Background: Guidelines recommend using multiple drugs in patients with heart failure (HF) with reduced ejection fraction, but there is a paucity of real‐world data on the simultaneous initiation of the 4 pharmacological pillars at discharge after a decompensation event. Methods and Results: A retrospective data mart, including patients diagnosed with HF, was implemented. Consecutively admitted patients with HF with reduced ejection fraction were selected through an automated approach and categorized according to the number/type of treatments prescribed at discharge. The prevalence of contraindications and cautions for HF with reduced ejection fraction treatments was systematically assessed. Logistic regression models were fitted to assess predictors of the number of treatments (≥2 versus <2 drugs) prescribed and the risk of rehospitalization. A population of 305 patients with a first episode of HF hospitalization and a diagnosis of HF with reduced ejection fraction (ejection fraction, <40%) was selected. At discharge, 49.2% received 2 current recommended drugs, β‐blockers were prescribed in 93.4%, while a renin‐angiotensin system inhibitor or an angiotensin receptor–neprilysin inhibitor was prescribed in 68.2%. A mineralocorticoid receptor antagonist was prescribed in 32.5%, although none of the patients showed contraindications to mineralocorticoid receptor antagonist prescription. A sodium‐glucose cotransporter 2 inhibitor could be prescribed in 71.1% of patients. On the basis of current recommendations, 46.2% could receive the 4 foundational drugs at discharge. Renal dysfunction was associated with <2 foundational drugs prescribed. After adjusting for age and renal function, use of ≥2 drugs was associated with lower risk of rehospitalization during the 30 days after discharge. Conclusions: A quadruple therapy could be directly implementable at discharge, potentially providing prognostic advantages. Renal dysfunction was the main prevalent condition limiting this approach.

Aims: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF. Methods and results: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e′ ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19–6.5, P < 0.01)], higher E/e′ ratio (MD 2.76 CI 1.54–3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04–2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04–9.57, P = 0.04]. Conclusions: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization.

Data on the early use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in patients with acute heart failure (HF) are conflicting, and mostly evaluating soft endpoints (i.e., indices of congestion, renal function, ejection fraction, and diuresis). The aim was to perform a meta-analysis of randomized controlled trials (RCTs) to assess their impact after an HF decompensation event. Two electronic databases were screened for eligible studies. Efficacy endpoints were all-cause death, cardiovascular death, HF hospitalization, length of hospital stay, and N-terminal pro-B-type natriuretic peptide (nt-proBNP). Safety endpoints included acute kidney injury (AKI), volume depletion, ketoacidosis, hypotension, hypoglycemia, non-cardiovascular death, urinary tract infection, genital infections, serious adverse events (AE), and AE leading to treatment discontinuation. Two pre-specified subgroup analyses were planned according to the specific SGLT2i and clinical setting [i.e., acute myocardial infarction (MI) versus non-acute MI]. 16 RCTs enrolling 15,073 patients were considered. Early initiation of SGLT2i significantly reduced the risk of HF hospitalizations [Risk ratio (RR) 0.79, 95 % Confidence interval (CI) 0.72-0.87], AKI (RR 0.76, 95 % CI 0.59-0.99), and nt-proBNP levels (MD -354 pg/mL). No significant difference was detected for any of the other endpoints. In the pre-specified subgroup analysis, a significant interaction was found between the SGLT2i type and the risk of AKI, in favor of empagliflozin. In patients recently hospitalized for acute HF, early administration of SGLT2i was associated with fewer readmissions for HF and AKI, as well as decongestant effects, without raising any safety concern.

Bicuspid aortic valve (BAV) is the most common congenital valvular anomaly, affecting roughly 1–2% of the population and predisposing to premature aortic stenosis and thoracic aortopathy. Surgical aortic valve replacement (SAVR) remains the standard therapy, while transcatheter aortic valve implantation (TAVI) is increasingly adopted across a broader range of risk profiles due to accumulating evidence and advancements in device technology. Observational registries and early trial data indicate that TAVI is technically feasible in selected BAV anatomies, with device-success rates exceeding 90%. Nonetheless, bicuspid morphology is still technically demanding, with several possible pitfalls during transcatheter procedure and pre-procedural planning compared with tricuspid valve. The rates of moderate-to-severe paravalvular leak (PVL), permanent pacemaker implantation (PPI), and annular complications remain high, especially in the presence of extensive calcifications with raphe or tapered roots, underscoring the importance of meticulous multimodality imaging, dedicated sizing algorithms, and device-specific strategies. Long-term durability signals are encouraging but remain limited, underlining the need for prospective trials with extended follow-up. This review summarizes current knowledge on BAV anatomy and its management, exploring the available evidence supporting the role of transcatheter approach in this challenging and unique scenario.

Background: The prevention of reperfusion injury remains an unmet need in ST‐elevation myocardial infarction (STEMI) patients. Several randomized controlled trials (RCTs) evaluated mild hypothermia as adjunctive therapy during STEMI, with conflicting results.Aims: To summarize the evidence about the efficacy and safety of mild hypothermia in patients with STEMI, as well as its conclusiveness through a trial sequential analysis (TSA).Methods: PubMed and Scopus electronic databases were screened for eligible studies until August 12, 2024. Efficacy endpoints were all‐cause death, infarct size (IS), left ventricular ejection fraction (LVEF), the occurrence of microvascular obstruction (MVO), thrombolysis in myocardial infarction (TIMI) flow grade 3, and the resolution of ST‐segment elevation (i.e., > 50−70% from baseline) after the procedure. Safety endpoints included: the incidence of atrial fibrillation (AF), infections, any bleeding, major bleeding, acute and subacute stent thrombosis (STh), cardiogenic shock/pulmonary oedema, and ventricular fibrillation/tachycardia. “Door‐to‐balloon time” was indicated as the procedural endpoint. Two pre‐specified subgroup analyses were planned according to the mean ischemic time and the site of hypothermia induction (intra‐coronary vs. extra‐coronary). A TSA was run to explore whether the effect estimate of each efficacy outcome could be influenced by further studies.Results: Ten RCTs were included. Hypothermia did not provide a benefit for any of the specified efficacy endpoints. Furthermore, it enhanced the risk of infection, the risk of STh in patients with a mean ischemic time of less than 4 h, and the risk of AF in patients undergoing extra‐coronary hypothermia. Finally, it was also associated with an increased “door‐to‐balloon time”, and a trend toward an increased risk of any bleeding. No significant difference was found for the other endpoints. TSA showed conclusive evidence of an absence of benefit of hypothermia on IS, MVO, LVEF, and TIMI three flow.Conclusions: Mild hypothermia is not beneficial and causes relevant delays in clinical management of STEMI patients, raising safety issues mainly related to the occurrence of STh, AF, and infections.

Background: Myocardial bridge (MB) is a frequent coronary artery anomaly. The aims of this study are to describe the use of antiplatelet therapy (APT) in a cohort of patients with MB and assess its impact on ischemic and bleeding events. Methods: The RIALTO (Myocardial Bridge Evaluation Towards Personalized Medicine) registry (ID: NCT05111418) is an ambispective multicenter observational registry, enrolling patients with a clinical indication to coronary angiography and evidence of MB. The present analysis included patients with MB without any preexisting indication for APT/anticoagulant therapy according to guidelines. Patients were categorized into 2 groups: single APT or no APT based on discharge prescriptions. The primary end point was the time to first occurrence of net adverse clinical events, defined as a composite of cardiovascular death, nonfatal myocardial infarction, unplanned or elective coronary angiography, ischemic cerebrovascular events, and any bleeding. Results: Out of 486 enrolled patients with MB, 221 (mean age: 60 years, 66% male) were included in this analysis. One hundred and forty‐one patients (64%) received single APT. At a median follow‐up of 1661 days, patients with MB receiving single APT had a higher rate of net adverse clinical events (adjusted hazard ratio [aHR], 6.2; P =0.03), mainly driven by a higher rate of minor bleeding events (aHR, 10.58; P =0.02), with no difference regarding ischemic events. Results were consistent after 1:1 propensity‐score matching sensitivity analyses. Conclusions: The prescription of single APT is common in patients with MB, and it seems to be associated with an increased risk of bleeding, in the absence of a beneficial effect on ischemic events.