Prasad, Abhiram

Objectives: To evaluate outcomes among cancer patients with preexisting coronary artery disease and cardiac stenting who subsequently underwent thoracic radiotherapy (RT). Methods: From 1998 to 2012, 147 patients received percutaneous coronary intervention (PCI) and then curative external beam RT (>30 Gy, except for Hodgkin lymphoma patients) involving the heart and the lungs. Heart-specific and lung-specific dosimetric parameters were correlated to overall survival (OS) and cardiac-specific survival by Cox variate methods. Results: The mean interval between PCI and cancer diagnosis was 1.8 years (range, 0.1 to 14.2 y). Hypertension was present in 105 patients (71%), and hyperlipidemia in 82 (56%). At the time of analysis, 69 patients (47%) were alive, 3 (2%) died of cardiac causes, and 53 (36%) died of cancer. In multivariate analyses, OS since PCI was related to cancer type (P=0.004). Decreased OS since cancer diagnosis was related to older age (P<0.001) and increased percentage of targeted volume or organ receiving 20 Gy or more for lung (P<0.001), even after controlling for sex, cancer type, and stage. However, for non–cancer-specific survival and major adverse cardiac event-free survival, older age and underlying cardiopulmonary comorbidities dominated (rather than heart and lung dosimetric parameters) in predicting worse outcome for these patients with preexisting coronary artery disease who later underwent RT. Conclusions: Cancer type, older age, and preexisting cardiopulmonary comorbidities and risk factors most significantly predicted clinical outcome and survival for these patients with existing coronary stents who subsequently received thoracic RT. Dosimetric detrimental effects were not significant in our study.

Background— High sensitivity C-reactive protein (hsCRP) has been identified as a predictor of adverse cardiovascular outcomes. Whether hsCRP is a useful biomarker for risk stratification in contemporary percutaneous coronary intervention remains unknown. Methods and Results— We conducted a prospective study among 513 patients undergoing non-emergency percutaneous coronary intervention and examined the relationship between pre- and postprocedural hsCRP levels and outcomes. The patients were divided according to the median preprocedural hsCRP level (0.3 mg/dL). Patients with high hsCRP had significantly more adverse clinical characteristics. Preprocedural hsCRP level was an independent predictor of periprocedural myocardial infarction (odds ratio per doubling of hsCRP 1.15 [95% confidence interval, 1.01–1.31]; P =0.038). Unadjusted mortality (29.7% versus 9.9%; P <0.001) and the combined end point of death or myocardial infarction (36.5% versus 16.0%, P <0.001) during a follow-up of 5 years were markedly greater in patients with high preprocedural hsCRP. Similar relationships existed for postprocedural hsCRP. However, after multivariable adjustment, neither preprocedural hsCRP levels (hazard ratio per doubling 0.96 [0.92, 1.00]; P =0.066) nor postprocedural hsCRP levels (hazard ratio 0.98 [0.94, 1.02]; P =0.27) were significantly associated with mortality. Conclusions— High hsCRP is associated with a greater independent risk of periprocedural myocardial infarction, as defined by the universal definition, but is not an independent determinant of mortality after percutaneous coronary intervention. Our findings suggest that routine measurement of hsCRP in patients undergoing percutaneous coronary intervention in contemporary practice is unlikely to be beneficial.

Aims: Percutaneous coronary intervention (PCI) is frequently accompanied by myocardial injury. The present study was performed to determine whether remote ischemic preconditioning (IP) induces cardioprotection during PCI. Methods: We enrolled 95 patients requiring nonemergency PCI for stable disease or unstable angina into this prospective clinical trial. Patients were randomized to either remote IP (induced by three 3‐min cycles of blood pressure cuff inflations to 200 mm Hg around the upper arm, followed by 3‐min of reperfusion n = 47) or sham control ( n = 48) immediately preceding PCI. The primary outcome measure was the frequency of post‐PCI myonecrosis, defined as a peak postprocedural cTnT T ≥0.03 ng/dL. Secondary outcome measures were the change in plasma high‐sensitivity C‐reactive protein (hsCRP) levels following PCI and in endothelial progenitor cells (EPC) counts following IP. Results: There was no difference in the primary endpoint of the frequency of PCI related myonecrosis which occurred in 22 (47%) and 19 (40%) patients in the remote IP and control groups, respectively, P = 0.42. There was significant increase in hsCRP post‐PCI in both groups ( P < 0.001), but there was no difference between the groups (median %change in hsCRP 46% vs. 54%, P = 0.73). There was no significant change in circulating early (CD34 −/CD133+/KDR+), intermediate (CD34+/CD133+/KDR+), or late (CD34+/CD133−/KDR+) EPC in the two groups immediately following IP. The composite rate of death, myocardial infarction, and target lesion revascularization at 1 year was 14.1% versus 13.7% ( P = 0.90). Conclusions: Our study indicates that remote IP immediately before PCI does not induce cardioprotection in low to moderate risk patients. © 2012 Wiley Periodicals, Inc.

Abstract Mind body therapies appear to reduce morbidity and mortality in patients with cardiovascular diseases, but there is limited understanding of the mechanisms that mediate this effect. Vascular endothelial dysfunction is a central feature of atherogenesis that is adversely impacted by mental stress. We conducted a systematic review and meta-analysis of the effect of mind body therapies on peripheral endothelial function in patients with and without established cardiovascular disease. The search included Medline, Cochrane Library, Scopus and Embase to identify studies up to November 2009. Eligible studies were randomized controlled trials that compared the effects of mind body therapies and placebo on endothelial function. Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. Three eligible trials enrolled a total of 258 patients. Sixty one (24 percent) were women and 53 percent had established cardiovascular disease. The trials had good methodological quality. Meta-analysis using random-effects model showed a non significant improvement of endothelial function by mind body therapies (standardized mean difference 0.15; 95% CI, -0.36 to 0.67, P=0.56). The analysis was underpowered due to small sample size. Circumstantial evidence indicates that mind body therapies may have a therapeutic benefit on endothelial dysfunction, however, the aggregate data from the three small randomized trials to date do not support this hypothesis. This biologically plausible effect requires additional investigation in adequately powered studies.

Background— Endothelin (ET-1) is one of the most potent vasoconstrictors and plays a seminal role in the pathogenesis of atherosclerosis. The present study was designed to test the hypothesis that long-term treatment with an endothelin-A (ET A ) receptor antagonist improves coronary endothelial function in patients with early coronary atherosclerosis. Methods and Results— Forty-seven patients with multiple cardiovascular risk factors, nonobstructive coronary artery disease, and coronary endothelial dysfunction were randomized in a double-blind manner to either the ET A receptor antagonist atrasentan (10 mg) or placebo for 6 months. Coronary endothelium-dependent vasodilation was examined by infusing acetylcholine (10 −6 to 10 −4 mol/L) in the left anterior descending coronary artery. N G -monomethyl- l -arginine was administered to a subgroup of patients. Endothelium-independent coronary flow reserve was examined by use of intracoronary adenosine and nitroglycerin. Baseline characteristics and incidence of adverse effects were similar between the 2 groups. There was a significant improvement in percent change of coronary blood flow in response to acetylcholine at 6 months from baseline in the atrasentan group compared with the placebo group (39.67%, 95% confidence interval 23.23% to 68.21%, versus −2.22%, 95% confidence interval −27.37% to 15.28%; P <0.001). No significant difference in the percent change of coronary artery diameter or change in coronary flow reserve was demonstrated. Coronary blood flow, coronary artery diameter, and the effect of N G -monomethyl- l -arginine were similar between the groups at baseline and at 6 months. Conclusions— This study demonstrates that 6-month treatment with atrasentan improves coronary microvascular endothelial function and supports the role of the endogenous endothelin system in the regulation of endothelial function in early atherosclerosis in humans. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271492.