Explore the vast range of titles available.

Background Left ventricular (LV) trabeculation are increasingly observed in patients with hypertrophic cardiomyopathy (HCM), but its clinical significance remains controversial. This study aims to clarify the characteristics of LV trabeculation and evaluate its prognostic value in HCM. Methods We evaluated 1028 patients with HCM undergoing cardiac magnetic resonance. For each patient, thickness of compacted and trabeculated myocardium was measured at 16 segments of LV. The extent of LV trabeculation was expressed as the maximal trabeculation/compaction (T/C) ratio in any of 16 segments. The primary endpoint was major adverse cardiovascular events (MACEs). The secondary endpoints were heart failure, thromboembolic events, and ventricular arrhythmias. There were 689 patients undergoing whole-exome sequencing. Results LV trabeculation predominantly located in midventricular-to-apical area, anterior, and lateral free walls in HCM. A greater extent of LV trabeculation was correlated with a higher prevalence of female, lower LV ejection fraction, and higher prevalence of extensive late gadolinium enhancement. During a median 4.8-year follow-up, a greater extent of LV trabeculation was associated with an increased risk of MACEs (adjusted hazard ratio [HR] 1.214, P  = 0.005), heart failure (adjusted HR 1.372, P  = 0.006), thromboembolic events (adjusted HR 1.242, P  = 0.032), and ventricular arrhythmias (adjusted HR 1.240, P  = 0.047). No gene was significantly associated with trabeculation at genome-wide level. Conclusions The distribution pattern of LV trabeculation was inhomogeneous and asymmetric in HCM. A greater extent of LV trabeculation was associated with poor prognosis. The progression of LV trabeculation might be the natural course of HCM. Graphical Abstract The distribution pattern of LV trabeculation in patients with HCM and the association between the extent of LV trabeculation and poor prognosis. CMR, cardiac magnetic resonance; HCM, hypertrophic cardiomyopathy; MACEs, major adverse cardiovascular events; LGE, late gadolinium enhancement; LV, left ventricular; LVEF, LV ejection fraction; WES, whole-exome sequencing

Background Potentially modifiable cardiovascular risk factors, including hypertension, diabetes, obesity, alcohol consumption, and smoking initiation, are associated with hypertrophic (HCM) and dilated (DCM) cardiomyopathies, representing promising targets for interventions. However, the causality and cross-ancestry generalizability of these associations remain uncertain. Methods Collecting summary-level data from genome-wide association studies for systolic (SBP) and diastolic (DBP) blood pressure, hypertension, type 2 diabetes, fasting glucose, glycated hemoglobin, body mass index (BMI), waist circumference (WC), alcohol consumption, smoking initiation, HCM, and DCM (sample size ranging from 38,288 to 1,812,017), we performed comprehensive two-sample univariable Mendelian randomization (MR) to evaluate the causal effect of each trait on HCM and DCM in both European and East Asian populations. We performed multivariable MR to investigate the independent effects of interrelated traits (SBP vs. DBP; BMI vs. WC). Results MR analyses identified reliable evidence of a causal effect of SBP on HCM (Europeans: odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.02–1.04; East Asians: OR = 1.06, 95% CI = 1.03–1.08). For DCM, reliable evidence of causal effects was identified for DBP (Europeans: OR = 1.04, 95% CI = 1.03–1.04; East Asians: OR = 1.07, 95% CI = 1.04–1.11), WC (Europeans: OR = 1.73, 95% CI = 1.58–1.89; East Asians: OR = 3.32, 95% CI = 1.22–9.03), and alcohol consumption (Europeans: OR = 1.50, 95% CI = 1.20–1.86; East Asians: OR = 1.32, 95% CI = 1.11–1.56). In Europeans, genetically predicted higher WC (OR = 1.75, 95% CI = 1.53–2.01) and smoking initiation (OR = 1.34, 95% CI = 1.16–1.56) specifically increased the risk of HCM and DCM, respectively, while genetically predicted higher alcohol consumption (OR = 1.68, 95% CI = 1.36–2.07) specifically increased the risk of HCM in East Asians. Conclusions This study provided reliable cross-ancestry genetic evidence supporting higher SBP as a causal risk factor for HCM and higher DBP, WC, and alcohol consumption as causal risk factors for DCM. These findings underscore the potential of precision prevention strategies targeting modifiable cardiovascular risk factors to reduce cardiomyopathy burden across populations.

Background Patients with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) exhibit structural and functional cardiac abnormalities. We aimed to identify imaging biomarkers for pre-clinical cardiomyopathy in healthy participants carrying cardiomyopathy-associated variants (G +). Methods We included 40,169 UK Biobank participants free of cardiac disease at the time of cardiac magnetic resonance imaging (CMR) and with whole exome sequencing. We validated 22 CMR measurements by associating them with incident atrial fibrillation (AF) or heart failure (HF). We subsequently assessed associations of these CMR measurements with HCM G+, DCM G + , or specific genes, utilising generalised linear models conditional on cardiac risk factors. Results Thirteen CMR measurements were associated with incident AF and 15 with HF. These included left ventricular (LV) ejection fraction (EF; hazard ratio [HR] 0.61, 95% confidence interval [95%CI] 0.54; 0.69) for HF and indexed maximum left atrial volume (LAVi max; HR 1.47, 95%CI 1.29; 1.67) for AF. Five measurements associated with HCM G + , amongst which right ventricular (RV) end-systolic volume (RV-ESV; odds ratio [OR] 0.62, 95%CI 0.53; 0.74), RV-EF (OR 1.36, 95%CI 1.19; 1.55), and right atrial (RA) EF (OR 1.22, 95%CI 1.08; 1.39). Associations overlapping with incident disease and HCM G + had opposite effect directions, such as RV-ESV with HF (HR 1.22, 95%CI 1.07; 1.40). Two CMR measurements associated with DCM G + : LV-ESVi (OR 1.35, 95%CI 1.15; 1.58) and LV-EF (OR 0.75, 95%CI 0.64; 0.88). We observed significant associations with individual cardiomyopathy genes, finding that mitral annular plane systolic excursion associated with TTN and TNNT2 , and LA pump volume and RA-EF associated with MYH7 . Conclusions We identified right-heart CMR measurements associated with HCM G + in healthy individuals, indicating early compensation of cardiac function. LV measurements associated with DCM G + , where CMR associations varied across individual DCM genes, suggesting distinct early pathophysiology.

Background Understanding restrictive cardiomyopathy (RCM) in children is limited, and currently, no prognostic model is available for assessing risk stratification in pediatric RCM. The authors elaborated on the clinical and genetic characteristics of pediatric RCM and developed a prediction model to assess the 1-year risk of major adverse cardiovascular events (MACE), aiding in determining the optimal timing for heart transplantation (HTx). Methods This multicenter retrospective cohort study collected data on children with RCM from 14 centers in China, with patient enrollment from January 1, 2013, to December 31, 2022, and follow-up concluding on August 1, 2023. It analyzed clinical and genetic characteristics and followed patients longitudinally for the development of MACE (including cardiac death, HTx, or equivalent events). A logistic regression model was developed to predict MACE one year post-diagnosis, with internal validation using bootstrapping. The model’s performance was evaluated in terms of its discrimination, calibration, and clinical utility. Results The study included 185 children with a median diagnosis age of 5.4 years (IQR, 3.1–9.4), and 110 (59%) were male. Significant heart failure was the primary clinical feature. TNNI3 mutations were present in 61% of cases, the most common in pediatric RCM. During the follow-up period, 114 patients (62%) experienced MACE, with the median MACE-free survival time for the entire cohort being 2.1 years post-diagnosis (IQR, 0.6–5.4). A prediction model was developed to estimate the one-year risk of MACE using four easily accessible clinical parameters: heart failure classification, brain natriuretic peptide levels, cardiac troponin levels, and a modified score for ST-segment deviation. Internal validation with bootstrapping confirmed accuracy, showing an optimism-adjusted C statistic of 0.78 (95% CI, 0.72–0.85) and a Brier score of 0.17 (95% CI, 0.14–0.21), with a calibration slope of 0.90 (95% CI, 0.63–1.27). Decision curve analysis indicated high net benefit across HTx treatment thresholds from 8.5% to 78.3%. Conclusions This model utilizes accessible clinical parameters to assess individual risk for MACE in pediatric RCM, potentially improving precision in healthcare strategies and supporting more informed clinical decision-making.

Background This study aimed to explore associations between the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet and the risk of incident cardiovascular disease (CVD) and arrhythmias, together with comparing to three other pre-existing diet quality indices. Methods A prospective analysis was conducted using the UK Biobank. MIND diet score, Mediterranean Diet Adherence Screener (MEDAS), Recommended Food Score (RFS), and Healthy Diet Indicator (HDI) were computed using the Oxford WebQ. Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results 193,983 participants were included in the CVD analyses, and 190,529 for arrhythmias. Compared with participants in the lowest quartile of MIND diet score, participants in the highest quartile had a lower risk of CVD (HR 0.86; 95% CI 0.81–0.91), ischemic heart disease (0.92; 0.85–0.98), stroke (0.86; 0.75–0.97), heart failure (0.79; 0.71–0.88), and total arrhythmias (0.93; 0.88–0.99), after adjusting for demographics, lifestyle, and chronic conditions. With further adjustment for metabolic profiles, the associations remain significant for CVD and its subtypes but become non-significant for arrhythmias. Strengths of association varied across diet scores, with associations for MEDAS (CVD and arrhythmias) and MIND (CVD subtypes). The associations with CVD were linear for MIND and MEDAS and non-linear for RFS. The association between MEDAS and arrhythmias was non-linear. We observed significant interactions by age and obesity for CVD. Conclusions The MIND diet was associated with CVD and arrhythmias, relying on a single day of dietary data to derive dietary patterns. The findings suggest that following the MIND diet was associated with a lower risk of CVD, heart failure specifically, and arrhythmias.

Background Low circulating transthyretin (TTR) concentration has been suggested as a biomarker of transthyretin tetramer instability, a prerequisite for the development of transthyretin cardiac amyloidosis. This study aimed to evaluate the associations between circulating TTR levels with incident atrial fibrillation (AF) and other arrhythmias. Methods This study used data from the UK Biobank. Participants with available TTR data and without prior arrhythmias were included. The primary outcome was new-onset AF. The secondary outcomes were new-onset supraventricular arrhythmias (SVA), bradyarrhythmias, cardiac block, and ventricular arrhythmias (VA). Multivariable Cox regression was applied to evaluate the associations between circulating TTR levels with arrhythmia outcomes. Results A total of 40,723 participants (mean age 56.7 ± 8.2 years; 55% women) were included. After adjusting for potential confounders, one standard deviation (SD) decrease in TTR levels was associated with an increased risk of incident AF ( HR 1.06, 95% CI 1.02–1.11). Furthermore, significant associations between low TTR with atrial structural remodeling were observed, manifesting as increased left atrial volume index ( β 0.51, 95% CI 0.09–0.92) and right atrial volume index ( β 0.87, 95% CI 0.39–1.40). In addition, there was a significant association between lower TTR levels with higher incident SVA risk, but not for bradyarrhythmias, cardiac block, or VA. A consistently significant interaction effect was identified between TTR levels and BMI for the risk of AF, SVA, bradyarrhythmias, and cardiac block (all P interaction  < 0.05), with lower TTR levels being significantly associated with a higher risk of AF ( HR 1.15, 95% CI 1.06–1.26), SVA ( HR 1.15, 95% CI 1.06–1.25), bradyarrhythmias ( HR 1.17, 95% CI 1.05–1.30), and cardiac block ( HR 1.15, 95% CI 1.02–1.29) among individuals with a BMI < 25 kg/m 2 . In addition, carriers of likely pathogenic or pathogenic TTR variants (LP/P) had lower levels of plasma TTR compared with noncarriers, as well as higher arrhythmia risks, especially for non-Val142Ile carriers. Conclusions Lower circulating TTR concentrations were associated with higher risk of incident AF. Exposure to low TTR and low BMI may be associated with a higher risk of AF, SVA, bradyarrhythmias, and cardiac block. Graphical Abstract Low circulating transthyretin levels predict incident AF. Abbreviations: TTR, transthyretin; AF, atrial fibrillation; SVA, supraventricular arrhythmias; VA, ventricular arrhythmias

Background Emerging epidemiological evidence implicates pulmonary dysfunction in cardiovascular pathogenesis, yet its arrhythmogenic potential remains poorly defined. Objectives We aimed to assess the link between ventilatory parameters, pulmonary disease phenotypes and risk of incident arrhythmias across diverse populations. Methods We analyzed data from 17,684 adults in two prospective cohort studies-the Atherosclerosis Risk in Communities (ARIC; n = 12,929) and Cardiovascular Health Study (CHS; n = 4,755). Adjudicated arrhythmia diagnoses (atrial fibrillation/flutter [AF/AFL], ventricular arrhythmias [VAs], high-grade atrioventricular [AV] block, and premature atrial/ventricular complexes [PAC/PVC]) were identified via hospitalization records and mortality data. Multivariable-adjusted Cox proportional hazards models quantified associations between forced expiratory volume in 1 s (FEV1%) predicted and forced vital capacity (FVC%) predicted quartiles with arrhythmia risk, adjusting for traditional cardiovascular risk factors. Results Over a median follow-up of 12.6 years, impaired FEV1% and FVC% corresponded to a graded increase in arrhythmia risk. Compared to the highest quartile, the lowest FEV1% predicted quartile had elevated hazards for any arrhythmias (HR 1.32, 95% CI 1.23–1.42), AF/AFL (HR 1.68, 1.52–1.85), VAs (HR 1.55, 1.29–1.86), high-grade AV block (HR 1.37, 1.08–1.73), and PAC/PVC (HR 1.42, 1.20–1.69). Similar trends were observed for FVC% predicted quartiles. These associations remained consistent in never-smoking individuals and across cohorts. Obstructive spirometry pattern was associated with the strongest arrhythmia risk, while restrictive ventilatory patterns showed relatively lower risk elevations. No association was observed with sick sinus syndrome. Conclusions Reduced pulmonary function suggested independent associations with incident arrhythmias across supraventricular, ventricular, and conduction system pathologies in two historical cohorts. These findings suggest that spirometric indices could potentially represent novel independent indicators for arrhythmia development worthy of further validation in contemporary settings,, with associations distinct from conventional cardiometabolic risk factors.

Background Chronic inflammatory cardiomyopathy (infl-CMP) is a long-term sequela caused by the chronicity of acute myocarditis, especially fulminant myocarditis (FM). Hydroxychloroquine (HCQ) may benefit these patients by inhibiting the excessive inflammatory response. Methods In this multicenter, randomized trial, we evaluated the efficacy and safety of HCQ in patients with chronic infl-CMP after FM. The primary outcome of the trial was a composite of the cardiovascular outcomes of time to cardiovascular death or heart transplant, hospitalization for heart failure or recurrence of myocarditis, permanent pacemaker, or implantable cardioverter defibrillator implantation. Secondary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular internal diastolic diameter (LVIDd), plasma levels of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) from baseline to 12 months. Results Fifty patients were randomized to receive HCQ combined with prednisolone (PDN) or PDN monotherapy for 12 months. Compared to PDN monotherapy, HCQ combined with PDN therapy reduced the primary composite outcome [hazard ratio (HR) = 0.28, 95% confidence interval (CI) = 0.11–0.71] and had significant changes in the increase of LVEF and the decrease of LVIDd, hs-cTnI, NT-proBNP, and hs-CRP in patients with infl-CMP. No serious drug-related adverse events were recorded in either group, indicating an acceptable safety profile. Furthermore, HCQ combined with PDN significantly reduced the levels of 16 plasma cytokines to levels comparable to healthy controls. Conclusions Twelve months of HCQ combined with PDN therapy significantly improved the prognosis and heart function, inhibited inflammation, and had acceptable safety in patients with infl-CMP after FM. Trial registration ClinicalTrials.gov identifier: NCT05961202. Graphical Abstract

Background Fibro-fatty replacement of the myocardium plays a key role in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and may be associated with progressive heart failure (HF). We aimed to investigate the characteristic of the fibro-fatty tissues of ACM patients and the plasma chemokines levels according to HF burden. Methods The expression level of markers for brown, beige, and white fat of fibro-fatty tissues was determined using a quantitative real-time polymerase chain reaction. Lipidomics analysis of fibro-fatty tissues ( n  = 10 for normal control [NC]; n  = 24 for ACM patients) was conducted using LC–MS. Single-cell RNA sequencing ( n  = 2 for NC; n  = 6 for ACM patients) was used to compare the immune environment in the myocardium. Immunostaining and enzyme-linked immunosorbent assay were used to examine the expression of CCL3 in the myocardium and plasma samples, respectively. Results The expression level of beige (TBX1 and TMEM26) and brown (TNFRSF9) fat markers were higher in the fibro-fatty tissues of ACM patients compared to NC. The fibro-fatty tissues revealed a significant increased level of saturated triglycerides (TGs) in ACM patients compared with NC. Single-cell RNA sequencing revealed the obvious accumulation of proinflammatory macrophages and a high expression level of proinflammatory markers in the myocardium of ACM patients compared to NC. The expression of CCL3 in the fibro-fatty tissues was positively correlated with HF progression in patients with ACM. Plasma CCL3 levels were significantly higher in patients with ACM compared to healthy volunteer. A total of 102 patients with ACM have been followed for a median of 7.8 years, indicating that plasma CCL3 levels could successfully predict the incidence of HF and heart transplantation (HTx)/death in patients with ACM (hazard ratio = 3.122 [95% confidence interval, 1.556–6.264]). The ROC curve analysis revealed the AUC value reached 0.814 for HF and 0.756 for HTx/death. Conclusions The increased level of saturated TGs and CCL3 in the fibro-fatty tissues might promote HF progression in ACM patients. Plasma CCL3 levels are useful for predicting HF-related adverse events in patients with ACM, but requiring further validation in larger and independent cohorts. Graphical Abstract

Background The presence and role of endogenous digoxin-like cardiotonic steroids (CTS) in humans is controversial. This study utilises a novel pipeline to quantify CTS and examines their interaction with digoxin within a randomised trial. Methods The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial randomised patients with permanent AF and symptoms of heart failure to low-dose digoxin or beta-blocker therapy; clinicaltrials.gov NCT02391337. Circulating CTS were detected and quantified using a new ultra-high-performance liquid chromatography tandem mass spectrometry (LC–MS/MS) pipeline. Results All 160 participants of the RATE-AF trial were included, with mean age 76 years (SD 8) and 46% women. Endogenous CTS detected and quantified in baseline samples included digoxigenin and digitoxigenin, plus low or unquantifiable levels of ouabain, telocinobufagin, cinobufagin, marinobufagenin, bufalin, cinobufotalin, dihydroouabain, and ouabagenin. Compared to beta-blockers, patients randomised to digoxin had better functional outcomes at 12 months for heart failure (− 0.57 New York Heart Association class, 95% CI − 0.82 to − 0.32; p  < 0.001) and atrial fibrillation (odds ratio 2.24 for a two-class improvement in modified European Heart Rhythm Association class, 95% CI 1.43–3.84; p  < 0.001), with lower NT-pro-B-type natriuretic peptide (geometric mean ratio 0.78, 95% CI 0.61 to 0.99; p  = 0.006). No interactions were observed for any baseline CTS with each outcome. Digoxin was associated with fewer adverse events (odds ratio 0.16, 95% CI 0.07–0.34; p  < 0.001), again without any interaction from circulating CTS. Digoxin levels by LC–MS/MS were strongly correlated with measurement by a clinical immunoassay ( r  = 0.87; p  < 0.001), and treatment with digoxin did not affect CTS concentrations at 6-month follow-up. Conclusions A range of CTS are detected in the circulation of patients with atrial fibrillation and heart failure. Within this randomised trial but limited by low circulating levels, CTS do not appear to interact with the ability of digoxin to improve wellbeing compared to conventional first-line treatment with beta-blockers. Graphical Abstract