Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.

BACKGROUND: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037). CONCLUSIONS: Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

Myocardial Extracellular Volume Fraction and T1 Mapping by Cardiac Magnetic Resonance Compared Between Patients With and Without Type 2 Diabetes, and the Effect of ECV and T2D on Cardiovascular Outcomes.

Background: To investigate the difference in myocardial extracellular volume fraction (ECV) by cardiac magnetic resonance (CMR) T1 mapping between patients with and without type 2 diabetes (T2D), and the effect of ECV and T2D on cardiovascular (CV) outcomes. Methods: All patients aged > 18 years with known or suspected coronary artery disease who underwent CMR for assessment of myocardial ischemia or myocardial viability at the Department of Cardiology of the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from September 2017 to December 2018 were screened for inclusion eligibility. Left ventricular ejection fraction (LVEF), late gadolinium enhancement, and T1 mapping were performed. ECV values were derived from myocardial native T1 and contrast-enhanced T1 values that were obtained using modified Look-Locker inversion recovery at the septum of the mid-cavity short-axis map. Demographic data, clinical characteristics, and CV outcomes were collected by retrospective chart review. Composite CV outcomes included CV death, acute coronary syndrome, heart failure hospitalization, or ventricular tachycardia (VT)/ventricular fibrillation. Results: A total of 739 subjects (mean age: 69.5 ± 14.0 years, 49.3% men) were included. Of those, 188 subjects had T2D (25.4%). ECV was significantly higher in T2D than in non-T2D (30.0 ± 5.9% vs. 28.8 ± 4.7%, p = 0.004). During the mean follow-up duration of 26.2 ± 8.5 months, 43 patients (5.8%) had a clinical composite outcome, as follows: three CV death (0.4%), seven acute coronary syndrome (0.9%), 33 heart failure hospitalization (4.5%), and one VT (0.1%). T2D, low LVEF, and high ECV were all identified as independent predictors of CV events. Patients with T2D and high ECV had the highest risk of CV events. Conclusion: Among patients with known or suspected coronary artery disease, patients with T2D had a higher ECV. T2D and high ECV were both found to be independent risk factors for adverse CV outcomes.

Automatic quantification of the myocardial extracellular volume by cardiac computed tomography: Synthetic ECV by CCT.

BACKGROUND: The quantification of extracellular volume fraction (ECV) by Cardiac Computed Tomography (CCT) can identify changes in the myocardial interstitium due to fibrosis or infiltration. Current methodologies require laboratory blood hematocrit (Hct) measurement - which complicates the technique. The attenuation of blood (HUblood) is known to change with anemia. We hypothesized that the relationship between Hct and HUblood could be calibrated to rapidly generate a synthetic ECV without formally measuring Hct. METHODS: The association between Hct and HUblood was derived from forty non-contrast thoracic CT scans using regression analysis. Synthetic Hct was then used to calculate synthetic ECV, and in turn compared with ECV using blood Hct in a validation cohort with mild interstitial expansion due to fibrosis (aortic stenosis, n = 28, ECVCT = 28 ± 4%) and severe interstitial expansion due to amyloidosis (n = 27; ECVCT = 54 ± 11%, p < 0.001). For histological validation, synthetic ECV was correlated with collagen volume fraction (CVF) in a separate cohort with aortic stenosis (n = 18). All CT scans were performed at 120 kV and 160 mAs. RESULTS: HUblood was a good predictor of Hct (R2 = 0.47; p < 0.01), with the regression model (Hct = [0.51 * HUblood] + 17.4) describing the association. Synthetic ECV correlated well with conventional ECV (R2 = 0.96; p < 0.01) with minimal bias and 2SD difference of 5.7%. Synthetic ECV correlated as well as conventional ECV with histological CVF (both R2 = 0.50, p < 0.01). Finally, we implemented an automatic ECV plug-in for offline analysis. CONCLUSION: Synthetic ECV by CCT provides instantaneous quantification of the myocardial extracellular space without the need for blood sampling.

Estimation of myocardial extracellular volume fraction with cardiac CT in subjects without clinical coronary artery disease: A feasibility study.

BACKGROUND: Use of CT for assessment of extracellular volume fraction (ECV) is a new approach toward the evaluation of diffuse and focal myocardial fibrosis. It has recently been demonstrated that a hybrid algorithm of half- and full-scan reconstruction can improve image quality of delayed-phase CT. OBJECTIVE: The purpose of this study was to evaluate reproducibility of CT measurement of ECV of the myocardium using pre-contrast and delayed-phase CT, and to investigate the association between ECV and location, age and gender in subjects without clinical coronary artery disease. METHODS: Thirty-eight subjects (ages 45-78, mean 65 years, 14 females) without coronary artery stenosis, stress perfusion deficits or myocardial delayed enhancement on comprehensive cardiac CT comprise the study population. Delayed-phase CT was reconstructed with the hybrid algorithm. ECV was calculated as a ratio of the change in Hounsfield unit of the myocardium and the left ventricular (LV) blood before and after contrast administration, multiplied by (1-hematocrit). RESULTS: Good inter- and intra-observer agreement was observed in CT measurement of ECV (intraclass correlation coefficient: 0.968 and 0.971, respectively). Mean ECV was 26.1 ± 2.0% (range 22.6-30.0%), and was positively related to age (r = 0.46, p = 0.003). Mean ECV in males was lower compared with females (25.5 ± 2.0% vs. 27.1 ± 1.8%, p = 0.02). There was no statistically significant difference in ECV between anterior, septal, inferior, and lateral segments. CONCLUSIONS: CT measurement of myocardial ECV showed high inter- and intra-observer reproducibility, and age-related increase and gender-related difference of ECV were demonstrated. This might enable additional CT evaluation of diffuse and focal myocardial fibrosis in various pathological conditions as part of a comprehensive cardiac CT examination.