Clinically-Significant Cardiac Pathology in Leber’s Hereditary Optic Neuropathy

Abstract

Purpose: To determine the association of clinically-significant cardiac pathology with status as a carrier or affected subject, and to compare previous findings on cardiac conduction in affected patients with Leber’s hereditary optic neuropathy (LHON), 11778 mutation, to a distinct pedigree.

Methods: Cardiac pathology was defined by past history of stroke, myocardial infarction, angina, and/or palpitations. Subjects were compared based on LHON status: control, carrier, or affected. A logistic regression model was constructed, controlling for age and body mass index (BMI). Data from a previously published cohort of affected Brazilian patients (n₁=23) and newly-acquired values from a distinct Italian cohort (n₂=21) were compared to a database of healthy controls (n₂=87). Each population underwent ECG testing, performed by a cardiologist, with measurement of PR interval and QTc duration. An unpaired student’s t-test was performed to determine if there was a difference between affected populations and controls.

Results: The final regression model indicates that LHON status is not correlated with an increased prevalence of cardiac pathology in the sample population. Age is a significant predictor, but interaction between age and status did not yield a significant difference between groups. BMI was not found to be a significant predictor of cardiac pathology. Mean PR intervals and standard deviations in the Italian pedigree, Brazilian pedigree and control population were 140.6±20.6, 127.2±26.1 and 136.9±9.1, respectively. There was no significant difference detected in mean PR interval between the Italian pedigree and healthy controls, thereby validating the previously-published findings in the Brazilian population. However, this study similarly demonstrated a subgroup of patients within the Italian pedigree who had a shortened PR interval (n=2). There was no significant difference in QTc duration between affected and control populations in either pedigree.

Conclusions: Carrier and affected populations of LHON do not demonstrate increased prevalence of clinically-significant cardiac pathology. This study validated the previously published findings of a non-significant difference in PR interval and QTc duration in affected patients with LHON and controls. A subgroup of subjects with shortened cardiac conduction may be indicative of patients at increased risk for conduction defects.