Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.

Here we evaluated whole-exome sequencing data from the randomized DECLARE-TIMI 58 trial, in which adults with type 2 diabetes and increased cardiovascular risk were randomized to dapagliflozin or placebo treatment.

在这里，我们评估了随机 DECLARE-TIMI 58 试验的全外显子组测序数据，该试验将有2型糖尿病和增加的心血管风险的成年人随机分配到达格列净或安慰剂治疗。

Pathogenic or likely pathogenic variants (P/LP) in high-confidence cardiomyopathy genes were identified, and treatment effects on hospitalization for HF (HHF) were compared between carriers of such variants and noncarriers.

在高可信度心肌病基因中识别出了致病或可能致病的变异体（P/LP），并将携带这些变异体的患者与非携带者在心力衰竭住院治疗效果上进行了比较。

Among 12,685 patients for whom sequence data were obtained, 121 carried a cardiomyopathy variant (76 dilated cardiomyopathy, 25 hypertrophic cardiomyopathy and 25 arrhythmogenic cardiomyopathy).

在获得序列数据的12,685名患者中，有121人携带心肌病变异体（76例扩张型心肌病，25例肥厚型心肌病和25例致心律失常性心肌病）。

Over a median follow-up of 4.2 years, dapagliflozin lowered the risk of HHF more strongly in carriers (hazard ratio0.18, 95% confidence interval0.04-0.86) than in noncarriers (hazard ratio0.70, 95% confidence interval0.57-0.86; P interaction 0.03).

在中位随访4.2年期间，达格列净在携带者中降低心力衰竭住院（HHF）风险的作用更强（风险比0.18，95%置信区间0.04-0.86），而在非携带者中风险比为0.70（95%置信区间0.57-0.86；P交互作用0.03）。

Absolute risk reduction was 13.0% in carriers and 1.0% in noncarriers (P interaction 0.03).

在携带者中绝对风险降低为13.0%，而在非携带者中为1.0%（P交互作用0.03）。

Most carriers (82%) had no prior HF, and in carriers without prior HF, treatment with dapagliflozin reduced the absolute risk of HHF by 12.8%, compared with a reduction of 0.6% in noncarriers (P interaction 0.01).

大多数携带者（82%）之前没有心力衰竭（HF）病史，在没有心力衰竭病史的携带者中，使用达格列净治疗可将心力衰竭住院（HHF）的绝对风险降低12.8%，而在非携带者中降低0.6%（P交互作用为0.01）。

The findings from this cohort of older and high-risk patients raise the possibility that SGLT2 inhibitor treatment should be started early to prevent HF in individuals who carry P/LP cardiomyopathy variants.

这项针对老年和高风险患者的研究结果提出了一个可能性，即应尽早开始使用SGLT2抑制剂治疗，以预防携带致病/可能致病（P/LP）心肌病变异的个体发生心力衰竭。

These results need to be confirmed in a prospective, dedicated trial of preventive HF treatments in carriers of P/LP cardiomyopathy-associated variants.

这些结果需要在一个前瞻性、专门针对携带P/LP心肌病相关变异的个体进行的预防性心力衰竭治疗试验中得到证实。