Heart failure & cardiomyopathiesCohort study
Interaction Between Genotype, Phenotype, and Prognosis in Patients With Dilated Cardiomyopathy
- Prospective cohort study
Authors' conclusion
Genetic background was associated with distinct myocardial fibrosis phenotypes and provided prognostic information beyond conventional CMR-derived fibrosis and functional phenotypes in DCM. Myocardial fibrosis partly mediates the association between non-TTN variants and adverse outcomes.
Study context
- Population
- Patients with dilated cardiomyopathy (DCM) who underwent whole-genome sequencing and cardiac magnetic resonance (CMR)163 (19.5%) with P/LP variants
- Participants
- 837 patients
- Exposure
- TTN variant vs non-TTN variant vs genotype-negative
- Non-TTN variantn = 78
- TTN variantn = 85
- Outcome
- CV death/heart transplantation, SCD and arrhythmic events
Main finding
As reported in the abstract
CV death/heart transplantation; SCD
Non-TTN variant vs Genotype-negativeAdjusted hazard ratio (95% CI)P value
CV death/heart transplantation; multivariable Cox
2.39(1.46–3.92)
P < 0.001SCD; multivariable Cox
3.26(1.59–6.65)
P = 0.001Observational data: associations, not effects.
Further findings
LGE prevalence
| Outcome | indirect HR (95% CI) | P value | |
|---|---|---|---|
| Mediation of non-TTN variant–adverse outcome association — LGE vs Genotype-negative | 1.26 (1.11–1.47) | P = 0.008 | |
| Mediation of non-TTN variant–adverse outcome association — ECV vs Genotype-negative | 1.29 (1.12–1.53) | P = 0.006 | |
| 0.512Indirect hr (log scale) |
- Late gadolinium enhancement (LGE) prevalence: P < 0.001
LGE prevalence
- Non-TTN: greater LGE extent, more ring-like and subepicardial patterns, higher native T1 and ECV
Outcomes by LGE, ECV and LVEF strata (subgroups)
- Non-TTN variants consistently had worse outcomes with LGE presence, greater LGE extent, elevated ECV and in both LVEF strata (≤35% and >35%)
- log-rank P < 0.05
Mediation of non-TTN variant–adverse outcome association
- LV end-diastolic volume index and LVEF showed no significant mediating effect
Original publication
Interaction Between Genotype, Phenotype, and Prognosis in Patients With Dilated Cardiomyopathy. JACC Cardiovasc Imaging. Published 28 September 2026. doi:10.1016/j.jcmg.2026.08.007
Summarised from the published abstract; every number is checked against it