Onset and progression of dilated cardiomyopathy in genotyped Doberman Pinschers with PDK4 and TTN variants: a 12.5-year longitudinal study

Allelic variants in pyruvate dehydrogenase kinase 4 (PDK4) and titin (TTN) are associated with dilated cardiomyopathy (DCM) in Doberman Pinschers. We aimed to characterize DCM onset, progression, and manifestation based on PDK4 and TTN variant status to inform genotype-specific clinical care. This prospective longitudinal study enrolled client-owned Doberman Pinschers at the University of Florida from October 2012 through March 2025. A total of 329 dogs with known PDK4 and TTN variant status underwent echocardiography and Holter monitoring. Dogs were categorized into nine genotype combinations and compared to wild-type controls (WT/WT). Analyses included linear regression, Fisher-Freeman-Halton exact test with Bonferroni correction, and Kaplan-Meier survival analysis. Among 329 dogs, 39.8% developed DCM, with males developing DCM earlier than females (median 85 vs. 94 months). Homozygous PDK4 variants were strongly associated with severe arrhythmias (44.5–50% prevalence vs. 2.4% in WT/WT, p < 0.001). The Het/Het group demonstrated significant age-related decline in fractional shortening ( p = 0.0118), as did the Hom/Hom group ( p = 0.025). Het/Het and Hom/Hom groups showed significant increases in left ventricular systolic dimensions with age ( p < 0.001). No significant survival differences were observed between genotype groups, although the Hom/Hom group approached statistical significance for earlier DCM-related death ( p = 0.054). This study identifies distinct genotype-specific DCM patterns in Doberman Pinschers, with PDK4 mutation carriers demonstrating high arrhythmogenesis and combined mutation carriers developing progressive systolic dysfunction. These findings support tailored monitoring strategies based on variant status.