Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Treatment of Unprotected Left Main Stenosis.

PURPOSE OF REVIEW: This article reviews the latest data on unprotected left main (ULM) percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery, with a focus on the NOBLE and EXCEL trials. RECENT FINDINGS: In EXCEL trial, the primary endpoint at 3 years was 15.4% in the PCI group and 14.7% in the CABG group (p = 0.02 for non-inferiority of PCI versus CABG). In NOBLE, the primary endpoint at 5 years was 28% and 18% for PCI and CABG, respectively (HR 1.51, CI 1.13-2.0, which did not meet the criteria for non-inferiority of PCI to CABG; p for superiority of CABG was 0.0044). Higher repeat revascularization and non-procedural myocardial infarction were noted in PCI group but there was no difference in all-cause or cardiac mortality between the two groups. A heart team approach with appropriate patient selection, careful assessment of LM lesions, and meticulous procedural technique makes PCI a valid alternative to CABG for ULM stenosis.

Neuroprotection in the Treatment of Acute Ischemic Stroke.

Neuroprotection remains one of the holy grails of acute ischemic stroke therapy. The ability to protect the ischemic brain from injury until reperfusion and then to protect the brain from reperfusion injury could theoretically improve freedom from disability among stroke survivors. This manuscript reviews the molecular and cellular pathophysiology of stroke and summarizes pharmacologic and other therapies that showed promise in pre-clinical testing as neuroprotection agents. However to date, no compelling efficacy data have been published regarding any pharmacologic or other therapies. Nonetheless the search for effective neuroprotection continues at stroke centers throughout the world.

Zofenopril Protects Against Myocardial Ischemia-Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability.

BACKGROUND: Zofenopril, a sulfhydrylated angiotensin-converting enzyme inhibitor (ACEI), reduces mortality and morbidity in infarcted patients to a greater extent than do other ACEIs. Zofenopril is a unique ACEI that has been shown to increase hydrogen sulfide (H2S) bioavailability and nitric oxide (NO) levels via bradykinin-dependent signaling. Both H2S and NO exert cytoprotective and antioxidant effects. We examined zofenopril effects on H2S and NO bioavailability and cardiac damage in murine and swine models of myocardial ischemia/reperfusion (I/R) injury. METHODS AND RESULTS: Zofenopril (10 mg/kg PO) was administered for 1, 8, and 24 hours to establish optimal dosing in mice. Myocardial and plasma H2S and NO levels were measured along with the levels of H2S and NO enzymes (cystathionine ß-synthase, cystathionine γ-lyase, 3-mercaptopyruvate sulfur transferase, and endothelial nitric oxide synthase). Mice received 8 hours of zofenopril or vehicle pretreatment followed by 45 minutes of ischemia and 24 hours of reperfusion. Pigs received placebo or zofenopril (30 mg/daily orally) 7 days before 75 minutes of ischemia and 48 hours of reperfusion. Zofenopril significantly augmented both plasma and myocardial H2S and NO levels in mice and plasma H2S (sulfane sulfur) in pigs. Cystathionine ß-synthase, cystathionine γ-lyase, 3-mercaptopyruvate sulfur transferase, and total endothelial nitric oxide synthase levels were unaltered, while phospho-endothelial nitric oxide synthase(1177) was significantly increased in mice. Pretreatment with zofenopril significantly reduced myocardial infarct size and cardiac troponin I levels after I/R injury in both mice and swine. Zofenopril also significantly preserved ischemic zone endocardial blood flow at reperfusion in pigs after I/R. CONCLUSIONS: Zofenopril-mediated cardioprotection during I/R is associated with an increase in H2S and NO signaling.

Trimetazidine Decreases Risk of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: We sought to synthesize and analyze the available data from randomized controlled trials (RCTs) for trimetazidine (TMZ) in the prevention of contrast-induced nephropathy (CIN). BACKGROUND: Contrast-induced nephropathy after coronary angiography is associated with poor outcomes. Trimetazidine is an anti-ischemic drug that might reduce incidence of CIN, but current data are inconclusive. METHODS: We searched MEDLINE/PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and ScienceDirect electronic databases for RCTs comparing intravenous hydration with normal saline (NS) and/or N-acetyl cysteine (NAC) versus TMZ plus NS ± NAC for prevention of CIN. We used RevMan 5.2 for statistical analysis with the fixed effects model. RESULTS: Of the 808 studies, 3 RCTs met criteria with 290 patients in the TMZ plus NS ± NAC group and 292 patients in the NS ± NAC group. The mean age of patients was 59.5 years, and baseline serum creatinine ranged from 1.3 to 2 mg/dL. Trimetazidine significantly reduced the incidence of CIN by 11% (risk difference 0.11; 95% confidence interval, 0.16-0.06; P < .01). There was no significant heterogeneity between the studies (I(2) statistic = 0). The number needed to treat to prevent 1 episode of CIN was 9. CONCLUSIONS: The addition of TMZ to NS ± NAC significantly decreased the incidence of CIN in patients undergoing coronary angiography. In conclusion, TMZ could be considered as a potential tool for prevention of CIN in patients with renal dysfunction.

Ad hoc percutaneous coronary intervention: a consensus statement from the Society for Cardiovascular Angiography and Interventions.

Percutaneous coronary interventions (PCI) may be performed during the same session as diagnostic catheterization (ad hoc PCI) or at a later session (delayed PCI). Randomized trials comparing these strategies have not been performed; cohort studies have not identified consistent differences in safety or efficacy between the two strategies. Ad hoc PCI has increased in prevalence over the past decade and is the default strategy for treating acute coronary syndromes. However, questions about its appropriateness for some patients with stable symptoms have been raised by the results of recent large trials comparing PCI to medical therapy or bypass surgery. Ad hoc PCI for stable ischemic heart disease requires preprocedural planning, and reassessment after diagnostic angiography must be performed to ensure its appropriateness. Patients may prefer ad hoc PCI because it is convenient. Payers may prefer ad hoc PCI because it is cost-efficient. The majority of data confirm equivalent outcomes in ad hoc versus delayed PCI. However, there are some situations in which delayed PCI may be safer or yield better outcomes. This document reviews patient subsets and clinical situations in which one strategy is preferable over the other.

Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A2A receptor agonist.

This study was undertaken to determine whether the myocardial infarct-sparing effect of ATL-146e, a selective adenosine A(2A) receptor agonist, persists without a rebound effect for at least 48 h and to determine the optimal duration of ATL-146e treatment in anesthetized dogs. Reperfusion injury after myocardial infarction (MI) is associated with inflammation lasting 24-48 h that contributes to ongoing myocyte injury. We previously showed that an ATL-146e infusion, starting just before reperfusion, decreased inflammation and infarct size in dogs examined 2 h after MI without increasing coronary blood flow. In the present study, adult dogs underwent 90 min of left anterior descending coronary artery occlusion. Thirty minutes before reperfusion, ATL-146e (0.01 microg x kg(-1) x min(-1); n = 21) or vehicle (n = 12) was intravenously infused and continued for 2.5 h (protocol 1) or 24 h (protocol 2). At 48 h after reperfusion hearts were excised and assessed for histological risk area and infarct size. Infarct size based on triphenyltetrazolium chloride (TTC) staining as a percentage of risk area was significantly smaller in ATL-146e-treated vs. control dogs (16.7 +/- 3.7% vs. 33.3 +/- 6.2%, P < 0.05; protocol 1). ATL-146e reduced neutrophil accumulation into infarcted myocardium of ATL-146e-treated vs. control dogs (30 +/- 7 vs. 88 +/- 16 cells/high-power field, P < 0.002). ATL-146e infusion for 24 h (protocol 2) conferred no significant additional infarct size reduction compared with 2.5 h of infusion. A 2.5-h ATL-146e infusion initiated 30 min before reperfusion results in marked, persistent (48 h) reduction in infarct size as a percentage of risk area in dogs with a reduction in infarct zone neutrophil infiltration. No significant further benefit was seen with a 24-h infusion.

The prevalence of extracardiac findings by multidetector computed tomography before atrial fibrillation ablation.

BACKGROUND AND OBJECTIVES: The study was designed to determine the prevalence of extracardiac findings discovered during multidetector computed tomography (CT) (MDCT) examinations before atrial fibrillation ablation. Multidetector CT has become a valuable tool in detailing left atrial anatomy before catheter ablation. The incidence of extracardiac findings has been reported for electron beam CT calcium scoring and coronary MDCT, but no data exist for the prevalence of extracardiac findings discovered before atrial fibrillation ablation with MDCT. METHODS AND RESULTS: Clinical reports from MDCT examinations before atrial fibrillation ablation and interpretations by 2 radiologists blinded to the clinical reports were reviewed for significant additional extracardiac findings and recommendations for follow-up. In 149 patients who underwent MDCT, the mean age was 55.9 +/- 11.0 years, 75% were men, and 47% had a history of smoking. Extracardiac findings were identified in 69% of patients with clinical, 90% of reader 1, and 97% of reader 2 interpretations (kappa = 0.086). Follow-up was recommended in 30% of clinical, 50% of reader 1, and 38% of reader 2 interpretations (kappa = 0.408). Pulmonary nodules were the most common additional finding and reason for suggested follow-up for all interpreters. CONCLUSIONS: The prevalence of extracardiac abnormalities detected by MDCT is considerable. Significant variability in their identification exists between interpreters, but there is good agreement about the need for further follow-up. It is important that those who interpret these examinations are adequately trained in the identification and interpretation of both cardiac and extracardiac findings.

Prognostic role of single-photon emission computed tomography (SPECT) imaging in myocardial viability.

PURPOSE OF REVIEW: Cardiac imaging is evolving rapidly. Appropriate use of this technology could reduce morbidity and mortality, but inappropriate use could have a significant financial burden. Single-photon emission computed tomography imaging is widely available. This review summarizes the clinical utility and limitations of the prognostic role of single-photon emission computed tomography imaging for myocardial viability in patients with coronary artery disease and left-ventricular dysfunction. RECENT FINDINGS: 201Tl single-photon emission computed tomography, 99mTc single-photon emission computed tomography with sestamibi or tetrofosmin, and 18F-fluorodeoxyglucose single-photon emission computed tomography are validated tools for assessing myocardial viability. These techniques have a very similar predictive value in determining regional and global response to revascularization. 201Tl single-photon emission computed tomography viability studies are predictive of reverse left-ventricular remodeling, symptom improvement, and patient outcome after revascularization. Combination imaging with dual-isotope simultaneous acquisition single-photon emission computed tomography or positron-emission tomography/single-photon emission computed tomography may improve the positive and negative predictive values of single-photon emission computed tomography-based viability studies. SUMMARY: Single-photon emission computed tomography-based myocardial viability testing is an important diagnostic modality due to widespread availability and reasonably good sensitivity and specificity for detecting viable myocardium and predicting clinical and functional responses to revascularization. In the future single-photon emission computed tomography viability techniques may have a prognostic role in predicting responses to cardiac resynchronization therapy and evaluating myocardial stem-cell transplantation.