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Colchicine attenuates cardiac hypertrophy by targeting the macrophage-driven Interleukin-6 suppression.

Hypertrophic cardiomyopathy (HCM), the most prevalent inherited cardiovascular disease, is strongly linked to progressive heart failure and sudden cardiac death (SCD). However, its underlying pathogenic mechanisms remain incompletely understood, and effective therapeutic strategies are still lacking. Here, we established two murine HCM models harboring high SCD risk-associated mutations. Single-cell RNA sequencing revealed immune activation and enhanced fibrotic remodeling in the myocardium of these models. Therefore, we hypothesized that colchicine, a widely used anti-inflammatory drug known to reduce cardiovascular events in multiple cardiac disorders, may also represent a promising therapeutic candidate for HCM. As we expected, colchicine treatment attenuated pathological remodeling in our study, as evidenced by reduced cardiomyocyte hypertrophy, decreased fibrosis, and downregulation of cardiac stress markers (Anp, Bnp) and fibrotic mediators (Ctgf, Col1a1, Col3a1). In addition, colchicine attenuated pro-inflammatory macrophage populations and suppressed IL-6 expression, thereby contributing to the preservation of cardiac function. These findings provide the first preclinical evidence that colchicine alleviates myocardial inflammation and fibrosis in HCM, underscoring its potential as a novel therapeutic strategy to reduce fibrosis, lower SCD risk, and improve patient outcomes.

Animals

Artificial intelligence-derived myocardial fibrosis on cardiac magnetic resonance for prognosis in cardiomyopathy: A systematic review of a sparse evidence base.

BACKGROUND: Myocardial fibrosis on cardiovascular magnetic resonance (CMR), assessed by late gadolinium enhancement (LGE) and parametric mapping, is an established predictor of adverse events in cardiomyopathy. We assessed whether artificial intelligence (AI) quantification of fibrosis adds independent prognostic value. METHODS: We searched six databases, a clinical-trials register, and a preprint server from inception to 13 June 2026. Eligible studies used AI to generate a fibrosis marker in adults with ischemic or nonischemic cardiomyopathy, with covariate-adjusted outcomes over ≥12 months. Risk of bias was assessed using PROBAST, PROBAST+AI, and QUIPS. Fewer than three comparable studies precluded meta-analysis; certainty was rated using GRADE. RESULTS: Of 448 records (381 after de-duplication), 18 full texts were reviewed and two included, one peer-reviewed and one preprint. In an ischemic-cardiomyopathy registry (Ghanbari et al.; n = 216 analytic, 26 events), AI-derived dense LGE scar predicted arrhythmic events (univariable hazard ratio [HR] 2.35, 95% CI 1.33-4.15), and AI-derived but not manual scar improved discrimination beyond guideline criteria (area under the curve 0.63 to 0.68; p = 0.02). In a nonischemic dilated-cardiomyopathy preprint (Kim et al.; n = 347, 119 events), automated extracellular volume ≥30% predicted cardiovascular death or heart-failure hospitalization (adjusted HR 2.00, 95% CI 1.32-3.03). Both were at high risk of bias, with data-derived thresholds and no external validation. CONCLUSIONS: Across only two studies, AI-derived fibrosis was independently associated with adverse cardiovascular events, but its added value over manual quantification remains unproven. Certainty was very low. The evidence base is sparse and not yet ready for clinical use.

Humans

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid &#x3b1;-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient &#x2264;66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score &#x2265;7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article

Finerenone and quality of life in heart failure: component-level analyses and clinical relevance of the Kansas City cardiomyopathy questionnaire.

AIMS: Finerenone was shown to improve overall health status, as measured by the aggregate 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) score, in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). This study aimed to contextualize KCCQ changes in a manner that is relevant to patients and clinicians, thereby improving understanding of this metric in HFmrEF/HFpEF. METHODS AND RESULTS: In this prespecified analysis of FINEARTS-HF, a double-blind, randomized, placebo-controlled trial of finerenone in HFmrEF/HFpEF, we performed exploratory assessments of treatment effects on mean score changes from baseline to 12 months for each of the 23 KCCQ components (scaled from 0 [worst] to 100 [best]) using multivariable linear regression. We further compared the impact of finerenone on the KCCQ-overall summary score (KCCQ-OSS) at 12 months with the expected decline per year. Of 6001 participants in FINEARTS-HF, 5006 completed the KCCQ both at baseline and 12 months (age: 72 &#xb1; 10 years, women: 45%, baseline KCCQ-OSS: 63.9 &#xb1; 22.0). Finerenone, compared with placebo, numerically improved all but one KCCQ component, with the greatest nominal improvement observed in lower limb oedema frequency (+2.5, 95% CI: 0.9-4.1), fatigue burden (+2.2, 95% CI: 0.9-3.5), fatigue frequency (+2.1, 95% CI: 0.7-3.6), and lower limb oedema burden (+1.8, 95% CI: 0.6-2.9). KCCQ-OSS at 12 months was inversely related to age, with finerenone shifting the age-KCCQ-OSS relationship by 4.7 (95% CI: 0.4-9.1) years. CONCLUSIONS: In FINEARTS-HF, finerenone was associated with modest improvements in health status-most notably lower limb oedema and fatigue-in patients with HFmrEF/HFpEF.

Humans

Bioepidemiology of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, primarily due to immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid, is an increasingly recognized cause of heart failure. Modern diagnostic advances suggest that ATTR, particularly in older adults, may be more prevalent than historically reported. METHODS: All Olmsted County decedents aged &#x2265;40 years from 1970 to 1976 were identified. Available ventricular myocardium from retained paraffin blocks was screened histologically for amyloid using sulfated Alcian blue staining; positive cases underwent grading and proteomic typing by laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Beyond prevalence estimation, this analysis characterizes amyloid type, deposition grade and distribution, associated comorbidities, and cause-of-death patterns, comparing amyloid-positive decedents with age- and sex-matched controls. RESULTS: Of 2,566 eligible deaths, 1,028 autopsy cases with evaluable myocardium formed the study cohort (mean age 70.5 years; 61.1% male; 97% White). Cardiac amyloid was present in 52 cases giving an overall prevalence of 5.1% (95% CI: 3.8-6.6, which rose from 0% under age 60 to 37.5% (95% CI: 21.1-56.3) in those &#x2265;90 years (p < 0.001). While prevalence estimates were higher in men above age 80 compared to women, there was no evidence of an interaction of age and sex (p = 0.90). The quantity of amyloid was sufficient for typing in 38 cases: ATTR (84.2%), AL (7.9%), serum amyloid A (5.3%), and apolipoprotein A-IV (2.6%). Adjusted estimates assuming untyped mild cases were ATTR-type increased ATTR prevalence to 4.5% (95% CI: 3.3-5.9) overall. Comorbidity profiles were similar between amyloid-positive and negative groups, though syncope and leg weakness were more common in amyloid-positive decedents. CONCLUSIONS: In an unselected autopsy cohort, cardiac amyloid was common, particularly ATTR in older adults. Prevalence increased steeply after age 80. These findings suggest that ATTR amyloidosis is not rare and is likely underdiagnosed and has similar prevalence in women and men, despite the male predominance reported in the literature.

Humans

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

Journal Article

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I.&#xa0;=&#xa0;50-66%) and Alzheimer's dementias(28.0%&#xa0;=&#xa0;95%C.I.&#xa0;=&#xa0;17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I.&#xa0;=&#xa0;17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I.&#xa0;=&#xa0;36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I.&#xa0;=&#xa0;38.3-45.6%), anxiety(32.0%;95%C.I.&#xa0;=&#xa0;26.5-37.6%), MDD&#xa0;+&#xa0;anxiety(24.7%;95%C.I.&#xa0;=&#xa0;17.9-34.3%), and dementia(19.8%;95%C.I.&#xa0;=&#xa0;12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I.&#xa0;=&#xa0;21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I.&#xa0;=&#xa0;12.0-46.0%), MDD in PVI patients (20.0%;95%C.I.&#xa0;=&#xa0;13.0-29.0%); in coronary artery disease: MDD&#xa0;+&#xa0;anxiety(19.8%;95%C.I.&#xa0;=&#xa0;16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I.&#xa0;=&#xa0;0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I.&#xa0;=&#xa0;0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I.&#xa0;=&#xa0;0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans

Responsiveness of muscle mass gain to different load intensities of resistance training in older women: A randomized crossover study.

BACKGROUND: Aging is associated with progressive declines in skeletal muscle mass (SMM) and substantial interindividual variability in adaptations to resistance training (RT). However, whether training load intensity influences hypertrophic responsiveness in older adults remains unclear. OBJECTIVE: To investigate the effects of two commonly prescribed RT loading schemes (15RM and 10RM) on estimated SMM adaptations and responsiveness in older women. METHODS: Twenty-seven older women (67.7&#xa0;&#xb1;&#xa0;4.9&#xa0;years; 65.7&#xa0;&#xb1;&#xa0;10.6&#xa0;kg; 154.5&#xa0;&#xb1;&#xa0;5.8&#xa0;cm) completed two 8-week RT interventions performed at 15RM and 10RM in a randomized crossover design, separated by a 12-week detraining period. Estimated SMM was assessed using dual-energy X-ray absorptiometry. Responsiveness was operationally defined using the standard error of measurement, and participants were classified as responders (RP) or non-responders (N-RP) according to changes in estimated SMM. RESULTS: Both loading schemes promoted significant and comparable increases in estimated SMM (15RM: +0.62&#xa0;&#xb1;&#xa0;0.4&#xa0;kg vs. 10RM: +0.43&#xa0;&#xb1;&#xa0;0.3&#xa0;kg). Overall, 61.1% of participants were classified as responders in at least one condition, whereas 38.9% were classified as non-responders. Responsiveness status was consistent across conditions for most participants, with 48.1% classified as responders under both loading schemes and 25.9% as non-responders under both conditions. Only seven participants (25.9%) changed responsiveness status between interventions. No clear pattern indicated a greater likelihood of responsiveness with either loading scheme. CONCLUSIONS: Results suggest that both the 10RM and 15RM RT protocols significantly increase estimated SMM in older women, with no significant differences between training conditions. Although substantial interindividual variability in adaptive responses exists, training load intensity does not appear to meaningfully influence responsiveness status in most individuals. These findings suggest that both loading schemes can be effectively prescribed to promote SMM gains in older women.

Aged

Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: Win-ratio reanalysis of the TRANSFORM-HF trial.

BACKGROUND: Loop diuretics are widely used for managing congestion in patients with heart failure (HF). The TRANSFORM-HF trial is a multicenter randomized study that enrolled heart failure patients, comparing a strategy of torsemide vs furosemide. The time-to-event analysis demonstrated neutral effects on all-cause death at 30 months and the composite of all-cause death and first rehospitalization at 12 months. We evaluated whether a hierarchical win-ratio (WR) framework integrating mortality, recurrent hospitalization, and patient-reported health status provides additional interpretive insight. METHODS: This study is a secondary analysis of the pragmatic, multicenter, open-label, randomized TRANSFORM-HF trial, conducted across 60 US hospitals that randomized 2,859 patients hospitalized with HF to torsemide or furosemide. The primary 12-month hierarchical composite outcome was defined as (1) all-cause mortality, (2) recurrent all-cause hospitalizations, and (3) lack of improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS). The primary statistical method was a WR analysis adjusting covariates via inverse probability weighting. Subgroup analyses evaluated potential heterogeneity across patient demographics and clinical characteristics. RESULTS: In the primary 12-month intention-to-treat analysis, the adjusted WR was 1.07 (95% CI, 0.98-1.16; P = .13), indicating no significant difference between torsemide and furosemide. A supplementary 30-month analysis with extended mortality follow-up yielded a similar estimate (adjusted WR, 1.06; 95% CI, 0.98-1.16; P = .14); hospitalization and KCCQ-CSS components were assessed through 12 months. As-treated sensitivity analyses were consistent with the neutral primary findings. Exploratory subgroup analyses were not adjusted for multiplicity and should be considered hypothesis-generating. CONCLUSIONS: The overall WR comparison between torsemide and furosemide showed no statistically significant difference in the primary 12-month analysis. The WR framework provided an interpretive decomposition across outcome domains but did not establish superiority of either loop diuretic strategy. All findings should be considered exploratory. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03296813, https://clinicaltrials.gov/study/NCT03296813.

Aged

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6&#xa0;months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12&#xa0;months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6&#xa0;months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p&#xa0;=&#xa0;0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p&#xa0;<&#xa0;0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p&#xa0;<&#xa0;0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6&#xa0;months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans