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.).

• MeSH
• kardiotonika škodlivé účinky   farmakologie   terapeutické užití   MeSH
• kardiovaskulární nemoci mortalita   MeSH
• kontrakce myokardu účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• močovina škodlivé účinky   analogy a deriváty   farmakologie   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční myosiny účinky léků   metabolismus   MeSH
• systolické srdeční selhání farmakoterapie   metabolismus   patofyziologie   MeSH
• tepový objem MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

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 being 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 (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure 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 <100 mmHg (n = 1127), estimated glomerular filtration rate <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.

• MeSH
• funkce levé komory srdeční účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• močovina analogy a deriváty   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• senioři MeSH
• srdeční selhání * farmakoterapie   patofyziologie   MeSH
• tepový objem účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

AIMS: To investigate the still uncertain independent prognostic impact of pulse pressure (PP) in acute heart failure (HF), in particular across the left ventricular ejection fraction (EF) phenotypes, and the potential contribution of PP in outlining the individual phenotypes. METHODS AND RESULTS: We prospectively evaluated 1-year death and rehospitalization in 4314 patients admitted for acute HF grouped by EF and stratified by their PP level on admission. In HF with reduced (< 40%) EF (HFrEF), the highest quartiles of PP had the lowest unadjusted [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98] and adjusted (HR 0.64 0.50-0.82) risk of 1 year all cause death compared to the lowest quartile. Its prognostic impact was partially mediated by systolic blood pressure (SBP). In HF with preserved (≥ 50%) EF (HFpEF), the intermediate quartile of PP showed the lowest 1 year all cause mortality in unadjusted (HR 0.598, CI 0.416-0.858) and adjusted (HR 0.55, 95% CI 0.388-0.801) models with no relationship with SBP. In a receiver operating characteristic analysis, a combination of PP > 60 mmHg and SBP > 140 mmHg was associated to a preserved EF with a high performance value. No prognostic significance of PP was found in the HF with mid-range EF subgroup. CONCLUSIONS: In acute HFrEF, there is an almost linear inverse relation between mortality and PP, partly mediated by SBP. In HFpEF, a J-shaped relationship between mortality and PP was present with a better prognosis at the nadir. A combination of PP > 60 mmHg with SBP > 140 mmHg may be clinically helpful as marker of a preserved left ventricular EF.

• MeSH
• arteria brachialis fyziologie   MeSH
• dysfunkce levé srdeční komory patofyziologie   MeSH
• krevní tlak fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• prospektivní studie MeSH
• registrace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční selhání * diagnóza   epidemiologie   mortalita   patofyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: The European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. METHODS AND RESULTS: The ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12 440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1 year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. CONCLUSION: The ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.

• MeSH
• akutní nemoc MeSH
• ambulantní péče MeSH
• chronická nemoc MeSH
• hospitalizace MeSH
• kardiologie MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita * MeSH
• následné studie MeSH
• příčina smrti MeSH
• prospektivní studie MeSH
• registrace * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• společnosti lékařské MeSH
• srdeční selhání krev   epidemiologie   patofyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

AIMS: Heart failure (HF) and dementia frequently coexist, but little is known about their types, relationships to each other and prognosis. The aims were to (i) describe patients with HF and dementia, assess (ii) the proportion of specific dementia disorders in types of HF based on ejection fraction and (iii) the prognostic role of types of HF and dementia disorders. METHODS AND RESULTS: The Swedish Heart Failure Registry (RiksSvikt) and The Swedish Dementia Registry (SveDem) were record-linked. Associations between dementia disorders and HF types were assessed with multinomial logistic regression and survival was investigated with Kaplan-Meier analysis and multivariable Cox regression. We studied 775 patients found in both registries (55% men, mean age 82 years). Ejection fraction was preserved in 38% of patients, reduced in 34%, and missing in 28%. The proportions of dementia disorders were similar across HF types. Vascular dementia was the most common dementia disorder (36%), followed by other dementias (28%), mixed dementia (20%), and Alzheimer disease (16%). Over a mean follow-up of 1.5 years, 76% of patients survived 1 year. We observed no significant differences in survival with regard to HF type (P = 0.2) or dementia disorder (P = 0.5). After adjustment for baseline covariates, neither HF types nor dementia disorders were independently associated with survival. CONCLUSIONS: Heart failure with preserved ejection fraction was the most common HF type and vascular dementia was the most common dementia disorder. The proportions of dementia disorders were similar across HF types. Neither HF types nor specific dementia disorders were associated with survival.

• MeSH
• Alzheimerova nemoc epidemiologie   MeSH
• lidé MeSH
• míra přežití MeSH
• registrace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční selhání mortalita   MeSH
• tepový objem fyziologie   MeSH
• vaskulární demence mortalita   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH