Chaomei Fan

Two Hundred Eight Patients With Apical Hypertrophic Cardiomyopathy in China: Clinical Feature, Prognosis, and Comparison of Pure and Mixed Forms

Apical hypertrophic cardiomyopathy (AHCM) is a relatively rare form of hypertrophic cardiomyopathy (HCM), originally described in Japan and later in the West. Limited information is available on this disease in China.

Comparison of the Prevalence, Clinical Features, and Long-term Outcomes of Midventricular Hypertrophy vs Apical Phenotype in Patients With Hypertrophic Cardiomyopathy

BACKGROUND Previous studies on the association between the distribution of left ventricle hypertrophy and the clinical features of hypertrophic cardiomyopathy (HCM) have yielded unclear results. The aim of this study was to investigate the differences in the prevalence, clinical features, management strategies, and long-term outcomes between patients with midventricular hypertrophic obstructive cardiomyopathy (MVHOCM) and patients with apical HCM (ApHCM). METHODS A retrospective study of 60 patients with MVHOCM and 263 patients with ApHCM identified in a consecutive single-centre cohort consisting of 2068 patients with HCM was performed. The prevalence, clinical features, and natural history of the patients in these 2 groups were compared. RESULTS Compared with ApHCM patients, patients with MVHOCM tended to be much younger and more symptomatic during their initial evaluation. Over a mean follow-up of 7 years, the probability of cardiovascular mortality and that of morbidity was significantly greater in MVHOCM patients compared with ApHCM patients (log-rank, P < 0.001). CONCLUSIONS Our results suggest that, compared with ApHCM, MVHOCM represents an uncommon presentation of the clinical spectrum of HCM that is characterized by progressive clinical deterioration leading to increased cardiovascular mortality and morbidity. Our results also underscore the importance of the timely recognition of MVHOCM for the prediction of prognosis and the early consideration of appropriate management strategies.

Long‐term survival after acute myocardial infarction in patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is associated with poor prognosis. It has been reported that there is no difference in in‐hospital mortality after acute myocardial infarction (AMI) between patients with and without HCM. However, whether there is a difference in long‐term survival after AMI between patients with and without HCM remains unclear.

The Prevalence and Long-Term Outcomes of Extreme Right versus Extreme Left Ventricular Hypertrophic Cardiomyopathy.

Objectives: Extreme left ventricular hypertrophy (LVH) is a known risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM). Extreme right ventricular hypertrophy (RVH) is rare, and whether it is linked to a poor outcome is unknown. This study was designed to investigate differences between HCM patients with extreme RVH and those with extreme LVH. Methods: Among 2,413 HCM patients, 31 with extreme RVH (maximum right ventricular wall thickness ≥10 mm) and 194 with extreme LVH (maximum left ventricular wall thickness ≥30 mm) were investigated. The main clinical features and natural history were compared between the 2 groups. Results: The prevalence of extreme RVH and extreme LVH was 1.3 and 8.0%, respectively. Patients with extreme RVH tended to be younger and female (p < 0.01). Cardiovascular-related mortality and morbidity within 10 years were significantly greater in the extreme RVH group (p < 0.05). Multivariate analysis demonstrated 3 independent predictors for cardiovascular mortality - extreme RVH, left ventricular end-diastolic dimension ≥50 mm, and age ≤18 years at baseline - and 2 for morbidity - extreme RVH and presyncope. Conclusions: Compared with extreme LVH, extreme RVH was quite uncommon in HCM and had a worse prognosis. A right ventricle examination should be performed in routine HCM evaluation.

Comparison of Long-Term Outcome between Apical and Asymmetric Septal Hypertrophic Cardiomyopathy

Objectives: As reported, diagnostic age, gender and presence of outflow tract obstruction have an impact on prognosis in patients with hypertrophic cardiomyopathy. The aim of this study was to compare the long-term outcome between apical hypertrophic cardiomyopathy (ApHCM) and asymmetric septal hypertrophic cardiomyopathy (ASHCM) after the exclusion of these factors. Methods: A total of 540 patients (270 with ApHCM and 270 with ASHCM) identified in a consecutive single-center cohort were retrospectively studied. The two groups were matched by diagnostic age, gender and the presence of outflow tract obstruction. Clinical characteristics and long-term outcomes were compared. Results: The mean follow-up duration in ASHCM and ApHCM were 6.6 ± 5.5 and 7.6 ± 4.1 years, respectively. During follow-up, 16 patients experienced cardiovascular death in the ASHCM group, while 2 patients experienced cardiovascular death in the ApHCM group (6.3 vs. 0.7%, p < 0.01). Cardiovascular morbidity in the ASHCM and ApHCM groups were 39.9 and 18.5% (p < 0.01). In the multivariate Cox regression analysis late gadolinium enhancement (LGE; HR 4.81, 95% CI 1.28-78.0, p = 0.03) and unexplained syncope (HR 9.68, 95% CI 1.9-17.2, p < 0.01) were independent predictors for cardiovascular mortality. Unexplained syncope was independently associated with a higher risk for sudden cardiac death (HR 4.3, 95% CI 1.2-15.3, p = 0.02). Conclusions: After eliminating the interference of diagnostic age, gender and outflow tract obstruction, ASHCM represented a worse prognosis with a higher incidence of cardiovascular mortality and morbidity than ApHCM. LGE was a strong predictor for cardiovascular death.

Clinical characteristics and prognosis of 60 patients with midventricular obstructive hypertrophic cardiomyopathy

Background Midventricular obstructive hypertrophic cardiomyopathy (MVOHCM) is a rare form of hypertrophic cardiomyopathy. Knowledge regarding the diagnosis, morbidity and cardiovascular mortality is limited. In this study, we aimed to describe the long-term outcomes of patients with MVOHCM followed in a tertiary referral centre. Methods A retrospective study of 60 patients with MVOHCM diagnosed at FuWai Hospital was performed. Clinical features, mortality and cardiovascular morbidity were analysed. Results The 60 patients with MVOHCM represented 2.9% of all the hypertrophic cardiomyopathy cases (n = 2068). At diagnosis, the mean age was 40.2 ± 15.0 years. During 7.1 ± 6.3 years of follow-up after diagnosis, the cardiovascular mortality was 15.0%. The probability of survival at 10 years was 77.0 ± 8.0%. The following two predictors of cardiovascular mortality were identified: severe ventricular septal hypertrophy at least 30 mm (hazard ratio, 3.19; P = 0.031) and unexplained syncope (hazard ratio, 4.59; P = 0.002) at baseline. Thirty patients (50.0%) had one or more morbid events, and the most frequent was nonsustained ventricular tachycardia. Apical aneurysm formation was identified in 20% of patients, and the patients with apical aneurysms were more inclined to experience nonsustained ventricular tachycardia than patients without apical aneurysm (58.3 vs. 16.7%; P = 0.003). Peak pressure gradient at least 70 mmHg (hazard ratio, 3.00; P = 0.01) at baseline was identified as the only predictor of apical aneurysm. Conclusion In Chinese patients, MVOHCM is associated with an unfavourable prognosis of cardiovascular mortality. One-half of these patients experience major cardiovascular events, and 20% develop an apical aneurysm, which significantly increases arrhythmia events. These data warrant measures to ensure the early recognition of MVOHCM followed by appropriate therapeutic interventions.

Survival after alcohol septal ablation versus conservative therapy in obstructive hypertrophic cardiomyopathy

BACKGROUND The impact of alcohol septal ablation (ASA) on the survival of patients with drug-refractory obstructive hypertrophic cardiomyopathy (HCM) remains unresolved. The aim of this study was to compare survival after ASA vs. conservative therapy. METHODS We studied a consecutive cohort of 274 patients with severe drug-refractory obstructive HCM, 229 in ASA group and 45 in conservative group. The primary endpoint was a composite of all-cause mortality and aborted cardiac arrest. RESULTS With a median follow-up of 4.3 years, primary endpoint occurred in 13 (5.7%) patients in the ASA group, and 8 (17.8%) patients in the conservative group. The 5- and 10-year survival free from primary endpoint of the ASA group (94.5% and 93.0%, respectively) was significantly better than that of the conservative group (78.3% and 72.2%, respectively, log-rank p = 0.009). Independent determinants of primary endpoint were ASA therapy (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.08-0.60; p = 0.003) and maximal septal thickness (HR 1.14; 95% CI 1.03-1.27; p = 0.011). CONCLUSIONS In patients with severe drug-refractory obstructive HCM, survival after ASA is favorable and better than that of conservative therapy. ASA seems to improve survival.

Long-Term Prognosis after Myectomy in Hypertrophic Obstructive Cardiomyopathy with Severe Left Ventricular Hypertrophy

Objectives: Patients with hypertrophic obstructive cardiomyopathy (HOCM) and severe left ventricular hypertrophy (maximal left ventricular wall thickness ≥30 mm) are at high risk of sudden cardiac death (SCD). In this study, we aimed to determine whether HOCM patients with severe hypertrophy had a lower incidence of SCD after myectomy. Methods: HOCM patients with severe hypertrophy were consecutively enrolled from Fuwai Hospital in China between 2000 and 2013. Long-term outcomes were retrospectively compared between the 2 groups, namely the myectomy group and medical group. Results: A total of 244 patients (118 in the myectomy group and 126 in the medical group) were involved. The mean follow-up durations for the myectomy and medical groups were 5.07 ± 3.73 and 6.23 ± 4.15 years, respectively. During the follow-up period, the annual cardiovascular mortality rate was 0.84% in the myectomy group and 2.04% in the medical group (p = 0.041). The annual SCD rate was 0.33% in the myectomy group and 1.40% in the medical group (p = 0.040). Multivariate Cox regression analysis showed that myectomy was independently associated with lower rates of cardiovascular death and SCD. Conclusions: In HOCM patients with severe hypertrophy, those that underwent myectomy had a lower risk of cardiovascular death and SCD than those treated with medicines only.

The clinical features, outcomes and genetic characteristics of hypertrophic cardiomyopathy patients with severe right ventricular hypertrophy

Introduction Severe right ventricular hypertrophy (SRVH) is a rare phenotype in hypertrophic cardiomyopathy (HCM) for which limited information is available. This study was undertaken to investigate the clinical, prognostic and genetic characteristics of HCM patients with SRVH. Methods HCM with SRVH was defined as HCM with a maximum right ventricular wall thickness ≥10 mm. Whole-genome sequencing (WGS) was performed in HCM patients with SRVH. Multivariate Cox proportional hazards regression models were used to identify risk factors for cardiac death and events in HCM with SRVH. Patients with apical hypertrophic cardiomyopathy (ApHCM) were selected as a comparison group. The clinical features and outcomes of 34 HCM patients with SRVH and 273 ApHCM patients were compared. Results Compared with the ApHCM group, the HCM with SRVH group included younger patients and a higher proportion of female patients and also displayed higher cardiovascular morbidity and mortality. The multivariate Cox proportional hazards regression models identified 2 independent predictors of cardiovascular death in HCM patients with SRVH, a New York Heart Association class ≥III (hazard ratio [HR] = 8.7, 95% confidence interval (CI): 1.43-52.87, p = 0.019) and an age at the time of HCM diagnosis ≤18 (HR = 5.5, 95% CI: 1.24-28.36, p = 0.026). Among the 11 HCM patients with SRVH who underwent WGS, 10 (90.9%) were identified as carriers of at least one specific sarcomere gene mutation. MYH7 and TTN mutations were the most common sarcomere mutations noted in this study. Two or more HCM-related gene mutations were observed in 9 (82%) patients, and mutations in either other cardiomyopathy-related genes or ion-channel disease-related genes were found in 8 (73%) patients. Conclusions HCM patients with SRVH were characterized by poor clinical outcomes and the presentation of multiple gene mutations.

Genetic anticipation in a special form of hypertrophic cardiomyopathy with sudden cardiac death in a family with 74 members across 5 generations

Abstract Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. The genetic anticipation of HCM and its associated etiology, sudden cardiac death (SCD), remains unclear. The aim of this study was to investigate the mechanism underlying the genetic anticipation of HCM and associated SCD. An HCM family including 5 generations and 74 members was studied. Two-dimensional echocardiography was performed to diagnose HCM. The age of onset of HCM was defined as the age at first diagnosis according to hospital records. The information on SCD was confirmed by verification by ≥2 family members and a review of hospital records. Whole-genome sequencing was performed on 4 HCM subjects and 1 healthy control in the family. The identified mutations were screened in all available family members and 216 unrelated healthy controls by Sanger sequencing. The median ages of onset of HCM were 63.5, 38.5, and 18.0 years in members of the second, third, and fourth generations of the family, respectively, and the differences between the generations were significant (P < 0.001). The age at SCD also decreased with each subsequent generation (P < 0.05). In particular, among the third-generation family members, SCD occurred between 30 and 40 years of age at approximately 8 AM, whereas among the fourth-generation family members, all 5 males who experienced SCD were 16 years of age and died at approximately 8 AM. The sarcomere gene mutations MYH7-A719H and MYOZ2-L169G were detected in the HCM individuals in this pedigree. Increases in the number of mutations and the frequency of multiple gene mutations were observed in the younger generations. Moreover, a structural variant was present in the HCM phenotype–positive subjects but was absent in the HCM phenotype–negative subjects. HCM may exhibit genetic anticipation, with a decreased age of onset and increased severity in successive generations. Multiple gene mutations may contribute to genetic anticipation in HCM and thus may be of prognostic value.