Department of Genetic Counselling, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
J Cardiovasc Transl Res. 2023 Dec;16(6):1303-1309. doi: 10.1007/s12265-023-10421-6. Epub 2023 Aug 7.
Predictors of myocardial recovery in heart failure (HF) are poorly understood. We explored if vinculin (VCL) variants are associated with myocardial recovery in dilated cardiomyopathy (DCM). Six infants with DCM with a VCL loss-of-function (LOF) variant were identified. Median age at diagnosis was 2 months, median LV ejection fraction was 24%, and median LV end-diastolic diameter z-score was 10.8. All patients received HF medications. Five patients (83%) showed normalization of LV function at a median age of 2.7 years. One patient progressed to end-stage HF requiring heart transplant. This case series identified a unique phenotype of HF with reduced ejection fraction at presentation that evolved to HF with recovered EF in over 80% of infant DCM cases with LOF VCL variants. These findings have prognostic implications for counseling and management of VCL-associated DCM and highlight a possible genetic basis for HF with recovered ejection fraction.
心力衰竭(HF)心肌恢复的预测因素了解甚少。我们探讨了粘着斑蛋白(VCL)变异是否与扩张型心肌病(DCM)的心肌恢复相关。鉴定了 6 例具有 DCM 和粘着斑蛋白丧失功能(LOF)变异的婴儿。诊断时的中位年龄为 2 个月,中位左心室射血分数为 24%,中位左心室舒张末期直径 z 评分 10.8。所有患者均接受 HF 药物治疗。5 名患者(83%)在中位年龄 2.7 岁时表现出左心室功能正常化。1 名患者进展为终末期 HF,需要心脏移植。该病例系列确定了一种独特的 HF 表型,即射血分数降低的 HF,80%以上具有 LOF VCL 变异的婴儿 DCM 病例发展为 EF 恢复的 HF。这些发现对 VCL 相关 DCM 的咨询和管理具有预后意义,并强调了 EF 恢复性 HF 的可能遗传基础。