Ventricular Arrhythmias in Acute Heart Failure. A Clinical Consensus Statement of the Association for Acute CardioVascular Care Association (ACVC), the European Heart Rhythm Association (EHRA) and the Heart Failure Association (HFA) of the ESC.

Patients presenting with or alerting emergency networks due to acute heart failure (AHF) form a diverse group with a plethora of symptoms, risks, comorbidities, and aetiologies. During AHF, there is an increased risk of destabilizing the functional substrate and modulatory adding to the risk of ventricular arrhythmias (VAs) already created by the structural substrate. New VAs during AHF have previously identified patients with higher intra-hospital and 60-day morbidity and mortality. Risk stratification and criteria/best time point for coronary intervention and implantable cardioverter defibrillator (ICD) implantation, however, are still controversial topics in this difficult clinical setting. The characteristics and logistics of prehospital emergency medicine, as well as the density of centers capable of treating AHF and VAs, differ massively throughout Europe. Scientific guidelines provide clear recommendations for the management of arrhythmias in chronic HF patients. However, the incidence, significance, and management of arrhythmias in patients with AHF have been less studied. This consensus paper aimed to address the identification and treatment of VAs that complicate the course of patients who have AHF, including cardiogenic shock.

Anticoagulation in Patients With Device-Detected Atrial Fibrillation With and Without a Prior Stroke or Transient Ischemic Attack: The NOAH-AFNET 6 Trial.

BACKGROUND: Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear. METHODS AND RESULTS: This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients). CONCLUSIONS: Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.

What is the Future Position of Factor XIa Inhibitors for Patients with Atrial Fibrillation?

Factor XIa (FXIa) may be involved in thrombus formation, but only to a lesser extent involved in haemostasis. Several novel FXIa inhibitors are under investigation, and Phase II trials demonstrated marked reduction of bleeding compared with standard treatment by factor Xa inhibitors. Asundexian is a small molecule that selectively inhibits FXIa. A large-scale Phase III clinical trial, OCEANIC-AF, has been initiated to compare the efficacy and safety between asundexian and apixaban. However, the OCEANIC-AF study was recently halted due to the inferior efficacy of asundexian versus the apixaban control arm. The present report describes up-to-date evidence of FXIa inhibitors and discusses the future position of FXIa inhibitors for patients with AF.

Sex Differences in Cardiovascular Management: A Call for Better Acknowledgment-Part 1 Pharmacological Differences in Women and Men; How Relevant Are They?

BACKGROUND: Sex differences (SDs) in pharmacology of cardiovascular (CV) drugs have been described previously; however, paradoxically, there are scarce recommendations in therapy based on these differences. It is of utmost importance to identify whether these SDs determine a modified clinical response and the potential practical implications for this, to provide a base for personalized medicine. AREA OF UNCERTAINTY: The aim of this article was to outline the most important pharmacological drivers of cardiovascular drugs that differ between women and men, along with their implications and challenges in clinical practice. DATA SOURCES: A detailed assessment of English-written resources reflecting SDs impact in CV drug pharmacology was performed using PubMed and Embase databases. RESULTS: Despite large variations in CV drug pharmacokinetics and pharmacodynamics in individuals, correcting for height, weight, surface area, and body composition compensate for most "sex-dependent" differences. In addition, individual, cultural, and social factors significantly impact disease management in women versus men. Gender-biased prescribing patterns and gender-dependent adherence to therapy also influence outcomes. The development of sex-specific guidelines requires that they should reflect the SDs implications for the management of a disease and that the evidence should be carefully evaluated as to whether there is an adequate representation of both sexes and whether sex-disaggregated data are reported. CONCLUSIONS: Pharmacological drivers are under the influence of an impressive number of differences between women and men. However, to establish their significance in clinical practice, an adequate representation of women in studies and the reporting of distinct results is mandatory.

Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.

Asymptomatic vs. symptomatic atrial fibrillation: Clinical outcomes in heart failure patients.

BACKGROUND: The outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. METHODS: In a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. RESULTS: A total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %). After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). CONCLUSIONS: In a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.