Jonathan W. Weinsaft

Assessment of Myocardial Scarring Improves Risk Stratification in Patients Evaluated for Cardiac Defibrillator Implantation

OBJECTIVES We tested whether an assessment of myocardial scarring by cardiac magnetic resonance imaging (MRI) would improve risk stratification in patients evaluated for implantable cardioverter-defibrillator (ICD) implantation. BACKGROUND Current sudden cardiac death risk stratification emphasizes left ventricular ejection fraction (LVEF); however, most patients suffering sudden cardiac death have a preserved LVEF, and many with poor LVEF do not benefit from ICD prophylaxis. METHODS One hundred thirty-seven patients undergoing evaluation for possible ICD placement were prospectively enrolled and underwent cardiac MRI assessment of LVEF and scar. The pre-specified primary endpoint was death or appropriate ICD discharge for sustained ventricular tachyarrhythmia. RESULTS During a median follow-up of 24 months the primary endpoint occurred in 39 patients. Whereas the rate of adverse events steadily increased with decreasing LVEF, a sharp step-up was observed for scar size >5% of left ventricular mass (hazard ratio [HR]: 5.2; 95% confidence interval [CI]: 2.0 to 13.3). On multivariable Cox proportional hazards analysis, including LVEF and electrophysiological-study results, scar size (as a continuous variable or dichotomized at 5%) was an independent predictor of adverse outcome. Among patients with LVEF >30%, those with significant scarring (>5%) had higher risk than those with minimal or no (≤5%) scarring (HR: 6.3; 95% CI: 1.4 to 28.0). Those with LVEF >30% and significant scarring had risk similar to patients with LVEF ≤30% (p = 0.56). Among patients with LVEF ≤30%, those with significant scarring again had higher risk than those with minimal or no scarring (HR: 3.9; 95% CI: 1.2 to 13.1). Those with LVEF ≤30% and minimal scarring had risk similar to patients with LVEF >30% (p = 0.71). CONCLUSIONS Myocardial scarring detected by cardiac MRI is an independent predictor of adverse outcome in patients being considered for ICD placement. In patients with LVEF >30%, significant scarring (>5% LV) identifies a high-risk cohort similar in risk to those with LVEF ≤30%. Conversely, in patients with LVEF ≤30%, minimal or no scarring identifies a low-risk cohort similar to those with LVEF >30%.

Detection of Left Ventricular Thrombus by Delayed-Enhancement Cardiovascular Magnetic Resonance : Prevalence and Markers in Patients With Systolic Dysfunction

OBJECTIVES This study sought to assess the prevalence and markers of left ventricular (LV) thrombus among patients with systolic dysfunction. BACKGROUND Prior studies have yielded discordant findings regarding prevalence and markers of LV thrombus. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) identifies thrombus on the basis of tissue characteristics rather than just anatomical appearance and is potentially highly accurate. METHODS Prevalence of thrombus by DE-CMR was determined in 784 consecutive patients with systolic dysfunction (left ventricular ejection fraction [LVEF] <50%) imaged between July 2002 and July 2004. Patients were recruited from 2 separate institutions: a tertiary-care referral center and an outpatient clinic. Comparison to cine-cardiovascular magnetic resonance (CMR) was performed. Follow-up was undertaken for thrombus verification via pathology evaluation or documented embolic event within 6 months after CMR. Clinical and imaging parameters were assessed to determine risk factors for thrombus. RESULTS Among this at-risk population (age 60 +/- 14 years; LVEF 32 +/- 11%), DE-CMR detected thrombus in 7% (55 patients) and cine-CMR in 4.7% (37 patients, p < 0.005). Follow-up was consistent with DE-CMR as a better reference standard than cine-CMR, including 100% detection among 5 patients with thrombus verified by pathology (cine-CMR, 40% detection), and logistic regression analysis testing the contributions of DE-CMR and cine-CMR simultaneously, which showed that only the presence of thrombus by DE-CMR was associated with follow-up end points (p < 0.005). Cine-CMR generally missed small intracavitary and small or large mural thrombus. In addition to traditional indices such as low LVEF and ischemic cardiomyopathy, multivariable analysis showed that increased myocardial scarring, an additional parameter available from DE-CMR, was an independent risk factor for thrombus. CONCLUSIONS In a broad cross section of patients with systolic dysfunction, thrombus prevalence was 7% by DE-CMR and included small intracavitary and small or large mural thrombus missed by cine-CMR. Prevalence increased with worse LVEF, ischemic etiology, and increased myocardial scarring.

Mortality Risk in Symptomatic Patients With Nonobstructive Coronary Artery Disease: A Prospective 2-Center Study of 2,583 Patients Undergoing 64-Detector Row Coronary Computed Tomographic Angiography

OBJECTIVES We examined mortality risk in relation to extent and composition of nonobstructive plaques by 64-detector row coronary computed tomographic angiography (CCTA). BACKGROUND The prognostic significance of nonobstructive coronary artery plaques by CCTA is poorly understood. METHODS We prospectively evaluated consecutive adults from 2 centers undergoing 64-detector row CCTA without prior documented coronary artery disease (CAD) and without obstructive (≥50%) CAD by CCTA. Luminal diameter stenosis severity was classified for each segment as none (0%) or mild (1% to 49%), and plaque composition was classified as noncalcified, calcified, or mixed. RESULTS During 3.1 ± 0.5 years, 54 intermediate-term (≥90 days) deaths occurred among 2,583 patients (2.09%), with 4 early (<90 days) deaths. Adjusted for CAD risk factors, the presence of any nonobstructive plaque was associated with higher mortality (hazard ratio [HR]: 1.98, 95% confidence Interval [CI]: 1.06 to 3.69, p = 0.03), with the highest risk among those exhibiting nonobstructive CAD in 3 epicardial vessels (HR: 4.75, 95% CI: 2.10 to 10.75, p = 0.0002) or ≥5 segments (HR: 5.12, 95% CI: 2.16 to 12.10, p = 0.0002). Higher mortality for nonobstructive CAD was observed even among patients with low 10-year Framingham risk (3.4%, p < 0.0001) as well as those with no traditional, medically treatable CAD risk factors, including diabetes mellitus, hypertension, and dyslipidemia (6.7%, p < 0.0001). No independent relationship between plaque composition and incident mortality was observed. Importantly, patients without evident plaque experienced a low rate of incident death during follow-up (0.34%/year). CONCLUSIONS The presence and extent of nonobstructive plaques augment prediction of incident mortality beyond conventional clinical risk assessment.

Multimodality Imaging of Diseases of the Thoracic Aorta in Adults: From the American Society of Echocardiography and the European Association of Cardiovascular Imaging Endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance

Steven A. Goldstein, MD, Co-Chair, Arturo Evangelista, MD, FESC, Co-Chair, Suhny Abbara, MD, Andrew Arai, MD, Federico M. Asch, MD, FASE, Luigi P. Badano, MD, PhD, FESC, Michael A. Bolen, MD, Heidi M. Connolly, MD, Hug Cu ellar-Cal abria, MD, Martin Czerny, MD, Richard B. Devereux, MD, Raimund A. Erbel, MD, FASE, FESC, Rossella Fattori, MD, Eric M. Isselbacher, MD, Joseph M. Lindsay, MD, Marti McCulloch, MBA, RDCS, FASE, Hector I. Michelena, MD, FASE, Christoph A. Nienaber, MD, FESC, Jae K. Oh, MD, FASE, Mauro Pepi, MD, FESC, Allen J. Taylor, MD, Jonathan W. Weinsaft, MD, Jose Luis Zamorano, MD, FESC, FASE, Contributing Editors: Harry Dietz, MD, Kim Eagle, MD, John Elefteriades, MD, Guillaume Jondeau, MD, PhD, FESC, Herv e Rousseau, MD, PhD, and Marc Schepens, MD, Washington, District of Columbia; Barcelona and Madrid, Spain; Dallas and Houston, Texas; Bethesda and Baltimore, Maryland; Padua, Pesaro, and Milan, Italy; Cleveland, Ohio; Rochester, Minnesota; Zurich, Switzerland; New York, New York; Essen and Rostock, Germany; Boston, Massachusetts; Ann Arbor, Michigan; New Haven, Connecticut; Paris and Toulouse, France; and Brugge, Belgium

Cardiac chamber volumes, function, and mass as determined by 64-multidetector row computed tomography: mean values among healthy adults free of hypertension and obesity.

OBJECTIVES We derived mean values for cardiac dimensions, volumes, function, and mass in a normotensive nonobese population free of cardiovascular disease. BACKGROUND Multidetector computed tomography (MDCT) permits study of cardiac chamber size, function, and mass. Age- and gender-specific mean values are not available. METHODS A total of 103 normotensive, nonobese adults (43% women, age 51 +/- 14 years) who presented consecutively to 2 medical centers for clinically indicated MDCTs with neither history of nor MDCT evidence of significant cardiovascular disease were studied for left ventricular (LV) and right ventricular (RV) end-systolic (ES) and end-diastolic (ED) linear dimensions and volumes; LV and RV ejection fraction (EF), and LV mass (LVM); and left atrial (LA) and right atrial (RA) end-systolic volumes (LAESV and RAESV, respectively) by 1-dimensional (1D), 2-dimensional (2D), and 3-dimensional (3D) measurements. RESULTS The LV volumes using 3D techniques were lower than 2D techniques (LVEDV mean 144 +/- 71 ml vs. 150 +/- 70 ml), with higher LVEF (63 +/- 15% vs. 57 +/- 13%) (p < 0.001 for both). Mean LVM/height(2.7) was 24.3 +/- 11.0 g/m(2.7) and mean relative wall thickness was 0.16 to 0.44. Evaluation by 20 versus 10 cardiac phases resulted in higher LVEF (mean difference: 3.4 +/- 9.0%, p < 0.001). For LVEDV, interobserver (r = 0.99, p < 0.001) and intraobserver (r(2) = 0.97, p < 0.001) correlations were high. Mean RVEDV was 82 +/- 57 ml and RVEF was 58 +/- 16. The LAESV determined by 3D techniques was higher than by that determined by 2D methods (102 +/- 48 ml vs. 87 +/- 57 ml, p = 0.0003). The RAESV determined by 3D techniques was 111.9 +/- 29.1 ml. The LV size and LVM were greater in men than in women (p < 0.01). The LV size declined with age (p < 0.01), but LVM did not. CONCLUSIONS This study establishes age- and gender-specific values for LV, RV, LA, and RA size, function, and mass in adults free of cardiovascular disease, hypertension, and obesity using 1D, 2D, and 3D methods. These data can be used as a reference for future MDCT studies.

Contrast-Enhanced Anatomic Imaging as Compared to Contrast-Enhanced Tissue Characterization for Detection of Left Ventricular Thrombus

OBJECTIVES This study sought to compare contrast-enhanced anatomic imaging and contrast-enhanced tissue characterization (delayed-enhancement cardiac magnetic resonance [DE-CMR]) for left ventricular (LV) thrombus detection. BACKGROUND Contrast echocardiography (echo) detects LV thrombus based on anatomic appearance, whereas DE-CMR imaging detects thrombus based on tissue characteristics. Although DE-CMR has been validated as an accurate technique for thrombus, its utility compared with contrast echo is unknown. METHODS Multimodality imaging was performed in 121 patients at high risk for thrombus due to myocardial infarction or heart failure. Imaging included 3 anatomic imaging techniques for thrombus detection (contrast echo, noncontrast echo, cine-CMR) and a reference of DE-CMR tissue characterization. LV structural parameters were quantified to identify markers for thrombus and predictors of additive utility of contrast-enhanced thrombus imaging. RESULTS Twenty-four patients had thrombus by DE-CMR. Patients with thrombus had larger infarcts (by DE-CMR), more aneurysms, and lower LV ejection fraction (by CMR and echo) than those without thrombus. Contrast echo nearly doubled sensitivity (61% vs. 33%, p < 0.05) and yielded improved accuracy (92% vs. 82%, p < 0.01) versus noncontrast echo. Patients who derived incremental diagnostic utility from DE-CMR had lower LV ejection fraction versus those in whom noncontrast echo alone accurately assessed thrombus (35 +/- 9% vs. 42 +/- 14%, p < 0.01), with a similar trend for patients who derived incremental benefit from contrast echo (p = 0.08). Contrast echo and cine-CMR closely agreed on the diagnosis of thrombus (kappa = 0.79, p < 0.001). Thrombus prevalence was lower by contrast echo than DE-CMR (p < 0.05). Thrombus detected by DE-CMR but not by contrast echo was more likely to be mural in shape or, when apical, small in volume (p < 0.05). CONCLUSIONS Echo contrast in high-risk patients markedly improves detection of LV thrombus, but does not detect a substantial number of thrombi identified by DE-CMR tissue characterization. Thrombi detected by DE-CMR but not by contrast echo are typically mural in shape or small in volume.

Assessment of the thoracic aorta by multidetector computed tomography: Age- and sex-specific reference values in adults without evident cardiovascular disease

BACKGROUND Dilatation of the aortic root and other segments of the thoracic aorta is important in the pathogenesis of aortic regurgitation and of aortic dissection. Although echocardiographic criteria exist to detect aortic root dilation, comparably standardized methods have not been developed to detect enlargement of the remainder of the thoracic aorta. Nongated axial chest computed tomography (CT), traditionally used to evaluate aortic size, does not account for the obliquity, systolic expansion, and nonaxial motion of the aorta during the cardiac cycle. Reference values for aortic diameters in anatomically correct double-oblique short axis images have not been established with the use of electrocardiogram (ECG)-gated 64-detector row multidetector CT (MDCT). OBJECTIVES To establish reference values for thoracic aortic diameters MDCT in healthy normotensive nonobese adults without evident cardiovascular disease. METHODS A total of 103 (43% women, age 51 +/- 14 years) consecutive normotensive, nonobese adults free of cardiac or aortic structural disease or arrhythmia underwent MDCT examination to determine aortic dimensions. RESULTS End-diastolic diameter 95% confidence intervals were 2.5-3.7 cm for the aortic root, 2.1-3.5 cm for the ascending aorta, and 1.7-2.6 cm for the descending thoracic aorta. Aortic diameters were significantly greater at end systole than end diastole (mean difference 1.9 +/- 1.2 mm for ascending and 1.3 +/- 1.8 for descending thoracic aorta, P < 0.001). Aortic root and ascending aortic diameter increased significantly with age and body surface area. CONCLUSIONS This study establishes age- and sex-specific ECG-gated MDCT reference values for thoracic aortic diameters in healthy, normotensive, nonobese adults to identify aortic pathology by MDCT. MDCT measurements of the thoracic aorta should use ECG-gated double-oblique short-axis images for accurate quantification.

Multidetector row computed tomography for identification of left atrial appendage filling defects in patients undergoing pulmonary vein isolation for treatment of atrial fibrillation: Comparison with transesophageal echocardiography

BACKGROUND Advances in multidetector computed tomography (MDCT) technology now permit three-dimensional cardiac imaging with high spatial and temporal resolution. Historically, transesophageal echocardiography (TEE) has been the gold standard for assessment of the left atrial appendage (LAA) in patients with atrial fibrillation and other atrial arrhythmias. Findings on TEE, including demonstration of LAA thrombus and dense nonclearing spontaneous echocardiographic contrast (SEC), predict future fatal and nonfatal thromboembolic events. OBJECTIVE The purpose of this study was to compare the diagnostic performance of 64-detector row MDCT in detecting LAA thrombus and dense nonclearing SEC as identified by TEE in patients undergoing pulmonary vein isolation for treatment of atrial fibrillation. METHODS A total of 72 consecutive patients (69.4% male; mean age 56.1 +/- 10.3 years) underwent both MDCT and TEE for evaluation of the LAA (median intertest interval 0 days, interquartile range 0-5 days). MDCT assessment of the LAA was performed by two methods: (1) comparison of Hounsfield unit (HU) densities in the LAA apex to the ascending aorta (AscAo) in the same axial plane and (2) nonquantitative visual identification of a filling defect in the LAA. TEE evaluation of the LAA included identification of echodense intracavitary masses in the LAA as well as pulsed-wave Doppler interrogation of the LAA ostium. RESULTS Patients with LAA thrombus or dense nonclearing SEC by TEE exhibited significantly lower LAA/AscAo HU ratios than patients who did not (0.82 +/- 0.22 vs 0.39 +/- 0.19, P <.001). LAA/AscAo HU cutoff ratios < or = 0.75 correlated to LAA thrombus or dense nonclearing SEC by TEE, with 100% sensitivity, 72.2% specificity, 28.6% positive predictive value, and 100% negative predictive value. HU ratios < or = 0.75 were associated with pulsed-wave Doppler velocities <50 cm/s of the LAA ostium (P <.001). In multivariable analysis, LAA/AscAo HU ratio < or = 0.75 remained a robust predictor of LAA thrombus or dense nonclearing SEC by TEE (P <.001). In contrast, MDCT identification of TEE-identified LAA thrombus or dense nonclearing SEC by visual detection of LAA filling defects resulted in lower sensitivity (50%) and negative predictive value (95.1%). CONCLUSION Current-generation MDCT successfully identifies LAA thrombus and dense nonclearing SEC with high sensitivity and moderate specificity. Importantly, LAA/AscAo HU ratios >0.75 demonstrate 100% negative predictive value for exclusion of LAA thrombus or dense nonclearing SEC. These results suggest that in patients undergoing pulmonary vein isolation procedures, MDCT examinations that demonstrate LAA/AscAo HU ratios >0.75 may preclude the need for preprocedural TEE.

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.

Automatic Left Ventricle Segmentation Using Iterative Thresholding and an Active Contour Model With Adaptation on Short-Axis Cardiac MRI

An automatic left ventricle (LV) segmentation algorithm is presented for quantification of cardiac output and myocardial mass in clinical practice. The LV endocardium is first segmented using region growth with iterative thresholding by detecting the effusion into the surrounding myocardium and tissues. Then the epicardium is extracted using the active contour model guided by the endocardial border and the myocardial signal information estimated by iterative thresholding. This iterative thresholding and active contour model with adaptation (ITHACA) algorithm was compared to manual tracing used in clinical practice and the commercial MASS Analysis software (General Electric) in 38 patients, with Institutional Review Board (IRB) approval. The ITHACA algorithm provided substantial improvement over the MASS software in defining myocardial borders. The ITHACA algorithm agreed well with manual tracing with a mean difference of blood volume and myocardial mass being 2.9 ± 6.2 mL (mean ± standard deviation) and -0.9 ± 16.5 g, respectively. The difference was smaller than the difference between manual tracing and the MASS software (approximately -20.0 ± 6.9 mL and -1.0 ± 20.2 g, respectively). These experimental results support that the proposed ITHACA segmentation is accurate and useful for clinical practice.