1Herzzentrum Dresden GmbH an der TU Dresden Klinik für Innere Medizin, Kardiologie und Intensivmedizin Dresden, Deutschland
Background/Introduction:
Cardiogenic shock (CS) is associated with high mortality and morbidity. Mechanical circulatory support systems like the micro-axial percutaneous left ventricular assist device (pLVAD) are used to stabilize hemodynamics. However, some patients additionally require inotropic drugs. Dobutamine is recommended as first choice despite a low level of evidence. The phosphodiesterase III-inhibitor enoximone is associated with more intense reduction of pulmonary vessel resistance making it attractive in CS pattern where right heart dysfunction is present. Furthermore, less positive chronotropic effects and hence less oxygen consumption might favor myocardial recovery in case of enoximone use. This study investigated differences in the outcome between dobutamine and enoximone use in patients with refractory CS despite pLVAD therapy.
Methods:
A large monocentric pLVAD registry was screened for patients with CS and additionally enoximone and/or dobutamine therapy. Propensity score matching was performed to account for baseline differences. Primary outcome measure was 30 day mortality. Secondary analyses included change in oxygen consumption after 24h, relative lactate clearance and its development over first 72h, new renal replacement therapy, the time to its initiation, new onset of atrial fibrillation and ventricular arrhythmias, mean norepinephrine dosage over 72h and in-hospital mortality.
Results:
A total of 673 patients were found in the study period with 401 treated because of cardiogenic shock of which 231 received additional inotropic support. After propensity score matching 44 patient pairs were identified for further analyses. In the enoximone group 17 of the 44 patients received enoximone and dobutamine. There were no significant differences between groups in baseline characteristics. Study population showed median age 68 years and typical cardiovascular risk factors of one third having diabetes and almost 80% had both arterial hypertension and known coronary artery disease. 68% of patients were male. They had severely reduced left ventricular function of 23.5% in enoximone and 20% in control group. 50% showed impaired right ventricular function. Main reasons for CS were acute coronary syndrome in 52.3% and 45.5% and decompensated dilated cardiomyopathy 40.9% and 45.5% of cases, respectively. Resuscitation was performed in 34.3% and 36.4 % with median time of 15 vs. 10min. The median baseline lactate was 5.5 mmol/l and 5.2 mmol/l.
Kaplan-Meier analysis (picture 1) of 30 day mortality was significantly higher in enoximone group. No significant difference was found in secondary endpoints although trend to higher mean norepinephrine dosage (0.27 vs. 0.49 µg/kg/h, p=0.079) and serum lactate levels (picture 2) was seen in enoximone group. New renal replacement therapy was started in 50% and 52.3% after 7.5h and 9 h, respectively. Ventricular arrhythmias occurred more often in enoximone group but failed level of significance (22.7 vs 40.9% p=0.108) as did In-hospital mortality (65.9% vs 77.3%, p=0.345).
Conclusions:
In this propensity score matched analysis of CS patients treated by pLVAD and additional medical inotropic support, the use of enoximone ± dobutamine versus dobutamine alone was associated with higher 30 day mortality. More intense vasodilatory effect of enoximone leading to aggravation of shock in this very sick population can be hypothesized.