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Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group’s objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide., Central Illustration, Highlights • ICHOM seeks to help standardize and align outcome measurement efforts globally. • Standardization and alignment of this sort does not exist for heart failure. • The heart failure working group developed a standard set of 17 outcomes to be measured. • ICHOM hopes this standardization effort will increase quality and value in heart failure care.

Objectives: This study sought to determine clinician and scientist involvement in heart failure (HF) clinical research and to describe the challenges of conducting clinical trials in the Un...

Background and objectives The 2016 ISHLT guidelines recommend that patients listed for orthotopic heart transplantation (OHT) undergo periodic surveillance right heart catheterization (RHC) to re-assess hemodynamics (Class I, level of evidence C). However, the impact of RHC on management remains unclear. The aim of this study was to determine the utility of both surveillance and clinically prompted RHCs in patients listed for OHT. Methods A retrospective study was conducted in adult patients listed for OHT at our hospital from 2006 through 2014. Each patient included had at least one RHC after being listed for OHT. The primary outcome was management change: hospitalization, surgery (OHT or mechanical circulatory support [MCS]), change in United Network for Organ Sharing (UNOS) status, or initiation/modification of vasoactive drugs, diuretics or neurohormonal blockade. Results Of the 194 patients included, 85 (43%) patients had more than one RHC. The median time between listing and transplantation was 115 days. Of the 376 RHCs performed, 187 (50%) were prompted by a clinical change; 189 (50%) were performed for surveillance. In 90.4% of clinically prompted RHCs and 42.9% of surveillance RHCs, a clinically important management change was implemented. Initiation/modification of vasoactive drugs, placement of MCS and/or change in UNOS transplant status occurred in 61 (33%) of the clinically prompted RHCs and 26 (14%) of the surveillance RHCs. Patients who underwent management change were more likely to receive a heart transplant (HR 1.58; CI 1.15-2.18) without an increased rate of death over the study period compared to those who did not have a management change. Multivariable analysis revealed that a hemoglobin level 0.9 mg/dL (OR 5.07; CI 2.09-12.3) were predictors of management change. Conclusions In patients awaiting OHT, RHCs prompted by clinical instability or routine surveillance resulted in frequent management changes, including earlier heart transplant and MCS implant. Our study supports the Class I recommendation to perform surveillance RHC in patients listed for OHT and suggests that centers should consider maintaining a low threshold for repeat RHC during the formal waiting time.

The coronavirus-2019 (COVID-19) infection pandemic has affected the care of patients with heart failure (HF) who have contracted COVID-19 as well as those without COVID-19 who have been impacted by the restructuring of health care delivery. Patients with HF and other cardiovascular comorbidities are at risk for severe disease and complications of infection. Similarly, COVID-19 has been demonstrated to cause myocarditis and may be implicated in new-onset cardiomyopathy. During this pandemic, special considerations are needed for patients with advanced HF, including those supported by durable left ventricular assist devices (LVADs) and heart transplant recipients. The purpose of this review is to summarize emerging data regarding the development of HF secondary to COVID-19 infection in patients with advanced HF and the implications of the pandemic for care of uninfected patients with HF.

The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium‐glucose cotransporters sodium‐glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin‐angiotensin‐aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.

The current heart failure clinical trial environment is strained by increasing complexity and cost, regulatory requirements, competing demands on stakeholders, implementation challenges, and decreasing patient and investigator participation. To begin the process of developing potentially effective strategies and tactics, stakeholders including patients; investigators; academic leaders; pharmaceutical and device industry representatives; society representatives; third-party payers; and government representatives from the U.S. Food and Drug Administration, National Institutes of Health, and Centers for Medicare and Medicaid Services convened in March of 2017. This paper summarizes the discussions, outlines current challenges and actionable opportunities, and makes targeted recommendations to achieve the goals of improving efficiency in clinical trials and speeding the development of effective heart failure therapies, including the formation of an organized Heart Failure Collaboratory.

James L. Januzzi, Jr, MD, FACC, Chair Luis C. Afonso, MBBS, FACC Brendan Everett, MD, FACC Adrian F. Hernandez, MD, MHS, FACC William Hucker, MD, PhD Hani Jneid, MD, FACC Joseph Edward Marine, MD, FACC Pamela Bowe Morris, MD, FACC Robert N. Piana, MD, FACC Karol E. Watson, MD, FACC Dharam

Mechanical assist devices have emerged as an established therapeutic option for patients with end-stage heart failure. Because preimplant hypoalbuminemia is a known risk factor for adverse outcomes, we hypothesized that change in albumin may be a prognostic indicator in patients with continuous-flow left ventricular assist devices (cfLVADs). This is a retrospective single-center study of patients who underwent cfLVAD implantation (HeartMate II and HeartWare HVAD) at an academic center from 2008 to 2014. After excluding those who died, were transplanted, or hospitalized during the first 3 months post-implant, albumin values were obtained and stratified by an increase or a decrease from pre-implant to 3 months post-implant on 171 (81% male, mean age 57 ± 16 years) patients (139 for the survival analysis and 90 for the hospitalization analysis). Decrease in albumin from pre-implant to 3 months after implant correlated with increased mortality (hazard ratio 2.93, confidence interval 1.57 to 5.44, p 0.01) and reduced time to next hospitalization (hazard ratio 1.70, confidence interval 1.03 to 2.81, p = 0.04). The Kaplan-Meier survival curve estimated a 49.43% 2-year survival rate in those whose albumin decreased versus 83.62% in those whose albumin increased over 3 months (p 0.01). Improved outcomes were seen in patients whose albumin normalized versus patients whose albumin remained normal over 3 months. In conclusion, our study is the first to demonstrate the importance of change in albumin from pre- to postimplant on the prognosis of cfLVAD patients. Future studies are needed to determine whether therapeutic intervention to improve albumin post-implant will prevent hospitalizations and improve outcomes.

[Figure][1] Approximately 6.5 million Americans experience heart failure (HF), which contributes to 1 in 8 deaths each year [(1)][2]. Current therapies improve survival for HF with reduced ejection fraction, but a result has been to increase the number of HF patients who progress to

Glenn N. Levine, MD, FACC, FAHA, Chair Patrick T. O’Gara, MD, FACC, FAHA, Chair-Elect Jonathan L. Halperin, MD, FACC, FAHA, Immediate Past Chair [‡‡][1] Sana M. Al-Khatib, MD, MHS, FACC, FAHA Kim K. Birtcher, PharmD, MS, AACC Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD

PurposeCardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers.MethodsRecommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology.ResultsA total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.RecommendationsIt is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

More women than men currently live with heart failure (HF) in the United States [(1)][1]; this imbalance is projected to persist over the next decade [(2)][2]. Sex influences biologic drivers, etiologies, background epidemiology, markers of risk, and care quality in HF. To bolster enrollment of

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

© Springer-Verlag Berlin Heidelberg 2016, Background Acute heart failure (AHF) with reduced leftventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and inotropes on the right- and/or left-sided congestion is unknown. Methods and results A systematic review, meta-analysis, and meta-regression of AHF studies using pulmonary artery catheter were performed using PubMed, Embase, and Cochrane library. Data from 35 studies, including 3016 patients, were studied. Included patients had a weighted mean age of 60 years, left-ventricular ejection fraction (LVEF) of 24 %, and plasma B-type natriuretic peptide (BNP) of 892 pg/ml. Both the left- and right-ventricular filling pressures were elevated: weighted mean pulmonary artery wedge pressure (PAWP) was 25 mmHg (range 17–31 mmHg) and right atrial pressure (RAP) 12 mmHg (range 7–18 mmHg). Vasodilators and inotropes had similar beneficial effects on PAWP [-6.3 mmHg (95 % CI -7.4 to -5.2 mmHg) and -5.8 mmHg (95 % CI -7.6 to -4.0 mmHg), respectively] and RAP [-2.9 mmHg (95 % CI -3.8 to -2.1 mmHg) and -2.8 mmHg (95 % CI -3.8 to -1.7 mmHg), respectively]. Among inotropes, inodilators, such as levosimendan, have greater beneficial effect on the left-ventricular filling pressure than dobutamine. Drug-induced improvement of PAWP tightly paralleled that of RAP with all studied drugs (r 2 = 0.90, p\0.001). Vasodilators and inotropes had no short-term effect of renal function. Conclusion The left- and right-sided filling pressures are similarly improved by vasodilators or inotropes, in AHF with reduced LVEF.

Sudden cardiac death (SCD) is a common cause of death in the general population, occurring in 300,000 to 350,000 people in the United States alone. Currently, there are no data supporting implantable cardioverter-defibrillator therapy in patients who underwent orthotopic heart transplant (OHT) with low left ventricular ejection fraction (LVEF). In this retrospective study, we included all patients who underwent primary OHT at our institution from 2007 to 2013. We compared the cause of death in patients who underwent OHT and evaluated the correlation of the cause of death and the patients' LVEF. Our objectives were to determine whether patients who underwent OHT with LVEF35% are at increased risk for SCD compared with those who underwent OHT with normal LVEF. To summarize our results, a total of 345 patients were included in our study (mean age 50 ± 14 years, 68% men). The mean follow-up was 1,260 ± 698 days. Forty patients (11.5%) died6 months after OHT. Surviving patients had higher LVEF compared with deceased patients (64 ± 7% and 50 ± 24%, respectively, p ≤0.001). In all, 10 (25%) of the deceased patients died suddenly, 9 (23%) from sepsis, and 8 (20%) from malignancy. Of the 11 deceased patients with LVEF ≤35%, 2 patients (18%) died suddenly compared with 9 SCDs among the 29 deceased patients (31%) with LVEF35% (p = 0.54). In conclusion, patients who underwent OHT who died were more likely to have LVEF35%, and a quarter of the deceased patients who underwent OHT died suddenly. A reduced LVEF was not associated with an increased risk of SCD.

BACKGROUND: The role of physical activity in heart failure (HF) risk among older women is unclear, particularly for HF with preserved (HFpEF) or reduced (HFrEF) ejection fraction. OBJECTIVES: To prospectively examine physical activity levels and HF incidence in 137,303 women, ages 50–79 years, and in a subset of 35,272 of these women where HFpEF and HFrEF was determined. METHODS: Women were free of HF and reported ability to walk at least one block without assistance at baseline. Recreational physical activity was self-reported. We documented 2523 cases of total HF, and 451 and 734 cases of HFrEF and HFpEF, respectively, during a mean 14- year follow-up. RESULTS: Controlling for age, race, education, income, smoking, alcohol, hormone therapy and hysterectomy status, when compared to women reporting no physical activity, inverse associations were observed across incremental tertiles of total physical activity for overall HF (hazard ratio: 0.89, 0.74, 0.65, trend p

Background Predicting which patients are unlikely to benefit from continuous flow left ventricular assist device (LVAD) treatment is crucial for the identification of appropriate patients. Previously developed scoring systems are limited to past eras of device or restricted to specific devices. Our objective was to create a risk model for patients treated with continuous flow LVAD based on the preimplant variables. Methods and Results We performed a retrospective analysis of all patients implanted with a continuous flow LVAD between 2006 and 2014 at the University of Pennsylvania and included a total of 210 patients (male 78%; mean age, 56±15; mean follow‐up, 465±486 days). From all plausible preoperative covariates, we performed univariate Cox regression analysis for covariates affecting the odds of 1‐year survival following implantation ( P P =0.2. From this base model, we performed step‐wise forward and backward selection for other covariates that improved power by minimizing Akaike Information Criteria while maximizing the Harrell Concordance Index. We then used Kaplan–Meier curves, the log‐rank test, and Cox proportional hazard models to assess internal validity of the scoring system and its ability to stratify survival. A final optimized model was identified based on clinical and echocardiographic parameters preceding LVAD implantation. One‐year mortality was significantly higher in patients with higher risk scores (hazard ratio, 1.38; P =0.004). This hazard ratio represents the multiplied risk of death for every increase of 1 point in the risk score. The risk score was validated in a separate patient cohort of 260 patients at Columbia University, which confirmed the prognostic utility of this risk score ( P =0.0237). Conclusion We present a novel risk score and its validation for prediction of long‐term survival in patients with current types of continuous flow LVAD support.

Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisions—both in content and structure—including, most recently, …

Mechanical circulatory support (MCS) offers a surgical option for advanced heart failure when optimal medical therapy is inadequate. MCS therapy improves prognosis, functional status, and quality of life.1,2 The INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) tracks patient selection and outcomes for all implanted US Food and Drug Administration–approved MCS devices. From June 2006 until December 2014, >15 000 patients received MCS, and >2000 implantations are performed annually. One-year survival with current continuous-flow devices is reported to be 80%, and 2-year survival, 70%.3 In patients awaiting heart transplantation, MCS provides a bridge to transplantation, and for others who are ineligible for heart transplantation, MCS provides permanent support or destination therapy. Indications and absolute and relative contraindications to durable MCS are listed in Table 1. View this table: Table 1. Indications and Contraindications to Durable Mechanical Support As of July 2014, 158 centers in the United States offer long-term MCS.3 Patients often live a substantial distance from the implanting center, necessitating active involvement of local first responders (emergency medical technicians, police, and fire department personnel), emergency department staff, primary care, and referring cardiologists. Because patients with MCS are becoming increasingly mobile, basic knowledge of equipment is necessary for personnel in public areas such as schools, public transportation, and airplanes/airports. Ambulatory patients with MCS can span the entire age spectrum from pediatrics to geriatrics. The aim of this document is to provide guidance for nonexperts in MCS and to facilitate the informed assessment, stabilization, and transport of the patient with MCS back to the MCS center for definitive therapy. In addition, the principles herein provide a foundation for emergency management and a framework to address the management of known MCS-associated complications and expected comorbid medical problems. Currently in the United States, the most frequently used durable devices are continuous-flow devices with …

Background 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. Objective We aimed to characterize the representation of older patients, women, and racial and ethnic minorities in HF trials. Methods We performed a systematic search of HF trials published between January 2001 and December 2016 that enrolled over 400 participants using PubMed/MEDLINE and ClinicalTrials.gov. A total of 118 trials that cumulatively enrolled 215,508 subjects were included. Trial findings were compared with large epidemiological studies indexed to hospitalization status and ejection fraction. Results Median number of participants per trial was 994 (IQR 543-1899) enrolled from a median of 82 (IQR 28-171) sites. Overall, 94 (80%) of trials enrolled patients with HF with reduced ejection fraction (HFrEF) exclusively. Mean age of trial participants was 65±11 years and 27% were women; no significant temporal trends were observed (P≥0.60 for both, Figure). Chronic HF with preserved ejection fraction (HFpEF) trials enrolled older participants (mean age of 71±7 years compared to 65±11 year for HFrEF and 66±12 years for acute HF (AHF) trials (P=0.01). Corresponding average ages in US epidemiological studies were 69 years for HFrEF, and 73 year for both HFpEF and AHF patients. HFpEF trials had a higher proportion of women (56%) compared with HFrEF (24%), or AHF (32%), P Conclusion In contemporary HF trials, older patients and women are consistently underrepresented. Race/ethnicity data are reported in less than half of the trials; when reported, such data show that enrollment of non-White patients increased over time

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.

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.

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.

2016 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE AND CHRONIC HEART FAILURE. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.

ACC/AHA : American College of Cardiology/American Heart Association ACCF/AHA : American College of Cardiology Foundation/American Heart Association ACE : angiotensin-converting enzyme ACEI : angiotensin-converting enzyme inhibitor ACS : acute coronary syndrome AF : atrial fibrillation