Prevalence and characteristics of normal electrocardiograms in hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is a genetic heart muscle disease characterized by left ventricular hypertrophy, affecting about 1 in 500 individuals. Sarcomeric gene mutations are found in 40–60% of cases. Despite its phenotypic diversity, the 12-lead ECG remains a key initial screening tool. Over 90% of HCM patients have ECG abnormalities, but a small, milder subgroup may present with a normal ECG, delaying diagnosis. Purpose This study aims to evaluate the prevalence and clinical characteristics of HCM patients with a normal ECG and explore its association with demographic and disease-specific variables. Methods HCM patients were retrospectively identified based on current ESC guideline criteria. Resting 12-lead ECGs at diagnosis were analyzed. Two definitions of abnormal ECG were used. The primary definition included atrial fibrillation, AV or bundle branch block, pathological Q waves, repolarization abnormalities, voltage criteria (Sokolow-Lyon ≥35 mm), low voltage, QTc 460 ms, or QRS 120 ms. The secondary definition added axis and PR interval abnormalities. ECGs not meeting these criteria were classified as normal. ECG status was analyzed as a binary variable ("Normal" vs. "Abnormal"). Results Among 682 patients with HCM, 11 patients (1.6%) had a completely normal ECG, while 98.4% showed at least one abnormal finding. Figure-1 summarizes the clinical, laboratory, imaging, and ECG characteristics. The most common abnormality was repolarization abnormality (82.6%), followed by LVH voltage criteria (70.2%). Normal ECGs were significantly associated with a lower NT-proBNP levels (p = 0.001), higher TAPSE (p = 0.047), lower PASP (p = 0.020), and less frequent presence of LGE on CMR (p = 0.035). Most patients had multiple ECG abnormalities, with 3 or 4 abnormal criteria being most common (18.6%). The number of ECG abnormalities varied by HCM subtype (p 0.001), highest in apical HCM. LGE presence and diffuse LGE pattern were associated with a higher number of ECG criteria (p 0.001 and p = 0.004, respectively). The number of ECG abnormalities correlated positively with wall thickness, NT-proBNP, left atrial diameter, pulmonary pressures, age, and SCD risk score, while negatively with TAPSE and LVEF. Figure 2 shows the distribution and frequency of ECG abnormalities in HCM patients, their associations with clinical parameters such as TAPSE, PASP, and NT-proBNP, and how the number of ECG criteria varies by HCM subtype and presence of LGE. Conclusion A completely normal ECG is exceedingly rare in patients with HCM. Abnormal ECG findings are more prevalent in apical HCM and are associated with greater disease burden. Patients with normal ECGs exhibit lower NT-proBNP levels, higher TAPSE, and less frequent LGE, suggesting a milder phenotype. Conversely, a higher number of ECG abnormalities correlates with increased SCD risk, lower LVEF and TAPSE, indicating that the extent of ECG abnormalities may reflect disease severity.Figure-1 Figure-2