Hemodynamic impact of low-dose dobutamine in patients with acute myocardial infarction at risk of cardiogenic shock – a randomized clinical trial

Background Despite widespread use of inotropic agents in the management of cardiogenic shock (CS) the scientific evidence is limited. DOBERMANN-D was the first double-blind, placebo-controlled, randomized, clinical trial (RCT) to evaluate the effects of an early 24-hour infusion of low-dose dobutamine in patients with acute myocardial infarction (AMI) at risk of CS development. The primary endpoint was neutral, with no difference in peak N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) within 48 hours. Purpose This predefined DOBERMANN-D sub-study evaluated the effect of inotropic support with dobutamine on hemodynamic parameters. Methods DOBERMANN-D enrolled 100 AMI patients at risk of CS development (ORBI risk score ≥10 corresponding to ≥8% risk). Patients were randomized 1:1 to a 24-hour infusion of dobutamine (dbt, 5 μg/kg/minute) or placebo initiated <2 hours after revascularization with percutaneous coronary intervention (PCI). Hemodynamic status was evaluated by serial measurements of blood pressure, heart rate, serum lactate, and creatinine concentrations within 48 hours from admission. The extent of myocardial injury was assessed with peak and temporal changes of troponin T (TnT) concentrations. Temporal changes were assessed using linear mixed models adjusted for the baseline value. Echocardiographic parameters obtained at admission and 3-month follow-up included left ventricular ejection fraction (LVEF), LV outflow tract velocity time integral (LVOT VTI), E/e’ lateral, and LV global longitudinal strain (GLS) and analyzed using analysis of covariance (ANCOVA). Patients were followed during admission and for three months for adverse events (AE) and serious AE (SAE). Results Of the 100 included patients (68 years; 23% female), 99% had STEMI, 39% Killip Class >1, and the median ORBI score was 12. During dbt infusion, mean arterial blood pressure (MAP) was lower (-7% difference, p=0.001, Figure 1A) and heart rate was higher (14% difference, p<0.001) but returned to levels after 24 hours comparable to those in the placebo group. Temporal changes in lactate (Figure 1B), creatinine, and TnT were similar between groups. No differences in echocardiographic parameters of LVEF (dbt: 37% vs placebo: 40%), LVOT VTI (dbt: 18 cm vs placebo: 19 cm), E/e’ lateral (dbt: 11.5 vs placebo: 10.5), or GLS (dbt: -12% vs placebo: -12%) were detected during admission nor at follow-up (Figure 1C-E). In the dbt group, LVEF and LVOT VTI increased and GLS decreased from admission to follow-up. In contrast, only LVEF changed in the placebo group. There were no differences in the incidence of AE or SAE between the groups during hospitalization nor at follow-up. Conclusions In this RCT of inotropic support with low-dose dobutamine in AMI patients at risk of CS, heart rate increased and MAP decreased, but did not confer measurable benefit in filling pressures, cardiac output surrogate, myocardial function, AE nor SAE compared with placebo.