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The medical profession should play a central role in evaluating the evidence related to drugs, …

Jeffrey L. Anderson, MD, FACC, FAHA, Chair; Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair[‡‡][1]; Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect; Nancy M. Albert, PhD, CCNS, CCRN, FAHA; Biykem Bozkurt, MD, PhD, FACC, FAHA; Ralph G. Brindis, MD, MPH, MACC; Mark A. Creager, MD, FACC

Objectives This study investigated how the initial intended strategy at left ventricular assist device (LVAD) implantation influenced patient outcomes. Background Left ventricular assist device implantation strategy impacts candidate selection, reimbursement, and clinical trial design; however, concepts of device strategy are continuing to evolve. Methods For patients entered in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) receiving a primary continuous flow LVAD between March 2006 and March 2011, initial strategies were bridge to transplant (BTT), bridge to candidacy (BTC) for transplant, and destination therapy (DT). Primary analyses compared BTT, BTC, and DT outcomes at 6, 12, and 24 months. Results Among 2,816 primary LVAD recipients, implant strategy was 1,060 (38%) BTT, 1,162 (42%) BTC (likely to be listed 796, moderately likely 282, unlikely 84), and 553 (20%) DT. Compared with BTC/DT, those listed at implant (BTT) had similar degrees of ventricular dysfunction and hemodynamic derangement but generally less comorbidity. Survival (alive with LVAD or transplanted) was superior at 24 months for BTT versus BTC versus DT (77.7% vs.70.1% vs. 60.7%, respectively, p Conclusions The currently accepted indications only account for 58% of LVAD implants. Across indications, patients differ by the number and types of comorbidities rather than the need for hemodynamic support. Regardless of initial implant strategy, patients often have long durations of support, and strategies often change over time, challenging the regulatory categorization of LVAD recipients as either BTT or DT.

Steven R. Bailey, MD, FACC, FSCAI, FAHA, Moderator Andrea M. Russo, MD, FACC, FHRS, Writing Group Liaison [⁎][1] Suraj Kapa, MD, Writing Group Liaison Michael B. Alexander, MD, FACC[§][2] Steven R. Bailey, MD, FACC, FSCAI, FAHA[∥][3] Ulrika Birgersdotter-Green, MD, FHRS[∥][3] Alan S.

At the Ethics of the Heart II: Ethical and Policy Challenges in Congenital Heart Disease Conference, March 16-17, 2012 in Philadelphia, Pennsylvania, one of the sessions focused on the issues related to end-stage heart failure in patients with congenital heart disease including utilizing the therapy of heart transplantation. This article will summarize the session related to repeat heart transplant that was based on discussion of actual patient cases, two adults and one pediatric, presented, respectively, by an adult and a pediatric heart transplant specialist. Outcome data related to retransplant for both adult and pediatric heart transplant populations are reviewed. The complicated ethical issues related to considerations of beneficence versus nonmalfeasance by a medical care team for an individual patient, patient autonomy related to adherence, and obligations to society to fairly allocate the scarce precious resource of donor organs are discussed.

At 40 years of age, the lifetime risk of developing heart failure (HF) is 1 in 5 for men and women in the United States. Approximately half of patients who are ultimately diagnosed with HF will die within 5 years1; the associated morbidity, hospitalization rate, and loss of functional capacity are more difficult to calculate. Among the 5 million American patients currently living with HF, it is estimated that 200 000 patients have American College of Cardiology/American Heart Association stage D or refractory HF, resulting in markedly diminished functional status and survival.1,2 In 2012, 2 therapies are available to potentially prolong survival and to improve quality of life for end-stage HF patients: heart transplantation and long-term mechanical circulatory support in the form of a ventricular assist device (VAD). For permanent mechanical support, also referred to as destination therapy (DT), the Food and Drug Administration approved the use of the HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) in January 2010. This device supports only the left ventricle; no biventricular device is approved for long-term therapy at this time. Response by Mehra and Domanski on p 3094 Many advanced HF patients are not appropriate candidates for transplantation or permanent LVAD because of comorbid conditions or age. After excluding these patients, clinicians must critically evaluate individual patient eligibility for transplantation or VAD. The indications for and complications expected after each procedure are increasingly recognized as distinct; the skills needed by clinicians who must care for these 2 types of patients are garnered in 2 complementary but separate experiential care settings. The therapies are neither equivalent in historical experience and outcomes nor interchangeable. Transplantation has been available for decades, with well-documented selection criteria, management protocols, and outcomes. As we begin to understand how to appropriately …

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients who have advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and Interagency Registry of Mechanically Assisted Circulatory Support.

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients with advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and the Interagency Registry of Mechanically Assisted Circulatory Support.

The comorbidities of hypertension, diabetes mellitus, obesity, hyperlipidemia, and metabolic syndrome are common in patients with heart failure (HF) and affect clinical outcomes.1–3 Interestingly, although these comorbidities are associated with the development of incident HF in the general population, in patients with established HF, their contributory roles to clinical outcomes are not predictable, and their management is quite challenging. Recent American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines have addressed the role of lifestyle modification,4 treatment of blood cholesterol,5 and management of overweight and obesity6 in the general population and in patients with increased cardiovascular risk, and a recent report from the Eighth Joint National Committee addressed the management of hypertension.7 However, these guidelines did not specifically address the management of such comorbidities in patients with HF. Similarly, the most recent ACCF/AHA HF practice guidelines8 in 2013 addressed the overall management of comorbidities in patients with HF in broad terms, but again, specific and detailed recommendations on how to manage hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome are lacking. The intent of this AHA scientific statement is to summarize data relevant to contributory risk and to provide guidance on the management of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in the development and prognosis of HF to provide recommendations (Table 1) and to foster communication between physicians and other healthcare professionals and patients on the management of these comorbidities. Recommendations in this document are based on published studies and the multidisciplinary expertise of the writing group and harmonized with published practice guidelines from the ACC/AHA4–6,8–12 and other organizations.7,13–15 View this table: Table 1. Applying Classification of Recommendations and Level of Evidence Hypertension is a worldwide epidemic; in many countries, 50% of …

Heart failure (HF) is a global epidemic affecting millions of individuals worldwide. Although important progress has been made in the management of HF, this condition remains a common cause of morbidity and death. Since the publication of the previous sets of guidelines for the management of HF, new diagnostic and therapeutic options for HF have emerged. Now, both the ESC and the ACC/AHA/HFSA have simultaneously published an update of their guidelines incorporating, among others, recommendations for the use of new pharmacological therapies for the treatment of HF. For this Viewpoint article, we have asked the chairs of the ESC Task Force, the chairs of the ACC/AHA/HFSA Writing Committee, and an independent opinion leader in the field to offer their expert insight into the new guidelines, highlighting what is new, what the main differences are between the two sets of guidelines, and what steps should be taken to improve the guidelines in future updates.

Jonathan L. Halperin, MD, FACC, FAHA, Chair Glenn N. Levine, MD, FACC, FAHA, Chair-Elect Sana M. Al-Khatib, MD, MHS, FACC, FAHA Kim K. Birtcher, PharmD, MS, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC Joaquin E. Cigarroa, MD, FACC Lesley H. Curtis, PhD, FAHA

Cardiac arrest, acute myocardial infarction (AMI), and stroke affect millions of people in the United States annually.1 Despite significant advances in medical treatments for these conditions, they remain a major public health problem and a leading cause of morbidity and mortality.1 A critical common element in optimizing care and outcomes for these conditions is the timely recognition of symptoms and initiation of treatment. For example, rapid initiation of cardiopulmonary resuscitation (CPR) is associated with improved survival from cardiac arrest.2 Similarly, early recognition and presentation after onset of symptoms of AMI and ischemic stroke enable implementation of critical therapies such as primary angioplasty and thrombolysis, which are known to improve outcomes.1 Indeed, the “Chain of Survival” for emergency cardiovascular and cerebrovascular care (ECCC) starts with prompt identification of the condition and early activation of the healthcare system to rapidly initiate care.3 Unfortunately, despite national efforts that include public education initiatives and clinical practice guideline recommendations from entities such as the American Heart Association (AHA), major gaps remain in the timely identification of symptoms and initiation of ECCC.4–6 As one example, studies of out-of-hospital cardiac arrest (OHCA) have consistently noted delays in the initiation of bystander CPR.7 For AMI, there have been advances in the provision of timely primary angioplasty for ST-segment elevation myocardial infarction (STEMI), as reflected by significant improvements in door-to-balloon times.8 However, the time from patient symptom onset to seeking care for possible myocardial infarction has not improved significantly.9,10 Similarly, for stroke, there continue to be advances in door-to-needle times, but stroke symptom recognition and seeking of treatment by patients and their families remain a major barrier to timely stroke care.11–16 Public and clinician education efforts alone are not sufficient to reduce gaps …

Despite >100 clinical trials, only 2 new drugs had been approved by the US Food and Drug Administration for the treatment of chronic heart failure in more than a decade: the aldosterone antagonist eplerenone in 2003 and a fixed dose combination of hydralazine–isosorbide dinitrate in 2005. In contrast, 2015 has witnessed the Food and Drug Administration approval of 2 new drugs, both for the treatment of chronic heart failure with reduced ejection fraction: ivabradine and another combination drug, sacubitril/valsartan or LCZ696. Seemingly overnight, a range of therapeutic possibilities, evoking new physiological mechanisms, promise great hope for a disease that often carries a prognosis worse than many forms of cancer. Importantly, the newly available therapies represent a culmination of basic and translational research that actually spans many decades. This review will summarize newer drugs currently being used in the treatment of heart failure, as well as newer strategies increasingly explored for their utility during the stages of the heart failure syndrome.

Dietary sodium restriction is arguably the most frequent self-care behavior recommended to patients with heart failure (HF)1,2 and is endorsed by all HF guidelines.2–10 However, the data on which this recommendation is drawn are modest, and the limited trials conducted have produced inconsistent findings. Americans consume ≈3700 mg sodium daily,11 whereas the US Department of Agriculture and the Department of Health and Human Services recommend 2300 mg daily intake for the general population, with a stricter recommendation of 1500 mg/d for those >50 years of age, blacks, or individuals with hypertension, diabetes mellitus, or chronic kidney disease.12 According to a recent report from the National Health and Nutrition Examination Survey, although 47.6% of persons aged ≥2 years meet the criteria to limit daily sodium intake to 1500 mg, the usual intake for 98.6% of those persons was >1500 mg; in 88.2% of the remaining population, daily intake was greater than the recommended

Background The CorCap cardiac support device (Acorn Cardiovascular, Inc, St Paul, Minn) is the first device that specifically addresses ventricular remodeling in heart failure by reducing wall stress. We previously reported outcomes from the Acorn randomized trial to a common closing date (22.9 months of follow-up). This report summarizes results of extended followup to 5 years. Methods A total of 107 patients were enrolled in the no–mitral valve repair/replacement stratum including 57 in the CorCap treatment group and 50 in the control (optimal medical therapy alone) group. Patients were assessed every year, until completing 5 years of follow-up, for survival, adverse events, major cardiac procedures, New York Heart Association (NYHA) functional status, and echocardiograms, which were read at a core laboratory. Results Overall survivals were similar between the treatment and control groups, demonstrating no late adverse effect on mortality. The treatment group had significant reductions in left ventricular end-diastolic volume ( P = .029) as well as a small increase in sphericity index. More patients in the treatment group improved by at least 1 NYHA functional class ( P = .0005). There was no difference in rates of adverse events. In a subgroup of patients with an intermediate left ventricular end-diastolic dimension, there was a significant reduction in the Kaplan-Meier estimate of the freedom from the composite end point of death and major cardiac procedures ( P = .04). Conclusions These cumulative data demonstrate the sustained reverse remodeling of the left ventricle and the long-term safety and efficacy of the CorCap cardiac support device as an adjunctive therapy for patients with heart failure who remain symptomatic despite optimal medical therapy.

Background— Prior studies have suggested using a panel of biomarkers that measure diverse biological processes as a prognostic tool in chronic heart failure. Whether this approach improves risk prediction beyond clinical evaluation is unknown. Methods and Results— In a multicenter cohort of 1513 chronic systolic heart failure patients, we measured a contemporary biomarker panel consisting of high-sensitivity C-reactive protein, myeloperoxidase, B-type natriuretic peptide, soluble fms-like tyrosine kinase receptor-1, troponin I, soluble toll-like receptor-2, creatinine, and uric acid. From this panel, we calculated a parsimonious multimarker score and assessed its performance in predicting risk of death, cardiac transplantation, or ventricular assist device placement in comparison to an established clinical risk score, the Seattle Heart Failure Model (SHFM). During a median follow-up of 2.5 years, there were 317 outcomes: 187 patients died; 99 were transplanted; and 31 had a ventricular assist device placed. In unadjusted Cox models, patients in the highest tertile of the multimarker score had a 13.7-fold increased risk of adverse outcomes compared with the lowest tertile (95% confidence interval, 8.75–21.5). These effects were independent of the SHFM (adjusted hazard ratio, 6.80; 95% confidence interval, 4.18–11.1). Addition of the multimarker score to the SHFM led to a significantly improved area under the receiver operating characteristic curve of 0.803 versus 0.756 ( P =0.003) and appropriately reclassified a significant number of patients who had the outcome into a higher risk category (net reclassification improvement, 25.2%; 95% confidence interval, 14.2–36.2%; P Conclusions— In ambulatory chronic heart failure patients, a score derived from multiple biomarkers integrating diverse biological pathways substantially improves prediction of adverse events beyond current metrics.

Background— Adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase was assessed in a randomized, double-blind, placebo-controlled, phase 2 study in patients with advanced heart failure. Methods and Results— Thirty-nine patients received intracoronary adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 efficacy parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P =0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P =0.05) on high-dose treatment versus placebo. There were no untoward safety findings. Conclusions— The Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) study demonstrated safety and suggested benefit of adeno-associated virus type 1/sarcoplasmic reticulum Ca 2+ -ATPase in advanced heart failure, supporting larger confirmatory trials. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00454818.

There have been no published recommendations about staffing needs for a heart failure (HF) clinic or an office setting focused on heart transplant. The goal of this survey was to understand the current staffing environment of HF, transplant, and mechanical circulatory support device (MCSD) programs in the United States and abroad. This report identifies current staffing patterns but does not endorse a particular staffing model.An online survey, jointly sponsored by the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), and the Heart Failure Society of America (HFSA), was sent to the members of all 3 organizations who had identified themselves as interested in HF, heart transplant, or both, between March 12, 2009, and May 12, 2009.The overall response rate to the 1,823 e-mail surveys was 23%. There were 257 unique practices in the United States (81% of total sites) and 58 international sites (19%); approximately 30% of centers were in a cardiovascular group practice and 30% in a medical school hospital setting. The large majority of practices delivered HF care in both an inpatient and outpatient environment, and slightly more centers were implanting MCSDs (47%) than performing cardiac transplantation (39%). Most practices (43%) were small, with4 staff members, or small- to medium-sized (34%), with 4 to 10 staff members, with only 23% being medium (11-20 staff) or large programs (20 staff). On average, a U.S. HF practice cared for 1,641 outpatients annually. An average HF program with transplant performed 10 transplants. Although larger programs were able to perform more transplants and see more outpatient HF visits, their clinician staffing volume tended to double for approximately every 500 to 700 additional HF visits annually. The average staffing utilization was 2.65 physician full-time equivalents (FTEs), 2.21 nonphysician practitioner (nurse practitioner or physician assistant) FTEs, and 2.61 nurse coordinator FTEs annually.The HF patient population is growing in number in the United States and internationally, and the clinicians who provide the highly skilled and time-consuming care to this population are under intense scrutiny as a result of focused quality improvement initiatives and reduced financial resources. Staffing guidelines should be developed to ensure that an adequate number of qualified professionals are hired for a given practice volume. These survey results are an initial step in developing such standards.

Objectives There have been no published recommendations about staffing needs for a heart failure (HF) clinic or an office setting focused on heart transplant. The goal of this survey was to understand the current staffing environment of HF, transplant, and mechanical circulatory support device

Purpose of review Significant technological advances have occurred in mechanical assist devices over the past decade. With improving hemodynamics and durability, ventricular assist devices (VADs) are being implanted with increasing frequency. Yet, several VAD-specific morbidities and technological challenges, which are reviewed, continue to limit the number of devices that are currently implanted. Recent findings We are beginning to understand the pathophysiology of complications specific to continuous-flow VADs, including bleeding and aortic insufficiency. Improved outcomes and durability with currently available continuous-flow VADs are evident, as compared with first-generation devices. A focus on enhancing quality of life with a VAD will be critical to widespread application of mechanical circulatory support to the heart failure patient population. Summary Advances in technology and surgical technique are continuing to minimize morbidity and mortality associated with mechanical assist devices. Continued technological advancements will allow increased utilization of mechanical circulatory support over the next decade.

The Food and Drug Administration (FDA) last approved a new oral drug (hydralazine–isosorbide dinitrate) for patients with heart failure and a reduced ejection fraction in 2005 — and this drug was recommended only for self-identified black patients who continued to have symptoms despite evidence-based treatment.1 TThe aldosterone antagonist eplerenone was approved for the treatment of heart failure in 2003. (In 2012, the European Medicines Agency approved ivabradine, which has not received FDA approval.) Now, a novel drug, LCZ696, a dual inhibitor of angiotensin II receptor and neprilysin, may prove to be the first disruptive agent to the heart-failure treatment algorithm, . . .

Despite the importance of age, sex, and race/ethnicity representativeness in clinical trials, limited data exist regarding the enrollment trends of these groups in contemporary heart failure (HF) trials.To characterize the representation of older patients, women, and racial and ethnic minorities in HF trials.We performed a systematic search of HF trials enrolling more than 400 participants published between January 2001 and December 2016 using PubMed/Medline and ClinicalTrials.gov. A total of 118 trials enrolling a cumulative 215 508 patients were included. Trial findings were compared with large epidemiologic studies indexed to hospitalization status and ejection fraction.Median number of participants per trial was 994 (interquartile range [IQR], 543-1899), enrolled from a median of 82 (IQR, 28-171) study sites. Overall, 94 trials (80%) enrolled patients with HF with reduced ejection fraction (HFrEF) exclusively. Mean (SD) age of trial participants was 65 (11) years (from 64 years in 2001 to 2004 to 65 years in 2013 to 2016), and 58 873 of 215 508 were women (27%; from 26% in 2001 to 2004 to 29% in 2013 to 2016); no significant temporal trends were observed (P ≥ .60 for both). Chronic HF with preserved ejection fraction (HFpEF) trials enrolled older participants (mean [SD] age, 71 [7] years compared with 65 [11] years for HFrEF and 66 [12] years for acute HF [AHF] trials; P = .01). Corresponding mean ages in US epidemiologic studies were 69 years for HFrEF and 73 years for both patients with HFpEF and patients with AHF. The HFpEF trials had a higher proportion of women (n = 4940 of 8845 [56%]) compared with HFrEF (n = 34 397 of 143 538 [24%]) or AHF (n = 11 013 of 34 633 [32%]) (P .001). Corresponding weighted proportions of women in HFpEF, HFrEF, and AHF trials in epidemiologic studies were 62%, 29%, and 50%, respectively. Distribution of racial/ethnic groups was reported in 55% (47%) of the trials; 22% of the participants were not white (n = 27 463 of 124 980), with significant increase over time from 13% in 2001 to 2004 (n = 5606 of 44 616) to 30% in 2013 to 2016 (8421 of 28 073) (P = .01).In contemporary HF trials, older patients and women are consistently underrepresented. Race/ethnicity data are reported in less than half of trials; when reported, such data show that enrollment of nonwhite patients increased over time.

Background— Intracardiac pressures in heart failure (HF) have been measured in patients while supine in the hospital but change at home with posture and activity. The optimal level of chronic ambulatory pressure is unknown. This analysis compared chronic intracardiac pressures to later HF events and sought a threshold above which higher pressures conferred worse outcomes. Methods and Results— Median pressures were measured every 24 hours from continuous 8-minute segments for 6 months after implantation of hemodynamic monitors in 261 patients with New York Heart Association class III-IV HF in the Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure Study. Baseline and chronic daily medians of estimated pulmonary artery diastolic, right ventricular systolic, and right ventricular end-diastolic pressures were compared with HF event rate. The group median for chronic 24-hour estimated pulmonary artery diastolic pressure was 28 mm Hg (excluding 7 days before and after events). Despite weight-guided management, events occurred in 100 of 261 (38%) patients. Event risk increased progressively with higher chronic 24-hour estimated pulmonary artery diastolic pressure, from 20% at 18 mm Hg to 34% at 25 mm Hg and 56% at 30 mm Hg, with similar relations for right ventricular pressures. Among patients with baseline day median estimated pulmonary artery diastolic pressures of ≥25 mm Hg, event risk was 1.10/6 mo when they remained chronically ≥25 mm Hg, but risk fell to 0.47 when 24-hour pressures declined to Conclusions— Despite current management, many patients with advanced HF live on a plateau of high filling pressures from which later events occur. This risk is progressively higher with higher chronic ambulatory pressures. It is not known whether more targeted intervention could maintain lower chronic ambulatory pressures and better outcomes.

Granting clinical staff privileges to physicians is a primary mechanism institutions use to uphold quality care. The Joint Commission on Accreditation of Healthcare Organizations requires that medical staff privileges be based on professional criteria specified in medical staff bylaws. Physicians

In 1986, the landmark vasodilator trial, the Vasodilator–Heart Failure Trial (V-HeFT-1), ushered in a modern therapeutic regimen that provided hope, for the first time, to millions of patients suffering from and dying of heart failure.1 Entry criteria for the trial were simple and confined to men with “impaired cardiac function and reduced exercise tolerance.” The primary end point was all-cause mortality. Most clinicians did not quibble about the borderline statistical significance of the overall study, recognizing that a new era of heart failure therapy and clinical trials had begun. The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS)2 and Studies of Left Ventricular Dysfunction (SOLVD)3 were published subsequently, in 1987 and 1991, respectively, further refining patient selection while molding a new generation of cardiologists, many of whom became heart failure specialists. Article see p 1985 Since those heady times, the evolution of therapy for heart failure has become increasingly complex. The managing clinician must integrate a number of factors about the individual heart failure patient before adding treatments to the pharmacological foundation of renin-angiotensin and β-adrenergic inhibition. Crucial historical or phenotypic variables may include left ventricular ejection fraction (LVEF), functional classification and/or exercise tolerance, history and timing of previous arrhythmias or myocardial infarction, QRS duration and current rhythm, duration of heart failure symptoms, adequacy of or intolerance to optimization of medical therapy, gender, race, cause of the cardiomyopathy, valvular competence, and renal function. Important patient characteristics currently determine eligibility for additional medications, electric devices, surgical procedures, cardiac transplantation, ventricular assist devices, endomyocardial biopsy, cardiac rehabilitation, hospitalization, or hospice. This process of exacting classification of disease has served other disciplines well; imagine outcome trials for the wide range of thrombolytic or antiplatelet agents without the concomitant and careful descriptors of the manifestations of the acute coronary syndrome.4 Likewise, …

Background Compare outcomes of ultrafiltration (UF) versus standard intravenous (IV) diuretics by continuous infusion or bolus injection in volume overloaded heart failure (HF) patients. In the Ultrafiltration versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated heart Failure (UNLOAD) study, UF produced greater fluid reduction and fewer HF rehospitalizations than IV diuretics in 200 hospitalized HF patients. Outcomes may be due to greater fluid removal, but UF removes more sodium/unit volume than diuretics. Methods and Results Outcomes of 100 patients randomized to UF were compared with those of patients randomized to standard IV diuretic therapy with continuous infusion (32) or bolus injections (68). Choice of diuretic therapy was by the treating physician. Forty-eight hour weight loss (kg): 5.0 ± 3.1 UF, 3.6 ± 3.5 continuous infusion, and 2.9 ± 3.5 bolus diuretics ( P = .001 UF versus bolus diuretic; P > .05 for the other comparisons). Net fluid loss (L): 4.6 ± 2.6 UF, 3.9 ± 2.7 continuous infusion, and 3.1 ± 2.6 bolus diuretics ( P P > .05 for the other comparisons). At 90 days, rehospitalizations plus unscheduled visits for HF/patient (rehospitalization equivalents) were fewer in UF group (0.65 ± 1.36) than in continuous infusion (2.29 ± 3.23; P = .016 versus UF) and bolus diuretics (1.31 ± 1.87; P = .050 versus UF) groups. No serum creatinine differences occurred between groups up to 90 days. Conclusions Despite similar fluid loss with UF and continuous diuretic infusion, fewer HF rehospitalizations equivalents occurred only with UF. Removal of isotonic fluid by UF compared with hypotonic urine by diuretics more effectively reduces total body sodium in congested HF patients.

September 18, 2013, marks 2 years since the monumental meeting of Heads of State at the United Nations in New York to take action against noncommunicable diseases (NCDs), which includes cancer, cardiovascular disease (CVD), diabetes mellitus, and chronic respiratory disease. Recognizing that the rising human and financial costs of NCDs required a profound shift in the way countries viewed development, United Nations member states gathered for the second time in history to address a health concern (the first being the United Nations General Assembly Special Session on HIV/AIDS in 2001). Supporting the United Nations Political Declaration on the Prevention and Control of NCDs, countries acknowledged NCDs as a development issue and made a commitment to address this global crisis by taking action on the major modifiable risk factors— including tobacco use, raised blood pressure, poor nutrition, physical inactivity—triggering the new pandemic of NCDs, as well as the social, economic, and political determinants that shape these lifestyle choices.1 Although the declaration was a political commitment, it was an important first step, bringing together health and development leaders from across the globe to ensure that progress would be made to reduce the burden of NCDs. The past 2 years have witnessed concrete commitments, meaning that our work is only just beginning. The World Heart Federation and its members spearheaded global advocacy, with other colleagues in the NCD community, calling on the World Health Organization and member states to commit to tangible and achievable goals.2 In 2012, a global target was adopted to reduce premature NCD mortality 25% by 2025—“25by25.”3 Now in 2013, this target, as well as 8 additional targets addressing modifiable risk factors and committing to the use of essential medicines, technologies, and drug therapies to prevent …

Granulomatous diseases are a rare cause of hypercalcemia. The pathogenesis is presumed to be from endogenous production of 1,25-dihydroxyvitamin D by activated macrophages in granulomatous lesions, which harbor the 1 α-hydroxylase enzyme. Herein the first case of hypercalcemia associated with giant cell myocarditis, an unusual type of granulomatous process, is reported. In this case, a patient with giant cell myocarditis had development of progressive heart failure and cardiorenal syndrome that required biventricular support. One year later, hypercalcemia associated with a relatively high 1,25-vitamin D level and a concomitantly suppressed parathyroid hormone level developed in the presence of stage 4 chronic kidney disease. Her other workup of hypercalcemia was unrevealing for vitamin D intoxication and multiple myeloma. Computed tomography of her chest showed no signs of hilar lymphadenopathy. Her calcium levels returned to normal with low-dose steroid therapy and have remained normal following a successful heart transplant. This case illustrates an unusual cause of hypercalcemia thought to be due to extrarenal calcitriol production associated with giant cell myocarditis.

Atrial fibrillation (AF) and heart failure have emerged as new cardiovascular epidemics over the last decade.1 Heart failure affects ≈5 million patients in the United States, and >550 000 patients are diagnosed with new heart failure each year.2 Although the incidence of heart failure remained stable over the past 50 years, the prevalence of heart failure in the United States has steadily increased. Heart failure is the primary reason for 12 to 15 million office visits and 6.5 million hospital days yearly.3 From 1990 to 1999, the annual number of hospitalizations increased from ≈800 000 to >1 million for heart failure as a primary diagnosis and from 2.4 to 3.6 million for heart failure as a primary or secondary diagnosis.4 The steadily increasing number of patients with heart failure is due partially to better treatment and “salvage” of patients with acute myocardial infarctions earlier in life.2 As a consequence, heart failure carries a significant economic burden on our society because it is the most common discharge diagnosis and because more Medicare dollars are spent for the diagnosis and treatment of heart failure than for any other diagnosis.5 In 2007, the American Heart Association estimated that $33 billion was spent on heart failure alone.6 AF is the most common arrhythmia in clinical practice, accounting for approximately one third of admissions resulting from cardiac rhythm disturbances. An estimated 2.3 million people in North America have AF. During the last 20 years, hospital admissions for AF have increased by 66% for a number of reasons, including the aging of the population, the rising prevalence of chronic heart disease, and more frequent diagnosis as a result of increased monitoring.7 The recent Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study projected that the prevalence of AF …

Background Heart failure (HF) remains a major cause of morbidity and mortality in North America. With an aging population and an unmet clinical need by current pharmacologic and device-related therapeutic strategies, novel treatment options for HF are being explored. One such promising strategy is gene therapy to target underlying molecular anomalies in the dysfunctional cardiomyocyte. Prior animal and human studies have documented decreased expression of SERCA2a, a major cardiac calcium cycling protein, as a major defect found in HF. Methods and Results We hypothesize that increasing the activity of SERCA2a in patients with moderate to severe HF will improve their cardiac function, disease status, and quality of life. Gene transfer of SERCA2a will be performed via an adeno-associated viral (AAV) vector, derived from a nonpathogenic virus with long-term transgene expression as well as a clinically established favorable safety profile. Conclusions We describe the design of a phase 1 clinical trial of antegrade epicardial coronary artery infusion (AECAI) administration of AAVI/SERCA2a (MYDICAR) to subjects with HF divided into 2 stages: in Stage 1, subjects will be assigned open-label MYDICAR in one of up to 4 sequential dose escalation cohorts; in Stage 2, subjects will be randomized in parallel to 2 or 3 doses of MYDICAR or placebo in a double-blinded manner.

Objectives The purpose of this study was to determine whether a heart failure (HF) management strategy using continuous intracardiac pressure monitoring could decrease HF morbidity. Background Patients with HF may experience frequent decompensations that require hospitalization despite intensive treatment and follow-up. Methods The COMPASS-HF (Chronicle Offers Management to Patients with Advanced Signs and Symptoms of Heart Failure) study was a prospective, multicenter, randomized, single-blind, parallel-controlled trial of 274 New York Heart Association functional class III or IV HF patients who received an implantable continuous hemodynamic monitor. Patients were randomized to a Chronicle (Medtronic Inc., Minneapolis, Minnesota) (n = 134) or control (n = 140) group. All patients received optimal medical therapy, but the hemodynamic information from the monitor was used to guide patient management only in the Chronicle group. Primary end points included freedom from system-related complications, freedom from pressure-sensor failure, and reduction in the rate of HF-related events (hospitalizations and emergency or urgent care visits requiring intravenous therapy). Results The 2 safety end points were met with no pressure-sensor failures and system-related complications in only 8% of the 277 patients who underwent implantation (all but 4 complications were successfully resolved). The primary efficacy end point was not met because the Chronicle group had a nonsignificant 21% lower rate of all HF-related events compared with the control group (p = 0.33). A retrospective analysis of the time to first HF hospitalization showed a 36% reduction (p = 0.03) in the relative risk of a HF-related hospitalization in the Chronicle group. Conclusions The implantable continuous hemodynamic monitor-guided care did not significantly reduce total HF-related events compared with optimal medical management. Additional trials will be necessary to establish the clinical benefit of implantable continuous hemodynamic monitor-guided care in patients with advanced HF.

The role of endomyocardial biopsy (EMB) in the diagnosis and treatment of adult and pediatric cardiovascular disease remains controversial, and the practice varies widely even among cardiovascular centers of excellence. A need for EMB exists because specific myocardial disorders that have unique prognoses and treatment are seldom diagnosed by noninvasive testing.1 Informed clinical decision making that weighs the risks of EMB against the incremental diagnostic, prognostic, and therapeutic value of the procedure is especially challenging for nonspecialists because the relevant published literature is usually cited according to specific cardiac diseases, which are only diagnosed after EMB. To define the current role of EMB in the management of cardiovascular disease, a multidisciplinary group of experts in cardiomyopathies and cardiovascular pathology was convened by the American Heart Association (AHA), the American College of Cardiology (ACC), and the European Society of Cardiology (ESC). The present Writing Group was charged with reviewing the published literature on the role of EMB in cardiovascular diseases, summarizing this information, and making useful recommendations for clinical practice with classifications of recommendations and levels of evidence. The Writing Group identified 14 clinical scenarios in which the incremental diagnostic, prognostic, and therapeutic value of EMB could be estimated and compared with the procedural risks. The recommendations contained in the present joint Scientific Statement are derived from a comprehensive review of the published literature on specific cardiomyopathies, arrhythmias, and cardiac tumors and are categorized according to presenting clinical syndrome rather than pathologically confirmed disease. The ultimate intent of this document is to provide an understanding of the range of acceptable approaches for the use of EMB while recognizing that individual patient care decisions depend on factors not well reflected in the published literature, such as local availability of specialized facilities, cardiovascular pathology expertise, and operator experience. The use of EMB …

The role of endomyocardial biopsy (EMB) in the diagnosis and treatment of adult and pediatric cardiovascular disease remains controversial, and the practice varies widely even among cardiovascular centers of excellence. A need for EMB exists because specific myocardial disorders that have unique

Purpose of reviewCardiac transplantation continues to be the treatment of choice for suitable patients with refractory heart failure. Patients referred for transplant tend to be older and have additional comorbidities that require newer strategies for subsequent immunosuppression. The review summari

Background Urgent heart transplant candidates classified as United Network for Organ Sharing status 1B who require continuous infusions of inotropic agents for hemodynamic stability often have hemodynamic, electrical, or multisystem decompensation. This multicenter trial will study both traditional safety and efficacy parameters and the physiologic mechanisms of benefit of the addition to conventional therapy of nesiritide, a recombinant analog of brain-type natriuretic peptide, in this population. Methods TMAC is a prospective, randomized, parallel, multicenter, double-blind, placebo-controlled study in patients awaiting heart transplantation who meet United Network for Organ Sharing status 1B criteria (N = 120) and receive continuous dobutamine or milrinone through a double-lumen central catheter for at least 3 consecutive days before randomization. Patients will receive standard care and continuous intravenous inotrope therapy plus a 28-day continuous infusion of nesiritide or placebo. There will be up to 6 months of follow-up. Primary efficacy end point will be days alive after treatment without renal, hemodynamic, or electrical worsening at completion. Secondary analyses will evaluate effects on hemodynamics, echocardiographic parameters, endogenous brain-type natriuretic peptide levels, modification of diet in renal disease–calculated glomerular filtration rate, and all-cause and cardiovascular mortality. Two mechanistic substudies will evaluate the effect on iohexol-determined glomerular filtration rate and assess changes in lung mechanics. Conclusion This investigation will provide key data for clinical profiles of heart transplant candidates bound to inotropic support. It will investigate the efficacy and safety (especially renal) of nesiritide and provide mechanistic insight into benefits of its use for the relief of breathlessness.

Objectives This study was designed to compare the safety and efficacy of veno-venous ultrafiltration and standard intravenous diuretic therapy for hypervolemic heart failure (HF) patients. Background Early ultrafiltration may be an alternative to intravenous diuretics in patients with decompensated HF and volume overload. Methods Patients hospitalized for HF with ≥2 signs of hypervolemia were randomized to ultrafiltration or intravenous diuretics. Primary end points were weight loss and dyspnea assessment at 48 h after randomization. Secondary end points included net fluid loss at 48 h, functional capacity, HF rehospitalizations, and unscheduled visits in 90 days. Safety end points included changes in renal function, electrolytes, and blood pressure. Results Two hundred patients (63 ± 15 years, 69% men, 71% ejection fraction ≤40%) were randomized to ultrafiltration or intravenous diuretics. At 48 h, weight (5.0 ± 3.1 kg vs. 3.1 ± 3.5 kg; p = 0.001) and net fluid loss (4.6 vs. 3.3 l; p = 0.001) were greater in the ultrafiltration group. Dyspnea scores were similar. At 90 days, the ultrafiltration group had fewer patients rehospitalized for HF (16 of 89 [18%] vs. 28 of 87 [32%]; p = 0.037), HF rehospitalizations (0.22 ± 0.54 vs. 0.46 ± 0.76; p = 0.022), rehospitalization days (1.4 ± 4.2 vs. 3.8 ± 8.5; p = 0.022) per patient, and unscheduled visits (14 of 65 [21%] vs. 29 of 66 [44%]; p = 0.009). No serum creatinine differences occurred between groups. Nine deaths occurred in the ultrafiltration group and 11 in the diuretics group. Conclusions In decompensated HF, ultrafiltration safely produces greater weight and fluid loss than intravenous diuretics, reduces 90-day resource utilization for HF, and is an effective alternative therapy. (The UNLOAD trial; http://clinicaltrials.gov/ct/show/NCT00124137?order=1; NCT00124137).

Heart failure (HF) is a growing global health concern that affects more than 20 million people worldwide. With an ever-growing segment of the population over the age of 65, the prevalence of HF and its associated costs are expected to increase exponentially over the next decade. Advances in the understanding of the pathophysiology and treatment of HF have resulted in the ability to enhance both the quantity and the quality of life of patients with HF. This article reviews the current understanding of the pathophysiology, cause, classification, and treatment of HF and describes areas of uncertainty that demand future study.

Mechanical assist devices have emerged as an established therapeutic option for patients with end-stage heart failure. Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (cf-LVAD) treatment is crucial for the identification of appropriate patients while excluding those considered futile. Previously developed scoring systems are limited to prior eras of device and medical support or restricted to specific devices. Methods: We performed a retrospective analysis of all patients implanted with a cf-LVAD (Heartmate II or HVAD) at our institution between 2005 and 2014. From all plausible pre-operative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1yr post implantation survival (p Results: A total of 204 patients (male 78%; mean age 57+15, mean follow up 465+486 days). After stepwise selection for variables that increased predictive power, a final optimized model was identified (Figure). One yr survival was significantly lower in patients with higher risk score (HR 2.48, p= Conclusion: We present a novel risk score and its validation for prediction of long-term survival in patients on cf-LVAD support. This score may prove useful for patient selection and identification of patients requiring adjuvant therapies

Background A 1.5‐day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's ( AHA's ) near‐term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. Methods and Results A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference. Presentation topics included updates on data as viewed from conventional medical and nonmedical sources, building and using Big Data repositories, articulation of the goals of data sharing, and principles of responsible data sharing. Facilitated breakout sessions were conducted to examine what each of the 7 stakeholder domains wants from Big Data under ideal circumstances and the possible roles that the AHA might play in meeting their needs. Important areas that are high priorities for further study regarding Big Data include a description of the methodology of how to acquire and analyze findings, validation of the veracity of discoveries from such research, and integration into investigative and clinical care aspects of future cardiovascular and stroke medicine. Potential roles that the AHA might consider include facilitating a standards discussion (eg, tools, methodology, and appropriate data use), providing education (eg, healthcare providers, patients, investigators), and helping build an interoperable digital ecosystem in cardiovascular and stroke science. Conclusion There was a consensus across stakeholder domains that Big Data holds great promise for revolutionizing the way cardiovascular and stroke research is conducted and clinical care is delivered; however, there is a clear need for the creation of a vision of how to use it to achieve the desired goals. Potential roles for the AHA center around facilitating a discussion of standards, providing education, and helping establish a cardiovascular digital ecosystem. This ecosystem should be interoperable and needs to interface with the rapidly growing digital object environment of the modern‐day healthcare system.

1.1 Document Development Process #### 1.1.1 Writing Committee Organization The Writing Committee was selected to represent the American College of Cardiology (ACC) and the Heart Failure Society of America (HFSA) and included a cardiovascular training program director, a heart failure

Heart failure (HF) is the most common cause for hospitalization among patients aged ≥65 years, affecting ≈6 million Americans; at 40 years, American men and women have a 1 in 5 lifetime risk of developing HF.1 There are 2 distinct HF phenotypes: a syndrome with normal or near-normal left ventricular ejection fraction (LVEF) referred to as HF with preserved EF (HFpEF)2 and the phenotype associated with poor cardiac contractility or HF with reduced EF (HFrEF). HFrEF is frequently caused by coronary artery disease with a male predominance; evidence-based strategies have been established for more than a decade. In contrast, the precise clinical criteria for HFpEF are not universally agreed on, the syndrome disproportionally affects women in 2:1 ratio, and there are no proven treatments.3–5 There are some commonalities between HFrEF and HFpEF in addition to the classic symptoms of breathlessness, edema, and fatigue: older age, diabetes mellitus, and a history of valvular disease are risk factors that are predictive of both clinical phenotypes.6 Risk factors associated with HFpEF include female sex, especially women with diabetes mellitus,7 higher body mass index, smoking, hypertension, concentric LV hypertrophy (LVH), and atrial fibrillation (AF).6,8,9 Risk factors associated with HFrEF include male sex, higher total cholesterol and heart rate, eccentric LVH, coronary artery disease, and left bundle-branch block.6,9 A remarkable lack of consensus exists with respect to the phenotypic characteristics of HFpEF, as evidenced by the divergent definitions of the European Study Group on Diastolic Heart Failure,10 the Framingham Group,11 and the European Society of Cardiology,12 to name just a few (Table).13 All include symptoms or signs but vary in specificity and a requirement for objective data. The definition of preserved LVEF is also inconsistent …