The Impact of Sacubitril/valsartan on Outcome in Patients Suffering from Heart Failure with a Concomitant Diabetes Mellitus

Background: Guidelines 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.

Aims: The 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 Results: Consecutive 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).

Conclusions: Sacubitril/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.