**4.1. Diagnosis of mitochondrial dysfunction in heart disease**

Although it has been widely accepted that mitochondria play a key role in cardiac pathological conditions, effectively diagnosing mitochondrial dysfunction in the clinical setting has been challenging. MDs often affect multiple organ systems in the body and clinical presentation varies; however, there are a few "tell-tale" signs and combinations that may enable clinicians to better identify MDs [148]. For example, patients with KSS, which is typically associated with single deletion mutations, may present with ptosis, retinal pigmentary abnormalities, ataxia, and cardiac conduction abnormalities [148]. In patients with myoclonic epilepsy with ragged-red fibers (MERRF), myoclonus, cerebellar ataxia, and elevated blood lactate are key symptoms in their presentations [149]. A high suspicion is important when considering a diagnosis of MD. Cardiologists who evaluate patients for hypertrophy, conduction abnormalities, and DCM should be aware of the spectrum of MD so that they can collaborate with MD specialists to make accurate diagnoses.

Since there are variabilities in the MD symptom presentations, in addition to the clinical diagnosis, a multiple-parametric approach that involves histological, biochemical, and genetic testing is required to identify abnormalities of blood, urine, or cerebrospinal fluid (CSF) analyte values, microscopic irregularities, biochemical deviations on polarographic assays, or a diagnostic genetic finding [150].
