Andrea Leo

Severity of coronary atherosclerosis in patients with a first acute coronary event: a diabetes paradox

AIMS We aimed to compare coronary artery disease (CAD) at the time of a first acute coronary syndrome (ACS) in type II diabetic and non-diabetic patients by coronary angiography and by optical coherence tomography (OCT). METHODS AND RESULTS Two different patient populations with a first ACS were enrolled for the angiographic (167 patients) and the OCT (72 patients) substudy. Angiographic CAD severity was assessed by Bogaty, Gensini, and Sullivan scores, whereas collateral development towards the culprit vessel was assessed by the Rentrop score. Optical coherence tomography plaque features were evaluated at the site of the minimum lumen area (MLA) and of culprit segment. In the angiographic substudy, at multivariate analysis, diabetes was associated with both the stenosis score and the extent index (P = 0.001). Furthermore, well-developed collateral circulation (Rentrop 2-3) towards the culprit vessel was more frequent in diabetic than in non-diabetic patients (73% vs. 16%, P = 0.001). In the OCT substudy, at MLA site lipid quadrants were less and the lipid arc was smaller in diabetic than in non-diabetic patients (2.3 ± 1.3 vs. 3.0 ± 1.2; P = 0.03 and 198° ± 121° vs. 260° ± 118°; P = 0.03). Furthermore, the most calcified cross-section along the culprit segment had a greater number of calcified quadrants and a wider calcified arc in diabetic than in non-diabetic patients (1.7 ± 1.0 vs. 1.2 ± 0.9; P = 0.03 and 126° ± 95° vs. 81° ± 80°; P = 0.03). Superficial calcified nodules were more frequently found in diabetic than in non-diabetic patients (79 vs. 54%, P = 0.04). CONCLUSIONS In spite of potent pro-inflammatory, pro-oxidant and pro-thrombotic stimuli operating in type II diabetes, diabetic patients exhibit substantially more severe coronary atherosclerosis than non-diabetic patients at the time of a first acute coronary event. Better collateral development towards the culprit vessel, a predominantly calcific plaque phenotype and, probably, yet unknown protective factors operating in diabetic patients may explain these intriguing paradoxical findings.

Plasma levels of thromboxane A2 on admission are associated with no-reflow after primary percutaneous coronary intervention

AIMS Thromboxane A2 (TXA2) is a key mediator of platelet activation and aggregation, and an important mediator of platelet-induced coronary artery constriction. We sought to investigate whether baseline plasma levels of TXA2 are associated with coronary no-reflow after primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS A total of 47 consecutive patients (age, 62.5 +/- 12.7; male sex, 76.6%) admitted to our hospital for a first ST-segment elevation myocardial infarction and undergoing PPCI within 12 h of onset of symptoms were enrolled. Admission TXA2 plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). Angiographic no-reflow was defined as a final TIMI flow of <or=2 or final TIMI flow of 3 with a myocardial blush grade of <2, whereas ST-segment resolution from baseline value of <or=50% was used as ECG index of no-reflow. At multivariable analysis TXA2 plasma levels, endothelin-1 (ET-1) plasma levels, and left anterior descending coronary artery (LAD) as culprit vessel were significant predictors of angiographic no-reflow (P = 0.04), whereas TXA2 and ET-1 plasma levels were the only independent predictors of lack of ST-segment resolution (P = 0.013 and 0.04, respectively). Of note, TXA2 tertiles were independent predictors of both angiographic no-reflow and lack of ST-segment resolution (OR, 3.5; 95% CI, 1.1-11; P = 0.03 and OR, 3; 95% CI, 1.3-7; P = 0.01, respectively). CONCLUSION TXA2 is an independent indicator of no-reflow that occurs after PPCI. This observation may open new therapeutic opportunity in the setting of PPCI.

Stress cardiomyopathy (tako-tsubo) triggered by nervous system diseases: A systematic review of the reported cases

BACKGROUND It is not clarified whether the transient, regional left ventricular dysfunction (TRLVD) associated with several neurological disorders shares the same pathophysiology with the classical tako-tsubo cardiomyopathy occurring without overt neurological disease, and whether it is appropriate to include these patients in a single stress cardiomyopathy (SCM) condition. METHODS In February 2012, we systematically explored major electronic medical information sources to identify cases of TRLVD triggered by neurological disorders. RESULTS The 81 selected papers reported a total of 124 patients, suffering from neurological disorders, in whom TRLVD occurred: 117 with central nervous system diseases, 6 with peripheral nervous system diseases and 1 with both systems involved. Most patients were females (n=102), mean age was 63 ± 15 years, and the majority presented with an apex-involving pattern. The most common disease described was subarachnoid hemorrhage (n=52), followed by stroke/transient ischemic attack (n=24), and seizures (n=18). TRLVD in neurological patients was often associated with need of inotropic support, orotracheal intubation, cerebrovascular spasm and delayed surgery. CONCLUSIONS TRLVD is a complication of neurological diseases, in particular in female patients in post-menopausal phase. The predilection for neurological damage at or close to the insular cortex highlights the pivotal role of sympathetic over-activation. Many other similarities with tako-tsubo support the inclusion in a single SCM category.

Predictors of thromboxane levels in patients with non-ST-elevation acute coronary syndromes on chronic aspirin therapy

High levels of thromboxane A2 (TxA2), a key mediator of platelet activation and aggregation, are associated with an increased risk of cardiovascular events. We aimed at assessing the predictors of higher plasma levels of TxB2, the stable metabolite of TxA2, in consecutive patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) on previous aspirin (ASA) treatment undergoing coronary angiography. Ninety-eight consecutive patients (age 61 ± 11, 75% males) with NSTE-ACS, on previous chronic ASA treatment, were prospectively enrolled in this study. Coronary disease extent was assessed by angiography according to the Bogaty score. In all patients, admission plasma levels of TxB2 (pg/ml) were measured by enzyme-linked immunosorbent assay, and patients showing TxB2 levels in the fourth quartile were compared to patients showing TxB2 levels in the lower quartiles. Multivariable logistic regression analysis showed that platelet count (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.02-1.63, p=0.04), multivessel coronary disease (OR 1.37, 95% CI 1.13-3.67, p=0.03), and coronary atherosclerosis extent index (OR 1.91, 95% CI 1.45-6.79, p=0.001) were independent predictors of TxB2 level upper quartile. Of note, C-reactive protein serum levels were similar in patients with TxB2 levels in the upper quartile as compared to those in the lower quartiles (p=0.49). In conclusion, NSTE-ACS patients with severe coronary atherosclerosis may have incomplete suppression of TxA2 production despite chronic ASA therapy. This finding suggests that additional efforts should be made to lower TxA2 levels in patients with widespread coronary artery disease.