Faculty Bibliography

Aims Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery. Methods and results Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS). Conclusion l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h

Background: In cardiogenic shock, causes of death usually are cardiac. However, a systemic inflammatory response syndrome may influence outcome. Methods: SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) Trial patients (n = 302) were analyzed regarding cause of death and re-hospitalization. Results: Deaths (n = 180) occurred </=30 days in 86% and >30 days in 14%. Known causes of death </=30 days were cardiac in 88% (37% arrhythmic) and non-cardiac in 12% (29% septic). Non-cardiac deaths </=30 days occurred later (206 [91,394] versus 41 [15,156] h, P<0.01) and were more frequently associated with signs of inflammation (43 versus 12%, P = 0.01) than cardiac deaths </=30 days. Known causes of in-hospital death >30 days (n = 19) were cardiac in 58% and non-cardiac in 42%. Among deaths </=30 days systemic vascular resistance index was higher (2,666+/-1,063 versus 2,090+/-731 dynes.sec.cm(-5) m(2), P = 0.05) than among deaths >30 days. Among the 116 survivors of the initial hospitalization with data available, 52 (45%) were readmitted, most of which due to heart failure (n = 22, 42%) and myocardial ischemia (n = 16, 31%). Conclusions: In CS, early deaths </=30 days are mainly cardiac. Non-cardiac deaths are associated with signs of inflammation. In survivors of the initial hospitalization, re-hospitalizations are due to heart failure and myocardial ischemia

CONTEXT: Cardiogenic shock complicating acute myocardial infarction (MI) remains a common and lethal disorder despite aggressive use of early revascularization. Systemic inflammation, including expression of inducible nitric oxide synthase (NOS) and generation of excess nitric oxide, is believed to contribute to the pathogenesis and inappropriate vasodilatation of persistent cardiogenic shock. Preliminary, single-center studies suggested a beneficial effect of NOS inhibition on hemodynamics, renal function, and survival in patients with cardiogenic shock. OBJECTIVE: To examine the effects of an isoform-nonselective NOS inhibitor in patients with MI and refractory cardiogenic shock despite establishment of an open infarct artery. DESIGN, SETTING, AND PATIENTS: International, multicenter, randomized, double-blind, placebo-controlled trial (Tilarginine Acetate Injection in a Randomized International Study in Unstable MI Patients With Cardiogenic Shock [TRIUMPH]) with planned enrollment of 658 patients at 130 centers. Participants were enrolled between January 2005 and August 2006 when the study was terminated early. INTERVENTION: Tilarginine (L-N(G)-monomethylarginine [L-NMMA]), 1-mg/kg bolus and 1-mg/kg per hour 5-hour infusion, vs matching placebo. MAIN OUTCOME MEASURES: The primary outcome was 30-day all-cause mortality among patients who received study medication. Secondary outcomes included shock resolution and duration, New York Heart Association (NYHA) functional class at 30 days, and 6-month mortality. RESULTS: Enrollment was terminated at 398 patients based on a prespecified futility analysis. Six-month follow-up was completed in February 2007. There was no difference in 30-day all-cause mortality between patients who received tilarginine (97/201 [48%]) vs placebo (76/180 [42%]) (risk ratio, 1.14; 95% confidence interval, 0.92-1.41; P = .24). Resolution of shock (133/201 [66%] tilarginine vs 110/180 [61%] placebo; P = .31) and duration of shock (median, 156 [interquartile range, 78-759] hours tilarginine vs 190 [100-759] placebo; P = .16) were similar. At 30 days a similar percentage of patients had heart failure (48% tilarginine vs 51% placebo; P = .51) with a similar percentage of those patients in NYHA class I/II (73% tilarginine vs 75% placebo; P = .27). After 6 months mortality rates were similar in the 2 groups (58% tilarginine vs 59% placebo; hazard ratio, 1.04; 95% confidence interval, 0.79-1.36; P = .80). CONCLUSIONS: Tilarginine, 1-mg/kg bolus and 5-hour infusion, did not reduce mortality rates in patients with refractory cardiogenic shock complicating MI despite an open infarct artery. Early mortality rates in this patient group are high. Further research is needed to develop effective therapies for patients with cardiogenic shock following acute MI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00112281

We sought to assess the microbiologic profile of patients with suspected sepsis who participated in the SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) trial, a randomized controlled trial of early coronary revascularization in patients with cardiogenic shock complicating acute myocardial infarction. A protocol-mandated SEPSIS form was completed prospectively for 54 patients (18%) with fever or leukocytosis suggestive of sepsis. These patients were divided further into those with positive (n = 40) or negative (n = 14) culture results. The predominant pathogen isolated in patients with positive culture results was Staphylococcus aureus (32%), followed by Klebsiella pneumoniae and Pseudomonas aeruginosa. Patients with both positive and negative culture results had longer median durations of mechanical ventilation (p <0.001 and p = 0.02), intra-aortic balloon pump (IABP) support (p = 0.074 and p = 0.021), and hospital stay (p <0.001 and p = 0.048) than controls. Sepsis was predicted by both duration of IABP support (p = 0.007) and use of multiple central catheters (p = 0.026). In conclusion, clinical sepsis is common after cardiogenic shock complicating acute myocardial infarction, particularly in patients who received prolonged IABP support or had multiple central catheters