Showing papers in "Jacc-Heart Failure in 2019"
TL;DR: A framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic "red flags" that can assist in its diagnosis among the wider population of patients with heart failure are proposed.
Abstract: Highlights •ATTR-CM is a life-threatening, progressive disease that is often underdiagnosed and misdiagnosed. •Certain clinical scenarios have been identified that now warrant screening for ATTR-CM. •Once ATTR-CM is suspected, a definitive diagnosis can usually be achieved noninvasively. •Accurate, early diagnosis of ATTR-CM is key to enabling appropriate patient care.
185 citations
TL;DR: Current knowledge of the pathophysiology of iron deficiency in heart failure, its prevalence and clinical impact, and its possible treatment options are highlighted.
Abstract: Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physic...
184 citations
TL;DR: The emerging role of catheter ablation relative to medical therapy in the management of heart failure with reduced ejection fraction is explored, along with indications for biventricular pacing modalities in cardiac resynchronization therapy.
Abstract: Highlights •Optimal treatment strategies for patients with HF and AF are unclear. •Current rate and rhythm control pharmacotherapies present challenges; however, randomized trials of catheter ablation have been promising. •Future research should focus on improving long-term outcomes in HF with AF and the effective primary prevention of HF in patients with AF.
148 citations
TL;DR: A more comprehensive approach to management is needed that targets deficits across multiple domains, including physical function and medical, cognitive, and social domains, to address the unique, multidimensional challenges to the care of these high-risk patients.
Abstract: Frailty, a syndrome characterized by an exaggerated decline in function and reserve of multiple physiological systems, is common in older patients with heart failure (HF) and is associated with worse clinical and patient-reported outcomes. Although several detailed assessment tools have been developed and validated in the geriatric population, they are cumbersome, not validated in patients with HF, and not commonly used in routine management of patients with HF. More recently, there has been an increasing interest in developing simple frailty screening tools that could efficiently and quickly identify frail patients with HF in routine clinical settings. As the burden and recognition of frailty in older patients with HF increase, a more comprehensive approach to management is needed that targets deficits across multiple domains, including physical function and medical, cognitive, and social domains. Such a multidomain approach is critical to address the unique, multidimensional challenges to the care of these high-risk patients and to improve their functional status, quality of life, and long-term clinical outcomes. This review discusses the burden of frailty, the conceptual underpinnings of frailty in older patients with HF, and potential strategies for the assessment, screening, and management of frailty in this vulnerable patient population.
142 citations
TL;DR: The emerging role of altered liver X receptor signaling in the pathogenesis of HF comorbidities as well as of the intestinal microbiome and its metabolites in HF and liver disease are fruitful areas for future research.
Abstract: Heart failure (HF) and liver disease often co-exist. This is because systemic disorders and diseases affect both organs (alcohol abuse, drugs, inflammation, autoimmunity, infections) and because of complex cardiohepatic interactions. The latter, which are the focus of this review, include the development of acute cardiogenic liver injury and congestive hepatopathy in HF as well as cardiac dysfunction and failure in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and sequelae following liver transplantation. The emerging role of altered liver X receptor signaling in the pathogenesis of HF comorbidities as well as of the intestinal microbiome and its metabolites in HF and liver disease are fruitful areas for future research.
139 citations
TL;DR: A systematic review and meta-analysis of exercise-based cardiac rehabilitation for heart failure supports the beneficial effects of ExCR on patient outcomes, and benefits appear to be consistent across ExCR program characteristics.
Abstract: Objectives This study performed a contemporary systematic review and meta-analysis of exercise-based cardiac rehabilitation (ExCR) for heart failure (HF). Background There is an increasing call for trials of models of ExCR for patients with HF that provide alternatives to conventional center-based provision and recruitment of patients that reflect a broader HF population. Methods The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PsycINFO databases were searched between January 2013 and January 2018. Randomized trials comparing patients undergoing ExCR to control patients not undergoing exercise were included. Study outcomes were pooled using meta-analysis. Metaregression examined potential effect modification according to ExCR program characteristics, and risk of bias, trial sequential analysis (TSA), and Grading of Recommendations Assessment Development and Evaluation (GRADE) were applied. Results Across 44 trials (n = 5,783; median follow-up of 6 months), compared with control subjects, ExCR did not reduce the risk of all-cause mortality (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.66 to 1.21; TSA-adjusted CI: 0.26 to 3.10) but did reduce all-cause hospitalization (RR: 0.70; 95% CI: 0.60 to 0.83; TSA-adjusted CI: 0.54 to 0.92) and HF-specific hospitalization (RR: 0.59; 95% CI: 0.42 to 0.84; TSA-adjusted CI: 0.14 for 2.46), and patients reported improved Minnesota Living with Heart Failure questionnaire overall scores (mean difference: −7.1; 95% CI: −10.5 to −3.7; TSA-adjusted CI: −13.2 to −1.0). No evidence of differential effects across different models of delivery, including center- versus home-based programs, were found. Conclusions This review supports the beneficial effects of ExCR on patient outcomes. These benefits appear to be consistent across ExCR program characteristics. GRADE and TSA assessments indicated that further high-quality randomized trials are needed.
130 citations
TL;DR: There is ample room for improvement of HFr EF therapy, even more than 25 years after convincing evidence that HFrEF treatment leads to better outcome, particularly in younger patients.
Abstract: Objectives This study investigated adherence to drug therapy guidelines in heart failure (HF) with reduced left-ventricular ejection fraction (LVEF) of Background Despite previous surveys of HF, important uncertainties remain regarding guideline adherence in a representative real-world population. Methods A cross-sectional registry in 34 Dutch HF outpatient clinics that included 10,910 patients with the diagnosis of HF was examined. Of that number, 8,360 patients had LVEF Results In the HFrEF group, 81% of the patients were treated with loop diuretics, 84% with renin-angiotensin-system (RAS) inhibitors, 86% with β-blockers, 56% with mineralocorticoid-receptor antagonists (MRA), and 5% with If-channel inhibition. Differences in medication use were minor among the 3 groups but were significant among centers. Inability to tolerate the medications was recorded in 9.4% patients taking RAS inhibitors, 3.3% taking β-blockers, and 5.4% taking MRAs. Median loop diuretic dose was 40 mg of furosemide equivalent, RAS inhibitor dose 50% of target, β-blocker dose 25% of target, and MRA dose 12.5 mg of spironolactone equivalent. Elderly patients were treated predominantly with diuretics and less often with RAS inhibitors, β-blockers, and MRAs. Conclusions This large contemporary HF registry showed a relatively high use of evidence-based treatment, particularly in younger patients. However, the average dose of evidence-based medication was still lower than recommended by guidelines. Furthermore, the more recently introduced If-channel inhibition has hardly been adopted. There is ample room for improvement of HFrEF therapy, even more than 25 years after convincing evidence that HFrEF treatment leads to better outcome.
123 citations
TL;DR: The interaction between spironolactone and sex in TOPCAT overall and in the present analysis was nonsignificant for the primary outcome, but there was a reduction in all-cause mortality associated with spironOLactone therapy in women, with a significant interaction between sex and treatment arm.
Abstract: Objectives This study sought to investigate sex differences in outcomes and responses to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF). Background HFpEF affects women more frequently than men. Sex differences in responses to effects of mineralocorticoid antagonists have not been reported. Methods This was an exploratory, post hoc, non-pre-specified analysis of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. Subjects with symptomatic HF and a left ventricular ejection fraction ≥45% were randomized to spironolactone or placebo therapy. Subjects enrolled from the Americas were analyzed. The primary outcome was a composite of cardiovascular (CV) death, cardiac arrest, or HF hospitalization. Secondary outcomes included all-cause mortality, CV, and non-CV mortality and CV, HF, and non-CV hospitalization. Sex differences in outcomes and treatment effects were determined using time-to-event analysis. Results In total, 882 of 1,767 subjects (49.9%) were women. Women were older with fewer comorbidities but worse patient-reported outcomes. There were no sex differences in outcomes in the placebo arm or in response to spironolactone for the primary outcome or its components. Spironolactone therapy was associated with reduced all-cause mortality in women (hazard ratio: 0.66; p = 0.01) but not in men (pinteraction = 0.02). Conclusions In TOPCAT, women and men presented with different clinical profiles and similar clinical outcomes. The interaction between spironolactone and sex in TOPCAT overall and in the present analysis was nonsignificant for the primary outcome, but there was a reduction in all-cause mortality associated with spironolactone therapy in women, with a significant interaction between sex and treatment arm. Prospective evaluation is needed to determine whether spironolactone therapy may be effective for treatment of HFpEF in women. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302)
117 citations
TL;DR: Standardized definition of remodeling and reliable tools to predict and monitor the presence, direction, and magnitude of cardiac remodeling are needed.
Abstract: In response to injury, hemodynamic changes, or neurohormonal activation, the heart undergoes a series of structural and functional changes that have been termed cardiac remodeling. Remodeling is defined as changes in cardiac geometry and/or function over time and can be measured in terms of changes in cardiac chamber dimensions, wall thickness, volumes, mass, and ejection fraction at serial imaging examinations. As to cardiac chambers, left ventricular (LV) remodeling has been best studied in patients with heart failure with reduced ejection fraction. Although LV remodeling may compensate for abnormal hemodynamic parameters and function in the short term, left unchecked, it is associated with worsening cardiac function and poor prognosis. On the other hand, reversing LV geometry and/or function closer to that of a normal heart (also known as reverse remodeling) is associated with improved cardiac function and better prognosis. Because of its close relationship with clinical outcomes, remodeling may potentially be targeted in clinical management and used in trials as a surrogate endpoint. Standardized definition of remodeling and reliable tools to predict and monitor the presence, direction, and magnitude of cardiac remodeling are needed. Together with clinical and imaging findings, circulating biomarkers (most notably N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin, and soluble suppression of tumorigenesis-2) may be helpful in this respect.
109 citations
TL;DR: EF change was associated with a wide range of important clinical, treatment, and organizational factors as well as with outcomes, particularly transitions to and from HFrEF.
Abstract: Objectives This study sought to evaluate the incidence, the predictors, and the associations with outcomes of changes in ejection fraction (EF) in heart failure (HF) patients. Background EF determines therapy in HF, but information is scarce about incidence, determinants, and prognostic implications of EF change over time. Methods Patients with ≥2 EF measurements registered in the Swedish Heart Failure Registry were categorized as heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with midrange ejection fraction (HFmrEF) (EF 40% to 49%), or heart failure with reduced ejection fraction (HFrEF) (EF Results Of 4,942 patients at baseline, 18% had HFpEF, 19% had HFmrEF, and 63% had HFrEF. During follow-up, 21% and 18% of HFpEF patients transitioned to HFmrEF and HFrEF, respectively; 37% and 25% of HFmrEF patients transitioned to HFrEF and HFpEF, respectively; and 16% and 10% of HFrEF patients transitioned to HFmrEF and HFpEF, respectively. Predictors of increased EF included female sex, cases of less severe HF, and comorbidities. Predictors of decreased EF included diabetes, ischemic heart disease, and cases of more severe HF. Use of renin-angiotensin-system inhibitors was associated with lower likelihood of EF increase, but not with EF decrease (i.e., stable EF). Increased EF was associated with a lower risk (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.55 to 0.69) and decreased EF with a higher risk (HR: 1.15; 95% CI: 1.01 to 1.30) of mortality and/or HF hospitalizations. Prognostic implications were most evident for transitions to and from HFrEF. Conclusions Increases in EF occurred in one-fourth of HFrEF and HFmrEF patients, and decreases occurred in more than one-third of patients with HFpEF and HFmrEF. EF change was associated with a wide range of important clinical and organizational factors as well as with outcomes, particularly transitions to and from HFrEF.
107 citations
TL;DR: Pulmonary congestion using a simplified 4-zone LUS method was common in patients with AHF and improved with therapy and the association between number of B-lines and short- and long-term outcomes persisted after adjusting for important clinical variables.
Abstract: Objectives This study sought to assess the prevalence, changes in, and prognostic importance of B-lines, a pulmonary congestion measure by using a simplified lung ultrasonography (LUS) method in acute heart failure (AHF). Background Pulmonary congestion is an important finding in AHF, but conventional methods for its detection are insensitive. Methods In a 2-site, prospective, observational study, 4-zone LUS was performed early during hospitalization for AHF (LUS1) and at discharge (LUS2). B-lines were quantified off-line, blinded to clinical findings and outcomes, by a core laboratory. Results Among 349 patients (median, 75 years of age; 59% men; mean ejection fraction 39%), the sum of B-lines in 4 zones ranged from 0 to 18 (LUS1). The risk of an adverse in-hospital event increased with rising number of B-lines on LUS1: the odds ratio for each B-line tertile was 1.82 (95% confidence interval [CI]: 1.14 to 2.88; p = 0.011). B-line count decreased from a median of 6 (LUS1) to 4 (LUS2; p Conclusions Pulmonary congestion using a simplified 4-zone LUS method was common in patients with AHF and improved with therapy. A higher number of B-lines at baseline and discharge identified patients at increased risk for adverse events.
TL;DR: There is an enduring need for using the teachable moment of HFr EF hospitalization for optimal initiation, continuation, and switching of GDMT to improve post-discharge patient outcomes and the quality of chronic HFrEF care.
Abstract: Patients with worsening heart failure with reduced ejection fraction (HFrEF) spend a large proportion of time in the hospital and other health care facilities. The benefits of guideline-directed medical therapy (GDMT) in the outpatient setting have been shown in large randomized controlled trials. However, the decision to initiate, continue, switch, or withdraw HFrEF medications in the inpatient setting is often based on multiple factors and subject to significant variability across providers. Based on available data, in well-selected, treatment-naive patients who are hemodynamically stable and clinically euvolemic after stabilization during hospitalization for HF, elements of GDMT can be safely initiated. Inpatient continuation of GDMT for HFrEF appears safe and well-tolerated in most hemodynamically stable patients. Hospitalization is also a potential time for switching from an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker to sacubitril/valsartan therapy in eligible patients, and is the subject of ongoing study. Therapy withdrawal or need for dose reduction is rarely required, but if needed identifies a particularly at-risk group of patients with progressive HF. If recurrent intolerance to neurohormonal blockers is observed, these patients should be evaluated for advanced HF therapies. There is an enduring need for using the teachable moment of HFrEF hospitalization for optimal initiation, continuation, and switching of GDMT to improve post-discharge patient outcomes and the quality of chronic HFrEF care.
TL;DR: The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral Regurgitation receiving optimal medical therapy.
Abstract: Objectives: This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling.Background: Functional mitral regurgitation (FM...
TL;DR: The potential applications of wearable devices in HF care are assessed, available data for wearables is summarized, and the future of wearables for improving the health of patients with HF is discussed.
Abstract: The adoption of mobile health (mHealth) devices is creating a unique opportunity to improve heart failure (HF) care. The rise of mHealth is driven by multiple factors including consumerism, policy changes in health care, and innovations in technology. Wearable health devices are one aspect of mHealth that may improve the delivery of HF care by allowing for medical data collection outside of a clinician's office or hospital. Wearable devices are externally applied and capture functional or physiological data in order to monitor and improve patients' health. Most wearable sensors capture data continuously and may be incorporated into accessories (e.g., a watch or clothing) or may be applied as a cutaneous patch. Wearable devices are often paired with another device, such as a smartphone, to collect, interpret, or transmit data. This study assessed the potential applications of wearable devices in HF care, summarizes available data for wearables, and discusses the future of wearables for improving the health of patients with HF.
TL;DR: The physiology of pericardial restraint in HF is discussed and the question of whether it can be targeted indirectly through medical interventions or directly through a number of existing and future therapies is explored.
Abstract: Highlights •The pericardium exerts a compressive contact force on the surface of the heart that becomes exaggerated in various forms of HF where cardiac volumes increase. •The resulting increase in pericardial restraint influences ventricular function and contributes to the hemodynamic changes that occur in HF, including the responses to vasodilation and decongestion with medical therapies. •The right atrial pressure is a reliable surrogate for pericardial pressure and provides a clinically relevant estimate of the degree of pericardial restraint. •A number of therapies in HF work in part through relief of relative pericardial restraint, and direct therapies including anterior pericardiotomy are undergoing investigation.
TL;DR: Males and females with HF showed different characteristics across the EF spectrum and reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF.
Abstract: Objectives This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum. Background Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials. Methods In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females. Results Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF. Conclusions Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.
TL;DR: Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies.
Abstract: Objectives The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial. Background Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy. Methods We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide. Results Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum–related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11). Conclusions Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255)
TL;DR: Frailty is common in CHF patients and is associated with increasing age, comorbidities, and severity of heart failure, and CFS had the highest sensitivity and specificity among screening tools and the lowest misclassification rate among all 6 frailty tools in identifying frailty according to the standard combined frailty index.
Abstract: Objectives: This study sought to report the prevalence of frailty, classification performance, and agreement among 3 frailty assessment tools and 3 screening tools in chronic heart failure (CHF) patients.
Background: Frailty is common in patients with CHF. There are many available frailty tools, but no standard method for evaluating frailty.
Methods: We used the following frailty screening tools: the clinical frailty scale (CFS); the Derby frailty index; and the acute frailty network frailty criteria. We used the following frailty assessment tools: the Fried criteria; the Edmonton frailty score; and the Deficit Index.
Results: A total of 467 consecutive ambulatory CHF patients (67% male; median age: 76 years; interquartile range [IQR]: 69 to 82 years; median N-terminal pro–B-type natriuretic peptide: 1,156 ng/l [IQR: 469 to 2,463 ng/l]) and 87 control patients (79% male; median age: 73 years (IQR: 69 to 77 years) were studied. The prevalence of frailty using the different tools was higher in CHF patients than in control patients (30% to 52% vs. 2% to 15%, respectively). Frail patients tended to be older, have worse symptoms, higher N-terminal pro–B-type natriuretic peptide levels, and more comorbidities. Of the screening tools, CFS had the strongest correlation and agreement with the assessment tools (correlation coefficient: 0.86 to 0.89, kappa coefficient: 0.65 to 0.72, depending on the frailty assessment tools, all p < 0.001). CFS had the highest sensitivity (87%) and specificity (89%) among screening tools and the lowest misclassification rate (12%) among all 6 frailty tools in identifying frailty according to the standard combined frailty index.
Conclusions: Frailty is common in CHF patients and is associated with increasing age, comorbidities, and severity of heart failure. CFS is a simple screening tool that identifies a similar group using more lengthy assessment tools.
TL;DR: Women with HFpEF demonstrate poorer diastolic reserve with higher echocardiographic and invasive measurements of left ventricular filling pressures at exercise, accompanied by lower systemic and pulmonary arterial compliance and poorer peripheral oxygen kinetics.
Abstract: Objectives This study sought to identify sex differences in central and peripheral factors that contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) by using complementary invasive hemodynamic and echocardiographic approaches. Background Women are overrepresented among patients with HFpEF, and there are established sex differences in myocardial structure and function. Exercise intolerance is a fundamental feature of HFpEF; however, sex differences in the physiological determinants of exercise capacity in HFpEF are yet to be established. Methods Patients with exertional intolerance with confirmed HFpEF were included in this study. Evaluation of the subjects included resting and exercise hemodynamics, echocardiography, and mixed venous blood gas sampling. Results A total of 161 subjects included 114 females (71%). Compared to males, females had a higher pulmonary capillary wedge pressure (PCWP) indexed to peak exercise workload (0.8 [0.5 to 1.2] mm Hg/W vs. 0.6 [0.4 to 1] mm Hg/W, respectively; p = 0.001) and lower systemic (1.1 [0.9 to 1.5] ml/mm Hg vs. 1 [0.7 to 1.2] ml/mm Hg, respectively; p = 0.019) and pulmonary (2.9 [2.2 to 4.2] ml/mm Hg vs. 2.4 [1.9 to 3] ml/mm Hg, respectively; p = 0.032) arterial compliance at exercise. Mixed venous blood gas analysis demonstrated a greater rise in lactate indexed to peak workload (0.05 [0.04 to 0.09] mmol/l/W vs. 0.04 [0.03 to 0.06] mmol/l/W, respectively; p = 0.007) in women compared to men. Women had higher mitral inflow velocity to diastolic mitral annular velocity at early filling (E/e′) ratios at rest and peak exercise, along with a higher ejection fraction and smaller ventricular dimensions. Conclusions Women with HFpEF demonstrate poorer diastolic reserve with higher echocardiographic and invasive measurements of left ventricular filling pressures at exercise, accompanied by lower systemic and pulmonary arterial compliance and poorer peripheral oxygen kinetics.
Brigham and Women's Hospital1, Novartis2, University of Minnesota3, Fudan University4, The George Institute for Global Health5, Baylor University Medical Center6, Charité7, Mayo Clinic8, Montreal Heart Institute9, University Medical Center Groningen10, University of Lorraine11, Medical University of South Carolina12, British Heart Foundation13, Harvard University14
TL;DR: The PARAGON-HF trial as discussed by the authors reported comprehensive baseline health-related quality of life (HRQL) using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period.
Abstract: Objectives This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with preserved ejection fraction (HFpEF) trial to date. Background There are limited data characterizing HRQL in patients with HFpEF using validated metrics. Methods The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to either sacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients Results In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p Conclusions HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF [PARAGON-HF] NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255)
TL;DR: Durable mechanical circulatory support with CF-LVADs remains underused in women, and when matched with similar male control subjects, women experienced higher mortality and lower rates of heart transplantation.
Abstract: Objectives This study examined sex-related differences in use and outcomes of continuous-flow left ventricular assist devices (CF-LVADs) among individuals awaiting heart transplantation using the United Network for Organ Sharing registry. Background Advanced therapies for heart failure including CF-LVADs remain underused in women. There have been contradictory results regarding sex-specific outcomes. Many studies have been limited by small sample sizes or included pulsatile-flow devices. Methods De-identified patient-level data were obtained from the United Network for Organ Sharing database. The database was queried to identify adult patients (≥18 years of age) who required mechanical circulatory support with HeartWare HVAD (Medtronic, Minneapolis, Minnesota), HeartMate II (Abbott, Lake Bluff, Illinois), or HeartMate 3 (Abbott) as bridge to heart transplantation between 2008 and 2018. Each patient was assigned a propensity score. The primary outcomes of interest were rates of transplantation and death. Results A total of 13,305 patients (2,771 women, 20.8%) received support with CF-LVAD in the study period. There were significant sex disparities in CF-LVAD use in listed patients (29.9% men vs. 18.9% women in 2017). Female patients receiving CF-LVAD support had lower chances of heart transplantation (55.1% vs. 67.5%), increased risk of waitlist mortality (7.0% vs. 4.2%), and delisting for worsening clinical status (8.5% vs. 4.7%) at 2 years post-implantation (all p Conclusions Durable mechanical circulatory support with CF-LVADs remains underused in women. When matched with similar male control subjects, women experienced higher mortality and lower rates of heart transplantation.
TL;DR: There are key differences between the clinical characteristics and multiorgan failure patterns in TC-CS compared to those in AMI-CS, which is associated with lower in-hospital mortality.
Abstract: Objectives This study sought to evaluate the clinical characteristics and outcomes of Takotusbo cardiomyopathy cardiogenic shock (TC-CS) in comparison to those of acute myocardial infarction cardiogenic shock (AMI-CS) among patients hospitalized in the United States. We additionally sought to compare the incidence of multiorgan failure and use of supportive therapies as well as the trends over time, given the increasing awareness and diagnosis of TC. Background CS is a major complication of TC; however, there are limited data, especially as to how TC-CS compares to AMI-CS. Methods The National Inpatient Sample Database was used to identify adults hospitalized with CS in the setting of TC and AMI from 2007 to 2014. We required patients admitted with TC to have undergone coronary angiography without intervention. Clinical characteristics and in-hospital outcomes in TC-CS patients were compared with those in AMI-CS patients. Multivariate regression and propensity matching were used to adjust for potential confounding factors. Results Between 2007 and 2014, there were 374,152 admissions for CS due to either TC or AMI, of which 4,614 patients (1.2%) had TC-CS. TC-CS admission patients were more likely to be younger, white females with fewer comorbidities. Rates of respiratory failure and mechanical ventilation were higher in TC-CS, but cardiac arrest and acute kidney injury were lower. There were no differences between cohorts in use of intra-aortic balloon pumps. TC-CS admissions had lower in-hospital mortality (15% vs. 37%, respectively) and hospital costs (U.S. dollars: $135,397 ± $127,617 vs. $154,827 ± $186,035, respectively) and were discharged home more often (45% vs. 36%, respectively) compared to AMI-CS admissions (all: p Conclusions There are key differences between the clinical characteristics and multiorgan failure patterns in TC-CS compared to those in AMI-CS. In-hospital mortality (15%) is lower in TC-CS.
TL;DR: The update analysis of patients discharged alive after TTS showed that long-term rates of overall mortality and recurrence were not trivial, and that some presenting features (older age, physical stressor, and atypical ballooning) were significantly associated with an unfavorable long- term prognosis.
Abstract: Objectives This study assessed the incidence of long-term adverse outcomes in patients with Takotsubo syndrome (TTS). Background The long-term prognosis of TTS is controversial. It is also unclear whether presenting characteristics are associated with the subsequent long-term prognosis. Methods We searched the PubMed, Embase, and Cochrane databases and reviewed cited references up to March 31, 2018, to identify studies with >6 months of follow-up data. Results Overall, we selected 54 studies that included a total of 4,679 patients (4,077 women and 602 men). Death during admission occurred in 112 patients (2.4%), yielding a frequency of 1.8% (95% confidence interval [CI]: 1.2% to 2.5%), with significant heterogeneity (I2 = 78%; p Conclusions Our update analysis of patients discharged alive after TTS showed that long-term rates of overall mortality and recurrence were not trivial, and that some presenting features (older age, physical stressor, and atypical ballooning) were significantly associated with an unfavorable long-term prognosis.
TL;DR: Among patients with heart failure with reduced ejection fraction, lowering NT-proBNP to <1,000 pg/ml by 12 months was associated with significant reverse remodeling and improved outcomes.
Abstract: Objectives: This study aims to assess the association between biomarker-guided therapy and left ventricular (LV) remodeling.Background: In patients with heart failure with reduced ejection ...
British Heart Foundation1, Copenhagen University Hospital2, University of Lorraine3, Ohio State University4, Brigham and Women's Hospital5, Stavanger University Hospital6, Baylor University Medical Center7, Montreal Heart Institute8, National Institutes of Health9, Medical University of South Carolina10
TL;DR: Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities.
Abstract: Objectives This study examined the relationship between income inequality and heart failure outcomes. Background The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes. Methods This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density. Results Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: 41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively. Conclusions Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.
TL;DR: Cardiac dysfunction is frequent in people living with HIV and there was evidence of lower prevalence of LVSD in studies published more recently, after taking into account the effect of regional variation.
Abstract: Objective To synthesize existing epidemiological data on cardiac dysfunction in HIV. Background Data on the burden and risk of human immunodeficiency virus (HIV) infection-associated cardiac dysfunction have not been adequately synthesized. We performed meta-analyses of extant literature on the frequency of several subtypes of cardiac dysfunction among people living with HIV. Methods We searched electronic databases and reference lists of review articles and combined the study-specific estimates using random-effects model meta-analyses. Heterogeneity was explored using subgroup analyses and meta-regressions. Results We included 63 reports from 54 studies comprising up to 125,382 adults with HIV infection and 12,655 cases of various cardiac dysfunctions. The pooled prevalence (95% confidence interval) was 12.3% (6.4% to 19.7%; 26 studies) for left ventricular systolic dysfunction (LVSD); 12.0% (7.6% to 17.2%; 17 studies) for dilated cardiomyopathy; 29.3% (22.6% to 36.5%; 20 studies) for grades I to III diastolic dysfunction; and 11.7% (8.5% to 15.3%; 11 studies) for grades II to III diastolic dysfunction. The pooled incidence and prevalence of clinical heart failure were 0.9 per 100 person-years (0.4 to 2.1 per 100 person-years; 4 studies) and 6.5% (4.4% to 9.6%; 8 studies), respectively. The combined prevalence of pulmonary hypertension and right ventricular dysfunction were 11.5% (5.5% to 19.2%; 14 studies) and 8.0% (5.2% to 11.2%; 10 studies), respectively. Significant heterogeneity was observed across studies for all the outcomes analyzed (I2 > 70%, p Conclusions Cardiac dysfunction is frequent in people living with HIV. Additional prospective studies are needed to better understand the burden and risk of various forms of cardiac dysfunction related to HIV and the associated mechanisms. (Cardiac dysfunction in people living with HIV–a systematic review and meta-analysis; CRD42018095374)
TL;DR: In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI, <20% of patients were receiving target doses of foundational guideline-directed medical therapy, even among those with SBP ≥110 mm Hg.
Abstract: Objectives This study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories. Background Patients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied. Methods Patients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs. Results Of the 3,095 patients eligible for analysis, 2,421 (78.2%) had SBP ≥110 mm Hg. The proportion of patients receiving target doses were 18.7% (95% CI: 17.3% to 20.0%; BB), 10.8% (95% CI: 9.7% to 11.9%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.5%; ARNI). Among those with SBP Conclusions In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI,
TL;DR: An up-to-date practical guide highlighting important elements for treatment initiation, dosing, anticipated adverse effects, and barriers to uptake of SGLT2 inhibitors is provided.
Abstract: The sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering therapies that have been shown to reduce risks of heart failure (HF) events in patients with type 2 diabetes mellitus (T2DM) at high-risk for or with cardiovascular disease. The United States Food and Drug Administration has expanded the regulatory label for empagliflozin and canagliflozin for use to lower cardiovascular risk in patients with T2DM and cardiovascular disease. SGLT2 inhibitors are being actively studied in the treatment of patients with HF, including in those without diabetes mellitus. Despite the accumulating data supporting this class of therapies in HF prevention, cardiologists infrequently prescribe SGLT2 inhibitors, potentially due to lack of familiarity with their use. We provide an up-to-date practical guide highlighting important elements for treatment initiation, dosing, anticipated adverse effects, and barriers to uptake.
TL;DR: Influenza infection is associated with increased in-hospital morbidity and mortality in patients with HF, and the need for efforts to mitigate the incidence of influenza, specifically in this high-risk patient cohort is emphasized.
Abstract: Objectives This study sought to determine whether influenza infection increases morbidity and mortality in patients hospitalized with heart failure (HF). Background Patients with HF may be at increased risk of morbidity and mortality from influenza infection. However, there are limited data for the associated hazards of influenza infection in HF patients. Methods We queried the 2013 to 2014 National Inpatient Sample database for all adult patients (18 years of age or older) admitted with HF with and without concomitant influenza infection. Propensity score matching was used to match patients across age, race, sex, and comorbidities. Outcomes included in-hospital mortality, in-hospital complications, length of stay, and average hospital costs. Results Of 8,189,119 all-cause hospitalizations in patients with HF, 54,590 (0.67%) had concomitant influenza infection. Patients with concomitant influenza had higher incidence of in-hospital mortality (6.2% vs. 5.4%, respectively; odds ratio [OR]: 1.15 [95% confidence interval [CI]: 1.03 to 1.30]; p = 0.02), acute respiratory failure (36.9% vs. 23.1%, respectively; OR: 1.95 [95% CI: 1.83 to 2.07]; p Conclusions Influenza infection is associated with increased in-hospital morbidity and mortality in patients with HF. Our results emphasize the need for efforts to mitigate the incidence of influenza, specifically in this high-risk patient cohort.
TL;DR: Therapeutic weight loss in obese patients without HF is associated with favorable hemodynamic effects, and randomized controlled trials evaluating strategies for weight loss for obese patients with heart failure such as the obese phenotype of heart failure with preserved ejection fraction are needed.
Abstract: Objectives The authors aimed to explore whether weight loss may improve central hemodynamics in obesity Background Hemodynamic abnormalities in obese heart failure with preserved ejection fraction patients are correlated with the amount of excess body mass, suggesting a possible causal relationship Methods Relevant databases were systematically searched from inception to May 2018, without language restriction Studies reporting invasive hemodynamic measures before and following therapeutic weight loss interventions in patients with obesity but no clinically overt heart failure were extracted Results A total of 9 studies were identified, providing data for 110 patients Six studies tested dietary intervention and 3 studies tested bariatric surgery Over a median duration of 97 months (range 075 to 230 months), a median weight loss of 43 kg (range 10 to 58 kg) was associated with significant reductions in heart rate (−9 beats/min, 95% confidence interval [CI]: −12 to −6; p Conclusions Therapeutic weight loss in obese patients without HF is associated with favorable hemodynamic effects Randomized controlled trials evaluating strategies for weight loss in obese patients with heart failure such as the obese phenotype of heart failure with preserved ejection fraction are needed