensive patients will need 2 or 3 drugs to control their BP. So, what explains the modest benefit? Possibly better medica- tion compliance, which was not rigorously measured. Missed opportunities for drug regimen intensification for high BP are common in primary care, with shared responsibility between patients (push-back), doctors (clinical inertia), and health systems (20 minutes for a new patient visit, and only 10 minutes for follow-up visits). Reliance on conventional office BP will over-estimate ambulatory BP due to the white coat reaction or under-estimate it due to masked hypertension in 3 out of every 4 patients. Ambulatory BP monitoring is the gold standard because it is the only way to obtain BP readings during normal daily activities and during sleep. We need to convince the Center for Medicare and Medicaid Services (CMS) to pay for it. I am not a big fan of frequent home BPmonitoring. Some patients will cherry-pick good readings to please the doctor. Others will check their BP whenever they feel stressed, with high readings indicating panic attacks. Some patients become so obsessed with their BP readings that daily (sometimes hourly) self-moni- toring becomes counterproductive; it can be very difficult to get such patients to stop. We should never instruct patients to take an extra BP pill if their home reading exceeds a certain level – this places far too much responsibility on the patient and it exacer- bates blood pressure lability. In this regard, PRN clonidine is the work of the devil! Based on this publication, I recommend that most patients mon- itor their blood pressure 2 to 4 weeks after each medication change – after sufficient time has elapsed to achieve steady state reductions in blood pressure.

Dr. Victor was Director of Cedars-Sinai Center for Hypertension, Associate Director, Clinical Research, and Burns and Allen Chair in Cardiology Research at Cedars-Sinai Heart Institute in Los Angeles, California.

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