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Background: Physicians' adherence to guideline-recommended therapy is associated with short-term clinical outcomes in heart failure (HF) with reduced ejection fraction (HFrEF). However, its impact on longer-term outcomes is poorly documented. Here, we present results from the 18-month follow-up of the QUALIFY registry.Methods and Results: Data at 18 months were available for 6118 ambulatory HFrEF patients from this international prospective observational survey. Adherence was measured as a continuous variable, ranging from 0 to 1, and was assessed for five classes of recommended HF medications and dosages. Most deaths were cardiovascular (CV) (228/394) and HF-related (191/394) and the same was true for unplanned hospitalizations (1175 CV and 861 HF-related hospitalizations, out of a total of 1541). According to univariable analysis, CV and HF deaths were significantly associated with physician adherence to guidelines. In multivariable analysis, HF death was associated with adherence level [subdistribution hazard ratio (SHR) 0.93, 95% confidence interval (CI) 0.87-0.99 per 0.1 unit adherence level increase; P = 0.034] as was composite of HF hospitalization or CV death (SHR 0.97, 95% CI 0.94-0.99 per 0.1 unit adherence level increase; P = 0.043), whereas unplanned all-cause, CV or HF hospitalizations were not (all-cause: SHR 0.99, 95% CI 0.9-1.02; CV: SHR 0.98, 95% CI 0.96-1.01; and HF: SHR 0.99, 95% CI 0.96-1.02 per 0.1 unit change in adherence score; P = 0.52, P = 0.2, and P = 0.4, respectively).Conclusion: These results suggest that physicians' adherence to guideline-recommended HF therapies is associated with improved outcomes in HFrEF. Practical strategies should be established to improve physicians' adherence to guidelines. [ABSTRACT FROM AUTHOR]

Aims: A network meta-analysis (NMA) of all recommended drug groups for the treatment of heart failure with reduced ejection fraction (HFrEF), including their combinations, was performed to assess the relative efficacy and incremental benefit.Methods and Results: A search was made in biomedical databases for randomized controlled trials published between 1987 and 2017 on angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers (BBs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs), ivabradine (IVA), or angiotensin receptor-neprilysin inhibitors (ARNI). A total of 58 relevant trials were identified. The relative efficacy of each treatment group (or combination) in terms of all-cause mortality, cardiovascular mortality, all-cause hospitalizations and hospitalizations for heart failure, per patient-year of follow-up, were combined in a random-effects Bayesian NMA. The pairwise comparison between each regimen and for each outcome was estimated. The NMA was dominated by 15 large-scale trials with between 1984 and 18 898 patient-years of follow-up. Combinations of drug groups showed incremental benefits on outcomes over single groups. The most effective combinations were ARNI+BB + MRA and ACEI+BB + MRA + IVA, showing reductions in all-cause mortality (vs. placebo) of 62% and 59%, respectively; hazard ratios were 0.38 [credible interval (CrI) 0.20-0.65] and 0.41 (CrI 0.21-0.70); and in all-cause hospitalizations with reductions of 42% for both. These two combinations were also the most effective for the other outcomes studied.Conclusion: Our analysis shows that the incremental use of combinations of disease-modifying therapies has resulted in the progressive improvement in mortality and hospitalization outcomes in HFrEF. Our findings support the current guideline recommendations. [ABSTRACT FROM AUTHOR]

Aims: In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization.Methods and Results: It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of ≤35%), in sinus rhythm, heart rate of ≥70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or ivabradine. Outcomes and the treatment effect of ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 ivabradine and 1459 placebo patients had HF duration of ≥4 weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF duration of ≥4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P < 0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P < 0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P < 0.0001); renal dysfunction: 31.5% vs. 21.5% (P < 0.0001); peripheral artery disease: 7.0% vs. 4.8% (P < 0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of ivabradine were independent of HF duration.Conclusions: Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials. [ABSTRACT FROM AUTHOR]

Aims In heart failure (HF) with reduced ejection fraction and sinus rhythm, heart rate reduction with ivabradine reduces the composite incidence of cardiovascular death and HF hospitalization. Methods and results It is unclear whether the duration of HF prior to therapy independently affects outcomes and whether it modifies the effect of heart rate reduction. In SHIFT, 6505 patients with chronic HF (left ventricular ejection fraction of =35%), in sinus rhythm, heart rate of =70 b.p.m., treated with guideline-recommended therapies, were randomized to placebo or ivabradine. Outcomes and the treatment effect of ivabradine in patients with different durations of HF were examined. Prior to randomization, 1416 ivabradine and 1459 placebo patients had HF duration of =4weeks and <1.5 years; 836 ivabradine and 806 placebo patients had HF duration of 1.5 years to <4 years, and 989 ivabradine and 999 placebo patients had HF duration of =4 years. Patients with longer duration of HF were older (62.5 years vs. 59.0 years; P <0.0001), had more severe disease (New York Heart Association classes III/IV in 56% vs. 44.9%; P <0.0001) and greater incidences of co-morbidities [myocardial infarction: 62.9% vs. 49.4% (P <0.0001); renal dysfunction: 31.5% vs. 21.5% (P <0.0001); peripheral artery disease: 7.0% vs. 4.8% (P <0.0001)] compared with patients with a more recent diagnosis. After adjustments, longer HF duration was independently associated with poorer outcome. Effects of ivabradine were independent of HF duration. Conclusions Duration of HF predicts outcome independently of risk indicators such as higher age, greater severity and more co-morbidities. Heart rate reduction with ivabradine improved outcomes independently of HF duration. Thus, HF treatments should be initiated early and it is important to characterize HF populations according to the chronicity of HF in future trials. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the impact of physicians' adherence to guideline-recommended medications for heart failure with reduced ejection fraction (HFrEF), including ≥50% prescription of recommended doses, on clinical outcomes at 6-month follow-up.Methods and Results: In QUALIFY, an international, prospective, observational, longitudinal survey, 6669 outpatients with HFrEF were recruited 1-15 months after heart failure (HF) hospitalization from September 2013 to December 2014 in 36 countries and followed up at 6 months. A global adherence to guidelines score was developed for prescription of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs) and ivabradine and their dosages. Baseline global adherence score was good in 23% of patients, moderate in 55%, and poor in 22%. At 6-month follow-up, poor adherence was associated with significantly higher overall mortality [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.42-3.44, P=0.001], cardiovascular mortality (HR 2.27, 95% CI 1.36-3.77, P=0.003), HF mortality (HR 2.26, 95% CI 1.21-4.2, P=0.032), combined HF hospitalization or HF death (HR 1.26, 95% CI 1.08-1.71, P=0.024) and cardiovascular hospitalization or cardiovascular death (HR 1.35, 95% CI 1.08-1.69, P=0.013). There was a strong trend between poor adherence and HF hospitalization (HR 1.32, 95% CI 1.04-1.68, P=0.069).Conclusion: Good adherence to pharmacologic treatment guidelines for ACEIs, ARBs, BBs, MRAs and ivabradine, with prescription of at least 50% of recommended dosages, was associated with better clinical outcomes during 6-month follow-up. Continuing global educational initiatives are needed to emphasise the importance of guideline recommendations for optimising drug therapy and prescribing evidence-based doses in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: This randomized, double-blind, placebo-controlled trial assessed whether heart rate (HR) reduction with ivabradine improves cardiac function in heart failure with preserved ejection fraction (HFpEF).Methods and Results: The prEserveD left ventricular ejectIon fraction chronic heart Failure with ivabradine studY (EDIFY) included 179 patients in New York Heart Association (NYHA) classes II and III, in sinus rhythm, with HR of ≥70 b.p.m., NT-proBNP of ≥220 pg/mL (BNP ≥80 pg/mL) and left ventricular ejection fraction of ≥45%. Ivabradine (or placebo) was titrated to 7.5 mg b.i.d. Patients were followed for 8 months on the change and assessed for three co-primary endpoints: echo-Doppler E/e' ratio, distance on the 6-min walking test (6MWT), and plasma NT-proBNP concentration. At baseline, median E/e' was 12.8 [interquartile range (IQR): 9.9-16.3], median distance on the 6MWT was 320 m (IQR: 247-375 m), and median NT-proBNP was 375 pg/mL (IQR: 253-701 pg/mL). Baseline median HR was 75 b.p.m. (IQR: 70-107 b.p.m.). A total of 171 patients (87 in the ivabradine group, 84 in the placebo group) were evaluated for treatment efficacy. After 8 months of treatment, findings showed a median change in HR of -13.0 b.p.m. (IQR: -18.0 to -6.0 b.p.m.) in the ivabradine group and -3.5 b.p.m. (IQR: -11.5 to 3.0 b.p.m.) in the placebo group [estimated between-group difference: 7.7 b.p.m.; 90% confidence interval (CI) -10 to -5.4; P < 0.0001]. No evidence of improvement was found in any of the three co-primary endpoints. There was almost no change in median E/e' in either of the two groups [median change: +1.0 (IQR: -0.8 to 2.9) in the ivabradine group; -0.6 (IQR: -2.2 to 1.4) in the placebo group; estimated between-group difference: 1.4, 90% CI 0.3-2.5; P = 0.135]. There were no meaningful changes in the other co-primary endpoints and no apparent trends. There was no significant safety concern.Conclusions: In patients with HFpEF, HR reduction with ivabradine did not improve outcomes. These findings do not support the use of ivabradine in HFpEF. [ABSTRACT FROM AUTHOR]

This randomized, double-blind, placebo-controlled trial assessed whether heart rate (HR) reduction with ivabradine improves cardiac function in heart failure with preserved ejection fraction (HFpEF). Methods and results The prEserveD left ventricular ejectIon fraction chronic heart Failure with ivabradine studY (EDIFY) included 179 patients in New York Heart Association (NYHA) classes II and III, in sinus rhythm, with HR of ≥70 b.p.m., NT-proBNP of ≥220 pg/mL (BNP ≥80 pg/mL) and left ventricular ejection fraction of ≥45%. Ivabradine (or placebo) was titrated to 7.5 mg b.i.d. Patients were followed for 8 months on the change and assessed for three co-primary endpoints: echo-Doppler E/e′ ratio, distance on the 6-min walking test (6MWT), and plasma NT-proBNP concentration. At baseline, median E/e′ was 12.8 [interquartile range (IQR): 9.9-16.3], median distance on the 6MWT was 320m (IQR: 247-375 m), and median NT-proBNP was 375 pg/mL (IQR: 253-701 pg/mL). Baseline median HR was 75 b.p.m. (IQR: 70-107 b.p.m.). A total of 171 patients (87 in the ivabradine group, 84 in the placebo group) were evaluated for treatment efficacy. After 8months of treatment, findings showed a median change in HR of -13.0 b.p.m. (IQR: -18.0 to -6.0 b.p.m.) in the ivabradine group and -3.5 b.p.m. (IQR: -11.5 to 3.0 b.p.m.) in the placebo group [estimated between-group difference: 7.7 b.p.m.; 90% confidence interval (CI) -10 to -5.4; P <0.0001]. No evidence of improvement was found in any of the three co-primary endpoints. There was almost no change in median E/e′ in either of the two groups [median change: +1.0 (IQR: -0.8 to 2.9) in the ivabradine group; -0.6 (IQR: -2.2 to 1.4) in the placebo group; estimated between-group difference: 1.4, 90% CI 0.3-2.5; P =0.135]. There were no meaningful changes in the other co-primary endpoints and no apparent trends. There was no significant safety concern. Conclusions In patients with HFpEF, HR reduction with ivabradine did not improve outcomes. These findings do not support the use of ivabradine in HFpE [ABSTRACT FROM AUTHOR]

Aims To evaluate the impact of physicians' adherence to guideline-recommended medications for heart failure with reduced ejection fraction (HFrEF), including ≥50% prescription of recommended doses, on clinical outcomes at 6-month follow-up. Methods and results In QUALIFY, an international, prospective, observational, longitudinal survey, 6669 outpatients with HFrEF were recruited 1-15 months after heart failure (HF) hospitalization from September 2013 to December 2014 in 36 countries and followed up at 6 months. A global adherence to guidelines score was developed for prescription of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs) and ivabradine and their dosages. Baseline global adherence score was good in 23% of patients, moderate in 55%, and poor in 22%. At 6-month follow-up, poor adherence was associated with significantly higher overall mortality [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.42-3.44, P=0.001], cardiovascular mortality (HR 2.27, 95% CI 1.36-3.77, P=0.003), HF mortality (HR 2.26, 95% CI 1.21-4.2, P=0.032), combined HF hospitalization or HF death (HR 1.26, 95% CI 1.08-1.71, P=0.024) and cardiovascular hospitalization or cardiovascular death (HR 1.35, 95% CI 1.08-1.69, P=0.013). There was a strong trend between poor adherence and HF hospitalization (HR 1.32, 95% CI 1.04-1.68, P=0.069). Conclusion Good adherence to pharmacologic treatment guidelines for ACEIs, ARBs, BBs, MRAs and ivabradine, with prescription of at least 50% of recommended dosages, was associated with better clinical outcomes during 6-month follow-up. Continuing global educational initiatives are needed to emphasise the importance of guideline recommendations for optimising drug therapy and prescribing evidence-based doses in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: During the post-discharge phase following a heart failure hospitalization (HFH), patients are at high risk of early readmission despite standard of care therapy. We examined the impact of chronic exposure to ivabradine on early readmissions in patients hospitalized for heart failure during the course of the SHIFT study (Systolic Heart Failure treatment with the If inhibitor ivabradine Trial).Methods and Results: A total of 1186 of the 6505 randomized patients experienced at least one HFH during the study, and had a more severe profile than those without HFH. Of these 1186 patients, 334 patients (28%) were rehospitalized within 3 months for any reason, mostly for cardiovascular causes (86%), including HFH (61%). Ivabradine was associated with fewer all-cause hospitalizations at 1 month [incidence rate ratio (IRR) 0.70, 95% confidence interval (CI) 0.50-1.00, P < 0.05], 2 months (IRR 0.75, 95% CI 0.58-0.98, P = 0.03), and 3 months (IRR 0.79, 95% CI 0.63-0.99, P = 0.04). A trend for a reduction in cardiovascular and HF hospitalizations was also observed in ivabradine-treated patients.Conclusion: We demonstrate in this post-hoc analysis that chronic exposure to ivabradine reduces the incidence of all-cause hospitalizations during the vulnerable phase after a HFH. Further studies are needed to investigate if in-hospital or early post-discharge initiation of ivabradine could be useful to improve early outcomes in patients hospitalized for HF. [ABSTRACT FROM AUTHOR]

The article highlights the results of several studies on heart failure including one on the effects of adaptive servo-ventilation in patients with heart failure and central sleep apnoea, one on the link between dipeptidyl peptidase 4 inhibitors and heart failure risk, and another on the relationship between moderate alcohol intake and risk of heart failure.

Aims: To assess physicians' adherence to guideline-recommended medications for the treatment of chronic heart failure (CHF) with reduced ejection fraction.Methods and Results: QUALIFY is an international prospective observational longitudinal survey of 7092 CHF outpatients recruited 1-15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries. We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors (ACEIs), beta-blockers, angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and ivabradine. The adherence score was good in 67%, moderate in 25%, and poor in 8% of patients. Adherence was lower in women than men but there were differences in age (65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men, P < 0.001) and the proportion of women at ≥50% target dose of beta-blockers was lower in those >67 years (median) (11% vs. 16.2%, P = 0.005). Geographic variations were observed with lower adherence scores in Central/Eastern European countries. The proportion of patients at target dose and ≥50% of target dose was low (27.9% and 63.3% for ACEIs, 14.8% and 51.8% for beta-blockers, 6.9% and 39.5% for ARBs, and 6.9% and 39.5% for ivabradine, respectively). It was also lower in patients most recently hospitalized (<6  vs. ≥6 months) except for beta-blockers.Conclusion: This international survey shows that adherence to guideline-recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal. Action plans aimed at improving adherence to guidelines are required. [ABSTRACT FROM AUTHOR]

Aims: To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status.Methods and Results: This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07-1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13-1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23-1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68-0.94 and HR 0.84, 95% CI, 0.75-0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo.Conclusions: Comorbid diabetes in chronic HF worsens the prognosis of systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients. [ABSTRACT FROM AUTHOR]

Aims To evaluate clinical profiles and outcomes in patients with systolic heart failure (HF) with or without diabetes, and the efficacy and safety of ivabradine (heart rate-lowering agent) with respect to diabetic status. Methods and results This is a post hoc analysis on patients in SHIFT, a randomized controlled trial in adults in sinus rhythm with systolic HF, left ventricular ejection fraction ≤35%, and resting heart rate ≥70 b.p.m. Patients were randomized to ivabradine (titrated to 7.5 mg bid) or placebo. Diabetic status was established by medical history at baseline. The primary composite endpoint (PCE) was cardiovascular death or hospitalisation for worsening HF. Of 6505 patients, 30% had diabetes, 32% of whom used insulin. The PCE was more frequent in patients with diabetes [adjusted hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.07 - 1.31; p = 0.001], as was hospitalization for worsening HF (adjusted HR 1.28, 95% CI 1.13- 1.44; P < 0.001), and was increased in patients treated with insulin (adjusted HR 1.43, 95% CI 1.23 - 1.66; P < 0.01 vs. non-diabetics). Ivabradine significantly reduced the PCE in patients with and without diabetes (adjusted HR 0.80, 95% CI 0.68 - 0.94 and HR 0.84, 95% CI, 0.75 - 0.95, respectively; interaction P was non-significant) vs. placebo. Adverse events were significantly more frequent in patients with diabetes (78%) than without (74%) (P < 0.001). Regardless of diabetic status, the incidence of serious adverse events was not significantly different between ivabradine and placebo. Conclusions Comorbid diabetes in chronic HF worsens the prognosis of systolic HF patients. Irrespective of diabetic status, ivabradine is effective and safe in these patients. [ABSTRACT FROM AUTHOR]

Aims Low systolic blood pressure ( SBP) is associated with poor outcomes in heart failure and complicates management. In a post hoc analysis, we investigated the efficacy and safety of ivabradine in the SHIFT population divided by tertiles of baseline SBP. Methods and Results The analysis comprised 2110 patients with SBP <115 mmHg, 1968 with 115≤ SBP <130 mmHg, and 2427 with SBP ≥130 mmHg. Patients with low SBP were younger, had lower ejection fraction, and were less likely to be at target beta-blocker dose than patients in the other SBP groups. Ivabradine was associated with a similar relative risk reduction of the composite outcome in the three SBP groups [ SBP <115 mmHg, hazard ratio ( HR) = 0.84, 95% confidence interval ( CI) 0.72-0.98; 115≤ SBP <130 mmHg, HR = 0.86, 95% CI 0.72 to 1.03; SBP ≥130 mmHg, HR = 0.77, 95% CI 0.66 to 0.92; P interaction = 0.68]. Similar results were found for cardiovascular mortality ( P interaction = 0.91), hospitalization because of heart failure ( P interaction = 0.79), all-cause mortality ( P interaction = 0.90), and heart failure mortality ( P interaction = 0.18). There was no evidence for a difference in safety profile according to SBP group. Conclusion The efficacy and safety of ivabradine is independent of SBP. This may have implications for the management of HF patients with low SBP and elevated heart rate. [ABSTRACT FROM AUTHOR]

In this article, the author focuses on championing the cardiovascular health innovation in Europe. It mentions that innovations related to the cardiovascular health in Europe are characterized by reductions in pharmaceutical productivity of research and development (R&D). It further mentions that European R&D is characterized by high costs due to longer timescales and a complex approval process, and high wages and operational expenditure.

A review of the article "Championing cardiovascular health innovation in Europe," by Michel Komajda and colleagues, is presented.

Aims A post-hoc analysis of the SHIFT trial was performed to explore whether ivabradine is beneficial in patients with systolic heart failure, in sinus rhythm, with resting heart rate ≥70 b.p.m., and whose guideline-recommended background therapy includes a mineralocorticoid receptor antagonist (MRA). Methods and results The effect of ivabradine on the primary composite endpoint of cardiovascular death or hospitalization for worsening heart failure, and its components, was explored in 3922 SHIFT patients with MRAs at baseline vs. 2583 patients without. Patients with MRAs were younger and were more likely to have severe heart failure and less coronary artery disease or hypertension than those without these drugs. Event rates in the placebo group were higher in patients with MRAs (33%) than in those without (23%) for the primary composite endpoint, with a 40% increase in relative risk (hazard ratio 1.40, 95% confidence interval 1.22–1.61). This was also true for secondary endpoints related to mortality or hospitalization. The effect of ivabradine on reducing the primary endpoint was similar in patients with and without MRAs (P = 0.916 for interaction, adjusted for prognostic factors at baseline), as were its effects on cardiovascular death (P = 0.279), hospitalizations for heart failure (P = 0.304), and death from heart failure and from all causes (P = 0.723 and 0.366, respectively). There was no difference in the safety of ivabradine in the two subpopulations. Conclusion Ivabradine improves outcomes in heart failure patients with heart rate ≥70 b.p.m. receiving multiple neurohormonal modulation treatments (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, and MRA). The addition of ivabradine to multiple neurohormonal modulation should therefore be considered when the heart rate is ≥70 b.p.m. [ABSTRACT FROM AUTHOR]

Objectives: This study used the SHIFT (Systolic Heart failure treatment with the I f inhibitor ivabradine Trial) database to assess the impact of background beta-blocker dose on response to ivabradine. Background: In systolic heart failure, reduction in relatively high heart rates improves clinical outcomes when achieved with beta-blockers and even more so when the sinus node inhibitor ivabradine also is added. Methods: Among patients with systolic heart failure, sinus rhythm, and heart rate ≥70 beats/min on recommended background therapy, maximally tolerated beta-blocker doses were subgrouped as no beta-blocker, <25%, 25% to <50%, 50% to <100%, and 100% of European Society of Cardiology–suggested target doses. The impact of ivabradine on cardiovascular death or heart failure hospitalization (primary endpoint) was analyzed in each subgroup as time-to-first event using Cox models adjusted for heart rate. The statistical models assessed heterogeneity and trend of the treatment effect across subgroups, and an additional analysis was made adjusting for the interaction of randomized treatment with baseline heart rate. Results: The primary endpoint and heart failure hospitalizations were significantly reduced by ivabradine in all subgroups with <50% of target beta-blocker dose, including no beta-blocker (p = 0.012). Despite an apparent trend to reduction in treatment-effect magnitude with increasing beta-blocker dose, no variation in treatment effect was seen in general heterogeneity interaction tests (p = 0.35). Across beta-blocker subgroups, treatment effect was borderline nonsignificant only for the primary endpoint (p = 0.056), and significance was further lost after adjusting for interaction between baseline heart rate and ivabradine effect (p = 0.14). Conclusions: The magnitude of heart rate reduction by beta-blocker plus ivabradine, rather than background beta-blocker dose, primarily determines subsequent effect on outcomes. (Effects of ivabradine on cardiovascular events in patients with moderate to severe chronic heart failure and left ventricular systolic dysfunction. A three-year randomised double-blind placebo-controlled international multicentre study; ISRCTN70429960) [Copyright &y& Elsevier]

This European consensus document aims to identify the main reasons for the apparent lack of progress in the introduction of new medicines for acute heart failure. Relevant issues include not only the heterogeneity of the patient group but also the pharmacology of the medicines themselves and the design of the trials. Above all, this document attempts to provide some pragmatic solutions to this complex syndrome to simplify the execution of meaningful therapeutic endeavours in this area of undoubted unmet clinical need in the future. [ABSTRACT FROM AUTHOR]

The article provides information on a study which identified the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in chronic heart failure. The characteristics of patients eligible for participation in the randomized, double-blind, placebo-controlled, parallel-group trial are described. Main outcome measure was the composite of cardiovascular death or hospital admission for worsening heart failure. Presented in details are the research findings.

Aims: Elevated heart rate is a significant marker for mortality and morbidity in cardiovascular disease including heart failure. Despite background treatment with a beta-blocker, many patients with heart failure and low ejection fraction maintain a heart rate above 70 b.p.m. Ivabradine reduces heart rate directly through inhibition of the If ionic current. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Several surveys show that patients with chronic heart failure (CHF) are sub-optimally managed and treatment guidelines are not implemented in clinical practice. Aims: To investigate awareness and perceptions of the 2005 European Society of Cardiology (ESC) guidelines for CHF. Methods: 467 cardiologists from seven European countries completed an on-line interview using a validated, semi-structured questionnaire including questions about awareness and relevance of CHF guidelines. To assess agreement with ESC guidelines, three fictitious patient cases were presented and respondents'' management choices compared with those of an expert panel based on the guidelines. Results: Awareness of CHF guidelines was high, with 98% aware of any guideline and 65% aware of ESC guidelines. ESC guidelines were considered relevant (51%) or very relevant (38%) for guiding treatment decisions. Up to 92% of respondents perceived that they adhered to the ESC guidelines. For the patient cases, ≤25% made treatment recommendations that completely matched those formulated by the expert panel. Respondents considered patient compliance (52%) and guideline complexity (46%) major barriers to implementation. Conclusion: Cardiologists reported high awareness of and a positive attitude towards ESC CHF guidelines. Provision of guidelines in a concise and accessible format is perceived as a key factor to improve implementation. [Copyright &y& Elsevier]

Background: Management guidelines for heart failure recommend ACE-I and β-blockers. The perception of difficult up-titration might have added to the slow uptake of β-blockers despite their mortality and morbidity benefits. Aims: CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination. Methods: Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril. Results: There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively. Conclusion: The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril. [Copyright &y& Elsevier]

Until now, the administration of antithrombotic therapy in patients with congestive heart failure has not been well codified. The incidence of thromboembolic complication, such as stroke, peripheral or pulmonary embolism, is regarded as too low to justify the use of anticoagulation in non-selected patients. However, other thrombotic complications may occur especially in patients with ischemic heart failure and represent potential targets for antithrombotic therapy. The objective of this paper is to review the available evidence in the absence of the results of large ongoing trials. [ABSTRACT FROM AUTHOR]

The article presents the scientific report of the Working Group on Heart Failure European Society of Cardiology from 2000-2001. It states that the group intends to organize a research in heart failure. It notes that the two main scientific activities that have been achieved this year is the guidelines for the diagnosis and treatment of heart failure, and their biannual meeting in Barcelona, Spain from June 9-12, 2001. Moreover, the website, science council, and study groups are also discussed.

The author discusses the article "Effect of Liraglutide, a Glucagon-like Peptide-1 Analogue, on Left Ventricular Function in Stable Chronic Heart Failure Patients With and Without Diabetes (LIVE)--A Multicentre, Double-Blind, Randomized, Placebo-Controlled Trial" by A. Jorsal et al. Topics include the failure of LIVE to show any improvement in ejection fraction (EF), the lack of benefit in heart failure and reduced ejection fraction, and lessons from other clinical trials with GLP-analogues.

Aims: A high resting heart rate (RHR) and low systolic blood pressure (SBP) are a risk factor and a risk indicator, respectively, for poor heart failure (HF) outcomes. This analysis evaluated the associations between baseline RHR and SBP with outcomes and treatment patterns in patients with HF and reduced ejection fraction (HFrEF) in the QUALIFY (QUality of Adherence to guideline recommendations for LIFe‐saving treatment in heart failure surveY) international registry. Methods and results: Between September 2013 and December 2014, 7317 HFrEF patients with a previous HF hospitalization within 1–15 months were enrolled in the QUALIFY registry. Complete follow‐up data were available for 5138 patients. The relationships between RHR and SBP and outcomes were assessed using a Cox proportional hazards model and were analysed according to baseline values as high RHR (H‐RHR) ≥75 bpm versus low RHR (L‐RHR) <75 bpm and high SBP (H‐SBP) ≥110 mmHg versus low SBP (L‐SBP) <110 mmHg and analysed according to each of the following four phenotypes: H‐RHR/L‐SBP, L‐RHR/L‐SBP, H‐RHR/H‐SBP and L‐RHR/H‐SBP (reference group). Compared to the reference group, H‐RHR/L‐SBP was associated with the worst outcomes for the combined primary endpoint of cardiovascular death and HF hospitalization (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.51–2.21, p < 0.001), cardiovascular death (HR 2.70, 95% CI 1.69–4.33, p < 0.001), and HF hospitalization (HR 1.62, 95% CI 1.30–2.01, p < 0.001). Low‐risk patients with L‐RHR/H‐SBP achieved more frequently ≥50% of target doses of angiotensin‐converting enzyme inhibitors (ACEIs) and beta‐blockers (BBs) than the other groups. However, 48% and 46% of low‐risk patients were not well treated with ACEIs and BBs, respectively (≤50% of target dose or no treatment). Conclusion: In patients with HFrEF and recent hospitalization, elevated RHR and lower SBP identify patients at increased risk for cardiovascular endpoints. While SBP and RHR are often recognized as barriers that deter physicians from treating with high doses of recommended drugs, they are not the only reason leaving many patients suboptimally treated. [ABSTRACT FROM AUTHOR]

Aims: In the SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial, ISRCTN70429960) study, ivabradine reduced cardiovascular death or heart failure (HF) hospitalizations in patients with HF and reduced ejection fraction (HFrEF) in sinus rhythm and with a heart rate (HR) ≥70 bpm. In this study, we sought to determine the clinical significance of the time durations of HR reduction and the significant treatment effect on outcomes among patients with HFrEF. Methods and results: The time to statistically significant reduction of the primary outcome (HF hospitalization and cardiovascular death) and its components, all‐cause death, and HF death, were assessed in a post‐hoc analysis of the SHIFT trial in the overall population (HR ≥70 bpm) and at HR ≥75 bpm, representing the approved label in many countries. Compared to placebo, the primary outcome and HF hospitalizations were significantly reduced at 102 days, while there was no effect on cardiovascular death, all‐cause death, and HF death at HR ≥70 bpm. In the population with a baseline HR ≥75 bpm, a reduction of the primary outcome occurred after 67 days, HF hospitalization after 78 days, cardiovascular death after 169 days, death from HF after 157 days and all‐cause death after 169 days. Conclusion: Treatment with ivabradine should not be deferred in patients in sinus rhythm with a HR of ≥70 bpm to reduce the primary outcome and HF hospitalizations, in particular in patients with HR ≥75 bpm. At HR ≥75 bpm, the time to risk reduction was shorter for reduction of hospitalization and mortality outcomes in patients with HFrEF after initiation of guideline‐directed medication, including beta‐blockers at maximally tolerated doses. [ABSTRACT FROM AUTHOR]

Cardiovascular disorders represent a major public health concern because of their high prevalence, morbidity, and mortality. Indeed hypertension, coronary artery disease, heart failure, stroke or peripheral vascular diseases are a major contributor to mortality and, because of the increase in life expectancy and aging, a pandemic both in developed and developing countries. The identification of numerous new morbid genes should provide useful diagnostic tools for the assessment of the genetic risk in a given family, especially in the younger generation where penetrance is often incomplete as observed in hypertrophic or dilated cardiomyopathy.

Focuses on the significance of the Human Genome Project in providing insight into the molecular basis of monogenic or complex cardiac disorders. Reasons for the cause of cardiac disorders; Prospects of using genomic information in diagnosis and treatment of cardiac diseases.

Opportunity for Global Impact Streamline the Trial Processes: Reinvent Simple Trials With Global Impact The COVID-19 pandemic has provided clinical trialists with an opportunity to rethink their trade and remember the landmark successes of the cardiovascular mega-trial concept established in the 1980s. Trials such as Randomised Evaluation of COVID-19 Therapy (RECOVERY)[15] and World Health Organization Solidarity[16] have been highly streamlined and designed to be easy to administer in the busy hospitals in which large numbers of COVID patients were being treated. Randomized controlled trials are the cornerstone for reliably evaluating therapeutic strategies.[1] However, during the past 25 years, the rules and regulations governing randomized trials and their interpretation have become increasingly burdensome,[2] and the cost and complexity of trials has become prohibitive.[3] The present model is unsustainable, and the development of potentially effective treatments is often stopped prematurely on financial grounds, while existing drug treatments or non-drug interventions (such as screening strategies or management tools) may not be assessed reliably. [Extracted from the article]

Aims: Guidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient‐centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF. Methods and results: Anonymous online questionnaires co‐developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline‐mandated medications over up‐titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline‐recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses. Conclusions: These surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient‐centred, needs‐driven quality improvement programmes. [ABSTRACT FROM AUTHOR]

Objectives: In the Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT), slowing of the heart rate with ivabradine reduced cardiovascular death or heart failure hospitalizations among patients with systolic chronic heart failure (CHF). Subsequently, in the Study Assessing the Morbidity-Mortality Benefits of the If Inhibitor Ivabradine in Patients with Coronary Artery Disease (SIGNIFY) slowing of the heart rate in patients without CHF provided no benefit for cardiovascular death or nonfatal myocardial infarction (primary composite end point), with secondary analyses suggesting possible harm in the angina subgroup. Therefore, we examined the impact of ivabradine in the patients with CHF plus angina in SHIFT. Methods: SHIFT enrolled adults with stable, symptomatic CHF, a left ventricular ejection fraction = 35% and a sinus rhythm with a resting heart rate ≥ 70 bpm. Outcomes were the SHIFT and SIGNIFY primary composite end points and their components. Results: Of 6,505 patients in SHIFT, 2,220 (34%) reported angina at randomization. Ivabradine numerically, but not significantly, reduced the SIGNIFY primary composite end point by 8, 11 and 11% in the SHIFT angina subgroup, nonangina subgroup and overall population, respectively. Ivabradine also reduced the SHIFT primary composite end point in all 3 subgroups. Conclusions: In SHIFT, ivabradine showed consistent reduction of cardiovascular outcomes in patients with CHF; similar results were seen in the subgroup of SHIFT patients with angina. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) is associated with prolonged and recurrent hospitalizations; the prognosis remains poor. Since 2013, the Caisse Primaire d'Assurance Maladie (CPAM) has set up a support program PRADO-IC (support program for returning home after hospitalisation for heart failure). The aim of this study was to evaluate the impact of PRADO-IC on the heart failure readmission rate and death rate at one year. From September 2016 to September 2018, all patients hospitalized for heart failure at Saint-Joseph Hospital were included in an observational study. The inclusion in PRADO-IC program was at physician's discretion. Two groups were compared according to the inclusion in PRADO-IC or not (T). The primary endpoints were the comparison of one-year mortality and heart failure readmission rate between the two groups. Six hundred and thirty-three patients were included, 262 in the PRADO-IC group and 371 in the non-PRADO group. Patients in the PRADO-IC cohort more frequently present severity criteria (age, weight, BNP level, arrhythmia, anemia, renal failure). Mortality at one year (19.5% vs 16.2%, p = 0.28) are equivalent in both groups. There were no significant differences in one-year rehospitalization rate for heart failure (HF) (35.1% in PRADO cohort vs 28% in T group, p = 0.06), the time to first hospitalization (74.5 days in PRADO vs 54.5 days in T, p = 0.55) and the length of hospitalization (6.0 days in PRADO vs 7.0 days in T, p = 0.29) between the two groups. Age, hyponatremia, anemia, cancer, HF re-hospitalization were variables linked to a risk of mortality, in a multivariable analysis. Our study shows that the PRADO-IC program concerned to the most severe patients. Despite this, the one-year mortality and the HF readmission rate are similar between the two groups. [ABSTRACT FROM AUTHOR]

Aims In patients with heart failure ( HF) and reduced ejection fraction, decreases or increases in NT-proBNP levels are associated with better and worse outcomes, respectively. The association in HF and preserved ejection fraction ( HF-PEF) is unknown. We examined the association between change in level of NT-proBNP and prognosis in patients with HF-PEF. Methods and results We examined the association between change in NT-proBNP from baseline to 6 months and cardiovascular ( CV) death or HF hospitalization in 2612 participants in the Irbesartan in Patients with Heart Failure and Preserved Systolic Function Study (I-Preserve). Change in NT-proBNP was modelled as a restricted cubic spline in a Cox model after adjusting for baseline NT-proBNP and known prognostic variables. Median change in NT-proBNP from baseline was −7 pg/ mL (interquartile range −143 to +108). After adjustment, a 1000 pg/ mL decrease in NT-proBNP from baseline was associated with a reduction in the risk of CV death or HF hospitalization [hazard ratio ( HR) 0.73, 95% confidence interval ( CI) 0.53-1.02]; a 1000 pg/ mL increase was associated with an increase in risk ( HR 2.01, 95% CI 1.50-2.69). Beyond a 1000 pg/ mL rise or fall, there was little additional change in risk. Addition of change in NT-proBNP at 6 months to a model with only baseline NT-proBNP improved the C-statistic from 0.752 to 0.769 ( P = 0.013). Conclusion In HF-PEF, a rise in NT-proBNP was associated with an increase in risk of CV death or HF hospitalization and a fall was associated with a trend towards a decrease in risk. NT-proBNP may be a useful marker to monitor prognosis in this condition. [ABSTRACT FROM AUTHOR]

Aims We identified easily obtained baseline characteristics associated with outcomes in patients with chronic heart failure (HF) and elevated heart rate (HR) receiving contemporary guideline-recommended therapy in the SHIFT trial, and used them to develop a prognostic model. Methods We selected the 10 best predictors for each of four outcomes (cardiovascular death or HF hospitalisation; all-cause mortality; cardiovascular mortality; and HF hospitalisation). All variables with p < 0.05 for association were entered into a forward stepwise Cox regression model. Our initial analysis excluded baseline therapies, though randomisation to ivabradine or placebo was forced into the model for the composite endpoint and HF hospitalisation. Results Increased resting HR, low ejection fraction, raised creatinine, New York Heart Association class III/IV, longer duration of HF, history of left bundle branch block, low systolic blood pressure and, for three models, age were strong predictors of all outcomes. Additional predictors were low body mass index, male gender, ischaemic HF, low total cholesterol, no history of hyperlipidaemia or dyslipidaemia and presence of atrial fibrillation/flutter. The c-statistics for the four outcomes ranged from 67.6% to 69.5%. There was no evidence for lack of fit of the models with the exception of all-cause mortality (p = 0.017). Similar results were found including baseline therapies. Conclusion The SHIFT Risk Model includes simple, readily obtainable clinical characteristics to produce important prognostic information in patients with chronic HF, systolic dysfunction, and elevated HR. This may help better calibrate management to individual patient risk. [ABSTRACT FROM AUTHOR]

Aims To test whether the efficacy and safety of the selective heart rate-reducing agent ivabradine changes according to age in chronic heart failure (HF) patients. Methods and results The ivabradine and placebo arms of SHIFT, which enrolled 6505 chronic HF patients, were combined and age distribution was divided by quartiles to give four groups (<53 years, n = 1522; 53 to <60 years, n = 1521; 60 to <69 years, n = 1750; and ≥69 years, n = 1712). The effects of ivabradine on cardiovascular outcomes, changes in heart rate, and adverse events, particularly bradycardia, were evaluated according to age group. A subgroup (602 patients) underwent 24 h ambulatory ECG Holter monitoring. The relative risk of the primary endpoint (cardiovascular death or hospitalization for worsening HF) was reduced by ivabradine in all age groups, ranging from 38% [hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.50–0.78, P < 0.001] in the youngest patients <53 years to 16% (HR 0.84, 95% CI 0.71–0.99, P = 0.035) in the oldest patients ≥69 years. Ivabradine up-titration reduced heart rate similarly in all age groups, by 11 b.p.m. As anticipated, bradycardia and phosphenes occurred more frequently with ivabradine, at a similar rate whatever the age. In the Holter substudy, there were no episodes of severe bradycardia and no clinically relevant pauses with ivabradine in any age group. Conclusions Age does not limit the appropriate use of ivabradine in patients with chronic HF and systolic dysfunction. The safety and efficacy of ivabradine are comparable across all age groups. [ABSTRACT FROM AUTHOR]

Congestiveheart failure (CHF) is associated with prolonged and recurrent hospitalizations, the prognosis remains poor. The aim of this study was to collect epidemiologic data at admission and at six month follow-up in a cohort of patients with CHF admitted to a single center between 2017 and 2019 (Saint Joseph Hospital, HSJ) and to compare these data with regional data (Ile-de-France, IdF). Local and regional data were provided by National Health Service, Regional Department of Ile de France(DRSM) using national data base. CHF in-hospital stay was defined by appropriate CIM 10 code reported on the final medical form. From 2017 to 2019, 1967 CHF in-hospital stays were collected, mean age of the population was 81.4 (=mean) ± 11.7 yearsIC 95% [80.8; 81.9], mean length of stay was 8.6 ± 6.8 days IC 95% [8.3; 8.9], in-hospital mortality was 5.3 %, 9.6% at 2nd month and 15.9% at 6th month. Readmission rate was 23.7%, time to readmission was 59.5 ± 47.5 days IC 95% [57.4; 61.6]. IdF data collected 60973 CHF in-hospital stays at the same period. Compared to the IdF population, our population was older (81.4 ± 11.6 versus 80.4 ± 12.6 years, p = 0.001). Length of stay was shorter (8.6 ± 6.8 versus 11.3 ± 10.1 days p<0.001), in-hospital mortality was lower (5.3% versus 7.8% p < 0.001), 2nd month and 6th month mortality was lower (respectively 9.6% versus 14.2% and 15.9% versus 21.3%, p <0.001), home discharge rate was higher (66.9% versus 60.8%, p < 0.001) in the HSJ population. The proportion of patients included in PRADO-IC program (Programme d'aide au retour à domicile–Insuffisance Cardiaque, Returning home support program) was higher in SJ population (22.6% versus 8.8% p < 0.001). CHF admission involved elderly patients, the in-hospital and 6th month mortality is high, with early and frequent readmissions. Differences between HSJ and IdF populations may be explained by the heterogeneity of health care facilities, management facilities and organization of transition of care. [ABSTRACT FROM AUTHOR]

Background: Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction, but additional data are needed about its effect on inpatient and outpatient heart failure events.Methods: We randomly assigned 5988 patients with class II through IV heart failure with an ejection fraction of >40% to double-blind treatment with placebo or empagliflozin (10 mg once daily), in addition to usual therapy, for a median of 26 months. We prospectively collected information on inpatient and outpatient events reflecting worsening heart failure and prespecified their analysis in individual and composite end points.Results: Empagliflozin reduced the combined risk of cardiovascular death, hospitalization for heart failure, or an emergency or urgent heart failure visit requiring intravenous treatment (432 versus 546 patients [empagliflozin versus placebo, respectively]; hazard ratio, 0.77 [95% CI, 0.67-0.87]; P<0.0001). This benefit reached statistical significance at 18 days after randomization. Empagliflozin reduced the total number of heart failure hospitalizations that required intensive care (hazard ratio, 0.71 [95% CI, 0.52-0.96]; P=0.028) and the total number of all hospitalizations that required a vasopressor or positive inotropic drug (hazard ratio, 0.73 [95% CI, 0.55-0.97]; P=0.033). Compared with patients in the placebo group, fewer patients in the empagliflozin group reported outpatient intensification of diuretics (482 versus 610; hazard ratio, 0.76 [95% CI, 0.67-0.86]; P<0.0001), and patients assigned to empagliflozin were 20% to 50% more likely to have a better New York Heart Association functional class, with significant effects at 12 weeks that were maintained for at least 2 years. The benefit on total heart failure hospitalizations was similar in patients with an ejection fraction of >40% to <50% and 50% to <60%, but was attenuated at higher ejection fractions.Conclusions: In patients with heart failure with preserved ejection fraction, empagliflozin produced a meaningful, early, and sustained reduction in the risk and severity of a broad range of inpatient and outpatient worsening heart failure events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977. [ABSTRACT FROM AUTHOR]

The article presents information on a study which determined the relationship between heart rate and events in patients with chronic heart failure. In the randomized placebo-controlled trial, the cardiovascular outcomes in the placebo and ivabradine groups was analyzed. Main outcome measure was cardiovascular death or hospital admission for worsening heart failure. It examines heart-rate reduction as mechanism for risk reduction by ivabradine. Findings of the study are discussed in detail.

Abstract: Background: We describe the baseline characteristics of subjects randomised in the largest placebo-controlled, morbidity-mortality trial to date in patients with heart failure and preserved ejection fraction — the irbesartan in heart failure with preserved systolic function trial (I-PRESERVE). Methods and results: 4133 patients with a mean age of 72 years (a third were 75 years or older) were randomised and 60% were women. The mean (SD) LVEF was 59 (9)% and almost 80% of patients were in NYHA Class III or IV. Approximately 80% of patients were also overweight or obese. Heart failure was reported by investigators to have a hypertensive aetiology in 64% of patients. Prior myocardial infarction was relatively uncommon (24%), as was coronary revascularisation (13%). Atrial fibrillation and diabetes each occurred in between a quarter and a third of patients. The following treatments were used at baseline: diuretic 83%, beta-blocker 59%, calcium channel blocker 40%, ACE inhibitor 25%, spironolactone 15% and digoxin 14%. Conclusions: Patients in I-PRESERVE are broadly representative of those seen in epidemiological studies and, because of this, the results of this trial should be generally applicable to “real world” patients with heart failure and preserved ejection fraction. [Copyright &y& Elsevier]

Background: In the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) trial, sotagliflozin, a sodium-glucose cotransporter-1 and sodium-glucose cotransporter-2 inhibitor, reduced total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure relative to placebo by 33%.Objective: To determine whether sotagliflozin increased the prespecified efficacy outcome of days alive and out of the hospital (DAOH) in the SOLOIST-WHF trial.Design: Randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT03521934).Setting: 306 sites in 32 countries.Participants: 1222 patients with type 2 diabetes and reduced or preserved ejection fraction who were recently hospitalized for worsening heart failure.Intervention: 200 mg of sotagliflozin once daily (with a possible dose increase to 400 mg) or matching placebo.Measurements: The primary analysis included hospitalizations for any reason on the basis of investigator-reported incidence and duration of admissions after randomization. Days alive and out of the hospital and its converse (days dead and days in the hospital) were analyzed using prespecified Poisson regression models.Results: Although similar proportions of patients in the sotagliflozin and placebo groups were hospitalized at least once (38.5% vs. 41.4%), fewer patients in the sotagliflozin group were hospitalized more than once (16.3% vs. 22.1%). There were 64 and 76 deaths in the sotagliflozin and placebo groups, respectively. The DAOH rate in the sotagliflozin group was 3% higher than in the placebo group (rate ratio [RR], 1.03 [95% CI, 1.00 to 1.06]; P = 0.027). This difference was primarily driven by a reduction in the rate of days dead (RR, 0.71 [CI, 0.52 to 0.99]; P = 0.041) rather than by a reduction in the rate of days hospitalized for any cause. For every 100 days of follow-up, patients in the sotagliflozin group were alive and out of the hospital for 3% or 2.9 more days than those in the placebo group (91.8 vs. 88.9 days); this difference reflected a 2.6-day difference in days dead (6.3 vs. 8.9 days) and a 0.3-day difference in days in the hospital (1.9 vs. 2.2 days).Limitation: Other than heart failure, the primary reason for each hospitalization was unspecified.Conclusion: Sotagliflozin increased DAOH, a metric that may provide an additional patient-centered outcome to capture the totality of disease burden. Future studies are needed to quantify the consequences of increasing DAOH in terms of health economics and patient quality of life.Primary Funding Source: Sanofi at initiation and Lexicon Pharmaceuticals at completion. [ABSTRACT FROM AUTHOR]

Aims: To assess the prevalence, type and clinical factors associated with left ventricular (LV) dysfunction in patients with type 2 diabetes mellitus (T2DM) by performing a comprehensive echocardiographic Doppler assessment including speckle tracking. Methods: Two hundred T2DM patients without overt cardiovascular disease were prospectively enrolled in a single‐centre cohort study between 2018 and 2019. Results: Left ventricular mass was increased in 24 patients (12%) and relative wall thickness (h/r) was increased in 46 patients (23%). Left atrial (LA) enlargement was observed in 27 patients (13.6%) and global longitudinal strain (GLS) was reduced in 38 patients (20.3%). In univariate analysis, LV hypertrophy (LVH) or increased h/r were associated with age, renal function, hypertension and B‐type natriuretic peptide (BNP) plasma level. LA dilation was associated with age, history of hypertension, diabetes duration and complications, insulin treatment, BNP level and renal function. GLS was associated with body mass index (BMI) and, in a borderline manner, with diabetes duration. In multivariate analysis, hypertension was associated with LVH and with h/r and a borderline relationship was observed for female gender (LVH), age and insulin treatment (h/r). Age, hypertension and, in a borderline manner, insulin treatment were associated with LA dilation. BMI and shorter diabetes duration were associated with reduced GLS. Conclusion: A high prevalence of asymptomatic cardiac dysfunction/structural abnormalities was observed in patients with T2DM without overt cardiac disease and was associated with either age, diabetes duration or treatment and with comorbidities including hypertension and obesity. Whether these preclinical abnormalities are associated with poor outcomes warrants further study. [ABSTRACT FROM AUTHOR]