Influencing and prognostic factors of end‐stage hypertrophic cardiomyopathy

Abstract

Aims

End‐stage hypertrophic cardiomyopathy (ES‐HCM) is a disease with severe complications and a poor prognosis. This study aimed to explore the influencing and prognostic factors of ES‐HCM.

Methods and results

A total of 1282 patients with HCM who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. The patients with HCM and left ventricular ejection fraction (LVEF) < 50% were defined as having ES‐HCM, and a control group (LVEF ≥ 50%) was generated from the collected medical records of HCM. The patients were matched in a ratio of 4:1 based on age and sex. Logistic regression analysis was used to determine the influencing factors of ES‐HCM. Kaplan–Meier survival analysis was performed to analyse the clinical outcomes of ES‐HCM patients. A total of 250 inpatients with HCM were enrolled in the study; 50 patients had ES‐HCM, and 200 had HCM with LVEF ≥ 50%. The mean age of the patients at enrolment was 62.5 ± 10.3 years, and 215 patients (215/250, 86.0%) were male. The median follow‐up time of the patients was 2.8 (1.4–5.4) years. The incidence of all‐cause death and cardiovascular death in patients with ES‐HCM was higher than those in patients with HCM and LVEF ≥ 50% (22/50 [44.0%] vs. 13/200 [6.5%]; 12/50 [24.0%] vs. 4/200 [2.0%], all P < 0.001). Multivariate logistic regression analysis showed that the influencing factors associated with ES‐HCM included age at first symptom onset (odds ratio [OR] = 0.95, 95% CI [0.90, 1.00], P = 0.042), New York Heart Association (NYHA) class (OR = 7.73, 95% CI [2.93, 20.41], P < 0.001), heart rate (OR = 1.07, 95% CI [1.02, 1.12], P = 0.003), QRS duration (OR = 1.03, 95% CI [1.00, 1.05], P = 0.020), left ventricular end‐diastolic diameter (LVEDD) (OR = 1.15, 95% CI [1.04, 1.28], P = 0.006), left atrial anteroposterior diameter (LAD) (OR = 1.13, 95% CI [1.03, 1.24], P = 0.012), and maximum left ventricular wall thickness (MLVWT) (OR = 0.80, 95% CI [0.68, 0.93], P = 0.005). Among the 50 patients with ES‐HCM, NYHA class (P < 0.001) and heart rate (P = 0.017) were each associated with a higher likelihood and earlier occurrence of heart transplantation or all‐cause mortality in univariate analyses.

Conclusions

The influencing factors for ES‐HCM included the age at first symptom onset, NYHA class, heart rate, QRS duration, LVEDD, LAD, and MLVWT. Both NYHA class and heart rate were related to the prognosis of ES‐HCM.

Introduction

Hypertrophic cardiomyopathy (HCM) is a hereditary heart disease, characterized by left ventricular hypertrophy and is caused by mutations in sarcomere protein-coding genes (or related genes) or an unknown aetiology.¹ As the disease progresses, few patients with HCM develop left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] < 50%), defined by Harris as the end-stage phase of hypertrophic cardiomyopathy (ES-HCM).² The pathophysiological mechanism of ES-HCM is not fully understood but may be associated with myocardial ischemia, myocardial fibrosis, and left ventricular remodelling etc.^3–5

Olivotto et al. proposed a systematic clinical staging for HCM: stage I (nonhypertrophic HCM), stage II (the ‘classic’ HCM phenotype), stage III (adverse remodelling), and stage IV (overt dysfunction).⁶ Most HCM patients are in stage II; the clinical phenotype is relatively stable, and generally, there is no or only mild myocardial fibrosis. As the disease progresses, extreme fibrosis and remodelling of the myocardium may occur. Stage IV coincides with the so-called ES-HCM, generally associated with haemodynamic decompensation and adverse outcomes. There are two common types of HCM: a dilated form with left ventricular dilation and a restrictive pattern with atrial dilation.^7,8 The prognosis of patients with ES-HCM has been quite poor, and the time from diagnosis to heart transplantation or death is approximately 2.7 ± 2 years,² with mortality as high as 11–13.2% per year.^2,9 It is crucial to identify patients with HCM who are more likely to develop ES-HCM. However, few studies have investigated the predictive factors and prognosis of ES-HCM. In this study, the medical records of inpatients with HCM were reviewed and analysed to explore the influencing and prognostic factors of ES-HCM.

Methods

Patients

Overall, 1282 patients with HCM aged ≥ 18 years who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. Patients with cardiac hypertrophy due to endocrine abnormalities or drugs, malignant tumours, immune diseases (including systemic lupus erythematosus, hyperthyroidism, and autoimmune haemolytic anaemia), and incomplete medical records were excluded.

HCM was defined as unexplained left ventricular (LV) hypertrophy with a maximal LV wall thickness of ≥15 mm or ≥13 mm and a family history of HCM. Patients were designated as having ES-HCM at the first documentation if the LVEF was <50% on a clinically performed echocardiographic study.

Fifty patients with ES-HCM (50/1282, 3.9%) met the inclusion criteria, and the matched population generated from the collected medical records of patients with HCM according to sex and enrollment age (±3 years) comprised 200 patients with left ventricular ejection fraction (LVEF) ≥ 50%. The two groups were matched at a ratio of 4:1.¹⁰

The clinical status of study participants was obtained through outpatient follow-up or telephone interviews after the first discharge. Patients who died from cardiovascular factors or other factors or underwent heart transplantation were regarded as reaching the endpoints. Follow-up began after enrolment in the study. The last follow-up of survivors was conducted on 30 September 2022.

Echocardiogram

An echocardiographic examination was performed with patients in the left lateral decubitus position using commercially available ultrasound machines (Vivid E7, GE Company, USA) according to the operating guidelines of the United States Ultrasound-Echocardiography Association.¹¹ The left ventricular end-diastolic diameter (LVEDD), left atrial anteroposterior diameter (LAD), right ventricular end-diastolic diameter (RVEDD), interventricular septal thickness (IVS), maximum left ventricular wall thickness (MLVWT), pulmonary artery internal dimension (PAD), LVEF, and left ventricular outflow tract (LVOT) gradient were recorded. LVEF was calculated from two-dimensional images by the modified Simpsons rule formula. Continuous-wave Doppler was used to estimate the peak instantaneous LVOT gradient.

Statistical analysis

The Kolmogorov–Smirnov (K–S) test was used to assess the normality of the data. Continuous data with a normal distribution are presented as means ± standard deviation (SD), whereas continuous data with a non-normal distribution are presented as medians and interquartile ranges. Student's t-test was used to compare continuous data following a normal distribution, and the Mann–Whitney U test was used to compare data with a non-normal distribution. Categorical data are presented as frequency (percentage), and comparisons between two groups were performed using the χ² test or Fisher's exact test (if the theoretical frequency was T < 5). Logistic regression was used to analyse the factors contributing to ES-HCM. In each group, Kaplan–Meier analysis was used to compare differences in adverse events, such as heart transplantation or all-cause death. Statistical significance was set at P < 0.05. All data were analysed using SPSS software (version 26.0, Armonk, NY: IBM Corp., USA).

Results

Baseline clinical characteristics of the patients

The patient enrolment process is shown in Figure 1. The mean age of the total population was 62.5 ± 10.3 years, with 215 (86.0%) being men and 35 (14.0%) women. The baseline characteristics of all patients with ES-HCM and the matched controls are shown in Table 1. Compared with patients with HCM and LVEF ≥ 50%, those with ES-HCM were younger at the date of their first symptoms (54.2 ± 12.8 vs. 58.6 ± 10.5, P = 0.014) and first diagnosis of HCM (56.8 ± 13.2 vs. 61.3 ± 10.2, P = 0.024), and more had a family history of HCM (6 [12.0%] vs. 4 [2.0%], P = 0.005). In addition, patients with ES-HCM had more complications of hyperuricemia, atrial fibrillation, and ventricular tachycardia, and patients with HCM and LVEF ≥ 50% had more complications of hypertension, and the difference between the two groups was statistically significant (P < 0.050). Furthermore, compared with HCM patients with LVEF ≥ 50%, patients with ES-HCM had a higher heart rate and a lower systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on admission (P < 0.010). In patients with ES-HCM, NYHA I–II and NYHA III–IV were 44.0% and 56.0%, respectively, while in patients with HCM and LVEF ≥ 50%, NYHA I–II and NYHA III–IV were 87% and 13%, respectively (P < 0.001). Regarding the treatment, patients with ES-HCM were more likely to use diuretics [39 (78.0%) vs. 39 (19.5%), P < 0.001] and spironolactone [35 (70.0%) vs. 33 (16.5%), P < 0.001], but less likely to use calcium channel blockers [5 (10.0%) vs. 80 (40.0%), P < 0.001] than patients with HCM and LVEF ≥ 50%. There was no significant difference in surgical treatment (percutaneous transluminal septal myocardial ablation or surgical septal myectomy) between the two groups.

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Table 1 Clinical characteristics of the study participants.

	Total (n = 250)	ES-HCM (n = 50)	HCM with LVEF ≥ 50% (n = 200)	P
Male, n (%)	215 (86)	43 (86)	172 (86)	1.000
Age at enrolment (mean ± SD, years)	62.5 ± 10.3	62.7 ± 10.3	62.5 ± 10.2	0.797
Age at first symptom onset, mean ± SD, years	57.7 ± 11.1	54.2 ± 12.8	58.6 ± 10.5	0.014
Age at diagnosis with HCM, mean ± SD, years	60.6 ± 11.0	56.8 ± 13.2	61.3 ± 10.2	0.024
Family history of HCM, n (%)	10 (4.0)	6 (12.0)	4 (2.0)	0.005
Symptom, n (%)
Polypnoea	87 (34.8)	37 (74.0)	50 (25.0)	<0.001
Palpitations	39 (15.7)	9 (18.0)	30 (15.1)	0.611
Chest tightness and pain	207 (82.8)	40 (80.0)	167 (83.5)	0.557
Syncope	11 (4.4)	3 (6.0)	8 (4.0)	0.572
Complication, n (%)
Hypertension	135 (54.0)	19 (38.0)	116 (58.0)	0.017
Diabetes	53 (21.2)	11 (22.0)	42 (21.0)	0.877
Hyperlipidaemia	74 (29.6)	10 (20.0)	64 (32.0)	0.096
Hyperuricemia, n (%)	93 (37.2)	28 (56.0)	65 (32.5)	0.002
Atrial fibrillation, n (%)	46 (18.4)	17 (34.0)	29 (14.5)	0.001
Atrial tachycardia, n (%)	29 (11.6)	6 (12.0)	23 (11.5)	0.921
Ventricular tachycardia, n (%)	21 (8.4)	10 (20.0)	11 (5.5)	0.001
Obesity, n (%)	33 (13.2)	5 (10.0)	28 (14.0)	0.499
Heart rate, median (IQR), b.p.m.	68.0 (61.0–78.0)	75.0 (63.0–91.0)	66.5 (60.0–75.0)	0.001
NYHA class, n (%)				<0.001
I	64 (25.6)	3 (6.0)	61 (30.5)
II	132 (52.8)	19 (38.0)	113 (56.5)
III	49 (19.6)	23 (46.0)	26 (13.0)
IV	5 (2.0)	5 (10.0)	0 (0.0)
SBP, median (IQR), mmHg	128.5 (116.0–140.0)	120.0 (105.0–126.5)	130.0 (118.0–140.0)	<0.001
DBP, median (IQR), mmHg	78.0 (70.0–84.0)	70.5 (64.8–80.0)	79.0 (70.0–85.0)	0.001
Pulse pressure, median (IQR), mmHg	50.0 (40.0–60.0)	45.0 (35.0–53.3)	50.0 (40.0–60. 0)	0.009
Treatment
ACEI/ARB, n (%)	123 (49.2)	22 (44.0)	101 (50.5)	0.411
Beta-blocker, n (%)	193 (77.2)	38 (76.0)	155 (77.5)	0.821
CCB, n (%)	85 (34.0)	5 (10.0)	80 (40.0)	<0.001
Diuretics, n (%)	78 (31.2)	39 (78.0)	39 (19.5)	<0.001
Spironolactone, n (%)	68 (27.2)	35 (70.0)	33 (16.5)	<0.001
Surgical treatment, n (%)	12 (4.8)	1 (2.0)	11 (5.5)	0.469

QTc and QRS durations were longer (449.5 [433.5–474.5] ms vs. 442.0 [426.3–451.0] ms, P = 0.006; 112.0 [102.0–147.0] ms vs. 100.0 [92.0–110.0] ms, P = 0.014), and the proportion of abnormal Q waves was higher (11 [22.0%] vs. 16 [8.0%], P = 0.004) in ES-HCM patients (Table 2). LVEF was 40.1 ± 6.2% in patients with ES-HCM and 68.5 ± 7.1% in patients with HCM and LVEF ≥ 50%. MLVWT and IVS were lower (16.4 [14.7–19.2] mm vs. 19.7 [17.4–21.9] mm, P < 0.001; 15.4 [13.7–17.8] mm vs. 17.0 [13.5–20.8] mm, P = 0.036), and LVEDD, LAD, RVEDD, and PAD were higher (52.5 ± 9.5 mm vs. 46.2 ± 5.0 mm; 46.7 ± 6.7 mm vs. 40.4 ± 6.5 mm; 22.3 [21.0–23.8] mm vs. 20.5 [19.1–22.0] mm; 22.7 ± 2.2 mm vs. 21.2 ± 2.3 mm; all P < 0.005) in ES-HCM patients than in patients with HCM with LVEF ≥ 50% (Table 2).

Table 2 Comparison of the results of ECG and UCG between patients of HCM and ES-HCM.

Result of ECG and UCG	Total (n = 250)	ES-HCM (n = 50)	HCM with LVEF ≥ 50% (n = 200)	P
ECG
QTc, median (IQR), ms	443.0 (428.75–453.0)	449.5 (433.5–474.5)	442.0 (426.3–451.0)	0.006
QRS duration, median (IQR), ms	102.0 (92.0–114.0)	112.0 (102.0–147.0)	100.0 (92.0–110.0)	<0.001
Abnormal Q wave, n (%)	27 (10.8)	11 (22.0)	16 (8.0)	0.004
LVEF, mean ± SD, %	62.8 ± 13.3	40.1 ± 6.2	68.5 ± 7.1	<0.001
LVEDD, mean ± SD, mm	47.5 ± 6.7	52.5 ± 9.5	46.2 ± 5.0	<0.001
LAD, mean ± SD, mm	41.6 ± 7.0	46.7 ± 6.7	40.4 ± 6.5	<0.001
MLVWT, median (IQR), mm	19.0 (16.7–21.6)	16.4 (14.7–19.2)	19.7 (17.4–21.9)	<0.001
IVS, median (IQR), mm	16.4 (13.5–19.8)	15.4 (13.7–17.8)	17.0 (13.5–20.8)	0.036
PAD, mean ± SD, mm	21.5 ± 2.3	22.7 ± 2.2	21.2 ± 2.3	<0.001
LVOT gradient at rest ≥30 mmHg, n (%)	30 (12.0)	0 (0.0)	30 (15.0)	0.004
RVEDD, median (IQR), mm	21.0 (19.2–22.2)	22.3 (21.0–23.8)	20.5 (19.1–22.0)	<0.001

The median follow-up time of all patients was 2.8 (1.4–5.4) years, 2.6 (1.0–4.3) years in patients with ES-HCM, and 2.9 (1.4–5.5) years in patients with HCM and LVEF ≥50% (P = 0.154, Table 3). The incidence of all-cause death and cardiovascular death among patients with ES-HCM was higher than those among patients with HCM and LVEF ≥ 50% (22/50 [44.0%] vs. 13/200 [6.5%]; 12/50 [24.0%] vs. 4/200 [2.0%], all P < 0.001). The cumulative incidence of heart transplantation or all-cause death in the two groups was plotted using the Kaplan–Meier method (Figure 2). The median time to heart transplantation or all-cause death in ES-HCM was 4.3 (0.7–7.8) years. With a rather short-term follow- up, fewer deaths occurred in patients with HCM and LVEF ≥ 50%, and there was no median survival time in patients with HCM and LVEF ≥ 50%. Patients with ES-HCM had a higher cumulative incidence of heart transplantation or all-cause death (log-rank test, P < 0.001; Figure 2). The 1-year and 3-year survival rates among patients with HCM and LVEF ≥ 50% were significantly higher than those among patients with ES-HCM (96.8% vs. 77.1%, P < 0.001; 94.7% vs. 55.8%, P < 0.001).

Table 3 Results of follow-up in the HCM and ES-HCM groups.

	Total (n = 250)	ES-HCM (n = 50)	HCM with LVEF ≥ 50% (n = 200)	P
Follow-up time, median (IQR), year	2.8 (1.4–5.4)	2.6 (1.0–4.3)	2.9 (1.4–5.5)	0.154
Lost to follow-up, n (%)	22 (8.8%)	3 (6.0%)	19 (9.5%)	-
Cardiovascular death, n (%)	16 (6.4%)	12 (24.0%)	4 (2.0%)	<0.001
Heart transplantation, n (%)	3 (1.2)	2 (4.0)	1 (0.5)	0.103
All-cause death, n (%)	35 (14.0)	22 (44.0)	13 (6.5)	<0.001
1-year survival rate,%	92.7%	77.1%	96.8%	<0.001
3-years survival rate,%	85.8%	55.8%	94.7%	<0.001

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Influencing factors of end-stage hypertrophic cardiomyopathy

Univariate logistic regression analysis was performed for each variable to identify the factors associated with ES-HCM. Since age and sex were matched in the two groups, they were excluded. Among the variables in the univariate analysis, age at first symptom onset, family history of HCM, NYHA class, heart rate, complications (hypertension, atrial fibrillation, ventricular tachycardia, and hyperuricaemia), QRS duration, QTc, abnormal Q wave, LVEDD, LAD, RVEDD, MLVWT, and PAD were significantly associated with ES-HCM (Table 4). The multivariate logistic regression model was successfully constructed and fitted well with the observed values (omnibus test, P < 0.001; Hosmer–Lemeshow test, P = 0.428; Table 5). Multivariate logistic regression analysis showed that the influencing factors associated with ES-HCM included age at first symptom onset (odds ratio [OR] = 0.95, 95% CI [0.90, 1.00], P = 0.042), NYHA class (OR = 7.73, 95% CI [2.93, 20.41], P < 0.001), heart rate (OR = 1.07, 95% CI [1.02, 1.12], P = 0.003), QRS duration (OR = 1.03, 95% CI [1.00, 1.05], P = 0.0200), LVEDD (OR = 1.15, 95% CI [1.04, 1.28], P = 0.006), LAD (OR = 1.13, 95% CI [1.03, 1.24], P = 0.012), and MLVWT (OR = 0.80, 95% CI [0.68, 0.93], P = 0.005; Table 4).

Table 4 Univariate and multivariate logistic regression of occurrence of ES-HCM.

	Single factor analysis	Multifactor analysis
P	P	OR	95% CI
Age at first symptom onset	0.014	0.042	0.95	0.90–1.00
Family history of HCM	0.004	0.927	1.13	0.09–14.10
NYHA class	<0.001	<0.001	7.73	2.93–20.41
Heart rate	0.001	0.003	1.07	1.02–1.12
Atrial fibrillation	0.002	0.694	0.74	0.16–3.38
Atrial tachycardia	0.921	0.850	1.20	0.18–8.14
Ventricular tachycardia	0.002	0.357	2.52	0.35–17.93
Hypertension	0.012	0.372	0.56	0.16–1.99
Diabetes	0.877	0.993	0.994	0.23–4.28
Hyperuricemia	0.003	0.089	3.02	0.85–10.78
Hyperlipidaemia	0.100	0.717	1.30	0.31–5.41
Obesity	0.457	0.164	0.24	0.03–1.77
QRS duration	<0.001	0.020	1.03	1.00–1.05
QTc	0.008	0.261	1.01	0.99–1.03
Abnormal Q wave	0.006	0.940	1.08	0.16–7.49
LVEDD	<0.001	0.006	1.15	1.04–1.28
RVEDD	<0.001	0.890	1.02	0.78–1.34
LAD	<0.001	0.012	1.13	1.03–1.24
IVS	0.055	0.265	1.02	0.98–1.06
MLVWT	<0.001	0.005	0.80	0.68–0.93
PAD	<0.001	0.151	1.20	0.94–1.54
LVOT	0.998	0.998	0.00	-

Table 5 Omnibus test and Hosmer–Lemeshow test.

	χ2	P
Omnibus test	153.755	<0.001
Hosmer–Lemeshow test	8.051	0.428

Prognostic factors of end-stage hypertrophic cardiomyopathy

The results of the multivariate logistic regression analysis showed that age at first symptoms, NYHA class, heart rate, QRS duration, LVEDD, LAD, and MLVWT were influencing factors associated with ES-HCM. Patients with ES-HCM were divided into groups according to NYHA class, quartile of heart rate,¹² QRS ≥ 120 ms,¹³ LVEDD > 55 mm,¹⁴ and LAD > 40 mm.¹⁵ The curve free of all-cause mortality or heart transplantation was obtained using the Kaplan–Meier method (Figure 3). Among the 50 patients with ES-HCM, NYHA class (log-rank, P < 0.001; Figure 3A) and heart rate (log-rank, P = 0.017; Figure 3B) were each associated with a higher likelihood and earlier occurrence of heart transplantation or all-cause mortality in univariate analyses. There was not statistical significance in the patiences with ES-HCM based on grouped by atrial fibrillation, atrial tachycardia, and ventricular tachycardia (Figure S1).

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Discussion

This study analysed the influencing factors and prognosis of ES-HCM in the Chinese population. There are differences in the occurrence, development, and prognosis of cardiovascular diseases between different genders.^16–18 People of different ages have different morbidities and prognosis of heart failure (HF).^19,20 To improve the accuracy of our conclusions, the subjects were analysed after matching by age and gender in this study.

NYHA class plays an important role in patients' diagnosis, treatment, and prognosis.^21–23 It has been shown that patients with HCM and left ventricular systolic dysfunction are at least twice as likely to have NYHA class III/IV compared to patients without systolic dysfunction.²⁴ In this study, the risk of ES-HCM increased with an increase in NYHA class (OR = 7.73, 95% CI [2.93, 20.41], P < 0.001]. In addition, increasing NYHA classes were associated with poor prognoses, such as rehospitalization and death, in HF patients with LVEF ≥ 45%.²⁵ Holland R et al. suggested that the patients' self-assigned NYHA class can also predict the rehospitalization rate, mortality, and quality of life in patients with HF.²² In this study, the cumulative incidence of heart transplantation or all-cause mortality increased the most, and the survival time was shortest in patients with NYHA IV, while no heart transplantation or mortality occurred in patients with NYHA I (log-rank, P < 0.001).

Custodis F et al. hypothesized that heart rate was a predictor of cardiovascular death and all-cause mortality in the general population and in patients with cardiovascular disease (CVD) and was a central factor affecting all stages of CVD.²⁶ Early studies have shown that tachycardia can induce heart failure, and many mechanisms have been proposed to explain left ventricular dysfunction caused by tachycardia.^27,28 In this study, heart rate was a risk factor associated with ES-HCM (OR = 1.07, 95% CI [1.02, 1.12], P = 0.003). In addition, early studies have shown that an elevated resting heart rate is associated with an increased risk of all-cause and cardiovascular mortality.^12,29 This study found that heart rate was associated with heart transplantation or all-cause death in ES-HCM patients (log-rank, P = 0.017). The heart rate of patients should be controlled at an appropriate level. Beta-blockers are generally considered the first drug therapy for patients with obstructive hypertrophic cardiomyopathy.^1,30 They can slow the heart rate, reduce myocardial oxygen consumption, relieve symptoms, and improve the quality of life. Beta-blockers were associated with a reduced risk of all-cause mortality in patients with heart failure and EF < 50%.³¹ HCM patients without significant outflow tract obstruction can benefit from approaches to heart failure with preserved ejection fraction, for example, beta-blockers.³⁰

Peter et al. found that greater left ventricular cavity size (hazard ratio [HR] = 1.1, 95% CI [1.0, 1.3]) and wall thickness (HR = 1.3, 95% CI [1.1, 1.4]) were significant predictors of developing incident HCM with LV systolic dysfunction.²⁴ However, we found that the risk of ES-HCM increased with greater LVEDD (OR = 1.15, 95% CI [1.04, 1.28], P = 0.006) but decreased with greater MLVWT (OR = 0.80, 95% CI [0.68, 0.93], P = 0.005). This finding may be related to age and sudden death in patients with HCM. Spirito et al. found that the magnitude of hypertrophy, a strong independent prognostic predictor, was directly related to the risk of sudden death, and compared with other subgroups, patients with MLVWT ≥ 30 mm were the youngest (mean age, 31 years).³² The average age of the enrolled population was over 60 years in this study, which impacted the results. Some patients with HCM have extreme myocardial hypertrophy, may not go to the hospital for diagnosis and treatment, and may experience sudden death before developing ES-HCM.

QRS duration and LAD were also associated with ES-HCM. QRS duration reflects the duration of ventricular depolarization, and QRS prolongation is associated with left ventricular systolic dysfunction.^33,34 The risk of ES-HCM increased with an increase in QRS duration (OR = 1.02, 95% CI [1.00, 1.05], P = 0.025). Early studies have shown that the left atrial diameter can independently predict cardiovascular events, such as HF and coronary heart disease.³⁵ This study found that the risk of incident ES-HCM increased with increasing LAD (OR = 1.12, 95% CI [1.02, 1.22], P = 0.015).

There is a current lack of effective treatments for patients with HCM. For patients with hypertrophic obstructive cardiomyopathy, guidelines recommend the use of drugs such as beta-blockers, calcium channel blockers, and disopyramide.^1,30 If drug therapy is ineffective, or the symptoms are not significantly improved, septal volume reduction therapy can be applied, such as surgical septal myectomy and alcohol septal ablation.^1,30,36 In recent years, the emergence of the targeted drug mavacamten has brought new hope for the treatment of HCM.³⁶ Myocardial fibrosis, an early manifestation of sarcomeregene mutations, is a hallmark of hypertrophic cardiomyopathy,⁴ for which slowing down or reversing myocardial fibrosis is essential. Some studies showed that N-acetylcysteine and valsartan can slow or inhibit myocardial fibrosis.^37,38 However, because of the lack of large sample sizes and long-term follow-up studies, whether anti-fibrosis treatment can improve the course and prognosis of HCM remains unclear and requires further research.

This study had some limitations. First, the population consisted only of inpatients, and the follow-up period was short, decreasing the generalizability of the results. Second, sarcomere gene mutations may be related to the occurrence and prognosis of ES-HCM; however, gene analysis could not be performed in this study because of the lack of gene detection in inpatients. In addition, this was a retrospective study, some of the examination results were incomplete, and most deaths occurred outside the hospital; the specific causes of death could not be clarified in the analysis. Finally, the subjects of this study were enrolled from a single centre, making further validation possible by including patients from multiple centres and a larger population.

Conclusions

The influencing factors for ES-HCM included age at first symptoms onset, NYHA class, heart rate, QRS duration, LVEDD, LAD, and MLVWT. Both NYHA class and heart rate were related to the prognosis of ES-HCM.

Acknowledgements

None.

Funding

This study was supported by National Key Clinical Specialty Discipline Construction Programs (2013544) and Fujian Province Key Clinical Specialty Discipline Construction Program (2012149).

Conflict of interest

The authors declare that there is no conflict of interest.

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