Screening for Cardiac Involvement in Mitochondrial Diseases

Background:
Primary mitochondrial disorders are rare hereditary diseases based on genetic mutations in either mitochondrial or nuclear DNA and lead to altered cell metabolism. Tissues with high energy requirements are predominantly affected so that patients present primarily with neuromuscular symptoms. Cardiac involvement is frequent and has been associated with both structural and electrocardiographic changes. Guidelines recommend ecg screening, whereas echocardiographic testing is only recommended for high risk patients.

Purpose:
The purpose of this study was to evaluate the frequency of echocardiographic and electrocardiographic changes in one of the largest cohorts of patients with primary mitochondrial disorder and to determine whether electrocardiographic testing alone may lead to under-diagnosis of cardiac involvement.

Methods:
We prospectively analyzed ECG and echocardiographic data from 117 patients with primary mitochondrial disease. Parameters included conduction intervals, structural measurements, and functional markers.

Results:
Overall left ventricular diameters and biventricular function were within normal range (see Table 1). Echocardiographic abnormalities were found in 32(27.4%) patients. 27(23.1%) displayed signs of left ventricular hypertrophy above 12 mm. 5(4.3%) patients  had reduced left ventricular function. Of those with left ventricular hypertrophy on echocardiogram,  6(22.2%) patients exhibited signs of hypertrophy on ecg and 7(26.0%) had bundle branch blocks (BBBs). Among patients with reduced LVEF, ECG findings included LBBB (n=1), positive Sokolow Lyon index(n=1), low voltage on ecg(n=1), sinistro-atrial pattern (n=1), and preexcitation (n=1).
ECG abnormalities occurred in 31(26.5%) patients: 13(11.1%) with positive Sokolow Lyon index, 13(11.1%) with BBBs, 2(1.7%) with AV block I, 1(0.9%) with complete AV block and pacemaker, 1(0.9%) with preexcitation. QTc prolongation was found in 13 men (>450ms) and 5 women (>470ms)(15.4% of patients). One case of atrial fibrillation was observed.

Conclusions:
Cardiac abnormalities are frequent in patients with mitochondrial disease. While electrocardiographic (ECG) findings such as conduction delays and repolarization changes are common, early structural changes—particularly left ventricular hypertrophy—often occur without corresponding ECG correlates. This dissociation highlights the importance of performing both echocardiography and ECG in the diagnostic evaluation and longitudinal monitoring of affected individuals, even in the absence of symptoms or ECG abnormalities

Age [years]	44.7	[32.6;56.8]
Male Sex	52	44.4%
BMI	22.3	[19.0;25.2]
PQ [ms]	144.0	[130.0;162.0]
QRS [ms]	94.0	[88.0;104.5]
QTC [ms]	425.0	[408.0;446.5]
IVSD [mm]	9.0	[8.0;11.0]
LVEF [%]	60.0	[55.0;62.8]
TAPSE [mm]	22.0	[19.5;24.8]

 Table 1: Patient characteristics

Figure: Distribution of mitochondrial disease diseases