Luca Monzo

Background: Concentrations of N-terminal pro-B type natriuretic peptide (NT-proBNP) are central to acute heart failure (AHF) diagnosis in dyspnoeic emergency departments (EDs) patients, but optimal thresholds remain uncertain. This study aimed to evaluate the diagnostic accuracy of various NT-proBNP thresholds for AHF, across the general population and in key subgroups (chronic kidney disease and obesity). Methods: A systematic review and meta-analysis were conducted, including studies published up to 28 August 2025, which reported the diagnostic performance of NT-proBNP thresholds for AHF in dyspnoeic ED patients. Results: The analysis included 31 studies comprising 26 948 patients. To exclude AHF, a fixed threshold of ≤300 ng/L yielded an area under the receiver operating characteristic curve (AUC) of 0.73 (0.69–0.77), with high sensitivity of 97.9% (96.9–98.5) and lower specificity of 46.2% (36.4–56.2); the negative predictive value of this threshold was 97.0% (96.5–97.4). Age-dependent thresholds (≥450 ng/L for patients aged <50 years, ≥900 ng/L for those aged 50–75 years, and ≥1800 ng/L for those aged ≥75 years), evaluated in 14 410 patients, achieved an AUC of 0.84 (0.83–0.85) with a more favourable balance between a sensitivity of 85.9% (85.0–86.7) and a specificity of 82.0% (81.2–82.9). In patients with chronic kidney disease (n = 2271), all fixed thresholds yielded AUC <0.80; age-dependent thresholds showed an AUC of 0.77 (0.75–0.78) with a specificity of 62.6% (59.4–65.7). In patients with obesity (body mass index ≥ 30 kg/m2), only age-dependent thresholds were assessed in 3562 patients; AUC was 0.82 (0.81–0.84), and sensitivity was 81.2% (79.2–83.1), broadly comparable to the overall population. Conclusion: A threshold ≤300 ng/L provides excellent rule-out performance for AHF, while age-dependent NT-proBNP thresholds offer superior diagnostic performance for ruling in AHF in the ED compared to fixed thresholds and demonstrate consistent accuracy across subgroups. However, evidence in patients with chronic kidney disease and obesity remains limited, both in terms of sample size and the range of thresholds evaluated.

BACKGROUND: Obesity is a major risk factor for atrial fibrillation and heart failure. We aimed to characterize left atrial (LA) structural and functional changes across body mass index (BMI) strata in patients with atrial fibrillation referred for catheter ablation. METHODS: We studied 1040 consecutive patients (67% men; mean age, 62 years; 71% in sinus rhythm). Participants were stratified by BMI (2 ). Comprehensive echocardiographic assessment of LA structure and function was integrated with invasive LA pressure measurements obtained via transseptal access during the ablation procedure. Associations across BMI strata were evaluated using regression analyses. RESULTS: Patients with higher BMI had larger estimated total blood and plasma volumes along with higher LA volumes and pressures, greater cyclic wall stress, and a rightward shift of the estimated LA pressure-volume relationship. Conversely, estimated operant LA stiffness did not differ across BMI strata. BMI-related differences in LA volume were attenuated by body surface area indexing but preserved with height-based indexing. Conventional volumetric indices of LA phasic function were similar across BMI strata, whereas available LA strain indices (n=107) were lower with greater adiposity, consistent with worse LA phasic function. Compared with patients without heart failure, those with heart failure exhibited more pronounced structural, functional, and hemodynamic atrial remodeling, consistent with a more advanced atrial myopathy phenotype. CONCLUSIONS: In patients undergoing atrial fibrillation ablation, higher BMI is associated with a predominantly load-related pattern of LA remodeling, characterized by larger LA volume and pressures, greater cyclic wall stress, and a rightward shift of the estimated pressure-volume relationship. BMI-associated early atrial remodeling may precede overt atrial dysfunction, potentially contributing to the link between excess adiposity, atrial fibrillation, and heart failure with preserved ejection fraction.

Summary: An administration of 3 hydroxy-butyrate (3-OHB) in experimental animals or humans is associated with an increase of cardiac output (CO), but whether this hemodynamic benefit reflects direct myocardial inotropy or heart unloading due to peripheral vasodilation remains unclear. It is also unknown if myocardial effects are due to engagement of receptor-mediated inotropic response, or due to improvement of myocardial bioenergetics. To address these questions, we studied integrated cardiovascular response (pressure-volume analysis of the left ventricle) and isolated left ventricular (LV) trabeculae from normotensive male HanSD rats (age 20-30 weeks) after administration of 3-OHB (1 mmol/l) and drugs targeting adrenergic and cAMP-dependent signaling – metoprolol, adenylyl cyclase inhibitor 2,5-dideoxyadenosine and isoprenaline, during Tyrode solution perfusion and 1 Hz pacing. Pressure-volume analysis demonstrated increased left ventricular end-systolic elastance (+34%), improved ventriculo-arterial coupling (+65%) and increased LV efficiency (+28%), indicating direct inotropic effect of 3OHB. In isolated LV trabeculae, 3-OHB increased twitch force in both groups, but increase was greater in healthy hearts (+55.8%) than in the HF group (+35.6%) ( p = 0.014). The inotropic effect of 3-OHB was not further augmented by coadministration of isoprenaline and was not attenuated by beta-1 adrenergic blockade or cAMP inhibition. Results suggest that 3-OHB directly improves LV inotropy and by a mechanism that is independent of receptor-mediated β-adrenergic signaling, most consistent with a direct bioenergetic pathway. These findings support 3-OHB as a candidate inotropic agent with a mechanistic profile distinct from conventional cAMP-dependent inotropes.

Acute heart failure (AHF) is a systemic condition characterised by multiorgan involvement that varies from subclinical to overt organ failure. The liver is particularly vulnerable due to its dual blood supply and sensitivity to haemodynamic and inflammatory disturbances. Abnormal liver function tests are highly prevalent in patients with AHF, reflecting major mechanisms: passive hepatic venous congestion from elevated central venous pressure, hepatocellular ischaemia from low cardiac output, systemic inflammation and poor metabolic status associated with cachexia. In patients with AHF, liver function tests at admission, during hospitalisation and at discharge are independently associated with rehospitalisation, cardiovascular and all-cause mortality. Persistent abnormalities after hospitalisation often reflect incomplete decongestion or irreversible structural liver changes. Therapeutic strategies focus on decongestion, optimisation of cardiac output and medication adjustments to avoid hepatotoxicity. Despite significant advances in understanding cardio-hepatic interactions, major gaps remain, including the lack of standardised definitions, limited mechanistic studies and the underrepresentation of patients with heart failure with preserved ejection fraction in contemporary research. Future research should explore targeted therapies to improve cardiohepatic interactions and patient outcomes.

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.

Ischemic cardiomyopathy (ICM) is a major cause of cardiovascular morbidity and mortality, characterized by a complex pathophysiological substrate and heterogeneous clinical trajectories. Despite decades of investigation, its diagnosis and management remain challenging, particularly regarding the role of coronary revascularization in addition to optimal medical therapy. Recent advances in pharmacotherapy, device-based interventions, and percutaneous techniques have expanded treatment options, but important evidence gaps persist. This state-of-the-art review critically appraises the contemporary diagnosis and management of ICM. Particular emphasis is placed on the integration of multimodality non-invasive imaging into clinical decision-making, the reinterpretation of myocardial viability and revascularization in light of recent randomized evidence, and the interface between chronic coronary syndrome guidance and heart failure with reduced ejection fraction care in patients with ischemic LV dysfunction. By integrating these domains, the review supports a management approach in which guideline-directed medical and device therapy remain foundational, whereas revascularization is individualized according to myocardial substrate, coronary anatomy, symptoms, comorbidities, procedural risk, and multidisciplinary Heart Team assessment.

Aims: Duchenne (DMD) and Becker (BMD) muscular dystrophies often progress to dilated cardiomyopathy and heart failure with reduced ejection fraction (HFrEF), a major cause of death in affected patients. Although guideline-directed medical therapy (GDMT) improves HFrEF outcomes, its real-world use in dystrophinopathies is poorly defined. We assessed GDMT utilization and optimization in the study population. Methods and results: HOPE-MD (Heart failure treatment OPtimization in patiEnts with Muscular Dystrophy) is a European, multicentre, registry including adults with genetically confirmed DMD or BMD and left ventricular ejection fraction (LVEF) ≤ 40%. GDMT was defined as concurrent use of a renin–angiotensin system inhibitor (RASi), beta-blocker, mineralocorticoid receptor antagonist (MRA), and sodium–glucose cotransporter-2 inhibitor (SGLT2i). Doses were categorized as target (≥100%), intermediate (50–99%), or low (<50%). Among 274 patients (age, 28 years; LVEF, 35%; DMD, 80%), 44 (16%) received GDMT at baseline, with only one quarter at ≥50% of the target dose. Underutilization was greatest for MRAs (n = 140, 51%) and SGLT2i (n = 60, 22%), whereas RASi (n = 246, 90%) and beta-blockers (n = 235, 86%) were frequently prescribed. After 24 months (n = 141), 40% received GDMT, and 22% received ≥50% of the target dose, primarily through MRA and SGLT2i initiation/uptitration. Contraindications accounted for only a small proportion of undertreatment. At a median follow-up of 2.2 (1.7–2.6) years, optimized GDMT was not associated with a statistically significant difference in the rates of death or HF hospitalization compared with low-dose or no GDMT (adjusted HR 0.70, 95% CI 0.28–1.74). Conclusion: In this European, multicentre registry, GDMT use and dose escalation were suboptimal in young patients with DMD/BMD and HFrEF.