Robert Manka

Prognostic Value of Cardiac Magnetic Resonance Stress Tests Adenosine Stress Perfusion and Dobutamine Stress Wall Motion Imaging

Background— Adenosine stress magnetic resonance perfusion (MRP) and dobutamine stress magnetic resonance (DSMR) wall motion analyses are highly accurate for the detection of myocardial ischemia. However, knowledge about the prognostic value of stress MR examinations is limited. We sought to determine the value of MRP and DSMR, as assessed during a single-session examination, in predicting the outcome of patients with known or suspected coronary artery disease. Methods and Results— In 513 patients (with known or suspected coronary disease, prior coronary artery bypass graft, or percutaneous coronary intervention), a combined single-session magnetic resonance stress examination (MRP and DSMR) was performed at 1.5 T. For first-pass perfusion imaging, the standard adenosine stress imaging protocol (140 &mgr;g · kg−1 · min−1 for 6 minutes, 3-slice turbo field echo-echo-planar imaging or steady-state free precession sequence, 0.05 mmol/kg Gd-DTPA) was applied, and for DSMR, the standard high-dose dobutamine/atropine protocol (steady-state free-precession cine sequence) was applied. Stress testing was classified as pathological if at MRP ≥1 segment showed an inducible perfusion deficit >25% transmurality or if at DSMR ≥1 segment showed an inducible wall motion abnormality. During a median follow-up of 2.3 years (range, 0.06 to 4.55 years), 19 cardiac events occurred (4.1%; 9 cardiac deaths, 10 nonfatal myocardial infarctions). The 3-year event-free survival was 99.2% for patients with normal MRP and DSMR and 83.5% for those with abnormal MRP and DSMR. Univariate analysis showed ischemia identified by MRP and DSMR to be predictive of cardiac events (hazard ratio, 12.51; 95% confidence interval, 3.64 to 43.03; and hazard ratio, 5.42; 95% confidence interval, 2.18 to 13.50; P<0.001, respectively); other predictors were diabetes mellitus, known coronary artery disease, and the presence of resting wall motion abnormality. By multivariate analysis, ischemia on magnetic resonance stress testing (MRP or DSMR) was an independent predictor of cardiac events. In a stepwise multivariate model (Cox regression), an abnormal magnetic resonance stress test result had significant incremental value over clinical risk factors and resting wall motion abnormality (P<0.001). Conclusions— In patients with known or suspected coronary artery disease, myocardial ischemia detected by MRP and DSMR can be used to identify patients at high risk for subsequent cardiac death or nonfatal myocardial infarction. For patients with normal MRP and DSMR, the 3-year event-free survival was 99.2%. MR stress testing provides important incremental information over clinical risk factors and resting wall motion abnormalities.

Intracoronary Injection of Bone Marrow–Derived Mononuclear Cells Early or Late After Acute Myocardial Infarction Effects on Global Left Ventricular Function

Background— Intracoronary administration of autologous bone marrow–derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. Methods and Results— In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was −0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, −1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, −2.61 to 3.71; P=0.73) for the late therapy group. Conclusions— Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location

AIMS Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lins correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.

High resolution three‐dimensional cardiac perfusion imaging using compartment‐based k‐t principal component analysis

Three‐dimensional myocardial perfusion imaging requires significant acceleration of data acquisition to achieve whole‐heart coverage with adequate spatial and temporal resolution. The present article introduces a compartment‐based k‐t principal component analysis reconstruction approach, which permits three‐dimensional perfusion imaging at 10‐fold nominal acceleration. Using numerical simulations, it is shown that the compartment‐based method results in accurate representations of dynamic signal intensity changes with significant improvements of temporal fidelity in comparison to conventional k‐t principal component analysis reconstructions. Comparison of the two methods based on rest and stress three‐dimensional perfusion data acquired with 2.3 × 2.3 × 10 mm3 during a 225 msec acquisition window in patients confirms the findings and demonstrates the potential of compartment‐based k‐t principal component analysis for highly accelerated three‐dimensional perfusion imaging. Magn Reson Med, 2011.

Dynamic 3-Dimensional Stress Cardiac Magnetic Resonance Perfusion Imaging Detection of Coronary Artery Disease and Volumetry of Myocardial Hypoenhancement Before and After Coronary Stenting

OBJECTIVES The aim of this study was to establish a new, dynamic 3-dimensional cardiac magnetic resonance (3D-CMR) perfusion scan technique exploiting data correlation in k-space and time with sensitivity-encoding and to determine its value for the detection of coronary artery disease (CAD) and volumetry of myocardial hypoenhancement (VOLUME(hypo)) before and after percutaneous coronary stenting. BACKGROUND Dynamic 3D-CMR perfusion imaging might improve detection of myocardial perfusion deficits and could facilitate direct volumetry of myocardial hypoenhancement. METHODS In 146 patients with known or suspected CAD, a 3.0-T CMR examination was performed including cine imaging, 3D-CMR perfusion under adenosine stress and at rest followed by delayed enhancement imaging. Quantitative invasive coronary angiography defined significant CAD (≥ 50% luminal narrowing). Forty-eight patients underwent an identical repeat CMR examination after percutaneous stenting of at least 1 coronary lesion. The 3D-CMR perfusion scans were visually classified as pathologic if ≥ 1 segment showed an inducible perfusion deficit in the absence of delayed enhancement. The VOLUME(hypo) was measured by segmentation of the area of inducible hypoenhancement and normalized to left-ventricular myocardial volume (%VOLUME(hypo)). RESULTS The 3D-CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 91.7%, 74.3%, and 82.9%, respectively. Before and after coronary stenting, %VOLUME(hypo) averaged to 14.2 ± 9.5% and 3.2 ± 5.2%, respectively, with a relative VOLUME(hypo) reduction of 79.4 ± 25.4%. Intrareader and inter-reader reproducibility of VOLUME(hypo) measurements was high (Lins concordance correlation coefficient, 0.96 and 0.96, respectively). CONCLUSIONS The 3D-CMR stress perfusion provided high image quality and high diagnostic accuracy for the detection of significant CAD. The VOLUME(hypo) measurements were highly reproducible and allowed for the assessment of the treatment effect achievable by percutaneous coronary stenting.

Additional Value of Myocardial Perfusion Imaging During Dobutamine Stress Magnetic Resonance for the Assessment of Coronary Artery Disease

Background—Dobutamine stress magnetic resonance (DSMR) imaging has emerged as a valuable tool for the detection of inducible wall motion abnormalities. The role of perfusion imaging during DSMR is not well defined. We examined whether the addition of myocardial perfusion imaging during DSMR provides incremental benefit for the evaluation of coronary artery disease. Methods and Results—DSMR was combined with perfusion imaging in 455 consecutive patients who were scheduled for clinically indicated invasive coronary angiography. Perfusion images were acquired in 3 standard short-views at rest and during maximum dobutamine-atropine stress. Wall motion and perfusion images were interpreted sequentially, blinded to other data. Significant (≥70%) stenoses were present in 285 patients on invasive coronary angiography. The use of DSMR combined with perfusion imaging versus DSMR increased sensitivity (91% versus 85%, P=0.001), but not specificity (70% versus 82%, P=0.001), resulting in identical overall diagnostic accuracy (84% versus 84%, P=NS; Youden index 0.61 versus 0.67). DSMR combined with perfusion imaging enabled the correct diagnosis of coronary artery disease in an additional 13% of DSMR-negative patients at the cost of 11% more false-positive cases. Conclusion—The addition of perfusion imaging during DSMR improves sensitivity for the diagnosis of coronary artery disease but does not enhance overall diagnostic accuracy because of a concomitant decrease in specificity.

Acute, subacute, and chronic myocardial infarction: quantitative comparison of 2D and 3D late gadolinium enhancement MR imaging

PURPOSE To assess a late gadolinium enhancement (LGE) single-breath-hold three-dimensional (3D) inversion recovery magnetic resonance (MR) imaging sequence for the quantification of myocardial scar mass and transmurality in comparison with a clinically established two-dimensional (2D) sequence. MATERIALS AND METHODS All patients gave written informed consent to participate in this institutional review board-approved study. Ninety patients (84 men; mean age, 54.4 years ± 10.8 [standard deviation]) with acute (n = 30), subacute (n = 30), or chronic (n = 30) myocardial infarction were included. Imaging was performed by using a 1.5-T clinical MR imaging system. Spatial resolution was identical for 3D and 2D images (1.5 × 1.5 mm(2); section thickness, 8 mm; no section gap). Quantitative comparisons of myocardial mass (in grams), scar mass (in grams), and scar transmurality (on a five-point scale) were performed by using the Pearson correlation and Bland-Altman analysis (for myocardial and scar mass) or κ statistics (for transmurality). RESULTS There were no significant differences between 2D and 3D data sets in terms of mean myocardial mass (2D: 148.3 g ± 35.1; 3D: 148.1 g ± 34.6; P = .76) and scar tissue mass (2D: 31.8 g ± 14.6; 3D: 31.6 g ± 15.5; P = .39), with strong and significant correlation regarding both myocardial mass (r = 0.982; P < .001) and scar tissue mass (r = 0.980; P < .001). Bland-Altman analysis showed a mean difference of 0.21 g ± 6.64 (range, -19.64 to 18.44 g) for myocardial mass and a mean difference of 0.26 g ± 2.88 (range, -7.15 to 7.74 g) for scar mass between the 2D and 3D data sets. Agreement regarding scar transmurality was good (κ = 0.75). Acquisition time was significantly shorter for 3D data sets (26.7 seconds ± 4.4 vs 367.7 seconds ± 56.4; P < .001). CONCLUSION Three-dimensional LGE MR imaging enables quantitative evaluation of scar tissue mass and transmurality in patients with acute, subacute, or chronic myocardial infarction at significantly reduced acquisition times compared with 2D LGE MR imaging.

Navigator-Gated 3D Blood Oxygen Level–Dependent CMR at 3.0-T for Detection of Stress-Induced Myocardial Ischemic Reactions

OBJECTIVES This study determined the value of navigator-gated 3-dimensional blood oxygen level-dependent (BOLD) cardiac magnetic resonance (CMR) at 3.0-T for the detection of stress-induced myocardial ischemic reactions. BACKGROUND Although BOLD CMR has been introduced for characterization of myocardial oxygenation status, previously reported CMR approaches suffered from a low signal-to-noise ratio and motion-related artifacts with impaired image quality and a limited diagnostic value in initial patient studies. METHODS Fifty patients with suspected or known coronary artery disease underwent CMR at 3.0-T followed by invasive X-ray angiography within 48 h. Three-dimensional BOLD images were acquired during free breathing with full coverage of the left ventricle in a short-axis orientation. The BOLD imaging was performed at rest and under adenosine stress, followed by stress and rest first-pass perfusion and delayed enhancement imaging. Quantitative coronary X-ray angiography (QCA) was used for coronary stenosis definition (diameter reduction > or =50%). The BOLD and first-pass perfusion images were semiquantitatively evaluated (for BOLD imaging, signal intensity differences between stress and rest [DeltaSI]; for perfusion imaging, myocardial perfusion reserve index [MPRI]). RESULTS The image quality of BOLD CMR at rest and during adenosine stress was considered good to excellent in 90% and 84% of the patients, respectively. The DeltaSI measurements differed significantly between normal myocardium, myocardium supplied by a stenotic coronary artery, and infarcted myocardium (p < 0.001). The receiver-operator characteristic analysis identified a cutoff value of DeltaSI = 2.7% for the detection of coronary stenosis, resulting in a sensitivity and specificity of 85.0% and 80.5%, respectively. An MPRI cutoff value of 1.35 yielded a sensitivity and specificity of 89.5% and 85.8%, respectively. The DeltaSI significantly correlated with the degree of coronary stenosis (r = -0.65, p < 0.001). Additionally, DeltaSI and MPRI showed substantial agreement (kappa value 0.66). CONCLUSIONS Navigator-gated 3-dimensional BOLD imaging at 3.0-T reliably detected stress-induced myocardial ischemic reactions and may be considered a valid alternative to first-pass exogenous contrast-enhancement studies.

Dual-Phase Cardiac Diffusion Tensor Imaging with Strain Correction

Purpose In this work we present a dual-phase diffusion tensor imaging (DTI) technique that incorporates a correction scheme for the cardiac material strain, based on 3D myocardial tagging. Methods In vivo dual-phase cardiac DTI with a stimulated echo approach and 3D tagging was performed in 10 healthy volunteers. The time course of material strain was estimated from the tagging data and used to correct for strain effects in the diffusion weighted acquisition. Mean diffusivity, fractional anisotropy, helix, transverse and sheet angles were calculated and compared between systole and diastole, with and without strain correction. Data acquired at the systolic sweet spot, where the effects of strain are eliminated, served as a reference. Results The impact of strain correction on helix angle was small. However, large differences were observed in the transverse and sheet angle values, with and without strain correction. The standard deviation of systolic transverse angles was significantly reduced from 35.9±3.9° to 27.8°±3.5° (p<0.001) upon strain-correction indicating more coherent fiber tracks after correction. Myocyte aggregate structure was aligned more longitudinally in systole compared to diastole as reflected by an increased transmural range of helix angles (71.8°±3.9° systole vs. 55.6°±5.6°, p<0.001 diastole). While diastolic sheet angle histograms had dominant counts at high sheet angle values, systolic histograms showed lower sheet angle values indicating a reorientation of myocyte sheets during contraction. Conclusion An approach for dual-phase cardiac DTI with correction for material strain has been successfully implemented. This technique allows assessing dynamic changes in myofiber architecture between systole and diastole, and emphasizes the need for strain correction when sheet architecture in the heart is imaged with a stimulated echo approach.

Different Prognostic Value of Functional Right Ventricular Parameters in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

Background—The value of standard 2-dimensional transthoracic echocardiographic parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. Methods and Results—We investigated the impact of RV fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for the prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Revised Task Force Criteria and underwent baseline transthoracic echocardiography, 37 (53%) patients experienced MACE during a median follow-up period of 5.3 (interquartile range, 1.8–9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time (P=0.03 for FAC, P=0.03 for TAPSE, and P=0.01 for TAPSE/BSA, each versus baseline). In contrast, median RV end-diastolic area increased (P=0.001 versus baseline). Based on the results of Kaplan–Meier estimates, the time between baseline transthoracic echocardiography and experiencing MACE was significantly shorter for patients with FAC <23% (P<0.001), TAPSE <17 mm (P=0.02), or right atrial short axis/BSA ≥25 mm/m2 (P=0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio, 1.08 per 1% decrease; 95% confidence interval, 1.04–1.12; P<0.001) on bivariable analysis. Conclusions—This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in patients with ARVC/D with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for transthoracic echocardiography in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower-risk ARVC/D cohorts.