Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.

WRITING GROUP MEMBERS Emelia J. Benjamin, MD, SCM, FAHA Michael J. Blaha, MD, MPH Stephanie E. Chiuve, ScD Mary Cushman, MD, MSc, FAHA Sandeep R. Das, MD, MPH, FAHA Rajat Deo, MD, MTR Sarah D. de Ferranti, MD, MPH James Floyd, MD, MS Myriam Fornage, PhD, FAHA Cathleen Gillespie, MS Carmen R. Isasi, MD, PhD, FAHA Monik C. Jiménez, ScD, SM Lori Chaffin Jordan, MD, PhD Suzanne E. Judd, PhD Daniel Lackland, DrPH, FAHA Judith H. Lichtman, PhD, MPH, FAHA Lynda Lisabeth, PhD, MPH, FAHA Simin Liu, MD, ScD, FAHA Chris T. Longenecker, MD Rachel H. Mackey, PhD, MPH, FAHA Kunihiro Matsushita, MD, PhD, FAHA Dariush Mozaffarian, MD, DrPH, FAHA Michael E. Mussolino, PhD, FAHA Khurram Nasir, MD, MPH, FAHA Robert W. Neumar, MD, PhD, FAHA Latha Palaniappan, MD, MS, FAHA Dilip K. Pandey, MBBS, MS, PhD, FAHA Ravi R. Thiagarajan, MD, MPH Mathew J. Reeves, PhD Matthew Ritchey, PT, DPT, OCS, MPH Carlos J. Rodriguez, MD, MPH, FAHA Gregory A. Roth, MD, MPH Wayne D. Rosamond, PhD, FAHA Comilla Sasson, MD, PhD, FAHA Amytis Towfighi, MD Connie W. Tsao, MD, MPH Melanie B. Turner, MPH Salim S. Virani, MD, PhD, FAHA Jenifer H. Voeks, PhD Joshua Z. Willey, MD, MS John T. Wilkins, MD Jason HY. Wu, MSc, PhD, FAHA Heather M. Alger, PhD Sally S. Wong, PhD, RD, CDN, FAHA Paul Muntner, PhD, MHSc On behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart Disease and Stroke Statistics—2017 Update

Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association

Author(s): Writing Group Members; Mozaffarian, Dariush; Benjamin, Emelia J; Go, Alan S; Arnett, Donna K; Blaha, Michael J; Cushman, Mary; Das, Sandeep R; de Ferranti, Sarah; Despres, Jean-Pierre; Fullerton, Heather J; Howard, Virginia J; Huffman, Mark D; Isasi, Carmen R; Jimenez, Monik C; Judd, Suzanne E; Kissela, Brett M; Lichtman, Judith H; Lisabeth, Lynda D; Liu, Simin; Mackey, Rachel H; Magid, David J; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Muntner, Paul; Mussolino, Michael E; Nasir, Khurram; Neumar, Robert W; Nichol, Graham; Palaniappan, Latha; Pandey, Dilip K; Reeves, Mathew J; Rodriguez, Carlos J; Rosamond, Wayne; Sorlie, Paul D; Stein, Joel; Towfighi, Amytis; Turan, Tanya N; Virani, Salim S; Woo, Daniel; Yeh, Robert W; Turner, Melanie B; American Heart Association Statistics Committee; Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2016 Update: A Report From the American Heart Association

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

Author(s): Go, Alan S; Mozaffarian, Dariush; Roger, Veronique L; Benjamin, Emelia J; Berry, Jarett D; Borden, William B; Bravata, Dawn M; Dai, Shifan; Ford, Earl S; Fox, Caroline S; Franco, Sheila; Fullerton, Heather J; Gillespie, Cathleen; Hailpern, Susan M; Heit, John A; Howard, Virginia J; Huffman, Mark D; Kissela, Brett M; Kittner, Steven J; Lackland, Daniel T; Lichtman, Judith H; Lisabeth, Lynda D; Magid, David; Marcus, Gregory M; Marelli, Ariane; Matchar, David B; McGuire, Darren K; Mohler, Emile R; Moy, Claudia S; Mussolino, Michael E; Nichol, Graham; Paynter, Nina P; Schreiner, Pamela J; Sorlie, Paul D; Stein, Joel; Turan, Tanya N; Virani, Salim S; Wong, Nathan D; Woo, Daniel; Turner, Melanie B; American Heart Association Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2013 Update A Report From the American Heart Association

Clinical investigation of antiarrhythmic devices. A statement for healthcare professionals from a joint task force of the North American Society of Pacing and Electrophysiology, the American College of Cardiology, the American Heart Association, and the Working Groups on Arrhythmias and Cardiac Pacing of the European Society of Cardiology.

On September 28, 2004, the Center of Medicare Services in the US Government published a “Draft Decision Memo for Implantable Defibrillators (CAG-00157R2)” in the Federal Register [1]. This decision resulted from an industry request for Medicare program coverage for high-risk sudden death populations stratified by the presence of cardiac disease and impaired left ventricular ejection fraction alone. This initiative, whose genesis can actually be traced back to the recognition of improved patient survival with ICD therapy in patients with left ventricular dysfunction that were initially reported in observational studies over 15 years ago and then in a subgroup analysis of the AVID study, had exceedingly important clinical and health care policy implications [2–4]. The current day trigger was the completion of several prospective studies using ICDs in high-risk cardiac patients that were reported in scientific meetings and have now finally been reported in peer-reviewed literature [5–12]. Despite the under publication status of these data and the lack of careful critical analysis, extensive commentary addressing many aspects of this issue emerged. Immediate implementation of ICD therapy in all such patients was often demanded. In this period, this commentator urged that there was a need for critical data analysis [13]. An initial coverage decision for coronary patients with intraventricular conduction defects and moderate to severe left ventricular dysfunction (ejection fraction <30%) was initially published. The September 28 memo now addresses the comprehensive spectrum of clinical study populations that have been studied for primary prevention of sudden death with ICD therapy, In this remarkable and astute analysis, the Federal Agency has taken a leadership role in defining the parameters of the debate and challenged the scientific establishment to engage in a responsible debate on important public health policy. The CMS analysis focuses on important large segments of cardiac patients at risk of sudden death, namely after recent myocardial infarction and ischemic or non-ischemic cardiomyopathy with heart failure and moderate or severe left ventricular systolic dysfunction. No conclusive evidence could be marshalled for benefit in recent MI patients. In patients with ischemic cardiomyopathy, increasing evidence of a potential benefit gradient related to QRS duration was identified. Subgroups with prolonged QRS complexes in several trials showed important reductions in hazard ratios with ICD therapy. In patients with normal QRS duration, hazard ratios were very modestly reduced (HR = 0.84 in SCD HeFT, with confidence intervals of 0.62–1.14) and benefits were reduced four fold. The point of subgroup division for QRS normalcy has been challenged but the concept of a benefit gradient remains intact. One would suspect that this relationship is one between two continuous variables and better expressed in other statistical presentations. However, this data is yet to be published. With a low end of benefit well below 1% annual mortality benefit, optimal patient selection is an issue that simply will not go away [14,15]. In another telling point, the CMS memo noted that the SCD HeFT trial was extended in duration to a mean follow-up of 45 months, potentially influencing trial outcome, yet only 21% of ICD patients experienced appropriate ICD therapy. ICD firing data, which used to a staple element of outcome reporting in early trials, has been notably consigned to a less prominent element in these trials despite advances differentiating inappropriate from appropriate firing and recurrences of slower stable and rapid highly unstable ventricular tachyarrhythmias. In a recent report in this Journal, Thakur and coworkers reported on such data in their center contributing to the very limited database in the peer reviewed literature on this subject [16]. Finally, the agency noted, “Female patients have been embarrassingly under-represented in all ICD trials.” It went on to state “no study has shown a significant improvement in mortality for women from ICD therapy compared to control therapy. A thorough assessment of whether the benefits and harms of ICDs differ

Federal guidelines for prophylactic ICD therapy in high risk populations for sudden cardiac death: is this a necessary course correction?

CATEGORIES Numbers identify subcategories. Parentheses indicate abbreviations used in figures

Is Justice Blind? Blinded and Unblinded

Implantable anti-tachycardia devices have become an additional therapeutic option for those patients afflicted with life-threatening tachyarrhythmias. Follow-up of these complex devices are time-consuming and, if mismanaged, may be dangerous to the patient. For these reasons, a special anti-tachycardia device clinic was started at Newark Beth Israel Medical Center in July 1984. From the inception of the clinic to September 1985, 24 patients were followed. Seventy-five percent had antitachycardia devices (ATDs) implanted for treatment of ventricular tachyarrhythmias (VT/VF) with the remaining 25% for supraventricular tachycardias. All patients were seen every 3 months or more often if clinically required. Of 112 ciinic examinations, 102 (91%) were scheduled appointments (group I) while the remaining 10 visits (group II) were unscheduled and preceded by symptomatic episodes. The problems detected in clinic (groups I and II) ranged from sudden failure of an AICD to apprehension. Appropriate nonoperative treatment was given during clinic evaluation for 60% of the problems detected in group II, while the remaining 40% required eventual surgical intervention. Compliance throughout the 15-month follow-up period was 100%. Major benefits of the clinic cited by patients and their families were continuity of care, the time allotted to meet the individual needs, and management of most problems on an out-patient basis.

A special outpatient clinic for following patients with implanted tachyarrhythmia devices.

The debate over prophylactic implantable defibrillator (ICD) use entered a new phase this year. The major clinical trials are in and reported [1–5]. The Center for Medicare Services (CMS) has made its initial determination for coverage of most, if not all, of the major population groups enrolled in the trials [6]. Hospitals and physicians are now examining new reporting requirements for Medicare reimbursement for these device implants. These requirements largely focus on the subpopulation being implanted and the choice of ICD system (single or dual chamber, biventricular pacing capability). No information is presently available on CMS intentions to monitor device function and patient outcome. Outcomes information in most of these trials had been largely reduced to mortality benefits. Occasional subgroup analyses and device use data was available in meeting presentations but had rarely been highlighted. An important difference from secondary prevention populations was a significantly lower appropriate device use pattern in the initial years of follow-up. Now, more detailed information is finally forthcoming. In an important analysis, the MADIT II trial reported a rather dismal outcome for patients using the device in the first three years of follow-up [7]. In an average follow up of 21 months, only 169 of 720 ICD patients (%) received an appropriate therapy for VT/VF. In the SCD-HeFT trial only 21.2% of devices were used. The MADIT II authors noted “Few baseline characteristics distinguished patients who received appropriate ICD therapy for their first ventricular tachyarrhythmic. The hazard ratios for the risk of death due to any cause in those who survived appropriate therapy for termination of VT and VF were 3.4 (p < 0.001) and 3.3 (p = 0.01), respectively, compared with those who survived without receiving ICD therapy,with a high frequency of heart failure and late nonsudden cardiac death after first successful ICD therapy for VF” [7]. It becomes clear from this analysis that baseline risk stratification using clinical, demographic and ejection fraction measures is inadequate for identifying those who derive long-term benefit from the device, use the device and adequately prognosticate outcomes. In this regard, the major loser is the patient who is in search of favorable outcome when he or she embarks on ICD therapy. Many who favored more rigorous baseline risk stratification at the initiation of these trials may yet have their day in the court of evidence based medicine. The use of noninvasive tests, and even invasive electrophysiologic testing, to risk stratify these patients remains on the table for discussion. On the surface the role of electrophysiologic study could appear to be very limited. Once again, the authors state “The 30 patients who received a shock to terminate their first episode of VF during follow-up were less likely to have been inducible at baseline electrophysiological testing than those who required no electrical therapy or who received their first electrical therapy for VT.” Another interpretation could be that patients presenting with VF early in their follow-up had either co-morbid conditions or irreversible intercurrent events that were not amenable to electrical therapy to prolong survival. The behaviour of patients who had inducible monomorphic ventricular tachycardia in all these studies, if available, needs to more extensively examined. Clearly, more detailed analysis of the findings of electrophysiologic study and, perhaps, a complete stimulation protocol would be of value in judging this issue. Equally important is the role that new noninvasive risk stratification tests such as T wave alternans assume in this environment. The Alternans Before Cardioverter Defibrillator (ABCD) Trial has completed enrollment and awaits follow up completion. Of importance is that patients with intraventricular conduction defects or on extensive beta blocker therapy for their disease or ventricular dysfunction are not good candidates for this test. Thus, we come to the crux of the question at hand. Can the medical marketplace resolve this challenge? Will we continue to examine this issue to identify the best candidates for prophylactic ICDs? This may be the only opportunity to answer the tough questions that potential recipients of such devices ask such as: “What is the likelihood of individual benefit?” ICDs have double digit complication rates and do these outweigh benefits in low risk populations [8]. Even tougher questions lie in the future: “Should

Sanjeev Saksena

Papers

Federal guidelines for prophylactic ICD therapy in high risk populations for sudden cardiac death: is this a necessary course correction?

Is Justice Blind? Blinded and Unblinded

A special outpatient clinic for following patients with implanted tachyarrhythmia devices.

Prophylactic ICDs: Can (and will) the Medical Marketplace Decide Their Role?