Search

Importance Secretory phospholipase A 2 (sPLA 2 ) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA 2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. Objective To determine the effects of sPLA 2 inhibition with varespladib on cardiovascular outcomes. Design, Setting, and Participants A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). Interventions Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. Main Outcomes and Measures The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. Results At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). Conclusions and Relevance In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA 2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. Trial Registration clinicaltrials.gov Identifier:NCT01130246

We report the case of a 57-year-old man who had presented with exertional angina early in 1997 and had subsequently undergone myocardial revascularization with the use of both internal mammary arteries. Two months after surgery, the patient was readmitted to the hospital with unstable angina. Coronary angiography revealed a 90% occlusion of the left internal mammary artery anastomosis, which was attached to the left anterior descending coronary artery. At reoperation, the left internal mammary artery was detached from the left anterior descending coronary artery, probed and injected with papaverine, checked for patency, and regrafted to the same coronary artery. Recycling of the left internal mammary artery was facilitated by the harvesting and routing technique that had been used during the previous operation. At the patient's 1-year follow-up visit, both Doppler echocardiography and coronary angiography showed patency of the recycled graft. We conclude that recycling of the left internal mammary artery is a safe and effective option in selected patients who require reoperation after myocardial revascularization.

The excellent results obtained with the use of the left internal mammary artery (IMA) for myocardial revascularization have led to the simultaneous use of other arterial conduits, particularly the right IMA.The present study includes the first 100 consecutive patients with ischemic heart disease who underwent myocardial revascularization with in situ bilateral IMA grafted to branches of the left coronary artery, performed at our center. Ninety-six (96%) were males and four (4%) were females, with a mean age of 58 +/- 8 years (range, 35-75 years). The main indication for myocardial revascularization was angina in 83 patients (83%) and heart failure in 17 (17%). Seventy patients had three-vessel disease.Hospital mortality was 1%, with one death due to left ventricular failure. Three patients had perioperative myocardial infarction, six experienced ventricular arrhythmia, two had acute renal failure and nine respiratory insufficiency. Dehiscence of the sternal wound occurred in four patients, evolving in mediastinitis in one. All discharged patients were checked after 26 +/- 6 months (range, 12-38 months). There were two deaths, one because of cardiac failure and one sudden death, with a two-year survival rate of 97 +/- 2%. Five patients (5%) required hospitalization because of angina, and the angiographic study showed stenosis/occlusion of one or both IMAs in four cases. Thirty-five (38%) of the remaining patients underwent a coronarographic (25 patients) or transthoracic Doppler study (10 patients) to evaluate patency of the IMAs. The patency index was 100% for the left IMA and 94% for the right IMA.Myocardial revascularization with bilateral IMA in situ can be performed with low hospital mortality and morbidity. Sternal dehiscence is the worst complication and appears to be more frequent in diabetic and elderly patients. Mid-term results are satisfactory, with a good survival rate and freedom from major cardiac events. However, a longer follow-up is necessary to better appreciate the advantages of myocardial revascualarization with in situ bilateral IMAs.

In patients with previous myocardial infarction and left ventricular asynergy, dipyridamole infusion may have the capacity to unmask myocardial viability through transient recovery of contractile function in asynergic segments. The purpose of this study was to assess simultaneous changes in myocardial perfusion and LV function--elicited by dipyridamole infusion--in infarcted, asynergic segments. The echo contrast agent Albunex was injected into the left coronary artery of 19 patients (17 males, age 49-70 years) with previous myocardial infarction and baseline left ventricular asynergy, both before and after dipyridamole infusion (up to 0.56 mg.kg-1, i.v.). Analysis was not possible in three patients due to inadequate image quality and in two due to weak contrast. There were no major adverse events, or changes in vital signs or demonstrated on the electrocardiogram. After dipyridamole, 7/14 patients, showed an improvement in regional function of asynergic segments ('responders'), whereas seven patients did not ('non-responders'). Among non-responders, five had a myocardial perfusion deficit corresponding to 41% of the total left ventricular area before dipyridamole and to 38% after dipyridamole. No baseline perfusion deficits were observed in the remaining two non-responders; one of these, however, developed transient asynergy and perfusion deficit after dipyridamole. Among responders, five showed a normal perfusion pattern, both before and after dipyridamole, while the remaining two showed a perfusion deficit which markedly decreased after dipyridamole (from 32% to 13% of total left ventricular area). Thus, residual contractile reserve of asynergic, infarcted ventricular segments appears to be associated with myocardial perfusion either preserved at baseline or recruitable by a coronary dilator stimulus.