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The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

Introduction: Effective management of ambulatory heart failure (HF) requires active patient (pt) participation. In telemonitoring of weights and symptoms, pt adherence to transmission is often halved within 6 months (M). Although ambulatory pulmonary pressure-guided management decreases hospitalizations and improves quality of life, the time course of pt perception of illness and sense of security in relation to monitoring frequency is not known. Hypothesis: Pts will perceive decreased impact of their HF during pulmonary pressure-guided management, which may contribute to their engagement in transmission of ambulatory PAP. Methods: The post-approval study for the implanted PA sensor was amended to include serial measurements of pt reported outcomes, (PRO, n=143), including the Brief Illness Perception Questionnaire (BIPQ). Treatment was adjusted to a target PA diastolic pressure 8 to 20 mmHg and adherence to transmitting pressure data from home was collected. Results: In the PRO cohort, mean age was 68 years, 58% were male, and 55% with HFpEF. Negative illness perception (BIPQ) decreased during each measurement interval. Pts reported improvement in symptoms, sense of security, sense of control and less impact of illness on their emotions at each time point, equally with HFpEF or HFrEF. In this cohort pt adherence to transmitting pressures was high throughout 24 M, Fig.1. Perception of illness was most favorable at 2 years, at which time there was a slight decline in transmission frequency. Conclusions: Pt perception of HF was positively impacted during ambulatory hemodynamic monitoring including improvement in symptoms, less emotional effect of illness, improved sense of security and control over their HF throughout follow-up. This was associated with high-level pt adherence to pressure data transmission. The optimal level of chronic monitoring for stable pts to maintain clinical benefit while minimizing disease awareness beyond 2 years is still unknown.

Article, see p 1671 Heart failure (HF) hospitalization presents a substantial burden to patients, hospitals, and payors. Hospitals face competing incentives from government payors because prolonged lengths of stay risk unreimbursed costs beyond the fixed reimbursement, whereas premature discharge increases the risk of 30-day readmission, for which hospitals can be penalized on a much broader scale. Clinicians have struggled to define the objective criteria regarding readiness for discharge from a HF hospitalization, which should address not only relief of congestion, but also evaluation of etiology, enhancement of guideline-directed therapies, review of disease trajectory, and consolidation of outpatient management. Once gaps in the transition process have been closed, the major cause of readmission is recurrent congestion. Regardless of how congestion is documented,1–3 patients who go home “wet” are likely to return “wetter”. Quality improvement and cost containment efforts are converging to design care pathways that begin early during hospitalization to ensure adequate decongestion by discharge. Employment of brain natriuretic peptide (BNP) levels as targets for therapy arose naturally from the robust predictive value of BNP levels and changes in levels, further supported by their close relationship with elevated cardiac filling pressures4,5 and recognized as a hemodynamic determinant of outcomes. Utility of a biomarker as a target for therapy requires not only clinical relevance, but also timely responsiveness to the therapy titration, and unique information beyond usual clinical assessments. Multiple trials have used natriuretic peptides as targets for adjustment of chronic outpatient therapy with neurohormonal antagonists6–10 (Figure). When uptitration was aggressive in response to persistently high levels of natriuretic peptides, outcomes were better than without such uptitration.9 However, when the design encouraged vigorous …

Background: Elevated pulmonary artery (PA) pressures in patients with heart failure are associated with a high risk for hospitalization and mortality. Recent clinical trial evidence demonstrated a direct relationship between lowering remotely monitored PA pressures and heart failure hospitalization risk reduction with a novel implantable PA pressure monitoring system (CardioMEMS HF System, St. Jude Medical). This study examines PA pressure changes in the first 2000 US patients implanted in general practice use. Methods: Deidentified data from the remote monitoring Merlin.net (St. Jude Medical) database were used to examine PA pressure trends from the first consecutive 2000 patients with at least 6 months of follow-up. Changes in PA pressures were evaluated with an area under the curve methodology to estimate the total sum increase or decrease in pressures (mm Hg-day) during the follow-up period relative to the baseline pressure. As a reference, the PA pressure trends were compared with the historic CHAMPION clinical trial (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association [NYHA] Functional Class III Heart Failure Patients). The area under the curve results are presented as mean±2 SE, and P values comparing the area under the curve of the general-use cohort with outcomes in the CHAMPION trial were computed by the t test with equal variance. Results: Patients were on average 70±12 years old; 60% were male; 34% had preserved ejection fraction; and patients were followed up for an average of 333±125 days. At implantation, the mean PA pressure for the general-use patients was 34.9±10.2 mm Hg compared with 31.3±10.9 mm Hg for CHAMPION treatment and 32.0±10.5 mm Hg for CHAMPION control groups. The general-use patients had an area under the curve of −32.8 mm Hg-day at the 1-month time mark, −156.2 mm Hg-day at the 3-month time mark, and −434.0 mm Hg-day after 6 months of hemodynamic guided care, which was significantly lower than the treatment group in the CHAMPION trial. Patients consistently transmitted pressure information with a median of 1.27 days between transmissions after 6 months. Conclusions: The first 2000 general-use patients managed with hemodynamic-guided heart failure care had higher PA pressures at baseline and experienced greater reduction in PA pressure over time compared with the pivotal CHAMPION clinical trial. These data demonstrate that general use of implantable hemodynamic technology in a nontrial setting leads to significant lowering of PA pressures.

Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0–6) after intervention. Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain ( P P P P Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01589120.

Most of the discussion after the passage of the 21st-Century Cures Act has focused on the law’s increased funding for biomedical research and its more controversial changes to drug and device approval. Little attention has been paid to the legislation’s changes to reimbursement for home infusion drugs. However, this less publicized aspect may ultimately limit patient access to home inotropic infusions, which are associated with decreased hospital admissions, lengths of hospital stay, and total spending for patients with advanced heart failure.1 The epidemiology of heart failure is changing and with it the epidemiology of home inotrope use. Patients are living longer with heart failure, now often not requiring advanced therapies, until they have become medically ineligible for ventricular assist devices or transplantation. At the same time, hospitals are facing increasing pressure to decrease lengths of stay and readmission rates. Home inotropic infusions can offer a practical solution to both challenges. As a result, the recent diffusion of home inotropic drugs, which include dobutamine or milrinone, has increased. Between 2010 and 2014, a 63% increase occurred in the number of beneficiaries receiving home milrinone and a 44% increase in the number receiving home dobutamine. As a result, in 2014, Medicare spent $243 million ($64 152 per beneficiary on average) for home milrinone, an increase of 55% …

Introduction: Advanced HF requires tremendous resources, and family caregivers generate significant health related cost-savings. Earlier work in the REVIVAL study demonstrated that increased baseline caregiver (CG) burden is associated with subjects exhibiting lower preference for ventricular assist device (VAD) therapy. Hypothesis: We examined whether 1) CG study participation and 2) CG burden predict combined outcome of death, VAD or UNOS 1 transplant in ambulatory advanced HF patients. Methods: We compared REVIVAL subjects with and w/o a participating CG, defined as a consented CG who completed at least one baseline quality of life (QOL) survey. Baseline characteristics were evaluated and the hazard ratio for CG vs. no CG for the combined outcome was determined by a Cox model. Results: Of 337 subjects, 95 (28%) identified participating CGs. CGs were 59 ± 14 yrs old, more commonly female (80%), a spouse/domestic partner (76%), and lived in the same home (86%). Subjects with a participating CG were older (62± 12 vs 59 ± 11 yrs, p=0.025). There were no differences in INTERMACS profile, NYHA class, HF risk scores, renal function or QOL. . Subjects without a participating CG were numerically more likely to experience the outcome of death, VAD or transplant by 1 year compared to those with a participating CG (26% vs. 17%), but the difference in event rate was not statistically significant (HR 1.65, CI 0.96-2.83, p=0.07). (Figure) There was no significant difference in primary endpoint based on CG burden or CG QOL as assessed by Oberst scale or EQ-5D index. Conclusions: In the REVIVAL study, less than one third of ambulatory advanced HF patients had a participating CG, raising the question of whether patients are more likely to progress to advanced HF if lacking a CG. Additionally, not having a participating CG may be related to worse HF outcomes. These data emphasize the need for larger studies to better understand the complex dynamics of the patient-caregiver dyad.

There was no specialty of heart failure (HF) 35 years ago. When therapies were minimally effective, most cardiologists were equally qualified to deliver them. In the early 1980s, improved outcomes with cyclosporine led to reimbursement for cardiac transplantation. Although performed in >120 000 patients, its major epidemiological contribution may have been concentration of HF at centers where physiology, team management, and therapies could be explored. As the impact of therapies has extended the HF journey (Figure1), further intervention to decrease disease progression may now be hindered by the term “heart failure” itself. Figure. Comparison of the patient journeys with heart failure (HF) in the era early after approval of cardiac transplantation and in the current era realizing the benefit of therapies that have decreased HF progression and decreased sudden death (red arrows). Blue shaded areas encompass patients with typical HF syndromes. Pink shaded area includes patients for whom a neutral label such as “cardiomyopathy” might encourage emphasis on therapy to prevent disease progression. ADHF indicates acute decompensated heart failure; EF, ejection fraction; and RV, right ventricular. Adapted from Udelson and Stevenson1 with permission. © 2016, American Heart Association, Inc. In the early era, most patients presented with class IV symptoms and died of pump failure or sudden death within a year without transplantation. All HF was assumed to be low-ejection-fraction HF, with congestion and hypoperfusion inseparable and inevitable. When therapy was limited to digitalis and diuretics to …

The emerging population of heart failure with improved ejection fraction, characterized in this issue of Circulation by Basuray et al1for 3 heart failure centers, testifies to the cumulative benefit of therapeutic advances during the past 30 years. The initial triage for referral to heart failure centers, many of which were launched with the approval of cyclosporine in 1984, was an assumed “less than six months to live,” derived from the classic Stanford experience in which most waiting transplant candidates who did not receive transplantation were dead within 6 months.2 Although the prognosis was not uniformly grim, most patients referred to transplant centers were dead within 1 to 2 years on the limited medical therapy of that time. Article see p 2380 The direct vasodilators hydralazine and nitrates were the first proven in a randomized trial to improve outcomes in any heart failure population.3 Angiotensin-converting enzyme inhibitors then were shown to improve outcomes in patients with myocardial infarction,4 asymptomatic and symptomatic chronic heart failure,5 and acute decompensated heart failure in hospital.6 In comparison with the hydralazine/nitrate regimens, the angiotensin-converting enzyme inhibitors offered superior survival benefit for New York Heart Association class I to II ambulatory patients, but outcomes were equivalent for class III.7 Benefit was subsequently shown in hospitalized class IV patients for captopril over hydralazine, when both were titrated to the same hemodynamic goals achieved on intravenous nitroprusside and diuretics, usually requiring the addition of oral nitrates to both.8 Increasing survival for the heart failure center referral population could soon be attributed to both the increasing use of angiotensin-converting enzyme inhibitors (ACEIs) and the diminished use of type I antiarrhythmic therapy,9 which was being replaced by amiodarone. During this time, experience was growing with β-blocker therapy, first used in Sweden …

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

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

Over the past 4 decades, patients with heart failure (HF) have derived substantial benefit from the major advances in our understanding of pathophysiology of the HF syndrome, which have led to evolving treatment paradigms. Morbidity and mortality for patients as documented in clinical trials for HF with reduced ejection fraction (HFrEF) have steadily decreased, and many patients with this syndrome have also enjoyed improved functional capacity and quality of life. However, there are major unmet needs. Hospital discharges with a primary HF diagnosis, an index of population disease burden and economic impact, remain >1 million annually with little change between 2000 and 2010.1 According to the American Heart Association’s Heart and Stroke Facts,2 the prevalence of HF will increase ≈50% between 2012 and 2030, resulting in >8 million people ≥18 years of age with HF.3 This daunting future reflects the increased prevalence of HF as the population ages, acute myocardial infarction survival improves, and HF survival itself increases at rates that exceed our impact to prevent the development of HF. The national and, indeed, international burden of HF reflects a growing component of HF with preserved ejection fraction (HFpEF), for which trials have been neutral, in contrast to the progress for HFrEF. These frustrating trial results reflect our incomplete understanding of the more heterogeneous complex of the HFpEF syndrome, which was only defined as an entity more recently. Knowledge in this area has evolved over the past few years, however, suggesting that positive results may be enabled by more targeted treatments rather than broad-brush interventions and a shift in focus to symptoms and daily quality of life as primary outcomes. In this review, we will use the lessons of the recent past to illuminate pathways forward in how the HF syndrome is conceptualized, how we might better …

Heart failure is the leading cause of hospitalization among adults >65 years of age in the United States. Annually, >1 million patients are hospitalized with a primary diagnosis of heart failure, accounting for a total Medicare expenditure exceeding $17 billion.1 Despite dramatic improvement in outcomes with medical therapy,2,3 admission rates following heart failure hospitalization remain high,4 with ≥50% patients readmitted to hospital within 6 months of discharge.5–7 Because reduction in readmission rates might simultaneously reduce costs and improve quality of care, public and private payers have increasingly targeted readmissions as a focus of pay-for-performance initiatives.8 In 2009, the US Center for Medicare & Medicaid Services began public reporting of all-cause readmission rates after heart failure hospitalization, and, in the following year, the Patient Protection and Affordable Care Act9 established financial penalties for hospitals with the highest readmission rates during the first 30 days after discharge. Increasing concern regarding the need to reduce readmissions has focused national research and hospital-driven efforts on the prediction of which patients with heart failure are likely to be readmitted and the design of interventions to prevent readmissions. Discharge from a heart failure hospitalization is followed by a readmission within 30 days in ≈24% of cases.5 Recurrent heart failure and related cardiovascular conditions account for only about half of readmissions in patients with heart failure, whereas other comorbid conditions account for the rest.10 Although the proportion of noncardiovascular admissions is higher in those with preserved ejection fraction (EF),11 overall readmission rates for heart failure remain similar whether the heart failure occurs with reduced or preserved EF.12 The rate and characteristics of readmission for patients with an initially low EF that recovers to ≥40% (heart failure with ‘better' EF) are yet to be …

The publication in this issue of Circulation of the Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure (ADVANCE) trial by Aaronson, Slaughter, and colleagues1 tracks continuing advance in the rapidly expanding field of mechanical circulatory support. As implantable device technology and the clinical learning curve have supported better outcomes over time, the journey is leaving the critically ill patients behind and moving into populations with less imminent risk of death, and will soon include more ambulatory patients for whom pivotal outcomes extend beyond stroke-free survival. The success of this trial stimulates questions about routes to new device approval, the length of our bridges, and the directions for travel beyond a bridge. Article see p 3191 The ADVANCE trial demonstrated that the new continuous flow centrifugal device serves as an effective bridge for patients awaiting a donor heart for transplantation.1 Previous devices approved for this indication include several configurations of pulsatile pumps and most recently a continuous flow axial pump. Approval for the bridging indication has required progressively more rigorous data but has never been supported by a randomized trial, because randomization to death or to device support is not reasonable in the face of progressive organ compromise and anticipated death from native heart collapse. Of the first 3 devices approved for the bridging indication, 2 offered no control population and 1 included a small historical control of patients in the same institutions who, for various reasons, did not receive a device.2,3 The present report raises the standard for bridging device approval, offering the first prospective comparison of outcomes with the new device with outcomes without it during the same time period, in this case with other devices currently available for left ventricular support. The control data population was …

Patients with heart failure and reduced ejection fraction account for about half of the 6 million patients with heart failure and the $35 billion spent annually on related medical costs. Over the past 25 years, heart failure management has evolved through randomized trials of specific therapy and the extensive clinical experience accumulated at referral centers, many of which arose initially to offer comprehensive medical care for patients in parallel with cardiac transplantation, as described by Fonarow et al in 1997.1 The recommended therapies have been the subject of extensive guidelines, from the first Agency for Health Care Policy and Research guidelines chaired by Konstam in 19942 to the most recent American College of Cardiology (ACC)/American Heart Association (AHA) guidelines chaired by Hunt in 20053 and updated by Jessup et al in 2009.4 Lessons from implementation of measures for acute myocardial infarction have translated into heart failure management, as described by O'Connor.5 Outcomes with heart failure have improved remarkably as these therapies have become widely implemented, and even disparities by race have begun to diminish, as underlined by Yancy et al6; however, the remaining burdens of readmission and mortality warrant ongoing efforts to further improve care for the diverse populations with heart failure. Article see p 585 The interventions of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) described in this issue of Circulation 7 successfully increased the number of therapies provided to patients with heart failure. Testing the impact of a strategy on practice is challenging, because the investigators cannot be blinded and are exposed to center effects, which may have played a role here. Simultaneous trends in continuing education and community practice also influence practice patterns over time. Data were collected by 34 …

The diversity of patient profiles and responses precludes a one-size-fits-all approach to heart failure. The randomized trials have provided us with some therapies that must be tried and others that can be tried. Offering significant although small benefits averaged over a population, these therapies are bolts of fabric stacked beside a tailor’s mannequin, the typical trial subject. The sequential patching of different medications in the order of their investigation, however, is not likely to yield the best regimen for any patient. There should be little disagreement on the principle of tailoring therapies for individuals, but what measurements should be taken? The primary goal for asymptomatic and mildly symptomatic heart failure is to prevent or delay disease progression. Once symptoms and the risk of mortality dominate, the goals are to relieve symptoms and prolong survival. It has been proposed that hemodynamic goals are not appropriate in the care of these patients with heart failure. To construct the clearest case to the contrary, this discussion will focus on patients with advanced heart failure as those in whom hemodynamic abnormalities are most apparent (although a case can also be made for contributions of early rises in intracardiac pressures, blunting of natriuretic peptide responses, fluid retention, and valvular regurgitation and disease progression). Advanced heart failure will be defined here in those patients with dilated ventricles and low ejection fraction who have persistent or recurrent symptoms limiting daily life (New York Heart Association class III and IV)1 despite initiation of angiotensin-converting enzyme inhibitors, β-blockers, and diuretics that may include spironolactone. Most patients will have had a prior hospitalization for heart failure. Therapy is currently outlined around a pattern from survival trial protocols. The regimen is then tailored further to symptoms and signs, which themselves often reflect hemodynamic changes in heart failure, although in most …

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or full revision is needed. This process gives priority to areas where major changes in text, particularly recommendations

Introduction: Standardized Clinical Assessment and Management Plans (SCAMPs) are a novel tool forthe prospective auditing of clinical outcomes and quality improvement in areas of practice variation. Using the SCAMP methodology to address heart failure (HF) discharges, two sites collaborated to investigate adherence to guideline-recommended achievement of optimal volume status and reasons for deviation in clinical practice. Methods: Consecutive patients hospitalized for chronic HF at a tertiary referral center (Brigham and Women’s Hospital, Boston MA, n=108, 55.3%) and community hospital with a dedicated heart failure program (Lancaster General Hospital, Lancaster PA, n=87, 44.6%) were enrolled in a HF SCAMP which recommended discharge only after complete decongestion (defined by jugular venous pressure Results: There were 195 patients enrolled. The average age at BWH was 64 years compared to 79 year at LGH. Overall, 57 (29%) patients had residual congestion at discharge, 37% of patients at BWH and 20% at LGH (p=0.01). However, the average weight change was -4.3kg at BWH and -3.8Kg at LGH. At BWH, the most common reason for inadequate decongestion was renal dysfunction (34% BWH vs. 6% LGH, p=0.04). At LGH, non-cardiac/chronic edema (“edema resistant”) was the most common reason (44% LGH vs. 17% BWH (p=0.08). Plan for continued diuresis at home was more common at LGH (LGH 19% vs. BWH 0%, p=0.03). At 90 days, 37% of congested patients and 23% of completely decongested patients had been readmitted (p=0.08). Conclusions: Nearly 1 in 3 patients admitted for worsening HF were discharged with residual congestion, which was more common at the tertiary care center and trended with higher readmission rates. The reasons for inadequate decongestion were different between sites.

Introduction: Clinical assessment of quality of life (QOL) is being increasingly adopted in the ambulatory management of heart failure (HF). Little is known about the impact of other conditions on QOL in clinical practice. Methods: Patients routinely presenting to the HF clinic completed a self-administered 1-page questionnaire prior to the visit that assessed QOL, functional status, and degree to which their HF, as well as other conditions, affected their QOL. Visual analog scales (VAS) were used to assess a) overall QOL, b) ease of breathing, and c) energy > fatigue. Scores ranged from 0 to 100 (higher scores representing better health status). Patients were asked if their QOL was affected more, equally, or less by their HF compared to other medical conditions. Data was analyzed with Pearson’s correlation coefficients, ANOVA and Chi-square tests. Results: A total of 1069 patients completed baseline QOL (mean age 57±16 years, 56% left ventricular ejection fraction [LVEF] ≥40%, 41% female). Mean QOL score was 63±28. Only 48% of patients felt that HF affected their QOL most while 20% felt HF was equal to other illnesses, 18% cited other medical problems and 14% non-medical problems as most important for their QOL. Patients reporting HF as the primary factor influencing QOL had significantly lower scores on all 3 VAS measures, the highest proportion of patients with low LVEF and the strongest correlation between QOL and VAS Breathing (R=0.68) (Table). Conclusions: Patients describing HF as their major limitation had the lowest QOL score and were most affected by dyspnea and fatigue. However, over half of ambulatory HF patients rate other medical and/or non-medical factors as equal or greater limitations to their QOL, suggesting this important clinical outcome will be difficult to impact by therapies targeted at HF alone, particularly in those with LVEF ≥40%.

Heart failure is estimated to affect 4 to 5 million Americans, with 550 000 new cases reported annually.1 In the past 3 decades, both the incidence and prevalence of heart failure have increased.1 2 3 Factors that have contributed to this increase are the aging US population and improved survival rates in patients with cardiovascular disease due to advancements in diagnostic techniques and medical and surgical therapies.2 4 5 6 Heart failure is a chronic, progressive disease that is characterized by frequent hospital admissions and ultimately high mortality rates. Because of its high medical resource consumption, heart failure is the most costly cardiovascular illness in the United States.7 Advances in the treatment of heart failure and early intervention to prevent decompensation may delay disease progression and improve survival. After initial evaluation, further diagnostic testing, and implementation of standard medical therapy, outpatient management strategies focus on maintenance of patient stability. Patient counseling/education, promotion of compliance, and discharge planning may further contribute to clinical stability and improved patient outcomes. A variety of outpatient heart failure management programs have been implemented during the past decade. These programs may also contribute to improved heart failure patient outcomes, including decreased symptoms, improved quality of life, reduced rates of hospital admission, and decreased healthcare costs. The purpose of the present report was to examine current heart failure management strategies and programs and to provide recommendations regarding (1) the use of an integrated approach to care through systematic assessment and management, (2) counseling and education of patients, (3) promotion of patient compliance with the treatment regimen, and (4) facilitation of hospital discharge/implementation of outpatient models of healthcare delivery. ### Pathophysiology and Definition of Heart Failure The syndrome of heart failure is a result of complex interactions among molecular, endocrine, and biodynamic systems. There are several pathophysiological mechanisms that are involved …

The ability to measure pressures within the heart has been one of the most important diagnostic and therapeutic tools within the cardiologist’s armamentarium over the past half century. Whereas this measurement initially required direct left ventricular puncture,1 transeptal catheterization,2 or retrograde placement of a catheter into the left ventricle, the advent of the Swan-Ganz catheter allowed for accurate estimation of left-sided filling pressures without requiring arterial or intraventricular access. These measurements have been useful to diagnose and treat hemodynamic compromise resulting from cardiac and pulmonary disease and other critical conditions associated with abnormal or unknown volume status. Article p 62 Accurate assessment of left-sided intracardiac filling pressures is particularly crucial for the management of chronic heart failure, in which congestion causes most of the disabling symptoms and hospitalizations.3 High left-sided filling pressures predict rehospitalizations and death, and the degree to which pressures can be reduced predicts survival.4 Skilled estimation of jugular venous pressure, particularly in conjunction with orthopnea, provides the most reliable clinical evidence of elevated left-sided filling pressures.5 However, the accuracy of jugular venous pressure for the detection of elevated right atrial pressure is

In Celtic mythology, there are pieces of ground considered to be “thin places” where the measured world comes closest to the infinite. Such places may have been set apart for burial grounds and other ritual sites. The Celtic phrase describing them derives from the Latin limen , a threshold or frontier where 2 countries meet (the root of “subliminal”).1 As physicians, we bear the privilege of escorting patients and families over the thin places. Krumholz and his colleagues2 have ventured to this border to provide valuable information as we ponder our responsibilities there. Once considered to be heroic, resuscitation has become routine. Communities are trained in CPR, defibrillators are on hand at many sporting events, and paramedics provide full advanced cardiac life support services in the home. The majority of patients admitted to hospitals seek survival, regardless of the severity of chronic illness. In 1 study, 90% of hospitalized patients expressed preference for resuscitation if their admission level of function could subsequently be restored.3 Of patients older than 55 years who had been discharged after an intensive care unit stay, 74% were certain that they would undergo another intensive care unit stay to prolong survival for as little as 1 month of additional life.4 In the current study, only 23% of patients stated that they did not wish resuscitation, and 40% of such patients subsequently changed their minds in favor of resuscitation. As patients live longer with chronic illness, death offers a welcome end to suffering for some, who should be allowed to take that journey unhindered. The majority of patients and their families appear to be anxious primarily to avoid prolonging a vegetative existence or dependency on mechanical ventilation.4 5 6 Fear of constant severe pain is also a common concern. The frequency of …

The demonstrated efficacy of implantable cardioverter-defibrillators (ICDs) for reducing sudden death in heart failure trial populations presents a critical challenge to those responsible for the allocation of healthcare resources.1–3 The current cost, multiplied by the prevalence of heart failure deemed high-risk, threatens to make this one enterprise the highest priced intervention for the Medicare population. The elegant cost-effectiveness analysis contributed by Dr Mark and colleagues from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) in this issue of Circulation provides an exemplary insight into this challenge.4 These investigators’ favorable conclusions are consistent with those from a meta-analysis by Sanders et al5 and with the slightly more conservative implications from the recent cost-effectiveness analysis of the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II by Zwanziger et al.6 Article p 135 This editorial will offer an alternative conclusion based on both back-of-the-envelope estimations and scrutiny of model assumptions regarding different phases of survival for heart failure populations. ICDs for primary prevention of sudden death in the heart failure population may be less cost-effective than other recommended heart failure therapies, which are prescribed to modify disease progression and symptoms, decreasing costly hospitalizations as well as mortality. Formal cost-effectiveness analysis is complex, but it may be illustrative to begin from simple considerations. A reasonable threshold for cost-effective intervention is often assigned as $40 000 per life-year saved, in line with the present article4 suggesting a cost of $38 389 per life-year saved and $41 530 per quality-adjusted life-year saved. This is approximately equal to the cost of the defibrillator device and implantation, as currently assessed for reimbursement. (The costs would be lower for the simpler device used in SCD-HeFT, which is not available now, and for outpatient implantation, which was common in SCD-HeFT but not the current standard.) This …

Background The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. Methods and Results At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months ( P P P P P =.08). Conclusions The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.

Shared decision making for advanced heart failure has become both more challenging and more crucial as duration of disease and treatment options have increased. High-quality decisions are chosen from medically reasonable options and are aligned with values, goals, and preferences of an informed patient. The top 10 things to know about decision making in advanced heart failure care are listed in Table 1. View this table: Table 1. Top Ten Things to Know Providers have an ethical and legal mandate to involve patients in medical decisions. Shared decision making recognizes that there are complex trade-offs in the choice of medical care.1 Shared decision making also addresses the ethical need to fully inform patients about the risks and benefits of treatments.2 In the setting of multiple reasonable options for medical care, shared decision making involves clinicians working with patients to ensure that patients' values, goals, and preferences guide informed decisions that are right for each individual patient. Grounded in the ethical principle of autonomy,3 judicial decisions (eg, Cruzan v Missouri Department of Health 4) and legislative actions (eg, the Patient Self-Determination Act5) have repeatedly affirmed the rights of patients or duly appointed surrogates to choose their medical therapy from among reasonable options.6 The formal process of informed consent before procedural interventions is an embodiment of this concept in that it underscores the clinician's obligation to ensure that the patient has the opportunity to be informed.3 An informed patient is one who is aware of the diagnosis and prognosis, the nature of the proposed intervention, the risks and benefits of that intervention, and all reasonable alternatives and their associated risks and benefits.7 A major purpose of a high-functioning healthcare system is to provide the resources with which an activated, informed patient can engage in productive discussions with a proactive, …

Almost 50 years ago, the National Heart, Lung, and Blood Institute launched the journey of mechanical circulatory support. These pioneers have included innovative engineers, cardiac surgeons, and stalwart patients accompanied by devoted families, who together have led us to a horizon where widespread clinical utilization is finally within sight. The pace of progress is always slower than projected. Despite our impatience, we should not rush too far beyond the light of the wagons onto terrain that is less hospitable to medical technological advances than it was 50 years ago. Since the approval of a continuous-flow destination device in January 2010, there has already been a 10-fold increase in the implantation of left ventricular assist devices (LVADs) for lifetime support, the major avenue for expansion of circulatory support. We would join advocates for more systematic evaluation of lifetime ventricular assist device (VAD) therapy in the patients listed with high priority for transplantation (a small population) and ambulatory patients with class IV symptoms (a population of unknown size and comorbidities). It is our position, however, that the current basis of evidence for selection and management of patients with LVAD does not support more aggressive acceleration of LVAD utilization than is already underway. After decades of painstaking incremental development, recent clinical progress has been rapid, with each device hailed as the breakthrough until overtaken by the next. The pulsatile Novacor (WorldHeart, Inc., Salt Lake City, UT) and Heartmate (Thoratec, Inc., Pleasanton, CA) devices were approved to keep people alive as a bridge to transplant without randomized comparison to medical therapy. The first and only randomized, controlled trial of an implantable circulatory support device compared with medical therapy was instead for lifetime support without transplantation; the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial with the pulsatile Heartmate …

Mariell Jessup, MD, FACC, FAHA, Chair [*][1] William T. Abraham, MD, FACC, FAHA[†][2] Donald E. Casey, MD, MPH, MBA[‡][3] Arthur M. Feldman, MD, PhD, FACC, FAHA[§][4] Gary S. Francis, MD, FACC, FAHA[§][4] Theodore G. Ganiats, MD[∥][5] Marvin A. Konstam, MD, FACC[¶][6] Donna M.

2009;53;1343-1382; originally published online Mar 26, 2009; J. Am. Coll. Cardiol. Rahko, Marc A. Silver, Lynne Warner Stevenson, and Clyde W. Yancy Francis, Theodore G. Ganiats, Marvin A. Konstam, Donna M. Mancini, Peter S. Mariell Jessup, William T. Abraham, Donald E. Casey, Arthur M. Feldman, Gary S. Heart and Lung Transplantation Developed in Collaboration With the International Society for Guidelines Cardiology Foundation/American Heart Association Task Force on Practice Management of Heart Failure in Adults: A Report of the American College of 2009 Focused Update: ACCF/AHA Guidelines for the Diagnosis and This information is current as of August 30, 2010 http://content.onlinejacc.org/cgi/content/full/53/15/1343 located on the World Wide Web at: The online version of this article, along with updated information and services, is

Advances in heart failure (HF) have prolonged survival but more patients (pts) die from HF than from any type of cancer. Quality of care improvement for HF has focused largely on initiation of life-saving treatments. Pts dying of HF were less likely to be supported by hospice and more likely to die in hospitals than pts with terminal cancer. Two end-of-life cohorts (HF and cancer) were identified using Medicare data. The HF cohort consisted of pts with 2 HF hospitalizations before cardiac death. The cancer cohort had registry-defined solid-organ cancer and death attributed to cancer. We assessed hospice use, ER visit, and acute hospitalization during 30 days prior to death and deaths in hospitals. Time trend and predictors of hospice use were also assessed. Among 7,930 HF pts with median age 82, 78% female and 5% black, 20% were referred to hospice compared to 51% in 7,565 cancer patients. The mean duration of hospice prior to death was longer with heart failure (68 for HF and 15 days for cancer). A modest rise in hospice use over time was parallel in the two groups. Acute care prior to death was higher for HF than cancer pts. (59 vs. 40% for ER visit and 62 vs. 45% for hospitalizations). More HF pts died in acute care hospitals than cancer pts (37 vs. 21%). Younger age, male gender, black race and dialysis therapy were associated with lower use of hospice in multivariate analyses. Although hospice use is increasing slowly over time, the contribution of hospice remains lower in HF, and more HF deaths occur in acute care settings. Further studies are needed to assess indications for hospice and acute care services in HF patients at the end of life.

Background— Approximately half of all patients with chronic heart failure (HF) have a decreased ejection fraction (EF) (systolic HF [SHF]); the other half have HF with a normal EF (diastolic HF [DHF]). However, the underlying pathophysiological differences between DHF and SHF patients are incompletely defined. The purpose of this study was to use echocardiographic and implantable hemodynamic monitor data to examine the pathophysiology of chronic compensated and acute decompensated HF in SHF versus DHF patients. Methods and Results— Patients were divided into 2 subgroups: 204 had EF P P P Conclusions— Significant structural and functional differences were found between patients with SHF and those with DHF; however, elevated diastolic pressures play a pivotal role in the underlying pathophysiology of chronic compensated and acute decompensated HF in both SHF and DHF.

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Table of Contents 1. Uses for HF Data Standards 1892 2. Balance Between Focus and Comprehensiveness 1893 3. Balance Between “Primary” and “Summary” Data Elements 1893 4. Variety of Disease States Leading to HF 1893 5. Acute and Chronic Care, Inpatient and Outpatient Care Venues 1893 6. Therapy for HF 1893 7. Outcomes Assessment for HF 1893 1. III. HF Clinical Data Standards Elements and Definitions 1893 The American College of Cardiology (ACC) and the American Heart Association (AHA) recognize …

What can we offer a 70-year-old retired schoolteacher hospitalized with congestion for the third time in 6 months? The LVEF is 21%. Shortness of breath interrupts sleeping and dressing, and peak oxygen consumption of 9 mL/kg per minute confirms NYHA Class IV status. He has noninsulin-dependent diabetes and chronic coronary artery disease, with patent grafts to thin-caliber vessels. His systolic blood pressure is 88 mm Hg and jugular venous pressure of 15 cm. Angiotensin-converting enzyme inhibitor (ACEI) and spironolactone were stopped during his last hospitalization because of progressive increase in serum creatinine to 3.8 mg/dL, currently 2.7, estimated clearance of 25 cc/min, and proteinuria. His regimen includes low doses of hydralazine and isosorbide dinitrate and digoxin, and he cannot tolerate beta-blockers. Although he is followed in an advanced heart failure management program, fluid retention has recurred despite torsemide 200 mg twice daily, intermittent metolazone, and compliance with 2-L fluid restriction, 2-g sodium diet, and daily weights. Serum sodium is 135 mEq/L, and B-type natriuretic protein (BNP) level is 1822 pg/mL. He expresses a willingness to try anything to feel better. This patient has recurrent heart failure despite having received the standard therapies known to improve outcome and clinical status.1 Renal dysfunction would preclude cardiac transplantation, which, in the setting of limited donor availability, would not often be offered to patients in this age group with major comorbidities. In patients with comprehensive home support, chronic inotropic infusion might be considered for palliation of end-stage symptoms, understanding that death is imminent and may be accelerated by inotropic therapy. For most patients with refractory “stage D” heart failure,2 the focus should shift toward comfort and planning with patient and family (Figure 1). Figure 1. Stream diagram demonstrating evaluation sequence for small number of patients not eligible for transplant but eligible for …

Background— Left ventricular assist devices (LVADs) have improved survival in patients with end-stage heart failure. Compared with previous trials, the Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure (REMATCH) trial enrolled patients with more advanced heart failure and high prevalence of intravenous inotropic therapy. This study analyzes, on a post hoc basis, outcomes in patients undergoing inotropic infusions at randomization. Methods and Results— Of 129 patients randomized, 91 were receiving intravenous inotropic therapy at randomization to LVAD or optimal medical management (OMM). Mean systolic pressure was 100 versus 107 mm Hg in those not receiving inotropes, serum sodium was 134 versus 137 mEq/L, and left ventricular ejection fraction was 17% for both groups. LVADs improved survival throughout follow-up for patients undergoing baseline inotropic infusions ( P =0.0014); for the LVAD group versus the OMM group, respectively, 6-month survival was 60% versus 39%, 1-year survival rates were 49% versus 24%, and 2-year survival rates were 28% versus 11%. For 38 patients not undergoing inotropic infusions, 6-month survival was 61% for those with LVADs and 67% for those with OMM, whereas 1-year rates were 57% and 40%, respectively ( P =0.55). Quality-of-life scores for survivors improved. Median days out of hospital for patients on inotropic therapy at randomization were 255 with LVAD and 105 with OMM. Conclusions— Despite severe compromise, patients undergoing inotropic infusions at randomization derived major LVAD survival benefit with improved quality of life. Patients not undergoing inotropic infusions had higher survival rates both with and without LVAD, but differences did not reach significance. Future studies should prespecify analyses of inotropic and other therapies to determine how disease severity and parallel medical treatment influence the benefits offered by mechanical circulatory support.

Application of mechanical cardiac support now requires consideration of a wider range of goals beyond bridging to transplantation to include destination therapy and perhaps bridging to recovery.1,2 Responsible dissemination of the technology requires identification of patient populations from which to select candidates most likely to benefit. At this early stage, benefit is most apparent against a high background mortality from end-stage heart failure. Heart failure affects an estimated 5 million patients in the United States. Of those, ≈60% have heart failure with left ventricular dilation and reduced ejection fraction. Trials demonstrating benefit of therapies for heart failure have focused primarily on mild–moderate heart failure with reduced ejection fraction, generally with annual mortality in the range of 8% to 18%.3 Advanced heart failure has been defined as symptoms limiting daily activity (New York Heart Association class III and IV) despite attempted therapy with angiotensin-converting enzyme inhibitors, β-blockers, digoxin, and diuretics,4 a description that applies to ≈300 000 to 800 000 patients in the United States. Although often labeled as “refractory,” many patients enjoy improved quality of life and decreased hospitalizations after referral to experienced heart failure centers, where aggressive medical strategies focus on relief of congestion. Surgical approaches include complex revascularization, valvular repair/replacement, or ventricular reconstruction. When technically successful, biventricular pacing can improve functional status for many of the 25% to 40% of patients with marked ventricular asynchrony.5 If early stabilization allows institution of β-adrenergic–blocking agents, prognosis is further improved.6 Dedicated heart failure management programs that facilitate patient education, compliance, and fluid balance have been integral to benefits observed with these therapies. The highest-risk heart failure populations are best identified after optimization of current therapies. Low left ventricular ejection fraction is not sufficient description of either function or prognosis once heart failure has become advanced. Neither …

Therapy with intravenous inotropic agents is most often initiated as short-term therapy during hospitalization to achieve one of several goals for acute management of decompensation, as described in part I of this report (Table).1 However, it may become difficult to wean these infusions in some patients as a heart failure progresses to late stages. View this table: Current Uses of Inotropic Agents in Heart Failure: Possible Trials ### Identification of Inotrope Dependence Many considered initially to be dependent on inotropic infusions can undergo successful weaning after complete diuresis of excess volume and careful adjustment of concomitant oral medications, which may be facilitated by hemodynamic monitoring to optimize loading conditions on oral agents.2,3 β-Adrenergic receptor antagonists would have been discontinued already in most cases. ACE inhibitors may need to be discontinued to maximize blood pressure and renal function, with addition of nitrates with or without hydralazine as needed for vasodilation. Dependence should not be declared until multiple interventions and weaning attempts have been made, in most cases requiring 2 to 3 weeks in the hospital, a systematic approach discussed by Hershberger et al.3 Although its magnitude can be debated, there is clearly a population of patients who are considered by experienced heart failure teams to be dependent on intravenous inotropic infusions despite multiple weaning attempts.4 It is assumed that such patients would not survive hospital discharge without ongoing inotropic support, although consensus has not been reached on exactly who they are. Dependence is most often manifested as symptomatic hypotension, recurrent congestive symptoms, or worsening renal function early after discontinuation of inotropic therapy. It should be emphasized that dependence for clinical purposes should be defined by limited clinical function, not by measured hemodynamic parameters, although these numbers have been required for Medicare coverage of home infusions in some states. For patients considered dependent, continuous inotropic …

Early descriptions of heart failure focused on the syndrome of congestion, an excess of the wet or melancholic humors, “dropsy,” or “backward” failure.1 Although associations with weak pulses and cool skin were also noted, more precise measurement of impaired contraction at the level of the heart and the myocyte itself later redefined heart failure as a malady of impaired forward function. Focus on forward failure was sharpened by dramatic initial responses to agents that stimulate contractility. However, the inability to sustain early improvements with inotropic agents was accompanied by increased mortality.2,3 Focusing instead on chronic responses, inhibition of the renin-angiotensin system and peripheral blockade of β-adrenergic receptors have been found over time to help preserve and in some cases improve contractility, decrease filling pressures, and prolong survival.4–6 These neurohormonal antagonists decrease the development and worsening of heart failure. In trial populations dominated by mild-moderate heart failure, the majority of patients with left ventricular dysfunction have preserved cardiac output at rest and are limited primarily by impaired volume regulation and diminished cardiac output responses to exercise. Despite the benefits of interventions for mild-moderate heart failure, it has remained a progressive disease. In the later stages of heart failure that lead to repeated hospitalization, resting flow decreases to vital organs, particularly the kidney. Inotropic therapy is frequently considered in hopes that either brief or prolonged stimulation of contractility to increase perfusion may help to restore compensation for a period of time. The decision to use inotropic therapy and the selection of inotropic agent should reflect the realistic goals of therapy for the individual with heart failure. The diversity of goals and settings has limited the performance of randomized controlled trials to establish evidence on which to base these therapies.7 Sharper focus on current practices and outcomes with inotropic …

Don’t be discouraged by the word failure. Your heart hasn’t failed to pump or stopped beating. Think of your heart as having a handicap that can be managed with the right treatments and lifestyle. There are at least 4 to 5 million people with heart failure in the United States, about half of whom are over 65. Many people with heart failure are able to lead active and satisfying lives. Success with heart failure depends on what you know and do to manage the handicap. Heart failure is a decreased ability of the heart to fill and empty. The major purpose of the heart is to circulate blood, which carries oxygen and nutrients to the body. In a normal heart, 50% to 70% of the blood in the pumping chambers is ejected out to the body with each contraction of the heart muscle. The normal heart has strength far beyond what we need every day. Even when the ejection fraction is low, the heart can often pump well enough for you to enjoy the usual activities in your life (Figure 1). Figure 1. Normal heart. Modified from Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine 5th ed. Philadelphia: Saunders; 1997. Anything that causes damage to the heart muscle can lead to heart failure. Damage can be caused by any of the following. Heart failure takes several different forms. In systolic …

Background During therapy to relieve congestion in advanced heart failure, cardiac filling pressures can frequently be reduced to near-normal levels with improved cardiac output. It is not known whether the early hemodynamic improvement and drug response can be maintained long term. Methods and Results After referral for cardiac transplantation with initially severe hemodynamic decompensation, 25 patients survived without transplantation to undergo hemodynamic reassessment after 8±6 months of treatment tailored to early hemodynamic response. Initial changes included net diuresis, increased ACE inhibitor doses, and frequent addition of nitrates. After 8 months of therapy, early reductions were sustained for pulmonary wedge pressure (24±9 to 15±5 mm Hg early; 12±6 mm Hg late) and systemic vascular resistance (1651±369 to 1207±281 dynes·s −1 ·cm −5 early; 1003±193 dynes·s −1 ·cm −5 late). Acute response to doses persisted at reevaluation. Sustained reduction in filling pressures was accompanied by a progressive increase in stroke volume (42±10 to 56±13 mL early; 79±20 mL late), improved functional class, and freedom from resting symptoms. Study design did not control for amiodarone, which was initiated for arrhythmias in 12 patients and associated with greater improvement in cardiac index (1.8 to 3.2 L·min −1 ·m −2 late on amiodarone versus 2.0 to 2.6 L·min −1 ·m −2 , P Conclusions During chronic therapy tailored to early hemodynamic response in advanced heart failure, acute vasodilator response persists, and near-normal filling pressures can be maintained in patients who survive without transplantation. Stroke volumes at low filling pressures increase further over time. Chronic hemodynamic improvement was accompanied by symptomatic improvement, but the contributions of the monitored hemodynamic approach, increased vasodilator doses, and comprehensive outpatient management have not yet been established.

Objective: To compare the efficacy and safety of nesiritide (B-type or brain natriuretic peptide [BNP]), IV nitroglycerin (NTG), and placebo (PL), when added to standard care (may have included IV diuretics, dobutamine, dopamine, and all chronic cardiac therapy). Methods: This multicenter, randomized, placebo- and active-controlled trial treated 489 hospitalized patients with dyspnea at rest due to acutely decompensated CHF. Patients with acute coronary syndromes, diastolic dysfunction, arrhythmias, or renal insufficiency were not excluded. …