Explore the vast range of titles available.

Beta-blockers have been the initial treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM) despite limited evidence of their efficacy. Aficamten is a cardiac myosin inhibitor that reduces left ventricular outflow tract gradients, improves exercise capacity, and decreases HCM symptoms when added to standard medications. Whether aficamten as monotherapy provides greater clinical benefit than beta-blockers as monotherapy remains unknown. We conducted an international, double-blind, double-dummy trial in which adults with symptomatic obstructive HCM were randomly assigned in a 1:1 ratio to receive aficamten (at a daily dose of 5 mg to 20 mg) plus placebo or metoprolol (at a daily dose of 50 mg to 200 mg) plus placebo. The primary end point was the change in peak oxygen uptake at week 24; secondary end points were improvement at week 24 in New York Heart Association (NYHA) functional class and changes at week 24 in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), left ventricular outflow tract gradient after the Valsalva maneuver, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, left atrial volume index, and left ventricular mass index. A total of 88 patients were assigned to the aficamten group and 87 to the metoprolol group. The mean age of the patients was 58 years, 58.3% were men, and the mean left ventricular outflow tract gradient was 47 mm Hg at rest and 74 mm Hg after the Valsalva maneuver. At 24 weeks, the change in the peak oxygen uptake was 1.1 ml per kilogram of body weight per minute (95% confidence interval [CI], 0.5 to 1.7) in the aficamten group and -1.2 ml per kilogram per minute (95% CI, -1.7 to -0.8) in the metoprolol group (least-squares mean between-group difference, 2.3 ml per kilogram per minute; 95% CI, 1.5 to 3.1; P<0.001). Patients who received aficamten had significantly greater improvements in NYHA class, KCCQ-CSS, left ventricular outflow tract gradient, NT-proBNP level, and left atrial volume index than patients who received metoprolol. No significant difference in left ventricular mass index was observed. Adverse events appeared to be similar in the two treatment groups. Among patients with symptomatic obstructive HCM, aficamten monotherapy was superior to metoprolol monotherapy in improving peak oxygen uptake and hemodynamics and decreasing symptoms. (Funded by Cytokinetics; MAPLE-HCM ClinicalTrials.gov number, NCT05767346.).

Advanced glycation end products(AGEs)/RAGE(receptor for AGEs) play divergent roles in cardiovascular disease. Our study is to evaluate the correlation between AGEs/RAGE in circulation (soluble AGEs/RAGE, sAGEs/sRAGE) and in myocardium (mAGEs/mRAGE), and to explore their relationship with cardiac function and prognostic value in hypertrophic obstructive cardiomyopathy (HOCM). 78 HOCM patients under septal myectomy were recruited. The soluble and myocardial AGEs/RAGE levels were determined by a commercial available ELISA kit at the time of baseline examination. Strain analysis in HOCM patients derived from cardiac magnetic resonance feature tracking, including global/septal radial strains (GRS/SRS), circumferential strains(GCS/SCS), and longitudinal strains(GLS/SLS). Histological fibrosis was assessed through masson's staining as collagen volume fraction (CVF). All patients were followed up for a composite endpoint for a median duration of 3.8 years. sAGEs/sRAGE were higher in HOCM patients than healthy controls(p = 0.025; p = 0.028). Log sRAGE was correlated with log mRAGE(r = 0.739, p < 0.01), CVF(r = -0.411, p < 0.01), GRS (r = 0.412, p < 0.01), GCS(r = 0.463, p < 0.01). Log mRAGE also showed a correlation with CVF(r = -0.439, p = 0.003), SRS (r = 0.4, p = 0.013) and SCS (r = 0.362, p = 0.03). Log mAGEs was correlated with log mRAGE(r = 0.376, p = 0.012). Multivariate COX analysis revealed that log sRAGE was a significant predictor for the occurrence of adverse events in HOCM patients(HR, 0.013; 95% CI, 0.001-0.313; p = 0.007). Circulating RAGE appears to act as a protective biomarker, as it is associated with better prognosis after septal myectomy, reducing fibrosis and improving cardiac function in HOCM patients. It is plausible that higher circulating RAGE levels may be derived from higher expression levels in the myocardium.

This study shows that myocardial fibrosis is an early characteristic of hypertrophic cardiomyopathy caused by sarcomere mutations. The C-terminal propeptide of procollagen type I was shown to be a serum biomarker of early myocardial fibrosis. Hypertrophic cardiomyopathy is caused by mutations in genes encoding sarcomere proteins. 1 , 2 With a prevalence of approximately 1 case per 500 persons in the general population, hypertrophic cardiomyopathy is the most common monogenic cardiac disorder. 3 The clinical diagnosis depends on the identification of unexplained left ventricular hypertrophy, but this finding is present only in persons with established disease and is typically absent in childhood. 4 In contrast, genetic diagnosis identifies pathogenic sarcomere mutations in persons at any age, including mutation carriers with overt hypertrophic cardiomyopathy and mutation carriers without hypertrophy who are at high risk for the development of disease. Studying . . .

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and is associated with a high risk of sudden cardiac death. HCM is characterized by pronounced hypertrophy of cardiomyocytes, fiber disarray and development of fibrosis and can be divided into a non-obstructive (HNCM) and obstructive form (HOCM) therefore requiring personalized therapeutic therapies. In the present study, we investigated the expression patterns of several circulating circular RNAs (circRNAs) as potential biomarkers in patients with HCM. We included 64 patients with HCM and 53 healthy controls to the study and quantitatively measured the expression of a set of circRNAs already known to be associated with cardiac diseases (circDNAJC6) and/or being highly abundant in blood (circTMEM56 and circMBOAT2). Abundancy of circRNAs was then correlated to relevant clinical parameters. Serum expression levels of circRNAs DNAJC6, TMEM56 and MBOAT2 were downregulated in patients with HCM. The inverse association between circRNA levels and HCM remained unchanged even after adjusting for confounding factors. All circRNAs, evaluated separately or in combination, showed a robust discrimination capacity when comparing control subjects with HCM, HNCM or HOCM patients (AUC from 0.722 to 0.949). Two circRNAs, circTMEM56 and circDNAJC6, significantly negatively correlated with echocardiographic parameters for HOCM. Collectively, circulating circRNAs DNAJC6, TMEM56 and MBOAT2 can distinguish between healthy and HCM patients. In addition, circTMEM56 and circDNAJC6 could serve as indicators of disease severity in patients with HOCM. Thus, circRNAs emerge as novel biomarkers for HCM facilitating the clinical decision making in a personalized manner.

Friedreich’s ataxia (FRDA) is an inherited neurodegenerative disorder frequently complicated by hypertrophic cardiomyopathy (HCM), a major cause of morbidity and mortality in these patients. Conventional protein biomarkers, such as high-sensitivity troponin or collagen turnover markers, provide only modest diagnostic accuracy, highlighting the need for more sensitive tools. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers, but independent validation in FRDA remains limited. We analyzed a cohort of FRDA patients ( n  = 34) and age-, sex-, and race-matched healthy controls ( n  = 34). Expression of a previously proposed miRNA signature was evaluated in plasma using RT-qPCR, with normalization to miR-16-5p, replicating prior methodology. Echocardiographic parameters were compared across subgroups. Associations between differential miRNA expression, comorbidities (diabetes mellitus, cardiomyopathy), and echocardiographic measures were evaluated. Receiver Operating Characteristic (ROC) curves and multivariable logistic regression assessed diagnostic performance. Five of seven candidate miRNAs were validated as differentially expressed in FRDA compared with controls. Among patients, miR-128-3p, miR-130b-5p, miR-151a-5p, miR-330-3p, and miR-142-3p were significantly up-regulated in those with diabetes. For cardiomyopathy, both miR-323a-3p (previously described by our group) and miR-625-3p showed strong associations. A multivariable model combining miR-323a-3p and miR-625-3p achieved promising discriminative performance for HCM (Area Under the Curve (AUC) = 0.84; sensitivity 80%; specificity 71.4%), outperforming traditional protein biomarkers. This two-miRNA panel offers robust non-invasive prediction of HCM in FRDA and highlights metabolic miRNAs as dual biomarkers for diabetes comorbidity. Prospective longitudinal studies and development of standardized diagnostic kits are warranted to integrate miRNA profiling into FRDA clinical care.

Background Circulating microRNAs may represent novel markers for cardiovascular diseases. We evaluated whether circulating miRNAs served as potential biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods Cardiac magnetic resonance imaging with postcontrast T 1 mapping was performed to non-invasively quantify diffuse myocardial fibrosis in HCM patients who were classified into two groups (T 1  < 470 ms or T 1  ≥ 470 ms, as likely or unlikely to have diffuse fibrosis, respectively). First, we screened 84 miRNAs using human serum/plasma miRNA array on plasma of 8 HCM patients (4/group based on T 1 time) and 4 healthy controls. From the results of this initial array, 16 miRNAs were selected based on their fold changes and relevance to myocardial fibrosis for further validation by Taqman real-time PCR in 55 HCM patients. Results Among the 16 miRNAs, the expression of miR-96-5p and miR-373-3p was low. The remaining 14 (miR-18a-5p, miR-146a-5p, miR-30d-5p, miR-17-5p, miR-200a-3p, miR-19b-3p, miR-21-5p, miR-193-5p, miR-10b-5p, miR-15a-5p, miR-192-5p, miR-296-5p, miR-29a-3p, and miR-133a-3p) were upregulated in HCM patients with T 1  < 470 ms compared with those with T 1  ≥ 470 ms, and 11 (except miR-192-5p, miR-296-5p and miR-133a-3p) were significantly inversely correlated with postcontrast T 1 values. Individual miRNA had moderate diagnostic value for diffuse myocardial fibrosis (AUC: 0.663–0.742), but the diagnostic value was greatly improved (AUC: 0.87) for a combination of 8 miRNAs. In comparison, circulating markers of collagen turnover did not have predictive values for diffuse myocardial fibrosis. Conclusions These findings suggest that circulating miRNAs provide attractive candidates as putative biomarkers for diffuse myocardial fibrosis in HCM.

Cardiac troponin I (cTnI) is a cardiac specific biomarker of myocardial damage in humans, dogs, and cats. The ADVIA Centaur XP High-Sensitivity Troponin I assay (AC-cTnI-HS) has been validated for use in humans and dogs, but not for use in cats. The study objective was to analytically validate the AC-cTnI-HS assay for use in cats and to evaluate cTnI measurements in healthy cats compared to those with cardiac disease to assess the clinical utility of this assay. Surplus serum samples from cats were used for analytical validation. Intra- and inter-assay variability, dilutional parallelism, and spiking recovery were assessed. Serum samples from 106 client-owned cats were evaluated. This group was comprised of 51 clinically healthy cats (structurally normal echocardiogram, normal systemic blood pressure, and unremarkable complete blood count and biochemistry profile), 25 cats with stage B1 hypertrophic cardiomyopathy, 7 with stage B2 hypertrophic cardiomyopathy, 7 with stage C cardiomyopathy of any type, 8 with congenital heart disease, and 8 cats with transient myocardial thickening and/or suspected to have myocarditis. Inter-assay and intra-assay coefficients of variation were between 2.7–8.3% and 1.5–4.0%, respectively. The mean ± standard deviation observed to expected ratios for dilutional parallelism and spiking recovery were 124.3 ± 42.8% and 92.9 ± 6.2%, respectively. Healthy cats had significantly lower cTnI concentrations than cats with hypertrophic cardiomyopathy stage B1 (P = 0.012), stage B2 (P = 0.004), or any cardiomyopathy ACVIM stage C (P = 0.002). The AC-cTnI-HS assay is precise, reproducible, linear, and accurate for measurement of cTnI concentrations in serum from cats. This study confirms that measurement of serum cTnI holds promise to have clinical utility as it was able to detect differences in serum cTnI concentrations between healthy cats and those with cardiac disease.

Background HCM‐AF score is a novel risk stratification tool for atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM). N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) has shown promise in predicting AF. We aim to explore the incremental value of NT‐proBNP over HCM‐AF score. Methods In this retrospective cohort study, 778 HCM patients were included. The primary endpoint was new‐onset AF. Spline curve analysis was conducted to identify the cut‐off value of NT‐proBNP. Harrell's C‐index and likelihood ratio test were conducted to explore the incremental value. Results After a follow‐up of 3.4 ± 2.3 years, AF occurred in 65 (8.4%) patients. The cut‐off of NT‐proBNP was 240 pg/mL. Incidence rates of AF per 1000 person‐years for the low, intermediate, and high HCM‐AF score groups were 8.7 (95% confidence interval [CI]: 3.5–17.7), 18.0 (95% CI: 7.7–48.8), and 59.6 (95% CI: 27.1–157.1), respectively, with the high HCM‐AF score group significantly higher. For the low and high NT‐proBNP groups, incidence rates were 9.2 (95% CI: 4.6–16.1) and 38.1 (95% CI: 20.3–79.4), respectively. High HCM‐AF score (hazard ratio [HR]: 3.55, 95% CI: 1.33–9.48; p = 0.011) and high NT‐proBNP (HR: 2.49, 95% CI: 1.21–5.10; p = 0.013) are independent predictors for AF. Addition of NT‐proBNP improved models based on HCM‐AF score, with C‐index increasing from 0.709 to 0.768 and likelihood ratio increasing from 33.15 to 51.02. Conclusion HCM‐AF score is reliable and robust for Asian HCM patients. NT‐proBNP demonstrated incremental value over HCM‐AF score in the prediction of new‐onset AF in patients with HCM. Future studies are warranted to incorporate HCM‐AF score and NT‐proBNP. In Asian patients with hypertrophic cardiomyopathy, integrating NT‐proBNP with the clinical HCM‐AF score provides significant incremental prognostic value. This combined multiparametric assessment enhances the predictive accuracy for new‐onset atrial fibrillation, enabling more precise risk stratification and targeted clinical management.

AimsCMR feature tracking strain (CMR-FT) provides prognostic information. However, there is a paucity of data in hypertrophic cardiomyopathy (HCM). We sought to analyze global CMR-FT parameters in all four cardiac chambers and to assess associations with NT-proBNP and cardiac troponin T (hsTnT) in patients with HCM.MethodsThis retrospective study included 144 HCM patients and 16 healthy controls with CMR at 1.5 T. Analyses were performed on standard steady-state free precession cine (SSFP) CMR data using a commercially available software. Global left ventricular (LV) strain was assessed as longitudinal (LVLAX-GLS), circumferential (LVLAX-GCS) and radial strain (LVLAX-GRS) on long -axis (LAX) and as LVSAX-GCS and LVSAX-GRS on short- axis (SAX). Right ventricular (RV-GLS), left atrial (LA-GLS) and right atrial (RA-GLS) strain were assessed on LAX.ResultsWe found LVLAX-GLS [− 18.9 (− 22.0, − 16.0), − 23.5 (− 25.5, − 22.0) %, p = 0.0001), LVSAX-GRS [86.8 (65.9–115.5), 119.6 (91.3–143.7) %, p = 0.001] and LALAX-GLS [LA2CH-GLS 29.2 (19.1–37.7), LA2CH-GLS 38.2 (34.3–47.1) %, p = 0.0036; LA4CH-GLS 22.4 (14.6–30.7) vs. LA4CH-GLS 33.4 (28.4–37.3) %, p = 0.0033] to be impaired in HCM compared to healthy controls despite normal LVEF. Furthermore, LV and LA strain parameters were impaired in HCM with elevated NT-proBNP and/or hsTnT, despite preserved LVEF compared to HCM with normal biomarker levels. There was a moderate correlation of LV and LA CMR-FT with levels of NT-proBNP and hsTnT.ConclusionCMR-FT reveals LV and LA dysfunction in HCM despite normal LVEF. The association between impaired LV strain and elevated NT-proBNP and hsTnT indicates a link between unapparent functional abnormalities and disease severity in HCM.Graphic abstract Typical CMR-FT findings in patients with hypertrophic cardiomyopathy

The value of the triglyceride-glucose (TyG) index for predicting the prognosis in patients with hypertrophic cardiomyopathy (HCM) and heart failure with preserved ejection fraction (HFpEF) remains unexplored. Patients from 15 centers were included. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular mortality and sudden cardiac death (SCD). Restricted cubic spline analyses, multivariate Cox regression analyses, competing risk models, subgroup and mediation analyses were used to assess the relationship between the TyG index and outcomes. A total of 1095 patients with HCM and HFpEF were included. During a median follow-up period of 69 months, 224 all-cause deaths, 142 cardiovascular deaths, and 56 SCDs occurred. Multivariable Cox regression showed that the highest TyG index quartile was associated with a lower incidence of all-cause (hazard ratio (HR) 0.74, 95% CI 0.56-0.99, P = .046) and cardiovascular mortality (HR 0.65, 95% CI 0.44-0.94, P = .024) compared to the lowest quartile. However, no significant association was found between the TyG index and SCD (HR 0.74, 95% CI 0.41-1.31, P = 0.300). The competing risk model confirmed a significant association between the TyG index and reduced cardiovascular mortality (HR, 0.56; 95%CI, 0.40-0.78, P = .001) but no significant association with SCD (HR, 0.69; 95% CI, 0.37-1.27, P = .230). Mediation analyses indicated N-terminal pro-B-type natriuretic peptide mediated the association between TyG index and cardiovascular survival, while serum creatinine had a suppression effect. A higher TyG index was associated with lower risks of all-cause and cardiovascular mortality but with no significant influence on SCD risk in patients with HCM and HFpEF.