Abstract Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary ...pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF.
Abstract Background A subset of patients hospitalized with acute heart failure experience in-hospital worsening heart failure, defined as persistent or worsening signs or symptoms requiring an ...escalation of therapy. Methods and Results We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital worsening heart failure. Our definition of in-hospital worsening heart failure included events such as escalation of medical therapy (eg, inotropic medications) more than 12 hours after admission. We considered candidate risk prediction variables routinely assessed at admission, including age, medical history, biomarkers, and renal function. We used logistic regression with robust standard errors to generate a risk model in a 66% random derivation sample; we validated the model in the remaining 34%. We evaluated the calibration and discrimination of the model in both samples. We evaluated 23,696 patients hospitalized with acute heart failure. Baseline characteristics were well matched in the derivation and validation samples, and the occurrence of in-hospital worsening heart failure was similar in both samples (15.4% and 15.6%, respectively). In the multivariable model, the strongest predictors of in-hospital worsening heart failure were increased troponin and creatinine. The model was well calibrated and had good discrimination in the derivation sample ( c statistic, 0.74) and validation sample ( c statistic, 0.72). Conclusions The ADHERE worsening heart failure risk model is a clinical tool with good discrimination for use in patients hospitalized with acute heart failure to identify those at increased risk for in-hospital worsening heart failure. This tool may be useful to target treatment strategies for patients at high risk for in-hospital worsening heart failure.
Nearly 800,000 of the 1 million patients hospitalized with acute heart failure (AHF) every year are initially treated by emergency physicians. Signs and symptoms are typically most severe at initial ...presentation, but with timely diagnostic and therapeutic management, rapid improvement can be achieved. As a direct result, emergency physicians set the tone for initial AHF management. They dictate early treatment decisions and determine whether patients are admitted or discharged and, if admitted, what the appropriate initial level of care should be (ie, observation, telemetry, intensive care unit status). Despite this key role, the emergency department (ED) phase of management is often overlooked in AHF research and clinical trials. Consequently, present understanding of AHF patients early in their course is poor, and phenotypic characterization has been limited. As a result, the proportion of AHF patients eligible for a given therapeutic intervention is not well known. Moreover, because the traditional approach to AHF clinical trials has relied on cardiology-based research teams to identify patients up to 24 hours after ED presentation, patients admitted to noncardiology services are often missed, and those who are captured tend to be enrolled long after initial therapy has improved acute symptoms. This has resulted in low-enrollment heart failure clinical trials, which has been approximated at 0.41 patients per site per month. We describe the landscape of initial ED management, explain how this may confound clinical trial results, and provide a multidimensional template for successful ED/cardiology collaboration aimed at improving patient enrollment and the conduct of AHF clinical trials in the United States.
Abstract Background Clinical trials involving novel therapies treating acute heart failure syndromes (AHFS) have shown limited success with regard to both efficacy and safety. As a direct result, ...outcomes have changed little over time and AHFS remains a disease process associated with largely no change in hospitalization rates (80%), hospital length of stay (median 4.5 days), and in-hospital (4-7%) and 60-day mortality (10%). Despite extensive emergency department (ED) involvement during the initial phase of AHFS management, clinical trials have enrolled patients after the ED phase of management, up to 48 hours after initial therapy, long after many patients have experienced significant beneficial effects of standard therapy. As standard therapy has provided symptomatic improvement in up to 70% of patients in these trials, it is not surprising that investigational agents started after 24 to 48 hours of standard therapy have shown limited clinical efficacy when compared with standard therapy. Methods and Results The ability to screen, enroll, and randomize in the emergency setting is fundamental. The unique environment, the ethical complexities of enrollment in emergency-based research, and the need for rapid and standardized study-compliant care represent key challenges to active recruitment in AHFS studies. Specifically, the ability to identify and enroll a large cohort of AHFS patients early (<6 hours) in their presentation has been cited as the primary barrier to the appropriate design of clinical trials that includes this early window. Conclusions In response, we have created a network of dedicated academic physicians with experience in clinical trials and acute management of heart failure who together can surmount this barrier and provide a framework for conducting early trials in AHFS.
Abstract The BLAST-AHF (Biased Ligand of the Angiotensin Receptor Study in Acute Heart Failure) study is designed to test the efficacy and safety of TRV027, a novel biased ligand of the angiotensin-2 ...type 1 receptor, in patients with acute heart failure (AHF). AHF remains a major public health problem, and no currently-available therapies have been shown to favorably affect outcomes. TRV027 is a novel biased ligand of the angiotensin-2 type 1 receptor that antagonizes angiotensin-stimulated G-protein activation while stimulating β-arrestin. In animal models, these effects reduce afterload while increasing cardiac performance and maintaining stroke volume. In initial human studies, TRV027 appears to be hemodynamically active primarily in patients with activation of the renin-angiotensin-aldosterone system, a potentially attractive profile for an AHF therapeutic. BLAST-AHF is an international prospective, randomized, phase IIb, dose-ranging study that will randomize up to 500 AHF patients with systolic blood pressure ≥120 mm Hg and ≤200 mm Hg within 24 h of initial presentation to 1 of 3 doses of intravenous TRV027 (1, 5, or 25 mg/h) or matching placebo (1:1:1:1) for at least 48 h and up to 96 h. The primary endpoint is a composite of 5 clinical endpoints (dyspnea, worsening heart failure, length of hospital stay, 30-day rehospitalization, and 30-day mortality) combined using an average z-score. Secondary endpoints will include the assessment of dyspnea and change in amino-terminal pro–B-type natriuretic peptide. The BLAST-AHF study will assess the efficacy and safety of a novel biased ligand of the angiotensin-2 type 1 receptor in AHF.
Background Familial hypercholesterolemia (FH) is a dominantly inherited disorder characterized by high plasma cholesterol levels and a very high risk of early heart disease. The prevalence of FH is ...estimated to be at least 1:500, with at least 3.6 million individuals in the Asia-Pacific region. Objective To assess awareness, knowledge, and perception of FH among practicing physicians in Japan, South Korea, and Taiwan. Methods Physicians from 3 economically developed Asian countries were requested to anonymously complete a structured Internet-based survey regarding FH. This survey sought responses on the clinical description, inheritance, prevalence, cardiovascular disease risk, practices, and opinions on screening. Results Of 230 physicians surveyed, 47% were aware of the heritability, 27% of the prevalence, and 13% of the risk of cardiovascular disease relating to FH. The majority (70%) perceived themselves to have an above-moderate familiarity with FH. Primary care physicians (59%) and lipid specialists (41%) were perceived as the best providers for caring for FH, including cascade screening services, with a lesser role perceived for cardiologists, endocrinologists, and no significant role for nursing staff. Only 35% of physicians were aware of specialist clinical services for lipid disorders in their geographic area. Conclusion Extensive education and training programs are required to complement the implementation of region-specific models of care for FH in Asia. Further enhancement of existing lipid services and facilities are also warranted to optimise service models.
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