Global Extracellular Volume Research Articles

Lower stress perfusion in patients with myocardial infarction with non-obstructive coronary arteries compared to controls in long-term follow-up with quantitative perfusion mapping

Abstract Introduction Myocardial infarction with non-obstructive coronary arteries (MINOCA) constitutes a heterogenous condition with different coronary, cardiac and non-cardiac etiologies. Cardiovascular magnetic resonance imaging (CMR) has emerged as an important diagnostic tool in recent years and is now recommended in patients with MINOCA as a working diagnosis. However, despite early CMR following admission for MINOCA, no cause can be found in around 25% of all patients. A pathophysiological mechanism may be diffuse global coronary microvascular dysfunction (CMD) which has emerged as an important cause of myocardial ischemia. Quantitative adenosine stress CMR perfusion mapping allows for absolute quantification of myocardial perfusion, reflecting CMD in the absence of obstructive coronary disease in MINOCA patients. Purpose To study the presence of CMD in MINOCA patients with an initial normal CMR scan compared to healthy controls. Methods Patients from the multicenter myocardial infarction in our city with normal Coronaries 2 (SMINC-2) study, with a normal CMR scan 2–4 days after hospitalization, and healthy age- and sex-matched controls underwent stress perfusion at 1.5T (MAGNETOM Aera). Native rest T1 and T2 short-axis maps were acquired. Quantitative perfusion maps were acquired during adenosine stress (140 micrograms/kg/min) and at rest following an intravenous contrast bolus (0.05 mmol/kg of gadoteric acid, Gd-DOTA). Post contrast T1 maps were acquired after intravenous contrast (total dose 0.2 mmol/kg) rendering extracellular volume (ECV) maps. Global native T1, T2, ECV and rest and stress perfusion values were acquired by averaging segmental values per patient. Myocardial perfusion reserve (MPR) was calculated as perfusion in stress divided by rest. Values were presented as mean±standard deviation and compared with the independent t-test in normally distributed data, and with the Mann-Whitney U test in non-normally distributed data. Clinical data regarding cardiovascular risk factors, smoking and medications were presented as numbers (percentages) and compared with Fisher's exact test. Rate pressure product (RPP) was calculated as systolic blood pressure multiplied by heart rate in rest and stress. Results In total, 15 patients (59±16 years old, 60% female), and 15 healthy age- and sex-matched controls, were included. There was a trend towards higher incidence of hypertension in patients compared to controls, however no difference in other risk factors (Table 1). Compared to controls, MINOCA patients had lower perfusion in stress (Figure 1). There was no difference in global native T1, T2, ECV, rest perfusion, MPR or hemodynamic parameters between the MINOCA patients and the controls (p>0.05 for all, Table 1). Conclusions Myocardial stress perfusion is lower in MINOCA patients with a normal initial CMR scan compared to age- and sex-matched controls suggesting CMD as a possible pathophysiological mechanism in MINOCA. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung Foundation

Increased myocardial extracellular volume is associated with myocardial iron overload and heart failure in thalassemia major.

Myocardial extracellular volume (ECV) by cardiovascular magnetic resonance (CMR) is a surrogate marker of diffuse fibrosis. We evaluated the association between ECV and demographics, CMR findings, and cardiac involvement in patients with thalassemia major (TM). A total of 108 β-TM patients (62 females, 40.16 ± 8.83 years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network, and 16 healthy subjects (6 females, 37.12 ± 16.13 years) underwent CMR. The protocol included assessment of T2*, native T1, and T2 values in all 16 myocardial segments for myocardial iron overload (MIO) quantification, cine images for left ventricular (LV) function quantification, post-contrast T1 mapping for ECV calculation, and late gadolinium enhancement (LGE) technique for replacement myocardial fibrosis detection. Global ECV values were significantly higher in females than in males. Global ECV values were significantly higher in patients with significant MIO (global heart T2* < 20 ms) than in patients without significant MIO, and both groups exhibited higher global ECV values than healthy subjects. No association was detected between native T1 and ECV values, while patients with reduced global heart T2 values showed significantly higher global ECV values than patients with normal and increased global heart T2. Global ECV values were not correlated with LV function/size and were comparable between patients with and without LGE. Compared to patients without heart failure, patients with a history of heart failure (N = 10) showed significantly higher global heart ECV values. In TM, increased myocardial ECV, potentially reflecting diffuse interstitial fibrosis, is associated with MIO and heart failure. • CMR-derived myocardial extracellular volume is increased in thalassemia major patients, irrespective of the presence of late gadolinium enhancement. • In thalassemia major, myocardial iron overload contributes to the increase in myocardial ECV, which potentially reflects diffuse interstitial fibrosis and is significantly associated with a history of heart failure.

18F-flutemetamol positron emission tomography in cardiac amyloidosis

PurposeBone-tracer scintigraphy has an established role in diagnosis of cardiac amyloidosis (CA) as it detects transthyretin amyloidosis (ATTR). Positron emission tomography (PET) with amyloid tracers has shown high sensitivity for detection of both ATTR and light-chain (AL) CA. We aimed to investigate the accuracy of 18F-flutemetamol in CA. MethodsWe enrolled patients with CA or non-amyloid heart failure (NA-HF), who underwent cardiac 18F-flutemetamol PET/MRI or PET/CT. Myocardial and blood pool standardized tracer uptake values (SUV) were estimated. Late gadolinium enhancement (LGE) and T1 mapping/ extracellular volume (ECV) estimation were performed. ResultsWe included 17 patients (12 with CA, 5 with NA-HF). PET/MRI was conducted in 13 patients, while PET/CT was conducted in 4. LGE was detected in 8 of 9 CA patients. Global relaxation time and ECV were higher in CA (1448 vs. 1326, P = 0.02 and 58.9 vs. 33.7%, P = 0.006, respectively). Positive PET studies were demonstrated in 2 of 12 patients with CA (AL and ATTR). Maximal and mean SUV did not differ between groups (2.21 vs. 1.69, P = 0.18 and 1.73 vs. 1.30, P = 0.13). ConclusionAlthough protein-independent binding is supported by our results, the diagnostic yield of PET was low. We demonstrate here for the first time the low sensitivity of PET for CA.

Measurement of myocardial extracellular volume using cardiac dual-energy computed tomography in patients with ischaemic cardiomyopathy: a comparison of different methods.

To clarify the consistency and efficiency of four methods for myocardial extracellular volume (ECV) measurement (manual method using dual-energy iodine [manual ECViodine], manual method using subtraction [manual ECVsub], automatic ECViodine, automatic ECVsub) in patients with ischaemic cardiomyopathy. Fifty patients with ischaemic cardiomyopathy who underwent coronary computed tomography angiography (CCTA) following dual-energy computed tomography (CT) with late iodine enhancement (LIE-DECT) were included. LIE with ischaemic patterns representing scarring could be detected using iodine maps in all patients. The global and remote ECVs of non-scarred myocardium were measured using four methods (manual ECViodine, automatic ECViodine, manual ECVsub, and automatic ECVsub). The consistency and time cost of the four methods were analysed. There were no significant differences in the mean global ECVs or remote ECVs among the four methods (p > 0.05). ECViodine resulted in a lower Bland-Altman limit of agreement than that of ECVsub for both global and remote measurements. Intraclass correlation coefficients of the automatic and manual ECViodine measurements demonstrated better concordance (0.804 and 0.859, respectively) than those of automatic and manual ECVsub (0.607 and 0.669, respectively) for both global and remote measurements. The measurement time for automatic ECV was less than that for manual ECV for both global and remote ECV measurements (all p < 0.001). ECV measurement using dual-energy iodine yielded good concordance, and the automatic method has the advantages of being simple and convenient, which can become a useful tool for quantification of myocardial fibrosis.

Quantitative analysis of late iodine enhancement using dual-layer spectral detector computed tomography: comparison with magnetic resonance imaging.

To evaluate the segmental myocardial extracellular volume (ECV) fraction and to define a threshold ECV value that can be used to distinguish positive late gadolinium enhancement (LGE) segments from negative myocardial segments using dual-layer spectral detector computed tomography (SDCT), with magnetic resonance imaging (MRI) as a reference. Fifty-six subjects with cardiac disease or suspected cardiac disease, underwent both late iodine enhancement on CT (CT-LIE) scanning and late gadolinium enhancement on MRI (MRI-LGE) scanning. Each procedure occurred within a week of the other. Global and segmental ECVs of the left ventricle were measured by CT and MRI images. According to the location and pattern of delayed enhancement on MRI image, myocardial segments were classified into 3 groups: ischemic LGE segments (group 1), nonischemic LGE segments (group 2) and negative LGE segments (group 3). The correlation and agreement between CT-ECV and MRI-ECV were compared on a per-segment basis. Receiver operating characteristic (ROC) curve analysis was performed to establish a threshold for LIE detection. Among the 56 patients, 896 segments were analyzed, and of these, 73 segments were in group 1, 229 segments were in group 2, and 594 segments were in group 3. In segmental analysis, CT-ECV in group 3 (27.0%; 24.9-28.9%) was significantly lower than that in group 1 (33.2%; 30.7-36.3%) and group 2 (34.9%; 32.3-39.8%; all P<0.001). Good correlations were seen between CT-ECV and MRI-ECV for all groups (group 1: r=0.920; group 2: r=0.936; group 3: r=0.799; all P<0.001). Bland-Altman analysis between CT-ECV and MRI-ECV showed a small bias in all 3 groups (group 1: -2.1%, 95% limits of agreement -11.3-7.1%; group 2: -0.6%, 95% limits of agreement -13.1-11.9%; group 3: 1.0%, 95% limits of agreement -12.7-14.7%). CT-ECV could differentiate between LGE-positive and LGE-negative segments with 83.1% sensitivity and 93.3% specificity at a cutoff of 31%. ECV values derived from CT imaging showed good correlation and agreement with MR imaging findings, and CT-ECV provided high diagnostic accuracy for discriminating between LGE-positive and LGE-negative segments. Thus, cardiac CT imaging might be a suitable noninvasive imaging technique for myocardial ECV quantification.

Extracellular volume is an independent predictor of arrhythmic burden in dilated cardiomyopathy

The current stratification of arrhythmic risk in dilated cardiomyopathy (DCM) is sub-optimal. Cardiac fibrosis is involved in the pathology of arrhythmias; however, the relationship between cardiovascular magnetic resonance (CMR) derived extracellular volume (ECV) and arrhythmic burden (AB) in DCM is unknown. This study sought to evaluate the presence and extent of replacement and interstitial fibrosis in DCM and to compare the degree of fibrosis between DCM patients with and without AB. This is a prospective, single-center, observational study. Between May 2019 and September 2020, 102 DCM patients underwent CMR T1 mapping. 99 DCM patients (88 male, mean age 45.2 ± 11.8 years, mean EF 29.7 ± 10%) composed study population. AB was defined as the presence of VT or a high burden of PVCs. There were 41 (41.4%) patients with AB and 58 (58.6%) without AB. Replacement fibrosis was assessed with late gadolinium enhancement (LGE), whereas interstitial fibrosis with ECV. Overall, LGE was identified in 41% of patients. There was a similar distribution of LGE (without AB 50% vs. with AB 53.7%; p = 0.8) and LGE extent (without AB 4.36 ± 5.77% vs. with AB 4.68 ± 3.98%; p = 0.27) in both groups. ECV at nearly all myocardial segments and a global ECV were higher in patients with AB (global ECV: 27.9 ± 4.9 vs. 30.3 ± 4.2; p < 0.02). Only indexed left ventricular end-diastolic diameter (HR 1.1, 95%CI 1.0–1.2; p < 0.02) and global ECV (HR 1.12, 95%CI 1.0–1.25; p < 0.02) were independently associated with AB. The global ECV cut-off value of 31.05% differentiated both groups (AUC 0.713; 95%CI 0.598–0.827; p < 0.001). Neither qualitative nor quantitative LGE-based assessment of replacement fibrosis allowed for the stratification of DCM patients into low or high AB. Interstitial fibrosis, expressed as ECV, was an independent predictor of AB in DCM. Incorporation of CMR parametric indices into decision-making processes may improve arrhythmic risk stratification in DCM.

Abstract 14147: Septal Native T1 is Higher in Patients With Pre-Capillary Pulmonary Hypertension Compared to Post-Capillary Pulmonary Hypertension

Introduction: Right heart catheterization (RHC) is used to diagnose and classify pulmonary hypertension (PH). Because RHC is invasive, there is growing interest in non-invasive PH evaluation techniques, such as cardiac magnetic resonance (CMR). Hypothesis: CMR-derived fibrosis indices [native T1 (NT1) and extracellular volume (ECV)] differ between pre-capillary PH (PRE-PH), post-capillary PH (POST-PH) and controls. Methods: RHC-defined PH patients and healthy controls (N=25, age=52+/-13 years) underwent CMR. A cardiologist classified patients into PRE-PH (N=29, age=55+/-8 years) and POST-PH (N=19, age=66+/-13 years) based on RHC measurements and clinical history. T1 maps of the left ventricle were acquired using a Modified Look-Locker Inversion Recovery sequence before and after administration of gadolinium contrast. T1 maps were manually segmented using the AHA 16 segment model to obtain segmental native and post-contrast T1. Segmental ECV was calculated using NT1, post-contrast T1, and hematocrit. Global ECV and NT1 were calculated by averaging all segments. Results: PRE-PH had higher NT1 than POST-PH in segments 8 (1077+/-39 vs 1046+/-36 ms, p=.01), 9 (1082+/-47 vs 1051+/-44 ms, p=.03), and 14 (1080+/-74 vs 1028+/-53 ms, p=.01). Global ECV and NT1 were higher in PRE-PH (31+/-4% and 1056+/-36 ms) than controls (28+/-4% and 1013+/-29 ms) (p=.017 and p=.000, respectively). Conclusions: NT1 was different between PRE-PH and POST-PH in mid- and apical-septal segments, however segmental ECV and global measures were not. NT1 may reflect more than just ECV expansion, providing additional insight into the myocardium. Regional NT1 may complement RHC for classifying PH.

Prognostic importance of acute phase extracellular volume evaluated by cardiac magnetic resonance imaging for patients with acute myocardial infarction.

Myocardial extracellular volume (ECV) by cardiac magnetic resonance (CMR) in the acute phase of acute myocardial infarction (MI) more precisely predicts the functional recovery of infarct-related wall motion abnormalities and left ventricular (LV) remodeling than late gadolinium enhancement (LGE). The purpose of this study was to evaluate the prognostic importance of acute phase ECV in patients with AMI. We evaluated 61 consecutive AMI patients using 3.0T CMR. CMR examination was performed median 10days (7-15days) after PCI. Primary endpoint was defined as major adverse cardiac event (MACE). The median follow-up duration was 3.1years, and MACE occurred in 11 (18%) patients. Although LVEF and % infarct LGE volume were not associated with MACE in this study population, higher infarct ECV predicted the MACE with a hazard ratio (HR) of 4.04 (P = 0.02). High global ECV, which was a combined assessment of infarct ECV and remote ECV, also predicted MACE with a HR of 5.24 (P = 0.035). The addition of infarct ECV to remote ECV (global chi-squared score: 1.4) resulted in a significantly increased global chi-squared score (6.7; P = 0.017). Furthermore, after adjusting for the calculated propensity score for high global ECV, it remained an independent predictor of MACE with HR of 5.10 (P = 0.04). The quantification of ECV in the acute phase among AMI patients may provide an incremental prognostic value for predicting MACE beyond that of clinical, angiographic, and functional variables.

Fibrosis in Hypertrophic Cardiomyopathy Patients With and Without Sarcomere Gene Mutations

Patients with hypertrophic cardiomyopathy (HCM) and an identified sarcomere mutation have worse outcomes than those without though the underlying mechanism is incompletely understood. The presence of replacement fibrosis measured by late gadolinium enhancement (LGE) and diffuse fibrosis measured by extracellular volume (ECV) using cardiac magnetic resonance imaging (CMR) are associated with ventricular arrhythmias and cardiac mortality. We aimed to associate these two forms of fibrosis with identified sarcomere mutations. Three hundred and thirty-six (336) patients with HCM underwent CMR at a single quaternary referral centre between January 2012 and February 2017. Genetic testing was performed in 73 of these patients, yielding an identified sarcomeric mutation in 29 (G+), no mutation in 39 (G-), and a variant of unknown significance (VUS) in five. LGE was more prevalent in G+ compared to G- patients (86 vs. 56%, OR 4.3, p=0.01) and was more extensive (7.5±5.5% of left ventricular [LV] mass vs. 3.0±3.0%, p<0.001). Global ECV from myocardial segments excluding LGE was similar among both groups (26.9±2.9 vs. 25.6±2.8%, p=0.46). However, in G+ patients ECV was greater in the hypertrophied regions of the basal anteroseptum (30.2±7.0 vs. 26.8±3.6%, p=0.004) and basal inferoseptum (28.1±4.3 vs. 26.2±2.9%, p=0.005). Genotyped HCM patients with an identified sarcomere mutation have greater LGE and greater regional, but not global, ECV than HCM patients without an identified mutation. This difference in fibrosis may contribute to worse outcomes in patients with an identified HCM mutation.

Multi-parametric cardiovascular magnetic resonance with regadenoson stress perfusion is safe following pediatric heart transplantation and identifies history of rejection and cardiac allograft vasculopathy

BackgroundThe progressive risk of graft failure in pediatric heart transplantation (PHT) necessitates close surveillance for rejection and coronary allograft vasculopathy (CAV). The current gold standard of surveillance via invasive coronary angiography is costly, imperfect and associated with complications. Our goal was to assess the safety and feasibility of a comprehensive multi-parametric CMR protocol with regadenoson stress perfusion in PHT and evaluate for associations with clinical history of rejection and CAV.MethodsWe performed a retrospective review of 26 PHT recipients who underwent stress CMR with tissue characterization and compared with 18 age-matched healthy controls. CMR protocol included myocardial T2, T1 and extracellular volume (ECV) mapping, late gadolinium enhancement (LGE), qualitative and semi-quantitative stress perfusion (myocardial perfusion reserve index; MPRI) and strain imaging. Clinical, demographics, rejection score and CAV history were recorded and correlated with CMR parameters.ResultsMean age at transplant was 9.3 ± 5.5 years and median duration since transplant was 5.1 years (IQR 7.5 years). One patient had active rejection at the time of CMR, 11/26 (42%) had CAV 1 and 1/26 (4%) had CAV 2. Biventricular volumes were smaller and cardiac output higher in PHT vs. healthy controls. Global T1 (1053 ± 42 ms vs 986 ± 42 ms; p < 0.001) and ECV (26.5 ± 4.0% vs 24.0 ± 2.7%; p = 0.017) were higher in PHT compared to helathy controls. Significant relationships between changes in myocardial tissue structure and function were noted in PHT: increased T2 correlated with reduced LVEF (r = − 0.57, p = 0.005), reduced global circumferential strain (r = − 0.73, p < 0.001) and reduced global longitudinal strain (r = − 0.49, p = 0.03). In addition, significant relationships were noted between higher rejection score and global T1 (r = 0.38, p = 0.05), T2 (r = 0.39, p = 0.058) and ECV (r = 0.68, p < 0.001). The presence of even low-grade CAV was associated with higher global T1, global ECV and maximum segmental T2. No major side effects were noted with stress testing. MPRI was analyzed with good interobserver reliability and was lower in PHT compared to healthy controls (0.69 ± − 0.21 vs 0.94 ± 0.22; p < 0.001).ConclusionIn a PHT population with low incidence of rejection or high-grade CAV, CMR demonstrates important differences in myocardial structure, function and perfusion compared to age-matched healthy controls. Regadenoson stress perfusion CMR could be safely and reliably performed. Increasing T2 values were associated with worsening left ventricular function and increasing T1/ECV values were associated with rejection history and low-grade CAV. These findings warrant larger prospective studies to further define the role of CMR in PHT graft surveillance.

Progressive myocardial injury in myotonic dystrophy type II and facioscapulohumeral muscular dystrophy 1: a cardiovascular magnetic resonance follow-up study

AimMuscular dystrophy (MD) is a progressive disease with predominantly muscular symptoms. Myotonic dystrophy type II (MD2) and facioscapulohumeral muscular dystrophy type 1 (FSHD1) are gaining an increasing awareness, but data on cardiac involvement are conflicting. The aim of this study was to determine a progression of cardiac remodeling in both entities by applying cardiovascular magnetic resonance (CMR) and evaluate its potential relation to arrhythmias as well as to conduction abnormalities.Methods and results83 MD2 and FSHD1 patients were followed. The participation was 87% in MD2 and 80% in FSHD1. 1.5 T CMR was performed to assess functional parameters as well as myocardial tissue characterization applying T1 and T2 mapping, fat/water-separated imaging and late gadolinium enhancement. Focal fibrosis was detected in 23% of MD2) and 33% of FSHD1 subjects and fat infiltration in 32% of MD2 and 28% of FSHD1 subjects, respectively. The incidence of all focal findings was higher at follow-up. T2 decreased, whereas native T1 remained stable. Global extracellular volume fraction (ECV) decreased similarly to the fibrosis volume while the total cell volume remained unchanged. All patients with focal fibrosis showed a significant increase in left ventricular (LV) and right ventricular (RV) volumes. An increase of arrhythmic events was observed. All patients with ventricular arrhythmias had focal myocardial changes and an increased volume of both ventricles (LV end-diastolic volume (EDV) p = 0.003, RVEDV p = 0.031). Patients with supraventricular tachycardias had a significantly higher left atrial volume (p = 0.047).ConclusionWe observed a remarkably fast and progressive decline of cardiac morphology and function as well as a progression of rhythm disturbances, even in asymptomatic patients with a potential association between an increase in arrhythmias and progression of myocardial tissue damage, such as focal fibrosis and fat infiltration, exists. These results suggest that MD2 and FSHD1 patients should be carefully followed-up to identify early development of remodeling and potential risks for the development of further cardiac events even in the absence of symptoms.Trial registration ISRCTN, ID ISRCTN16491505. Registered 29 November 2017 – Retrospectively registered, http://www.isrctn.com/ISRCTN16491505

Radiation-Induced Myocardial Fibrosis in Long-Term Esophageal Cancer Survivors.

Radiation-induced cardiac toxicity is a potential lethal complication. The aim of this study was to assess whether there is a dose-dependent relationship between radiation dose and myocardial fibrosis in patients who received neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). Forty patients with EC treated with a transthoracic esophagectomy with (n = 20) or without (n = 20) nCRT (CROSS study regimen) were included. Cardiovascular magnetic resonance imaging (1.5 Tesla) for left ventricular (LV) function, late gadolinium enhancement, and T1 mapping were performed. Extracellular volume (ECV), as a surrogate for collagen burden, was measured for all LV segments separately. The dose-response relationship between ECV and mean radiation dose per LV myocardial segment was evaluated using a mixed-model analysis. Seventeen nCRT and 16 control patients were suitable for analysis. The mean time after treatment was 67.6 ± 8.1 (nCRT) and 122 ± 35 (controls) months (P = .02). In nCRT patients, we found a significantly higher mean global ECV of 28.2% compared with 24.0% in the controls (P < .001). After nCRT, LV myocardial segments with elevated ECV had received significantly higher radiation doses. In addition, a linear dose-effect relation was found with a 0.136% point increase of ECV for each Gy (P < .001). There were no differences in LV function measures and late gadolinium enhancement between both groups. Myocardial ECV was significantly higher in long-term EC survivors after nCRT compared with surgery only. Moreover, this ECV increase was linear with the radiation dose per LV segment, indicating radiation-induced myocardial fibrosis.

Cardiovascular magnetic resonance imaging reveals asymptomatic cardiomyopathy in newly diagnosed, HIV-infected South African adults

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): University of Stellenbosch Cardiology Research Fund and United States National Institutes of Health/Fogarty International Center Background Cardiovascular disease (CVD) is a leading cause of death and disability in people living with HIV (PLWH). The coronary disease burden in high income countries contrast what is experienced in low- and middle-income countries where cardiomyopathy remains prevalent. Cardiovascular magnetic resonance imaging (CMR) has the unique ability to characterise tissues to obtain "virtual histology". Our data support a high burden of myocardial disease, already present at the time of HIV diagnosis in a young South African cohort. Purpose Early, undiagnosed myocardial pathology in some antiretroviral therapy (ART) naïve persons appear to precede the development of poorly prognostic HIV associated cardiomyopathy. The burden and mechanisms underlying the progression to more advanced disease in treatment naïve PLWH remain largely unknown, as does the modifying effect of ART on these abnormalities. Studying early myocardial disease and its progression with serial CMR evaluation will improve our understanding of disease evolution. Methods 24 newly diagnosed, ART naïve adults without known CVD underwent a contrasted, 1.5T CMR study. Assessments included: Left ventricular (LV) volumes, mass, ejection fraction (EF), native and post-contrast T1 mapping, T2 mapping, extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging. Quantitative measurements were obtained using a semi-automated software. Qualitative LGE findings were reviewed by an EACVI level III accredited cardiologist. Results The median age of the cohort was 33, interquartile range (IQR) 30-43 years. Median CD4 count was 250, IQR 152-520 cells/uL. All patients had non-dilated LV"s according to indexed end diastolic volumes (Mean: 85 ± 15ml/m²). No patient had overt systolic dysfunction (Mean EF: 62 ± 6%). Non-trivial pericardial effusions were present in 71% of cases. Indexed LV mass measured normal (Mean: 65 ± 12g/m²). Mean global native T1 and T2 values were 1043 ± 46 and 49 ± 4ms respectively. Native T1 values were highest in the septum and inferior wall (Mean: 1054 ± 50 and 1047 ± 51ms respectively). Mean global ECV was 28 ± 4%. Non-ischaemic LGE was present in 71% of participants. In those with LGE, midmyocardial enhancement of the inferior septum represented 71% of abnormalities (Figure). Conclusion In this young cohort of newly diagnosed HIV-infected persons, the prevalence of myocardial abnormalities were high. The midmyocardial LGE and abnormal mapping parameters (high for our scanner and high normal for published data) suggest myocardial inflammation and fibrosis already present at HIV-diagnosis. This was most appreciable in the septum and inferior walls, and likely represents a diffuse process that may progress to symptomatic cardiomyopathy over time. Serial evaluation on ART and comparison with a matched HIV-negative control group is planned. This will allow quantitative comparison of tissue characterisation and explore the nature and evolution of these abnormalities. Abstract Figure. Late gadolinium enhancement (Arrows)

Regional Amyloid Burden Differences Evaluated Using Quantitative Cardiac MRI in Patients with Cardiac Amyloidosis.

ObjectiveThis study aimed to investigate the regional amyloid burden and myocardial deformation using T1 mapping and strain values in patients with cardiac amyloidosis (CA) according to late gadolinium enhancement (LGE) patterns.Materials and MethodsForty patients with CA were divided into 2 groups per LGE pattern, and 15 healthy subjects were enrolled. Global and regional native T1 and T2 mapping, extracellular volume (ECV), and cardiac magnetic resonance (CMR)-feature tracking strain values were compared in an intergroup and interregional manner.ResultsOf the patients with CA, 32 had diffuse global LGE (group 2), and 8 had focal patchy or no LGE (group 1). Global native T1, T2, and ECV were significantly higher in groups 1 and 2 than in the control group (native T1: 1384.4 ms vs. 1466.8 ms vs. 1230.5 ms; T2: 53.8 ms vs. 54.2 ms vs. 48.9 ms; and ECV: 36.9% vs. 51.4% vs. 26.0%, respectively; all, p < 0.001). Basal ECV (53.7%) was significantly higher than the mid and apical ECVs (50.1% and 50.0%, respectively; p < 0.001) in group 2. Basal and mid peak radial strains (PRSs) and peak circumferential strains (PCSs) were significantly lower than the apical PRS and PCS, respectively (PRS, 15.6% vs. 16.7% vs. 26.9%; and PCS, −9.7% vs. −10.9% vs. −15.0%; all, p < 0.001). Basal ECV and basal strain (2-dimensional PRS) in group 2 showed a significant negative correlation (r = −0.623, p < 0.001). Group 1 showed no regional ECV differences (basal, 37.0%; mid, 35.9%; and apical, 38.3%; p = 0.184).ConclusionQuantitative T1 mapping parameters such as native T1 and ECV may help diagnose early CA. ECV, in particular, can reflect regional differences in the amyloid deposition in patients with advanced CA, and increased basal ECV is related to decreased basal strain. Therefore, quantitative CMR parameters may help diagnose CA and determine its severity in patients with or without LGE.

Abstract 16798: Evidence of Abnormal T1 Mapping in Arrhythmic Mitral Valve Prolapse Without Significant Mitral Regurgitation

Background: Prior cardiac magnetic resonance (CMR) studies have reported abnormal T1 mapping, reflective of diffuse myocardial fibrosis, in patients with mitral valve prolapse (MVP) and ventricular arrhythmias. However, T1 mapping was derived from conventional Look-Locker sequences and/or obtained in selected MVP patients with severe mitral regurgitation (MR) and a clinical indication for CMR. Hypothesis: We hypothesize that extracellular volume (ECV) fraction, a marker of diffuse fibrosis derived from research-based, MOLLI T1 mapping sequences, is increased in MVP subjects with ventricular arrhythmias, even in the absence of significant MR. Methods: We performed CMRs in 10 consecutive, randomly selected MVP patients identified through our echocardiographic database, age/gender matched to 10 controls free of significant cardiac disease. All 10 MVPs underwent ambulatory EKG monitoring. CMR images were acquired using a GE 3.0T Discovery MR750w scanner. Global ECV fraction was calculated using pre- and 10 minutes post-contrast T1 times after administration of 0.1 mmol/kg of gadobutrol (Gadavist). Late gadolinium enhancement (LGE) was also obtained. MR fraction was quantified by velocity encoded CMR. Mild MR was defined as MR fraction &lt; 16%. Results: MVP patients had significantly higher ECV fraction compared to controls (mean ECV (%) 32 ± 4 vs 20 ± 6, p = 0.0002), with 5/10 demonstrating non-sustained VT on ambulatory EKG monitoring. The majority (9/10 or 90%) of MVPs had mild or no MR (MR fraction &lt; 16%), and 1/10 or 10% had moderate MR (MR fraction 18%). Only one individual in the MVP group had late gadolinium enhancement (LGE) in the papillary muscles. Conclusion: MVP with ventricular arrhythmias is associated with increased global ECV reflective of diffuse myocardial fibrosis, even in the absence of significant MR or LGE. Our preliminary findings highlight for the first time a primary interstitial derangement in MVP. Larger studies are needed to understand the mechanisms and prognostic significance of primary diffuse fibrosis in MVP.

Proteoglycan remodeling is accelerated in women with angina pectoris and diffuse myocardial fibrosis: the iPOWER Study

Abstract Background Women with angina and no obstructive coronary artery disease (CAD) have an unfavourable prognosis, possibly due to coronary microvascular disease and diffuse myocardial fibrosis (DMF). In DMF myocardial extracellular matrix (ECM) proteins are actively remodeled by matrix metalloproteinase (MMP). Purpose We investigated MMP-mediated degradation of the protegoglycans biglycan and versican in women with angina pectoris and possible DMF assessed by cardiac magnetic resonance T1 mapping. Methods Seventy-one women with angina pectoris and no obstructive CAD were included. Asymptomatic age-matched women served as controls (n=32). Versican and biglycan were measured in serum by specific competitive enzyme-linked immunosorbent assays. T1 mapping was performed by cardiac magnetic resonance with gadolinium measuring T1 and extracellular volume (ECV). Results Both biglycan and versican levels were higher in symptomatic women compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p&amp;lt;0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p&amp;lt;0.001), respectively (Figure 1) and were moderately correlated to global ECV (r2=0.38, p&amp;lt;0.001 and r2=0.26, p=0.015 respectively). Conclusion Turnover of biglycan and versican was increased in symptomatic compared to asymptomatic women and associated to ECV, supporting a link between angina with no obstructive CAD and fibrotic cardiac remodeling. The examined biomarkers may prove to be suitable for monitoring active ECM remodeling. Figure 1. Levels of BGM and VCANM Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This work was supported by The Danish Heart Foundation, the Danish Research Fund (Den Danske Forskningsfond) and by University of Copenhagen.

Myocardial Native T1 Predicts Load-Independent Left Ventricular Chamber Stiffness In Patients With HFpEF

ObjectivesThis study sought to evaluate the potential of cardiac magnetic resonance T1 mapping to detect load-independent left ventricular (LV) chamber stiffness by histological confirmation. BackgroundAccurate noninvasive diagnosis of LV diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) remains challenging. MethodsNineteen HFpEF patients (14 female, 65 ± 16 years of age) without primary cardiomyopathy were prospectively enrolled. Cine, late gadolinium enhancement cardiac magnetic resonance, and triple-slice T1 mapping using a modified Look-Locker inversion recovery sequence were performed at 3-T. Extracellular volume (ECV) was quantified from pre- and post-contrast T1 values of the blood and myocardium with hematocrit correction. LV stiffness constant (beta) was assessed by calculating the slope of the end-diastolic pressure–volume relationship curve during vena cava occlusion. Biopsy samples were used for quantification of collagen volume fraction (CVF) and myocardial cell size. ResultsSix patients showed focal scar on late gadolinium enhancement. There was no significant difference in histological CVF between patients with and without focal myocardial scarring (p = 0.2). Septal ECV rather than native T1 was a better surrogate marker for detecting histological CVF (r = 0.54; p = 0.02, and r = 0.44; p = 0.06, respectively). Global native T1 and ECV, but not native T1 and ECV in the septal myocardium, correlated well with the beta of passive LV stiffness, and had similar ability for predicting LV stiffness to histological CVF (r = 0.54, 0.50, 0.53, all p < 0.05, respectively). When the beta ≥0.054 was considered as moderately increased LV stiffness, global native T1 ≥1,362 ms provided 88% sensitivity and 64% specificity with the C-statistic of 0.81 (95% confidence interval: 0.56 to 0.95). ConclusionsMyocardial native T1 provides comparable ability in predicting LV stiffness to ECV and histological CVF and may be useful for monitoring patients with HFpEF who have renal dysfunction, allergy to gadolinium, or wheezing that can simulate asthma. Our feasibility study shows the potential of native T1 to allow for insight of heterogeneous pathophysiology and better risk stratification of HFpEF.

Relation of Late Gadolinium Enhancement and Extracellular Volume Fraction to Ventricular Arrhythmias in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) represents a major cause of sudden cardiac death in young adults. Late gadolinium enhancement (LGE) and extracellular volume (ECV) by T1 mapping are cardiac magnetic resonance (CMR) techniques to quantify fibrosis in HC. The relationships of LGE and ECV with ventricular arrhythmia, left ventricular (LV) diastolic function, and risk factors for sudden cardiac death (SCD) in HC are unclear. We studied 103 HC patients (mean age 51 ± 14, 42% women) who underwent CMR from 2012 to 2014. Global LGE and mean ECV were evaluated in relation to history of nonsustained ventricular tachycardia (NSVT), diastolic function by echocardiography, and SCD risk factors. LGE was present in 71 (69%) subjects. Wide variation was demonstrated in LGE (0.5% to 45.9%) and mean ECV (17.6% to 47.4%). Prevalence of NSVT increased continuously with LGE and was greater in subjects with ECV above the study population mean (27%). Increased LGE was associated with LV diastolic dysfunction and LV wall thickness. In conclusion, while ECV appears to have a threshold (27%) above which it is associated with NSVT, LGE demonstrates a more robust relationship with NSVT and measures of diastolic dysfunction.

Left Ventricular Fibrosis in Middle-Age Athletes and Physically Active Adults.

Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) and T1 mapping techniques enable the quantification of focal and diffuse myocardial LGE, respectively. Studies have shown evidence of fibrosis in middle-age athletes, but not relative to physically active (PA) adults who perform recommended physical activity levels. Therefore, we examined cardiac remodeling and presence of left ventricular (LV) LGE and T1 values in both recreational middle-age endurance athletes (EA) and PA adults. Healthy EA and PA adults (45-65 yr) completed a standardized 3-T CMR protocol with ventricular volumetry, LV LGE, and T1 mapping. Seventy-two EA and 20 PA participants (mean age, 53 ± 5 vs 56 ± 4 yr; P < 0.01; V˙O2peak = 50 ± 7 vs 37 ± 9 mL·kg·min, P < 0.0001) were examined, with CMR data available in 89/92 participants. Focal LV LGE was observed in 30% of participants (n = 27/89): 33% of EA (n = 23/69; 33%) and 20% of PA (n = 4/20; 20%). LGE was present at the right ventricular hinge point (n = 21/89; 23.5%) or identified as ischemic (n = 2/89; 2%) or nonischemic (n = 4/89; 4%). Focal LV LGE was observed similarly in both EA and PA (P = 0.25). EA had larger LV chamber sizes and T1 native values (1169 ± 35 vs 1190 ± 26, P = 0.02) compared with PA, with similar LV ejection fraction. Global extracellular volume (ECV) was similar in both EA and PA (22.6% ± 3.5% vs 21.5% ± 2.6%, P = 0.26), with no relationship between global ECV and LV mass (r = -0.16, P = 0.19). Focal LGE at the right ventricular hinge point was detected at the same frequency in both groups, was unrelated to demographic or clinical indices, and was found without evidence of global ECV expansion in EA, suggesting a physiologic remodeling response. The long-term clinical implications of hinge-point LGE require clarification using prospective, long-term follow-up studies.

Associations between Cardiac Magnetic Resonance T1 Mapping Parameters and Ventricular Arrhythmia in Patients with Chagas Disease.

Chronic Chagas disease can progress to myocardial involvement with intense fibrosis, which may predispose patients to sudden cardiac death through ventricular arrhythmia. The associations of myocardial fibrosis detected by cardiac magnetic resonance (CMR) parameters with non-sustained ventricular tachycardia (NSVT) were evaluated. This cross-sectional study included patients in early stages of Chagas disease (n = 47) and a control group (n = 15). Patients underwent cardiac evaluation, including CMR examination. Myocardial fibrosis assessment by CMR with measurement of late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV) was performed. There was an increase in myocardial fibrosis CMR parameters and ventricular arrhythmias among different stages of Chagas disease, combined with a decrease in the left ventricular ejection fraction (LVEF) by CMR and also in the right ventricular systolic function by S' wave on tissue Doppler. Fibrosis mass and ECV were associated with the Rassi score, ventricular extrasystole, and E/e' ratio in a logistic regression model adjusted for age and gender. The ECV maintained an association with the presence of NSVT, even after adjustments for fibrosis mass and LVEF assessed by CMR. The receiver-operating characteristic area under the curve for global ECV (0.85; 95% CI: 0.71-0.99) and NSVT was greater than that for fibrosis mass (0.75; 95% CI: 0.54-0.96), although this difference was not statistically significant. Extracellular volume could be an early marker of increased risk of ventricular arrhythmia in Chagas disease, presenting an independent association with NSVT in the initial stages of chronic Chagas cardiomyopathy, even after adjustment for fibrosis mass and LVEF.