Vasopressors and Inotropes in Acute Myocardial Infarction Related Cardiogenic Shock: A Systematic Review and Meta-Analysis

Vasopressors and inotropes are routinely used in acute myocardial infarction (AMI) related cardiogenic shock (CS) to improve hemodynamics. We aimed to investigate the effect of routinely used vasopressor and inotropes on mortality in AMI related CS. A systematic search of MEDLINE, EMBASE and CENTRAL was performed up to 20 February 2019. Randomized and observational studies reporting mortality of AMI related CS patients were included. At least one group should have received the vasopressor/inotrope compared with a control group not exposed to the vasopressor/inotrope. Exclusion criteria were case reports, correspondence and studies including only post-cardiac surgery patients. In total, 19 studies (6 RCTs) were included, comprising 2478 CS patients. The overall quality of evidence was graded low. Treatment with adrenaline, noradrenaline, vasopressin, milrinone, levosimendan, dobutamine or dopamine was not associated with a difference in mortality between therapy and control group. We found a trend toward better outcome with levosimendan, compared with control (RR 0.69, 95% CI 0.47–1.00). In conclusion, we found insufficient evidence that routinely used vasopressors and inotropes are associated with reduced mortality in patients with AMI related CS. Considering the limited evidence, this study emphasizes the need for randomized trials with appropriate endpoints and methodology

Pre-PCI versus immediate post-PCI Impella initiation in acute myocardial infarction complicated by cardiogenic shock

BACKGROUND: In selected patients with an acute myocardial infarction (AMI) complicated by Cardiogenic shock (CS), mechanical circulatory support with Impella may be beneficial, although conclusive evidence is still lacking. Nevertheless, it has been suggested that Impella initiation prior to primary PCI might improve survival. OBJECTIVE: To investigate the effect pre-PCI versus immediate post-PCI Impella initiation on short term mortality. METHODS: A prospective, single center, observational study, was performed including all patients with STEMI complicated by CS, treated with primary PCI and Impella. Thirty day mortality was compared between patients with Impella initiation pre-PCI and immediately post-PCI. RESULTS: A total of 88 patients were included. In the pre-PCI group (n = 21), admission heart rate was lower (84 versus 94 bpm, p = 0.04) and no IABP was implanted before Impella initiation, versus 17.9% in post-PCI group (n = 67), p = 0.04. Total 30-day all-cause mortality was 58%, and was lower in pre-PCI group, 47.6% versus 61.2% in the post-PCI group, however not statistically significant (HR 0.7, 95% CI 0.3-1.3, p = 0.21). Thirty-day cardiac mortality was significantly lower in the pre-PCI group, 19% versus 44.7% in the post-PCI group (HR 0.3, 95% CI 0.09-0.96, p = 0.042). CONCLUSION: Pre-PCI Impella initiation in AMICS patients was not associated with a statistically significant difference in 30-day all-cause mortality, compared to post-PCI Impella initiation

Cytochrome P-450 2C9 exerts a vasoconstrictor influence on coronary resistance vessels in swine at rest and during exercise

A significant endotheliumdependent vasodilation persists after inhibition of nitric oxide synthase (NOS) and cyclooxygenase (COX) in the coronary vasculature, which has been linked to the activation of cytochrome P-450 (CYP) epoxygenases expressed in endothelial cells and subsequent generation of vasodilator epoxyeicosatrienoic acids. Here, we investigated the contribution of CYP 2C9 metabolites to regulation of porcine coronary vasomotor tone in vivo and in vitro. Twenty-six swine were chronically instrumented. Inhibition of CYP 2C9 with sulfaphenazole (5 mg/kg iv) alone had no effect on bradykinininduced endothelium-dependent coronary vasodilation in vivo but slightly attenuated bradykinin-induced vasodilation in the presence of combined NOS/COX blockade with N ω-nitro-L-arginine (20 mg/kg iv) and indomethacin (10 mg/kg iv). Sulfaphenazole had minimal effects on coronary resistance vessel tone at rest or during exercise. Surprisingly, in the presence of combined NOS/COX blockade, a significant coronary vasodilator response to sulfaphenzole became apparent, both at rest and during exercise. Subsequently, we investigated in isolated porcine coronary small arteries (~250 μm) the possible involvement of reactive oxygen species (ROS) in the paradoxical vasoconstrictor influence of CYP 2C9 activity. The vasodilation by bradykinin in vitro in the presence of NOS/COX blockade was markedly potentiated by sulfaphenazole under control conditions but not in the presence of the ROS scavenger N-(2-mercaptoproprionyl)-glycine. In conclusion, CYP 2C9 can produce both vasoconstrictor and vasodilator metabolites. Production of these metabolites is enhanced by combined NOS/COX blockade and is critically dependent on the experimental conditions. Thus production of vasoconstrictors slightly outweighed the production of vasodilators at rest and during exercise. Pharmacological stimulation with bradykinin resulted in vasodilator CYP 2C9 metabolite production when administered in vivo, whereas vasoconstrictor CYP 2C9 metabolites, most likely ROS, were dominant when administered in vitro