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Articles by R Mehran
Total Records ( 9 ) for R Mehran
  K. W Davidson , M. M Burg , I. M Kronish , D Shimbo , L Dettenborn , R Mehran , D Vorchheimer , L Clemow , J. E Schwartz , F Lesperance and N. Rieckmann

Context  Depression consistently predicts recurrent events and mortality in patients with acute coronary syndrome (ACS), but it has 2 core diagnostic criteria with distinct biological correlates—depressed mood and anhedonia (loss of pleasure or interest).

Objective  To determine if depressed mood and/or anhedonia predict 1-year medical outcomes for patients with ACS.

Design  Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within 1 week of admission, patients underwent a structured psychiatric interview assessing clinically impairing depressed mood, anhedonia, and major depressive episode (MDE). Also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity using the Beck Depression Inventory.

Setting  Cardiac units of 3 university hospitals in New York and Connecticut.

Participants  Consecutive sample of 453 patients with ACS (age, 25-93 years; 42% women).

Main Outcomes Measures  All-cause mortality (ACM) and documented major adverse cardiac events (MACEs)—myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization)—actively surveyed for 1 year after admission.

Results  There were 67 events (16 deaths and 51 MACEs; 14.8%): 108 (24%) and 77 (17%) patients had anhedonia and depressed mood, respectively. Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity. Findings were confirmed using depressed mood and anhedonia subscores from the Beck Depression Inventory in place of clinician interview ratings.

Conclusions  Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity. Correlates of anhedonia may add to the understanding of the link between depression and heart disease.

  A Maehara , G. S Mintz , A. J Lansky , B Witzenbichler , G Guagliumi , B Brodie , M. A Kellett , H Parise , R Mehran and G. W. Stone

Background— Vascular responses to drug-eluting stents in ST-segment elevation myocardial infarction are unknown. In the prospective, multicenter Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients with ST-segment elevation myocardial infarction within 12 hours of symptom onset were randomized 3:1 to TAXUS EXPRESS paclitaxel-eluting stents (PES) or EXPRESS bare metal stents (BMS).

Methods and Results— A formal intravascular ultrasound substudy enrolled 464 patients with baseline and 13-month follow-up imaging at 36 centers. Overall, 446 lesions in 402 patients were suitable for standard qualitative and quantitative analyses, which were performed at an independent blinded core laboratory. The primary prespecified end point was the in-stent percent net volume obstruction at follow-up. Median stent length measured 23.4 mm (first and third quartiles, 18.5 and 31.9 mm). PES compared with BMS significantly reduced 13-month percent net volume obstruction (6.5% [first and third quartiles, 2.2% and 10.8%] versus 15.6% [first and third quartiles, 7.2% and 28.8%]; P<0.0001). PES compared with BMS also resulted in more late-acquired stent malapposition (29.6% versus 7.9%; P=0.0005) resulting from positive vessel remodeling. Plaque and/or thrombus protrusion through stent struts was initially present in 70.4% of PES and 64.8% of BMS; all resolved during follow-up. New aneurysm formation, stent fracture, and subclinical thrombus were uncommon, although seen only in PES.

Conclusions— PES compared with BMS significantly reduce neointimal hyperplasia in patients with ST-segment elevation myocardial infarction but also result in a high frequency of late-acquired stent malapposition as a result of positive vessel remodeling. Ongoing long-term follow-up is required to establish the clinical significance of these findings.

Clinical Trial Registration— URL: Unique identifier: NCT00433966.

  S. J Pocock , R Mehran , T. C Clayton , E Nikolsky , H Parise , M Fahy , A. J Lansky , M. E Bertrand , A. M Lincoff , J. W Moses , E. M Ohman , H. D White and G. W. Stone

Background— Both ischemic and hemorrhagic complications increase mortality rate in acute coronary syndromes. Their frequency and relative importance vary according to individual patient risk profiles. We sought to develop prognostic models for the risk of myocardial infarction (MI) and major bleeding to assess their impact on risk of death and to examine the manner in which alternative antithrombotic regimens affect these risks in individual patients.

Methods and Results— The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial randomized 13 819 patients with acute coronary syndrome to heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. By logistic regression, there were 5 independent predictors of MI within 30 days (n=705; 5.1%) and 8 independent predictors of major bleeding (n=645; 4.7%), only 2 of which were common to both event types. In a covariate-adjusted, time-updated Cox regression model, both MI and major bleeding significantly affected subsequent mortality rate (hazard ratios, 2.7 and 2.9, respectively; both P<0.001). Treatment with bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor was associated with a nonsignificant 8% increase in MI and a highly significant 50% decrease in major bleeding. Given the individual patient risk profiles and the fact that bivalirudin prevented 6 major bleeds for each MI that might occur from its use, the estimated reduction in bleeding was greater than the estimated increase in MI by bivalirudin alone rather than heparin plus a glycoprotein IIb/IIIa inhibitor for nearly all patients.

Conclusions— Consideration of the individual patient risk profile for MI and major bleeding and the relative treatment effects of alternative pharmacotherapies permits personalized decision making to optimize therapy of patients with acute coronary syndrome.

Clinical Trial Registration— Identifier: NCT00093158.

  T. A Sanborn , R Ebrahimi , S. V Manoukian , B. T McLaurin , D. A Cox , F Feit , M Hamon , R Mehran and G. W. Stone

Background— The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial demonstrated that bivalirudin monotherapy significantly reduces major bleeding compared with heparin (unfractionated or enoxaparin) or bivalirudin plus a glycoprotein IIb/IIIa inhibitor in acute coronary syndromes. Whether vascular closure devices (VCD) impact these results is unknown. Therefore, this study sought to determine whether VCD impact major access site bleeding (ASB) in patients with acute coronary syndromes undergoing early invasive management by the femoral approach.

Methods and Results— Major ASB in ACUITY was defined as ASB requiring interventional or surgical correction, hematoma ≥5 cm at the access site, retroperitoneal bleeding, or hemoglobin drop ≥3 g/dL with ecchymosis or hematoma <5 cm, oozing blood, or prolonged bleeding (>30 minutes) at the access site. Stepwise logistical regression was performed to identify the independent determinants of ASB. Of 11 621 patients undergoing angiography with or without percutaneous coronary intervention by the femoral approach, 4307 (37.1%) received a VCD and 7314 (62.9%) did not. Rates of major ASB were lower with VCD compared with no VCD (2.5% versus 3.3%, relative risk, 0.76; 95% CI, 0.61 to 0.94; P=0.01) and were lowest in patients treated with bivalirudin monotherapy and a VCD (0.7%). Stepwise logistic regression revealed that a VCD (odds ratio, 0.78; 95% CI, 0.61 to 0.99; P=0.04) and bivalirudin monotherapy (odds ratio, 0.35; 95% CI, 0.25 to 0.49; P<0.0001) were both independent determinates of freedom from major ASB.

Conclusion— In patients with acute coronary syndromes undergoing an early invasive management strategy by the femoral approach, the use of a VCD, bivalirudin monotherapy, or both minimizes rates of major ASB.

Clinical Trial Registration— URL: Unique Identifier: NCT00093158.

  C Oviedo , A Maehara , G. S Mintz , H Araki , S. Y Choi , K Tsujita , T Kubo , H Doi , B Templin , A. J Lansky , G Dangas , M. B Leon , R Mehran , S. J Tahk , G. W Stone , M Ochiai and J. W. Moses

Background— Angiographic classifications of the location and severity of disease in the main vessel and side branch of coronary artery bifurcations have been proposed and applied to distal left main coronary artery (LMCA) bifurcation.

Methods and Results— We reviewed 140 angiograms of distal LMCA and ostial left anterior descending (LAD) and left circumflex (LCX) artery lesions with preintervention intravascular ultrasound (IVUS) of both the LAD and LCX arteries as well as the LMCA. Of 140 patients, 92.9% had at least 1 cross section with ≥40% IVUS plaque burden versus 57.2% of patients with an angiographic diameter stenosis ≥50%. Contrary to angiographic classifications, IVUS showed that bifurcation disease was rarely focal and that both sides of the flow divider were always disease-free. Continuous plaque from the LMCA into the proximal LAD artery was seen in 90%, from the LMCA into the LCX artery in 66.4%, and from the LMCA into both the LAD and LCX arteries in 62%. Plaque localized to either the LAD or LCX ostium and not involving the distal LMCA was seen in only 9.3% of LAD arteries and 17.1% of LCX arteries. Plaque distribution was not influenced by the LAD/LCX angiographic angle, lesion severity, LMCA length, or remodeling. We proposed an IVUS classification for bifurcation lesions illustrating longitudinal and circumferential spatial plaque distribution.

Conclusions— Angiographic classification of LMCA bifurcation lesions is rarely accurate. IVUS shows that the carina is always spared and that the disease is diffuse rather than focal.

Clinical Trial Registration— URL: Unique identifier: NCT00180466.

  A. J Lansky , K Goto , E Cristea , M Fahy , H Parise , F Feit , E. M Ohman , H. D White , K. P Alexander , M. E Bertrand , W Desmet , M Hamon , R Mehran , J Moses , M Leon and G. W. Stone

Contemporary adjunctive pharmacology and revascularization strategies have improved the prognosis of patients with acute coronary syndromes (ACSs). We sought to identify the clinical and angiographic predictors of cardiac ischemic events in patients with ACSs treated with an early invasive strategy.

Methods and Results—

Multivariable logistic regression was used to analyze the relation between baseline characteristics and 30-day and 1-year composite ischemia (death, myocardial infarction, or unplanned revascularization) among the 6921 ACS patients included in the prespecified angiographic substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Of the 6921 patients, 3826 (55.3%) were treated with percutaneous coronary intervention, 755 (10.9%) with coronary artery bypass grafting, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) patients at 30 days and in 1153 (17.4%) at 1 year. Renal insufficiency, biomarker elevation, ST-segment deviation, nonuse of aspirin or thienopyridine, insulin-treated diabetes, older age, baseline lower hemoglobin value, history of percutaneous coronary intervention, and current smoking were independently associated with 30-day or 1-year ischemic events. Angiographic characteristics predicting ischemic events included number of diseased vessels, moderate/severe calcification, worst percent diameter stenosis, jeopardy score, lower left ventricular ejection fraction, lesion eccentricity, and thrombus. With use of receiver operating characteristic methodology, the c statistic improved for the predictive model by adding angiographic to clinical parameters for the 30-day composite ischemia (from 0.62 to 0.68) and myocardial infarction (from 0.64 to 0.71) and 1-year composite ischemia (from 0.61 to 0.65) and myocardial infarction (from 0.63 to 0.69) end points.


Among ACS patients managed with an early invasive strategy, baseline angiographic markers of disease burden, calcification, lesion severity, lower left ventricular ejection fraction, and morphological characteristics provided important added independent predictive value for 30-day and 1-year ischemic outcomes, beyond the well-recognized clinical risk factors. These findings emphasize the prognostic importance of the diagnostic angiogram in the risk stratification of patients presenting with ACSs.

Clinical Trial Registration—

URL: Unique identifier: NCT00093158.

  R. J Solomon , R Mehran , M. K Natarajan , S Doucet , R. E Katholi , C. S Staniloae , S. K Sharma , M Labinaz , J. L Gelormini and B. J. Barrett

Background and objectives: The relationship of contrast-induced nephropathy (CIN) to long-term adverse events (AEs) is controversial. Although an association with AEs has been previously reported, it is unclear whether CIN is causally related to these AEs.

Design, setting, participants, & measurements: We obtained long-term (≥1 yr) follow-up on 294 patients who participated in a randomized, double-blind comparison of two prevention strategies for CIN (iopamidol versus iodixanol). A difference in the incidence of AEs between patients who had developed CIN and those who had not was performed using a 2 test and Poisson regression analysis. A similar statistical approach was used for the differences in AEs between those who received iopamidol or iodixanol. Multiple definitions of CIN were used to strengthen and validate the results and conclusions.

Results: The rate of long-term AEs was higher in individuals with CIN (all definitions of CIN). After adjustment for baseline comorbidities and risk factors, the adjusted incidence rate ratio for AEs was twice as high in those with CIN. Randomization to iopamidol reduced both the incidence of CIN and AEs.

Conclusions: The parallel decrease in the incidence of CIN and AEs in one arm of this randomized trial supports a causal role for CIN.

  S. S Brar , S Hiremath , G Dangas , R Mehran , S. K Brar and M. B. Leon

Background and objectives: Infusion of sodium bicarbonate has been suggested as a preventative strategy but reports are conflicting on its efficacy. The aim of this study was to assess the effectiveness of hydration with sodium bicarbonate for the prevention of contrast-induced acute kidney injury (CI-AKI).

Design, setting, participants, & measurements: Medline, EMBASE, Cochrane library, and the Internet were searched for randomized controlled trials comparing hydration between sodium bicarbonate and chloride for the prevention of CI-AKI between 1966 and November 2008. Fourteen trials that included 2290 patients were identified. There was significant heterogeneity between studies (P heterogeneity = 0.02; I2 = 47.8%), which was largely accounted for by trial size (P = 0.016). Trials were therefore classified by size.

Results: Three trials were categorized as large (n = 1145) and 12 as small (n = 1145). Among the large trials, the incidence of CI-AKI for sodium bicarbonate and sodium chloride was 10.7 and 12.5%, respectively; the relative risk (RR) [95% confidence interval (CI)] was 0.85 (0.63 to 1.16) without evidence of heterogeneity (P = 0.89, I2 = 0%). The pooled RR (95% CI) among the 12 small trials was 0.50 (0.27 to 0.93) with significant between-trial heterogeneity (P = 0.01; I2 = 56%). The small trials were more likely to be of lower methodological quality.

Conclusions: A significant clinical and statistical heterogeneity was observed that was largely explained by trial size and published status. Among the large randomized trials there was no evidence of benefit for hydration with sodium bicarbonate compared with sodium chloride for the prevention of CI-AKI. The benefit of sodium bicarbonate was limited to small trials of lower methodological quality.

  R Mehran , S. J Pocock , G. W Stone , T. C Clayton , G. D Dangas , F Feit , S. V Manoukian , E Nikolsky , A. J Lansky , A Kirtane , H. D White , A Colombo , J. H Ware , J. W Moses and E. M. Ohman

To evaluate the associations of myocardial infarction (MI) and major bleeding with 1-year mortality. Both MI and major bleeding predict 1-year mortality in patients presenting with acute coronary syndrome (ACS). However, the risk of each of these events on the magnitude and timing of mortality has not been well studied.

Methods and Results

A multivariable Cox regression model was developed relating 13 independent baseline predictors to 1-year mortality for 13 819 patients with moderate and high-risk ACS enrolled in the Acute Catheterization and Urgent Intervention Triage strategy trial. After adjustment for baseline predictors, Cox models with major bleeding and recurrent MI as time-updated covariates estimated the effect of these events on mortality hazard over time. Within 30 days of randomization, 705 patients (5.1%) had an MI, 645 (4.7%) had a major bleed; 524 (3.8%) died within a year. The occurrence of an MI was associated with a hazard ratio of 3.1 compared with patients not yet having an MI, after adjustment for baseline predictors. However, MI within 30 days markedly increased the mortality risk for the first 2 days after the event (adjusted hazard ratio of 17.6), but this risk declined rapidly post-infarct (hazard ratio of 1.4 beyond 1 month after the MI event). In contrast, major bleeding had a prolonged association with mortality risk (hazard ratio of 3.5) which remained fairly steady over time throughout 1 year.


After accounting for baseline predictors of mortality, major bleeds and MI have similar overall strength of association with mortality in the first year after ACS. MI is correlated with a dramatic increase in short-term risk, whereas major bleeding correlates with a more prolonged mortality risk.

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