Heart Failure And A Reduced Ejection Fraction Research Articles

Medicines optimization prior to discharge in patients admitted to hospital with heart failure.

Approximately half of patients with heart failure and a reduced ejection fraction (HeFREF) are discharged from hospital on triple therapy [angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs)]. We investigated what proportion of patients are on optimal doses prior to discharge and how many might be eligible for initiation of sacubitril-valsartan or sodium-glucose co-transporter-2 inhibitors (SGLT2Is). Between 2012 and 2017, 1277 patients admitted with suspected heart failure were enrolled at a single hospital serving a local community around Kingston upon Hull, UK. Eligibility for sacubitril-valsartan or SGLT2I was based on entry criteria for the PIONEER-HF, DAPA-HF, and EMPEROR-Reduced trials. Four hundred fifty-five patients had HeFREF with complete data on renal function, heart rate, and systolic blood pressure (SBP) prior to discharge. Eighty-three per cent of patients were taking an ACE-I or ARB, 85% a BB, and 63% an MRA at discharge. More than 60% of patients were eligible for sacubitril-valsartan and >70% for SGLT2I. Among those not already receiving a prescription, 37%, 28%, and 49% were eligible to start ACE-I or ARB, BB, and MRA, respectively. Low SBP (≤105mmHg) was the most frequent explanation for failure to initiate or up-titrate therapy. Most patients admitted for heart failure are eligible for initiation of life-prolonging medications prior to discharge. A hospital admission may be a common missed opportunity to improve treatment for patients with HeFREF.

Primary prevention implantable cardioverter defibrillator in cardiac resynchronization therapy recipients with advanced chronic kidney disease.

The implantable cardioverter defibrillator (ICD) is effective for the prevention of sudden cardiac death (SCD) in patients with heart failure and a reduced ejection fraction (HFrEF). The benefit of the ICD in patients with advanced CKD, remains elusive. Moreover, the benefit of the ICD in patients with advanced chronic kidney disease (CKD) and HFrEF who are cardiac resynchronization therapy (CRT) recipients may be attenuated. We hypothesized that patients with CKD who are CRT recipients may derive less benefit from the ICD due to the competing risk of dying prior to experiencing an arrhythmia. The study population included 1,015 patients receiving CRT with defibrillator (CRT-D) device for primary prevention of SCD who were enrolled in either (Multicenter Automated Defibrillator Implantation Trial) MADIT-CRT trial or the Ranolazine in High-Risk Patients with Implanted Cardioverter Defibrillator (RAID) trial. The cohort was divided into two groups based on the stage of CKD: those with Stage 1 to 3a KD, labeled as (S1-S3a)KD. The second group included patients with Stage 3b to stage 5 kidney disease, labeled as (S3b-S5)KD. The primary endpoint was any ventricular tachycardia (VT) or ventricular fibrillation (VF) (Any VT/VF). The cumulative incidence of Any VT/VF was 23.5% in patients with (S1-S3a)KD and 12.6% in those with (S3b-S5)KD (p < 0.001) The incidence of Death without Any VT/VF was 6.6% in patients with (S1-S3a)KD and 21.6% in patients with (S3b-S5)KD (p < 0.001). A Fine and Gray multivariate competing risk regression model showed that Patients with (S3b-S5)KD had a 43% less risk of experiencing Any VT/VF when compared to those with (S1-S3a)KD (HR = 0.56, 95% CI [0.33-0.94] p = 0.03. After two years of follow up, there was almost a 5-fold increased risk of Death without Any VT/VF among patients with (S3b-S5)KD when compared to those with (S1-S3a)KD [HR = 4.63, 95% CI (2.46-8.72), p for interaction with time = 0.012]. Due to their lower incidence of arrhythmias and higher risk of dying prior to experiencing an arrhythmia, the benefit of the ICD may be attenuated in CRT recipients with advanced CKD. Future prospective trials should evaluate whether CRT without a defibrillator may be more appropriate for these patients.

Impact of SGLT2 Inhibitor Therapy on Right Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction

Background: The impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in addition to optimal medical therapy (OMT) on the right ventricular (RV) systolic function using advanced echocardiographic analysis among outpatients with heart failure and a reduced ejection fraction (HFrEF) has thus far been poorly investigated. Methods: This was a single-center, prospective, single-blinded study in which an echocardiographic expert was blinded to the allocation of the treatment. A total of 36 outpatients with HFrEF were randomized to either OMT or OMT+SGLT2i. Both groups underwent an echocardiographic examination of the RV systolic function at the baseline and at the 3-month follow-up (3mFU). Results: The patients in both groups did not significantly differ with respect to the relevant baseline comorbidities, therapy, and clinical characteristics. The patients receiving OMT+SGLT2i showed a significant improvement from the baseline to the 3mFU in all the measured RV echocardiographic parameters, while for the OMT group, a significant improvement after the 3mFU was observed for TAPSE and s'. The mean percent change from the baseline to the 3mFU was significant when comparing OMT+SGLT2i to the OMT group concerning RV FWS (+91% vs. +28%, p = 0.039), TR maxPG (-27% vs. +19%, p = 0.005), and TR Vmax (-17% vs. +13%, p = 0.008), respectively. Conclusions: Adding SGLT2i to OMT in patients with HFrEF resulted in a greater improvement in the RV systolic function from the baseline to the 3mFU compared to the OMT alone.

695 PRESCRIBING A COMPREHENSIVE THERAPY WITH THE FOUR FOUNDATIONAL TREATMENTS OF HEART FAILURE WITH REDUCED EJECTION FRACTION AMONG IN-PATIENTS AT DISCHARGE

Abstract Background Current guidelines recommend that patients with heart failure and a reduced ejection fraction (HFrEF) should receive four foundational treatments, i.e. renin-angiotensin system inhibitor (RASi) or angiotensin-receptor neprilysin inhibitor (ARNi), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i). There is emerging consensus that simultaneous initiation or rapid sequencing provide greater benefit, enhancing tolerability of these therapies and improving outcomes. However, implementation of a comprehensive approach is limited by common underuse and underdosing, and paucity of data exists on initiating the four pharmacological pillars of HFrEF during hospitalization or at discharge. Aim To investigate the feasibility of a comprehensive pharmacological approach in patients with HFrEF at discharge after an episode of heart failure (HF) hospitalization in a tertiary referral center. Methods In-patients with HFrEF and a first HF hospitalization (2019-2021) were categorized according to the number/type of treatments prescribed at discharge. Prevalence of contraindications and cautions for HFrEF treatments – as defined by current European Society of Cardiology (ESC) guidelines on HF – was as assessed. Logistic regression models were fitted to assess predictors of number of treatments prescribed and risk of re-hospitalization. Results Among 305 patients with HFrEF, 49.2% received at least two current recommended drugs. A β-blocker was prescribed in 93.4% of patients, and a RASi/ARNi in 68.2%. Based on current recommendations, 46.2% of patients could receive four foundational drugs. An MRA was prescribed in 32.5% of patients and 100% of patients did not show contraindications to MRA use. Renal dysfunction was present in 13.1% of patients, while hypotension in 11.8%. Bradycardia and renal dysfunction were associated with lower number of drugs prescribed [adjusted OR (95% CI) 0.18 (0.06-0.50), and 0.50 (0.39-0.64), respectively]. A higher number of drugs used was associated with no rehospitalization during the 30 days after discharge [OR (95% CI) 0.22 (0.10-0.49) per number of pillars increase]. Conclusions Based on the presence/absence of contraindications, a quadruple therapy could be implementable in a contemporary cohort of HFrEF in-patients at discharge. Renal dysfunction and bradycardia were the main prevalent conditions limiting the achievement of a more comprehensive therapeutic approach. Use of a higher number of drugs was associated with lower risk of re-hospitalization within 30 days after discharge.

Epidemiology of Worsening Heart Failure in a Population-based Cohort from Alberta, Canada: Evaluating Eligibility for Treatment With Vericiguat

BackgroundPatients with heart failure (HF) and a reduced ejection fraction (HFrEF) who experience worsening HF (WHF) events are at increased risk of adverse outcomes and experience significant morbidity and mortality. We herein describe the epidemiology of these patients and identify those potentially eligible for vericiguat therapy in this population-based study. Methods and ResultsThis retrospective cohort study included hospitalized or emergency department patients with a primary diagnosis of HF and a left ventricular ejection fraction (LVEF) of less than 45% diagnosed between April 1, 2009, and March 31, 2019 in Alberta, Canada, with follow-up to March 31, 2020. Inclusion criteria from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection (VICTORIA) trial were applied to explore eligibility for vericiguat. Among 25,629 patients with HF and LVEF data, 9948 (38.8%) had HFrEF, of which 5259 (52.8%) experienced WHF at some point during a median 5.8 years of follow-up, and 38.3% of those met the vericiguat trial eligibility criteria. Compared with patients with HFrEF without WHF, those with WHF were older, with more comorbidities, worse renal function, and similar LVEF status, but greater use of HF medications at baseline. At the time of WHF, 27% of those with HFrEF and WHF were on triple therapy, 50.6% were on dual therapy, and 15.4% were on monotherapy. All-cause mortality and the composite outcome of all-cause mortality or cardiovascular hospitalization at 1-year of follow-up were higher in the HFrEF with WHF cohort compared with HFrEF without WHF (adjusted hazard ratios of 1.92 and 1.51, respectively, both P < .0001). ConclusionsApproximately one-half of patients with HFrEF experienced WHF over the long-term follow-up. Most were not on triple therapy, highlighting the underuse of the existing standard-of-care treatments and opportunities for application of newer therapies; more than one-third of patients with HFrEF may be eligible for vericiguat. Lay SummaryAmong patients with heart failure (HF), those who experience worsening HF (WHF) are at increased risk of adverse outcomes. A few new therapies, including vericiguat, have emerged recently for patients with HF and reduced ejection fraction. However, the epidemiology, treatment patterns, and outcomes of patients with WHF in large representative populations is unclear. In the current study, approximately one-half of the patients with HF and reduced ejection fraction experienced WHF and 38.3% were potentially eligible for vericiguat therapy. The guideline-recommended therapies were under-utilized among patients with WHF, which highlights the need for initiatives to address this care gap.

The First Year of Noninvasive Remote Telemonitoring in Chronic Heart Failure Is not Cost Saving but Improves Quality of Life: The Randomized Controlled CardioBBEAT Trial.

Introduction: Remote telemonitoring (RTM) for patients with chronic heart failure (HF) holds promise to improve prognosis and well-being beyond the standard of care (SoC). The CardioBBEAT trial assessed the health economic and clinical impact of an interactive bidirectional RTM system (Motiva®) versus SoC for patients with HF and a reduced ejection fraction (HFrEF), in Germany. Methods: This multicenter, randomized controlled trial enrolled 621 patients with HFrEF (mean age 63.0 ± 11.5 years, 88% men). The primary endpoint was the integrated effect of the intervention on total costs and nonhospitalized days alive after 12 months, reported as incremental cost-effectiveness ratio (ICER). Costs (in k€) were based on actual charges of patients' statutory health insurance. Among secondary outcome measures were mortality and disease-specific quality of life. Results: We found a neutral effect on nonhospitalized days alive (RTM mean 341 ± 59 days, SoC 346 ± 45 days; p = 0.298) associated with increased total costs (RTM 18.5 ± 39.5 k€, SoC 12.8 ± 22.0 k€; p = 0.046). This yielded an ICER of -1.15 k€/day. RTM did not impact mortality risk. All quality of life scales were consistently and meaningfully improved in the RTM group at 12 months compared to SoC (all p < 0.01). Conclusions: The first 12 months of RTM were not cost-effective compared to SoC in patients with HFrEF, but associated with a relevant improvement in disease-specific quality of life. The balanced assessment of the potential benefit of RTM requires integration of both the societal and patient perspective. ClinTrials.gov (NCT02293252).

Do the Favorable Effects of Digoxin and SGLT2 Inhibitors Really Differ in Patients with Heart Failure and a Reduced Ejection Fraction? A Provocative Side-by-Side Examination of Trial Outcomes

In the 2021 heart failure guidelines from the European Society of Cardiology, there is a striking difference in the recommendations for the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and digoxin. SGLT2 inhibitors have a class IA recommendation, and their use is strongly advocated for all patients with heart failure and a reduced ejection fraction (HFrEF). In contrast, digoxin carries a class IIB recommendation that suggests its possible consideration in patients with HFrEF in sinus rhythm.

Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction.

ObjectiveRecent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality.MethodsFrom 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients.ResultsOf 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75–0.94, p = 0.002) for mortality and 0.85 (0.78–0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years.ConclusionsThis study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.Supplementary InformationThe online version of this article (10.1007/s12471-021-01591-6) contains supplementary material, which is available to authorized users.

When and How to Use Sodium-Glucose Cotransporter 2 Inhibitors in Patients With Heart Failure With Reduced Ejection Fraction or Chronic Kidney Disease

The role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in preventing heart failure (HF) in people with type 2 diabetes (T2DM) is now part of current treatment recommendations. Two large clinical trials (DAPA-HF and EMPEROR-Reduced) have recently highlighted the important impact of SGLT2 inhibitors in patients with HF and a reduced ejection fraction (HFrEF), with significant outcome benefits on HF hospitalisations and cardiovascular mortality, and similar effects in patients with and without T2DM. These benefits were observed on top of excellent background HF therapy, and there were no treatment interactions between SGLT2 inhibitors and background HF therapy. There were no increases in adverse events of interest in the SGLT2 inhibitor arm, including volume depletion, adverse renal events, hypoglycemia, amputation, and ketoacidosis, demonstrating the favourable safety profile of this treatment in HFrEF. Approximately 40%-50% of patients with HFrEF have chronic kidney disease (CKD), and the recently reported results of the DAPA-CKD trial indicate that dapagliflozin can prevent renal and cardiovascular outcomes in patients with established CKD, whether diabetes is present or not. Although the mechanisms of action of SGLT2 inhibitors are not fully understood, the hypotheses that have been proposed for their HF outcome benefits include a reduction of preload via osmotic diuresis, lowering of afterload, reduction in myocardial mass, alteration of myocardial energy substrate toward a more efficient glucose metabolism, modulation of renal sympathetic afferent tone, and increased erythropoiesis. We here present a summary of the evidence as well as a practical perspective on prescribing SGLT2 inhibitors in patients with HFrEF, with or without diabetes.

How Should We Sequence the Treatments for Heart Failure and a Reduced Ejection Fraction?: A Redefinition of Evidence-Based Medicine.

How Should We Sequence the Treatments for Heart Failure and a Reduced Ejection Fraction?: A Redefinition of Evidence-Based Medicine.

PCV6 Sacubitril/Valsartan and Its IMPACT on Sudden Death in Heart Failure Patients in Portugal

Sudden death is an important cause of death among patients with heart failure (HF) and a reduced ejection fraction (HFrEF), even in less symptomatic patients. We aimed to estimate the number of sudden deaths avoided with sacubitril/valsartan versus enalapril in a population of HF patients in Portugal. A Markov model calibrated with data from the PARADIGM-HF trial was used to describe HFrEF progression and associated outcomes, including sudden death. The model was adapted to the Portuguese reality based on the EPICA HF epidemiologic study. Drug discontinuation was not considered. Results are reported as sudden deaths estimated to be avoided following treatment with sacubitril/valsartan versus enalapril in a population of HF patients in Portugal. A 5-year time horizon was considered. By May 2020, a total of 13,076 HF patients were on treatment with sacubitril/valsartan in Portugal. For this population, assuming a mean age of 65 years and 56% women (based on the EPICA study), sacubitril/valsartan may potentially avoid 287 sudden deaths versus enalapril in a 5-year period of time. Out of this, 143 sudden deaths avoided are estimated to be among women. If assumed that the population of patients treated with sacubitril/valsartan is older (mean age of 70 years), 304 sudden deaths may potentially be avoided for the same time horizon. In this analysis, we estimate that sacubitril/valsartan may potentially avoid a substantial higher number of sudden deaths in HF patients than the current standard of care in Portugal. More awareness should be raised around the risk of sudden death in HF in order to maximize health outcomes.

SGLT2 inhibitors for heart failure with reduced ejection fraction: a real EMPEROR?

ABSTRACT Introduction: In individuals with type 2 diabetes mellitus, sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and serious adverse renal events, both in randomized controlled trials and observational studies. Areas covered: In this paper, the authors critically discuss the rationale, results, and implications of the recent placebo-controlled EMPEROR-Reduced trial [NCT03057977], which evaluated empagliflozin in subjects with chronic heart failure and a reduced ejection fraction (HFrEF), with or without diabetes. A parallel with the DAPA-HF trial, investigating dapagliflozin in a similar albeit not fully overlapping population, is also provided. The authors finally provide the reader with their expert perspectives. Expert opinion: EMPEROR-Reduced confirmed and extended the findings from DAPA-HF, especially on renal outcomes, thus strengthening the rationale for considering SGLT2 inhibitors among established treatments in HFrEF. Forthcoming guidelines supported by the knowledge of the clinical pharmacology of SGLT2 inhibitors will hopefully assist cardiologists, nephrologists, and general practitioners in selecting the target population and promoting safe prescribing.

Sodium-glucose cotransporter2 inhibitors: A drug with antidiabetic and cardioprotective properties.

Recently, two large double-blind randomized controlled trials testing the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with heart failure with and without diabetes have led to a paradigm shift for the indication of this class of drugs. Key clinical features and main results in these two studies are summarized in Table 1 and 2. The dapagliflozin and prevention of adverse outcomes in heart failure (DAPA-HF) trial included 4744 patients with heart failure and a reduced ejection fraction (HFrEF).

Tolerability, Safety, and Hemodynamics of Sacubitril-Valsartan in Acutely Decompensated Heart Failure Patients with Cardiogenic Shock

Introduction A recent randomized clinical study established the safety of the angiotensin receptor-neprilysin inhibitor (ARNI), sacubitril-valsartan (S/V), in patients hospitalized with acute decompensated heart failure after achieving hemodynamic stability. Transitioning patients in cardiogenic shock managed with pulmonary artery catheters directly from intravenous vasoactive (i.e. vasodilators or inotropes) drugs to S/V represents a potentially novel use for ARNIs. The tolerability and hemodynamic characteristics of S/V in patients with cardiogenic shock has not been previously established. Methods A single-center, retrospective analysis of all patients with heart failure and a reduced ejection fraction (HFrEF) (EF Results Twenty-two patients in the CICUs with HFrEF were started on S/V. The baseline characteristics, pertinent lab values, and hemodynamic profile (CI, SVR), are presented (Image 1). Ninety-five percent (n=21) of patients were on either of sodium nitroprusside, milrinone, dobutamine, or a combination these agents, at the time of initiation. Seventy-seven percent (n=17/22) patients were discharged on S/V with improved hemodynamics (Image 1,2). Hypotension was the most common reason for discontinuation (n=4) however one patient had both acute kidney injury and hypotension (n=1); no patients had hyperkalemia or death (n=0) (Image 2). Two of five intolerant patients were initiated on moderate (49-51) dose S/V. Conclusions The novel use S/V as oral vasodilator therapy in patients with cardiogenic shock shows favorable hemodynamic impact and tolerability. Long term tolerability and outcomes are required.

Baroreflex Activation Therapy (BAT) in Patients with Heart Failure and a Reduced Ejection Fraction (HFrEF): The BeAT-HF Trial

Baroreflex Activation Therapy (BAT) in Patients with Heart Failure and a Reduced Ejection Fraction (HFrEF): The BeAT-HF Trial

Clinical outcomes of Β-blocker therapy in cocaine-associated heart failure

BackgroundCocaine is associated with deleterious effects in the heart, including HFrEF. Although β-blockers are recommended for this condition in other populations, their use is discouraged in cocaine users due to the possibility of exacerbating cocaine-related cardiovascular complications. This study was designed to determine if patients with heart failure and a reduced ejection fraction (HFrEF) who continue to use cocaine have better outcomes when they receive β-blocker therapy than when they do not. MethodsWe performed a retrospective analysis of 72 β-blocker-naïve patients with HFrEF and active cocaine use. Patients who were prescribed β-blockers as part of their therapy were compared to those who were not, and clinical and structural outcomes were compared after 12 months of treatment. ResultsWhen patients with HFrEF and active cocaine use received β-blocker therapy, they were more likely to have an improvement in their New York Heart Association functional class (p = 0.0106) and left ventricular ejection fraction (p = 0.0031) than when they did not receive β-antagonists. In addition, the risk of cocaine-related cardiovascular events (p = 0.0086) and of heart failure hospitalizations (p = 0.0383) was significantly lower in patients who received β-blockade than those who did not. Conclusionsβ-Blocker therapy is associated with improvement in the exercise tolerance and the left ventricular ejection fraction in patients with HFrEF and active cocaine use. They are also associated with a lower incidence of cocaine-related cardiovascular events and HFrEF-related readmissions.

Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications

Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction.

Aliskiren alone or in combination with enalapril vs. enalapril among patients with chronic heart failure with and without diabetes: a subgroup analysis from the ATMOSPHERE trial.

Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes. ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril. At baseline, 1944 (27.7%) patients had diabetes. Median follow-up was shorter in patients with diabetes compared with those without (24 months vs. 46 months). Among patients with diabetes, the primary endpoint of cardiovascular death or hospitalization for heart failure occurred in 216 patients (33.1%) in the enalapril group (reference), 172 (27.4%) in the aliskiren group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67-1.00; P = 0.053], and 196 (29.5%) in the combination group (HR 0.86, 95% CI 0.71-1.04; P = 0.13). The effects of the treatments studied did not differ significantly compared with patients without diabetes. In patients with diabetes, aliskiren monotherapy was associated with a lower risk of symptomatic hypotension compared to enalapril [42 (6.7%) vs. 65 (10.0%); P = 0.04], whereas other adverse events were generally balanced between the three groups. In patients with HFrEF and diabetes, there was no signal of harm and a trend towards benefit when direct renin inhibition monotherapy was compared with an angiotensin-converting enzyme inhibitor, whereas combined aliskiren and enalapril treatment led to more adverse events with no improvement in outcomes. Treatment effects did not differ in patients with diabetes compared with those without. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658.

Treatment of heart failure in real-world clinical practice: findings from the REFLECT-HF registry in patients with NYHA class II symptoms and a reduced ejection fraction.

Optimal medical therapy (OMT) for patients with chronic heart failure and a reduced ejection fraction (HF-REF) includes angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, and mineralocorticoid receptor antagonists, plus a diuretic. We hypothesized that OMT is less often prescribed in HF-REF patients (≤35%) with New York Heart Association (NYHA) class II symptoms compared with those with NYHA class III/IV symptoms. This was a cross-sectional, observational, multicenter survey of hospital-based cardiologists, office-based cardiologists, and general practitioners in Germany. Out of a total of 384 patients enrolled, 144 had REF ≤35%. Patients with REF had NYHA class II symptoms in 39.6% (n = 57) and NYHA class III/IV symptoms in 60.4% (n = 87). The REF/NYHA class II group had a higher proportion of males than the REF/NYHA class III/IV group. For angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers, prescription rates were high and comparable between groups. However, prescription rates for mineralocorticoid receptor antagonists were lower compared with other guideline-recommended treatments. Multivariate analyses indicated that OMT prescription was reduced for older patients and increased for patients cared for by an office-based cardiologist. Given the high proportion of patients with reduced left ventricular systolic function but only minor symptoms, HF-REF appears to be underdiagnosed, and a higher proportion of patients than are currently recognized could potentially be candidates for OMT.

Circulation: Heart Failure Editors’ Picks

Summary : Lifelong exercise training maintains a youthful compliance of the left ventricle (LV), whereas a year of exercise training started later in life fails to reverse LV stiffening, possibly because of accumulation of irreversible advanced glycation end products. Alagebrium is a novel drug that breaks advanced glycation end product crosslinks and improves LV stiffness in aged animals. In this study, the authors prescribed alagebrium (200 mg daily) or placebo combined with aerobic exercise training or contact control in healthy, sedentary older individuals for 1 year. The authors evaluated overall cardiac function by the use of several modalities, including invasive pressure–volume measurements, exercise testing, and cardiac MRI before and after the training. To the authors’ knowledge, this is the first study to evaluate the effects of alagebrium and exercise training in healthy aged humans. After intervention, exercise training significantly increased exercise capacity, LV mass, and LV end-diastolic volume. Conversely, alagebrium had little effect on exercise capacity or LV geometry. However, alagebrium showed a modest improvement in LV stiffness compared with placebo. This favorable effect of alagebrium on LV stiffness was most prominent in individuals with combined alagebrium and exercise training. Conclusions : Alagebrium had no effect on hemodynamics, LV geometry, or exercise capacity in healthy, previously sedentary seniors. However, it did show a modestly favorable effect on age-associated LV stiffening.1 Summary : Maximum oxygen consumption (peak VO2) and efficiency of ventilation (VE) during exercise (VE/VCO2 slope) are known to stratify adults in heart failure for 1-year survival. On the basis of adult data, a recent American Heart Association scientific statement suggested that peak VO2<50% predicted for age and sex should be considered substantial impairment in exercise performance in children with heart disease and therefore a class I indication for heart transplant listing. This single-center study examined the association of …