Off-label use of drug-eluting versus bare metal stents: a lesion-specific systematic review of long-term outcomes.

OBJECTIVE: The purpose of this systematic review was to evaluate differences in lesion-specific outcomes with the "off-label" use of drug-eluting stents (DES) versus bare metal stents (BMS). METHODS: MEDLINE, PubMed, the Cochrane databases, and other Web were searched for studies evaluating off-label use of DES and BMS with the same characteristics. Of 1,258 abstracts or manuscripts reviewed, 112 studies were included (total N = 23,438). Studies were excluded if patients received both types of stent or no stent; lesion type was unknown; lesion-specific outcomes for ≥6 months were unavailable; or <25 patients were enrolled. RESULTS: Overall mortality at 6-12 months was approximately 3% for BMS and DES for off-label use. Increase in mortality was greater from 6-12 months to 2 years with BMS than with DES (3.3%-9.1%; 2.8%-4.1%); however, rates were similar at 3 years (BMS: 18.8%; DES:15.3%). Myocardial Infarction rates were similar for both types at 6-12 months (BMS: 6.5%; DES: 6.0%). Overall rates of stent thrombosis were 1.8% and 1.7% for BMS and DES, respectively. Similar or slightly lower rates of stent thrombosis were seen for most lesion types, except higher rates for small vessels for BMS (5.2%) and true bifurcation for DES (3.3%). Rates of target lesion revascularization (TLR) were 7.5% for BMS and 19.6% for DES at 6-12 months. At 2-years TLR remained lower than DES. When the combined group was compared to registry data alone, similar values were seen. CONCLUSIONS: Rates of mortality, myocardial infarction (MI), and stent thrombosis were similar in patients receiving BMS or DES, while TLR rates were lower in DES patients.

Unrecognized non-Q-wave myocardial infarction: prevalence and prognostic significance in patients with suspected coronary disease.

BACKGROUND: Unrecognized myocardial infarction (UMI) is known to constitute a substantial portion of potentially lethal coronary heart disease. However, the diagnosis of UMI is based on the appearance of incidental Q-waves on 12-lead electrocardiography. Thus, the syndrome of non-Q-wave UMI has not been investigated. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can identify MI, even when small, subendocardial, or without associated Q-waves. The aim of this study was to investigate the prevalence and prognosis associated with non-Q-wave UMI identified by DE-CMR. METHODS AND FINDINGS: We conducted a prospective study of 185 patients with suspected coronary disease and without history of clinical myocardial infarction who were scheduled for invasive coronary angiography. Q-wave UMI was determined by electrocardiography (Minnesota Code). Non-Q-wave UMI was identified by DE-CMR in the absence of electrocardiographic Q-waves. Patients were followed to determine the prognostic significance of non-Q-wave UMI. The primary endpoint was all-cause mortality. The prevalence of non-Q-wave UMI was 27% (50/185), compared with 8% (15/185) for Q-wave UMI. Patients with non-Q-wave UMI were older, were more likely to have diabetes, and had higher Framingham risk than those without MI, but were similar to those with Q-wave UMI. Infarct size in non-Q-wave UMI was modest (8%+/-7% of left ventricular mass), and left ventricular ejection fraction (LVEF) by cine-CMR was usually preserved (52%+/-18%). The prevalence of non-Q-wave UMI increased with the extent and severity of coronary disease on angiography (p<0.0001 for both). Over 2.2 y (interquartile range 1.8-2.7), 16 deaths occurred: 13 in non-Q-wave UMI patients (26%), one in Q-wave UMI (7%), and two in patients without MI (2%). Multivariable analysis including New York Heart Association class and LVEF demonstrated that non-Q-wave UMI was an independent predictor of all-cause mortality (hazard ratio [HR] 11.4, 95% confidence interval [CI] 2.5-51.1) and cardiac mortality (HR 17.4, 95% CI 2.2-137.4). CONCLUSIONS: In patients with suspected coronary disease, the prevalence of non-Q-wave UMI is more than 3-fold higher than Q-wave UMI. The presence of non-Q-wave UMI predicts subsequent mortality, and is incremental to LVEF. TRIAL REGISTRATION: Clinicaltrials.gov NCT00493168.

Three-dimensional breathhold magnetization-prepared TrueFISP: a pilot study for magnetic resonance imaging of the coronary artery disease.

PURPOSE: X-ray angiography is currently the standard test for the assessment of coronary artery disease. A substantial minority of patients referred for coronary angiography have no significant coronary artery disease. The purpose of this work was the evaluation of the accuracy of a three-dimensional (3D) breathhold coronary magnetic resonance angiography (MRA) technique in detecting hemodynamically significant coronary artery stenoses in a patient population with x-ray angiographic correlation. MATERIALS AND METHODS: Sequential subjects (n = 33, M/F = 22/11, average age = 57) who were referred for conventional coronary angiography were enrolled in the study. The study protocol was approved by our institutional review board. Each subject gave written informed consent. Volume-targeted 3D breathhold coronary artery scans with ECG-triggered, segmented True Fast Imaging with Steady-state Precession (TrueFISP) were acquired for the left main (LM), left anterior descending (LAD), and right coronary arteries (RCAs). Coronary MRA was evaluated with conventional angiography as the gold standard. RESULTS: The overall sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing any hemodynamically significant coronary artery disease (> or =50% diameter reduction) with coronary MRA was 87%, 57%, 72%, 68%, and 80%, respectively. The sensitivity of the technique in the LM, LAD, and RCA was 100%, 83%, and 100%, respectively. The NPV of the technique in the LM, LAD, and RCA was 100%, 82%, and 100%, respectively. CONCLUSIONS: Three-dimensional breathhold True Fast Imaging with Steady-state Precession is a promising technique for coronary artery imaging. It has a relatively high sensitivity and NPV. Results of this study warrant further technical improvements and clinical evaluation of the technique.

Outcomes and complications associated with off-label and untested use of drug-eluting stents.

CONTEXT: Limited data exist regarding use of drug-eluting stents outside of approved indications in real-world settings. OBJECTIVES: To determine the frequency, safety, and effectiveness of drug-eluting stents for off-label (restenosis, bypass graft lesion, long lesions, vessel size outside of information for use recommendation) and untested (left main, ostial, bifurcation, or total occlusion lesions) indications in percutaneous coronary intervention (PCI). DESIGN, SETTING, AND PATIENTS: Observational, prospective, multicenter registry to evaluate in-hospital, 30-day, and 1-year outcomes among patients undergoing PCI between January and June 2005 in 140 US academic and community medical centers. Of 7752 PCI-treated patients, 6993 (90%) received drug-eluting stents; of these, 5851 (84%) received no other devices. Standard, off-label, and untested use was determined in 5541 (95%) of these 5851 patients, constituting the study cohort. MAIN OUTCOME MEASURES: Frequency of off-label and untested use, 1-year repeat target vessel revascularization, and composite of death, myocardial infarction (MI), or stent thrombosis at in-hospital follow-up and during 1 year of follow-up. RESULTS: Of 5541 patients receiving drug-eluting stents, 2588 (47%) received stents for off-label or untested indications. Adjusted in-hospital risk of death, MI, or stent thrombosis was not statistically different with off-label or untested vs standard use. At 30 days, the risk of this composite end point was significantly higher with off-label use (adjusted hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.24-3.48; P = .005) but not untested use (adjusted HR, 1.45; 95% CI, 0.79-2.67; P = .23). Excluding early events, this end point was not different at 1 year with off-label use (adjusted HR, 1.10; 95% CI, 0.79-1.54; P = .57) or untested use (adjusted HR, 0.91; 95% CI, 0.60-1.38; P = .66). At 1 year, compared with standard use, significantly higher rates of target vessel revascularization were associated with off-label use (adjusted HR, 1.49; 95% CI, 1.13-1.98; P = .005) and untested use (adjusted HR, 1.49; 95% CI, 1.10-2.02; P = .01), although absolute rates were low (standard, 4.4% [n = 113]; off-label, 7.6% [n = 95]; untested, 6.7% [n = 72]). CONCLUSIONS: In contemporary US practice, off-label and untested use of drug-eluting stents is common. Compared with standard use, relative early safety is lower with off-label use, and the long-term effectiveness is lower with both off-label and untested use. However, the absolute event rates remain low.

Coronary magnetic resonance angiography using magnetization-prepared contrast-enhanced breath-hold volume-targeted imaging (MPCE-VCATS).

OBJECTIVES: Coronary artery x-ray angiography (XRA) is currently the gold standard for the assessment of coronary artery disease. A substantial minority of patients referred for coronary angiography have no significant coronary artery disease. The purpose of this study is to evaluate magnetization-prepared contrast-enhanced breath-hold volume-targeted imaging (MPCE-VCATS), a new 3-dimensional breath-hold coronary magnetic resonance angiography (MRA) technique, in detecting hemodynamically significant coronary artery stenoses in a patient population, with XRA correlation. MATERIALS AND METHODS: A total of 19 subjects who were referred for conventional coronary angiography were enrolled in the study. ECG-triggered MPCE-VCATS coronary artery scans were acquired for the left main coronary artery (LCA), left anterior descending (LAD), and right coronary artery (RCA). Coronary MRA and XRA results were compared. RESULTS: The overall sensitivity, accuracy, and negative predictive value for diagnosing any hemodynamically significant coronary artery disease (> or =50% diameter reduction) was 91%, 80%, and 90%, respectively. The sensitivity of the technique in the LCA, LAD, and RCA was 100%, 100% and 78%, respectively. The negative predictive value of the technique was 100%, 100%, and 71%, respectively. DISCUSSION: MPCE-VCATS is a promising technique for coronary artery imaging. It has a relatively high sensitivity as well as a high NPV. The results of the study may indicate a future role for the technique in obviating the need for some patients to undergo XRA.

A comparison of arterial closure devices to manual compression in liver transplantation candidates undergoing coronary angiography.

Whether arterial closure devices can be used safely in a coagulopathic population undergoing cardiac catheterization and at high risk for groin complications, such as liver transplant candidates, is unknown. In this prospective, non-randomized consecutive series of 80 liver transplant candidates undergoing coronary angiography, manual compression and arterial closure devices were compared. Ilio-femoral angiography was performed to determine suitability for use of the closure device. Bleeding and vascular complications were recorded along with time to ambulation. Arterial closure devices were used in 31 patients (39%), whereas manual compression was used in 49 patients (50 procedures) (61%). There were no significant differences between the two groups with respect to age, sex, cardiac risk factors, peripheral vascular disease, baseline platelet count or baseline INR. There were 10 total vascular complications out of 50 procedures (20%) in the manual compression group compared to 2 vascular complications out of 31 procedures in the arterial closure device group (6%; p = 0.12). The time to ambulation was significantly less in the group receiving arterial closure devices versus manual compression (4.2 1.8 hours versus 6.6 3.7 hours, respectively; p = 0.0003). In coagulopathic patients at higher risk for groin complications, arterial closure devices can be safely used and decrease time to ambulation compared to manual compression.

Clinical experience and patient outcomes associated with the TandemHeart percutaneous transseptal assist device among a heterogeneous patient population.

There is a paucity of literature describing the outcomes associated with the use of TandemHeart percutaneous ventricular assist device (PVAD). The literature is limited by analyzing only subsets of patients. We present the clinical outcomes and safety associated with the use of TandemHeart among a series of heterogeneous patients requiring PVAD support. We reviewed the clinical experience, hemodynamic variables, survival outcomes, and complications associated with the implantation of TandemHeart support device among 25 patients presenting to our institution. Indications for PVAD implantation were cardiogenic shock (56%), ST-segment elevation myocardial infarction (STEMI) (20%), postpericardiotomy (16%), and high-risk percutaneous coronary interventions (PCI) or ventricular tachycardia (VT) ablation (8%). TandemHeart was used for an average of 4.8 ± 2.1 days and demonstrated significant hemodynamic improvements (pre- and postimplantation left ventricular ejection fractions were 21.5% ± 15% and 24.5% ± 10.5%, respectively [p = 0.06]). The cardiac index improved from a mean 2.04 ± 075 L/min/m² to 2.45 ± 073 L/min/m² (p = 0.09). The mixed venous oxygen saturation (SVO2) increased from 55.14 ± 13.34 to 66.43 ± 7.43 (p = 0.008) after implantation. TandemHeart was used as a bridge to left ventricular assist device implantation (44%) or recovery (20%). Thirty-six percent of patients died on support or shortly after PVAD removal. Thirty, 90-day, and long-term (>90 days) survival rates were 56%, 52%, and 36%, respectively. Procedure-related complications were reported in 13 patients (56%), and the majority (90%) was related to vascular access (bleeding or pseudoaneurysm). The TandemHeart device is a safe therapeutic option as a bridge-to-recovery or bridge-to-bridge for patients with hemodynamic compromise regardless of the etiology. The favorable hemodynamic profile, postimplantation survival rates, and manageable complications support its use to assist hemodynamic recovery in patients refractory to conventional therapy.

Determinants of myocardial salvage during acute myocardial infarction: evaluation with a combined angiographic and CMR myocardial salvage index.

OBJECTIVES: This study examined the contribution of symptom-to-reperfusion time, collateral flow, and antegrade flow in the infarct-related artery on myocardial salvage using a combined angiographic-cardiac magnetic resonance (CMR) method. BACKGROUND: The myocardium supplied by an acutely occluded artery defines the anatomical area at risk for infarction. This area can be determined independently of residual coronary flow to the risk region. Moreover, the difference between this area and infarct size constitutes viable myocardium that has been salvaged. METHODS: In 121 subjects presenting with ST-segment elevation myocardial infarction revascularized by primary percutaneous intervention, the angiographic anatomical area at risk was retrospectively measured using the Bypass Angioplasty Revascularization Investigation Myocardial Jeopardy Index (BARI score). Within 1 week, CMR was performed in the entire cohort and repeated in 89 subjects at 5 +/- 3 months to determine infarct size and wall motion recovery. The myocardial salvage index (MSI) was computed as (BARI score - infarct size)/left ventricular mass. RESULTS: The MSI was negligible in patients with Thrombolysis In Myocardial Infarction (TIMI) flow grade < or =1, absent collateral vessels, and >4 h of symptom-to-reperfusion time, as compared with patients with TIMI flow grade >1 or existent collateral vessels (0.2 +/- 1.0 vs. 6.1 +/- 2.0, p < 0.001). The initial TIMI flow grade, time to reperfusion, presence of microvascular obstruction, and collateral flow were found to be independent predictors of MSI and infarct transmurality (p < 0.05 for both). The BARI score was only predictive of MSI (p < 0.001). The MSI correlated inversely with wall motion score at baseline (R = -0.27, p < 0.01) and at follow-up (R = -0.38, p < 0.001). Infarct transmurality also correlated with wall motion score at baseline (R = 0.52, p < 0.001) and at follow-up (R = 0.58, p < 0.001). Increasing MSI (p < 0.01) and decreasing infarct transmurality (p < 0.001) were associated with an improvement in wall motion and prognosis. CONCLUSIONS: Early mechanical reperfusion and maintenance of antegrade or collateral flow independently preserves myocardial salvage primarily through a reduction in infarct transmurality. This novel integration of coronary angiography and CMR techniques to quantify myocardial salvage predicts functional recovery and improved prognosis.

Angiographic and magnetic resonance imaging evaluation of in-hospital delay in primary percutaneous intervention delivery on myocardial salvage.

Shortening symptom-to-reperfusion time improves prognosis in patients with ST-segment elevation myocardial infarction. Accordingly, current guidelines target a door-to-balloon time <90 minutes, irrespective of symptom-to-door time; nevertheless, the relation between door-to-balloon and symptom-to-door time and its potential impact on myocardial salvage remains largely unknown. We investigated the influence of door-to-balloon guideline fulfillment on myocardial salvage in patients presenting with different symptom-to-door times. Contrast-enhanced magnetic resonance study was performed acutely to measure infarct size in 172 patients admitted for primary percutaneous coronary intervention of their first ST-segment elevation myocardial infarction to 2 tertiary hospitals. The Bari score was adapted to quantify the angiographic area at risk, and the myocardial salvage index (MSI) was computed as percent area at risk that spared necrosis. Increased symptom-to-balloon time was associated with a significant decrease in MSI only within the first 5 hours (p <0.001). Accomplishment of a target door-to-balloon <90 minutes was associated with a significant increase in MSI only in patients presenting within the first hour of symptom onset (48.5 ± 30.9 vs 29.6 ± 22.3%, p <0.05). Achieving a door-to-balloon time <60 minutes further increased MSI in patients presenting within the second hour of symptoms (43.5 ± 8.6 vs 26.3 ± 20.5%, p <0.01). In conclusion, myocardial salvage progressively decreases up to 5 hours after symptom onset. However, the benefit of the recommended door-to-balloon time appears to be confined to patients presenting within 1 hour of symptom onset.

Drug-eluting versus bare-metal stents in unprotected left main coronary artery stenosis a meta-analysis.

OBJECTIVES: We undertook a meta-analysis to assess outcomes for drug-eluting stents (DES) and bare-metal stents (BMS) in percutaneous coronary intervention for unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND: Uncertainty exists regarding the relative performance of DES versus BMS in percutaneous coronary intervention for unprotected left main coronary stenosis. METHODS: Of a total of 838 studies, 44 met inclusion criteria (n = 10,342). The co-primary end points were mortality, myocardial infarction (MI), target vessel/lesion revascularization (TVR/TLR), and major adverse cardiac events (MACE: mortality, MI, TVR/TLR). RESULTS: Event rates for DES and BMS were calculated at 6 to 12 months, at 2 years, and at 3 years. Crude event rates at 3 years were mortality (8.8% and 12.7%), MI (4.0% and 3.4%), TVR/TLR (8.0% and 16.4%), and MACE (21.4% and 31.6%). Nine studies were included in a comparative analysis (n = 5,081). At 6 to 12 months the adjusted odds ratio (OR) for DES versus BMS were: mortality 0.94 (95% confidence interval [CI]: 0.06 to 15.48; p = 0.97), MI 0.64 (95% CI: 0.19 to 2.17; p = 0.47), TVR/TLR 0.10 (95% CI: 0.01 to 0.84; p = 0.01), and MACE 0.34 (95% CI: 0.15 to 0.78; p = 0.01). At 2 years, the OR for DES versus BMS were: mortality 0.42 (95% CI: 0.28 to 0.62; p < 0.01), MI 0.16 (95% CI: 0.01 to 3.53; p = 0.13), and MACE 0.31 (95% CI: 0.15 to 0.66; p < 0.01). At 3 years, the OR for DES versus BMS were: mortality 0.70 (95% CI: 0.53 to 0.92; p = 0.01), MI 0.49 (95% CI: 0.26 to 0.92; p = 0.03), TVR/TLR 0.46 (95% CI: 0.30 to 0.69; p < 0.01), and MACE 0.78 (95% CI: 0.57 to 1.07; p = 0.12). CONCLUSIONS: Our meta-analysis suggests that DES is associated with favorable outcomes for mortality, MI, TVR/TLR, and MACE as compared to BMS in percutaneous coronary intervention for unprotected left main coronary artery stenosis.

Detection of stent fractures: a comparison of 64-slice CT, conventional cine-angiography, and intravascular ultrasonography.

RATIONAL AND OBJECTIVES: We evaluated the ability of 64-slice computed tomography (CT), conventional cine-angiography, and intravascular ultrasound (IVUS) to detect stent fractures under ideal conditions. Coronary stent fracture has been implicated as one of the mechanisms of stent thrombosis and, perhaps, in-stent restenosis. However, the preferred imaging modality in detecting fractures in coronary stents has not been well established. MATERIALS AND METHODS: Four different types of commonly used coronary stents (Cypher, Taxus, Vision, Hepacoat) each with three strut fractures (Cypher, 5; Taxus, 5; Vision, 4; Hepacoat, 5) were nominally deployed in polyurethane tubes and imaged with 64-slice CT, conventional cine-angiography, and IVUS. For each stent type, an unfractured control stent was also imaged. RESULTS: Overall accuracy (84.1% vs. 73.9%), sensitivity (80.7 vs. 77.2%), and specificity (100% vs. 58.3%) for stent fracture detection was higher with 64 multislice CT compared to conventional cine-angiography. Stent fractures were not accurately detected by IVUS. Fracture detection by multislice CT was best when the stents were imaged at 45 degrees to the z-axis. CONCLUSIONS: Under ideal in vitro conditions, CT has a high accuracy when used to evaluate coronary stent fractures. The overall accuracy, sensitivity, and specificity of detecting stent fractures are lower by conventional cine-angiography. Stent fractures were not detected using IVUS.

Correspondence between the 17-segment model and coronary arterial anatomy using contrast-enhanced cardiac magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to investigate the correspondence between the coronary arterial anatomy and supplied myocardium based on the proposed American Heart Association 17-segment model. BACKGROUND: Standardized assignment of coronary arteries to specific myocardial segments is currently based on empirical assumptions. METHODS: A cardiac magnetic resonance study was performed in 93 subjects following acute myocardial infarction treated with primary percutaneous coronary intervention. Two observers blindly reviewed all angiograms to examine the location of the culprit lesion and coronary dominance. Two additional observers scored for the presence of cardiac magnetic resonance hyperenhancement (HE) on a 17-segment model. Segments were divided based on anatomical landmarks such as the interventricular grooves and papillary muscles. RESULTS: In a per-segment analysis, 23% of HE segments were discordant with the empirically assigned coronary distribution. Presence of HE in the basal anteroseptal, mid-anterior, mid-anteroseptal, or apical anterior wall was 100% specific for left anterior descending artery occlusion. The left anterior descending artery infarcts frequently involved the mid-anterolateral, apical lateral, and apical inferior walls. No segment was 100% specific for right coronary artery or left circumflex artery (LCX) occlusion, although HE in the basal anterolateral wall was highly specific (98%) for LCX occlusion. Combination of HE in the anterolateral and inferolateral walls was 100% specific for a LCX occlusion, and when extended to the inferior wall, was also 100% specific for a dominant or codominant LCX occlusion. CONCLUSIONS: Four segments were completely specific for left anterior descending artery occlusion. No segment can be exclusively attributed to the right coronary artery or LCX occlusion. However, analysis of adjacent segments increased the specificity for a given coronary occlusion. These findings bring objective evidence in the appropriate segmentation of coronary arterial perfusion territories and assist accurate assignment of the culprit vessel in various imaging modalities.

Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging.

AIMS: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk. METHODS AND RESULTS: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA. CONCLUSION: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.