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Background Hypertrophic Cardiomyopathy(HCM) is a genetically heterogeneous condition with varying presentations and clinical trajectories. The influence of genotype status on clinical manifestations remains unexplored. This study evaluated in a cohort of phenotype-positive HCM (P+) individuals the associations between genotype and clinical, arrhythmia and echocardiographic parameters.Aim To compare clinical characteristics, symptom burden, echocardiographic(ECHO) parameters, and comorbidity between gene-positive(G+) and gene-negative(G-) HCM subjects in a regional HCM cohort.Methods 255 subjects with HCM, stratified by G+ (n=89, 34.9%) and G- (n=166, 65.1%) were studied for clinical variables including hypertension(HTN), Type 2 Diabetes(T2D), Chronic Kidney Disease(CKD), obesity, New York Heart Association(NYHA) functional class, HCM related symptom burden assessed by a Total Symptom Score(TSS) (dyspnoea, chest pain, palpitations, syncope), ECHO parameters and arrhythmia.Results G- subjects were older than G+ (62.82 ± 18.47 vs 48.03 ± 20.10 years, p < 0.001). Males predominated (68.9% vs 47.9%, p < 0.001). BMI was similar (30.11 ± 7.16 vs 29.13 ± 6.55, p = 0.056). Symptom Burden and Functional Capacity: G+ subjects had higher NYHA Class I (75.7% vs 49.7%, p < 0.001) and less NYHA Class III-IV (5.0% vs 15.3%, p < 0.001). TSS was lower in G+ subjects (0.53 ± 0.80 vs 1.03 ± 0.99, p < 0.001), palpitations being predominant (18.1%). Dyspnoea (13.0% vs 30.6%, p < 0.001) and chest pain (11.6% vs 26.2%, p = 0.001) were more frequent in G- subjects. ECHO Findings: G- subjects had more severe phenotype: greater interventricular septal diameter at first (1.6126 ± 0.4768 vs 1.5109 ± 0.6610 mm, p < 0.001) and last ECHO(1.6846 ± 0.3983 vs 1.5884 ± 0.6270 mm, p < 0.001); larger left atrial size (4.1438 ± 0.6676 vs 3.9898 ± 1.0109, p < 0.001); higher prevalence of LV outflow tract obstruction (13.3% vs 1.6%, p < 0.001) and apical HCM at first (14.7% vs 5.6%, p = 0.013) and last ECHO (23.3% vs 11.3%, p = 0.009). Arrhythmia: AF prevalence was similar at first (6.1% vs 6.9%, p = 0.773) and last ECG (10.7% vs 14.5%, p = 0.335). Ventricular tachycardia was more frequent in G+ subjects (7.3% vs 3.8%, p = 0.175), with more Implantable Cardioverter Defibrillator (ICD) implantation (26.3% vs 20.8%, p = 0.248). Comorbidities: G- subjects had more comorbidities(1.09 ± 0.98 vs 0.76 ± 0.91, p < 0.001), including HTN (42.6% vs 20.0%, p < 0.001), T2D (20.8% vs 8.6%, p = 0.003), and CKD (14.2% vs 6.4%, p = 0.026). Obesity tended to be more common in G+ subjects(41.4% vs 31.7%, p = 0.071).Conclusion G- HCM subjects are older with a higher burden of symptoms and comorbidities and demonstrate more severe cardiac abnormalities. In contrast, G+ subjects present earlier and exhibit a milder predominantly arrhythmic phenotype. These findings underscore the heterogeneous nature of HCM and the need for tailored clinical management strategies based on genotypic and phenotypic differences.