Chetan Shenoy

A Comparison of Contemporary Definitions of Contrast Nephropathy in Patients Undergoing Percutaneous Coronary Intervention and a Proposal for a Novel Nephropathy Grading System

Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) has multiple definitions. We attempted to identify the optimal definition of CIN. In 985 patients undergoing PCI (derivation group), we assessed the prognostic significance of 4 commonly used contemporary definitions of CIN (increases in serum creatinine after PCI [deltaCr] >1.0 mg/dl, >0.5 mg/dl, and >25% after PCI; and the American College of Cardiology National Cardiovascular Data Registry definition) with respect to 6-month major adverse cardiovascular events (MACEs) and all-cause mortality (at 863 +/- 324 days). Incidence of CIN ranged widely (2.0% to 15%) depending on the definition used. Only 2 definitions (deltaCr >0.5 mg/dl, >25%) consistently correlated with study outcomes. Using these 2 definitions, we devised a new grading system (grade 0 deltaCr <or=25% and <or=0.5 mg/dl; grade 1 deltaCr >25% but <or=0.5 mg/dl; and grade 2 deltaCr >0.5 mg/dl). Nephropathy grades (0 vs 1 vs 2) showed significant correlation with 6-month MACEs (12.4 vs 19.4 vs 28.6%, p = 0.003) and all-cause mortality (10.2 vs 10.4 vs 40.9%, p <0.0001). In multivariate analyses, the grading system showed an independent association with MACEs and mortality. The prognostic value of nephropathy grades was prospectively confirmed in an independent validation group of 539 patients. In conclusion, of the 4 contemporary definitions of CIN, only deltaCr >25% and >0.5 mg/dl consistently predicted adverse events after PCI. By unifying these 2 definitions, we devised a novel nephropathy grading system that is predictive of 6-month MACEs and all-cause mortality after PCI.

LV Thrombus Detection by Routine Echocardiography : Insights Into Performance Characteristics Using Delayed Enhancement CMR

OBJECTIVES This study sought to evaluate performance characteristics of routine echo for left ventricular thrombus (LVT). BACKGROUND Although the utility of dedicated echocardiography (echo) for LVT is established, echo is widely used as a general test for which LVT is rarely the primary indication. We used delayed-enhancement cardiac magnetic resonance (DE-CMR) as a reference to evaluate LVT detection by routine echo. METHODS Dedicated LVT assessment using DE-CMR was prospectively performed in patients with left ventricular systolic dysfunction. Echoes were done as part of routine clinical care. Echo and CMR were independently read for LVT and related indexes of LVT size, shape, and image quality/diagnostic confidence. Follow-up was done for embolic events and pathology validation of LVT. RESULTS In this study, 243 patients had routine clinical echo and dedicated CMR within 1 week without intervening events. Follow-up supported DE-CMR as a reference standard, with >5-fold difference in endpoints between patients with versus without LVT by DE-CMR (p = 0.02). LVT prevalence was 10% by DE-CMR. Echo contrast was used in 4% of patients. Echo sensitivity and specificity were 33% and 91%, with positive and negative predictive values of 29% and 93%. Among patients with possible LVT as the clinical indication for echo, sensitivity and positive predictive value were markedly higher (60%, 75%). Regarding sensitivity, echo performance related to LVT morphology and mirrored cine-CMR, with protuberant thrombus typically missed when small (p ≤ 0.02). There was also a strong trend to miss mural thrombus irrespective of size (p = 0.06). Concerning positive predictive value, echo performance related to image quality, with lower diagnostic confidence scores for echoes read positive for LVT in discordance with DE-CMR compared with echoes concordant with DE-CMR (p < 0.02). CONCLUSIONS Routine echo with rare contrast use can yield misleading results concerning LVT. Echo performance is improved when large protuberant thrombus is present and when the clinical indication is specifically for LVT assessment.

Identifying the Etiology: A Systematic Approach Using Delayed Enhancement Cardiovascular Magnetic Resonance

In patients who have heart failure, treatment and survival are directly related to the cause. Clinically, as a practical first step, patients are classified as having either ischemic or non-ischemic cardiomyopathy, a delineation usually based on the presence or absence of epicardial coronary artery disease. However, this approach does not account for patients with non-ischemic cardiomyopathy who also have coronary artery disease, which may be either incidental or partly contributing to myocardial dysfunction (mixed cardiomyopathy). By allowing direct assessment of the myocardium, delayed-enhancement cardiovascular magnetic resonance (DE-CMR) may aid in addressing these conundrums. This article explores the use of DE-CMR in identifying ischemic and non-ischemic myopathic processes and details a systematic approach to determine the cause of cardiomyopathy.

Clinical Outcomes in Patients With the Concomitant Use of Clopidogrel and Proton Pump Inhibitors After Percutaneous Coronary Intervention An Analysis From the Guthrie Health Off-Label Stent (GHOST) Investigators

Background— The concomitant use of proton pump inhibitors (PPIs) with clopidogrel is suspected to be associated with an adverse impact on clinical outcomes in patients with coronary artery disease. We sought to evaluate whether the use of PPIs with clopidogrel was associated with worse clinical outcomes after percutaneous coronary intervention (PCI) compared with the use of clopidogrel alone. Methods and Results— We studied 2651 consecutive patients discharged alive after coronary stenting for stable or unstable coronary artery disease between 2001 and 2007. All patients received aspirin indefinitely and a thienopyridine for 1 to 12 months. Patients were categorized into 2 groups: those taking a PPI [PPI (+), n=751] and those not taking a PPI [PPI (−), n=1900] at discharge. The primary end points were the 6-month incidence of major adverse cardiovascular events (MACE) (composite of death, myocardial infarction, target vessel revascularization, and stent thrombosis) and net adverse clinical events (NACE) (composite of MACE and thrombolysis in myocardial infarction major or minor bleeding), which were evaluated using propensity-adjusted Cox regression analysis. In addition, propensity-matched analysis was performed in 685 pairs of patients. The PPI (+) group was older and had more comorbid conditions than the PPI (−) group. In propensity-adjusted as well as propensity-matched analyses, the use of PPIs was not associated with an increased risk of MACE or NACE. Conclusions— The use of PPIs with dual antiplatelet therapy was not associated with any adverse influence on MACE or NACE after PCI.

Clinical Outcomes in Patients With the Concomitant Use of Clopidogrel and Proton Pump Inhibitors After Percutaneous Coronary Intervention

Background— The concomitant use of proton pump inhibitors (PPIs) with clopidogrel is suspected to be associated with an adverse impact on clinical outcomes in patients with coronary artery disease. We sought to evaluate whether the use of PPIs with clopidogrel was associated with worse clinical outcomes after percutaneous coronary intervention (PCI) compared with the use of clopidogrel alone. Methods and Results— We studied 2651 consecutive patients discharged alive after coronary stenting for stable or unstable coronary artery disease between 2001 and 2007. All patients received aspirin indefinitely and a thienopyridine for 1 to 12 months. Patients were categorized into 2 groups: those taking a PPI [PPI (+), n=751] and those not taking a PPI [PPI (−), n=1900] at discharge. The primary end points were the 6-month incidence of major adverse cardiovascular events (MACE) (composite of death, myocardial infarction, target vessel revascularization, and stent thrombosis) and net adverse clinical events (NACE) (composite of MACE and thrombolysis in myocardial infarction major or minor bleeding), which were evaluated using propensity-adjusted Cox regression analysis. In addition, propensity-matched analysis was performed in 685 pairs of patients. The PPI (+) group was older and had more comorbid conditions than the PPI (−) group. In propensity-adjusted as well as propensity-matched analyses, the use of PPIs was not associated with an increased risk of MACE or NACE. Conclusions— The use of PPIs with dual antiplatelet therapy was not associated with any adverse influence on MACE or NACE after PCI.

Dual antiplatelet therapy for more than 12 months after percutaneous coronary intervention: insights from the Guthrie PCI Registry

Objective: To assess the impact of dual antiplatelet (DAP) therapy of >12 months on long-term death and myocardial infarction (MI) after percutaneous coronary intervention (PCI). Design, setting and patients: Prospective, single-centre, observational study of 1859 consecutive patients who underwent successful PCI of a native coronary artery and survived event-free for at least 12 months. Main outcome measures: Combined end point of death or non-fatal MI determined by survival analysis and propensity-adjusted multivariable Cox regression. Similar analyses were performed in the two stent subsets: bare metal stents (n = 835), drug-eluting stents (n = 1024); and three high-risk subsets: diabetic patients (n = 486), patients presenting with MI (n = 713), and those with ACC/AHA type C lesions (n = 717). Results: Baseline characteristics were as follows: mean (SD) age 64 (12) years, male 69%, diabetic 26%, presentation with MI 38%, mean (SD) ejection fraction 49 (12)%, mean (SD) vessel diameter 3.1 (0.5) mm. Duration of DAP was 27 (11) months in “DAP >12 months” and 4.1 (4.1) months in “DAP ⩽12 months” (p<0.001). At a median follow-up of 3.4 years after PCI, “DAP >12 months” vs “DAP ⩽12 months” had similar incidence of death or MI (9.4% vs 10.3%, log-rank p = 0.83). After multivariable adjustment, DAP therapy >12 months was not associated with lower incidence of death or MI than DAP therapy ⩽12 months (adjusted HR = 1.01; 95% CI 0.74 to 1.37, p = 0.95). Analysis of each of the five predefined subsets showed similar results. Conclusions: In patients who undergo successful native coronary PCI and survive event-free for at least 12 months, continuation of dual antiplatelet therapy beyond 12 months does not confer long-term protection from death or MI.

Left atrial passive emptying function during dobutamine stress MR imaging is a predictor of cardiac events in patients with suspected myocardial ischemia.

OBJECTIVES The aim of this study was to determine the prognostic value of assessing left atrial function during dobutamine stress testing. BACKGROUND Left ventricular diastolic dysfunction precedes systolic wall motion abnormalities in the ischemic cascade. Severity of left ventricular diastolic function during cardiac stress is not characterized well by current clinical imaging protocols but may be an important prognostic factor. We hypothesized that abnormal early left atrial emptying measured during dobutamine stress cardiac magnetic resonance will reflect these diastolic changes and may be associated with cardiovascular outcomes. METHODS We enrolled 122 consecutive patients referred for dobutamine stress cardiac magnetic resonance for suspected myocardial ischemia. Left atrial volumes were retrospectively measured by the biplane area-length method at left ventricular end-systole (VOL(max)) and before atrial contraction (VOL(bac)). Left atrial passive emptying fraction defined by (VOL(max) - VOL(bac)) × 100%/VOL(max) and the absolute percent increase in left atrial passive emptying fraction during dobutamine stress (ΔLAPEF) were quantified. RESULTS Twenty-nine major adverse cardiac events (MACE) occurred during follow-up (median 23 months). By Kaplan-Meier analysis, patients with ΔLAPEF <10.8 (median) experienced higher incidence of MACE than did patients with a ΔLAPEF >10.8 (p = 0.004). By univariable analysis, ΔLAPEF was strongly associated with MACE (unadjusted hazard ratio for every 10% decrease = 1.56, p < 0.005). By multivariable analysis, every 10% decrease in ΔLAPEF carried a 57% increase in MACE, after adjustment to presence of myocardial ischemia and infarction. CONCLUSIONS Reduced augmentation of left atrial passive emptying fraction during dobutamine stress demonstrated strong association with MACE. We speculate that reduced left atrial passive emptying reserve during inotropic stress may represent underlying diastolic dysfunction and warrants further investigation.

Drug-Eluting Stents in Patients with Chronic Kidney Disease: A Prospective Registry Study

Background Chronic kidney disease (CKD) is strongly associated with adverse outcomes after percutaneous coronary intervention (PCI). There are limited data on the effectiveness of drug-eluting stents (DES) in patients with CKD. Methodology/Principal Findings Of 3,752 consecutive patients enrolled in the Guthrie PCI Registry between 2001 and 2006, 436 patients with CKD - defined as a creatinine clearance <60 mL/min - were included in this study. Patients who received DES were compared to those who received bare metal stents (BMS). Patients were followed for a mean duration of 3 years after the index PCI to determine the prognostic impact of stent type. Study end-points were all-cause death, myocardial infarction (MI), target vessel revascularization (TVR), stent thrombosis (ST) and the composite of major adverse cardiovascular events (MACE), defined as death, MI or TVR. Patients receiving DES in our study, by virtue of physician selection, had more stable coronary artery disease and had lower baseline risk of thrombotic or restenotic events. Kaplan-Meier estimates of proportions of patients reaching the end-points were significantly lower for DES vs. BMS for all-cause death (p = 0.0008), TVR (p = 0.029) and MACE (p = 0.0015), but not MI (p = 0.945) or ST (p = 0.88). Multivariable analysis with propensity adjustment demonstrated that DES implantation was an independent predictor of lower rates of all-cause death (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.25–0.92), TVR (HR 0.50, 95% CI 0.27–0.94) and MACE (HR 0.62, 95% CI 0.41–0.94). Conclusions In a contemporary PCI registry, selective use of DES in patients with CKD was safe and effective in the long term, with lower risk of all-cause death, TVR and MACE and similar risk of MI and ST as compared with BMS. The mortality benefit may be a result of selection bias and residual confounding, or represent a true finding; a hypothesis that warrants clarification by randomized clinical trials.

Cardiovascular Complications of Breast Cancer Therapy in Older Adults

Older adults frequently have pre-existing and cancer-related risk factors for cardiovascular toxicity from cancer treatment. In this review, we discuss the risk factors and strategies for prevention and management of cardiovascular complications in older women with breast cancer.

Distinct effects of unfractionated heparin versus bivalirudin on circulating angiogenic peptides.

Background Human studies of therapeutic angiogenesis, stem-cell, and progenitor-cell therapy have failed to demonstrate consistent clinical benefit. Recent studies have shown that heparin increases circulating levels of anti-angiogenic peptides. Given the widely prevalent use of heparin in percutaneous and surgical procedures including those performed as part of studies examining the benefit of therapeutic angiogenesis and cell-based therapy, we compared the effects of unfractionated heparin (UFH) on angiogenic peptides with those of bivalirudin, a relatively newer anticoagulant whose effects on angiogenic peptides have not been studied. Methodology/Principal Findings We measured soluble fms-like tyrosine kinase-1 (sFLT1), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble Endoglin (sEng) serum levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective percutaneous coronary intervention. Compared to baseline values, sFLT1 and PlGF levels increased by 2629±313% and 253±54%, respectively, within 30 minutes of UFH therapy (p<0.01 for both; n = 8). VEGF levels decreased by 93.2±5% in patients treated with UFH (p<0.01 versus baseline). No change in sEng levels were observed after UFH therapy. No changes in sFLT1, PlGF, VEGF, or sEng levels were observed in any patients receiving bivalirudin (n = 8). To further explore the direct effect of anticoagulation on circulating angiogenic peptides, adult, male wild-type mice received venous injections of clinically dosed UFH or bivalirudin. Compared to saline controls, sFLT1 and PlGF levels increased by >500% (p<0.01, for both) and VEGF levels increased by 221±101% (p<0.05) 30 minutes after UFH treatment. Bivalirudin had no effect on peptide levels. To study the cellular origin of peptides after anticoagulant therapy, human coronary endothelial cells were treated with UFH and demonstrated increased sFLT1 and PlGF levels (ANOVA p<0.01 for both) with reduced VEGF levels (ANOVA p<0.05). Bivalirudin had no effect on peptide levels in vitro. Conclusions/Significance Circulating levels of sFLT1, PlGF, and VEGF are significantly altered by UFH, while bivalirudin therapy has no effect. These findings may have significant implications for clinical studies of therapeutic angiogenesis, stem-cell and progenitor-cell therapy.