What does this research mean for the field?

Carriers of desmosomal and LMNA gene variants with dilated cardiomyopathy face the highest risk of sudden cardiac death and life-threatening ventricular arrhythmias, independent of left ventricular ejection fraction. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the prognostic impact of genetic variant carrier status on arrhythmic and clinical outcomes in a large cohort of patients with dilated cardiomyopathy.

July 8, 2026Journal of the American College of CardiologyOpen Access

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy

Q: What are the key findings of this study?

Desmosomal and LMNA gene variants identify the subset of dilated cardiomyopathy patients at greatest risk for sudden cardiac death and life-threatening ventricular arrhythmias, regardless of left ventricular ejection fraction.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Dilated Cardiomyopathy (DCM) (n=487). Intervention: Pathogenic or likely pathogenic genetic variants (including desmosomal and LMNA) vs. Non-carriers (variant-negative patients). Primary outcome: All-cause mortality (p=0.99).

View Full Paper

Ask AI

Bookmark

Key result

Desmosomal and LMNA variants identify DCM patients at highest risk for life-threatening arrhythmias regardless of LVEF.

P=0.99
n=487

Why the study?

Genotype-phenotype correlations in dilated cardiomyopathy and the effects of gene variants on clinical outcomes remain poorly understood.

Does genetic variant carrier status predict adverse clinical outcomes in patients with dilated cardiomyopathy?

Key Points

To evaluate the prognostic impact of genetic variant carrier status on arrhythmic and clinical outcomes in a large cohort of patients with dilated cardiomyopathy.
Analyzed 487 dilated cardiomyopathy patients (including 429 probands; 329 US and 158 Italian patients) using next-generation sequencing classified into functional gene groups.
Tracked clinical outcomes over a median follow-up of 125 months (10.4 years) for all-cause mortality, heart failure progression (DHF/HTx/VAD), and sudden cardiac death or malignant ventricular arrhythmias (SCD/VT/VF).
Identified 183 pathogenic or likely pathogenic variants in 178 patients (37%), with no significant difference in all-cause mortality between carriers and non-carriers (p=0.99).
Observed a trend toward worse SCD/VT/VF (p=0.062) and DHF/HTx/VAD (p=0.061) among variant carriers compared to non-carriers.
Carriers of LMNA variants experienced higher rates of SCD/VT/VF (p=0.002 vs variant-negative) and DHF/HTx/VAD (p<0.001), while desmosomal variant carriers had similarly elevated arrhythmic risk (p=0.006 vs variant-negative), independent of left ventricular ejection fraction.

Study Design

Type

Cohort (n=487)

Multicenter

Yes

Structured PICO

Does genetic variant carrier status predict adverse clinical outcomes in patients with dilated cardiomyopathy?

Population

487 patients with dilated cardiomyopathy (mean age 41, 32% female) followed for a median of 10.4 years to assess the prognostic role of genetic variant carrier status.

Exposure

Carrier status for pathogenic or likely pathogenic genetic variants (including TTN, LMNA, structural cytoskeleton-Z disk, desmosomal, sarcomeric, and ion channel genes)

Comparator

Non-carriers (variant-negative patients)

Outcome

Composite outcome measures: 1) all-cause mortality; 2) heart failure related death, heart transplantation or destination left ventricular assist device implantation (DHF/HTx/VAD); 3) sudden cardiac death or malignant ventricular arrhythmias (SCD/VT/VF)composite

Main Result

p-value: p=0.99

Genetic testing in dilated cardiomyopathy, particularly identifying desmosomal and LMNA variants, provides critical prognostic information for arrhythmic risk stratification independent of LVEF.

Limitations

Observational nature of the study
Small number of patients belonging to each functional gene group
Comprehensive co-segregation analysis was not performed due to limited availability of samples from relatives
Data on endomyocardial biopsy, cardiac magnetic resonance and electrophysiological testing were available in only a subset of patients

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

May refine arrhythmic risk stratification in DCM beyond LVEF; leaves open whether genotype guides ICD decisions.

Cite This Study

Gigli et al. (2019) conducted a cohort in Dilated Cardiomyopathy (DCM) (n=487). Pathogenic or likely pathogenic genetic variants (including desmosomal and LMNA) vs. Non-carriers (variant-negative patients) was evaluated on All-cause mortality (p=0.99). Desmosomal and LMNA gene variants identify the subset of dilated cardiomyopathy patients at greatest risk for sudden cardiac death and life-threatening ventricular arrhythmias, regardless of left ventricular ejection fraction.

synapsesocial.com/papers/6a4ebec98d6b14ebdbbc88aa https://doi.org/10.1016/j.jacc.2019.06.072

View Full Paper

Ask AI

Bookmark

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Also Consider

Also Consider