Scientists have identified a metabolic biomarker that could help track the progression of arrhythmogenic cardiomyopathy (AC) - an inherited heart condition that can kill swiftly and without warning - in a study of heart tissue and plasma from patients with AC. Even in patients with a family history of AC, sudden cardiac death is often the first detectable symptom of the disease. There are currently no clinical assessments specific for AC, and patients can remain outwardly healthy for up to 40 years. Now, building on prior work that indicated metabolic abnormalities in the heart muscle of AC patients, Jiang-Ping Song and colleagues have found that high levels of ketone bodies in the plasma of AC patients could serve as a reliable predictor of AC progression. The researchers compared heart tissue from a cohort of 13 AC patients with heart tissue from 13 healthy donors and found increased expression of enzymes involved in ketone metabolism in the AC patients' hearts. They also compared plasma samples from AC patients, healthy volunteers, and patients diagnosed with other cardiopulmonary diseases, and found elevated levels of ketone bodies - especially β-hydroxybutyrate - in the AC patient samples. Using both a mouse model of AC and cardiomyocytes derived from stem cells generated from AC patients, the researchers found further evidence for ketone-producing metabolic pathways as a hallmark of AC. In a final validation step, the researchers compared plasma from a cohort of 65 AC patients, 94 of their relatives, and 62 healthy volunteers, and found elevated β-hydroxybutyrate levels in the AC patients and some of their relatives. The findings suggest that β-hydroxybutyrate could serve as a reliable predictor of AC progression in those suspected to be at risk of the disease.