Background The nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) better encapsulates the associated metabolic milieu. While MASLD is associated with increased heart failure (HF) risk, characteristics and outcomes of MASLD in patients with HF remain unclear.This paper aims to examine the prevalence and clinical correlates of MASLD in patients with HF from the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) Registry.Methods MASLD was defined as evidence of hepatic steatosis, with at least one of five metabolic criteria (among body mass index, glucose, blood pressure, triglycerides and high-density lipoprotein thresholds). Findings were externally validated in Clinical Data Analysis and Reporting System (CDARS), a Hong Kong HF cohort and BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF), a HF cohort across 11 European countries.Results Of 2698 patients with HF in ASIAN-HF, 927 (34.4%) had MASLD. They were younger, more often women and more likely to have HF with preserved ejection fraction (HFpEF) compared with those without MASLD. All-cause mortality was lower in MASLD versus non-MASLD (7.1% vs 11.7%, p=0.001), even after multivariable adjustment (adjusted HR (aHR) 0.58, 95% CI 0.39 to 0.86, p=0.007). All-cause mortality was also lower in MASLD versus non-MASLD in CDARS and BIOSTAT-CHF; however, after multivariable adjustment, the association remained significant only in CDARS (aHR 0.82, 95% CI 0.80 to 0.84, p<0.001) and was attenuated in BIOSTAT-CHF (aHR 1.08, 95% CI 0.67 to 1.73, p=0.750). Using waist-to-height ratio instead of body mass index in the MASLD definition reclassified <3% of patients.Conclusions In patients with HF, MASLD is highly prevalent, especially in younger women with HFpEF and is associated with better 1-year survival than in those without MASLD.
Background Exercise systolic blood pressure (SBP) indexed to fitness, expressed as SBP divided by peak metabolic equivalents (SBP/METpeak), is associated with cardiovascular events in patients undergoing exercise testing. We aimed to characterise the cardiac phenotype and outcomes of patients with elevated exercise SBP indexed to fitness.Methods We analysed 530 participants with suspected angina from the CE-MARC trial who had complete exercise treadmill testing, invasive coronary angiography (ICA) and cardiovascular magnetic resonance (CMR) imaging. High SBP/METpeak was defined as ≥18 mm Hg/METs. Obstructive coronary artery disease (CAD) was defined by quantitative ICA as ≥70% stenosis in a major epicardial artery. Inducible ischaemia and myocardial scar were assessed by stress perfusion and late gadolinium enhancement CMR, respectively. Major adverse cardiovascular events (MACE) were defined as all-cause death and acute coronary syndrome.Results High SBP/METpeak was present in 310 participants (58.5%) and prevalence increased progressively with the number of diseased vessels, presence of ischaemia and myocardial scar (p<0.01 for all). During a median follow-up of 15.9 years, high SBP/METpeak was associated with MACE after adjustment for age, sex, obstructive CAD, ischaemia and myocardial scar (adjusted HR per 1-unit increase, 1.02 (95% CI 1.00 to 1.03), p=0.012). Higher SBP/METpeak identified a worse prognosis in subgroups with and without obstructive CAD and in those with and without ischaemia or infarction (log-rank, p<0.005 for all).Conclusions Among patients with suspected angina, high SBP/METpeak was associated with myocardial ischaemia and scar and adverse long-term outcomes. However, this association appeared to be driven predominantly by lower exercise capacity rather than peak SBP. SBP/METpeak may therefore represent an exploratory integrated exercise marker requiring external validation.
Background The subcutaneous implantable cardioverter-defibrillator (S-ICD) avoids intravascular leads but does not provide chronic bradycardia pacing or antitachycardia pacing. We performed an updated systematic review and meta-analysis comparing S-ICD with transvenous ICD therapy, prioritising contemporary randomised evidence and clinically relevant device trade-offs.Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 (PROSPERO: CRD420261328562), PubMed/MEDLINE, Embase and CENTRAL were searched from inception and rerun on 14 September 2026. Randomised evidence was prioritised, with non-randomised evidence analysed separately as supportive. Published time-to-event HRs were retained where available; sparse binary outcomes were analysed without blanket continuity correction, and incompatible endpoints or follow-up horizons were reported separately.Results 23 reports representing 15 study/cohort families were included. In the published Prospective Randomized Comparison of Subcutaneous and Transvenous Implantable Cardioverter Defibrillator Therapy (PRAETORIAN)–Avoid Transvenous Leads in Appropriate Subjects (ATLAS) individual-participant-data analysis Transvenous Leads in Appropriate Subjects (ATLAS) individual-participant-data analysis, S-ICD was associated with a higher hazard of first inappropriate shock (HR 1.61, 95% CI 1.06 to 2.45). Trial-level analysis also showed a higher hazard of first appropriate shock (HR 1.54, 95% CI 1.14 to 2.09), although this finding was sensitive to the uncertainty method. Conversely, randomised evidence showed fewer lead-related complications with S-ICD in PRAETORIAN (HR 0.24, 95% CI 0.10 to 0.54) and fewer major lead-related perioperative complications in ATLAS (risk difference −4.4 percentage points, 95% CI −6.9 to −1.9). The two-trial all-cause mortality estimate was imprecise (HR 1.22, 95% CI 0.89 to 1.66). Infection, pneumothorax and tamponade outcomes were sparse and definition-dependent. PRAETORIAN-Extended Long-Term Follow-Up (XL) provided supportive extended follow-up but was not treated as an independent trial.Conclusions Randomised evidence suggests fewer lead-related and invasive device complications with S-ICD but a higher hazard of first inappropriate shock. First-appropriate-shock inference was method-sensitive, while mortality and rare-event comparisons remained uncertain. Device selection should therefore consider pacing and antitachycardia-pacing requirements, future procedures, infection severity and patient preferences without inferring equivalence from non-significant results.PROSPERO registration number CRD420261328562.
Background Double outlet right ventricle (DORV) encompasses a range of congenital heart defects. Although survival to adulthood has improved, late risks, particularly life-threatening arrhythmias and sudden cardiac death (SCD) persist.Objectives We evaluated long-term outcomes in an adult DORV cohort, including SCD risk and device therapy.Methods This multicentre, retrospective cohort study enrolled adults with DORV under follow-up at two UK tertiary centres from 2000 to 2023. Patients were classified by anatomical subtype and surgical strategy. The primary composite outcome was all-cause mortality, heart or heart–lung transplantation, aborted SCD or appropriate implantable cardioverter-defibrillator (ICD) shock.Results Among 254 patients (median age 20 (IQR 17.6 to 29.2) years; 52.8% male), 61.4% had biventricular repair. Complex (n=90, 35.4%) and Fallot-type (n=79, 31.1%) DORV predominated. Over a median 12.4 (7.4 to 17.3) years, 47 (18.5%) patients died: heart failure (40.4%) and SCD (25.5%) were leading causes. Aborted SCD occurred in 4 (1.6%) cases, 4 (1.6%) underwent heart transplantation and 10 (4.0%) received appropriate ICD shocks. One in eight patients experienced ventricular tachycardia and one in three developed supraventricular tachycardia. In exploratory multivariable analysis restricted to patients with biventricular repair, older age, pulmonary hypertension and baseline QRS >180 ms were associated with the composite outcome.Conclusions Amongst adult survivors of DORV, late mortality due to heart failure and SCD was considerable, whereas transplantation was uncommon. In the biventricular-repair subgroup, older age, baseline QRS >180 ms and pulmonary hypertension were associated with adverse outcome in exploratory analysis; these findings require validation.
Objective Gene therapies are increasingly being developed and evaluated to treat complex diseases with multiple genetic causes, including cardiovascular diseases (CVDs). However, these studies have not yet been reviewed systematically. We aimed to conduct a scoping review of randomised controlled trials of gene therapies for CVDs and create an evidence map of the included literature.Methods We searched six databases for studies published from November 2018 to March 2025. Our search yielded 9106 records, and 1864 publications were reviewed at the full-text level.Results We included 28 randomised controlled trials (RCTs) evaluating interventions delivered by RNA interference (13 RCTs; 46%), antisense oligonucleotides (9 RCTs; 32%), plasmids (4 RCTs; 14%) and other vectors (adeno-associated virus and adenovirus; 2 RCTs; 7%). Cardiovascular indications included dyslipidaemia (12 RCTs; 43%), ischaemia (4 RCTs; 14%), transthyretin amyloidosis (4 RCTs; 14%), heart failure (2 RCTs; 7%) and other CVDs (6 RCTs; 21%). Samples included an average of 183 participants (range: 5–655); studies followed these participants for an average of 13 months (range: 3–97). Interventions were efficacious in most (22 RCTs; 85%) of the 26 studies that reported efficacy outcomes, but effects lasted less than 1 year in most studies (69%; 18 RCTs). Serious adverse events varied widely by study (range: 0%–62% of intervention group participants), but 19 RCTs reported that less than 10% of intervention group participants experienced a SAE.Conclusions Gene therapies for CVDs were reported to be efficacious in most RCTs, but their effects lasted less than 1 year in 69% of studies. Gene therapies for CVDs show promise in their efficacy and relative safety, but more research is needed to evaluate their long-term effects and risks.
