Steven D. Wolff

Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial Infarction The INFUSE-AMI Randomized Trial

CONTEXT Thrombus embolization during percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) is common and results in suboptimal myocardial perfusion and increased infarct size. Two strategies proposed to reduce distal embolization and improve outcomes after primary PCI are bolus intracoronary abciximab and manual aspiration thrombectomy. OBJECTIVE To determine whether bolus intracoronary abciximab, manual aspiration thrombectomy, or both reduce infarct size in high-risk patients with STEMI. DESIGN, SETTING, AND PATIENTS Between November 28, 2009, and December 2, 2011, 452 patients presenting at 37 sites in 6 countries within 4 hours of STEMI due to proximal or mid left anterior descending artery occlusion undergoing primary PCI with bivalirudin anticoagulation were randomized in an open-label, 2 x 2 factorial design to bolus intracoronary abciximab delivered locally at the infarct lesion site vs no abciximab and to manual aspiration thrombectomy vs no thrombectomy. INTERVENTIONS A 0.25-mg/kg bolus of abciximab was administered at the site of the infarct lesion via a local drug delivery catheter. Manual aspiration thrombectomy was performed with a 6 F aspiration catheter. MAIN OUTCOME MEASURES Primary end point: infarct size (percentage of total left ventricular mass) at 30 days assessed by cardiac magnetic resonance imaging (cMRI) in the abciximab vs no abciximab groups (pooled across the aspiration randomization); major secondary end point: 30-day infarct size in the aspiration vs no aspiration groups (pooled across the abciximab randomization). RESULTS Evaluable cMRI results at 30 days were present in 181 and 172 patients randomized to intracoronary abciximab vs no abciximab, respectively, and in 174 and 179 patients randomized to manual aspiration vs no aspiration, respectively. Patients randomized to intracoronary abciximab compared with no abciximab had a significant reduction in 30-day infarct size (median, 15.1%; interquartile range [IQR], 6.8%-22.7%; n = 181, vs 17.9% [IQR, 10.3%-25.4%]; n = 172; P = .03). Patients randomized to intracoronary abciximab also had a significant reduction in absolute infarct mass (median, 18.7 g [IQR, 7.4-31.3 g]; n = 184, vs 24.0 g [IQR, 12.1-34.2 g]; n = 175; P = .03) but not abnormal wall motion score (median, 7.0 [IQR, 2.0-10.0]; n = 188, vs 8.0 [IQR, 3.0-10.0]; n = 184; P = .08). Patients randomized to aspiration thrombectomy vs no aspiration had no significant difference in infarct size at 30 days (median, 17.0% [IQR, 9.0%-22.8%]; n = 174, vs 17.3% [IQR, 7.1%-25.5%]; n = 179; P = .51), absolute infarct mass (median, 20.3 g [IQR, 9.7-31.7 g]; n = 178, vs 21.0 g [IQR, 9.1-34.1 g]; n = 181; P = .36), or abnormal wall motion score (median, 7.5 [IQR, 2.0-10.0]; n = 186, vs 7.5 [IQR, 2.0-10.0]; n = 186; P = .89). CONCLUSION In patients with large anterior STEMI presenting early after symptom onset and undergoing primary PCI with bivalirudin anticoagulation, infarct size at 30 days was significantly reduced by bolus intracoronary abciximab delivered to the infarct lesion site but not by manual aspiration thrombectomy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00976521.

Baseline Correction of Phase Contrast Images Improves Quantification of Blood Flow in the Great Vessels

PURPOSE Phase-contrast Cardiovascular Magnetic Resonance Imaging (CMR) generally requires the analysis of stationary tissue adjacent to a blood vessel to serve as a baseline reference for zero velocity. However, for the heart and great vessels, there is often no stationary tissue immediately adjacent to the vessel. Consequently, uncorrected velocity offsets may introduce substantial errors in flow quantification. The purpose of this study was to assess the magnitude of these flow errors and to validate a clinically applicable method for their correction. MATERIALS AND METHODS In 10 normal volunteers, phase-contrast CMR was used to quantify blood flow in the main pulmonary artery (Qp) and the aorta (Qs). Following image acquisition, phase contrast CMR was performed on a stationary phantom using identical acquisition parameters so as to provide a baseline reference for zero velocity. Aortic and pulmonary blood flow was then corrected using the offset values from the phantom. RESULTS The mean difference between pulmonary and aortic flow was 26 +/- 21 mL before correction and 7.1 +/- 6.6 mL after correction (p = 0.002). The measured Qp/Qs was 1.25 +/- 0.20 before correction and 1.05 +/- 0.07 after correction (p = 0.001). CONCLUSION Phase-contrast CMR can have substantial errors in great vessel flow quantification if there is no correction for velocity offset errors. The proposed method of correction is clinically applicable and provides a more accurate measurement of blood flow.

Discordance between echocardiography and MRI in the assessment of mitral regurgitation severity: a prospective multicenter trial.

BACKGROUND The decision to undergo mitral valve surgery is often made on the basis of echocardiographic criteria and clinical assessment. Recent changes in treatment guidelines recommending surgery in asymptomatic patients make the accurate assessment of mitral regurgitation (MR) severity even more important. OBJECTIVES The purpose of this study was to compare echocardiography and magnetic resonance imaging (MRI) in the assessment of MR severity using the degree of left ventricular (LV) remodeling after surgery as the reference standard. METHODS In this prospective multicenter trial, MR severity was assessed in 103 patients using both echocardiography and MRI. Thirty-eight patients subsequently had isolated mitral valve surgery, and 26 of these had an additional MRI performed 5 to 7 months after surgery. The pre-surgical estimate of regurgitant severity was correlated with the postoperative decrease in LV end-diastolic volume. RESULTS Agreement between MRI and echocardiographic estimates of MR severity was modest in the overall cohort (r = 0.6; p < 0.0001), and there was a poorer correlation in the subset of patients sent for surgery (r = 0.4; p = 0.01). There was a strong correlation between post-surgical LV remodeling and MR severity as assessed by MRI (r = 0.85; p < 0.0001), and no correlation between post-surgical LV remodeling and MR severity as assessed by echocardiography (r = 0.32; p = 0.1). CONCLUSIONS The data suggest that MRI is more accurate than echocardiography in assessing the severity of MR. MRI should be considered in those patients when MR severity as assessed by echocardiography is influencing important clinical decisions, such as the decision to undergo MR surgery.

Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator

Background The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter–defibrillator (ICD) that was “non–MRI‐conditional” (i.e., not approved by the Food and Drug Administration for MRI scanning). Methods Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. Results MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self‐terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P‐wave and R‐wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. Conclusions In this study, device or lead failure did not occur in any patient with a non–MRI‐conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361.)

Correlation of Aortic Valve Area Obtained by the Velocity-Encoded Phase Contrast Continuity Method to Direct Planimetry using Cardiovascular Magnetic Resonance

BACKGROUND Aortic stenosis (AS) is the most common valvular heart disease resulting in surgical intervention. Transthoracic echocardiography (TTE) utilizing the continuity equation is commonly used to determine aortic valve area (AVA). However, sometimes TTE can be limited by poor acoustic windows, heavy valvular calcification, or eccentric jet morphology. Cardiovascular magnetic resonance (CMR) provides an alternative non-invasive method for the evaluation of AVA using direct planimetry. Prior studies have shown good correlation between CMR and other modalities, such as TTE, TEE, and cardiac catheterization. CMR can also assess AVA by using the continuity equation employing velocity-encoded phase contrast (VEPC) imaging. We sought to assess whether velocity-encoded phase-contrast MRI can provide an alternate means of quantifying AVA by CMR. METHODS Twenty-two consecutive AS patients were imaged with CMR. AVA was determined by VEPC imaging and by direct planimetry. RESULTS Mean AVA by planimetry was 1.05+/-0.41 cm2 and 1.00+/-0.4 cm2 by VEPC, with a strong correlation (R2=0.86, p<0.0001) between the two methods. The mean difference of AVA was 0.05+/-0.15 (95% CI=[0.02-0.08]), and the limits of agreement were -0.26 to 0.36 cm2. The mean difference between 2 observers for planimetry was 0.030+/-0.07 (95% CI=[0.02-0.04]) with limits of agreement of -0.11 to 0.16 cm2 and for VEPC was 0.008+/-0.085 (95% CI=[-0.01-0.026]) with limits of agreement of -0.16 to 0.18 cm2. CONCLUSIONS VEPC CMR is an alternative method to direct planimetry for accurately determining AVA. Both techniques can be easily incorporated into a single CMR exam to increase the confidence of AVA determination utilizing cardiac magnetic resonance imaging.

Intralesional Abciximab and Thrombus Aspiration in Patients With Large Anterior Myocardial Infarction One-Year Results From the INFUSE-AMI Trial

Background—Whether intralesional abciximab administration and thrombus aspiration confer clinical benefits to patients undergoing primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction is controversial. Methods and Results—A total of 452 patients with ST-segment–elevation myocardial infarction caused by proximal or mid left anterior descending artery occlusion undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation were randomized in a 2×2 factorial design to bolus abciximab delivered locally at the infarct lesion site versus no abciximab and to manual thrombus aspiration versus no aspiration. Treatment with intralesional abciximab, thrombus aspiration, or both therapies compared with no active therapy before stent implantation resulted in lower 1-year rates of death (4.5% versus 10.4%; P=0.03), severe heart failure (4.2% versus 10.3%; P=0.02), and stent thrombosis (0.9% versus 3.8%; P=0.046). Between 30 days and 1 year of follow-up, treatment with intralesional abciximab compared with no abciximab was associated with a lower rate of death (1.4% versus 4.9%; P=0.04) and composite major adverse ischemic events (3.3% versus 7.8%; P=0.04), with nonsignificantly different overall 1-year rates of mortality, composite ischemic events, and heart failure–related events. Thrombus aspiration compared with no aspiration was associated with lower rates of new-onset severe heart failure between 30 days and 1 year (0.9% versus 4.5%; P=0.02) and of rehospitalization for heart failure from randomization to 1 year (0.9% versus 5.4%; P=0.0008), with nonsignificantly different rates of mortality. Conclusions—Intralesional abciximab and thrombus aspiration may have long-term benefits in patients with anterior ST-segment–elevation myocardial infarction presenting early after symptom onset and undergoing primary percutaneous coronary intervention with bivalirudin anticoagulation. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00976521.

Rationale and design of the INFUSE-AMI study: A 2 × 2 factorial, randomized, multicenter, single-blind evaluation of intracoronary abciximab infusion and aspiration thrombectomy in patients undergoing percutaneous coronary intervention for anterior ST-segment elevation myocardial infarction

BACKGROUND Whether thrombus aspiration and local glycoprotein IIb/IIIa administration reduce infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been established in multicenter studies. DESIGN INFUSE-AMI is a multicenter, open-label, controlled, single-blind randomized study enrolling 452 subjects with anterior STEMI and an occluded proximal or mid-left anterior descending artery with thrombosis in myocardial infarction 0, 1, or 2 grade flow undergoing primary PCI with bivalirudin anticoagulation. Subjects are randomized in a 2 × 2 factorial to one of the following 4 arms: (1) local infusion of abciximab using the ClearWay RX Local Therapeutic Infusion Catheter (ClearWay, Atrium Medical Corp, Hudson, NH) after aspiration with a 6F Export Aspiration Catheter (Medtronic, Inc, Minneapolis, MN), (2) local infusion of abciximab using the ClearWay RX Infusion Catheter and no aspiration, (3) no local infusion of abciximab and aspiration with a 6F Export Aspiration Catheter, or (4) no local infusion of abciximab and no aspiration. The primary end point is infarct size (percentage of total left ventricular mass) at 30 days measured by cardiac magnetic resonance imaging. Other secondary end points include microvascular obstruction by cardiac magnetic resonance imaging at 5 days, ST-segment resolution, angiographic myocardial perfusion, thrombus burden, angiographic complications, and clinical events through 1-year follow-up. Safety end points include major and minor bleeding. SUMMARY INFUSE-AMI is testing the hypothesis that the intracoronary administration of an abciximab bolus with or without thrombus aspiration before stent implantation compared to no infusion with or without thrombus aspiration reduces infarct size among patients undergoing primary PCI for anterior STEMI who are treated with bivalirudin.

Quantification of left ventricular remodeling in response to isolated aortic or mitral regurgitation

BackgroundThe treatment of patients with aortic regurgitation (AR) or mitral regurgitation (MR) relies on the accurate assessment of the severity of the regurgitation as well as its effect on left ventricular (LV) size and function. Cardiovascular Magnetic Resonance (CMR) is an excellent tool for quantifying regurgitant volumes as well as LV size and function. The 2008 AHA/ACC management guidelines for the therapy of patients with AR or MR only describe LV size in terms of linear dimensions (i.e. end-diastolic and end-systolic dimension). LV volumes that correspond to these linear dimensions have not been published in the peer-reviewed literature. The purpose of this study is to determine the effect of regurgitant volume on LV volumes and chamber dimensions in patients with isolated AR or MR and preserved LV function.MethodsRegurgitant volume, LV volume, mass, linear dimensions, and ejection fraction, were determined in 34 consecutive patients with isolated AR and 23 consecutive patients with MR and no other known cardiac disease.ResultsThere is a strong, linear relationship between regurgitant volume and LV end-diastolic volume index (aortic regurgitation r2 = 0.8, mitral regurgitation r2 = 0.8). Bland-Altman analysis of regurgitant volume shows little interobserver variation (AR: 0.6 ± 4 ml; MR 4 ± 6 ml). The correlation is much poorer between regurgitant volume and commonly used clinical linear measures such as end-systolic dimension (mitral regurgitation r2 = 0.3, aortic regurgitation r2 = 0.5). For a given regurgitant volume, AR causes greater LV enlargement and hypertrophy than MR.ConclusionCMR is an accurate and robust technique for quantifying regurgitant volume in patients with AR or MR. Ventricular volumes show a stronger correlation with regurgitant volume than linear dimensions, suggesting LV volumes better reflect ventricular remodeling in patients with isolated mitral or aortic regurgitation. Ventricular volumes that correspond to published recommended linear dimensions are determined to guide the timing of surgical intervention.

Utilization and likelihood of radiologic diagnostic imaging in patients with implantable cardiac defibrillators.

To examine imaging utilization in a matched cohort of patients with and without implantable cardioverter defibrillators (ICD) and to project magnetic resonance imaging (MRI) utilization over a 10‐year period.

Effect of bismuth breast shielding on radiation dose and image quality in coronary CT angiography

BackgroundCoronary computed tomographic angiography (CCTA) is associated with high radiation dose to the female breasts. Bismuth breast shielding offers the potential to significantly reduce dose to the breasts and nearby organs, but the magnitude of this reduction and its impact on image quality and radiation dose have not been evaluated.MethodsRadiation doses from CCTA to critical organs were determined using metal-oxide-semiconductor field-effect transistors positioned in a customized anthropomorphic whole-body dosimetry verification phantom. Image noise and signal were measured in regions of interest (ROIs) including the coronary arteries.ResultsWith bismuth shielding, breast radiation dose was reduced 46%-57% depending on breast size and scanning technique, with more moderate dose reduction to the heart, lungs, and esophagus. However, shielding significantly decreased image signal (by 14.6 HU) and contrast (by 28.4 HU), modestly but significantly increased image noise in ROIs in locations of coronary arteries, and decreased contrast-to-noise ratio by 20.9%.ConclusionsWhile bismuth breast shielding can significantly decrease radiation dose to critical organs, it is associated with an increase in image noise, decrease in contrast-to-noise, and changes tissue attenuation characteristics in the location of the coronary arteries.