Search

Empagliflozin reduces cardiovascular death (CVD) or heart failure hospitalization (HHF) in patients with heart failure and preserved ejection fraction (HFpEF). Treatment effects and safety in relation to resting heart rate (RHR) have not been studied.The interplay of RHR and empagliflozin effects in EMPEROR-Preserved was evaluated. We grouped patients (n = 5988) according to their baseline RHR (70 bpm [n = 2650], 70-75 bpm [n = 967],75 bpm [n = 1736]) and explored the influence of RHR on CVD or HHF (primary outcome) and its components in sinus rhythm or atrial fibrillation/flutter (AF) and adverse events. We studied the efficacy of empagliflozin across the RHR spectrum. Compared to placebo, empagliflozin did not change heart rate over time. The primary outcome (p for trend = 0.0004) and its components CVD (p trend = 0.0002), first HHF (p for trend = 0.0099) and all-cause death (p 0.0001) increased with RHR only in sinus rhythm but not AF. The risk increase with RHR was similar in patients with heart failure and mildly reduced ejection fraction (left ventricular ejection fraction [LVEF] 40-49%) and HFpEF (LVEF ≥50%). Baseline RHR had no influence on the effect of empagliflozin on the primary outcomes (p for trend = 0.20), first HHF (p for trend = 0.49). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the RHR groups.Resting heart rate associates with outcomes only in sinus rhythm but not in AF. Empagliflozin reduced outcomes over the entire RHR spectrum without increase of adverse events.

In heart failure (HF), acute decompensation can occur quickly and unexpectedly because of worsening of chronic HF or to new‐onset HF diagnosed for the first time (‘de novo’). Patients presenting with acute HF (AHF) have a poor prognosis comparable with those with acute myocardial infarction, and any delay of treatment initiation is associated with worse outcomes. Recent HF guidelines and recommendations have highlighted the importance of a timely diagnosis and immediate treatment for patients presenting with AHF to decrease disease progression and improve prognosis. However, based on the available data, there is still uncertainty regarding the optimal ‘time‐to‐treatment’ effect in AHF. Furthermore, the immediate post‐worsening HF period plays an important role in clinical outcomes in HF patients after hospitalization and is known as the ‘vulnerable phase’ characterized by high risk of readmission and early death. Early and intensive treatment for HF patients in the ‘vulnerable phase’ might be associated with lower rates of early readmission and mortality. Additionally, in the chronic stable HF outpatient, treatments are often delayed or not initiated when symptoms are stable, ignoring the risk for adverse outcomes such as sudden death. Consequently, there is a dire need to better identify HF patients during hospitalization and after discharge and treating them adequately to improve their prognosis. HF is an urgent clinical scenario along all its stages and disease conditions. Therefore, time plays a significant role throughout the entire patient's journey. Therapy should be optimized as soon as possible, because this is beneficial regardless of severity or duration of HF. Time lavished before treatment initiation is recognized as important modifiable risk factor in HF.

ZusammenfassungInzidenz und Prävalenz der Herzinsuffizienz steigen weltweit. Trotz zahlreicher wissenschaftlicher und klinischer Innovationen ist sie weiterhin mit einer hohen Morbidität und Mortalität behaftet, sodass eine leitliniengerechte Diagnostik und Therapie von entscheidender Bedeutung sind. Die kardiale Dekompensation zählt zu den häufigsten Aufnahmegründen in deutschen Krankenhäusern. Somit stellt die Behandlung herzinsuffizienter Patienten eine erhebliche Herausforderung für das deutsche Gesundheitssystem dar. Dieser Artikel fasst die neuesten wissenschaftlichen Erkenntnisse zur akuten und chronischen Herzinsuffizienz der Jahre 2018 bis 2020 zusammen.

Aims Atrial fibrillation (AF) is common in patients with diabetes and heart failure (HF) and increases the future risk of adverse cardiovascular (CV) outcomes. This analysis from the EMPA-REG OUTCOME trial explores CV and renal outcomes in patients with vs. without AF at baseline and assesses the benefits of empagliflozin. Methods and results Analyses were conducted on patients distinguished by the presence (n = 389) or absence (n = 6631) of AF at baseline. Outcome events were more frequent in patients with AF than those without AF. Empagliflozin compared to placebo reduced CV death or HF hospitalisation consistently in patients with AF [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.36-0.92] and without AF (HR 0.67, 95% CI 0.55-0.82, Pinteraction = 0.56). Similar results were observed for the components of this endpoint, all-cause mortality, new or worsening nephropathy, first introduction of loop diuretics, or occurrence of oedema. The absolute number of prevented events was higher in patients with AF, resulting in larger absolute treatment effects of empagliflozin. New loop diuretics or oedema were associated with increased rates of subsequent events, and rates appeared lower in those randomised to empagliflozin. Conclusions In patients with type 2 diabetes mellitus and established CV disease, those with AF at baseline had higher rates of adverse HF outcomes than those without AF. Irrespective of the presence of AF, empagliflozin reduced HF-related and renal events. The absolute number of prevented events is higher in patients with AF than without AF. Patients with diabetes, CV disease and AF may especially benefit from use of empagliflozin.

Clinical research in cardiology 110(8), 1150-1158 (2021). doi:10.1007/s00392-021-01867-2, Published by Springer, Berlin

The incidence and prevalence of heart failure are increasing worldwide. Despite numerous scientific and clinical innovations the mortality and morbidity rates in heart failure patients remain high, so that guideline-conform diagnostics and treatment are of decisive importance. Cardiac decompensation is one of the leading reasons for hospital admissions in Germany. Thus, the treatment of patients with heart failure represents a substantial challenge for the German healthcare system. This article highlights the latest scientific knowledge on acute and chronic heart failure from the years 2018-2020.Inzidenz und Prävalenz der Herzinsuffizienz steigen weltweit. Trotz zahlreicher wissenschaftlicher und klinischer Innovationen ist sie weiterhin mit einer hohen Morbidität und Mortalität behaftet, sodass eine leitliniengerechte Diagnostik und Therapie von entscheidender Bedeutung sind. Die kardiale Dekompensation zählt zu den häufigsten Aufnahmegründen in deutschen Krankenhäusern. Somit stellt die Behandlung herzinsuffizienter Patienten eine erhebliche Herausforderung für das deutsche Gesundheitssystem dar. Dieser Artikel fasst die neuesten wissenschaftlichen Erkenntnisse zur akuten und chronischen Herzinsuffizienz der Jahre 2018 bis 2020 zusammen.

Aims Atrial fibrillation is the most prevalent sustained arrhythmia associated with arrhythmic ventricular contractions, incident heart failure, increased morbidity and mortality. The relationship between arrhythmic contractions and ventricular remodelling is incompletely understood. The aim of this study was to characterize the influence of irregular contractions on pro-fibrotic signalling in neonatal rat ventricular cardiomyocytes (NRVM). Methods and results Neonatal rat ventricular cardiomyocytes were paced via field stimulation at 3 Hz for 24 h. Irregularity was created by pseudorandomized variation of stimulation intervals and compared to regular pacing. Treatment of neonatal cardiac fibroblasts (NCF) with medium of irregularly paced NRVM increased protein expression of collagen I (206 ± 62%, P = 0.0121) and collagen III (51 ± 37%, P = 0.0119). To identify the underlying mechanism, expression of pro-fibrotic connective tissue growth factor (CTGF) and transforming growth factor beta (TGF-β) was assessed. In irregularly paced NRVM, increased protein expression of CTGF (80 ± 22%, P = 0.0035) and TGF-β (122 ± 31%, P = 0.0022) was associated with enhanced excretion of both proteins into the medium. Electron paramagnetic resonance spectroscopy revealed an increased production of reactive oxygen species (46 ± 21%, P = 0.0352) after irregular pacing accompanied by increased 8-hydroxydeoxyguanosine staining (214 ± 53%, P = 0.0011). Irregular pacing was associated with elevated mRNA levels of anti-oxidative superoxide dismutase 1 (25 ± 7%, P = 0.0175), superoxide dismutase 3 (20 ± 7%, P = 0.0309), and catalase (20 ± 7%, P = 0.046). Conclusion These data demonstrate that irregular pacing is an important inductor of pro-fibrotic signalling in NRVM involving paracrine effects of CTGF and TGF-β as well as increased oxidative stress. Thus, irregularity of the heart beat might directly be involved in the progression of maladaptive remodelling processes in atrial fibrillation.

Heart failure (HF) treatment should be optimized in addition to guideline-directed and recommended drugs to achieve an appropriate heart rate (i.e. 50-60 bpm) by ivabradine in patients with a heart rate70 bpm in sinus rhythm and with an ejection fraction ≤35%. Heart rate reduction was to reduce cardiovascular death and HF hospitalization dependent on baseline resting heart rate. In particular in patients at a heart rate75 bpm, a reduction in cardiovascular death, all-cause death, HF death, HF hospitalization and all-cause hospitalization has been observed. The optimal heart rate achieved appears to be between 50-60 bpm, if well tolerated as in these patients the lowest event rate is observed on treatment. Heart rate reduction is, therefore, a treatable risk factor in chronic HF. Observational studies support the concept that it is a risk indicator in other cardiovascular and non-cardiovascular conditions. Whether heart rate reduction is also modifying risk in other conditions than chronic HF should be explored in prospective clinical trials.