Heart Failure In Sinus Rhythm Research Articles

The impact of ethnicity on clinical outcomes in patients with heart failure and atrial fibrillation

Abstract Introduction Heart failure (HF) and atrial fibrillation (AF) are increasingly prevalent and associated with substantial morbidity (1,2). When HF and AF co-exist, the outcome profile is significantly worse than for either condition in isolation (3). Ethnic background is known to influence disease outcomes and treatment efficacy (4), but there is limited knowledge about how HF, AF and ethnicity interact on mortality and hospital admission. Purpose This study aims to address the null hypothesis of no difference in death and cardiovascular events comparing non-white and white patients with HF and concomitant AF, and assess the differential impact of ethnicity in patients with these conditions. Methods Individual patient data were obtained from 12 randomized controlled trials (RCTs) in patients with HF. RCT data were harmonised and meta-analysed to investigate the interaction of baseline heart rhythm (sinus rhythm versus atrial fibrillation) and ethnicity (non-white versus white). The primary outcome of all-cause mortality and secondary outcome of cardiovascular (CV)-related mortality were analysed using adjusted Cox regression models and propensity-score matching. Results 16,713 HF patients were included of which 1,899 (11%) were non-white, median age 66 (interquartile range [IQR] 57-73) and 4,703 (28%) women. During median follow-up of 1.4 years (IQR 0.8-2.3), death occurred in 394 (21%) non-white patients and 2,142 (15%) white patients; adjusted hazard ratio (HR) 1.36, 95% CI 1.20-1.54; p<0.001. The impact of ethnicity was greater in patients with coexisting HF and AF (non-white versus white HR 2.05; 95% CI 1.55-2.70; p<0.001), than in those with HF in sinus rhythm (non-white versus white HR 1.24; 95% CI 1.08-1.41; p=0.002). A significant interaction was evident between ethnicity and rhythm status for all-cause mortality (p=0.003), with similar findings using propensity-score matching (Figure 1). An exploratory analysis of beta-blockers versus placebo demonstrated divergent efficacy with respect to mortality for non-white (HR 1.00, 95% CI 0.79-1.27; p=0.99) and white patients (HR 0.70, 95% CI 0.63-0.78; p<0.001); p-interaction=0.008 (Figure 2). For cardiovascular hospitalisation, the non-white cohort also had higher rates, with greatest disparity in patients with combined HF and AF (non-white versus white HR 1.80, 95% CI 1.63-2.37; p<0.001) compared to HF in sinus rhythm (non-white versus white HR 1.23, 95% CI 1.11-1.36; p<0.001); p-interaction=0.012 in propensity-matching. Conclusion Non-white patients with HF suffer from substantially higher rates of death and hospitalisation than corresponding white patients, with the presence of comorbid AF significantly worsening this ethnicity-related disparity. In those with HF in sinus rhythm, beta blockers were found to be significantly less effective at reducing mortality in non-white patients.Figure 1 Figure 2

Left atrial strain measurement in patients with heart failure and atrial fibrillation compared to a control group

Abstract Background Left atrial (LA)-strain measurement is a non-invasive and widely available echocardiographic method to detect atrial cardiomyopathy as a process of structural and functional remodeling. The aim of this study is to measure LA-strain in patients with heart failure (HF) and atrial fibrillation (AF), compared to patients without structural heart disease and to evaluate whether or not LA-Strain could be part of a multi-modality assessment that influences therapy strategies and prognosis in patients suffering AF. Methods This study includes 18 patients with HF in sinus rhythm who underwent CRT implantation (HF group), 25 patients with persistent AF and preserved ejection fraction (EF) who underwent left atrial catheter ablation (AF group) and 22 patients without structural heart disease or AF who underwent electrophysiological study (control group). All subjects received measurement of reservoir (LASr), conduit (LAScd) and contraction (LASct) LA strain imaging using two-dimensional speckle tracking echocardiography (2D-STE). Results Patient characteristics in the HF-group showed mean age 68y (SD 10,6), mean EF 29% (SD 6,8), 66% male compared to the AF-group with mean age 66y (SD 8.0), mean EF 60% (SD 5.1), 68% male. The control-group showed mean age 55y (SD 13.8), mean EF 60% (SD 5.4), 55% male. For LASr we found normal values in the control groups and reduced values in the HF und AF group (HF: mean 20% [9 – 45%], AF: mean 24% [7 – 52%], control: mean 42% [30 – 67%]). In LASr, LAScd and LASct there was a statistically significant difference between the HF and the control group (p < 0.001) as well as the AF and control group (p < 0.001), whereas there was no difference between AF and HF group (p = 0.444). Discussion Patients with persistent AF show similar LA-strain compared to patients with HF and patients without structural heart disease present significant better LA strains. The findings of this study suggest, that LA strain analysis might contribute to comprehensive assessment of patients with AF especially as a simple imaging method. A limitation of our results could be the significant younger age of our control group (p = 0.004) as fibrotic remodeling increases in advanced age. It remains to be analyzed whether early AF treatment could prevent further fibrotic remodeling and whether measuring LA strain could provide further information for risk stratification and the definition of therapeutic intervention strategies.

Embolic stroke of undetermined source - ESUS: a new challenge for the cardiologist

Embolic stroke of undetermined source (ESUS) is a new clinical entity which requires an accurate diagnostic work-up. The involvement of the cardiologist in this challenge is of paramount importance as in many cases an occult cardioembolic source is detectable. In the absence of subclinical atrial fibrillation detectable by prolonged ECG monitoring, potential causes of ESUS include atrial cardiomyopathy, left ventricular dysfunction or heart failure, aortic plaques and patent foramen ovale. The assessment of a causal relationship between these cardiac abnormalities and ESUS is often a difficult challenge and the randomized clinical trials performed so far failed to demonstrate a superiority of direct oral anticoagulants (DOAC) over aspirin. In selected individual patients with heart failure in sinus rhythm with high CHA2DS2-VASc score, or aortic plaques with thrombotic component, oral anticoagulation with DOAC might be considered even in the absence of evidence from randomized clinical trials.

Heart Rate Reduction and Outcomes in Heart Failure Outpatients

Aim. Pharmacologic reduction in heart rate with beta-blockers (BB) or ivabradine is associated with improved survival in heart failure (HF) with sinus rhythm. We analyzed the association of different heart rate-reducing drug treatments on outcomes in HF outpatients. Methods. Consecutive patients with HF in sinus rhythm referred to a specialized tertiary service were prospectively enrolled from August 2015 until March 2018. Clinical characteristics were assessed at baseline. We performed Cox regression analyses to examine the effect of the resting heart rate and different heart rate-reducing drug regimens on all-cause mortality and a composite endpoint of “all-cause mortality or heart transplantation” over a mean follow-up of 3.1 years. Results. Of the 278 patients included, 213 (76.6%) were male, the median age was 57.0 years (IQR 49.0–66.1), and 185 (73.7%) had an ejection fraction <40%. Most patients received BB in submaximal [n = 118] or maximum dose [n = 136]. Patients on BB in maximum dose plus ivabradine [n = 24] were younger (53.0 vs. 58.0 years) and had a lower EF (25 vs. 31%). Higher resting heart rate was associated with an increased risk of death or transplantation (HR 1.03 [1.01, 1.06], p = 0.0072), even after adjusting for age and sex. There were no differences between the groups concerning all-cause mortality or the composite endpoint. Conclusion. Our prospective study confirms the association between low heart rate and survival in HF patients receiving various heart rate-reducing medications. We could not identify a specific effect of either regimen.

THE INFLUENCE OF HYPERTENSION ON HEART FAILURE'S PHENOTYPES IN PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION, IN COMPARISON TO PATIENTS WITH HEART FAILURE AND SINUS RHYTHM

Objective: Atrial fibrillation is being characterised as both an etiological factor and a consequence for developing heart failure, while it does the same for the latter. Our aim was to identify whether and in which way, the presence of hypertension influences the development of the three phenotypes of heart failure in patients with heart failure and atrial fibrillation, as well as in patients with heart failure alone. Design and method: We analysed 194 patients: 97 with heart failure and atrial fibrillation (group A) and 97 patients with heart failure in sinus rhythm (group B), randomly selected from 2019 to 2021. The phenotypes of heart failure were selected according to 2021 European Society of Cardiology Guidelines: patients with heart failure with reduced ejection fraction (1), with mildly reduced ejection fraction (2) and with preserved ejection fraction (3). Results: In patients belonging to A1 group (n = 44) the result was that hypertension has not played a significant role in developing this phenotype (p = 0.1347), in comparison to patients in B1 group (n = 30), where the association between hypertension and heart failure with reduced ejection fraction was statistically significant (p = 0.0263). What is more, patients in A2 group (n = 14), as well as those in B2 group (n = 24), were not associated with the presence of hypertension (p = 0.4686, respectively p = 0.5638). As well as the latter, hypertension did not influence the development of heart failure with preserved ejection fraction in both groups. Conclusions: Taking into consideration that hypertension illustrates a common aetiology for both pathologies mentioned above, we discovered that hypertension's presence influenced more the heart failure in sinus rhythm group, concluding that atrial fibrillation associated with heart failure did not pose an additive risk factor for hypertension developing. In addition, regarding the phenotypes, it was heart failure with a reduced ejection fraction that was influenced by hypertension. Further researches will improve the comprehensive relationship between hypertension, atrial fibrillation and heart failure, leading towards better management strategies.

THE IMPACT OF HYPERTENSION IN PATIENTS PRESENTING HEART FAILURE WITH AND WITHOUT ATRIAL FIBRILLATION

Objective: Both atrial fibrillation and heart failure represent etiological factors for each other, while hypertension does the same for them. Our aim consisted in identifying the degree of which the presence of hypertension contributed as a risk factor for developing atrial fibrillation in patients suffering from heart failure. Design and method: We analysed 129 patients with heart failure in sinus rhythm and 158 patients with heart failure and atrial fibrillation, both group patients being randomly selected from year 2019 to 2021. The study included patients admitted to a chronic patient care unit. Results: We performed a Fisher's exact test based on a contingency table including N = 132 patients with heart failure and atrial fibrillation exposed to the presence of hypertension, as well as N = 105 patients with heart failure in sinus rhythm without hypertension (nominal values of the groups are shown in Fig. 1). With the risk for the exposed (R1) being 0.557 and the risk for the unexposed (R0) 0.52, we obtained an RR of 1.071, meaning that patients with hypertension have a 1.071-fold increased risk of developing atrial fibrillation in patients with heart failure. Also, there is an association between atrial fibrillation and hypertension (RR>1). Conclusions: The link between atrial fibrillation, heart failure and hypertension is a well-debated topic in the medical world. In this study, we illustrated that although hypertension represents a frequent comorbidity, in patients with heart failure it encounters more often in association with atrial fibrillation, rather than in patients with sinus rhythm. This finding has led us to believe that our aim as medical practitioners would consist in a better blood pressure control, as well as improved treatment adherence, in order to prevent the development of atrial fibrillation and heart failure pathogenesis.

The effect of anticoagulants on clinical outcomes of mortality, stroke, myocardial infarction, pulmonary embolism, and major bleeding for patients with heart failure in sinus rhythm.

One to two percent of the population in developed countries are affected by chronic heart failure and this increases to greater than 10% in those over 70 years old. Heart failure (HF) predisposes patients to thromboembolic events. Anticoagulants are often used to prevent thromboembolic events in specific patient populations, such as those with atrial fibrillation. Currently, no guidance exists on the long-term use of anticoagulants for patients with HF in sinus rhythm. This article critically appraises a systematic review which assesses whether the long-term use of oral anticoagulants reduces total mortality and stroke in patients with HF in sinus rhythm.

Anticoagulation versus placebo for heart failure in sinus rhythm.

People with chronic heart failure (HF) are at risk of thromboembolic events, including stroke, pulmonary embolism, and peripheral arterial embolism; coronary ischaemic events also contribute to the progression of HF. The use of long-term oral anticoagulation is established in certain populations, including people with HF and atrial fibrillation (AF), but there is wide variation in the indications and use of oral anticoagulation in the broader HF population. To determine whether long-term oral anticoagulation reduces total deaths and stroke in people with heart failure in sinus rhythm. We updated the searches in CENTRAL, MEDLINE, and Embase in March 2020.We screened reference lists of papers and abstracts from national and international cardiovascular meetings to identify unpublished studies. We contacted relevant authors to obtain further data. We did not apply any language restrictions. Randomised controlled trials (RCT) comparing oral anticoagulants with placebo or no treatment in adults with HF, with treatment duration of at least one month.We made inclusion decisions in duplicate, and resolved any disagreements between review authors by discussion, or a third party. Two review authors independently assessed trials for inclusion, and assessed the risks and benefits of antithrombotic therapy by calculating odds ratio (OR), accompanied by the 95% confidence intervals (CI). We identified three RCTs (5498 participants). One RCT compared warfarin, aspirin, and no antithrombotic therapy, the second compared warfarin with placebo in participants with idiopathic dilated cardiomyopathy, and the third compared rivaroxaban with placebo in participants with HF and coronary artery disease. We pooled data from the studies that compared warfarin with a placebo or no treatment. We are uncertain if there is an effect onall-cause death (OR 0.66, 95% CI 0.36 to 1.18; 2 studies, 324 participants; low-certainty evidence); warfarin mayincreasethe risk of major bleeding events (OR 5.98, 95% CI 1.71 to 20.93, NNTH 17). 2 studies, 324 participants; low-certainty evidence). None of the studies reported stroke as an individual outcome. Rivaroxabanmakes little to no difference to all-cause death compared with placebo (OR 0.99, 95% CI 0.87 to 1.13; 1 study, 5022 participants; high-certainty evidence). Rivaroxaban probably reduces the risk of stroke compared to placebo (OR0.67, 95% CI0.47 to 0.95; NNTB 101; 1 study, 5022 participants; moderate-certainty evidence), and probably increases the risk of major bleeding events (OR1.65, 95% CI1.17 to 2.33; NNTH 79; 1 study, 5008 participants; moderate-certainty evidence). Based on the three RCTs, there is noevidence that oral anticoagulant therapy modifies mortalityin people with HF in sinus rhythm. The evidence is uncertain if warfarin has any effect on all-cause death compared to placebo or no treatment, but it may increase the risk of major bleeding events.There is no evidence of a differencein the effect ofrivaroxabanon all-cause death compared to placebo. It probably reducesthe risk of stroke, but probably increases the risk of major bleedings. The available evidence does not support the routine use of anticoagulation in people with HF who remain in sinus rhythm.

Efficacy and Safety of Oral Anticoagulants in Patients with Systolic Heart Failure in Sinus Rhythm: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Cohort Studies.

Introduction There is conflicting evidence on the risk–benefit ratio of oral anticoagulants (OAC) in heart failure (HF) patients without atrial fibrillation. We aimed to evaluate the efficacy and safety of OAC in HF patients in sinus rhythm. Methods A systematic literature search was conducted using PubMed and Embase. We included randomized controlled trials (RCT) and cohort studies, comparing OAC with antiplatelet or no treatment/placebo in patients with HF. Outcomes evaluated were stroke, myocardial infarction (MI), all-cause mortality, and major bleeding. Results Five RCTs and three cohort studies were included. OAC was associated with a reduced risk of ischemic stroke when compared with no treatment/placebo (odds ratio [OR] = 0.67, 95% confidence interval [CI]: [0.47, 0.94]) and antiplatelet therapy (OR = 0.55, 95% CI: [0.37, 0.81]). No significant reduction was found in MI, when OAC was compared with no treatment/placebo (OR = 0.82, 95% CI: [0.63, 1.07]) or antiplatelet therapy (OR = 1.04, 95% CI: [0.60, 1.81]). The all-cause mortality analysis showed no significant reduction when comparing OAC with no treatment/placebo (OR = 0.99, 95% CI: [0.87, 1.12]) or antiplatelet therapy (OR = 1.00, 95% CI: [0.86, 1.16]). The nonsignificant effect of OAC on all-cause mortality was supported by a meta-analysis of the three cohort studies (OR = 1.02, 95% CI: [0.75, 1.38]). Patients treated with OAC had a significantly higher risk of major bleeding than patients receiving antiplatelet therapy (OR = 2.16, 95% CI: [1.55, 3.00]) and a numerically higher risk when compared with no treatment/placebo (OR = 2.38, 95% CI: [0.87, 6.49]). Conclusion The present study does not support the routine use of OAC in patients with HF in sinus rhythm.

P1635A risk score for prediction of TIA/ischemic stroke in patients with heart failure and sinus rhythm

Abstract Background Prediction of ischemic cerebral events in patients with heart failure (HF) in the absence of atrial fibrillation (AF) is challenging. Purpose To prospectively test a staged approach to identify patients with HF and sinus rhythm who are at high risk of developing TIA/ischemic stroke (TIA/IS) during the first two years after diagnosis. Methods The analysis is based on patient data reported in the Swedish Heart Failure Register from January 2003 until December 2013. Patients with AF and those treated with anticoagulants were excluded. The study population was categorized in two groups according to left ventricular ejection fraction: LVEF ≤40% and LVEF >40%. Factors associated with TIA/IS were determined by univariate proportional hazard regression. The risk score included: age (1p for 65–74y; 2p for 75–84y; 3p for ≥85y), previous ischemic heart disease (1p), hypertension (1p), diabetes mellitus (1p), TIA/IS (2p), and kidney dysfunction (1p). Two-year hazard ratios with death as competing risk were computed. The probability of observing the outcome was calculated using the cumulative incidence function. Results A total of 16,865 patients (mean age 72.1±13.2y) were included in the study, 39.9% women; 59.7% had LVEF ≤40%. The two-year crude rate of TIA/IS, hemorrhagic stroke, and all-cause mortality were 3.3%, 0.3%, and 26%, respectively. An incremental absolute risk for TIA/IS was observed for patients with LVEF ≤40% and score 1- ≥6: 1.6, 2.3, 3.6, 2.9, 6.3, and 7.1%, respectively. The corresponding HRs with 95% confidence interval (CI) and the patients with 0 points as reference group were: 2.8 (1.1–7.3), 4.0 (1.6–10.1), 6.6 (2.7–16.2), 5.5 (2.2–13.8), 14.4 (5.8–35.9) for score 1- ≥6, where all p-values were less than 0.05 and Wald χ2 for overall model fit <0.0001. The cumulative incidence per 1000 person-years was: 8.2 (5.4–12.5), 11.8 (8.3–16.7), 19.4 (15.1–24.8), 16.3 (12.6–21.1), 36.6 (29.4–45.4), and 42.1 (33.0–53.8), respectively. In patients with LVEF >40% and score 1–≥6, the absolute TIA/IS risk was: 1.3, 3.1, 3.1, 3.3, 4.6, and 5.3%, respectively. The corresponding HRs with 95% CI and patients with 1 point as reference group was: 2.4 (1.1–5.2), 2.5 (1.2–5.3), 2.7 (1.3–5.7), 3.9 (1.8–8.2); and 4.6 (2.2–9.8), for score 1- ≥6 (all p<0.05 and Wald χ2 for overall model fit p=0.0002). The cumulative incidence per 1000 person-year was: 6.7 (3.4–13.2), 16.0 (10.8–23.8), 16.7 (12.5–22.2), 18.0 (13.9–23.4), 25.8 (19.4–34.3), and 30.6 (21.7–43.0), for score 1- ≥6, respectively. Conclusion In the current study, a risk score compiling age and specific comorbidity was shown to predict increased risk of TIA/IS, regardless of LVEF, during the first two years after diagnosis in patients with incident HF in sinus rhythm.

Prevalence and Incidence of Atrial Fibrillation in Ambulatory Patients With Heart Failure

Heart failure (HF) and atrial fibrillation (AF) commonly co-exist. We aimed to determine the prevalence and incidence of AF in ambulatory patients with HF. HF was defined by the presence of symptoms or signs supported by objective evidence of cardiac dysfunction: either a left ventricular ejection fraction (LVEF) ≤45% (HF and a reduced ejection fraction, HFrEF), or LVEF >45% and a raised plasma concentration of amino-terminal pro-B type natriuretic peptide (NT-proBNP >220 ng/L; HFpEF). Of 3,570 patients with HF, 1,164 were in AF at baseline (33%), with a higher prevalence among patients with HFpEF compared with HFrEF (40% vs 26%, respectively, p <0.001). Compared with patients with HF in sinus rhythm, those in AF were older, had more severe symptoms and higher NT-proBNP, worse renal function, and were more likely to receive loop diuretics, despite having a higher LVEF. Of those in sinus rhythm, 1,372 patients had HFrEF and 1,034 had HFpEF. The incidence of AF at 1 year (3.0%) was similar for each phenotype (p = 0.73). Increasing age, male gender, history of paroxysmal AF, and higher plasma concentrations of NT-proBNP were independent predictors of incident AF during a median follow-up of 1,574 (interquartile range: 749 to 2,821) days; the predictors were similar for each phenotype. In conclusion, the prevalence of AF is high, especially in patients with HFpEF, but its incidence is modest. This may be because their onset is near simultaneous with the development of AF precipitating the onset of HF.

A comparison of anticoagulation, antiplatelet, and placebo treatment for patients with heart failure reduced ejection fraction in sinus rhythm: a systematic review and meta-analysis.

Previous meta-analyses have not recommended routine warfarin use in heart failure (HF) patients but included limited data on contemporary anticoagulants and practices. We conducted an updated meta-analysis in light of newer literature evaluating rivaroxaban in this patient population. The aim of this meta-analysis was to assess if anticoagulation is associated with a decrease in all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for HF exacerbation without an increased risk of major bleeding. A systematic search was conducted for randomized controlled trials to evaluate the use of antithrombotic therapy in patients with HF in sinus rhythm. Outcomes evaluated included all-cause mortality (ACM), non-fatal stroke, MI, hospitalization for HF exacerbation, and major bleeding. Five trials met criteria with a total of 9390 patients included. Four of the five trials evaluated warfarin use and one trial evaluated rivaroxaban. When anticoagulation was compared to control (antiplatelet and placebo groups), a significant reduction in ischemic stroke was found (OR 0.57; 95% CI, 0.42 to 0.78; P = 0.0005, I2 = 6.9%) and no significant difference was found in the risk of ACM, MI, or HF hospitalization. A significant increase in major bleeding was observed in the anticoagulation group when compared to the control group (OR 2.00; 95% CI, 1.45 to 2.75; P = < 0.0001, I2 = 25.79%). Anticoagulation in HF patients in normal sinus rhythm does not appear to reduce mortality rate, prevent MI, or decrease HF hospitalizations. Use reduces risk of ischemic stroke but is counterbalanced with an increase in major bleeding.

Anticoagulation in heart failure without atrial fibrillation: gaps and dilemmas in current clinical practice.

Data from observational and post-hoc analyses suggest that heart failure (HF) itself may be associated with higher risk of thromboembolic events compared to populations without HF. Although oral anticoagulants (OACs) might be a therapeutic option in individual cases, anticoagulation therapy in HF patients in sinus rhythm is not generally recommended, as the implementation of OACs in clinical practice in this HF population is not supported by large randomized clinical trials to date. Indeed, the available data suggest that the risk of major bleeding overshadows the potential anti-thromboembolic benefit of OACs in HF patients in sinus rhythm with no net beneficial effect on mortality rates. In this review we explore the current available evidence for the clinical outcomes of anticoagulation therapy in patients with HF in sinus rhythm, highlighting the current gaps in knowledge, which may guide the design of future randomized clinical trials focusing on the efficacy and safety of anticoagulant therapy in this HF population.

Оптимизация дигиталисной терапии в клинической практике

In recent years there has been a marked decrease in cardiac glycosides use in patients with heart failure in sinus rhythm and atrial fibrillation. The results of published studies contradict each other. Some of them doubt the favorable effect of digoxin in patients with heart failure; others refute the increase in the lethality and frequency of hospitalizations associated with the use of digoxin. In this regard, we found it important to analyze these reports impartially and reflect modern views on the mechanisms of cardiac glycosides, the pharmacokinetics and the possibility of optimizing digitalis therapy in cardiac practice.

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials.

Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.

Resting Heart Rate and Ischemic Stroke in Patients with Heart Failure

Background: Although high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm. Methods: We examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review. Results: During 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR <64 beats/min) compared to other groups; 22/573 (KM 5.3%) in 64-70 beats/min, 13/465 (KM 3.5%) in 71-79 beats/min, and 21/519 (KM 5.4%) in RHR >79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR <64/beats/min; p = 0.038), along with a history of stroke or transient ischemic attack and left ventricular ejection fraction. Conclusions: In contrast to its beneficial effect on mortality and hospital re-admissions, lower RHR may increase the risk of ischemic stroke in patients with systolic heart failure in sinus rhythm.

The role of Ivabradine in Diastolic Heart Failure with preserved Ejection Fraction. A Doppler-Echocardiographic study.

Background:Ivabradine (IVA) is effective in patients with coronary artery disease (CAD) or systolic heart failure in sinus rhythm. Its action consists in reducing heart rate (HR) and improving the time of left ventricular (LV) diastolic filling. The aim of this study was to evaluate the effects of IVA added to conventional therapy on patients with diastolic heart failure (DHF) and preserved ejection fraction (HFpEF).Methods:We evaluated 25 patients with DHF in the New York Heart Association (NYHA) Class II-III and sinus rhythm. In these, IVA per os (5 mg/twice a day) was added to the conventional medical therapy and given for 12 weeks. Immediately before the beginning of IVA therapy and 3 months later, patients underwent echocardiographic evaluation by two-dimensional (2D) ultrasound and tissue Doppler imaging (TDI). The patterns of diastolic mitral inflow and pulmonary venous flow were recorded using 2D echocardiography, while the diastolic phase of mitral flow was recorded by TDI, from the lateral mitral annulus.Results:Three months after the addition of IVA to conventional treatment, HR significantly decreased in comparison to the baseline values. On the contrary, the echocardiographic indexes of LV diastolic dysfunction improved.Conclusions:These results testify that the addition of IVA to conventional therapy in patients with HFpEF can improve LV diastolic function evaluated by 2D and tissue Doppler-echocardiographic patterns. These Doppler-echocardiographic results match with the clinical improvement of patients evaluated.

Heart Rate Control in Non-Paroxysmal Atrial Fibrillation. A New Indication for Ivabradine?

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with poor quality of life and high rate of hospitalization in elderly frail patients. In patients with non-paroxysmal AF, optimizing heart rate is often the main goal but available drugs fail to reach heart rate control in about 30% of cases and this often happens because their doses can not be implemented due to side effects. Ivabradine is a pure heart rate lowering agent acting through the inhibition of If current in the sinus atrial cells, and it is widely used for patients with stable angina and chronic heart failure in sinus rhythm. According to very preliminary data, ivabradine shows heart rate lowering proprieties in non-paroxysmal AF when used alone or in association to other heart rate lowering drugs. Interestingly, studies suggest that this seems to translate into clinical benefits such as improvement of exercise tolerance and ejection fraction. However, new trials are needed to confirm the effectiveness and safety of ivabradine in non-paroxysmal AF.

Does aspirin detract from the benefits of mineralocorticoid receptor antagonists in patients with heart failure and a reduced left ventricular ejection fraction? Probably!

Does aspirin detract from the benefits of mineralocorticoid receptor antagonists in patients with heart failure and a reduced left ventricular ejection fraction? Probably!

How do warfarin and aspirin compare in adults with congestive heart failure in sinus rhythm?

How do warfarin and aspirin compare in adults with congestive heart failure in sinus rhythm?