Systematic review and meta-analysis of cardiac involvement in mitochondrial myopathy

Abstract

ObjectiveOur goal was to perform a systematic review of the literature to demonstrate the prevalence of cardiac abnormalities identified using cardiac investigations in patients with mitochondrial myopathy (MM).MethodsThis systematic review surveys the available evidence for cardiac investigations in MM from a total of 21 studies including 825 participants. Data were stratified by genetic mutation and clinical syndrome.ResultsWe identified echocardiogram and ECG as the principal screening modalities that identify cardiac structural (29%) and conduction abnormalities (39%) in various MM syndromes. ECG abnormalities were more prevalent in patients with m.3243A>G mutations than other gene defects, and patients with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) had a higher prevalence of ECG abnormalities than patients with other clinical syndromes. Echocardiogram abnormalities were significantly more prevalent in patients with m.3243A>G or m.8344A>G mutations compared with other genetic mutations. Similarly, MELAS and MERRF had a higher prevalence compared with other syndromes. We observed a descriptive finding of an increased prevalence of ECG abnormalities in pediatric patients compared with adults.ConclusionsThis analysis supports the presence of a more severe cardiac phenotype in MELAS and myoclonic epilepsy with ragged red fibres syndromes and with their commonly associated genetic mutations (m.3243A>G and m.8344A>G). This provides the first evidence basis on which to provide more intensive cardiac screening for patients with certain clinical syndromes and genetic mutations. However, the data are based on a small number of studies. We recommend further studies of natural history, therapeutic response, pediatric participants, and cardiac MRI as areas for future investigation.

Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects

“…A few recent studies proposed that cardiac surveillance for mitochondrial patients can be stratified based on the clinical syndrome or phenotype alone. 7 8 30 However, such recommendations have limitations, given that the phenotype–genotype correlation is not always evident. For instance, CPEO and myopathy are common clinical features seen in adult patients with mitochondrial disease and the genetic causes are highly heterogeneous, which include primary mtDNA point mutations such as m.3243A>G, single, large-scale mtDNA deletions or multiple mtDNA deletions secondary to nuclear gene defects as outlined previously.…”

“… 3–6 However, the spectrum of cardiac manifestation among patients with nDNA defects has only been described in isolated case reports or small case series. 7 At present, regular cardiac surveillance is routinely recommended for all patients with mitochondrial disease irrespective of the underlying genetic aetiology. 8 …”

Novel myocardial markers GADD45G and NDUFS5 identified by RNA-sequencing predicts left ventricular reverse remodeling in advanced non-ischemic heart failure: a retrospective cohort study

“…mitochondrial disease (MD), can involve myocardium and induce cardiac dysfunction through disrupted mitochondrial respiratory chain functions [37]. In addition, even isolated cardiac phenotype is found in MD [38]. Thus, inherent but underdiagnosed MD might be included in the study population.…”

Mitochondrial Syndromes Revisited

“…A recent systematic review showed that patients with MELAS had significantly more electrocardiography and echocardiography (especially left ventricular hypertrophy) abnormalities than patients with other mitochondrial phenotypes. A common and well-described cardiac complication overrepresented in MELAS was Wolff–Parkinson–White syndrome (WPW) [ 28 ]. The worst prognosis can be independently predicted by a personal history of seizures and left ventricular hypertrophy in these patients [ 29 ].…”