Israel Medical Association Journal

Background: Hypertrophic cardiomyopathy (HCM) is a familial disease with autosomal dominant inheritance and age-dependent penetrance, caused primarily by mutations of sarcomere genes. Because the clinical variability of HCM is related to its genetic heterogeneity, genetic studies may improve the diagnosis and prognostic evaluation in HCM.

Objectives: To analyze the impact of genetic diagnosis on the clinical management of HCM.

Methods: Genetic studies were performed for either research or clinical reasons. Once the disease-causing mutation was identified, the management plan was reevaluated. Family members were invited to receive genetic counseling and encouraged to be tested for the mutation.

Results: Ten mutations in sarcomere protein genes were identified in 9 probands: 2 novel and 8 previously described. Advanced heart failure or sudden death in a young person prompted the genetic study in 8 of the 9 families. Of 98 relatives available for genotyping, only 53 (54%) agreed to be tested. The compliance was higher in families with sudden death and lower in what appeared to be sporadic HCM or elderly-onset disease. Among the healthy we identified 9 carriers and 19 non-carriers. In 6 individuals the test result resolved an uncertainty about "possible HCM." In several cases the genetic result was also used for family planning and played a role in decisions on cardioverter-defibrillator implantation.

Conclusions: Recurrence of a same mutation in different families created an opportunity to apply the information from the literature for risk stratification of individual patients. We suggest that the clinical context determine the indication for genetic testing and interpretation of the results.

Background: Patients with hypertrophic cardiomyopathy are prone to ventricular arrhythmias and sudden death. Identifying patients at risk of sudden death is difficult.

Objectives: To determine whether microvolt T-wave alternans detected during exercise or rapid atrial pacing can identify patients with HCM[1] who are at risk of ventricular arrhythmias and sudden death.

Methods: This prospective observational study included 21 patients with HCM: 11 with hypertrophic obstructive cardiomyopathy, 9 with non-obstructive hypertrophic cardiomyopathy, and 1 with apical hypertrophic cardiomyopathy. TWA[2] was measured while the patients were on anti-arrhythmic medication.

Results: TWA was positive in 9 patients (43%) and negative in 12 (57%). Three patients were resuscitated after sudden death before their enrolment in the study and two patients developed ventricular tachycardia and fibrillation respectively during the study period. After combining the endpoint of sudden death from a ventricular arrhythmia and the presence of ventricular arrhythmias on a Holter monitor, there was no significant correlation between the presence of a positive TWA and the presence of ventricular arrhythmias on the Holter monitor or a history of sudden death.  

Conclusion: TWA cannot be used as a non-invasive test for detecting patients with HCM and electrical instability. TWA is not useful for predicting sudden death in patients with HCM.

Background: Left ventricular outflow gradient is associated with increased morbidity and mortality in hypertrophic cardiomyopathy. Alcohol septal ablation is the alternative to surgery in cases refractory to drug therapy. The implication of LVOG[1] measured 1 week post-ASA[2] for prediction of outcome is unknown.

Objective: To observe the pattern of LVOG course and prediction of long-term clinical and hemodynamic outcome of ASA.

Methods: Baseline clinical and echocardiographic parameters were prospectively recorded in 14 consecutive patients with a first ASA, at the time of ASA, 3 and 7 days after ASA (in-hospital) and 3 and ≥ 12 months after ASA (last follow-up).

Results: There was improvement in NYHA class, exercise parameters and LVOG in 11 of 14 patients (P < 0.005 in all). Maximal creatine kinase level was lower than 500 U/L in those without such improvement and 850 U/L or higher in successful cases. LVOG dropped from 79 ± 30 to 19 ± 6 mmHg after the ASA. LVOG was 50 ± 21 mmHg on day 3, 39 ± 26 on day 7, 32 ± 26 at 3 months and 24 ± 20 mmHg at last follow-up. LVOG identified 27% sustained procedural successes on day 3 and 73% on day 7. The overall predictive accuracy of the test for sustained success and failure was 36% on day 3 and 71% on day 7. Combination of maximal CK[3] and LVOG on day 7 showed four distinct outcome patterns: "early success" with low LVOG and high CK (73% of successful cases), "late success" with high LVOG and high CK, and "early failure" and "late failure" with both low CK and high or low LVOG, respectively
Conclusion: LVOG measurement 7 days post-ASA combined with maximal CK levels predicts late procedural outcome in the majority of patients

Background: Long-term follow-up in apical hypertrophic cardiomyopathy is rare.

Objective: To study the natural history of the disease.

Methods: We followed 11 patients, 5 women and 6 men, for 5-20 years.

Results: At presentation all 11 patients had typical features of apical hypertrophic cardiomyopathy, with dyspnea in 3 and chest pains in 8, of whom 5 were typical of angina and 3 had myocardial infarction. R-wave voltage and T-wave negativity progressively decreased in magnitude at serial electrocardiograms in four patients. Perfusion defects were detected on thallium myocardial scintigraphy in three, increased apical uptake in two, and normal in one patient. Apical aneurysm with normal coronary arteries developed in a patient who had sustained ventricular tachycardia. All of the 10 catheterized patients had normal coronaries except for one with significant left anterior descending artery stenosis and another with a minor lesion. Symptomatic sustained ventricular tachycardia was found in two patients, one of whom required the implantation of an internal cardioverter-defibrillator.

Conclusions: Apical hypertrophic cardiomyopathy may develop morphologic and electrocardiographic changes with life-threatening arrhythmias necessitating close follow-up and treatment.