Letter by Singh et al Regarding Article, "Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)".
Letter by Singh et al Regarding Article, "Effect of Empagliflozin on Left Ventricular Volumes in Patients With Type 2 Diabetes, or Prediabetes, and Heart Failure With Reduced Ejection Fraction (SUGAR-DM-HF)".
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Singh 等人关于文章“恩格列净对 2 型糖尿病或糖尿病前期和射血分数降低的心力衰竭 (SUGAR-DM-HF) 患者左心室容量的影响”的信函。
DOI：
10.1161/circulationaha.120.053057
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发表时间：
2021
期刊：
影响因子：
37.8
通讯作者：
Singh JS
中科院分区：
文献类型：
--
作者：
Singh JS
特别值得注意的是观察到左心室（LV）容量减少，这在改革试验（SGLT 2抑制对心力衰竭和糖尿病患者左心室重塑的影响研究）中未观察到，这是我们之前使用达格列净进行的一项非常相似的试验。2作者正确地指出，改革参与者的射血分数较高（45.5% vs 32.5%），左心室容积较小（左心室收缩末期容积：52 vs 77 mL/m2），基线时纽约心脏协会功能分级较好（45% vs纽约心脏协会功能分级I级0%）。然而，两项试验之间还有一个重要的差异：改革观察到治疗组中更多的参与者减少或停止了袢利尿剂治疗（53.6%对10.7%; P< 0.001），1年时袢利尿剂剂量总体平均减少29.06 mg（P= 0.001），而在本研究中，作者报告袢利尿剂剂量无差异。这表明观察到的LV体积减少的原因可归因于钠-葡萄糖连接转运蛋白2（SGLT 2）抑制剂的已知利尿作用。射血分数或整体纵向应变（收缩力指标）和LV质量或NT-proBNP（[N末端B型利钠肽前体]心室内压力超负荷指标）不变进一步支持了这一点。在改革试验中未观察到LV容量超负荷的减少，因为在研究期间同时减少了袢利尿剂的使用（这是当时监管机构强制要求的）。有趣的是，尽管本研究中的队列与改革相比射血分数更差，LV体积更大，纽约心脏协会功能分级更差，在改革中，只有57.1%的患者在基线时使用袢利尿剂（剂量未报告），而所有患者均使用袢利尿剂（平均剂量为49.8 mg/d）。这一结果表明，本研究中的受试者可能接受了次优剂量的利尿剂，并从恩格列净产生的额外利尿作用中显著获益。事实上，我们最近报告了恩格列净导致心力衰竭伴射血分数降低患者在合并袢利尿剂治疗时24小时尿量增加。3第3天尿量增加（平均差异为535 mL; P= 0.005），第6周尿量增加（平均差异为545 mL; P= 0.005）。同样，来自DAPA-HF 4和EMPEROR-Reduced试验5的分析报告称，利尿剂治疗减少的受试者更有可能使用SGLT 2抑制剂，而利尿剂强化的受试者更有可能使用安慰剂。综上所述，Lee et al的这项研究有力地证明了SGLT 2抑制剂的利尿获益，并加强了在射血分数降低的心力衰竭患者中使用适当剂量的利尿剂实现等血容量的理由。然而，我们认为，迄今为止，在大型SGLT 2抑制剂结局试验中观察到的显著发病率和死亡率获益的真正机制仍不清楚。显然，还需要做更多的工作。
Of particular interest was the observation of reduced left ventricular (LV) volumes, which was not seen in the REFORM trial (Research Into the Effect of SGLT2 Inhibition on Left Ventricular Remodeling in Patients With Heart Failure and Diabetes Mellitus), which was a very similar trial we conducted previously with dapagliflozin. 2 The authors correctly point out that participants in REFORM had higher ejection fraction (45.5% vs 32.5%), smaller LV volumes (left ventricular end-systolic volume: 52 vs 77 mL/m2), and better New York Heart Association Functional Class (45% vs 0% in New York Heart Association Functional Class I) at baseline. However, there was 1 other important difference between the trials: REFORM saw more participants reducing or stopping their loop diuretic therapy in the treatment arm (53.6% vs 10.7%; P< 0.001) with an overall mean reduction in loop diuretic dose by 29.06 mg (P= 0.001) at 1 year, whereas in the current study the authors report no difference in loop diuretic dose. This suggests that the reason for reductions in LV volumes observed was attributable to the known diuretic effect of sodium-glucose linked transporter type 2 (SGLT2) inhibitors. This is supported further by the unchanged ejection fraction or global longitudinal strain (measures of contractility) and LV mass or NT-proBNP ([N-terminal pro-B-type natriuretic peptide] measures of intraventricular pressure overload). This reduction in LV volume overload was not observed in the REFORM trial because there was a concomitant reduction in loop diuretics during the study period (which was mandated by the regulatory authorities at the time).It is interesting that although the cohort in the present study had poorer ejection fraction, larger LV volumes, and worse New York Heart Association Functional Class compared with REFORM, only 57.1% were prescribed a loop diuretic at baseline (dose not reported) compared with everyone being on loop diuretics (mean dose, 49.8 mg/d) in REFORM. This finding suggests that participants in the present study were likely to be on suboptimal doses of diuretics and benefited significantly from the additional diuresis generated by empagliflozin. Indeed, we recently reported that empagliflozin caused an increase in 24-hour urinary volume in patients with heart failure with reduced ejection fraction on concomitant loop diuretic therapy. 3 There was higher urine output at day 3 (mean difference, 535 mL; P= 0.005) which was sustained at week 6 (mean difference, 545 mL; P= 0.005). Similarly, analyses from the DAPA-HF4 and EMPEROR-Reduced trials5 reported that participants who saw reductions in diuretic therapy were significantly more likely to be on an SGLT2 inhibitor, while those who saw intensification of diuretics were more likely to be on placebo. Putting all of this together, this study by Lee et al has powerfully demonstrated the diuretic benefit of SGLT2 inhibitors and strengthens the case for achieving euvolemia with appropriate doses of diuretics in heart failure with reduced ejection fraction. However, we believe the jury is still out on the true mechanism of the striking morbidity and mortality benefits seen in the large SGLT2-inhibitor outcome trials thus far. It is clear that more work is needed.
影响因子：
16.2
作者：
Singh, Jagdeep S. S.;Mordi, Ify R.;Lang, Chim C.
通讯作者：
Lang, Chim C.