Article Impact Level: HIGH Data Quality: STRONG Summary of European Heart Journal, ehaf605. https://doi.org/10.1093/eurheartj/ehaf605 Dr. Nerea Mora-Ayestarán et al.
Points
- Patients with high-risk arrhythmic genotypes for dilated cardiomyopathy also experience a substantially higher rate of advanced heart failure events compared to other genetic and non-genetic groups.
- This specific patient cohort demonstrated an 85% increased hazard for heart transplantation, ventricular assist device implantation, or heart failure-related death during the multi-year study follow-up period.
- The same high-risk genetic group also had a 2.5-fold higher risk of developing malignant ventricular arrhythmias, confirming the dual threat posed by these specific genetic mutations.
- These findings support early identification and referral of genetically high-risk patients to specialized heart failure units for more aggressive management, even when their symptoms are still mild.
- This research advances precision medicine by highlighting the need for targeted therapies, with future efforts focusing on gene therapy and editing to correct the underlying genetic defects.
Summary
A Spanish multicenter study involving 1203 genotyped patients with dilated cardiomyopathy (DCM) aimed to determine if high-risk arrhythmic genotypes are also associated with more advanced heart failure (AHF) complications. Patients were categorized by genotype: high-risk arrhythmic genes (LMNA, FLNC, desmosomal genes, PLN, TMEM43, RBM20), TTN, other pathogenic genes, and genotype-negative. The primary endpoint was a composite of ventricular assist device implantation, heart transplant, and AHF-related mortality, while the secondary endpoint was malignant ventricular arrhythmias (MVA).
Over a median follow-up of 5.7 years, AHF events occurred in 24.3% of patients in the high-risk arrhythmic group (n = 185), compared to 18.7% with other gene variants, 13.0% with TTN variants, and 10.1% of genotype-negative patients. This conferred a significantly higher risk for the high-risk group (hazard ratio, 1.85; 95% confidence interval, 1.31–2.61) compared to the other cohorts combined. MVA occurred in 29.7% of the high-risk group, who faced a more than two-fold increased risk (hazard ratio, 2.52; 95% confidence interval, 1.81–3.51) compared to other groups.
Multivariate analysis identified the high-risk arrhythmic genotype as the leading independent predictor of AHF events. For MVA, both the high-risk genotype and the presence of late gadolinium enhancement were independent predictors of outcome. The study concludes that DCM patients with high-risk arrhythmic genotypes also experience a greater burden of AHF, supporting a differential therapeutic approach that extends beyond arrhythmia prevention to include more aggressive heart failure management.
Link to the article: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf605/8242426
References Mora-Ayestarán, N., Ochoa, J. P., Gómez-González, C., Navarro-Peñalver, M., Gallego-Delgado, M., Larrañaga-Moreira, J. M., Robles-Mezcua, A., Basurte-Elorz, M. T., Rodriguez-Palomares, J. F., Climent-Paya, V., Jiménez-Jaímez, J., Mogollón-Jiménez, M. V., García-Granja, P. E., García-Álvarez, A., Peña-Peña, M. L., Alvarez Barredo, M., Ripoll-Vera, T., Palomino-Doza, J., Bayes-Genis, A., … Domínguez, F. (2025). Arrhythmic genotypes in dilated cardiomyopathy and risk of advanced heart failure. European Heart Journal, ehaf605. https://doi.org/10.1093/eurheartj/ehaf605
