The impact of sacubitril/valsartan on outcome in patients suffering from heart failure with a concomitant diabetes mellitus
Authors: El‐Battrawy Ibrahim , Demmer Jonathan , Abumayyaleh Mohammad , Crack Carina , Pilsinger Christina , Zhou Xiaobo , Mügge Andreas , Akin Ibrahim , Aweimer Assem 
Published: December 2022

AbstractBackgroundGuidelines classify sacubitril/valsartan as a significant part of medical treatment of heart failure with reduced ejection fraction (HFrEF). Data have shown that the HbA1c levels in patients with diabetes mellitus could be impacted by sacubitril/valsartan. A possible positive effect in diabetes patients treated with sacubitril/valsartan on outcome and echocardiography parameters is not well studied yet.AimsThe aim of the present study was to compare the impact of sacubitril/valsartan on life‐threatening arrhythmias, atrial fibrillation, different echocardiography parameters and congestion rate in patients suffering from HFrEF according to the diagnosis diabetes mellitus or no diabetes mellitus.Methods and resultsConsecutive 240 patients with HFrEF from 2016 to 2020 were treated with sacubitril/valsartan and separated to concomitant diabetes mellitus (n = 87, median age 68 years interquartile range (IQR) [32–87]) or no diabetes mellitus (n = 153, median age 66 year IQR [34–89]). Different comorbidities and outcome data were evaluated over a follow‐up period of 24 months. Arterial hypertension (87% vs. 64%; P < 0.01) and coronary artery disease (74% vs. 60%; P = 0.03) were more often documented in patients with diabetes mellitus compared with patients without diabetes mellitus. Over the follow‐up of 24 months several changes were noted in both subgroups: Median left ventricular ejection fraction (EF) increased significantly in non‐diabetes (27% IQR [3–44] at baseline to 35% IQR [13–64]; P < 0.001), but not in diabetic patients (29% IQR [10–65] at baseline to 30% IQR [13–55]; P = 0.11). Accordingly, NT‐proBNP and troponin‐I levels decreased significantly in non‐diabetes patients (NT‐brain natriuretic peptide [NT‐proBNP] from median 1445 pg/mL IQR [12.6–74 676] to 491 pg/mL IQR [13–4571]; P < 0.001, troponin‐I levels from 0.099 ng/mL IQR [0.009–138.69] to 0.023 ng/mL IQR [0.006–0.635]; P < 0.001), but not in diabetic patients (NT‐proBNP from 1395 pg/mL IQR [100–29 924] to 885 pg/mL IQR [159–4331]; P = 0.06, troponin‐I levels from 0.05 ng/mL IQR [0.013–103.0] to 0.020 ng/mL IQR [0.015–0.514]; P = 0.27). No significant change of laboratory parameters e. g. glomerular filtration rate, potassium level and creatinine levels were found in diabetes or non‐diabetes patients. Comparing further echocardiography data, left atrial surface area, right atrial surface area, E/A ratio did not show a significant change either in the diabetes or non‐diabetes group. However, the tricuspid annular plane systolic excursion was significantly increased in non‐diabetes mellitus patients (from 17 mm IQR [3–31] to 18 mm [2.5–31]; P = 0.04), and not in diabetic s patients (17.5 mm IQR [8–30] to 18 mm IQR [14–31]; P = 0.70); the systolic pulmonary artery pressure remained unchanged in both groups. During follow‐up, a similar rate of ventricular tachyarrhythmias was observed in both groups. The congestion rate decreased significantly in both groups, in diabetes patients (44.4% before sacubitril/valsartan and 13.5% after 24 months treatment; P = 0.0009) and in non‐diabetic patients (28.4% before sacubitril/valsartan and 8.4% after 24 months treatment; P = 0.0004). The all‐cause mortality rate was higher in patients with diabetes mellitus as compared with those without diabetes (25% vs. 8.1%; P < 0.01).ConclusionsSacubitril/valsartan reverses cardiac remodelling in non‐diabetes patients. However, it reduces the congestion rate in diabetes and non‐diabetes patients. The rates of ventricular tachyarrhythmias were similar in DM compared with non‐DM over follow‐up. The mortality rate remained to be over follow‐up higher in diabetes patients compared with non‐diabetes; however, it was lower compared with published data on diabetes and concomitant HFrEF not treated with sacubitril/valsartan.