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Background: Genetic-guided P2Y 12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y 12 inhibitor therapy on cumulative ischemic and bleeding events., Objectives: Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events., Methods: The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y 12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI's primary analysis was time to first event in LOF carriers., Results: Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39)., Conclusions: Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI [TAILOR-PCI]; NCT01742117)., Competing Interests: Funding Support and Author Disclosures Funding for this research was provided by the National Institutes of Health (NIH) grants U01HL128606 to Drs Pereira and Farkouh and U01HL128626 to Dr Bailey. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the views of the National Heart, Lung, and Blood Institute (NHLBI) or the National Institutes of Health. Dr Farkouh has received grants from NHLBI, Amgen, Novartis, and Novo Nordisk. Mr Lennon has received grants from the National Institutes of Health (NIH)/NHLBI and receiving nonfinancial support from Spartan Biosciences. Dr So has received grants from Eli Lilly Canada, Spartan Biosciences, Roche Diagnostics, and Aggredyne Inc; and has received personal fees from AstraZeneca Canada, Bayer Canada, and Servier Canada. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Novo Nordisk A/C, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, Tolmar Pharmaceuticals, and Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and the TIMI Study Group (Brigham Health). Dr Lerman has received personal fees from Itamar Medical, Phillips/Volcano, Shahal, and Wei Jian RC Inc. Dr Tanguay has received personal fees from Mayo Clinic, AstraZeneca, Bayer, Daiichi Sankyo, Servier, Novartis, and BMS-Pfizer Alliance. Dr Welsh has received grants and/or personal fees from AstraZeneca, Pfizer, Bayer, Canadian Cardiac Society, Mayo Clinic, Boehringer Ingelheim, and Novartis. Dr Bailey has received grants from NIH. Dr Pereira has received grants from the NHLBI. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Importance: After percutaneous coronary intervention (PCI), patients with CYP2C19*2 or *3 loss-of-function (LOF) variants treated with clopidogrel have increased risk of ischemic events. Whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes is unknown., Objective: To determine the effect of a genotype-guided oral P2Y12 inhibitor strategy on ischemic outcomes in CYP2C19 LOF carriers after PCI., Design, Setting, and Participants: Open-label randomized clinical trial of 5302 patients undergoing PCI for acute coronary syndromes (ACS) or stable coronary artery disease (CAD). Patients were enrolled at 40 centers in the US, Canada, South Korea, and Mexico from May 2013 through October 2018; final date of follow-up was October 2019., Interventions: Patients randomized to the genotype-guided group (n = 2652) underwent point-of-care genotyping. CYP2C19 LOF carriers were prescribed ticagrelor and noncarriers clopidogrel. Patients randomized to the conventional group (n = 2650) were prescribed clopidogrel and underwent genotyping after 12 months., Main Outcomes and Measures: The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia at 12 months. A secondary end point was major or minor bleeding at 12 months. The primary analysis was in patients with CYP2C19 LOF variants, and secondary analysis included all randomized patients. The trial had 85% power to detect a minimum hazard ratio of 0.50., Results: Among 5302 patients randomized (median age, 62 years; 25% women), 82% had ACS and 18% had stable CAD; 94% completed the trial. Of 1849 with CYP2C19 LOF variants, 764 of 903 (85%) assigned to genotype-guided therapy received ticagrelor, and 932 of 946 (99%) assigned to conventional therapy received clopidogrel. The primary end point occurred in 35 of 903 CYP2C19 LOF carriers (4.0%) in the genotype-guided therapy group and 54 of 946 (5.9%) in the conventional therapy group at 12 months (hazard ratio [HR], 0.66 [95% CI, 0.43-1.02]; P = .06). None of the 11 prespecified secondary end points showed significant differences, including major or minor bleeding in CYP2C19 LOF carriers in the genotype-guided group (1.9%) vs the conventional therapy group (1.6%) at 12 months (HR, 1.22 [95% CI, 0.60-2.51]; P = .58). Among all randomized patients, the primary end point occurred in 113 of 2641 (4.4%) in the genotype-guided group and 135 of 2635 (5.3%) in the conventional group (HR, 0.84 [95% CI, 0.65-1.07]; P = .16)., Conclusions and Relevance: Among CYP2C19 LOF carriers with ACS and stable CAD undergoing PCI, genotype-guided selection of an oral P2Y12 inhibitor, compared with conventional clopidogrel therapy without point-of-care genotyping, resulted in no statistically significant difference in a composite end point of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia based on the prespecified analysis plan and the treatment effect that the study was powered to detect at 12 months., Trial Registration: ClinicalTrials.gov Identifier: NCT01742117.

Background: Endothelial dysfunction is regarded as the early stage of atherosclerosis and is associated with cardiovascular (CV) events. This study was designed to determine whether assessment of coronary endothelial function (CEF) is safe and can reclassify risk in patients with early coronary artery disease beyond the Framingham risk score (FRS)., Methods and Results: CEF was evaluated using intracoronary acetylcholine in 470 patients who presented with chest pain and nonobstructive coronary artery disease. CV events were assessed after a median follow-up of 9.7 years. The association between CEF and CV events was examined, and the net reclassification improvement index (NRI) was used to compare the incremental contribution of CEF when added to FRS.The mean age was 53 years, and 68% of the patients were women with a median FRS of 8. Complications (coronary dissection) occurred in three (0.6%) and CV events in 61 (13%) patients. In univariate analysis, microvascular CEF [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.72-0.97, P=0.032] and epicardial CEF (HR 0.73, 95% CI 0.59-0.90, P=0.01) were found to be significant predictors of CV events, whereas FRS was not (HR 1.05, 95% CI 0.85-1.26, P=0.61). When added to FRS, microvascular CEF correctly reclassified 11.3% of patients [NRI 0.11 (95% CI 0.019-0.21)], epicardial CEF correctly reclassified 12.1% of patients [NRI 0.12 (95% CI -0.02 to 0.26)], and the combined microvascular and epicardial CEF correctly reclassified 22.8% of patients [NRI 0.23 (95% CI 0.08-0.37)]., Conclusion: CEF testing is safe and adds value to the FRS, with superior discrimination and risk stratification compared with FRS alone in patients presenting with chest pain or suspected ischemia.

Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-γ (1257 vs 1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312), TNF-α (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence-associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease. We observed some correlation between some senescence markers and physical performance but no improvement in frailty with rapamycin was noted. (NCT01649960).

Background: Erectile dysfunction (ED) is associated with an increased risk for cardiovascular disease, stroke, and all-cause mortality, independent of conventional cardiovascular risk factors. Coronary endothelial dysfunction is independently associated with ED in men with early coronary atherosclerosis. We aimed to investigate whether coronary microvascular dysfunction predicts development of ED in patients presenting with coronary atherosclerosis without critical stenoses., Patients and Methods: Coronary microvascular function was evaluated in 130 men with coronary atherosclerosis without critical stenoses by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4 years, patients were assessed for the development of ED by administration of a questionnaire., Results: In all, 68 (50%) men had microvascular endothelial dysfunction at baseline; 35 (51%) men with microvascular endothelial dysfunction developed ED on follow-up compared with 19 (31%) men without microvascular endothelial dysfunction. Men who developed ED had a lower coronary blood flow response (% [INCREMENT]CBF) compared with men who did not develop ED, with mean±SD of 25.4±71.3 versus 81.7±120 (P=0.003). In univariate analysis, microvascular endothelial dysfunction was a predictor for the development of ED, with relative risk of 2.4 (1.2-4.9) (P=0.016). In multivariate logistic regression adjusting for traditional cardiovascular risk factors (age, hypertension, hyperlipidemia, diabetes, vascular disease, and family history of coronary artery disease), only microvascular endothelial dysfunction (P=0.027) and age (P=0.044) remained significant predictors of development of ED., Conclusion: Coronary microvascular dysfunction is a predictor of the development of ED in men with coronary atherosclerosis without critical stenoses. This study underscores the systemic involvement of the endothelial function in vascular disease.

Objectives: We report on the real-world, multicenter experience of the Impella 2.5 circulatory support system during high-risk PCI, a subset of the larger USpella Registry., Background: Standard of care for most patients with compromised ventricular function with multivessel or high-risk coronary lesions has been coronary artery bypass grafting. In poor operative candidates, high-risk PCI is increasingly considered, despite an increased risk for periprocedural hemodynamic compromise., Methods: 175 consecutive patients who underwent high-risk PCI with prophylactic support of the Impella 2.5 were evaluated. The primary safety endpoint was the incidence of major adverse cardiac events (MACE) at 30 days. Secondary endpoints included safety and efficacy related to the device and patient outcomes, including survival at 12 months., Results: Overall angiographic revascularization was successful in 99% of patients and in 90% of those with multivessel revascularization, resulting in a reduction of the mean SYNTAX score post-PCI from 36 ± 15 to 18 ± 15 (P < 0.0001) and an improvement of the ejection fraction (from 31 ± 15% to 36 ± 14%, P < 0.0001). In 51% of patients, the functional status improved by one or more NYHA class (P < 0.001). At 30-day follow-up, the rate of MACE was 8%, and survival was 96%, 91%, and 88% at 30 days, 6 months, and 12 months, respectively., Conclusions: The use of Impella 2.5 in high-risk PCI appeared feasible and safe in the real-world setting. The utilization of the Impella 2.5 was successful, resulting in favorable short- and midterm angiographic, procedural and clinical outcomes., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: The purpose of this study was to determine the extent to which effectiveness of cardiac and diabetes treatment strategies varies by patient age., Background: The impact of age on the effectiveness of revascularization and hyperglycemia treatments has not been thoroughly investigated., Methods: In the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial, 2,368 patients with documented stable heart disease and type 2 diabetes were randomized to receive prompt revascularization versus initial medical therapy with deferred revascularization and insulin sensitization versus insulin provision for hyperglycemia treatment. Patients were followed for an average of 5.3 years. Cox regression and mixed models were used to investigate the effect of age and randomized treatment assignment on clinical and health status outcomes., Results: The effect of prompt revascularization versus medical therapy did not differ by age for death (interaction p = 0.99), major cardiovascular events (interaction p = 0.081), angina (interaction p = 0.98), or health status outcomes. After intervention, participants of all ages had significant angina and health status improvement. Younger participants experienced a smaller decline in health status during follow-up than older participants (age by time interaction p < 0.01). The effect of the randomized glycemia treatment on clinical and health status outcomes was similar for patients of different ages., Conclusions: Among patients with stable heart disease and type 2 diabetes, the relative beneficial effects of a strategy of prompt revascularization versus initial medical therapy and insulin-sensitizing versus insulin-providing therapy on clinical endpoints, symptom relief, and perceived health status outcomes do not vary by age. Health status improved significantly after treatment for all ages, and this improvement was sustained longer among younger patients. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Background: The economic outcomes of clinical management strategies are important in assessing their value to patients., Methods and Results: Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized patients with type 2 diabetes mellitus and angiographically documented, stable coronary disease to strategies of (1) prompt revascularization versus medical therapy with delayed revascularization as needed to relieve symptoms and (2) insulin sensitization versus insulin provision. Before randomization, the physician declared whether coronary artery bypass grafting or percutaneous coronary intervention would be used if the patient were assigned to revascularization. We followed 2005 patients for medical utilization and costs and assessed the cost-effectiveness of these management strategies. Medical costs were higher for revascularization than medical therapy, with a significant interaction with the intended method of revascularization (P<0.0001). In the coronary artery bypass grafting stratum, 4-year costs were $80 900 for revascularization versus $60 600 for medical therapy (P<0.0001). In the percutaneous coronary intervention stratum, costs were $73 400 for revascularization versus $67 800 for medical therapy (P<0.02). Costs also were higher for insulin sensitization ($71 300) versus insulin provision ($70 200). Other factors that significantly (P<0.05) and independently increased cost included insulin use and dose at baseline, female sex, white race, body mass index > or =30, and albuminuria. Cost-effectiveness based on 4-year data favored the strategy of medical therapy over prompt revascularization and the strategy of insulin provision over insulin sensitization. Lifetime projections of cost-effectiveness showed that medical therapy was cost-effective compared with revascularization in the percutaneous coronary intervention stratum ($600 per life-year added) with high confidence. Lifetime projections suggest that revascularization may be cost-effective in the coronary artery bypass grafting stratum ($47 000 per life-year added) but with lower confidence., Conclusions: Prompt coronary revascularization significantly increases costs among patients with type 2 diabetes mellitus and stable coronary disease. The strategy of medical therapy (with delayed revascularization as needed) appears to be cost-effective compared with the strategy of prompt coronary revascularization among patients identified a priori as suitable for percutaneous coronary intervention.

Objectives: Our aim was to examine the prognostic importance of hemorrhagic and ischemic complications after percutaneous coronary intervention (PCI) in unselected patients., Background: In randomized trials of PCI, major bleeding and periprocedural myocardial infarction (pMI) have been associated with increased mortality. Whether similar associations exist among un-selected PCI patients is unknown., Methods: We used data from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry-a multicenter registry of unselected patients undergoing PCI-to examine the association between both in-hospital bleeding and pMI and 1-year mortality. Cardiac enzyme levels were assessed in all patients, and pMI was defined as a peak creatine kinase-MB value >or=3x the upper limit of normal. Post-PCI bleeding was classified by Thrombolysis In Myocardial Infarction criteria., Results: After excluding patients with elevated pre-PCI creatine kinase-MB values and ST-segment elevation myocardial infarction at presentation (n = 1,626), a total of 5,961 patients were available for evaluation. Rates of post-PCI bleeding and pMI were 3.0% and 7.1%, respectively; 1-year all-cause mortality was 2.8%. After multivariable adjustment, both post-PCI bleeding (adjusted hazard ratio [HR]: 3.83, 95% confidence interval: 2.48 to 5.90, p < 0.001) and pMI (adjusted HR: 1.84, 95% confidence interval: 1.17 to 2.89, p = 0.009) were independently associated with 1-year mortality. Time period-specific analyses demonstrated that the adjusted HR for bleeding was similar for 30-day mortality and mortality between 1 month and 1 year, while the adjusted HR for pMI was greater for 30-day mortality as compared with mortality between 1 month and 1 year., Conclusions: Among unselected PCI patients, both post-PCI bleeding and pMI are independently associated with increased 1-year mortality. Continued efforts to reduce these complications after PCI are warranted.

Background/objective: Endothelial dysfunction and atherosclerosis are systemic disorders, but are often characterised by segmental involvement and complications. A potential mechanism for local involvement early in the disease process may be related to plaque composition. This study was designed to test the hypothesis that in patients with minimal coronary atherosclerosis, coronary artery segments with abnormal endothelial function have specific plaque characteristics., Methods: Intravascular ultrasound (IVUS) images were obtained from 30 patients who underwent coronary endothelial function assessment. Spectral analysis of the IVUS radiofrequency data was used for assessment of plaque composition. IVUS findings of the coronary sections were compared according to the corresponding endothelial response to acetylcholine., Results: Sections with a decrease epicardial coronary arterial diameter in response to acetylcholine had smaller baseline lumen (7.5 (2.4) mm(2) vs 8.8 (3.3) mm(2), p = 0.006) but larger plaque burden (37.1% (9.4%) vs 31% (7%), p = 0.003) than sections with normal endothelial response. Sections with endothelial dysfunction had larger necrotic core plaques: 0.13 (0.03-0.33) mm(2) vs 0.0 (0.0-0.07), p<0.001 and more dense calcium: 0.03 (IQR 0.0-0.13) mm(2) vs 0.0 (0.0-0.10) mm(2), p<0.01), than those with normal endothelial response. Only necrotic core area was associated with endothelial dysfunction (p<0.001) after adjusting for other measures., Conclusions: This study suggests that local coronary endothelial dysfunction in patients with minimal coronary atherosclerosis is associated with plaque characteristics that are typical of vulnerable plaques.

Objectives: We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial., Background: Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined., Methods: In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005., Results: Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >or=70% (OR: 2.86), proximal left anterior descending stenosis >or=50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >or=65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003)., Conclusions: The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305).

Background: Myocardial bridging refers to intramyocardial systolic compression of a segment of an epicardial coronary artery. We aimed to identify the clinical significance of myocardial bridging by assessing the clinical presentation in non-obstructive coronary artery disease among a cohort of consecutive patients presenting for coronary angiography., Materials and Methods: A retrospective review of our institution's database between September 2002 and March 2005 was conducted to review coronary angiography reports of 14,416 patients. The study group included 226 patients (prevalence=1.57%) with isolated myocardial bridging and <50% stenosis in the non-bridged arteries. Cases with myocardial bridging were classified according to the percentage of systolic compression of the left anterior descending artery into group I (<50% compression), group II (50-70% compression) and group III (compression >or= 70%)., Results: Mean age was 57.6+/-15.5 years; 59% were men. The mean duration of follow-up was 12+/-2 months. The left anterior descending was the most common site of bridging (210, 93%). There was a significant difference between groups I and III with respect to the percentage of patients who presented with non-fatal myocardial infarction (P=0.02). Unstable angina had the highest association with myocardial bridging, but there was no significance among the level of myocardial bridging severity and the clinical presentation of angina., Conclusions: Myocardial bridging is not a benign variation of coronary anatomy. It is associated with angina and myocardial infarction in patients with >or= 70% systolic compression. The bridged segment may be a cause of enhanced atherosclerotic plaque formation.

Objective: To evaluate whether adding comorbid conditions to a risk model can help predict in-hospital outcome and long-term mortality after percutaneous coronary intervention (PCI)., Design: Retrospective chart review, Setting: Academic medical centre., Patients: 7659 patients who had 9032 PCIs., Interventions: PCI performed at Mayo Clinic between 1 January 1999 and 30 June 2004., Main Outcome Measures: The Mayo Clinic Risk Score (MCRS) and the coronary artery disease (CAD)-specific index for determination of comorbid conditions in all patients., Results: The mean (SD) MCRS score was 6.5 (2.9). The CAD-specific index was 0 or 1 in 46%, 2 or 3 in 30% and 4 or higher in 24%. The rate of in-hospital major adverse cardiovascular events (MACE) increased with higher MCRS and CAD-specific index (Cochran-Armitage test, p<0.001 for both models). The c-statistic for the MCRS for in-hospital MACE was 0.78; adding the CAD-specific index did not improve its discriminatory ability for in-hospital MACE (c-statistic = 0.78; likelihood ratio test, p = 0.29). A total of 707 deaths after dismissal occurred after 7253 successful procedures. The c-statistic for all-cause mortality was 0.69 for the MCRS model alone and 0.75 for the MCRS and CAD-specific indices together (likelihood ratio test, p<0.001), indicating significant improvement in the discriminatory ability., Conclusions: Addition of comorbid conditions to the MCRS adds significant prognostic information for post-dismissal mortality but adds little prognostic information about in-hospital complications after PCI. Such health-status measures should be included in future risk stratification models that predict long-term mortality after PCI.

We investigated the influence of > or =70% luminal coronary artery stenosis on regional diastolic deformation at rest using 2-dimensional strain echocardiography. We prospectively imaged patients during/within 24 hours of coronary angiography. Longitudinal systolic (SRs), early (SRe), and late diastolic strain rates, systolic, early, and late diastolic strain and times to isovolumic relaxation and peak SRe were measured in the 3 major vascular territories. Regions subtended by > or =70% coronary stenosis were labeled ischemic. Ischemic regions were compared with the same region in patients without significant coronary stenosis. Of 61 enrolled patients (38 men), 39 had > or =70% coronary stenosis (1 vessel in 14, 2 vessels in 15, 3 vessels in 10), and 15 had normal coronary arteries. There were no significant differences between the normal and ischemic groups with regard to age (59 +/- 13 vs 64 +/- 10 years, p = 0.20), clinical variables (dyslipidemia, smoking, diabetes), systolic (130 +/- 26 vs 139 +/- 31 mm Hg, p = 0.38) or diastolic (72 +/- 13 vs 72 +/- 11 mm Hg, p = 0.81) blood pressure and ejection fraction (58 +/- 12% vs 56 +/- 11%, p = 0.66). SRs and SRe were significantly decreased in ischemic compared with normal regions in all vascular distributions. SRs and SRe together (values below cutoff) or SRe alone were the most specific (93%) and SRe or SRs below cutoff the most sensitive (93%) parameters for detecting ischemic regions. In conclusion, analysis of regional deformation by 2-dimensional strain echocardiography enables detection of significantly diseased coronary arteries at rest. Altered diastolic deformation at rest identifies regions subtended by > or =70% coronary stenosis with high specificity.

Bifurcation lesions of the coronary circulation are difficult to treat with standard balloon technology and are associated with relatively low procedural success rates and high complication rates. We hypothesized that effective debulking of bifurcation lesions with rotational atherectomy would improve observed results. Fifteen patients underwent rotational atherectomy of such lesions. Both limbs of the bifurcation were rotablated in seven patients and one limb in eight; seven patients also underwent stent deployment. Successful angiographic results were obtained in all limbs (<30% residual stenoses). One patient had a non-Q-wave myocardial infarction. No other significant complications occurred. We conclude that rotablation of bifurcation coronary stenoses is feasible, safe, and associated with a high likelihood of angiographic success.

Among patients undergoing percutaneous coronary revascularization, cigarette smoking remained associated with fewer lesions in the target artery even after adjusting for age, extent of coronary artery disease, diabetes mellitus, and hypertension. These findings support the hypothesis that smokers have less active, yet more active, coronary artery disease.

Compounds which inhibit the coagulation cascade and antagonize platelet function are fundamental to the successful treatment of acute coronary syndromes. In a high proportion of patients with acute myocardial infarction, unstable angina, or sudden cardiac death, the acute ischaemic event is precipitated by intracoromry thrombus. Occlusive or non-occlusive thrombi have been found in the majority of cases, either in vivo or at autopsy. Aspirin and unJracrionuted heparin have been the cornerstones of untithrombotic therapy in such patients for the past decade, but while their benefits have been convincingly demonstrated, there are signiJicant pharmacokinetic, pharmacodynamic, and clinical limitations. These limitations have provided the impetus for the development of newer antithrombotic agents with several theoretical advantages over aspirin and heparin.This paper has four aims. First it reviews the pathogenesis of intracoronary thrombi in acute coronary artery syndromes. Second, it outlines the limitations of current antithrombotic therapies. Third, it explores the potential advantages of new antithrombin and antiplatelet compounds, which may be understood and classified by their mechanism of action (Table 1); how the theoretical advantages may translate into clinical practice will be examined. Fourth, the initial clinical experience with these new agents will be reviewed briefly. [ABSTRACT FROM PUBLISHER]