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Ibrahim El-Battrawy, Jonathan Demmer, Mohammad S.A. Abumayyaleh, Carina Crack, Christina Pilsinger, Xiao-Bo Zhou, Andreas Mügge, Ibrahim Akin, Assem Aweimer

• \(\bf Background:\) 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. \(\bf Aims:\) 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. \(\textbf {Methods and results:}\) Consecutive 240 patients with HFrEF from 2016 to 2020 were treated with sacubitril/valsartan and separated to concomitant diabetes mellitus (\(\it n\) = 87, median age 68 years interquartile range (IQR) [32–87]) or no diabetes mellitus (\(\it n\) = 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%; \(\it P\) < 0.01) and coronary artery disease (74% vs. 60%; \(\it P\) = 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]; \(\it P\) < 0.001), but not in diabetic patients (29% IQR [10–65] at baseline to 30% IQR [13–55]; \(\it P\) = 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]; \(\it P\) < 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]; \(\it P\) < 0.001), but not in diabetic patients (NT-proBNP from 1395 pg/mL IQR [100–29 924] to 885 pg/mL IQR [159–4331]; \(\it P\) = 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]; \(\it P\) = 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]; \(\it P\) = 0.04), and not in diabetic s patients (17.5 mm IQR [8–30] to 18 mm IQR [14–31]; \(\it P\) = 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; \(\it P\) = 0.0009) and in non-diabetic patients (28.4% before sacubitril/valsartan and 8.4% after 24 months treatment; \(\it P\) = 0.0004). The all-cause mortality rate was higher in patients with diabetes mellitus as compared with those without diabetes (25% vs. 8.1%; \(\it P\) < 0.01). \(\bf Conclusions:\) 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.