Heart rate and its reduction in chronic heart failure and beyond

Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR >70 b.p.m. increased the risk of hospitalization, and >75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the I_f Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo‐controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.     

Favourable effects of heart rate reduction with intravenous administration of ivabradine in patients with advanced heart failure

BACKGROUND: Heart rate (HR) reduction may be useful in treatment of patients with heart failure (HF). There are no data on the haemodynamic effects of ivabradine (a selective I(f) current inhibitor) in advanced HF patients. AIMS: To assess the haemodynamic effects of ivabradine in patients with advanced HF and markedly depressed left ventricular (LV) function. METHODS AND RESULTS: Ten NYHA class III patients (50+/-12 years, LV ejection fraction 21+/-7%) underwent 24-h haemodynamic monitoring. Ivabradine 0.1 mg/kg was infused over 90', followed by 0.05-0.075 mg/kg in the subsequent 90'. Baseline HR was 93+/-8 bpm, cardiac index (CI) 2.2+/-0.6 l/min*m2; LV stroke volume 44+/-11 ml and systolic work 39+/-13 g. Ivabradine significantly reduced HR, by a maximum of 27% (to 68+/-9 bpm) at 4 h, without decreasing CI. Ivabradine increased stroke volume and LV systolic work by a maximum of 51% (to 66+/-17 ml) and 53% (to 58+/-20 g) at 4 h. No serious adverse events occurred. CONCLUSION: In patients with advanced HF and markedly depressed LV function, the acute administration of ivabradine is well tolerated, effectively reduces HR, markedly increases stroke volume and preserves cardiac output. Ivabradine appears a promising approach for the treatment of patients with moderate and advanced heart failure.     

心力衰竭加重并左室射血分数降低患者的QRS时限与预后

目的观察住院期间QRs时限对心力衰竭并左室射血分数降低预后的影响。方法回顾性分析心力衰竭并左室射血分数降低（≤40％）或正常的住院患者住院期间的QRs波群时限。结果3002例患者纳入研究,其中正常QRS波群时限1745例（〈120ms）,QRS波群延长（≥120ms）1257例。平均随访10个月,基础QRS波群时限正常患者全因死亡率为18．8％,基础QRS波群延长患者为28．3％（nR。1．62,95％CIL38～1．88）。基础QRS波群正常患者心血管死亡和心力衰竭住院率为31．5％和35．8％,延长者则为39．0％和43．6％（朋=1．40、1．42;95％CIL25-1．60、1．18-1．72）。QRS波群时限延长与增加全因死亡率危险性相关（HR=1．25：95％C11．03～1．52）,并增加心血管死亡或心力衰竭住院率（HR=1．21、1．28,95％CIL10～1．40、1．12～1．38）。基础Qas波群延长患者最后住院心电图QRS波群正常者仅为4．0％。结论延长的QRS波群在LVEF降低患者中十分多见,是出院后高患病率和高死亡率的独立预测因素。     

心率在LVEF降低型及保留型心力衰竭患者预后中的作用

目的 探讨不同左室射血分数(LVEF)心力衰竭(心衰)患者的临床特点及不同静息心率对预后的评估价值.方法 回顾性分析2014年1月至2017年1月于邢台市第三医院心血管内科收治的326例心衰患者,根据射血分数(EF)值分为EF降低组(n=177)及EF保留组(n=149),比较两组患者的一般基线资料,分析不同EF值患者...     

Detrended fluctuation analysis can detect the impairment of heart rate regulation in patients with heart failure with preserved ejection fraction

BackgroundThe impairment of short-term heart rate regulation in patients with heart failure with preserved ejection fraction (HFpEF) can cause acute hemodynamic collapse. Detrended fluctuation analysis (DFA) is a useful tool for the diagnosis of heart diseases and the prediction of mortality. In DFA, the short-term scaling exponent α is decreased in heart failure. However, its change in HFpEF patients remains unclear.MethodsTwenty patients diagnosed with HFpEF [defined as brain natriuretic peptide (BNP) >100 pg/mL, ejection fraction (EF) ≥50%, and without significant valvular disease], 20 diagnosed with non-HFpEF (BNP > 100 pg/mL and EF < 50%), and 20 control subjects generally matched for age and gender were enrolled. Holter electrocardiography was performed, and heart rate variability was calculated. In the DFA, the scaling exponents in 1000 beats were calculated for each 15-min segment and the average of all segments was used. We compared both the short-term (<11 beats, α1) and long-term (≥11 beats, α2) scaling exponents among the three groups.ResultsIn the HFpEF, non-HFpEF, and control groups, α1 was 0.73 ± 0.27, 0.66 ± 0.29, and 1.01 ± 0.20 (p < 0.01), and α2 was 0.95 ± 0.08, 0.88 ± 0.11, and 0.96 ± 0.07 (p < 0.01), respectively. The α1 exponent was significantly decreased in the HFpEF group (p < 0.01 vs. control) and the non-HFpEF group (p < 0.01 vs. control), while the α2 exponent was significantly decreased in the non-HFpEF group only (p < 0.05 vs. HFpEF and control).ConclusionsShort-term heart rate regulation is impaired in patients with HFpEF, while patients with non-HFpEF have both short-term and long-term impairment.     

Heart rate awareness in patients with chronic stable heart failure. A multi-center observational study

Aims

We assessed adherence to European Society of Cardiology heart rate guidelines (i.e. heart rates less than 70 bpm) in patients with chronic stable heart failure. We also investigated the percent of patients on target doses of rate controlling drugs.

Methods

Multicenter study involving 549 patients from 12 heart failure centers in the Republic of Ireland. Patients in sinus rhythm with stabilized heart failure treatment and without recent cardiac events were included. Resting heart rates, demographics, co-morbidities and heart failure therapies were recorded.

Results

Heart rates ≥ 70 bpm were noted in 176 (32.1%) patients with 117 (21.3%) having rates > 75 bpm. Non-achievement of target heart rates were unrelated to age, gender or most cardiovascular risk factors. However, 42% of patients with diabetes (p < 0.01), 56% of those with COPD (p < 0.0001) and 46% of those with NYHA Class 3 (p < 0.05) did not achieve target heart rates.Fifty eight (11%) subjects were not on beta-blockers and of these forty subjects (69%) (p < 0001) did not achieve target heart rates.Of those on beta-blockers only 25% were at target dose. However, beta-blocker dosage was unrelated to achieving target heart rates.Ivabradine was used in 11% of patients with 10% at target dosage.

Conclusion

This study highlights that a third of “stabilized” chronic heart failure patients have not reached recommended target heart rates. Respiratory problems, diabetes and marked dyspnea were associated with poorer rate control. Guideline unawareness, inadequate beta-blocker titration and under use of ivabradine may prevent patients gaining the proven benefits of heart rate control.     

The predictive value of global longitudinal strain in patients with heart failure mid-range ejection fraction

BackgroundHeart failure (HF) with mid-range ejection fraction (HFmrEF) is defined as HF with a left ventricular (LV) ejection fraction (LVEF) of 41–49%. However, the change in LV function and the subsequent prognosis in these patients remain unclear. We aimed to investigate whether LV global longitudinal strain (LV GLS) could differentiate the changes in LVEF and predict the clinical outcomes in patients with HFmrEF.MethodsAccording to the changes in LVEF on follow-up echocardiography, 273 outpatients with HFmrEF were divided into 3 groups: HFwEF (HF with worse EF: <40%), HFsEF (HF with similar EF: 40–49%), and HFrecEF (HF with recovered EF: >50%). Further, the LV GLS at diagnosis was evaluated.ResultsThe average follow-up duration was 31 months. Among patients with HFmrEF, the more impaired the LV GLS at baseline, the higher probability of HFwEF development. In comparison with patients with HFwEF and HFsEF, those with HFrecEF had a lower risk of hospitalization for HF. At a cut-off value of ?11%, LV GLS differentiated the subsequent risk of cardiovascular death in patients with HFmrEF. In Cox regression, patients with LV GLS >?11% had a high risk of cardiovascular death.ConclusionIn patients with HFmrEF, LV GLS is associated with LVEF changes and subsequent cardiovascular death. Patients with HFrecEF had a lower risk of hospitalization for HF.     

Knowledge about self-efficacy and outcomes in patients with heart failure and reduced ejection fraction

Aim

Although education in self-management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self-rated knowledge of self-management is associated with outcomes. The aim of this study was to assess the relationship between patient-reported knowledge of self-management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF).

Methods and results

Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the ‘self-efficacy’ questions of the Kansas City Cardiomyopathy Questionnaire. One question quantifies patients' understanding of how to prevent heart failure exacerbations (‘prevention’ question) and the other how to manage complications when they arise (‘response’ question). Self-reported answers from patients were pragmatically divided into: poor (do not understand at all, do not understand very well, somewhat understand), fair (mostly understand), and good (completely understand). Cox-proportional hazard models were used to evaluate time-to-first occurrence of each endpoint, and negative binomial regression analysis was performed to compare the composite of total (first and repeat) heart failure hospitalizations and cardiovascular death across the above-defined groups. Of patients (n = 17 629) completing the ‘prevention’ question, 4197 (23.8%), 6897 (39.1%), and 6535 (37.1%) patients had poor, fair, and good self-rated knowledge, respectively. Of those completing the ‘response’ question (n = 17 637), 4033 (22.9%), 5463 (31.0%), and 8141 (46.2%) patients had poor, fair, and good self-rated knowledge, respectively. For both questions, patients with ‘poor’ knowledge were older, more often female, and had a worse heart failure profile but similar treatment. The rates (95% confidence interval) per 100 person-years for the primary composite outcome for ‘poor’, ‘moderate’ and ‘good’ self-rated knowledge in answer to the ‘prevention’ question were 12.83 (12.11–13.60), 12.08 (11.53–12.65) and 11.55 (11.00–12.12), respectively, and for the ‘response’ question were 12.88 (12.13–13.67), 12.22 (11.60–12.86) and 11.56 (11.07–12.07), respectively. The lower event rates in patients with ‘good’ self-rate knowledge were accounted for by lower rates of cardiovascular (and all-cause) death and not hospitalization for worsening heart failure.

Conclusions

Poor patient-reported ‘self-efficacy’ may be associated with higher rates of mortality. Evaluation of knowledge of ‘self-efficacy’ may provide prognostic information and a guide to which patients may benefit from further education about self-management.     

Increased heart rate and atherosclerosis: potential implications of ivabradine therapy

Despite all the therapeutic advances in the field of cardiology, cardiovascular diseases, and in particular coronary artery disease, remain the leading cause of death and disability worldwide, thereby underlining the importance of acquiring new therapeutic options in this field. A reduction in elevated resting heart rate (HR) has long been postulated as a therapeutic approach in the management of cardiovascular disease. An increased HR has been shown to be associated with increased progression of coronary atherosclerosis in animal models and patients. A high HR has also been associated with a greatly increased risk of plaque rupture in patients with coronary atherosclerosis. Endothelial function may be an important link between HR and atherosclerosis. An increased HR has been shown experimentally to cause endothelial dysfunction. Inflammation plays a significant role in the pathogenesis and progression of atherosclerosis. In the literature, there is data that shows an association between HR and circulating markers of vascular inflammation. In addition, HR reduction by pharmacological intervention with ivabradine (a selective HR-lowering agent that acts by inhibiting the pacemaker ionic current If in sinoatrial node cells) reduces the formation of atherosclerotic plaques in animal models of lipid-induced atherosclerosis. The aim of this editorial is to review the possible role of ivabradine on atherosclerosis.     

Catheter ablation of atrial fibrillation in heart failure with reduced ejection fraction

Atrial fibrillation and heart failure are increasing in prevalence, and frequently coexist. Despite the desire to restore sinus rhythm in heart failure patients, large studies comparing rate control to pharmacologic rhythm control have failed to show superiority of either approach. This may in part be due to the inefficacy and higher risk of adverse effects with antiarrhythmic drugs in HF patients. As such, catheter ablation for atrial fibrillation in patients with heart failure with reduced ejection fraction has been increasingly explored as a treatment modality. We review the contemporary evidence regarding patient selection, efficacy, safety, and impact of catheter ablation on outcomes in patients with atrial fibrillation and heart failure with reduced ejection fraction.