Wilfried Mullens

Background and Aims: Randomized evidence comparing conduction system pacing (CSP) and biventricular pacing (BVP) following atrioventricular node ablation in patients with refractory atrial fibrillation (AF) and heart failure (HF) remains limited. This study evaluated whether CSP with left bundle branch area pacing is non-inferior to BVP in patients undergoing atrioventricular node ablation. Methods: CONDUCT-AF was an investigator-initiated, multicentre, randomized trial conducted across 10 European centres. Patients with refractory AF, HF with left ventricular ejection fraction (LVEF) < 50%, narrow QRS duration (≤120 ms), and N-terminal pro-B-type natriuretic peptide > 600 ng/L were randomized 1:1 to CSP or BVP. The primary endpoint was the change in LVEF after 6 months, assessed by an independent core laboratory. Secondary endpoints included echocardiographic, clinical, and procedural outcomes. Analyses followed the intention-to-treat principle. Results: Eighty-two patients were randomized (mean age 72 ± 7 years, 46% male). At 6 months, LVEF improved similarly in CSP {from 36% [95% confidence interval (CI) 33–39] to 46% [95% CI 44–49]; P < .001} and BVP group [from 34% (95% CI 31–36) to 46% (95% CI 43–49); P < .001]. The between-group difference was .4% (95% CI −3.1–3.8; P = .002 for non-inferiority). Changes in left ventricular volumes, clinical parameters, and composite endpoint of worsening HF or cardiovascular death were comparable between groups. Paced QRS [mean difference −14 ms (95% CI −19 to −9; P < .001)] and procedural and fluoroscopy times were significantly shorter with CSP compared with BVP. Conclusions: In HF patients with refractory AF undergoing atrioventricular node ablation, CSP with left bundle branch area pacing was non-inferior to BVP for LVEF improvement at 6 months, providing comparable clinical outcomes and a favourable procedural profile.

Aims: Obesity and atrial fibrillation (AF) are global epidemics, often co-existing and compounding cardiovascular risk. While catheter ablation has emerged as an effective strategy for rhythm control in symptomatic AF, it remains unclear whether obesity modifies its benefit. This post hoc analysis of the CABANA trial investigates the influence of baseline obesity on clinical outcomes after catheter ablation vs. drug therapy in AF patients. Methods and results: A total of 2170 CABANA participants with available body mass index (BMI) were included. Obesity was defined by BMI ≥ 30 kg/m2, and Class II obesity by BMI ≥ 35 kg/m2. Adverse outcomes, AF recurrence, and functional status were analysed using Cox, mixed-effects, and generalized estimating equation models, assessing treatment-by-obesity interactions. Obese patients exhibited higher comorbidity burden, worse baseline functional status, and more persistent AF compared to non-obese counterparts. Higher BMI was associated with increased cardiovascular hospitalization and a higher New York Heart Association functional class. Catheter ablation significantly reduced the risk of AF recurrence and improved symptom burden and functional capacity, irrespective of obesity status. No significant interaction was found between BMI and treatment effect on the primary composite endpoint of cardiovascular hospitalization or all-cause mortality. However, patients with Class II obesity or higher had worse absolute outcomes despite similar relative benefits from ablation. Conclusion: While obesity is associated with worse baseline status and outcomes, it was not shown to significantly alter the relative effectiveness of AF ablation compared to drug therapy. These findings support a multifaceted approach integrating rhythm control with upstream interventions targeting obesity-related atrial remodelling and comorbidity management.

Managing cardiorenal syndrome in acute decompensated heart failure remains a major challenge in contemporary cardiology. While pharmacological decongestion with diuretics is the cornerstone of therapy and is effective in most patients, worsening renal function and diuretic resistance continue to pose challenges in selected cases. Device-based therapies are increasingly explored to target key pathophysiological mechanisms underlying cardiorenal dysfunction. This expert review builds on a conceptual framework for device-based therapies. Rather than cataloguing individual technologies, we apply a functional framework that classifies devices according to their primary mode of action: reduction of venous or lymphatic congestion (‘pullers’), augmentation of arterial perfusion (‘pushers’), and direct removal of sodium and/or fluid (‘removers’). For each category, we integrate pathophysiological rationale with available clinical evidence, highlighting the predominance of early-phase physiological evidence and the need for randomized studies demonstrating benefit beyond optimized contemporary medical care.

BACKGROUND: Atrial functional mitral regurgitation (AFMR) characterizes a high-risk phenotype in heart failure with preserved ejection fraction (HFpEF). Although sacubitril/valsartan reduces functional mitral regurgitation (MR) in HF with reduced EF (HFrEF), its impact on exercise hemodynamics and the dynamic burden of AFMR in HFpEF remains to be elucidated. METHODS: This multicenter, randomized, open-label trial with blinded primary endpoint assessment assigned 84 patients with symptomatic HFpEF and at least moderate AFMR within the previous year to sacubitril/valsartan (n=41) or standard-of-care (SOC; n=43). The primary outcome was the 6-month change in the exercise mean pulmonary arterial pressure to cardiac output (mPAP/CO) slope, assessed using cardiopulmonary exercise testing with simultaneous echocardiography (CPETecho). Secondary outcomes included changes in peak oxygen consumption (peak VO ₂ ), Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels, left atrial (LA) volume and function, and AFMR severity in rest and during stress. RESULTS: At 6 months, sacubitril/valsartan significantly improved the mPAP/CO slope compared with SOC (adjusted between-group difference in change, –0.93 mm Hg/L/min; 95% CI, –1.80 to –0.07; P =0.035). This hemodynamic benefit was accompanied by improvements in peak VO ₂ (mean change, +0.9 versus –0.6mL/kg/min; P =0.002) and KCCQ (median increase, 10 versus 2 points; P =0.002). Significant reductions in NT-proBNP and LA volume were observed ( P P =0.020). Target dose was achieved in 60% of patients, with symptomatic hypotension as the primary titration-limiting factor. CONCLUSIONS: In HFpEF and AFMR, sacubitril/valsartan was associated with improvements in exercise hemodynamics and peak VO ₂ , along with attenuation of the exercise-induced increase in AFMR. These findings suggest a phenotype-specific benefit, warranting confirmation in larger, placebo-controlled, clinical outcome trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05991284. EudraCT: 2023-506634-70-00

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, with particularly poor outcomes in low- and middle-income countries (LMICs). Despite strong evidence for guideline-directed medical therapy in terms of mortality/morbidity reduction and improvement in quality of life, the real-world implementation remains suboptimal, even in high-income settings. In LMICs, barriers are compounded by limited access to diagnostics, essential pharmaceutical and device therapy, alongside socioeconomic constraints and fragmented healthcare systems. Structural inequities, including the underrepresentation of LMIC populations in clinical trials, further restrict the applicability of evidence-based interventions. This position document highlights key challenges to guideline implementation in resource-limited settings, including affordability, workforce shortages, cultural practices, and gaps in infrastructure and insurance coverage. Strategies to address these barriers include the use of accessible diagnostics, decentralization of care, expanded roles for non-specialist providers, and telemedicine-supported continuity of care. Broader systemic reforms, including improved insurance systems, stronger referral networks and the integration of primary prevention, are critical. Finally, equitable representation of LMIC populations in clinical research should be prioritized to ensure the safety and efficacy of future therapies. Bridging the gaps in HF care at the global level requires context-specific adaptation of international guidelines, targeted healthcare system strengthening, and innovative care delivery models that make evidence-based HF treatment accessible, affordable, and sustainable.

Left bundle branch area pacing is being increasingly adopted in routine clinical practice as a more physiological alternative to right ventricular and biventricular pacing. Understanding the concepts of this pacing modality may be a hurdle for the non-electrophysiologist and specialists alike. This review article aims to explain in a didactic manner the anatomical and electrophysiological principles underlying left bundle branch area pacing.

Background and Aims: Optimizing guideline-directed medical therapy (GDMT) remains vital for heart failure (HF) management. However, non-labelled dosing of sacubitril–valsartan is increasingly reported. This global survey characterized real-world sacubitril–valsartan prescribing patterns and evaluated pharmacist involvement in HF teams. Methods: The validated 26-item IKNOW-HF survey was disseminated globally to clinicians treating patients with HF. Participation was voluntary and anonymous. Results: Out of 1829 responses from 76 countries, 1285 (70.3%) were complete, predominantly from cardiologists 1031 (80.2%). Non-labelled sacubitril–valsartan dosing was reported by 1107 (86.1%) respondents, heavily driven by general cardiologists 326 (90%) and clinicians in the low- and lower-middle-income countries 195 (96%). Predictors of non-labelled dosing included practicing in Asia [odds ratio (OR) 0.347; 95% confidence interval (CI) (0.214–0.563)] and having over 10 years of experience [OR 0.695; 95% CI (0.489–0.990)]. The presence of a cardiology pharmacist trended towards a fewer non-labelled prescriptions [OR 0.542; 95% CI (0.283–1.039), P-value = 0.065], whereas management by HF specialist trended towards increased non-labelled usage [OR 1.443; 95% CI (0.981–2.122), P-value = 0.063]. Conclusions: The IKNOW-HF survey reveals a substantial variation between guideline-recommended and real-world prescribing practices, with over 80% of responding clinicians utilizing non-labelled dosing. The higher prevalence among HF specialists likely reflects a pragmatic salvage strategy for advanced HF patients intolerant to standard target doses. These findings highlight the need for further education, pragmatic clinical trials evaluating real-world dosing outcomes, and broader integration of specialized pharmacists to optimize GDMT.