We found that in LQTS patients over age 40 years, development of CD is an independent and significant risk factor for LQTS-related cardiac events. Syncope before age 40 is an independent and significant risk factor. Factors such as diabetes and hypertension that increase the risk for CD were not associated with an increased risk for LQTS-related cardiac events.
The altered substrate in CD (ischemia, scar, and possibly reduced ejection fraction) may lower the threshold for afterdepolarization in LQTS, a critical factor in the initiation of torsade de pointes that is thought to be the arrhythmogenic mechanism in LQTS-related cardiac events.11
Only one patient died suddenly in this study population. It is unclear whether the use of implantable cardioverter defibrillators in 15% of the patients without CD and 30% of the patients with CD contributed to this low sudden cardiac death rate. We do not have information on the frequency of life-saving appropriate shock therapy in these defibrillator-treated patients. However, when these defibrillator patients were excluded from the analysis, the findings in the Cox risk model were essentially unchanged.
Beta-blockers were utilized in a majority of the patients, and this medication was not associated with a significant reduction in cardiac events in the overall study population (). However, beta-blockers were associated with a significant reduction in cardiac events in the higher-risk patients who had syncope before age 40 (hazard ratio=0.56, p=0.04). This finding is consistent with our prior experience in younger LQTS patients in which beta-blocker efficacy was evident only in higher-risk patients.3,4
An important question relates to the accuracy of the diagnosis of CD in this study population. We relied exclusively on data from a prespecified medical questionnaire that was completed by all study participants older than 40 years of age. Patient recall is generally quite good for hospitalizations related to acute myocardial infarction, coronary angioplasty, or coronary artery bypass surgery. The diagnosis of angina is a bit softer, but we required for this diagnosis that the patient had physician-prescribed antianginal sublingual nitrate therapy for treatment of chest pain. We feel confident that the diagnosis of CD was accurate in these patients, but we may have missed the diagnosis of CD in a small percentage of patients who experienced coronary symptoms but responded negatively to the questionnaire. Unfortunately, we do not have information from hospital records or coronary angiographic data to verify the diagnosis of CD, and we have no data on the severity of the coronary disease or associated myocardial dysfunction.
Since CD can produce cardiac arrhythmias that result in syncope, aborted cardiac arrest, and sudden cardiac death, is it appropriate to categorize these events as LQTS-related cardiac end points, especially in the over 40 age group? Syncope is a frequent event in LQTS and relatively infrequent in CD, and syncope dominated the events in this study and accounted for more than 50% of the end points (), much like the findings in several of our prior LQTS studies in patients younger than 40 years of age.3,4
This is the first study to investigate the influence of CD on LQTS risk in older LQTS patients. The development of CD is associated with increased risk for LQTS-related cardiac events, especially syncope, and this finding highlights the need for more effective preventive therapy when coronary disease develops in older LQTS patients.