Impact of Chronic Antiplatelet Therapy on Infarct Size and Bleeding in Patients With Acute Myocardial Infarction.

BACKGROUND: Patients hospitalized with acute myocardial infarction (AMI) are often on prior single antiplatelet therapy (SAPT) or a dual antiplatelet therapy (DAPT). Whether chronic SAPT or DAPT is beneficial or associated with an increased risk in AMI is still controversial. METHODS AND RESULTS: We prospectively enrolled 1718 consecutive patients with AMI (798 ST-segment elevation myocardial infarction and 920 non-ST-segment elevation myocardial infarction) who were divided according to their chronic APT (no APT, SAPT, or DAPT). The study primary end point was the infarct size, as estimated by troponin I peak. Incidence of major bleeding was also evaluated. Five hundred thirty-six (31%) patients were on chronic SAPT and 215 (13%) on DAPT. A graded increase in Global Registry of Acute Coronary Events (GRACE) and Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) risk scores was found going from patients without APT to those with DAPT, while a progressive smaller troponin I peak was observed with the increasing number of chronic antiplatelet agents (11.2 [interquartile range: 2-45] ng/mL, 6.6 [1-33] ng/mL, and 4.1 [1-24] ng/mL; P < .001 for trend). This result was maintained after adjustment for baseline ischemic risk profile (GRACE score) and other major confounders ( P < .001). The incidence of bleeding was higher in patients on chronic APT than in those without APT (5.2% vs 2.4%; P = .002). However, when the bleeding risk was adjusted for the CRUSADE risk score, chronic SAPT (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 0.77-2.53) and DAPT (OR: 0.70, 95% CI: 0.29-1.70) were not associated with an increased bleeding risk. CONCLUSION: In patients with AMI, chronic APT is associated with higher baseline ischemic and bleeding risks. Despite this and unexpectedly, they have a smaller infarct size and similar adjusted bleeding risk.

Feasibility and Accuracy of Automated Software for Transthoracic Three-Dimensional Left Ventricular Volume and Function Analysis: Comparisons with Two-Dimensional Echocardiography, Three-Dimensional Transthoracic Manual Method, and Cardiac Magnetic Resonance Imaging.

BACKGROUND: Recently, a new automated software package (HeartModel) was developed to obtain three-dimensional (3D) left ventricular (LV) volumes using a model-based algorithm (MBA) with a "one-button" simple system and user-adjustable slider. The aims of this study were to verify the feasibility and accuracy of the MBA in comparison with other commonly used imaging techniques in a large unselected population, to evaluate possible accuracy improvements of free operator border adjustments or changes of the slider's default position, and to identify differences in method accuracy related to specific pathologies. METHODS: This prospective study included consecutive 200 patients. LV volumes and ejection fraction were obtained using the MBA and compared with the two-dimensional biplane method, the 3D full-volume (3DFV) modality, and, in 90 of 200 cases, cardiac magnetic resonance (CMR) measurements. To evaluate the optimal position of the slider with respect to the 3DFV and CMR modalities, a set of threefold cross-validation experiments was performed. Optimized and manually corrected LV volumes obtained using the MBA were also tested. Linear correlation and Bland-Altman analysis were used to assess intertechnique agreement. RESULTS: Automatic volumes were feasible in 194 patients (94.5%), with a mean processing time of 29 ± 10 sec. MBA-derived volumes correlated significantly with all evaluated methods, with slight overestimation of two-dimensional biplane and slight underestimation of CMR measurements. Higher correlations were found between MBA and 3DFV measurements, with negligible differences both in volumes (overestimation) and in LV ejection fraction (underestimation), respectively. Optimization of the user-adjustable slider position improved the correlation and markedly reduced the bias between the MBA and 3DFV or CMR. The accuracy of MBA volumes was lower in some pathologies for incorrect definition of LV endocardium. CONCLUSIONS: The MBA is highly feasible, reproducible, and rapid, and it correlates highly with the traditional 3DFV method. It may represent a valid alternative to 3DFV measurement for everyday clinical use.

Nitric oxide synthetic pathway in patients with microvascular angina and its relations with oxidative stress.

A decreased nitric oxide (NO) bioavailability and an increased oxidative stress play a pivotal role in different cardiovascular pathologies. As red blood cells (RBCs) participate in NO formation in the bloodstream, the aim of this study was to outline the metabolic profile of L-arginine (Arg)/NO pathway and of oxidative stress status in RBCs and in plasma of patients with microvascular angina (MVA), investigating similarities and differences with respect to coronary artery disease (CAD) patients or healthy controls (Ctrl). Analytes involved in Arg/NO pathway and the ratio of oxidized and reduced forms of glutathione were measured by LC-MS/MS. The arginase and the NO synthase (NOS) expression were evaluated by immunofluorescence staining. RBCs from MVA patients show increased levels of NO synthesis inhibitors, parallel to that found in plasma, and a reduction of NO synthase expression. When summary scores were computed, both patient groups were associated with a positive oxidative score and a negative NO score, with the CAD group located in a more extreme position with respect to Ctrl. This finding points out to an impairment of the capacity of RBCs to produce NO in a pathological condition characterized mostly by alterations at the microvascular bed with no significant coronary stenosis.

Nitric oxide synthetic pathway in red blood cells is impaired in coronary artery disease.

BACKGROUND: All the enzymatic factors/cofactors involved in nitric oxide (NO) metabolism have been recently found in red blood cells. Increased oxidative stress impairs NO bioavailability and has been described in plasma of coronary artery disease (CAD) patients. The aim of the study was to highlight a potential dysfunction of the metabolic profile of NO in red blood cells and in plasma from CAD patients compared with healthy controls. METHODS: We determined L-arginine/NO pathway by liquid-chromatography tandem mass spectrometry and high performance liquid chromatography methods. The ratio of oxidized and reduced forms of glutathione, as index of oxidative stress, was measured by liquid-chromatography tandem mass spectrometry method. NO synthase expression and activity were evaluated by immunofluorescence staining and ex-vivo experiments of L-[(15)N2]arginine conversion to L-[(15)N]citrulline respectively. RESULTS: Increased amounts of asymmetric and symmetric dimethylarginines were found both in red blood cells and in plasma of CAD patients in respect to controls. Interestingly NO synthase expression and activity were reduced in CAD red blood cells. In contrast, oxidized/reduced glutathione ratio was increased in CAD and was associated to arginase activity. CONCLUSION: Our study analyzed for the first time the whole metabolic pathway of L-arginine/NO, both in red blood cells and in plasma, highlighting an impairment of NO pathway in erythrocytes from CAD patients, associated with decreased NO synthase expression/activity and increased oxidative stress.