Influence of diabetes on sacubitril/valsartan titration and clinical outcomes in patients hospitalized for heart failure.

Diabetes mellitus is associated with worse outcomes and lower attainment of disease-modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co-morbidity. TRANSITION, a randomized, open-label study compared sacubitril/valsartan initiation pre-discharge vs. post-discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10-week and 26-week post-randomization. Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre-discharge or post-discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non-diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non-diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non-diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre-discharge or post-discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non-diabetes subgroups at 10 weeks, respectively: pre-discharge (7.5% vs. 7.1%) or post-discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT-proBNP (P < 0.005) and hs-TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non-diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non-diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks. Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up-titration and tolerability as in those without diabetes.The study was funded by Novartis Pharma AG, Basel,Switzerland.S

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Coexisting frailty with heart failure

Abstract People over 65 years of age constitute over 80% of patients with heart failure (HF) and the incidence of HF is 10 per 1,000 in people aged above 65 years. Approximately 25% of older patients with HF exhibit evidence of frailty. Frail patients with cardiovascular disease (CVD) have a worse prognosis than non-frail patients, and frailty is an independent risk factor for incident HF among older people. Planning the treatment of individuals with HF and concomitant frailty, one should consider not only the limitations imposed by frailty syndrome (FS) but also those associated with the underlying heart disease. It needs to be emphasized that all patients with HF and concomitant FS require individualized treatment

An expert opinion of the Heart Failure Association of the Polish Cardiac Society on the 2021 European Society of Cardiology guidelines for the diagnosis and treatment of acute and chronic heart failure: Heart failure guidelines from a national perspective

The Polish expert opinion of the Heart Failure Association of the Polish Cardiac Society on the 2021 European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of heart failure points to differences in many aspects related to heart failure in Poland compared with other European countries. These differences include population issues, epidemiology, diagnostic and treatment options, or the organization of healthcare. This expert opinion also includes a review of new results of clinical trials completed after the publication of the ESC guidelines

Initiation of sacubitril/valsartan shortly after hospitalisation for acutely decompensated heart failure in patients with newly diagnosed ( de novo

Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF.; TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12-1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF.; After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk-benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF.; ClinicalTrials.gov, NCT02661217

Characteristics, treatments and 1-year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long-Term Registry.

To describe the characteristics and assess the 1-year outcomes of hospitalized (HHF) and chronic (CHF) heart failure patients with chronic obstructive pulmonary disease (COPD) enrolled in a large European registry between May 2011 and April 2013. Overall, 1334/6920 (19.3%) HHF patients and 1322/9409 (14.1%) CHF patients were diagnosed with COPD. In both groups, patients with COPD were older, more frequently men, had a worse clinical presentation and a higher prevalence of co-morbidities. In HHF, the increase in the use of heart failure (HF) medications at hospital discharge was greater in non-COPD than in COPD for angiotensin-converting enzyme inhibitors (+13.7% vs. +7.2%), beta-blockers (+20.6% vs. +11.8%) and mineralocorticoid receptor antagonists (+20.9% vs. +17.3%), thus widening the gap in HF treatment already existing between the two groups at admission. In CHF patients, there was a similar increase in the use of these medications after enrollment visit in the two groups, leaving a significant difference of 8.2% for beta-blockers in favour of non-COPD patients (89.8% vs. 81.6%, P  COPD frequently coexists in HHF and CHF, worsens the clinical course of the disease, and significantly impacts its therapeutic management and prognosis. The matter should deserve greater attention from the cardiology community

Coordinated heart failure care in Poland: towards optimal organisation of the health care system

Heart failure has becoming an increasing medical, economic, and social problem globally. The prevalence of this syndrome is rising, and despite unequivocal positive effects of modern therapy, reduction of mortality has been achieved at the cost of more frequent hospitalisations. Unlike in many European countries, in Poland heart failure is usually recognised later, at a more advanced stage of the disease, leaving less time for ambulatory treatment and resulting in a high number of hospitalisations. The current paper presents the most important data regarding morbidity and mortality due to heart failure in Poland. The experts in the field focus on the key source of high costs of therapy and highlight several critical organisational deficits present in the Polish health care system. This background information builds a basis for a concept of coordinated care for patients with heart failure. The paper discusses the fundamental elements of the system of coordinated care for patients with heart failure necessary to enhance the diagnosis, improve therapeutic effects, and reduce medical, economic, and social costs.Heart failure has becoming an increasing medical, economic, and social problem globally. The prevalence of this syndrome is rising, and despite unequivocal positive effects of modern therapy, reduction of mortality has been achieved at the cost of more frequent hospitalisations. Unlike in many European countries, in Poland heart failure is usually recognised later, at a more advanced stage of the disease, leaving less time for ambulatory treatment and resulting in a high number of hospitalisations. The current paper presents the most important data regarding morbidity and mortality due to heart failure in Poland. The experts in the field focus on the key source of high costs of therapy and highlight several critical organisational deficits present in the Polish health care system. This background information builds a basis for a concept of coordinated care for patients with heart failure. The paper discusses the fundamental elements of the system of coordinated care for patients with heart failure necessary to enhance the diagnosis, improve therapeutic effects, and reduce medical, economic, and social costs

Advanced heart failure: a position statement of the Heart Failure Association of the European Society of Cardiology

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)