Greater sodium avidity in acute heart failure (AHF) is associated with worse outcomes, but whether kidney tubule injury is associated with sodium avidity and impaired diuretic responsiveness remains underexplored. We evaluated 339 participants from the ROSE-AHF trial, which enrolled patients hospitalized for AHF with kidney dysfunction and randomized them to the dopamine, nesiritide, or placebo group. Urinary kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) were measured at enrolment. Associations between these biomarkers and urinary sodium (uNa) concentration at baseline, fractional excretion of sodium (FeNa), as well as total uNa output and urine output over 72-h were assessed using multivariable regression models. Higher KIM-1 and NAG values at baseline were associated with lower uNa concentration at baseline [-6.1% (-8.5%, -3.7%), P < 0.001 and -5.9% (-9.2%, -2.6%), P & .001, respectively, per two-fold increase in each biomarker]. Higher baseline KIM-1 and NAG were also associated with lower FeNa [-6.1% (-8.5%, -3.6%), P < .001 and -5.2% (-8.6%, -3.6%), P = 0 .001, respectively, per two-fold increase in each biomarker]. Higher baseline KIM-1 was associated with lower total uNa excretion over 72-h [-3.6% (-6.8%, -0.2%), P = 0.037 per two-fold increase]. None of the biomarkers were associated with urine output over 72-h. Kidney tubular injury, as assessed by urine KIM-1 and NAG, is associated with greater sodium avidity and higher KIM-1 is associated with impaired diuretic responsiveness in AHF.

The most clinically representative murine models of heart failure with preserved ejection fraction (HFpEF) include a '2-hit' model combining nitrosative stress with metabolic perturbation and a '3-hit' model that also includes ageing. Both models have important limitations with regard to substrain and sex. The 2-hit model protocol was modified to reproduce HFpEF in both C57BL/6N and 6J mice by increasing L-NAME doses (0.5 g/L to 1.75 g/L) and protocol lengths (7 weeks to 13 weeks). For the 3-hit model, in addition to deoxycorticosterone pivalate (DOCP), we added 1% NaCl drinking water to enhance and prolong the effect of DOCP ('4-hit'). To maintain the phenotype, a second bolus of DOCP was administered after 8 weeks. HFpEF was successfully induced in C57BL/6J mice when exposed to a 13-week 2-hit L-NAME protocol with gradually increasing dosage from 1.0 to 1.75 g/L. For the 4-hit mice, a clear HFpEF phenotype was observed in C57BL/6N and 6J mice in both male and females, and maintained for up to 12 weeks. These modifications ensure the 2-hit model is induced in J substrain of C57BL/6 mice. The 4-hit model prevents aldosterone escape and enhances reproducibility across sexes and substrains.

Heart failure (HF) management guidelines offer evidence-based recommendations but can be difficult to implement in primary care. This randomized controlled trial evaluated a multifaceted intervention to improve adherence to pharmacological and nonpharmacological HF management guidelines in primary care. Patients hospitalized with HF were randomized 1:1 to an intervention or control group. The intervention group received guideline-based inpatient education, a postdischarge plan including referral to cardiac rehabilitation (CR) and scheduled general practitioner follow-ups at 1 and 4 weeks, and 3 months, supported by a cardiologist-approved medication titration plan. The control group received usual care. The primary outcome, measured at 6 months, was adherence to five recommended treatments: (i) ACEI/ARB/ARNI ≥50% target dose, (ii) beta blocker ≥50% target dose, (iii) MRA at any dose, (iv) anticoagulation for atrial fibrillation, and (v) CR referral. Adherence was compared using chi-squared tests and logistic regression.Of 225 participants (25% female), a greater proportion in the intervention group achieved the primary outcome (61.8% vs. 28.7%; P < .01). The unadjusted odds ratio showed that the intervention group was 6.27 times more likely to achieve the outcome compared to the control group (95% confidence interval [CI], 3.35-11.76, P < .01). This difference was driven by higher prescription rates of ACEI/ARB/ARNI and beta blocker, and higher referral rates to CR. Hospital-based support for HF-management in primary care improved adherence to pharmacological and non-pharmacological components of guideline-recommended care. Greater implementation of transitional care processes of this nature has the potential to improve clinical outcomes for patients with HF.

Patients with first-degree atrioventricular (AV) block and mechanical AV dyssynchrony can present with heart failure (HF)-like symptoms. AV-optimized conduction system pacing (CSP) can improve haemodynamics and symptoms, but selection criteria remain uncertain. We aimed to identify electrocardiographic and echocardiographic predictors of an acute haemodynamic response to AV-optimized CSP in symptomatic first-degree AV block. Nineteen patients (mean age 60.5 ± 21.1 years; 37% female) with symptomatic first-degree AV block underwent baseline electrocardiography and echocardiography followed by AV-optimized conduction system pacing and repeat echocardiographic assessment. Electrocardiographic parameters (PR interval, P wave duration/PR interval ratio) and echocardiographic indices (E/A wave confluence, A-Q interval, and DFT/RR ratio) were tested for association with change in left ventricular stroke volume (LVSV).The mean PR interval was 395 ± 61 ms, the mean A-Q interval 155 ± 65 ms, and the mean DFT/RR ratio 0.34 ± 0.1. E/A wave confluence was present in 15 patients (79%). AV-optimized pacing increased LVSV by 7.8 ± 3.9 ml, corresponding to an 11.8 ± 5.7% relative increase (P < .01). Echocardiographic parameters were associated with LVSV response, including A-Q interval (r = 0.63, P = .004), DFT/RR ratio (r = -0.59, P = .008), and E/A wave confluence (r = 0.57, P = .01). Electrocardiographic parameters were not associated with LVSV change. Echocardiographically assessed mechanical AV dyssynchrony, rather than electrocardiographic parameters, is associated with an acute haemodynamic response to pacing. Echocardiographic evaluation may help identify patients with prolonged PR interval who could benefit from AV-optimized CSP.

Single-pill combinations (SPC, polypills) have proven effective in cardiovascular areas, yet no such therapy exists for patients with heart failure (HF) despite substantial polypharmacy and pill burden in this population. Simplifying treatment through an HF-specific SPC containing key guideline-directed medical therapy (GDMT) components could improve adherence and outcomes. Two prospective, electronic surveys were conducted between June and October 2025 to assess real-world attitudes towards a polypill in HF with ejection fraction ≤50%. The physician-oriented survey (22 questions) was distributed internationally and explored GDMT practices, perceived needs, barriers, and potential preferred composition of an HF dedicated SPC. The patient-oriented survey (11 questions) explored medication burden, adherence, and perceptions of a potential polypill use. A total of 250 physicians and 126 patients participated. Among physicians, 77% reported a clear need for strategies to simplify GDMT optimisation in HFrEF, with cost (66%) and polypharmacy (54%) being selected as the most frequent barriers. Nearly all physicians (95%) recognized a real clinical need for an HF-specific SPC, and most perceived it as clinically useful (88%), logistically feasible (76%), and acceptable to patients (94%). Approximately 48% of physicians declared that they would use it regularly, and another 49% would use it in selected patients. The preferred composition of HF-specific SPC included a beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor (61.2%).Among patients, polypharmacy was common (70% taking ≥6 drugs daily), and 75% admitted to occasional non-adherence. Most responders (82%) would support a solution that reduces the pill burden, and 83% would take an HF-specific SCP if offered, particularly if there is no extra cost. Both physicians and patients showed strong openness and willingness towards an HF-specific SPC, supporting further development and evaluation of HF-specific polypill strategies.

The global burden of heart failure (HF) is rising, with a shift towards more cases of heart failure with preserved ejection fraction (HFpEF). Given evolving epidemiology, an updated assessment of outcome differences between HFpEF and heart failure with reduced ejection fraction (HFrEF) is needed. This systematic review and meta-analysis aimed to provide a contemporary, large-scale comparison of clinical outcomes between HFpEF and HFrEF. A systematic review and meta-analysis were conducted to compare all-cause mortality, cardiovascular (CV) mortality, and HF hospitalizations in HFpEF (EF: >50%) and HFrEF (EF: <40%). Risk ratios (RR) and maximally adjusted hazard ratios (HR) with 95% confidence intervals (CI) were pooled using random-effects models. Additional analyses included prior HF hospital admissions, in-hospital mortality, and length of hospital stay. A total of 101 studies were included. HFpEF patients had lower all-cause mortality [RR: 0.78; 95% CI: 0.69-0.88; P < .001; adjusted HR: 0.71; 95% CI: 0.62-0.80; P < .001; 112 vs 148 per 1000 patient-years (PY)], CV mortality [RR: 0.64; 95% CI: 0.53-0.79; P < .001; adjusted HR: 0.65; 95% CI: 0.56-0.75; P < .001; 73 vs 110 per 1000 PY], and HF hospitalizations [RR: 0.75; 95% CI: 0.63-0.91; P = .003; adjusted HR: 0.87; 95% CI: 0.78-0.98; P = .02; 171 vs 225 per 1000 PY] compared to HFrEF. HFpEF patients experience lower mortality and hospitalization risks than HFrEF patients, even after adjustment for confounders. However, high absolute event rates in HFpEF highlight the need for effective treatment strategies to improve outcomes.PROSPERO registration ID: CRD42024619499.

Severe tricuspid regurgitation (STR) is associated with adverse outcomes. This nationwide registry describes the prevalence, aetiology, clinical, and echocardiographic profile of STR using contemporary classifications, and evaluates the prognostic impact of a modified right heart failure staging (RHFS). We prospectively enrolled consecutive patients with STR from 48 centres over 6 months and followed them for 1 year. TR severity (severe, massive, torrential) and aetiology were defined using current recommendations. A modified RHFS incorporating RV remodelling and systolic dysfunction was applied. We included 1247 patients (mean age 76.7 ± 10.5 years; 70.2% women): 64.9% had severe TR, 24.1% massive TR, and 11.0% torrential TR. V-STR due to left-heart disease was the most frequent aetiology (49.9%), followed by A-STR (19.8%). During follow-up, HF hospitalization occurred in 20.8%, cardiovascular death in 9.2%, and 12.3% underwent tricuspid intervention. In multivariable analysis, Stages III-IV of the modified RHFS were independently associated with HF hospitalization (HR 1.58; 95% CI 1.13-2.23; P = .008) and cardiovascular mortality (HR 2.01; 95% CI 1.27-3.18; P = .003). Massive (HR 1.72; 95% CI 1.02-2.91; P = .041) and torrential TR (HR 2.57; 95% CI 1.24-5.34; P = .011) were also associated with cardiovascular mortality. Massive and torrential TR identify patients at the highest risk. The modified RHFS stratifies patients with STR into prognostic categories and may help guide the timing of intervention.

It has become increasingly recognized that heart failure with a preserved ejection fraction (HFpEF) results from an inflammatory process, congestion, and metabolic dysbiosis rather than an intrinsic structural heart abnormality. Recent studies have highlighted the close link between the heart, the liver, and the pancreas, which are organically connected via the same inflammatory processes and pathways. Liver congestion and fibrosis are responsible for the inflammatory process and the lack of metabolic adaptation, whereas pancreatic ischaemia and insufficiency of the exocrine glands aggravate malnutrition and cachexia, worsening the heart condition. Acute pancreatitis may cause heart failure and arrhythmia through injury and systemic inflammatory response syndrome (SIRS), an inflammatory process mediated by the cytokines released during the injury process. Recognition of this hepato-pancreato-cardiac axis offers a paradigm shift towards integrated management of HFpEF, emphasizing anti-inflammatory, metabolic, and haemodynamic interventions. Future research integrating multi-organ imaging, inflammatory biomarkers, and therapeutic trials such as GLP-1 receptor agonists, SGLT2 inhibitors, and cytokine blockers will be critical to disrupt this tri-organ inflammatory circuit and improve outcomes in HFpEF.