Showing papers in "Jacc-cardiovascular Imaging in 2012"

Prognostic Value of Late Gadolinium Enhancement in Clinical Outcomes for Hypertrophic Cardiomyopathy

Abstract: Objectives The objective of this study was to perform a systematic review and meta-analysis of the predictive value of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for future cardiovascular events and death in hypertrophic cardiomyopathy (HCM) Background The utility of LGE for detecting myocardial fibrosis is well established The prognostic value of LGE in HCM has been described in several studies, but controversy exists given the limited power of these studies to predict future events Methods We searched multiple databases including PubMed for studies of LGE in HCM that reported selected clinical outcomes (cardiovascular mortality, sudden cardiac death [SCD], aborted SCD, and heart failure death) We performed a systematic review of the literature and meta-analysis to determine pooled odds ratios for these clinical events Results Four studies evaluated 1,063 patients over an average follow-up of 31 years The pooled prevalence of LGE was 60% The pooled odds ratios (OR) demonstrate that LGE by CMR correlated with cardiac death (pooled OR: 292, 95% confidence interval [CI]: 101 to 842; p = 0047), heart failure death (pooled OR: 568, 95% CI: 104 to 3107; p = 0045), and all-cause mortality (pooled OR: 446, 95% CI: 153 to 1301; p = 0006), and showed a trend toward significance for predicting sudden death/aborted sudden death (pooled OR: 239, 95% CI: 087 to 658; p = 0091) Conclusions Late gadolinium enhancement by CMR has prognostic value in predicting adverse cardiovascular events among HCM patients There are significant relationships between LGE and cardiovascular mortality, heart failure death, and all-cause mortality in HCM Additionally, LGE and SCD/aborted SCD displayed a trend toward significance The assessment of LGE by CMR has the potential to provide important information to improve risk stratification in HCM in clinical practice

Myocardial Edema as Detected by Pre-Contrast T1 and T2 CMR Delineates Area at Risk Associated With Acute Myocardial Infarction

Abstract: Objectives The aim of this study was to determine whether cardiac magnetic resonance (CMR) in vivo T1 mapping can measure myocardial area at risk (AAR) compared with microspheres or T2 mapping CMR. Background If T2-weighted CMR is abnormal in the AAR due to edema related to myocardial ischemia, then T1-weighted CMR should also be able to detect and accurately quantify AAR. Methods Dogs (n = 9) underwent a 2-h coronary occlusion followed by 4 h of reperfusion. CMR of the left ventricle was performed for mapping of T1 and T2 prior to any contrast administration. AAR was defined as regions that had a T1 or T2 value (ms) >2 SD from remote myocardium, and regions with microsphere blood flow (ml/min/g) during occlusion Results The relaxation parameters T1 and T2 were increased in the AAR compared with remote myocardium (mean ± SD: T1, 1,133 ± 55 ms vs. 915 ± 33 ms; T2, 71 ± 6 ms vs. 49 ± 3 ms). On a slice-by-slice basis (n = 78 slices), AAR by T1 and T2 mapping correlated (R2 = 0.95, p Conclusions For determining AAR after acute myocardial infarction, noncontrast T1 mapping and T2 mapping sequences yield similar quantitative results, and both agree well with microspheres. The relaxation properties T1 and T2 both change in a way that is consistent with the presence of myocardial edema following myocardial ischemia/reperfusion.

Is discordance of coronary flow reserve and fractional flow reserve due to methodology or clinically relevant coronary pathophysiology

Abstract: Objectives The purpose of this study was to determine whether observed discordance between coronary flow reserve (CFR) and fractional flow reserve (FFR) is due to methodology or reflects basic coronary pathophysiology. Background Despite the clinical importance of coronary physiological assessment, relationships between its 2 most common tools, CFR and FFR, remain poorly defined. Methods The worst CFR and stress relative uptake were recorded from 1,500 sequential cardiac positron emission tomography cases from our center. From the literature, we assembled all combined, invasive CFR-FFR measurements, including a subset before and after angioplasty. Both datasets were compared with a fluid dynamic model of the coronary circulation predicting relationships between CFR and FFR for variable diffuse and focal narrowing. Results A modest but significant linear relationship exists between CFR and FFR both invasively (r = 0.34, p Conclusions CFR is linearly related to FFR for progressive stenosis superimposed on diffuse narrowing. The relative contributions of focal and diffuse disease define the slope and values along the linear CFR and FFR relationship. Discordant CFR and FFR values reflect divergent extremes of focal and diffuse disease, not failure of either tool. With such discordance observed by invasive and noninvasive techniques and also fitting fluid dynamic predictions, it reflects clinically relevant basic coronary pathophysiology, not methodology.

Prognostic Value of Coronary CT Angiography and Calcium Score for Major Adverse Cardiac Events in Outpatients

Abstract: Objectives This study sought to evaluate the prognostic value of coronary artery calcium score (CACS) and coronary computed tomography angiography (CTA) for major adverse cardiac events (MACE). Background The prognostic value of CACS has been well described. Few studies use the rich information of coronary CTA to predict future clinical outcomes and compare CACS with coronary CTA. Methods We followed up 5,007 outpatients who were suspected of having coronary artery disease (CAD) and who underwent cardiac CTA. Cardiac CT was assessed for CACS and the extent, the location, the stenosis severity, and the composition of the plaque in coronary CTA. The endpoint was MACE, defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. Results Follow-up was completed in 4,425 patients (88.4%), with a median follow-up period of 1,081 days. At the end of the follow-up period, 363 (8.2%) patients had experienced MACE. Cumulative probability of 3-year MACE increased across CT strata for CACS (CACS 0, 2.1%; CACS 1 to 100, 12.9%; CACS 101 to 400, 16.3%; and CACS >400, 33.8%; log-rank p Conclusions The CACS and coronary CTA findings have prognostic value and have incremental value over routine risk factors for MACE, and coronary CTA is superior to CACS. Cardiac CT seems to be a promising noninvasive modality with significant prognostic value.

LV Mass Assessed by Echocardiography and CMR, Cardiovascular Outcomes, and Medical Practice

Abstract: The authors investigated 3 important areas related to the clinical use of left ventricular mass (LVM): accuracy of assessments by echocardiography and cardiac magnetic resonance (CMR), the ability to predict cardiovascular outcomes, and the comparative value of different indexing methods. The recommended formula for echocardiographic estimation of LVM uses linear measurements and is based on the assumption of the left ventricle (LV) as a prolate ellipsoid of revolution. CMR permits a modeling of the LV free of cardiac geometric assumptions or acoustic window dependency, showing better accuracy and reproducibility. However, echocardiography has lower cost, easier availability, and better tolerability. From the MEDLINE database, 26 longitudinal echocardiographic studies and 5 CMR studies investigating LVM or LV hypertrophy as predictors of death or major cardiovascular outcomes were identified. LVM and LV hypertrophy were reliable cardiovascular risk predictors using both modalities. However, no study directly compared the methods for the ability to predict events, agreement in hypertrophy classification, or performance in cardiovascular risk reclassification. Indexing LVM to body surface area was the earliest normalization process used, but it seems to underestimate the prevalence of hypertrophy in obese and overweight subjects. Dividing LVM by height to the allometric power of 1.7 or 2.7 is the most promising normalization method in terms of practicality and usefulness from a clinical and scientific standpoint for scaling myocardial mass to body size. The measurement of LVM, calculation of LVM index, and classification for LV hypertrophy should be standardized by scientific societies across measurement techniques and adopted by clinicians in risk stratification and therapeutic decision making.

Gender and the extent of coronary atherosclerosis, plaque composition, and clinical outcomes in acute coronary syndromes.

Abstract: Objectives This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men. Background Pathological studies suggest that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques. Methods A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound [IVUS]) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis. Results Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (>70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p 2 , PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive. Conclusions The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.

Diagnostic Performance of CMR Imaging Compared With EMB in Patients With Suspected Myocarditis

Abstract: Objectives The goal of this study was to assess the diagnostic performance of cardiac magnetic resonance (CMR) compared with endomyocardial biopsy in patients with suspected acute myocarditis (AMC) and chronic myocarditis (CMC). Background Several studies have reported an encouraging diagnostic performance of CMR in myocarditis. However, the comparison of CMR with clinical data only and the use of preselected patient populations are important limitations of the majority of these reports. Methods One hundred thirty-two consecutive patients with suspected AMC (defined by symptoms ≤14 days; n = 70) and CMC (defined by symptoms >14 days; n = 62) were included. Patients underwent cardiac catheterization with left ventricular endomyocardial biopsy and CMR, including T 2 -weighted imaging for assessment of edema, T 1 -weighted imaging before and after contrast administration for evaluation of hyperemia, and assessment of late gadolinium enhancement. CMR results were considered to be consistent with the diagnosis of myocarditis if 2 of 3 CMR techniques were positive. Results Within the total population, myocarditis was the most common diagnosis on endomyocardial biopsy analysis (62.9%). Viral genomes were detected in 30.3% (40 of 132) of patients within the total patient population and significantly more often in patients with AMC than CMC (40.0% vs. 19.4%; p = 0.013). For the overall cohort of patients with either suspected AMC or CMC, the diagnostic sensitivity, specificity, and accuracy of CMR were 76%, 54%, and 68%, respectively. The best diagnostic performance was observed in patients with suspected AMC (sensitivity, 81%; specificity, 71%; and accuracy, 79%). In contrast, diagnostic performance of CMR in suspected CMC was found to be unsatisfactory (sensitivity, 63%; specificity, 40%; and accuracy, 52%). Conclusions The results of this study underline the usefulness of CMR in patients with suspected AMC. In contrast, the diagnostic performance of CMR in patients with suspected CMC might not be sufficient to guide clinical management.

Emerging trends in CV flow visualization

Abstract: Blood flow patterns are closely linked to the morphology and function of the cardiovascular system. These patterns reflect the exceptional adaptability of the cardiovascular system to maintain normal blood circulation under a wide range of workloads. Accurate retrieval and display of flow-related information remains a challenge because of the processes involved in mapping the flow velocity fields within specific chambers of the heart. We review the potentials and pitfalls of current approaches for blood flow visualization, with an emphasis on acquisition, display, and analysis of multidirectional flow. This document is divided into 3 sections. First, we provide a descriptive outline of the relevant concepts in cardiac fluid mechanics, including the emergence of rotation in flow and the variables that delineate vortical structures. Second, we elaborate on the main methods developed to image and visualize multidirectional cardiovascular flow, which are mainly based on cardiac magnetic resonance, ultrasound Doppler, and contrast particle imaging velocimetry, with recommendations for developing dedicated imaging protocols. Finally, we discuss the potential clinical applications and technical challenges with suggestions for further investigations.

Carotid Plaque Burden as a Measure of Subclinical Atherosclerosis Comparison With Other Tests for Subclinical Arterial Disease in the High Risk Plaque BioImage Study

Abstract: Objectives The purpose of this study was to compare carotid plaque burden, carotid intima-media thickness (cIMT), ankle-brachial index (ABI), and abdominal aortic diameter (AAD) to coronary artery calcium score (CACS) in people without known cardiovascular disease. Background The clinical utility of risk factors to predict cardiovascular events is limited. Detection of subclinical atherosclerosis by noninvasive tests such as CACS, cIMT, carotid plaque burden, AAD, and ABI may improve risk prediction above that of established risk scoring models, namely, Framingham Risk Score. Methods The High Risk Plaque BioImage study investigated 6.101 asymptomatic persons and reports baseline CACS, cIMT, ABI, and AAD. In addition, we present findings from a new 3-dimensional–based ultrasound approach, where the carotid artery was investigated in cross section from proximal in the neck to as distal as possible. From the resulting 10-s video, plaque was outlined on cross-sectional images and all plaque areas were summarized into “plaque burden.” Results The mean age was 68.8 years, and 65.3% of subjects had intermediate Framingham Risk Score (6% to 20% 10-year risk). Carotid plaques were identified in 78% of cases, abnormal ABI in 10%, AAD >20 mm in 28%, and coronary calcium in 68% of participants. Carotid plaque burden was found to correlate stronger with CACS (chi-square 450, p Conclusions In the BioImage study, a new 3-dimensional–based ultrasound method identified more carotid plaques than in previous studies. Compared to other methods, carotid plaque burden was the strongest cross-sectional predictor of CACS, and its clinical utility as predictor of future cardiovascular events is being evaluated in the BioImage study. (BioImage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725 )

Detection of High-Risk Atherosclerotic Plaque: Report of the NHLBI Working Group on Current Status and Future Directions

Abstract: The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis.

Real-time 3D echocardiographic quantification of left atrial volume: multicenter study for validation with CMR

Abstract: Objectives We studied in a multicenter setting the accuracy and reproducibility of 3-dimensional echocardiography (3DE)–derived measurements of left atrial volume (LAV) using new, dedicated volumetric software, side by side with 2-dimensional echocardiography (2DE), using cardiac magnetic resonance (CMR) imaging as a reference. Background Increased LAV is associated with adverse cardiovascular outcomes. Although LAV measurements are routinely performed using 2DE, this methodology is limited because it is view dependent and relies on geometric assumptions regarding left atrial shape. Real-time 3DE is free of these limitations and accordingly is an attractive alternative for the evaluation of LAV. However, few studies have validated 3DE-derived LAV measurements against an accepted independent reference standard, such as CMR imaging. Methods We studied 92 patients with a wide range of LAV who underwent CMR (1.5-T) and echocardiographic imaging on the same day. Images were analyzed to obtain maximal and minimal LAV: CMR images using standard commercial tools, 2DE images using a biplane area-length technique, and 3DE images using Tomtec LA Function software. Intertechnique comparisons included linear regression and Bland-Altman analyses. Reproducibility of all 3 techniques was assessed by calculating the percentage of absolute differences in blinded repeated measurements. Kappa statistics were used to compare 2DE and 3DE classification of normal/enlarged against the CMR reference. Results 3DE-derived LAV values showed higher correlation with CMR than 2DE measurements (r = 0.93 vs. r = 0.74 for maximal LAV; r = 0.88 vs. r = 0.82 for minimal LAV). Although 2DE underestimated maximal LAV by 31 ± 25 ml and minimal LAV by 16 ± 32 ml, 3DE resulted in a minimal bias of −1 ± 14 ml for maximal LAV and 0 ± 21 ml for minimal LAV. Interobserver and intraobserver variability of 2DE and 3DE measurements of maximal LAV were similar (7% to 12%) and approximately 2 times higher than CMR (4% to 5%). 3DE classified enlarged atria more accurately than 2DE (kappa: 0.88 vs. 0.71). Conclusions Compared with CMR reference, 3DE-derived LAV measurements are more accurate than 2DE-based analysis, resulting in fewer patients with undetected atrial enlargement.

Integrating Noninvasive Absolute Flow, Coronary Flow Reserve, and Ischemic Thresholds Into a Comprehensive Map of Physiological Severity

Abstract: Noninvasive, absolute myocardial perfusion and coronary flow reserve (CFR) can be imaged by many techniques. However, such data must be interpreted for clinical application regardless of its source. Currently, no guide exists for physiological integration. Therefore, we propose 2-dimensional scatter plots of stress flow and CFR with superimposed thresholds for normal flow, reduced flow without ischemia, definite ischemia, and transmural infarction to allow for automatic and objective classification. Application of this schema to 1,500 studies demonstrates that flow capacity relates inversely to risk factors and atherosclerotic burden. Interpreting stress flow to make clinical decisions requires rest flow or CFR for broad application to all patients. Although relative uptake images alone are adequate for some patients, it can either under- or over-estimate flow capacity in many persons. Our standardized framework could prompt future studies leading to a trial of revascularization guided by absolute flow measurements.

The napkin-ring sign indicates advanced atherosclerotic lesions in coronary CT angiography.

Abstract: Objectives This study sought to determine the accuracy of plaque pattern assessment by coronary computed tomography angiography (CCTA) to differentiate between early and advanced atherosclerotic lesions as defined by histology. Background A ringlike attenuation pattern of coronary atherosclerotic plaques termed as napkin-ring sign (NRS) was described in CCTA of patients who had acute coronary syndrome. Methods All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local ethics committees was obtained. We investigated 21 coronary arteries of 7 donor hearts. Overall, 611 histological sections were obtained and coregistered with CCTA images. The CCTA cross sections were read in random order for conventional plaque categories (noncalcified [NCP], mixed [MP], calcified [CP]) and plaque patterns (homogenous, heterogeneous with no napkin-ring sign [non-NRS], and heterogeneous with NRS). Results No plaque was detected in 134 (21.9%), NCP in 254 (41.6%), MP in 191 (31.3%), and CP in 32 (5.2%) CCTA cross sections. The NCP and MP were further classified into homogenous plaques (n = 207, 46.5%), non-NRS plaques (n = 200, 44.9%), and NRS plaques (n = 38, 8.6%). The specificities of NCP and MP to identify advanced lesions were moderate (57.9%, 95% confidence interval [CI]: 50.1% to 65.6%, and 72.1%, 95% CI: 64.7% to 79.4%, respectively), which were similar to the homogenous and heterogeneous plaques (62.6%, 95% CI: 54.8% to 70.3%, and 67.3%, 95% CI: 58.6% to 76.1%, respectively). In contrast, the specificity of the NRS to identify advanced lesions was excellent (98.9%, 95% CI: 97.6% to 100%). The diagnostic performance of the pattern-based scheme to identify advanced lesions was significantly better than that of the conventional plaque scheme (area under the curve: 0.761 vs. 0.678, respectively; p = 0.001). Conclusions The assessment of the plaque pattern improves diagnostic accuracy of CCTA to identify advanced atherosclerotic lesions. The CCTA finding of NRS has a high specificity and high positive predictive value for the presence of advanced lesions.

Prevalence of nonstenosing, complicated atherosclerotic plaques in cryptogenic stroke.

Abstract: Objectives Our goal was to assess the prevalence of complicated American Heart Association (AHA) lesion type VI plaques in the carotid arteries of patients with cryptogenic stroke. Background In up to 40% of ischemic stroke patients, no definite cause can be established despite extensive workup (i.e., cryptogenic stroke). To test the hypothesis if nonstenosing complicated carotid plaques may be the underlying etiology in some of these patients, we used high-resolution black-blood carotid magnetic resonance imaging (MRI), which can quantitatively assess plaque composition and morphology with good correlation to histopathology. Specifically, we focused on AHA type VI plaques, which are characterized by hemorrhage, thrombus, or fibrous cap rupture. Methods Thirty-two consecutive patients (22 male; mean age 71.7 ± 11.9 years) with cryptogenic stroke and nonstenosing ( Results AHA type VI plaques were found in 12 of 32 arteries (37.5%) ipsilateral to the stroke, whereas there were no AHA type VI plaques contralateral to the stroke (p = 0.001). The most common diagnostic feature of AHA type VI plaques was intraplaque hemorrhage (75%), followed by fibrous plaque rupture (50%) and luminal thrombus (33%). Conclusions This pilot study suggests that arterio-arterial embolism from complicated, nonstenosing carotid atherosclerotic plaques may play a role in a subgroup of patients previously diagnosed with cryptogenic stroke. To further evaluate the significance of AHA type VI plaques in cryptogenic stroke, future studies will have to analyze both clinical and imaging follow-up data, including event rates for secondary strokes.

A practical guide to multimodality imaging of transcatheter aortic valve replacement.

Abstract: The advent of transcatheter aortic valve replacement (TAVR) is one of the most widely anticipated advances in the care of patients with severe aortic stenosis. This procedure is unique in many ways, one of which is the need for a multimodality imaging team-based approach throughout the continuum of the care of TAVR patients. Pre-procedural planning, intra-procedural implantation optimization, and long-term follow-up of patients undergoing TAVR require the expert use of various imaging modalities, each of which has its own strengths and limitations. Divided into 3 sections (pre-procedural, intraprocedural, and long-term follow-up), this review offers a single source for expert opinion and evidence-based guidance on how to incorporate the various modalities at each step in the care of a TAVR patient. Although much has been learned in the short span of time since TAVR was introduced, recommendations are offered for clinically relevant research that will lead to refinement of best practice strategies for incorporating multimodality imaging into TAVR patient care.

A Long-Term Prognostic Value of Coronary CT Angiography in Suspected Coronary Artery Disease

Abstract: Objectives The aim of this study was to assess the long-term prognostic role of multidetector computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD). Background Use of CTA is increasing in patients with suspected CAD. Although there is a large body of data supporting the prognostic role of CTA for major adverse cardiac events in the intermediate term, its long-term prognostic role in patients with suspected CAD is not well studied. Methods Between February 2005 and March 2008, 1,304 consecutive patients were prospectively studied with CTA for detecting the presence and assessing extent of CAD (disease extension and coronary plaque scores). Patients were classified according to the presence of normal coronaries and nonobstructive ( 50%) coronary lesions. The composite rates of hard cardiac events (cardiac deaths and nonfatal myocardial infarctions) and all cardiac events (including late revascularization) were the endpoints of the study. Results Seventy patients were excluded because their CTA data were uninterpretable. Of the remaining 1,234 patients, clinical follow-up (mean 52 ± 22 months) was obtained for 1,196 (97%). A total of 475 events were recorded, with 136 hard events (18 cardiac deaths and 118 nonfatal myocardial infarctions) and 123 late revascularizations. A total of 216 patients with early elective revascularizations were excluded from the survival analysis. Significant independent predictors of events in multivariate analysis were multivessel disease and left main CAD. Cumulative event-free survival was 100% for hard and all events in patients with normal coronary arteries, 88% for hard events and 72% for all events in patients with nonobstructive CAD, and 54% for hard events and 31% for all events in patients with obstructive CAD. Multivessel CAD was associated with a higher rate of hard cardiac events. Conclusions CTA provides prognostic information in patients with suspected CAD and unknown cardiac disease, showing excellent long-term prognosis when there is no evidence of atherosclerosis and allowing risk stratification when CAD is present.

Impact of Statin Therapy on Plaque Characteristics as Assessed by Serial OCT, Grayscale and Integrated Backscatter–IVUS

Abstract: Objectives The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. Background Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics. Methods Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months. Results Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (−6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p Conclusions Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.

Image Quality and Radiation Exposure With Prospectively ECG-Triggered Axial Scanning for Coronary CT Angiography: The Multicenter, Multivendor, Randomized PROTECTION-III Study

Abstract: Objectives The purpose of this study was to evaluate image quality and radiation dose using a prospectively electrocardiogram (ECG)–triggered axial scan protocol compared with standard retrospective ECG-gated helical scanning for coronary computed tomography angiography. Background Concerns have been raised regarding radiation exposure during coronary computed tomography angiography. Although the use of prospectively ECG-triggered axial scan protocols may effectively lower radiation dose compared with helical scanning, it is unknown whether image quality is maintained in a clinical setting. Methods In a prospective, multicenter, multivendor trial, 400 patients with low and stable heart rates were randomized to either an axial or a helical coronary computed tomography angiography scan protocol. The primary endpoint was to demonstrate noninferiority in image quality with the axial scan protocol, which was assessed on a 4-point scale (1 = nondiagnostic, 4 = excellent image quality). Secondary endpoints included radiation dose and the rate of downstream testing during 30-day follow-up. Results Image quality in patients scanned with the axial scan protocol (score 3.36 ± 0.59) was not inferior compared with helical scan protocols (3.37 ± 0.59) (p for noninferiority Conclusions In patients with stable and low heart rates, the prospectively ECG-triggered axial scan protocol maintained image quality but reduced radiation exposure by 69% compared with helical scanning. Axial computed tomography data acquisition should be strongly recommended in suitable patients to avoid unnecessarily high radiation exposure. (Prospective Randomized Trial on Radiation Dose Estimates of CT Angiography in Patients Scanned With a Sequential Scan Protocol [PROTECTION-III]; NCT00612092 )

Role of FDG PET-CT in Takayasu arteritis: sensitive detection of recurrences

Abstract: Objectives The aim of this study was to investigate whether the maximum standardized uptake value (max SUV) of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) provides a quantitative indication of disease activity in Takayasu arteritis (TA) cases. Background The clinical value of FDG-PET for assessing TA has been investigated. Clinical evaluation of disease activity is often difficult, because most patients develop recurrent inflammation while receiving corticosteroid treatment. Methods Thirty-nine TA patients underwent FDG-PET/CT at Tokyo Medical and Dental University from 2006 to 2010 (35 women and 4 men; median age, 30 years). Disease activity was defined according to National Institutes of Health criteria. Biomarkers including C-reactive protein and erythrocyte sedimentation rate were measured. Forty subjects without vasculitis served as control subjects. Results The max SUV was significantly higher in active than in inactive cases and control subjects (active [n = 27], median value, 2.7 vs. inactive [n = 12], 1.9; control [n = 40], 1.8; p Conclusions FDG-PET/CT is useful for detection of active inflammation not only in patients with active TA before treatment but also in relapsing patients receiving immunosuppressive agents. The max SUV is useful for assessing subtle activity of TA with high sensitivity.

CMR Imaging Assessing Viability in Patients With Chronic Ventricular Dysfunction Due to Coronary Artery Disease: A Meta-Analysis of Prospective Trials

Abstract: Objectives The purpose of this study was to compare the diagnostic accuracy of cardiac magnetic resonance (CMR) assessing myocardial viability in patients with chronic left ventricular (LV) dysfunction due to coronary artery disease using 3 techniques: 1) end-diastolic wall thickness (EDWT); 2) low-dose dobutamine (LDD); and 3) contrast delayed enhancement (DE). Background CMR has been proposed to assess myocardial viability over the past decade. However, the best CMR strategy to evaluate patients being contemplated for revascularization has not yet been determined. Some centers advocate DE CMR due to its high sensitivity to identify scar, whereas others favor the use of LDD CMR for its ability to identify contractile reserve. Methods A systematic review of MEDLINE, Cochrane, and Embase for all the prospective trials assessing myocardial viability in subjects with chronic LV dysfunction using CMR was performed using a standard approach for meta-analysis for diagnostic tests and a bivariate analysis of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results A total of 24 studies of CMR evaluating myocardial viability with 698 patients fulfilled the inclusion criteria. Eleven studies used DE, 9 studies used LDD, and 4 studies used EDWT. Our meta-analysis indicates that among CMR methods, DE CMR provides the highest sensitivity as well as the highest NPV (95% and 90%, respectively) for predicting improved segmental LV contractile function after revascularization, followed by EDWT CMR, whereas LDD CMR demonstrated the lowest sensitivity/NPV among all modalities. On the other hand, LDD CMR offered the highest specificity and PPV (91% and 93%, respectively), followed by DE CMR, whereas EDWT showed the lowest of these parameters. Conclusions DE CMR provides the highest sensitivity and NPV, whereas LDD CMR provides the best specificity and PPV. In light of these findings, integrating these 2 methods should provide increased accuracy in evaluating patients with chronic LV dysfunction being considered for revascularization.

Metabolic syndrome, diabetes, and incidence and progression of coronary calcium: the Multiethnic Study of Atherosclerosis study.

Abstract: Objectives This study sought to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM) versus those with neither condition. Background MetS and DM are associated with subclinical atherosclerosis as evidenced by CAC. Methods The MESA (Multiethnic Study of Atherosclerosis) included 6,814 African American, Asian, Caucasian, and Hispanic adults 45 to 84 years of age, who were free of cardiovascular disease at baseline. Of these, 5,662 subjects (51% women, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac computed tomography scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%) to incidence and progression in subjects with neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years. Results Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals [CI]) for incident CAC were 1.7 (95% CI: 1.4 to 2.0), 1.9 (95% CI: 1.4 to 2.4), and 1.8 (95% CI: 1.4 to 2.2) (all p Conclusions Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared with individuals without these conditions, with progression also predicting coronary heart disease events in those with MetS and DM.

RV dysfunction in pulmonary hypertension is independently related to pulmonary artery stiffness.

Abstract: Objectives: This study investigated whether right ventricular (RV) adaptation to chronic pressure overload is associated with pulmonary artery (PA) stiffness beyond the degree of severity of pulmon...

Combined CT Coronary Angiography and Stress Myocardial Perfusion Imaging for Hemodynamically Significant Stenoses in Patients With Suspected Coronary Artery Disease: A Comparison With Fractional Flow Reserve

Abstract: Objectives We sought to determine the accuracy of combined coronary computed tomography angiography (CTA) and computed tomography stress myocardial perfusion imaging (CTP) in the detection of hemodynamically significant stenoses using fractional flow reserve (FFR) as a reference standard in patients with suspected coronary artery disease. Background CTP can be qualitatively assessed by visual interpretation or quantified by the transmural perfusion ratio determined as the ratio of subendocardial to subepicardial contrast attenuation. The incremental value of each technique in addition to coronary CTA to detect hemodynamically significant stenoses is not known. Methods Forty symptomatic patients underwent FFR and 320-detector computed tomography assessment including coronary CTA and CTP. Myocardial perfusion was assessed using the transmural perfusion ratio and visual perfusion assessment. Computed tomography images were assessed by consensus of 2 observers. Transmural perfusion ratio Results Coronary CTA detected FFR-significant stenoses with 95% sensitivity and 78% specificity. The additional use of visual perfusion assessment and the transmural perfusion ratio both increased the specificity to 95%, with sensitivity of 87% and 71%, respectively. The area under the receiver-operating characteristic curve for coronary CTA + visual perfusion assessment was significantly higher than both coronary CTA (0.93 vs. 0.85, p = 0.0003) and coronary CTA + the transmural perfusion ratio (0.93 vs. 0.79, p = 0.0003). Per-vessel and per-patient accuracy for coronary CTA, coronary CTA + the transmural perfusion ratio, and coronary CTA + visual perfusion assessment was 83% and 83%, 87% and 92%, and 92% and 95%, respectively. Conclusions In suspected coronary artery disease, combined coronary CTA + CTP identifies patients with hemodynamically significant stenoses with >90% accuracy compared with FFR. When interpreted with coronary CTA, visual perfusion assessment provided superior incremental value in the detection of FFR-significant stenoses compared with the quantitative transmural perfusion ratio assessment.

Effects of p38 mitogen-activated protein kinase inhibition on vascular and systemic inflammation in patients with atherosclerosis.

Abstract: Objectives This study sought to determine the effects of a p38 mitogen-activated protein kinase inhibitor, losmapimod, on vascular inflammation, by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography imaging. Background The p38 mitogen-activated protein kinase cascade plays an important role in the initiation and progression of inflammatory diseases, including atherosclerosis. Methods Patients with atherosclerosis on stable statin therapy (n = 99) were randomized to receive losmapimod 7.5 mg once daily (lower dose [LD]), twice daily (higher dose [HD]) or placebo for 84 days. Vascular inflammation was assessed by FDG positron emission tomography/computed tomography imaging of the carotid arteries and aorta; analyses focused on the index vessel (the artery with the highest average maximum tissue-to-background ratio [TBR] at baseline). Serum inflammatory biomarkers and FDG uptake in visceral and subcutaneous fat were also measured. Results The primary endpoint, change from baseline in average TBR across all segments in the index vessel, was not significantly different between HD and placebo (ΔTBR: −0.04 [95% confidence interval [CI]: −0.14 to +0.06], p = 0.452) or LD and placebo (ΔTBR: −0.02 [95% CI: −0.11 to +0.06], p = 0.579). However, there was a statistically significant reduction in average TBR in active segments (TBR ≥1.6) (HD vs. placebo: ΔTBR: −0.10 [95% CI: −0.19 to −0.02], p = 0.0125; LD vs. placebo: ΔTBR: −0.10 [95% CI: −0.18 to −0.02], p = 0.0194). The probability of a segment being active was also significantly reduced for HD when compared with placebo (OR: 0.57 [95% CI: 0.41 to 0.81], p = 0.002). Within the HD group, reductions were observed in placebo-corrected inflammatory biomarkers including high-sensitivity C-reactive protein (% reduction: −28% [95% CI: −46 to −5], p = 0.023) as well as FDG uptake in visceral fat (ΔSUV: −0.05 [95% CI: −0.09 to −0.01], p = 0.018), but not subcutaneous fat. Conclusions Despite nonsignificant changes for the primary endpoint of average vessel TBR, HD losmapimod reduced vascular inflammation in the most inflamed regions, concurrent with a reduction in inflammatory biomarkers and FDG uptake in visceral fat. These results suggest a systemic anti-inflammatory effect. (A Study to Evaluate the Effects of 3 Months Dosing With GW856553, as Assessed FDG-PET/CT Imaging; NCT00633022)

Sustained acceleration in carotid atherosclerotic plaque progression with intraplaque hemorrhage: A long-term time course study

Abstract: Objectives This study sought to determine the immediate and long-term effects of intraplaque hemorrhage (IPH) on plaque progression in the carotid artery. Background Previous studies have associated IPH in the carotid artery with more rapid plaque progression. However, the time course and long-term effect remain unknown. Carotid magnetic resonance imaging is a noninvasive imaging technique that has been validated with histology for the accurate in vivo detection of IPH and measurement of plaque burden. Methods Asymptomatic subjects with 50% to 79% carotid stenosis underwent carotid magnetic resonance imaging at baseline and then serially every 18 months for a total of 54 months. Subjects with IPH present in at least 1 carotid artery at 54 months were selected. Subsequently, presence/absence of IPH and wall volume were determined independently in all time points for both sides. A piece-wise progression curve was fit by using a linear mixed model to compare progression rates described as annualized changes in wall volume between periods defined by their relationship to IPH development. Results From 14 subjects who exhibited IPH at 54 months, 12 arteries were found to have developed IPH during the study period. The progression rates were –20.5 ± 13.1, 20.5 ± 13.6, and 16.5 ± 10.8 mm3/year before, during, and after IPH development, respectively. The progression rate during IPH development tended to be higher than the period before (p = 0.080) but comparable to the period after (p = 0.845). The progression rate in the combined period during/after IPH development was 18.3 ± 6.5 mm3/year, which indicated significant progression (p = 0.008 compared with a slope of 0) and was higher than the period before IPH development (p = 0.018). No coincident ischemic events were noted for new IPH. Conclusions The development of IPH posed an immediate and long-term promoting effect on plaque progression. IPH seems to alter the biology and natural history of carotid atherosclerosis. Early identification of patients with IPH may prove invaluable in optimizing management to minimize future sequelae.

Aortic Valve Calcium Independently Predicts Coronary and Cardiovascular Events in a Primary Prevention Population

Abstract: Objectives This study sought to test whether aortic valve calcium (AVC) is independently associated with coronary and cardiovascular events in a primary-prevention population. Background Aortic sclerosis is associated with increased cardiovascular morbidity and mortality among the elderly, but the mechanisms underlying this association remain controversial. Also, it is unknown whether this association extends to younger individuals. Methods We performed a prospective analysis of 6,685 participants in MESA (Multi-Ethnic Study of Atherosclerosis). All subjects, ages 45 to 84 years and free of clinical cardiovascular disease at baseline, underwent computed tomography for AVC and coronary artery calcium scoring. The primary, pre-specified combined endpoint of cardiovascular events included myocardial infarctions, fatal and nonfatal strokes, resuscitated cardiac arrest, and cardiovascular death, whereas a secondary combined endpoint of coronary events excluded strokes. The association between AVC and clinical events was assessed using Cox proportional hazards regression with incremental adjustments for demographics, cardiovascular risk factors, inflammatory biomarkers, and subclinical coronary atherosclerosis. Results Over a median follow-up of 5.8 years (interquartile range: 5.6 to 5.9 years), adjusting for demographics and cardiovascular risk factors, subjects with AVC (n = 894, 13.4%) had higher risks of cardiovascular (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 1.10 to 2.03) and coronary (HR: 1.72; 95% CI: 1.19 to 2.49) events compared with those without AVC. Adjustments for inflammatory biomarkers did not alter these associations, but adjustment for coronary artery calcium substantially attenuated both cardiovascular (HR: 1.32; 95% CI: 0.98 to 1.78) and coronary (HR: 1.41; 95% CI: 0.98 to 2.02) event risk. AVC remained predictive of cardiovascular mortality even after full adjustment (HR: 2.51; 95% CI: 1.22 to 5.21). Conclusions In this MESA cohort, free of clinical cardiovascular disease, AVC predicts cardiovascular and coronary event risk independent of traditional risk factors and inflammatory biomarkers, likely due to the strong correlation between AVC and subclinical atherosclerosis. The association of AVC with excess cardiovascular mortality beyond coronary atherosclerosis risk merits further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487 )

Coronary flow reserve during dipyridamole stress echocardiography predicts mortality

Abstract: Objectives The goal of this study was to evaluate the ability of coronary flow reserve (CFR) over regional wall motion to predict mortality in patients with known or suspected coronary artery disease (CAD). Background CFR evaluated using pulsed Doppler echocardiography testing on left anterior descending artery is the state-of-the-art method during vasodilatory stress echocardiography. Methods In a prospective, multicenter, observational study, we evaluated 4,313 patients (2,532 men; mean age 65 ± 11 years) with known (n = 1,547) or suspected (n = 2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFR evaluation of left coronary descending artery (LAD) by Doppler. Overall mortality was the only endpoint analyzed. Results Stress echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was 2.35 ± 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR ≤2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36), 146 patients died. The 4-year mortality was markedly higher in subjects with CFR ≤2 than in those with CFR >2, both considering the group with ischemia (39% vs. 7%; p Conclusions CFR on LAD is a strong and independent indicator of mortality, conferring additional prognostic value over wall motion analysis in patients with known or suspected CAD. A negative result on stress echocardiography with a normal CFR confers an annual risk of death

A Quantitative Pixel-Wise Measurement of Myocardial Blood Flow by Contrast-Enhanced First-Pass CMR Perfusion Imaging: Microsphere Validation in Dogs and Feasibility Study in Humans

Abstract: Objectives The aim of this study was to evaluate fully quantitative myocardial blood flow (MBF) at a pixel level based on contrast-enhanced first-pass cardiac magnetic resonance (CMR) imaging in dogs and in patients. Background Microspheres can quantify MBF in subgram regions of interest, but CMR perfusion imaging may be able to quantify MBF and differentiate blood flow at a much higher resolution. Methods First-pass CMR perfusion imaging was performed in a dog model with local hyperemia induced by intracoronary adenosine. Fluorescent microspheres were the reference standard for MBF validation. CMR perfusion imaging was also performed on patients with significant coronary artery disease (CAD) by invasive coronary angiography. Myocardial time-signal intensity curves of the images were quantified on a pixel-by-pixel basis using a model-constrained deconvolution analysis. Results Qualitatively, color CMR perfusion pixel maps were comparable to microsphere MBF bull's-eye plots in all animals. Pixel-wise CMR MBF estimates correlated well against subgram (0.49 ± 0.14 g) microsphere measurements (r = 0.87 to 0.90) but showed minor underestimation of MBF. To reduce bias due to misregistration and minimize issues related to repeated measures, 1 hyperemic and 1 remote sector per animal were compared with the microsphere MBF, which improved the correlation (r = 0.97 to 0.98), and the bias was close to zero. Sector-wise and pixel-wise CMR MBF estimates also correlated well (r = 0.97). In patients, color CMR stress perfusion pixel maps showed regional blood flow decreases and transmural perfusion gradients in territories served by stenotic coronary arteries. MBF estimates in endocardial versus epicardial subsectors, and ischemic versus remote sectors, were all significantly different (p Conclusions Myocardial blood flow can be quantified at the pixel level (∼32 μl of myocardium) on CMR perfusion images, and results compared well with microsphere measurements. High-resolution pixel-wise CMR perfusion maps can quantify transmural perfusion gradients in patients with CAD.

Plaque composition and clinical outcomes in acute coronary syndrome patients with metabolic syndrome or diabetes.

Abstract: Objectives The goal of this study was to characterize the extent and composition of coronary atherosclerosis in patients with diabetes mellitus or the metabolic syndrome (Met Syn) presenting with acute coronary syndromes (ACS). Background Diabetes and Met Syn patients have increased rates of major adverse cardiac events (MACE), yet a systematic description of nonculprit lesions for these high-risk groups is incomplete. Methods In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, ACS patients underwent 3-vessel quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention (PCI). Subsequent MACE (cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina) were adjudicated to the originally treated culprit versus untreated nonculprit lesions in 3 patient groups: 1) diabetes; 2) Met Syn; and 3) neither. Median length of follow-up was 3.4 years. Results Of 673 patients, 119 (17.7%) had diabetes and 239 (35.5%) had Met Syn. The cumulative 3-year MACE rate was 29.4% in patients with diabetes, 21.3% with Met Syn, and 17.4% with neither (p = 0.03). MACE adjudicated to untreated nonculprit lesions occurred in 18.7%, 11.7%, and 9.7% of patients, respectively (p = 0.06). Nonculprit lesions in diabetes and Met Syn patients were longer and had greater plaque burden, smaller lumen areas, with greater necrotic core and calcium content. Diabetes and Met Syn patients with future MACE had greater necrotic core and calcification compared with the normal cardiometabolic group. Conclusions In this PCI ACS population, patients with diabetes and Met Syn had higher 3-year MACE rates. Lesion length, plaque burden, necrotic core, and calcium content were significantly greater among nonculprit lesions of patients with diabetes and Met Syn, but only necrotic core and calcium were significantly greater in the nonculprit lesions of patients with a future MACE in this exploratory analysis.

Quantification of Extracellular Matrix Expansion by CMR in Infiltrative Heart Disease

Abstract: Objectives The aim of this study was to perform direct quantification of myocardial extracellular volume fraction (ECF) with T1-weighted cardiac magnetic resonance (CMR) imaging in patients suspected to have infiltrative heart disease. Background Infiltrative heart disease refers to accumulation of abnormal substances within the myocardium. Qualitative assessment of late gadolinium enhancement (LGE) remains the most commonly used method for CMR evaluation of patients suspected with myocardial infiltration. This technique is widely available and can be performed in a reproducible and standardized manner. However, the degree of extracellular matrix expansion due to myocardial infiltration in the intercellular space has, to date, not been amenable to noninvasive quantification with LGE. Methods We performed 3-T CMR in 38 patients (mean age 68 ± 15 years) who were referred for assessment of infiltrative heart disease and also in 9 healthy volunteers as control subjects. The T1 quantification by Look-Locker gradient-echo before and after contrast determined segmental myocardial partition coefficients. The ECF was obtained by referencing the tissue partition coefficient for gadolinium to the plasma volume fraction in blood, derived from serum hematocrit. Cine CMR and LGE imaging in matching locations were also performed. Results Seventeen patients (45%) had cardiac amyloidosis (CA) (biopsy-confirmed or clinically highly probable), 20 (53%) had a non-amyloid cardiomyopathy, and 1 had lysosomal storage disease. Median global ECF was substantially higher in CA patients (0.49) compared with non-amyloid cardiomyopathy patients (0.33, p Conclusions The CMR ECF quantification identified substantial expansion of the interstitial space in patients with CA compared with volunteers. Further studies using this technique for diagnosis and assessment of the severity of myocardial infiltration are warranted.