Ehtisham Mahmud

Integration of pre-hospital electrocardiograms and ST-elevation myocardial infarction receiving center (SRC) networks: impact on Door-to-Balloon times across 10 independent regions.

OBJECTIVES The aim of this study was to evaluate the rate of timely reperfusion for ST-elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (PPCI) in regional STEMI Receiving Center (SRC) networks. BACKGROUND The American College of Cardiology Door-to-Balloon (D2B) Alliance target is a >75% rate of D2B <or=90 min. Independent initiatives nationwide have organized regional SRC networks that coordinate universal access to 9-1-1 with the pre-hospital electrocardiogram (PH-ECG) diagnosis of STEMI and immediate transport to a SRC (designated PPCI-capable hospital). METHODS A pooled analysis of 10 independent, prospective, observational registries involving 72 hospitals was performed. Data were collected on all consecutive patients with a PH-ECG diagnosis of STEMI. The D2B and emergency medical services (EMS)-to-balloon (E2B) times were recorded. RESULTS Paramedics transported 2,712 patients with a PH-ECG diagnosis of STEMI directly to the nearest SRC. A PPCI was performed in 2,053 patients (76%) with an 86% rate of D2B <or=90 min (95% confidence interval: 84.4% to 87.4%). Secondary analyses of this cohort demonstrated a 50% rate of D2B <or=60 min (n = 1,031), 25% rate of D2B <or=45 min (n = 517), and an 8% rate of D2B <or=30 min (n = 155). A tertiary analysis restricted to 762 of 2,053 (37%) cases demonstrated a 68% rate of E2B <or=90 min. CONCLUSIONS Ten independent regional SRC networks demonstrated a combined 86% rate of D2B <or=90 min, and each region individually surpassed the American College of Cardiology D2B Alliance benchmark. In areas with regional SRC networks, 9-1-1 provides entire communities with timely access to quality STEMI care.

Effect of prehospital 12-lead electrocardiogram on activation of the cardiac catheterization laboratory and door-to-balloon time in ST-segment elevation acute myocardial infarction.

Reducing door-to-balloon (D + B) time during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction (STEMI) reduces mortality. Prehospital 12-lead electrocadiography (ECG) with cardiac catheterization laboratory (CCL) activation may reduce D + B time. Paramedic-performed ECG was initiated in the city of San Diego in January 2005 with STEMI diagnosis based on an automated computer algorithm. We undertook this study to determine the effect of prehospital CCL activation on D + B time for patients with acute STEMI brought to our institution. All data were prospectively collected for patients with STEMI including times to treatment and clinical outcomes. We evaluated 78 consecutive patients with STEMI from January 2005 to June 2006, and the study group consisted of all patients with prehospital activation of the CCL (field STEMI; n = 20). The control groups included concurrently-treated patients with STEMI during the same period who presented to the emergency department (nonfield STEMI; n = 28), and all patients with STEMI treated in the preceding year (2004) (historical STEMI; n = 30). Prehospital CCL activation significantly reduced D + B time (73 +/- 19 minutes field STEMI, 130 +/- 66 minutes nonfield STEMI, 141 +/- 49 minutes historical STEMI; p <0.001) with significant reductions in door-to-CCL and CCL-to-balloon times as well. The majority of patients with field STEMI achieved D + B times of <90 minutes (80% field STEMI, 25% nonfield STEMI, 10% historical STEMI; p <0.001). In conclusion, this study demonstrates that prehospital electrocardiographic diagnosis of STEMI with activation of the CCL markedly reduces D + B time.

Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel.

OBJECTIVES The goal of this study was to identify factors associated with lower platelet inhibition (PI) with clopidogrel in subjects with cardiovascular disease (CVD). BACKGROUND A heterogeneous platelet reactivity response to clopidogrel exists, and the clinical or biochemical predictors of suboptimal PI with clopidogrel remain unclear. METHODS This study prospectively enrolled subjects with CVD requiring treatment with clopidogrel (75 mg daily for > or =7 days or 600-mg bolus > or =24 h before recruitment). A bedside rapid platelet function assay (VerifyNow, Acccumetrics, San Diego, California) to measure maximal and clopidogrel-mediated platelet reactivity was utilized, and factors associated with lower PI were identified. RESULTS A heterogeneous, normally distributed PI (mean 40.8 +/- 26.2%) response to clopidogrel was observed in 157 subjects (age 67.2 +/- 12.2 years; 59.9% men). Multiple variable analysis of clinical and biochemical factors known to affect platelet reactivity revealed lower PI in patients with an elevated plasma fibrinogen level (> or =375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (> or =25 kg/m(2)). On testing for interaction, elevated fibrinogen level was associated with diabetic status, resulting in lower PI in diabetic patients (23.9 +/- 3.9% vs. 45.1 +/- 4.5%, p < 0.001), but not nondiabetic patients (44.7 +/- 4.4% vs. 46.3 +/- 4.8%, p = 0.244). Increased BMI remained independently associated with lower PI after clopidogrel therapy regardless of diabetic status or fibrinogen level (36.8 +/- 9.0% vs. 49.0 +/- 7.0%, p < 0.001). CONCLUSIONS Elevated plasma fibrinogen (> or =375 mg/dl) in the presence of diabetes mellitus and increased BMI (> or =25 kg/m(2)) are associated with lower PI with clopidogrel in patients with CVD.

Correlation of left ventricular diastolic filling characteristics with right ventricular overload and pulmonary artery pressure in chronic thromboembolic pulmonary hypertension.

OBJECTIVES This study was designed to determine a quantitative relationship between right ventricular (RV) pressure overload and left ventricular (LV) diastolic filling characteristics in patients with chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND Right ventricular pressure overload in patients with CTEPH causes abnormal LV diastolic filling. However, a quantitative relationship between RV pressure overload and LV diastolic function has not been established. METHODS We analyzed pre- and postoperative diastolic mitral inflow velocities and right heart hemodynamic data in 39 consecutive patients with CTEPH over the age of 30 (55 +/- 11 years) with mean pulmonary artery pressure >30 mm Hg who underwent pulmonary thromboendarterectomy (PTE). RESULTS After PTE, mean pulmonary artery pressure (mPAP) decreased from 50 +/- 11 to 28 +/- 9 mm Hg (p < 0.001) while cardiac output (CO) increased from 4.4 +/- 1.1 to 5.7 +/- 0.9 l/m (p < 0.001). Mitral E/A ratio (E/A) increased from 0.74 +/- 0.22 to 1.48 +/- 0.69 (p < 0.001). E/A was < 1.25 in all patients pre-PTE. After PTE, all patients with E/A >1.50 had mPAP <35 mm Hg and CO >5.0 l/min. E/A correlated inversely with mPAP (r = 0.55, p < 0.001) and directly with CO (r = 0.53, p < 0.001). CONCLUSIONS E/A is consistently abnormal in patients with CTEPH and increases post-PTE. Moreover, E/A varies inversely with mPAP and directly with CO. Following PTE, E/A >1.5 correlates with the absence of severe pulmonary hypertension (mPAP >35 mm Hg) and the presence of normal cardiac output (> 5.0 l/m).

Clinical efficacy of drug-eluting stents in diabetic patients: a meta-analysis

OBJECTIVES The purpose of this study was to compare estimates for revascularization and major adverse cardiac events (MACE) (death, myocardial infarction, repeat revascularization) in diabetic patients treated with paclitaxel- and sirolimus-eluting stents (PES and SES). BACKGROUND Outcomes in diabetic patients treated with PES and SES have not been adequately evaluated. METHODS We searched MEDLINE/EMBASE from January 2002 to February 2007 and identified abstracts/presentations from this period at major cardiology conferences. Randomized controlled trials (RCTs) and registries were included if data for diabetic patients treated with PES or SES were available. Point estimates with 95% confidence intervals (CIs) were computed as summary statistics. RESULTS In RCTs (13 trials; n = 2,422) similar point estimates for target lesion revascularization (TLR) (PES: 8.6%, 95% CI 6.5% to 11.3%; SES: 7.6%, 95% CI 5.8% to 9.9%) and MACE (PES: 15.4%, 95% CI 12.4% to 19.1%; SES: 12.9%, 95% CI 8.5% to 19.2%) were observed. In head-to-head trials (4 RCTs), no difference in the likelihood of TLR (PES vs. SES) was observed (odds ratio [OR] 1.37, 95% CI 0.64 to 2.9, p = 0.42). In registries (16 registries; n = 10,156), point estimates for target vessel revascularization (TVR) (PES: 5.8%, 95% CI 3.9% to 8.5%; SES: 7.2%, 95% CI 4.6% to 11.2%) and MACE (PES: 10.1%, 95% CI 7.3% to 13.8%; SES: 11.9%, 95% CI 8.6% to 16.4%) were also similar. In registries reporting outcomes with both stents (8 registries for TVR and 7 registries for MACE), the likelihood of TVR (PES vs. SES) (OR 0.77, 95% CI 0.54 to 1.10, p = 0.15) and MACE (OR 0.83, 95% CI 0.68 to 1.01, p = 0.056) were nonsignificantly lower with PES. CONCLUSIONS This analysis of over 11,000 diabetic patients treated with drug-eluting stents demonstrates single-digit revascularization rates. Furthermore, revascularization and MACE estimates are similar with both PES and SES.

Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions.

The relationships between oxidation-specific epitopes (OSE) and lipoprotein (a) [Lp(a)] and progressive atherosclerosis and plaque rupture have not been determined. Coronary artery sections from sudden death victims and carotid endarterectomy specimens were immunostained for apoB-100, oxidized phospholipids (OxPL), apo(a), malondialdehyde-lysine (MDA), and MDA-related epitopes detected by antibody IK17 and macrophage markers. The presence of OxPL captured in carotid and saphenous vein graft distal protection devices was determined with LC-MS/MS. In coronary arteries, OSE and apo(a) were absent in normal coronary arteries and minimally present in early lesions. As lesions progressed, apoB and MDA epitopes did not increase, whereas macrophage, apo(a), OxPL, and IK17 epitopes increased proportionally, but they differed according to plaque type and plaque components. Apo(a) epitopes were present throughout early and late lesions, especially in macrophages and the necrotic core. IK17 and OxPL epitopes were strongest in late lesions in macrophage-rich areas, lipid pools, and the necrotic core, and they were most specifically associated with unstable and ruptured plaques. Specific OxPL were present in distal protection devices. Human atherosclerotic lesions manifest a differential expression of OSEs and apo(a) as they progress, rupture, and become clinically symptomatic. These findings provide a rationale for targeting OSE for biotheranostic applications in humans.

sirolimus eluting stents

The sirolimus-eluting stent (SES) Cypher was the first commercially available drug-eluting stent. The use of this stent has resulted in significantly lower rates of restenosis and lesion revascularization compared to bare metal stents and balloon angioplasty. In this review, angiographic and clinical outcomes in patients treated with SES are compared to those treated with bare metal stents and other drug-eluting stents. Furthermore, efficacy and safety outcomes of SES in complex lesions (left main stenosis, bifurcation lesions, chronic total occlusions, long lesions and small vessels) and high risk populations (diabetes and acute myocardial infarction) are presented.

Release and capture of bioactive oxidized phospholipids and oxidized cholesteryl esters during percutaneous coronary and peripheral arterial interventions in humans

OBJECTIVES This study sought to assess whether oxidized lipids are released downstream from obstructive plaques after percutaneous coronary and peripheral interventions using distal protection devices. BACKGROUND Oxidation of lipoproteins generates multiple bioactive oxidized lipids that affect atherothrombosis and endothelial function. Direct evidence of their role during therapeutic procedures, which may result in no-reflow phenomenon, myocardial infarction, and stroke, is lacking. METHODS The presence of specific oxidized lipids was assessed in embolized material captured by distal protection filter devices during uncomplicated saphenous vein graft, carotid, renal, and superficial femoral artery interventions. The presence of oxidized phospholipids (OxPL) and oxidized cholesteryl esters (OxCE) was evaluated in 24 filters using liquid chromatography, tandem mass spectrometry, enzyme-linked immunosorbent assays, and immunostaining. RESULTS Phosphatidylcholine-containing OxPL, including (1-palmitoyl-2-[9-oxo-nonanoyl] PC), representing a major phosphatidylcholine-OxPL molecule quantitated within plaque material, [1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphocholine], and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, were identified in the extracted lipid portion from all vascular beds. Several species of OxCE, such as keto, hydroperoxide, hydroxy, and epoxy cholesteryl ester derivatives from cholesteryl linoleate and cholesteryl arachidonate, were also present. The presence of OxPL was confirmed using enzyme-linked immunoassays and immunohistochemistry of captured material. CONCLUSIONS This study documents the direct release and capture of OxPL and OxCE during percutaneous interventions from multiple arterial beds in humans. Entrance of bioactive oxidized lipids into the microcirculation may mediate adverse clinical outcomes during therapeutic procedures.

Comparison by Meta-Analysis of Drug-Eluting Stents and Bare Metal Stents for Saphenous Vein Graft Intervention

This meta-analysis was undertaken to assess the efficacy and safety of drug-eluting stents (DESs) compared to bare metal stents (BMSs) in saphenous vein graft (SVG) interventions. DESs decrease the risk of target vessel revascularization in native coronary arteries compared to BMSs. The ideal treatment strategy in patients with SVG disease is unknown. A search of the published reports was conducted to identify studies that compared DESs and BMSs in SVG intervention with a minimum follow-up of 6 months. A total of 19 studies (2 randomized trials and 17 registries), including 3,420 patients who had undergone SVG intervention (DESs, n = 1,489 and BMS, n = 1,931), met the selection criteria. The mean length of follow-up was 20 + or - 12 months. Using the fixed effect model, target vessel revascularization was less frequently performed in patients who had undergone SVG intervention with a DES than with a BMS (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49 to 0.72). The incidence of myocardial infarction was lower in patients with a DES than in those with a BMS (OR 0.69, 95% CI 0.49 to 0.99). No differences were found in the risk of death (OR 0.78, 95% CI 0.59 to 1.02) or stent thrombosis (OR 0.41, 95% CI 0.15 to 1.11) between the 2 groups. In conclusion, these findings support the use of DESs in SVG lesions.

Comparison of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors in patients undergoing an invasive strategy: A meta-analysis of randomized clinical trials

OBJECTIVE This meta-analysis was performed to assess the efficacy and safety of bivalirudin compared with unfractionated heparin or enoxaparin plus glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Pharmacotherapy for patients undergoing PCI includes bivalirudin, heparin, and GP IIb/IIIa inhibitors. We sought to compare ischemic and bleeding outcomes with bivalirudin versus heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI. METHODS A literature search was conducted to identify fully published randomized trials that compared bivalirudin with heparin plus GP IIb/IIIa inhibitors in patients undergoing PCI. RESULTS A total of 19,772 patients in 5 clinical trials were included in the analysis (9785 patients received bivalirudin and 9987 patients received heparin plus GP IIb/IIIa inhibitors during PCI). Anticoagulation with bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in no difference in major adverse cardiovascular events (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96 to 1.19), death (OR 0.93, 95% CI 0.72 to 1.21), or urgent revascularization (OR 1.06, 95% CI 0.86 to 1.30). There is a trend towards a higher risk of myocardial infarction (OR 1.12, 95% CI 0.99 to 1.28) but a significantly lower risk of TIMI major bleeding with bivalirudin (OR 0.55, 95% CI 0.44 to 0.69). CONCLUSION In patients who undergo PCI, anticoagulation with bivalirudin as compared with unfractionated heparin or enoxaparin plus GP IIb/IIIa inhibitors results in similar ischemic adverse events but a reduction in major bleeding.