Apical hypertrophic cardiomyopathy (HC) is considered to have a favorable prognosis, but recent observations have suggested less benign clinical courses. We investigated the outcomes in patients with apical HC and evaluated the predictors. All 454 patients with apical HC (316 men, age 61 ± 11 years) were recruited. Major cardiovascular events (MACE) were defined as unplanned hospitalization because of heart failure, stroke, or cardiovascular mortality. The patients were divided into 2 groups: group 1 with MACE and group 2 without MACE. During the follow-up period (43 ± 20 months), the all-cause mortality rate was 9% (39 of 454), and 110 patients (25%) had MACE. The subjects in group 1 were older and a greater proportion had diabetes, hypertension, and atrial fibrillation. On the echocardiogram, the left atrial volume index (left atrial volume index 36 ± 17 vs 31 ± 12 ml/m 2 ), transmitral E velocity (65 ± 17 vs 61 ± 16 cm/s), mitral annulus Ea velocity (4.5 ± 1.4 vs 5.1 ± 1.8 cm/s), Sa velocity (5.8 ± 1.4 vs 6.6 ± 1.4 cm/s), E/Ea ratio (15 ± 5 vs 13 ± 5), and right ventricular systolic pressure (31 ± 8 vs 28 ± 7 mm Hg) were significantly different between groups 1 and 2 (p <0.05 for all). The left atrial volume index (for each 1-ml/m 2 increase, hazard ratio 1.01, 95% confidence interval 1.00 to 1.03; p = 0.047), Sa velocity (hazard ratio 0.83, 95% confidence interval 0.72 to 0.96, p = 0.014), and E/Ea ratio (hazard ratio 1.04, 95% confidence interval 1.00 to 1.09, p = 0.030) were independent predictors of a poor prognosis, along with age and the presence of diabetes or hypertension. In conclusion, the clinical outcomes of patients with apical HC were less benign in older patients and in those with hypertension or diabetes. In addition, the left atrial volume index, Sa velocity, and E/Ea ratio were predicters of a poor prognosis in patients with apical HC.
Apical hypertrophic cardiomyopathy (HC) is a variant of HC and is common in East Asia. Apical HC is characterized by myocardial hypertrophy occurring predominantly at the left ventricular (LV) apical portion, with an “ace of spades” configuration of the left ventricle and giant negative T-wave inversion on the electrocardiogram. Apical HC is believed to have a relatively favorable prognosis according to preliminary reports that included limited numbers of patients. In recent years, however, the condition has been reported to be less benign than previously thought. Many case reports have also described potentially fatal clinical manifestations, including malignant arrhythmias and sudden cardiac death, and apical HC can impose pressure overload and impair the coronary flow of the LV apex, inducing myocardial ischemia. However, information regarding the clinical outcomes and prognostic factors in patients with apical HC remains insufficient. The aim of the present study was to investigate the prognosis of patients with apical HC undergoing treatment at a large-volume tertiary referral center and to determine the clinical and echocardiographic predictors of a poor outcome.
Methods
A total of 454 patients who were diagnosed with apical HC at the Severance Cardiovascular Hospital (Yonsei University College of Medicine, Seoul, Republic of Korea) from 2003 to 2009 were consecutively entered into this retrospective study. During this period, a total of 1,204 subjects were diagnosed with HC at the center. Of these 1,204 patients, 454 (38%) were diagnosed with apical HC. The criteria for the diagnosis of apical HC included a demonstration of asymmetric LV hypertrophy confined predominantly to the LV apical portion with an apical wall thickness of ≥15 mm and a ratio of maximal apical to LV posterior wall thickness of ≥1.5 at end-diastole assessed using standard 2-dimensional transthoracic echocardiography. The exclusion criteria included LV systolic dysfunction (LV ejection fraction <50%), significant valvular disease, or significant coronary artery disease. Patients with apical HC were further classified into 2 types: those with isolated asymmetric apical HC were classified as having “pure” apical HC, and patients with coexistent hypertrophy of the interventricular septum, in whom hypertrophy was the greatest at the apex without basal septal hypertrophy were classified as having “mixed” apical HC. The institutional review board of Yonsei University College of Medicine approved the present study, which was conducted in compliance with the Declaration of Helsinki.
The demographic data and clinical characteristics were gathered at presentation and the diagnosis of apical HC and at the most recent follow-up visit. The electrocardiographic, ambulatory electrocardiographic monitoring, coronary computed tomographic, or coronary angiographic findings were reviewed simultaneously. The clinical courses of the patients were monitored by cardiologists at enrollment and at 3-month intervals during the follow-up period. Data from the later follow-up visits were obtained by a review of the medical records and telephone interviews. Cardiovascular (CV) mortality was defined as death secondary to myocardial infarction, intractable arrhythmia, heart failure, or stroke. The dates and causes of mortality were also obtained from the Korea National Statistical Office. Major adverse CV events (MACE) were defined as the occurrence of heart failure requiring unplanned hospitalization, CV mortality, or stroke. Other CV morbidities, such as atrial fibrillation, nonfatal myocardial infarction, or syncope, were also investigated.
Comprehensive transthoracic echocardiography was performed using commercially available equipment (Vivid 7, GE Vingmed, Horten, Norway, or Sonos 5500, Philips Medical System, Andover, Massachusetts). Standard 2-dimensional measurements were obtained as recommended by the American Society of Echocardiography in the left lateral position. The maximum apical wall thickness was obtained from the standard apical 4- and 2-chamber views at end-diastole. The left atrial (LA) dimensions were measured at end-systole, and the LA volume was calculated using the prolate ellipsoid model. The LA volume index was calculated as the LA volume divided by the body surface area and reported as milliliters per square meter. Early mitral inflow velocity (E) and late mitral inflow velocity (A) were measured using the pulsed wave Doppler method by placing the sample volume at the level of the mitral valve leaflet tips. Tissue Doppler-derived early diastolic mitral annular velocity (Ea), late diastolic mitral annular velocity (Aa), and peak systolic mitral annular velocity (Sa) were measured from the septal corner of the mitral annulus in the apical 4-chamber view. The right ventricular systolic pressure was calculated from tricuspid regurgitant flow velocity as determined in the continuous-wave Doppler mode. The echocardiographic data were gathered and analyzed by 2 experienced echocardiographers who were unaware of all clinical data.
Continuous data are expressed as the mean ± SD, and normality tests were performed for each variable. Categorical variables are expressed as absolute values and relative frequencies. The baseline characteristics of the 2 groups were compared using 2-sample t tests for continuous variables, and chi-square tests and Fisher’s exact tests for categorical variables. Cox multiple regression analysis was used to quantify the relations between the interval to MACE and each potential risk factor, simultaneously accounting for the effects of other patient characteristics. Receiver operating characteristics curves were used to examine the accuracy of variables in predicting the clinical outcomes. Longitudinal data were analyzed using Kaplan-Meier estimates, with the log-rank test. p Values <0.05 were considered significant.
Results
The clinical characteristics of the patients at enrollment are summarized in Table 1 . A considerable number of patients had a history of co-morbidities such as hypertension and diabetes mellitus. Most patients were asymptomatic at presentation, and group 2 had more asymptomatic subjects; however, this difference was not statistically significant. The most common symptom in enrolled patients when they were diagnosed with apical HC at our institution was dyspnea; however, severe heart failure (New York Heart Association functional class III-IV/IV) was rare. As summarized in Table 1 , the prescribed medications were different (warfarin and statin), consistent with the different medical histories of the 2 groups.
| Variable | All (n = 454) | MACE | p Value ⁎ | |
|---|---|---|---|---|
| Yes (n = 110) | No (n = 344) | |||
| Age at presentation (years) | 61 ± 11 | 65 ± 11 | 60 ± 11 | <0.0001 |
| Men | 316 (70%) | 69 (63%) | 247 (72%) | 0.072 |
| Body surface area (m 2 ) | 1.74 ± 0.18 | 1.72 ± 0.17 | 1.76 ± 0.18 | 0.114 |
| Hypertension | 232 (51%) | 76 (69%) | 156 (46%) | <0.0001 |
| Diabetes mellitus | 69 (15%) | 29 (27%) | 40 (12%) | 0.008 |
| Initial symptom | ||||
| Asymptomatic | 353 (78%) | 79 (72%) | 274 (80%) | 0.233 |
| Chest pain | 31 (7%) | 7 (6%) | 24 (7%) | 0.798 |
| Dyspnea | 68 (15%) | 5 (5%) | 63 (18%) | 0.132 |
| New York Heart Association class II | 63 (14%) | 4 (4%) | 59 (17%) | 0.101 |
| New York Heart Association class III or IV | 5 (1%) | 1 (1%) | 4 (1%) | 0.663 |
| Palpitation | 22 (5%) | 5 (5%) | 18 (5%) | 0.890 |
| Syncope | 5 (1%) | 2 (2%) | 3 (1%) | 0.786 |
| Prescribed medications | ||||
| β Blockers | 142 (31%) | 42 (39%) | 100 (29%) | 0.073 |
| Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers | 140 (31%) | 46 (43%) | 94 (28%) | 0.181 |
| Calcium channel blockers | 118 (26%) | 33 (30%) | 85 (25%) | 0.271 |
| Diuretics | 55 (12%) | 19 (18%) | 36 (11%) | 0.057 |
| Antiplatelet agents | 124 (27%) | 40 (37%) | 84 (25%) | 0.014 |
| Warfarin | 26 (6%) | 14 (13%) | 12 (4%) | <0.0001 |
| Statin | 72 (16%) | 32 (29%) | 40 (12%) | <0.0001 |
The echocardiographic parameters at enrollment are described in Table 2 . The proportion of pure apical HC was slightly greater than that of the mixed type. The echocardiographic subtypes did not differ between groups 1 and 2. The LA volume index was significantly greater, and the E/Ea ratio was significantly greater in group 1, suggesting more chronic and more severe diastolic dysfunction and greater LV filling pressure than in group 2. The mitral annulus velocities during systole and early diastole (Sa and Ea, respectively) were significantly lower in group 1 than in group 2. The Aa velocities were measured when the patients were in sinus rhythm and were also significantly lower in group 1. The right ventricular systolic pressures were significantly greater in group 1 than in group 2.
| Variable | All (n = 454) | MACE | p Value ⁎ | |
|---|---|---|---|---|
| Yes (n = 110) | No (n = 344) | |||
| Apical hypertrophic cardiomyopathy type | 0.660 | |||
| Pure | 244 (54%) | 55 (50%) | 190 (55%) | |
| Mixed | 210 (46%) | 55 (50%) | 154 (45%) | |
| Interventricular septum thickness (mm) | 11 ± 2 | 11 ± 2 | 11 ± 2 | 0.289 |
| Posterior wall thickness (mm) | 11 ± 2 | 11 ± 2 | 10 ± 2 | 0.234 |
| Left ventricular end-diastolic dimension (mm) | 49 ± 4 | 49 ± 4 | 49 ± 4 | 0.575 |
| Left ventricular end-systolic dimension (mm) | 31 ± 3 | 31 ± 4 | 31 ± 3 | 0.545 |
| Left ventricular ejection fraction (%) | 69 ± 6 | 68 ± 6 | 70 ± 6 | 0.084 |
| Left atrial volume index (ml/m 2 ) | 32 ± 13 | 36 ± 17 | 31 ± 12 | <0.0001 |
| Early mitral inflow velocity (cm/s) | 62 ± 16 | 65 ± 17 | 61 ± 16 | 0.033 |
| Late mitral inflow velocity (cm/s) | 66 ± 19 | 68 ± 18 | 65 ± 19 | 0.295 |
| Deceleration time (ms) | 197 ± 42 | 202 ± 49 | 195 ± 40 | 0.156 |
| Mitral annular systolic velocity (cm/s) | 6.4 ± 1.5 | 5.8 ± 1.4 | 6.6 ± 1.4 | <0.0001 |
| Mitral annular early diastolic velocity (cm/s) | 4.9 ± 1.7 | 4.5 ± 1.4 | 5.1 ± 1.8 | 0.002 |
| Mitral annular late diastolic velocity (cm/s) | 7.9 ± 1.8 | 7.2 ± 1.7 | 8.0 ± 1.8 | <0.0001 |
| Early mitral inflow/mitral annular early diastolic ratio | 13.6 ± 4.9 | 15 ± 5 | 13 ± 5 | <0.0001 |
| Right ventricular systolic pressure (mm Hg) | 29 ± 8 | 31 ± 8 | 28 ± 7 | 0.002 |
During the mean follow-up of 43 ± 20 months, the all-cause mortality and cardiovascular mortality rate was 9% (39 of 454) and 5% (22 of 454), respectively, and 110 patients (25%) had MACE. Figure 1 shows the all-cause mortality rate and event-free survival rate of the study patients. Considering the age and co-morbidities of the enrolled subjects, the occurrence of mortality was not so frequent. However, a considerable number of the patients experienced MACE ( Figure 1 ). The clinical events the patients experienced during the follow-up periods are listed in Table 3 . MACE occurred in 110 patients (25%) of the enrolled population. A total of 39 patients (9%) died during the monitoring period, and 22 cases (5%) of mortality were of CV origin. Six deaths (1%) were suspected to be due to sudden cardiac death. Death because of to stroke and heart failure occurred in 7 (2%) and 11 (2%) patients, respectively. All 88 patients (19%) were hospitalized for the management of heart failure, and 26 patients (6%) experienced ischemic stroke during monitoring. Nonfatal myocardial infarction occurred in 2 patients without significant coronary artery disease and was confirmed by coronary angiography in both cases. A total of 62 patients (14%) had atrial fibrillation at presentation, and new-onset atrial fibrillation occurred in 10 patients (2%) during follow-up.
| Morbidity | n (%) |
|---|---|
| Total mortality | 39 (9%) |
| Cardiovascular mortality | 22 (5%) |
| Noncardiovascular mortality | 17 (4%) |
| Cardiovascular morbidities | |
| Hospitalization due to heart failure | 88 (19%) |
| Stroke | 26 (6%) |
| Nonfatal myocardial infarction | 2 (0%) |
| Atrial fibrillation | 72 (16%) |
| Pre-existing | 62 (14%) |
| New onset | 10 (2%) |
| Syncope or presyncope | 5 (1%) |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
