Setti Martina, Iseppi Manuela, Verdonschot Job A J, Rizzi Jacopo G, Paldino Alessia, Pio Loco Detto Gava Carola, Barbati Giulia, Dal Ferro Matteo, Venner Max F G H M, Raafs Anne G, Gigli Marta, Stolfo Davide, De Luca Antonio, De Angelis Giulia, Capovilla Teresa M, Graw Sharon, Ribichini Flavio L, Taylor Matthew, Mestroni Luisa, Heymans Stephane R B, Sinagra Gianfranco, Merlo Marco
Center for Diagnosis and Treatment of Cardiomyopathies, Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy.
European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart).
Eur J Heart Fail. 2025 Apr 29. doi: 10.1002/ejhf.3671.
Left ventricular reverse remodelling (LVRR) is a prognostic marker in patients with dilated (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC). The utility of combining late gadolinium enhancement (LGE) and genetic testing in predicting LVRR in DCM/NDLVC remains a knowledge gap. This study aimed to assess an integrated approach including LGE data and genetics to predict LVRR in DCM/NDLVC patients.
This multicentre observational study included DCM/NDLVC patients with: (i) baseline echocardiographic left ventricular ejection fraction (LVEF) <50%; (ii) genetic testing; (iii) baseline cardiac magnetic resonance (CMR); (iv) 12-month follow-up echocardiographic data. LVRR was defined as LVEF increase ≥10% or LVEF ≥50% (if baseline LVEF <45%) at 12 months. Outcome measures were: (i) all-cause mortality, heart transplant, or left ventricular assist device implantation (D/HT/LVAD); (ii) sudden cardiac death or major ventricular arrhythmias (SCD/MVA). Arrhythmogenic genes studied were LMNA, DSP, FLNC, and RBM20. Among 1757 DCM/NDLVC with genetic data, 616 met eligibility (462 DCM, 154 NDLVC; age 51 ± 14 years, 34% female). LVRR occurred in 314 patients (51%): 251 (54%) in DCM and 63 (41%) in NDLVC (p = 0.004). Independent predictors of LVRR within 1 year included titin truncating variants, absence of arrhythmogenic genes, and absence of LGE ring-like pattern. In patients with LVEF <35%, only the presence of LGE ring-like pattern and arrhythmogenic genes remained independently related to a lower rate of LVRR and increased SCD/MVA risk.
In a large genetically and CMR characterized DCM/NDLVC cohort, arrhythmogenic genotypes and LGE ring-like pattern were inversely related to LVRR, particularly in patients with LVEF <35%.
左心室逆向重构（LVRR）是扩张型心肌病（DCM）和非扩张型左心室心肌病（NDLVC）患者的预后标志物。在DCM/NDLVC中，联合延迟钆增强（LGE）和基因检测预测LVRR的效用仍存在知识空白。本研究旨在评估一种包括LGE数据和遗传学的综合方法，以预测DCM/NDLVC患者的LVRR。
这项多中心观察性研究纳入了符合以下条件的DCM/NDLVC患者：（i）基线超声心动图左心室射血分数（LVEF）<50%；（ii）基因检测；（iii）基线心脏磁共振成像（CMR）；（iv）12个月随访的超声心动图数据。LVRR定义为12个月时LVEF增加≥10%或LVEF≥50%（如果基线LVEF<45%）。观察指标为：（i）全因死亡率、心脏移植或左心室辅助装置植入（D/HT/LVAD）；（ii）心源性猝死或重大室性心律失常（SCD/MVA）。研究的致心律失常基因包括LMNA、DSP、FLNC和RBM20。在1757例有基因数据的DCM/NDLVC患者中，616例符合条件（462例DCM，154例NDLVC；年龄51±14岁，34%为女性）。314例患者（51%）发生了LVRR：DCM患者中有251例（54%），NDLVC患者中有63例（41%）（p=0.004）。1年内LVRR独立预测因素包括肌联蛋白截短变异、不存在致心律失常基因以及不存在LGE环状模式。在LVEF<35%的患者中，仅LGE环状模式和致心律失常基因的存在与较低的LVRR发生率和增加的SCD/MVA风险独立相关。
在一个大型的具有遗传学和CMR特征的DCM/NDLVC队列中，致心律失常基因型和LGE环状模式与LVRR呈负相关，尤其是在LVEF<35%的患者中。
