Study Population
Fifty-five patients with non-obstructive HCM [40 males, 15 females, aged 22–66 (44.7 ± 9.8) years], diagnosed at the Longyan First Affiliated Hospital of Fujian Medical University from January 2022 to March 2023 were selected. HCM was diagnosed according to the 2014 ESC Guidelines [5]: wall thickness ≥ 15 mm in LV myocardial segments (or ≥ 13 mm in cases of affected first-degree relatives) that could not be explained by abnormal loading conditions. The exclusion criteria were as follows: NYHA functional class ≥ IV, resting blood pressure ≥ 180/100 mmHg (poor control of medications), combined with acute myocardial infarction, any condition that does not tolerate exercise, patients who have undergone surgical LV outflow tract evacuation or septal alcohol ablation, obstruction of the left or middle LV outflow tract, hypertension, aortic stenosis, or other distinct diseases causing cardiac hypertrophy.
A control group was also selected comprising 55 healthy volunteers [38 males, 17 females, aged 25–63 (46.9 ± 10.9) years] with normal 12-lead electrocardiogram (ECG) and echocardiogram and matched for age and sex. All participants signed a written informed consent form, and the study was approved by the hospital ethics review committee (approval number: LYREC2022-015-03).
Conventional echocardiography and myocardial workGE Vivid E95 color Doppler ultrasound diagnostic apparatus (GE Medical Systems, Milwaukee, WI, United States) with an M5Sc-D probe (frequency 1.5–4.5 MHz) was used. Images were digitally stored and analyzed offline using EchoPAC 203 workstation. Participants were placed in the left lateral recumbent position and connected to the limb lead ECG. When the patient's respiration and heart rate were stable, the patient's age, height, and weight were entered, and the BSA was calculated. The LVEDd, LVESd, LAD, MWT at end-diastole, LVEF measured using Simpson's method, mitral valve early diastolic flow E peak (E), mitral valve late diastolic flow A peak (A), mitral annulus early diastolic septal side, and lateral wall-side peak velocity (e') were measured from the parasternal long-axis view and four-chamber apical views. Then, the mean E/e' was calculated. All parameter measurements and analyses were conducted in accordance with the American Society of Echocardiography and the British Society of Echocardiography guidelines [23, 24].
The probe was placed on the apical part of the heart, and apical four-chamber, three-chamber, and two-chamber heart images were acquired and stored for three consecutive cardiac cycles.
The images were imported into EchoPac 203 image analysis software, and the endocardium of the apical four-chamber, two-chamber, and three-chamber heart images were traced, the width of the region of interest was adjusted to wrap around the entire myocardium, and the systolic and diastolic pressures of the patient's brachial artery were entered. The software automatically measured and calculated the overall LV GLS (Fig. 1), PSD, GWI, GCW, GWW, GWE, and PSL (Fig. 2).
Cardiopulmonary exercise test
Participants' height and weight were recorded, and BMI was calculated. A symptom-limited bicycle exercise test with standard incremental power was performed using a cardiopulmonary exercise system (Nanjing HigherMed Health Technology Co., Ltd., China) under the supervision of a cardiologist. The process included 3 min rest, 3 min no load, and 60 r/min speed cycling warm-up, followed by cycling at a constant speed to maintain 15–30 W/min incremental load power until the maximum exercise endurance (6–10 min) was achieved, then the recovery period was entered to maintain a cycling speed of 30–40 r/min for > 5 min. The gas collation mask was worn during exercise and connected to the volume sensor. The exhaled breath was continuously and automatically collected and analyzed through a gas sampling tube to continuously monitor heart rate, blood pressure, oxygen saturation, and 12-lead ECG. Peak VO2, AT, VO2/HR, and METs are indicators of exercise tolerance and were derived at the end of the exercise test. The VE/VCO2 slope was also derived and is an indicator of gas exchange. An abnormal blood pressure response to exercise was defined as an increase in peak SBP of < 20 mmHg from baseline and a decrease in SBP from baseline during recovery from exercise [25].
The exercise test was terminated under the following conditions: (1) The patient presented with chest pain, dyspnea, dizziness, palpitations, pain in the lower extremities, or fatigue and asked for termination; (2) ECG showed horizontal or downward sloping depression of the ST segment in adjacent leads ≥ 0.2 mV for ≥ 2 min; (3) Decrease in SBP ≥ 10 mmHg, SBP consistently below baseline with increasing power, SBP ≥ 220 mmHg, and/or diastolic blood pressure ≥ 110 mmHg; and (4) Severe arrhythmias, such as ventricular tachycardia, multiple premature ventricular beats, second or third degree atrioventricular conduction block, or sinus arrest.
Statistical Analysis
Statistical analysis was performed using SPSS version 26 (IBM, Armonk, NY). Continuous variables are expressed as means ± standard deviations. Comparisons between groups were made using two independent samples Student’s t-tests. Continuous variables with skewed distribution were denoted by M (P25, P75), and the Mann–Whitney U test was used for comparison between two groups. Categorical variables are expressed as frequencies and percentages, and comparisons between groups were made using χ2 or Fisher's exact test. Correlation analyses were performed using Pearson’s correlation coefficient. Intraclass correlation coefficients were calculated for inter-observer and intra-observer agreement in 20 randomly selected patients to evaluate reproducibility. P values < 0.05 were considered to indicate statistical significance.