Higher Extracellular Volume Research Articles

RETRACTED ARTICLE: Prognostic value of heart failure in hemodialysis-dependent end-stage renal disease patients with myocardial fibrosis quantification by extracellular volume on cardiac magnetic resonance imaging

BackgroundEnd-stage renal disease (ESRD) patients are at high cardiovascular risk, and myocardial fibrosis (MF) accounts for most of their cardiac events. The purpose of this study is to investigate the prognostic value and risk stratification of MF as measured by extracellular volume (ECV) on cardiac magnetic resonance (CMR) for heart failure (HF) in patients with hemodialysis-dependent ESRD.MethodsSixty-six hemodialysis ESRD patients and 25 matched healthy volunteers were prospectively enrolled and underwent CMR to quantify multiple parameters of MF by T1 mapping and late gadolinium enhancement (LGE). All ESRD patients were followed up for 11–30 months, and the end-point met the 2016 ESC guidelines for the definition of HF.ResultsOver a median follow-up of 18 months (range 11–30 months), there were 26 (39.39%) guideline-diagnosed HF patients in the entire cohort of ESRD subjects. The native T1 value was elongated, and ECV was enlarged in the HF cohort relative to the non-HF cohort and normal controls (native T1, 1360.10 ± 50.14 ms, 1319.39 ± 55.44 ms and 1276.35 ± 56.56 ms; ECV, 35.42 ± 4.42%, 31.85 ± 3.01% and 26.97 ± 1.87%; all p<0.05). In the cardiac strain analysis, ECV was significantly correlated with global radial strain (GRS) (r = − 0.501, p = 0.009), global circumferential strain (GCS) (r = 0.553, p = 0.005) and global longitudinal strain (GLS) (r = 0.507, p = 0.008) in ESRD patients with HF. Cox proportional hazard regression models revealed that ECV (hazard ratio [HR] = 1.160, 95% confidence interval: 1.022 to 1.318, p = 0.022) was the only independent predictor of HF in ESRD patients. It also had a higher diagnostic accuracy for detecting MF (area under the curve [AUC] = 0.936; 95% confidence interval: 0.864 to 0.976) than native T1 and post T1 (all p ≤ 0.002). Kaplan-Meier analysis revealed that the high-ECV group had a shorter median overall survival time than the low-ECV group (18 months vs. 20 months, log-rank p = 0.046) and that ESRD patients with high ECV were more likely to have HF.ConclusionsMyocardial fibrosis quantification by ECV on CMR T1 mapping was shown to be an independent risk factor of heart failure, providing incremental prognostic value and risk stratification for cardiac events in ESRD patients.Trial registrationChinese Clinical Trial Registry ChiCTR-DND-17012976, 13/12/2017, Retrospectively registered.

Prevalence and pattern of cardiovascular magnetic resonance late gadolinium enhancement in highly trained endurance athletes

BackgroundIntensive endurance exercise may induce a broad spectrum of right ventricular (RV) adaptation/remodelling patterns. Late gadolinium enhancement (LGE) has also been described in cardiovascular magnetic resonance (CMR) of some endurance athletes and its clinical meaning remains controversial. Our aim was to characterize the features of contrast CMR and the observed patterns of the LGE distribution in a cohort of highly trained endurance athletes.MethodsNinety-three highly trained endurance athletes (> 12 h training/week at least during the last 5 years; 36 ± 6 years old; 53% male) and 72 age and gender-matched controls underwent a resting contrast CMR. In a subgroup of 28 athletes, T1 mapping was also performed.ResultsHigh endurance training load was associated with larger bi-ventricular and bi-atrial sizes and a slight reduction of biventricular ejection fraction, as compared to controls in both genders (p < 0.05). Focal LGE was significantly more prevalent in athletes than in healthy subjects (37.6% vs 2.8%; p < 0.001), with a typical pattern in the RV insertion points. In T1 mapping, those athletes who had focal LGE had higher extracellular volume (ECV) at the remote myocardium than those without (27 ± 2.2% vs 25.2 ± 2.1%; p < 0.05).ConclusionsHighly trained endurance athletes showed a ten-fold increase in the prevalence of focal LGE as compared to control subjects, always confined to the hinge points. Additionally, those athletes with focal LGE demonstrated globally higher myocardial ECV values. This matrix remodelling and potential presence of myocardial fibrosis may be another feature of the athlete’s heart, of which the clinical and prognostic significance remains to be determined.

Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants’ smoking and sporting habits were measured by a questionnaire. Physical inactivity was associated with a reduction of left ventricular ejection fraction (LV-EF), stroke volume, early diastolic peak filling rate and peak ejection rate of the left ventricle as well as right ventricular stroke volume. LV-EF was reduced in subjects with almost no physical activity compared to subjects with regular physical activity (68.4%, 95%CI 66.8–70.1% vs. 70.8%, 95%CI 69.2–72.3%, p < 0,05). Smokers had lower right ventricular end-diastolic volumes (80.6 ml/m², 95%CI 76.7–84.5 ml/m²; never-smokers: 85.5 ml/m², 95%CI 82.6–88.3 ml/m²; p < 0.05) but higher extracellular volume fractions (ECV) and fibrosis volumes (34.3 ml, 95%CI 32.5–36.0 ml, vs. 31.0 ml, 95%CI 29.6–32.3 ml, p < 0.01). We conclude that asymptomatic individuals without known cardiovascular diseases show differences in cardiac function and structure depending on their physical activity and smoking habits. This underlines the importance of prevention and health education.

Prognostic Role of T1 Mapping Parameters in Ischemic and Non-Ischemic Cardiomyopathies: A Systematic Review and Metaanalysis

Introduction T1 mapping is a novel cardiac magnetic resonance (CMR) based technique for characterization of myocardial tissue. Extracellular volume (ECV) fraction represents estimation of myocardial extracellular space and is useful for evaluation and quantification of myocardial fibrosis. However, their role in prognosis and assessing outcomes in cardiovascular diseases has not been well described. Methods We performed a systematic review and metaanalysis evaluating the prognostic role of T1 mapping parameters in patients in patients with ischemic and non-ischemic cardiomyopathies. PubMed, Embase, Cochrane Central databases were searched from inception to Feb 2019 for relevant studies. Primary outcome measure was combined endpoint of death or adverse cardiovascular events (including cardiovascular death/hospitalization for heart failure). Hazard Ratios (HR) from included studies were pooled in metaanalysis using random effect model. Results 5 studies with 1462 participants were included in the analysis. Mean age was 62.3 years, 46.9% of participants were females and mean follow up period was 16.3 months. Of these, 43.6% (637) had non-ischemic cardiomyopathy and heart failure, 32.9% (481) had heart failure, 6.4% (94) had valvular heart disease, 3.8% (55) had coronary artery disease and 5.3% (78) had other cardiac diseases. We found that higher ECV was associated with increased risk for combined outcome of death or adverse cardiovascular events (HR-1.09, 95% CI (1.05-1.14), P Conclusion ECV has independent prognostic value and can help in risk stratification of patients with ischemic and non-ischemic cardiomyopathies.

Myocardial Fibrosis in Classical Low-Flow, Low-Gradient Aortic Stenosis.

Background Few data exist on the degree of interstitial myocardial fibrosis in patients with classical low-flow, low-gradient aortic stenosis (LFLG-AS) and its association with left ventricular flow reserve (FR) on dobutamine stress echocardiography. This study sought to evaluate the diffuse interstitial fibrosis measured by T1 mapping cardiac magnetic resonance technique in LFLG-AS patients with and without FR. Methods Prospective study including 65 consecutive patients (41 LFLG-AS [mean age, 67.1±8.4 years; 83% men] and 24 high-gradient aortic stenosis used as controls) undergoing dobutamine stress echocardiography to assess FR and cardiac magnetic resonance to determine the extracellular volume (ECV) fraction of the myocardium, indexed ECV (iECV) to body surface area and late gadolinium enhancement. Results Interstitial myocardial fibrosis measured by iECV was higher in patients with LFLG-AS with and without FR as compared with high-gradient aortic stenosis (35.25±9.75 versus 32.93±11.00 versus 21.19±6.47 mL/m2, respectively; P<0.001). However, both ECV and iECV levels were similar between LFLG-AS patients with and without FR ( P=0.950 and P=0.701, respectively). Also, FR did not correlate significantly with ECV (r=-0.16, P=0.31) or iECV (r=0.11, P=0.51). Late gadolinium enhancement mass was also similar in patients with versus without FR but lower in high-gradient aortic stenosis (13.3±10.2 versus 10.5±7.5 versus 4.8±5.9 g, respectively; P=0.018). Conclusions Patients with LFLG-AS have higher ECV, iECV, and late gadolinium enhancement mass compared with high-gradient aortic stenosis. Moreover, among patients with LFLG-AS, the degree of myocardial fibrosis was similar in patients with versus those without FR. These findings suggest that diffuse myocardial fibrosis may not be the main factor responsible for the absence of FR in LFLG-AS patients.

Abstract 16905: Relationship Between Cardiac Magnetic Resonance Derived Regional Systolic Strain and Myocardial Tissue Characteristics in Children With Duchenne Muscular Dystrophy

Background: Duchenne Muscular dystrophy (DMD) is an X linked disorder associated with deterioration in cardiac function. Identification of subclinical abnormalities using cardiac magnetic resonance (CMR) may provide an earlier marker to trigger therapy. We aimed to correlate regional left ventricle (LV) myocardial native T1 and extracellular volume (ECV) with regional strain in children with DMD. Methods: Fourteen boys with DMD (median 14 years, range 9-18) underwent CMR to measure segmental native T1 and ECV at the basal and mid-ventricular level. Native T1 and ECV were measured from the MOLLI sequence using cvi42 software. Circumferential (CS) and longitudinal (LS) strain values were assessed in the corresponding cine images using an in-house developed, semi-automated deformation technique. Associations of T1 and ECV with strain were examined using Pearson correlation coefficient. Results: The majority had LVEF &gt;50% (79%). Median global basal CS (-20.5%) and mid-cavity CS (-18.9%) were normal, but the global LS was reduced (-15.2%). Regions with LGE and CS abnormalities were similar (inferior and inferolateral) but differed from regions with increased T1 &amp; ECV (inferoseptal, anteroseptal) and LS abnormalities (inferoseptal and anteroseptal). CS and LS abnormalities were noted more in mid-cavity than basal segments. There were strong correlations between lower CS and higher native T1 in four segments, and correlations with higher ECV in all segments (Table 1). LS showed no correlations with either native T1 or ECV. Conclusions: Native T1 and ECV abnormalities were noted in segments not associated with positive LGE. The relationship between native T1, ECV and CS suggest that regional diffuse fibrosis is associated with subclinical systolic dysfunction and is detectable on CMR prior to global abnormalities. These findings may provide evidence for early medical therapy aimed at delaying cardiac dysfunction in DMD.

Myocardial extracellular volume quantified by magnetic resonance is increased in cirrhosis and related to poor outcome.

The underlying pathogenesis of cirrhotic cardiomyopathy remains unclear. Structural myocardial changes including diffuse fibrosis may be involved and can be accurately assessed by cardiac MRI (CMR) with quantification of the extracellular volume (ECV).This is the first application of this technique in patients with cirrhosis. We aimed to investigate the presence of diffuse myocardial fibrosis and to determine the relation to disease severity, cardiac function and outcome. A prospective study including 52 cirrhotic patients and 10 healthy controls. All patients underwent CMR with ECV quantification, tissue Doppler echocardiography, and biochemical assessments. Patients were followed up for a median of 25months with registration of death and liver transplantation (LT). Myocardial ECV was higher in the patients compared with healthy controls (31.2±6 vs 27.4±3%, P=.04). Furthermore, ECV increased across the Child Pugh A/B/C classes (26.9±4/31.5±5/34.4±6%, P=.02). Four-teen patients experienced the composite end-point of death/LT during follow-up and these patients had higher ECV (33.2±4 vs 30.4±6%, P=.04). In a univariate Cox regression analysis ECV was associated with poor transplant-free survival (HR 3.6 [1.1-11.6]; P=.03). However, MELD and CRP remained the strongest predictors in a multivariate analysis. ECV correlated with cardiac index (r=0.44, P=.001), CRP (r=0.46, P=.001), proANP (r=0.50, P<.001), and proBNP (r=0.40, P=.005). Myocardial ECV is increased in patients with cirrhosis and seems related to disease severity and transplant-free survival. These changes most likely reflect subclinical diffuse myocardial fibrosis and may represent a structural element of cirrhotic cardiomyopathy.

Myocardial T1 mapping and extracellular volume quantification in patients with left ventricular non-compaction cardiomyopathy.

From pathophysiological mechanisms to risk stratification and management, much debate and discussion persist regarding left ventricular non-compaction cardiomyopathy (LVNC). This study aimed to characterize myocardial T1 mapping and extracellular volume (ECV) fraction by cardiovascular magnetic resonance (CMR), and investigate how these biomarkers relate to left ventricular ejection fraction (LVEF) and ventricular arrhythmias (VA) in LVNC. Patients with LVNC (n = 36) and healthy controls (n = 18) were enrolled to perform a CMR with T1 mapping. ECV was quantified in LV segments without late gadolinium enhancement (LGE) areas to investigate diffuse myocardial fibrosis. Patients with LVNC had slightly higher native T1 (1024 ± 43 ms vs. 995 ± 22 ms, P = 0.01) and substantially expanded ECV (28.0 ± 4.5% vs. 23.5 ± 2.2%, P < 0.001) compared to controls. The ECV was independently associated with LVEF (β = -1.3, P = 0.001). Among patients without LGE, VAs were associated with higher ECV (27.7% with VA vs. 25.8% without VA, P = 0.002). In LVNC, tissue characterization by T1 mapping suggests an extracellular expansion by diffuse fibrosis in myocardium without LGE, which was associated with myocardial dysfunction and VA, but not with the amount of non-compacted myocardium.

Associations and prognostic significance of diffuse myocardial fibrosis by cardiovascular magnetic resonance in heart failure with preserved ejection fraction

BackgroundIncreased myocardial fibrosis may play a key role in heart failure with preserved ejection fraction (HFpEF) pathophysiology. The study aim was to evaluate the presence, associations, and prognostic significance of diffuse fibrosis in HFpEF patients compared to age- and sex-matched controls.MethodsWe prospectively included 118 consecutive HFpEF patients. Diffuse myocardial fibrosis was estimated by extracellular volume (ECV) quantified by cardiovascular magnetic resonance with the modified Look-Locker inversion recovery sequence. We determined an ECV age- and sex-adjusted cutoff value (33%) in 26 controls.ResultsMean ECV was significantly higher in HFpEF patients versus healthy controls (32.9 ± 4.8% vs 28.2 ± 2.4%, P < 0.001). Multivariate logistic regression showed that body mass index (BMI) (odds ratio (OR) =0.92 [0.86–0.98], P = 0.011), diabetes (OR = 2.62 [1.11–6.18], P = 0.028), and transmitral peak E wave velocity (OR = 1.02 [1.00–1.03], P = 0.022) were significantly associated with abnormal ECV value. During a median follow-up of 11 ± 6 months, the primary outcome (all-cause mortality or first heart failure hospitalization) occurred in 38 patients. In multivariate Cox regression analysis, diabetes (hazard ratio (HR) =1.98 [1.04; 3.76], P = 0.038) and hemoglobin level (HR = 0.81 [0.67; 0.98], P = 0.028) were significant predictors of composite outcome. The ECV ability to improve this model added significant prognostic information. We then developed a risk score including diabetes, hemoglobin and ECV > 33% demonstrating significant prediction of risk and validated this score in a validation cohort of 53 patients. Kaplan–Meier curves showed a significant difference according to tertiles of the probability score (P < 0.001).ConclusionAmong HFpEF patients, high ECV, likely reflecting abnormal diffuse myocardial fibrosis, was associated with a higher rate of all-cause death and first HF hospitalization in short term follow up.Trial registrationCharacterization of Heart Failure With Preserved Ejection Fraction. Trial registration number: NCT03197350. Date of registration: 20/06/2017. This trial was retrospectively registered.

Cardiovascular magnetic resonance evidence of myocardial fibrosis and its clinical significance in adolescent and adult patients with Ebstein\u2019s anomaly

BackgroundMyocardial fibrosis is a common pathophysiological process that is related to ventricular remodeling in congenital heart disease. However, the presence, characteristics, and clinical significance of myocardial fibrosis in Ebstein’s anomaly have not been fully investigated. This study aimed to evaluate myocardial fibrosis using cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and T1 mapping techniques, and to explore the significance of myocardial fibrosis in adolescent and adult patients with Ebstein’s anomaly.MethodsForty-four consecutive patients with unrepaired Ebstein’s anomaly (34.0 ± 16.2 years; 18 males), and an equal number of age- and gender-matched controls, were included. A comprehensive CMR protocol consisted of cine, LGE, and T1 mapping by modified Look-Locker inversion recovery (MOLLI) sequences were performed. Ventricular functional parameters, native T1, extracellular volume (ECV), and LGE were analyzed. Associations between myocardial fibrosis and disease severity, ventricular function, and NYHA classification were analyzed.ResultsLGE was found in 10 (22.7%) patients. Typical LGE in Ebstein’s anomaly was located in the endocardium of the septum within the right ventricle (RV). The LV ECV of Ebstein’s anomaly were significantly higher than those of the controls (30.0 ± 3.8% vs. 25.3 ± 2.3%, P < 0.001). An increased ECV was found to be independent of the existence of LGE. Positive LGE or higher ECV (≥30%) was associated with larger fRV volume, aRV volume, increased disease severity, and worse NYHA functional class. In addition, ECV was significantly correlated with the LV ejection fraction (P < 0.001).ConclusionsBoth focal and diffuse myocardial fibrosis were observed in adolescent and adult patients with Ebstein’s anomaly. Increased diffuse fibrosis is associated with worse LV function, increased Ebstein’s severity, and worse clinical status.

A prospective study examining the role of myocardial Fibrosis in outcome following mitral valve repair IN DEgenerative mitral Regurgitation: rationale and design of the mitral FINDER study

BackgroundThe optimal management of chronic severe primary degenerative mitral regurgitation (MR) is to repair the valve but identification of the optimal timing of surgery remains challenging. Current guidelines suggest ‘watchful waiting’ until the onset of symptoms or left ventricular (LV) dysfunction but these have been challenged as promoting ‘rescue surgery’. Better predictors are required to inform decision-making in relation to the necessity and timing of surgery. Chronic volume overload is a stimulus for adverse adaptive LV remodelling. Subclinical reduction in LV strain before mitral repair predicts a fall in LV ejection fraction following surgery and is thought to reflect the development of myocardial fibrosis in response to chronic volume overload. Myocardial fibrosis can be detected non-invasively using cardiac magnetic resonance (CMR) imaging techniques as an expansion of the extracellular volume (ECV).Methods/designThis study investigates whether: 1) patients with above median ECV will have smaller reduction in end-systolic volume index (as a measure of the degree of reverse LV remodelling) on CMR following mitral valve repair, compared to those with below median ECV; and 2) higher ECV on CMR, validated through histology, adversely impacts upon post-operative complications and symptomatic improvement following surgery.This is a multi-centre, prospective, cross-sectional comparison of patients prior to and 9 months following surgery for chronic severe primary degenerative MR. To establish the natural history of ECV in MR, an additional cohort of patients with asymptomatic MR who do not wish to consider early repair will be followed. Investigations include CMR, cardiopulmonary exercise test, stress echocardiography, signal-averaged electrocardiogram, 24-h electrocardiogram monitoring, laboratory tests and patient-reported outcome measures. Patients undergoing surgery will have cardiac biopsies performed at the time of mitral valve repair for histological quantification of fibrosis.DiscussionThis study will advance our understanding of ventricular remodelling in MR, its impact on patient symptoms and ventricular response following surgery. Establishing the link between myocardial fibrosis (measured on CMR and validated through histology), with early ventricular dysfunction, will offer physicians a novel non-invasive biomarker that can further inform the timing of surgery.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT02355418) on 30th November 2015.

Myocardial fibrosis detected by magnetic resonance in systemic sclerosis patients – Relationship with biochemical and echocardiography parameters

ObjectivesSystemic scleroderma (SSc) is a rare connective tissue disease presenting with fibrosis affecting skin and internal organs. Cardiovascular magnetic resonance (CMR) with quantification of extracellular volume (ECV) and T1 mapping might help to detect heart involvement. We aimed to evaluate whether myocardial involvement correlates with functional and laboratory parameters. MethodsThirty-three asymptomatic SSc patients (29 women, aged 56.6±12.2years) and 20 controls (10 women, 53.7±13.1years) were examined using CMR, echocardiography, functional pulmonary test and laboratory assessment. ResultsSSc patients had higher ECV (27.5±2.8 vs. 22.8±1.9%, P<0.0001) and native T1 values (1258.9±51.2 vs. 1192.2±32.6, P<0.0001) compared to controls. Plasma level of growth differentiation factor 15 (GDF-15) and galectin-3 correlated with ECV (r=0.35; P=0.0076 and r=0.38; P=0.0081) and native T1 (r=0.31; P=0.023 and r=0.35; P=0.012). GDF-15 was also negatively correlated with diffusing capacity of the lung for carbon monoxide (r=−0.58; P=0.0004) and positively correlated with modified Rodnan skin score (r=0.59; P=0.0003). Conventional echocardiography parameters were similar in SSc patients and controls. However, the global longitudinal peak systolic strain (GLPS) was lower in SSc patients compared to controls (18.6±1.6 vs. 21.1±1.2%; P<0.0001). GLPS also negatively correlated with native T1 (r=−0.35; P=0.0097), ECV (r=−0.33; P=0.014), GDF 15 (r=−0.31; P=0.022), and galectin-3 (r=−0.37; P=0.0076). ConclusionsAsymptomatic heart involvement is common in SSc patients and includes focal and diffuse myocardial fibrosis. GDF-15 and galectin-3 were positively correlated with myocardial fibrosis parameters. Future outcome studies must show whether measurement of GDF-15 and galectin-3 in SSC patients might be may be useful in clinical practice.

P3324Clinical significance of higher extracellular volume in patients with apical and non- apical hypertrophic cardiomyopathy

P3324Clinical significance of higher extracellular volume in patients with apical and non- apical hypertrophic cardiomyopathy

Left ventricular function in patients with hypertrophic cardiomyopathy and its relation to myocardial fibrosis and exercise tolerance.

We sought to determine the relation between myocardial extracellular volume (ECV), left ventricular (LV) diastolic function, and exercise tolerance in patients with hypertrophic cardiomyopathy (HCM). Forty five HCM patients with an ejection fraction >50% and no previous septal reduction therapy underwent imaging by CMR and transthoracic echocardiography. CMR was used to quantify LV volumes, mass, EF, LA volumes, scar burden, pre and post contrast T1 relaxation times and ECV. Echocardiography was used to measure outflow tract gradients, mitral inflow and annular velocities, circumferential strain, systolic, early and late diastolic strain rates. Exercise duration and peak oxygen consumption were noted. HCM patients had increased native T1 relaxation time and ECV vs. controls [ECV controls: 24.7 (23.2-26.4) vs. HCM: 26.8 (24.6-31.3)%, P = 0.014]. Both parameters were significantly associated with LV diastolic dysfunction, circumferential strain, diastolic strain rate and peak oxygen consumption (r = -0.73, P < 0.001). Compared to controls, HCM patients have significantly longer native T1 relaxation time and higher ECV. These structural changes lead to worse LV global and segmental diastolic function and in turn reduced exercise tolerance.

Hypertrophic cardiomyopathy and left ventricular hypertrophy in hypertensive heart disease with mildly reduced or preserved ejection fraction: insight from altered mechanics and native T1 mapping

To explore the relationship between extracellular volume (ECV), native T1, and systolic strain in hypertrophic cardiomyopathy (HCM) and hypertensive patients with left ventricular hypertrophy (HTN LVH) with mildly reduced or preserved ejection fraction. T1 mapping was performed in 45 patients with late gadolinium enhancement positive (LGE+) HCM (mean age, 53±6 years), 11 patients with LGE- (LGE-) HCM (mean age, 56±5 years), and 20 patients with HTN LVH (mean age, 55±6 years) on at 3 T magnetic resonance imaging (MRI) using the modified look-locker inversion-recovery (MOLLI) pulse sequence. Mean T1 value, ECV and circumferential strain parameters were determined for each patient. Overall, the HCM patients had higher native T1 values (1242.92±68.94) and ECV (0.31±0.05) in comparison to those of the HTN LVH patients (1197±46.80, 0.27±0.04; p<0.05). In the subgroup analysis, the HCM LGE+ patients had the highest native T1 values among the three groups. The HCM LGE+ patients had higher ECV than the LGE- patients. HCM LGE- patients had higher ECV than HTN LVH patients (p<0.05). Peak systolic circumferential strain and early diastolic strain rates were reduced in the HCM LGE+ patients in comparison to the HCM LGE- and HTN LVH patients (p<0.05). Reduced peak systolic and early diastolic circumferential strain rates were associated with increased levels of ECV and native T1 values among all the patients. HCM LGE+ patients had higher native T1 values, higher ECV, and an associated reduction in early diastolic strain rates and peak systolic circumferential strains when compared to the HCM LGE- and HTN LVH patients with mildly reduced or preserved ejection fraction.

The Association between Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance T1 Mapping and Myocardial Dysfunction in Diabetic Rabbits

The objective of this study was to assess the relationship between imaging surrogates for diffuse fibrosis and myocardial dysfunction. Thirty-six New Zealand white rabbits were classified into two groups: a control group (n = 18) and an alloxan-induced diabetes mellitus (DM) group (n = 18). For all rabbits, conventional ultrasonography, two-dimensional speckle tracking, and cardiac magnetic resonance (CMR) T1 mapping were performed; all of the rabbits were then sacrificed for Masson’s staining. The extracellular volume (ECV) was calculated from pre- and post-contrast T1 values and compared with myocardial function measured by echocardiography using Pearson’s correlation. In the DM group, ECV increased as the duration of diabetes increased, consistent with the changes in myocardial fibrosis verified by pathology. Moreover, ECV was strongly correlated with the early diastolic strain rate (r = −0.782, p < 0.001) and moderately correlated with the radial systolic peak strain (r = 0.478, p = 0.045). Thus, ECV is an effective surrogate for myocardial diffuse fibrosis on CMR imaging, and higher ECV values are associated with an increased impairment of myocardial diastolic function.

Diffuse Myocardial Fibrosis Is a Common Feature of Sickle Cell Anemia That Is Associated with Diastolic Dysfunction and Restrictive Cardiac Physiology

Background: We have recently shown that the cardiomyopathy of sickle cell anemia (SCA) is characterized by restrictive physiology (diastolic dysfunction, left atrial [LA] enlargement and normal systolic function) superimposed on hyperdynamic features (left ventricular [LV] enlargement and eccentric hypertrophy) (JACC Cardiovasc Imaging 9:244-253;2016; PNAS 2016 in press). Similar to other restrictive cardiomyopathies, SCA-related cardiomyopathy may lead to mild, secondary pulmonary hypertension (PH) with elevated tricuspid regurgitant jet velocity (TRV), and can be complicated by arrhythmias and sudden death. Diastolic dysfunction is the principal pathology leading to restrictive physiology. Myocardial fibrosis is a common cause of non-SCA restrictive physiology, but the cause of the diastolic dysfunction that underlies SCA-related cardiomyopathy is undetermined. Focal fibrosis, as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR), is rare in SCA. However, diffuse myocardial fibrosis, which is not detected by LGE, has not been studied before in SCA. Therefore, we aimed to detect myocardial fibrosis in SCA using a novel CMR T1-mapping technique to quantify the myocardial extracellular volume (ECV) fraction, which correlates with histologic diffuse fibrosis.Methods: We conducted a prospective study of children and adults with SCA (NCT02410811) who underwent CMR, echocardiography, and laboratory testing (including N-terminal pro-brain type natriuretic peptide [NT-proBNP], a marker of ventricular stress). ECV was measured from pre- and post-gadolinium T1 maps using a modified Look-Locker inversion recovery (MOLLI) sequence. Chamber sizes and cardiac performance were evaluated using CMR, while TRV and diastolic parameters were measured by echocardiography.Results: Twenty-five patients with a median age of 19 years (range 6-61 years) were evaluated. ECV was increased in all SCA patients (mean 44 ± 8% vs. 25 ± 3% in normal subjects, P<0.001). One patient had focal fibrosis by LGE and one had systolic dysfunction. Among patients with normal systolic function, 17 patients (71%) had diastolic abnormalities and 7 (29%) had normal diastolic function. Seven out of 17 patients with diastolic abnormalities (29% of the total group) met the definition of diastolic dysfunction, and 10 had inconclusive classification. Patients with diastolic dysfunction had significantly higher ECV (49 ± 7% vs 37 ± 4%, P=0.01; Panel A), NT-proBNP (191 ± 261 vs. 33 ± 33 pg/mL, P=0.04; Panel B), and lower hemoglobin (8.4±0.3 vs.10.9±1.4 g/dL, P=0.004, Panel C) compared to patients with normal diastolic function. Systolic function was similar in both groups (LV ejection fraction 61 ± 4% vs. 62 ± 3.4%, P=0.86). In patients with higher ECV (³40%), LV diastolic abnormalities were more common (99% vs 33%, P=0.003) and LA volume index was significantly increased (57 ± 11 vs. 46 ± 12 mL/m2, P=0.04) compared to patients with ECV <40%. Increased ECV was associated with anemia (R=-0.46, P=0.03; Panel D) and elevated NT-proBNP (R=0.62, P=0.001; Panel E), but not with LV ejection fraction (P=0.66; Panel F), LV mass (P=0.92) or TRV (P=0.65).Conclusions: ECV is markedly elevated in SCA, indicating the presence of significant diffuse myocardial fibrosis in all patients studied. High ECV is associated with more severe anemia, diastolic dysfunction, and high NT-proBNP. Diffuse myocardial fibrosis is a novel process underlying diastolic dysfunction and SCA-related cardiomyopathy, the features of which may be mistaken for pulmonary arterial hypertension. Identifying and therapeutically targeting the root-cause of myocardial fibrosis, or interrupting the development of myocardial fibrosis, should be studied to mitigate cardiopulmonary disease and decrease early mortality in SCA. [Display omitted] DisclosuresQuinn:Silver Lake Research Corporation: Consultancy; Eli Lilly: Research Funding; Amgen: Research Funding.

Age at onset and seizure frequency affect white matter diffusion coefficient in patients with mesial temporal lobe epilepsy.

In mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS), structural abnormalities are present not only in the hippocampus but also in the white matter with ipsilateral predominance. Although the timing of epilepsy onset is commonly associated with clinical and semiological dissimilarities, limited data exist regarding white matter diffusion changes with respect to age at epilepsy onset. The aim of this study was to investigate diffusion changes in the white matter of patients with unilateral MTLE-HS with respect to clinical parameters and to compare them with an age- and sex-matched healthy control group. Apparent diffusion coefficients (ADCs) were derived using monoexponential approaches from 22 (11 early and 11 late age at onset) patients with unilateral MTLE-HS and 22 age- and sex-matched control subjects after acquiring diffusion-weighted images on a 3T MRI system. Data were analyzed using two-tailed t-tests and multiple linear regression models. In the group with early onset MTLE-HS, ADC was significantly elevated in the ipsilateral hemispheric (p=0.04) and temporal lobe white matter (p=0.01) compared with that in controls. These differences were not detectable in late onset MTLE-HS patients. Apparent diffusion coefficient of the group with early onset MTLE-HS was negatively related to age at epilepsy onset in the ipsilateral hemispheric white matter (p=0.03) and the uncinate fasciculus (p=0.03), while in patients with late onset MTLE-HS, ADC was no longer dependent on age at epilepsy onset itself but rather on the seizure frequency in the ipsilateral uncinate fasciculus (p=0.03). Such diffusivity pattern has been associated with chronic white matter degeneration, reflecting myelin loss and higher extracellular volume which are more pronounced in the frontotemporal regions and also depend on clinical features. In the group with early onset MTLE-HS, the timing of epilepsy seems to be the major cause of white matter abnormalities while in late onset disease, it has a secondary role in provoking diffusion changes.

T1-Mapping in Daily Cardiac Magnetic Resonance Imaging Practice: Combined Use of Native T1 and Extracellular Volume Quantification

T1-Mapping in Daily Cardiac Magnetic Resonance Imaging Practice: Combined Use of Native T1 and Extracellular Volume Quantification Introduction: Dual T1-mapping allows for a comprehensive assessment of myocardial tissue by combining detection of edema in the native scan and quantification of extracellular volume (ECV) after administration of Gadolinium (Gd). Recent studies proved the diagnostic value of T1-mapping in different pathologies. The aim of this study was, to evaluate the practicability and robustness of T1-mapping in assessing common pathologies in daily cardiac magnetic resonance (CMR) practice. Methods: From October 2012 to October 2013, we investigated 136 consecutive patients undergoing clinically indicated CMR examination by performing additional T1-mapping measurements. We used a Modified-Look-Locker-Inversion-Recovery (MOLLI) sequence with 3 inversion pulses and a 4-(1)-3-(1)-2 readout pattern. For extracellular volume calculation a second scan was performed 10min. after administration of 0.2mmol/kg body weight gadopentetate dimeglumine. Diagnosis was based on clinical information and standard CMRsequences comprising native T2-weighted dark-blood turbo spin echo (TSE) sequences, pre- and early post-Gd T1-weighted darkblood TSE sequences and Late Gadolinium Enhancement. The study population comprised a control group, patients with acute and chronic myocarditis, patients with acute and chronic infarction, patients with dilated and hypertrophic cardiomyopathy, patients with aortic stenosis and patients with amyloidosis or sarcoidosis. Results: Native T1 showed a significant difference when compared with a control in acute myocarditis, acute myocardial infarction, hypertrophic and dilated cardiomyopathy, and amyloidosis. ECV showed significant differences to the control group in all cohorts of pathologies. Particularly high native T1 values were observed in acute myocarditis, acute myocardial infarction, hypertrophic cardiomyopathy and amyloidosis, a high ECV was found in acute and chronic myocarditis, acute and chronic myocardial infarction, sarcoidosis and amyloidosis. Conclusion: Native T1-mapping and ECV correlated well with myocardial alterations in commonly diagnosed cardiac disorders. It proved reliable and robust in daily clinical practice and allows for a good differentiation between normal findings and common pathological CMR diagnoses. The combined use of native T1 and ECV quantification is a promising approach for comprehensive assessment of the myocardium and may improve diagnostic accuracy of CMR in myocardial disease.

Higher extracellular volume is associated with longer bypass times at corrective surgery and reduced exercise tolerance in children late after repair of tetralogy of Fallot

Higher extracellular volume is associated with longer bypass times at corrective surgery and reduced exercise tolerance in children late after repair of tetralogy of Fallot