Jose A Ramires

Comparison between Adventitial and Intimal Inflammation of Ruptured and Nonruptured Atherosclerotic Plaques in Human Coronary Arteries

OBJECTIVE To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS In the adventitia, the numbers of lymphocytes and microvessels/mm2 were 69.5+/-88.3 and 60.9+/- 32.1 in culprit lesions and 16.4 +/- 21.1 and 44.3+/-16.1 in stable lesions (p<0.05); within the plaques, the mean number of lymphocytes was 24+/-40.8 in culprit lesions and 10.9+/-13.2 in stable ones (p=0.17). The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001). The confocal images showed holes in the external elastic membrane. CONCLUSION Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability.

CMV and transplant-related coronary atherosclerosis: an immunohistochemical, in situ hybridization, and polymerase chain reaction in situ study.

Accelerated graft coronary atherosclerosis is the main obstacle to long-term survival in patients who have had a heart transplant. A possible involvement of the human cytomegalovirus (HCMV) in this type of coronary atherosclerosis has been postulated by many authors but has not been definitively demonstrated. In an attempt to clarify the role of HCMV infection in the pathogenesis of this complication, we looked for in situ antigens or DNA of HCMV in 30 coronary artery segments obtained at necropsy from patients who had undergone orthotopic cardiac transplantation at the São Paulo Heart Institute. We tried to correlate these HCMV markers with the presence of inflammation and/or atherosclerosis in histologic sections. The patients were grouped as follows: GI, less than 170 days of graft survival and absent/mild atherosclerosis; GII, more than 170 days of graft survival and absent/mild atherosclerosis; GIII, more than 170 days of graft survival and severe/moderate atherosclerosis (170 days was the shortest graft survival time associated with atherosclerosis). The search for HCMV genome and antigens in the coronary artery sections was performed using immunohistochemistry, in situ hybridization, and polymerase chain reaction in situ techniques. Immunohistochemistry and in situ hybridization revealed no evidence of HCMV in all 30 cases. Polymerase chain reaction in situ revealed scarce HCMV-positive lymphocytes in two cases (one each from GI and GIII) located in the adventitial layer. These findings preclude a direct role for the HCMV in the pathogenesis of accelerated graft coronary atherosclerosis. However, the possibility of an indirect effect of the virus, such as an immune-mediated inflammatory response by the host that increases the expression of histocompatibility antigens, leading to tissue injury, cannot be excluded.

The BARI 2D Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus with Stable Ischemic Heart Disease. Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background— The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results— Outcome data were analyzed by intention to treat; the Kaplan–Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P=0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P=0.76). In the coronary artery bypass grafting stratum (n=763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P=0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P=0.010) and cardiac death or MI (P=0.03) were also less frequent. Reduction in MI (P=0.001) and cardiac death/MI (P=0.002) was significant only in the insulin sensitization group. Conclusions— In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Inflammatory response after coronary stent implantation: Importance of plaque morphology determined by intravascular ultrasound

Results: Slow or no-reflow was persistent in 14 (60.9%) patients receiving saline, 7 (30.4%) patients receiving adenosine and 1 (4.8%) patient receiving the combination. IC injection with saline did not produce any improvement in TIMI flow (0.9liO.2 to 1.13kO.3, p=O.574). However, IC injection with adenosine produced improvement in TIMI flow (1.09iO.Z to 2.04*0.3, p=O.O159) and IC injection with combination also resulted in improvement of TIMI flow (0.67iO.2 to 2.6leO.2, p<O.OOOl). Treatment of slow or noreflow in saline group of patients by crossover with combination was associated with reestablishment of TIMI II in 1 (7.1%) and TIMI III in 13 (92.9%) patients. In case of adenosine group of patients the treatment by crossover with combination was associated with reestablishment of TIMI II flow in 2 (28.6%) and TIMI Ill in 5 (71.4%) patients. No untoward complications were noted during the drug administrations. Conclusions: Eventhough IC administration of adenosine produces improvement in TIMI flow, but the number of patients with no-reflow after prophylactic administration of drugs was minimum in case of combination. Thus, IC administration of combination of adenosine and sodium nitroprusside acts better as compared to adenosine administered &Xle.

Performance of an automated external cardioverter defibrillator for in-hospital ventricular malignant arrhythmia

Purpose: Ventricular fibrillation (VF) and ventricular tachycardia (VT) are the major underlying rhythm during in-hospital cardiac arrest. For a patient in VFNT the probability of successful defibrillation and subsequent suwival to hospital discharge is directly and negatively related to the time interval between onset of the arrhythmia and delivery of the first shock. The data about this interval in clinical practice is heterogeneous and ~nconclusive, however the literature estimates it to be about 60 seconds in monitored units. Continuos ECG monitoring allows identification of such arrhythmias and alert nursmg and medical staff. The time delay between the arrhyihmlc event and human intervention is still a challenge for clinical practice. Methods: We reported the use of an automated external cardioverter defibrillator (AECD) in 45 patients considered to be at higher risk for malIgnant arrhythmia for 24 to 48 hours. The inclusion criteria was acute coronary syndrome, cardiogemc shock and previous episode of sudden death or malignant ventricular arrhythmia. The exclusion cnteria was the use of pacemaker or an implantable cardioverier defibrillator and an R-wave amplitude less than 0.7mV peak to peak at themonitor. Results: We recorded 17 episodes of VTNF in 3 patients. The median time between the beginning of the arrhythmia and the first defibrillation was 33.37 s (range 21 to 65 s). The sensibility and specificity were 100%. The success of the defibrillation was 94.11% (16/ 17) for the first shock and 100% (l/l) for the second shock. There was no adverse event during the study penod and no episodes of inappropriate therapy delivery (the detection was accurate in all episodes sensitivity 100%). Conclusion: AECD was safe and effective. It presents the possibility of providing consistently rapid identification and response to ventricular malignant arrhyihmla.