Identification of high risk patients with hypertrophic cardiomyopathy in a northern Greek population

Hypertrophic Cardiomyopathy (HCM) is a genetically transmitted cardiac disease characterized by myocardial hypertrophy in the absence of any other cause capable of producing the magnitude of hypertrophy present [1]. The incidence of HCM in general population is 0.2% [2]. The clinical spectrum of the disease is diverse ranging from an asymptomatic course throughout life to severe heart failure, stroke or sudden cardiac death [1]. HCM is the most common cause of sudden death (SD) in young people, including trained athletes [3]. The percentage of HCM patients who are in high risk for SD constitutes only a minority of all HCM population [4] but the incidence of SD in this subset is high (at least 5% annually) [5]. The identification of this small but important proportion of high risk HCM patients has been the clue in the clinical evaluation of these patients [4, 6‐8].

Highest risk for SD in HCM has been associated with any of the following noninvasive clinical markers [4, 6, 7, 9‐11]: prior cardiac arrest or spontaneous sustained ventricular tachycardia; family history of premature SD; syncope; nonsustained ventricular tachycardia (NSVT) on ambulatory (Holter) ECG recordings; abnormal blood pressure response (ABPR) to exercise; and extreme left ventricular (LV) hypertrophy with maximum wall thickness (MWT) ≥30 mm. Northern Greece has a population of about 3 million. People affected by HCM, in this area, are estimated to be 6.000. Concentrated epidemiologic and clinical data concerning the risk of SD and the natural history of HCM in this area are lacking. The purpose of our study was the identification of high risk HCM patients coming from Northern Greece.

The study cohort consisted from 123 patients with HCM who are currently followed up in our Institution, and who completed all noninvasive clinical tests for risk stratification, ie, personal and family history, clinical evaluation, 12-lead ECG, transthoracic echocardiography, 24-h ECG monitoring, and symptom-limited upright exercise test. Patients with documented sustained ventricular tachycardia or out-of-hospital cardiac arrest and those who were on amiodarone at first evaluation were excluded. Patients' follow up commenced the time the first diagnosis was made even if the diagnosis preceded baseline patient evaluation in our clinic. The diagnosis of HCM was based on the echocardiographic appearance of left ventricular MWT greater or equal than 15 mm, in the absence of any other cause capable of producing such hypertrophy [12, 13]. HCM was also considered present in patients with MWT 13 or 14 mm in the presence of a positive family history for HCM and/or ECG changes compatible with HCM. The patients were evaluated every 12 months, except otherwise was indicated.

Demographic and clinical characteristics of the 123 patients are outlined in Table 1. Patients' age at initial evaluation was 52.3 ± 15.6 years (16 to 83 years). Patients' mean age at the time of first diagnosis was 48.3 ± 16.4 (5 to 81 years), 82 patients (66.6%) were male. Nine patients (7.3%) were diagnosed as having HCM with congestive evolution. The diagnosis of congestive form was based on echocardiographic appearance of left ventricular MWT greater or equal than 15 mm with reduced ejection fraction (<50%) in the absence of any cause of secondary hypertrophy. In 3 patients the diagnosis confirmed by myocardial biopsy (extended myocardial disarray with hypertrophied myofibrils and areas of fibrosis). Coronary angiography and left heart catheterization was also performed in the remaining patients with HCM and systolic impairment. All these patients had normal coronaries without any valvulopathy more than moderate in severity. Coronary artery disease confirmed by coronary angiography was present in 6 patients (4.8%).

It is well established that in HCM-patients with a history of sustained ventricular tachycardia or documented cardiac arrest the risk of SD is sufficiently high to warrant prophylactic therapy, irrespective of the presence of other risk factors [11, 16] (Figure 2). Risk stratification in patents without a history of sustained ventricular tachycardia or documented cardiac arrest is a big clinical challenge and sometimes very difficult. Among the various clinical and echocardiographic variables considered, the simple model (based on a small number of generally accepted risk factors) proposed by Elliott et al [4] is, for the time, the most acceptable. The 5 non-invasive clinical markers indicating high risk for SD studied by Elliott et al [4] were family history of premature SD; syncope; NSVT on ambulatory (Holter) ECG recordings; ABPR to exercise; and extreme LV hypertrophy with MWT ≥30 mm. Our study group of 123 patients with HCM is unique by virtue of representing a regional cohort from a distinctive region of Northern Greece. Purpose of this study was the risk stratification of our patients, coming from a representative Northern Greek population, according to the previous referred clinical markers.

About half of our patients were referred from other centres for evaluation and treatment, and the other half was firstly diagnosed and evaluated in our clinic. As a consequence of this process, our study does not incorporate a substantial degree of patient selection bias. Our data indicates that a 60% of patients had no risk factors (55% in the study by Elliott et al [4]). A high percentage (20%) had 2 or more risk factors (12% in the study by Elliott et al [4], but in this study syncope and family history of premature SD were considered together as a single risk factor). In the study by Elliott et al [4] the presence of two or more risk factors was associated with a 4% to 5% estimated annual SD risk. Survival analysis was not performed in our study, since during the short follow-up period there was no any death among patients, and the objectives of this study was mainly the identification of the risk factors in our cohort. Although an ABPR to exercise is considered as a prognostic factor only in patients younger than 40 years of age [17], this marker was also examined in older patients, in order to collect homogeneous data in all patients. Additionally, a history of premature SD was considered positive if SD was happened before the age of 50 (<40 years in the study by Elliot et al [4]). The fact that almost 5% of patients without any risk factors experience sudden death [4], indicates that other variables, such as subaortic obstruction, atrial fibrillation and myocardial ischemia, must be taken into account in the risk stratification process.

This study for the first time confirms that, although a 60% of patients with HCM coming from a regional Greek population are in low risk for SD, a substantial proportion (almost 20%) carries a high risk for SD justifying prophylactic therapy with amiodaron or ICD implantation.