Do We Do Genetic Testing Early Enough for Cardiomyopathies?

Background: Cardiomyopathies are the most common indication for ventricular assist device (VAD) therapy and can have a variety of etiologies. Therefore, genetic testing is part of regular workup but requires time. The myosin regulatory light chain 2 (MYL2) gene encodes the light chain of myosin, in both the heart and skeletal muscles. To date, all 13 patients described in the literature with variants in the MYL2 gene demonstrated progressive muscle weakness and died within the first year of life.

Methods: A female premature infant of 36^6/7 weeks gestational age presented with tachycardia and biventricular hypertrophy directly after birth, which was considered to be due to intrauterine ischemic myocardial damage. At the age of 4.5 months, severe cardiac decompensation (monoplane ejection fraction [EF] 20%, pH 6.9, lactate 12 mmol/L) occurred during a viral infection. The patient showed rapid clinical improvement. Magnetic resonance imaging (MRI), echocardiography (EF 60%), and cardiac catheterization results (cardiac index 3.6 L/min/m²) were within normal range before discharge. Biopsy demonstrated myocardial damage without viral detection. With conspicuous muscular hypotension, a superordinate syndromic disease was suspected and genetic testing was initiated.

Results: Even before the genetic results were obtained, another viral infection triggered a second cardiac decompensation. The patient needed a left ventricular assist device (LVAD), and subsequently a right atrial vent with an oxygenator due to increasing right heart failure as a bridge to decision therapy. A myocardial muscle biopsy, taken during VAD implantation, demonstrated advanced muscle damage. Mitochondriopathy screening was performed using fibroblast growth factor 21 (FGF-21), which was clearly positive (>15,000 pg/mL). After receiving the genetic results with evidence of a stop mutation in the MYL2 gene, therapy had to be discontinued in the absence of a therapeutic goal. Mitochondrial DNA testing was unremarkable.

Conclusion: Rare genetic diseases that do not initially appear obvious can have a major impact on treatment decisions in patients with unclear cardiomyopathy. Therefore, complete genetic testing should be performed as soon as possible and if necessary supplemented by mitochondriopathy screening, although it is unclear whether FGF-21 provides clear information in the context of cardiac decompensation.

Publication History

Article published online:
11 February 2025