Post-contrast T1 Time Research Articles

Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure.

Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan-Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 μg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

Diabetes and Myocardial Fibrosis: A Systematic Review and Meta-Analysis

ObjectivesThis systematic review and meta-analysis investigated the association of diabetes and glycemic control with myocardial fibrosis (MF). BackgroundMF is associated with an increased risk of heart failure, coronary artery disease, arrhythmias, and death. Diabetes may influence the development of MF, but evidence is inconsistent. MethodsThe authors searched EMBASE, Medline Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar for observational and interventional studies investigating the association of diabetes, glycemic control, and antidiabetic medication with MF assessed by histology and cardiac magnetic resonance (ie, extracellular volume fraction [ECV%] and T1 time). ResultsA total of 32 studies (88% exclusively on type 2 diabetes) involving 5,053 participants were included in the systematic review. Meta-analyses showed that diabetes was associated with a higher degree of MF assessed by histological collagen volume fraction (n = 6 studies; mean difference: 5.80; 95% CI: 2.00-9.59) and ECV% (13 studies; mean difference: 2.09; 95% CI: 0.92-3.27), but not by native or postcontrast T1 time. Higher glycosylated hemoglobin levels were associated with higher degrees of MF. ConclusionsDiabetes is associated with higher degree of MF assessed by histology and ECV% but not by T1 time. In patients with diabetes, worse glycemic control was associated with higher MF degrees. These findings mostly apply to type 2 diabetes and warrant further investigation into whether these associations are causal and which medications could attenuate MF in patients with diabetes.

Extracellular volume quantification using synthetic haematocrit assessed from native and post-contrast longitudinal relaxation T1 times of a blood pool

BackgroundIn terms of cardiovascular magnetic resonance are haematocrit values required for calculation of extracellular volume fraction (ECV). Previously published studies have hypothesized that haematocrit could be calculated from T1 blood pool relaxation time, however only native T1 relaxation time values have been used and the resulting formulae had been both in reciprocal and linear proportion. The aim of the study was to generate a synthetic haematocrit formula from only native relaxation time values first, calculate whether linear or reciprocal model is more precise in haematocrit estimation and then determine whether adding post-contrast values further improve its precision.MethodsOne hundred thirty-nine subjects underwent CMR examination. Haematocrit was measured using standard laboratory methods. Afterwards T1 relaxation times before and after the application of a contrast agent were measured and a statistical relationship between these values was calculated.ResultsDifferent linear and reciprocal models were created to estimate the value of synthetic haematocrit and ECV. The highest coefficient of determination was observed in the combined reciprocal model “− 0.047 + (779/ blood native) − (11.36/ blood post-contrast)”.ConclusionsThis study provides more evidence that assessing synthetic haematocrit and synthetic ECV is feasible and statistically most accurate model to use is reciprocal. Adding post-contrast values to the calculation was proved to improve the precision of the formula statistically significantly.

T1-mapping and extracellular volume in patients with hypertrophic cardiomyopathy without focal myocardial injury in late gadolinium enhancement sequence

Abstract Funding Acknowledgements Type of funding sources: None. Background The LGE (late gadolinium enhancement) sequence is a recognized classic tool for imaging focal myocardial injury. The T1-mapping sequence to assess native T1 myocardial time, post-contrast T1 time, and myocardial extracellular volume (ECV) is a widely studied tool for imaging focal and diffused myocardial injury. Purpose The aim of the study was to evaluate the native T1 time, the post-contrast T1 time and the myocardial extracellular volume in the T1-mapping sequence in patients with hypertrophic cardiomyopathy without focal LGE myocardial injury. Methods The study group consisted of 28 consecutive patients who met the criteria for diagnosis of hypertrophic cardiomyopathy without focal LGE myocardial injury (HCM group; mean age 52.17 ± 6.35 years). 28 patients without cardiomyopathy (CON group; mean age 51.76 ± 6.49 years) with similar anthropometric parameters were selected by the case-to-case method as a control group. All patients underwent 1.5 T cardiac magnetic resonance, including cinematographic sequences (CINE), LGE sequence and T1-mapping sequences before (native) and 20-minutes after intravenous administration of a paramagnetic agent (post-contrast). In the T1-mapping sequences, the mean T1 time of the whole myocardium (T1 whole myocardium) was assessed, as well as the T1 time in the basal layers (T1 basal), middle layers (T1 middle) and apical layers (T1 apical) of the myocardium. Moreover, the mean T1 time was assessed in the 16-segment myocardial AHA model (T1 segment 1-16). The extracellular volume of the myocardium was estimated in an analogous way. Results In CINE sequences, in the HCM group compared to the CON group, the end-diastolic thickness of the anterior part of interventricular septum, the end-diastolic thickness of the left ventricular posterior wall and the left ventricular mass index were significantly higher. The studied groups did not differ in left ventricular ejection fraction. In both groups, no foci of myocardial injury in the LGE sequence were found. There were no statistically significant differences in T1 times between the study groups. In the HCM group as compared to the CON group, the ECV whole myocardium, ECV basal, ECV apical and ECV segments 1-3, 8, 13-16 were statistically significantly higher. Conclusion Patients with hypertrophic cardiomyopathy without myocardium focal injury in the LGE sequence are characterized by higher myocardial ECV values, assessed in the T1-mapping sequence.

Electrophysiologic and imaging evidence for an occult myopathic substrate in patients with idiopathic ventricular arrhythmias

BackgroundIdiopathic VA are traditionally considered benign, although occasional patients develop an ectopy-mediated cardiomyopathy (EMC). It is unclear whether patients with idiopathic VA in the absence of left ventricular (LV) dysfunction harbor a subclinical cardiomyopathy. We aim to assess for cardiomyopathic substrate in patients with idiopathic ventricular arrhythmias (VA) using imaging and electrophysiologic markers of early fibrosis. MethodsCardiac magnetic resonance (CMR) imaging and ventricular electroanatomic mapping was performed in 3 groups: patients undergoing ablation for idiopathic VA without (Group 1, n = 17) and with LV dysfunction (Group 2 [presumed EMC], n = 12) plus a control group undergoing ablation of supraventricular tachycardia (Group 3, n = 16). Global LV strain, T1 mapping and extended electrogram (EGM) characteristics were compared. ResultsGlobal strain was impaired in patients with presumed EMC (Group 2, p < 0.001). Native T1 times did not differ between groups, however patients in both idiopathic VA groups (Groups 1 and 2) had shorter post-contrast T1 times at 8 min compared to SVT controls (Group 3, p = 0.04). Similarly, the duration of the bipolar EGM was subtly prolonged in both Group 1 and 2 compared to Group 3 (p = 0.002). There were no between group differences in unipolar or bipolar voltage, the no. of bipolar EGM deflections or the maximal unipolar EGM dV/dt. ConclusionPatients with idiopathic VAs and apparently structurally normal hearts may have subtle CMR and electrophysiologic changes similar in magnitude to that seen in frank presumed EMC, possibly suggestive of an occult cardiomyopathic process.

CMR-Verified Myocardial Fibrosis Is Associated With Subclinical Diastolic Dysfunction in Primary Aldosteronism Patients.

ObjectivesThe main cardiac features of primary aldosteronism (PA) are impaired left ventricular (LV) diastolic function, and some articles also reported more cardiac fibrosis in PA patients. However, the correlation between LV dysfunction and diffuse myocardial fibrosis in PA remains unknown.MethodsWe enrolled 84 PA patients and 28 essential hypertension (EH) patients in West China Hospital. Cardiac magnetic resonance imaging (CMR) contrast enhancement was arranged for all subjects. Postcontrast T1 time and left ventricular myocardial strains and strain rates were measured.Results76 PA patients and 27 essential hypertension (EH) patients were included in the final analysis. Blood pressure, LV mass indexes, and LV ejection fractions were comparable in both groups, while the global circumferential peak diastolic strain rate (PDSR) was lower (0.9 ± 0.3 vs. 1.1 ± 0.4, p <0.01) and the postcontrast T1 time was shorter (520 ± 38 vs. 538 ± 27, p = 0.01) in PA patients than those in EH patients. Postcontrast T1 time (p = 0.01) was independently related to global circumferential PDSR after adjusting for age and duration of hypertension in PA patients. Furthermore, plasma aldosterone concentration was negatively associated with postcontrast T1 time (R = −0.253, p = 0.028) in PA patients.ConclusionsThe global circumferential PDSR derived by CMR is decreased, and the diffuse myocardial fibrosis is increased in PA patients compared to those in blood pressure matched EH patients. The severity of cardiac diastolic dysfunction independently relates to the degree of diffuse myocardial fibrosis in PA patients, and the diffuse myocardial fibrosis may be caused by high PAC level.Clinical Trial Registration http://www.chictr.org.cn/listbycreater.asp, identifier ChiCTR2000031792.

Real-time cardiovascular magnetic resonance tissue characterisation in patients undergoing transcatheter aortic valve replacement

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Research Foundation (DFG, CRC 1002, D1) Background Myocardial fibrosis is a major determinant of outcome in aortic stenosis (AS). Novel fast real-time (RT) cardiac magnetic resonance (CMR) mapping techniques allow comprehensive quantification of fibrosis but have not yet been compared against standard techniques and histology. Methods Patients with severe AS underwent CMR before (n = 110) and left ventricular (LV) endomyocardial biopsy (n = 46) at transcatheter aortic valve replacement (TAVR). Midventricular short axis (SAX) native, post-contrast T1 and extracellular volume fraction (ECV) maps were generated using commercially available MOLLI (native: 5(3)3, post-contrast: 4(1)3(1)2) and RT single-shot inversion recovery fast low-angle shot (FLASH) with radial undersampling. Focal late gadolinium enhancement was excluded from T1 and ECV regions of interest. ECV and LV mass were used to calculate LV matrix volumes. Variability and agreements were assessed between RT, MOLLI and histology using intraclass correlation coefficients, coefficients of variation and Bland Altman analyses. Results RT and MOLLI derived ECV were similar for midventricular SAX slice coverage (26.2 vs. 26.5, p = 0.073) and septal region of interest (26.2 vs. 26.5, p = 0.216). MOLLI native T1 time was in median 20 ms longer compared to RT (p &amp;lt; 0.001). Agreement between RT and MOLLI was best for ECV (ICC &amp;gt;0.91), excellent for post-contrast T1 times (ICC &amp;gt;0.81) and good for native T1 times (ICC &amp;gt;0.62). Diffuse collagen volume fraction by biopsies was in median 7.8%. ECV (RT r = 0.345, p = 0.039; MOLLI r = 0.40, p = 0.010) and LV matrix volumes (RT r = 0.45, p = 0.005; MOLLI r = 0.43, p = 0.007) were the only parameters associated with histology. Conclusions RT mapping offers fast and sufficient ECV and LV matrix volume calculation in AS. ECV and LV matrix volume represent robust and universally comparable parameters with associations to histologically assessed fibrosis and may emerge as potential targets for clinical decision making.

Myocardial Substrate Characterization by CMR T1 Mapping in Patients With NICM and No LGE Undergoing Catheter Ablation of VT.

The goal of this study was to characterize the relationship between DF, the electroanatomic mapping (EAM) substrate, and outcomes of catheter ablation of VT in NICM. A substantial proportion of patients with nonischemic dilated cardiomyopathy (NICM) and ventricular tachycardia (VT) do not have scar detectable by cardiac magnetic resonance late gadolinium enhancement (LGE) imaging. In these patients, the significance of diffuse fibrosis (DF) detected with T1 mapping has not been previously investigated. This study included 51 patients with NICM and VT undergoing catheter ablation (median age 55 years; 77% male subjects) who had no evidence of LGE on pre-procedural cardiac magnetic resonance. Post-contrast T1 relaxation time determined on the septum was assessed as a surrogate of DF burden. The extent of endocardial low-voltage areas (LVAs) at EAM was correlated with T1 mapping data. Bipolar LVAs were present in 22 (43%) patients (median extent 15 cm2 [8 to 29 cm2]) and unipolar LVA in all patients (median extent 48 cm2 [26 to 120 cm2]). A significant inverse correlation was found between T1 values and both unipolar-LVA (R2=0.64; β=-0.85; p<0.01) and bipolar-LVA (R2=0.16; β=-1.63; p<0.01). After a median follow-up of 45 months (22 to 57 months), 2 (4%) patients died, 3 (6%) underwent heart transplantation, and 8 (16%) experienced VT recurrence. Shorter post-contrast T1 time was associated with an increased risk of VT recurrence (hazard ratio: 1.16; 95% confidence interval: 1.03 to 1.33 per 10ms decrease; p=0.02). In patients with NICM and no evidence of LGE undergoing catheter ablation of VT, DF estimated by using post-contrast T1 mapping correlates with the voltage abnormality at EAM and seems to affect post-ablation outcomes.

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.

Real-time cardiac magnetic resonance tissue characterisation for fibrosis assessment in aortic stenosis

Abstract Background Myocardial fibrosis is a major determinant of outcome in aortic stenosis (AS). Novel fast real-time (RT) cardiac magnetic resonance (CMR) mapping techniques allow comprehensive quantification of fibrosis but have not yet been adequately validated against standard techniques and histology. Methods Patients with severe AS underwent CMR before (n=110) and left ventricular (LV) endomyocardial biopsy (n=46) at transcatheter aortic valve replacement (TAVR). Midventricular short axis native, post-contrast T1 and extracellular volume fraction (ECV) maps were generated using commercially available 5(3)3 MOLLI and RT single-shot inversion recovery fast low-angle shot (FLASH) with radial undersampling. ECV and LV mass were used to calculate LV matrix volumes. Variability and agreements were assessed between RT, MOLLI and histology using intraclass correlation coefficients, coefficients of variation and Bland Altman analyses. Results RT and MOLLI derived ECV were similar for myocardium (26.2 vs. 26.5, p=0.073) and inter-ventricular septum (26.2 vs. 26.5, p=0.216). MOLLI native T1 time was in median 20 ms longer compared to RT (p&amp;lt;0.001). Agreement between RT and MOLLI was best for ECV (ICC &amp;gt;0.91), excellent for post-contrast T1 times (ICC &amp;gt;0.81) and good for native T1 times (ICC &amp;gt;0.62). Diffuse collagen volume fraction by biopsies was in median 7.8%. ECV (RT r=0.345, p=0.039; MOLLI r=0.40, p=0.010) and LV matrix volumes (RT r=0.45, p=0.005; MOLLI r=0.43, p=0.007) were the only parameters associated with histology. Conclusions RT mapping offers precise T1 and ECV assessments with similar agreement with histology as compared to conventional MOLLI techniques. Single-shot real time techniques may be advantageous in sicker patients prone to dyspnoea or arrhythmia. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Research Foundation

P0254MYOCARDIAL TISSUE CHARACTERIZATION IN LIVING KIDNEY DONORS 5 YEARS AFTER NEPHRECTOMY

Abstract Background and Aims Uraemic cardiomyopathy is characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. Diffuse interstitial fibrosis of the myocardium, assessed using cardiac magnetic resonance imaging (CMR) techniques of native T1-mapping and extracellular volume (ECV), has been demonstrated in end stage chronic kidney disease (CKD) and in patients with stage 3 CKD and normal left ventricular mass. In living kidney donors estimated glomerular filtration rate (eGFR) declines by a third after donation, with 60% having a resultant eGFR comparable with stage 3 CKD. Recent studies have demonstrated small increases in LV mass at 12 months after donation as well as functional sequelae of reduced global circumferential strain and apical torsion. We sought to establish whether living kidney donors had CMR evidence of diffuse interstitial cardiac fibrosis which might contribute to observed functional correlates. Method A cross sectional blinded study of living kidney donors (n=50) and healthy controls (n=45) who underwent 3 Tesla CMR and blood samples for biomarkers of fibrosis. A modified look-locker inversion recovery (MOLLI) 5(3)3 sampling scheme was used for T1 mapping followed by T2 mapping sequences at the mid LV slice. Five minutes after the administration of gadolinium (Gadovist®) contrast (0.15mmol/kg), standard T1-weighted gradient echo inversion recovery images were repeated for the assessment of late gadolinium enhancement (assessment for focal fibrosis). Post contrast MOLLI images were acquired using identical slice positions as native images using a 4(1)3(1)2 sampling scheme 15 minutes after the administration of gadolinium. Native and post contrast T1 time was used to calculate ECV. Results There were no differences in demographics between groups; age (donors 54 ± 12yrs vs. healthy controls 50 ± 13yrs, p=0.128), ethnicity (89% Caucasian) or male gender (37%). LV mass and volumes were not significantly different. Forty four donors and 34 controls consented to receive gadolinium contrast. Native T1 in the septal mid LV slice was not significantly different between groups (donors 1223 ± 35ms vs. controls 1210 ± 36ms, p=0.102). There was also no difference in T2 time of the septal mid LV slice (donors 40 ± 2ms vs. controls 40 ± 4ms vs. p=0.455). Late gadolinium enhancement was seen in five living kidney donors in a right ventricular insertion point pattern but there was no mid wall or ischaemic pattern enhancement. There was no difference in septal ECV at the mid LV slice (donors 25 ± 2% vs. controls 25 ± 2%, p=0.896). There was also no corresponding difference in fibroblast growth factor-23 (RU/ml) in donors 74 [58-105] vs. controls 59 [47-75], p=0.081 or soluble α-klotho (pg/ml) in donors 610 [503-810] vs. controls 703 [550-955], p=0.061. Conclusion Septal T1 times and ECV in living kidney donors at 5 years from donation are no different from healthy controls. Biomarkers of cardiac fibrosis are also comparable to healthy controls in this small cohort. We found no CMR evidence of the ultrastructural changes reported in uraemic cardiomyopathy in the hearts of living kidney donors at 5 years from donation.

Prognostic significance of T1 mapping parameters in heart failure with preserved ejection fraction: a systematic review.

Heart failure with preserved ejection fraction (HFpEF) accounts for almost one-half of all heart failure (HF) patients and continues to increase in prevalence. While mortality with heart failure with reduced ejection fraction (HFrEF) has decreased over the past few decades with use of evidence-based HFrEF therapy, mortality related to heart failure with HFpEF has not changed significantly over the same time period. The combination of poor prognosis and lack of effective treatment options creates a pressing need for novel strategies for better patient characterization. We conducted a systematic review to evaluate the prognostic value of cardiac magnetic resonance (CMR)-derived T1 relaxation time and extracellular volume fraction (ECV) in HFpEF patients. PubMed, Embase, and Cochrane Central were searched for relevant studies. The primary outcomes of interest were hospitalization for HF and all-cause mortality. Five studies with 2741 patients were included. Four studies reported correlation of outcomes with ECV, 2 studies reported correlation of outcomes with native T1 time, and 1 study reported correlation of outcomes with post-contrast T1 time. All five studies showed significant correlation of CMR-derived parameters with adverse outcomes including event-free survival to cardiac event, all cause, and cardiac mortality. CMR-determined ECV is strongly correlated with adverse outcomes in HFpEF cohorts.

Real-time cardiovascular magnetic resonance T1 and extracellular volume fraction mapping for tissue characterisation in aortic stenosis

BackgroundMyocardial fibrosis is a major determinant of outcome in aortic stenosis (AS). Novel fast real-time (RT) cardiovascular magnetic resonance (CMR) mapping techniques allow comprehensive quantification of fibrosis but have not yet been compared against standard techniques and histology.MethodsPatients with severe AS underwent CMR before (n = 110) and left ventricular (LV) endomyocardial biopsy (n = 46) at transcatheter aortic valve replacement (TAVR). Midventricular short axis (SAX) native, post-contrast T1 and extracellular volume fraction (ECV) maps were generated using commercially available modified Look-Locker Inversion recovery (MOLLI) (native: 5(3)3, post-contrast: 4(1)3(1)2) and RT single-shot inversion recovery Fast Low-Angle Shot (FLASH) with radial undersampling. Focal late gadolinium enhancement was excluded from T1 and ECV regions of interest. ECV and LV mass were used to calculate LV matrix volumes. Variability and agreements were assessed between RT, MOLLI and histology using intraclass correlation coefficients, coefficients of variation and Bland Altman analyses.ResultsRT and MOLLI derived ECV were similar for midventricular SAX slice coverage (26.2 vs. 26.5, p = 0.073) and septal region of interest (26.2 vs. 26.5, p = 0.216). MOLLI native T1 time was in median 20 ms longer compared to RT (p < 0.001). Agreement between RT and MOLLI was best for ECV (ICC > 0.91), excellent for post-contrast T1 times (ICC > 0.81) and good for native T1 times (ICC > 0.62). Diffuse collagen volume fraction by biopsies was in median 7.8%. ECV (RT r = 0.345, p = 0.039; MOLLI r = 0.40, p = 0.010) and LV matrix volumes (RT r = 0.45, p = 0.005; MOLLI r = 0.43, p = 0.007) were the only parameters associated with histology.ConclusionsRT mapping offers fast and sufficient ECV and LV matrix volume calculation in AS patients. ECV and LV matrix volume represent robust and universally comparable parameters with associations to histologically assessed fibrosis and may emerge as potential targets for clinical decision making.

P1023Upstream therapy with spironolactone in patients with atrial fibrillation may reduce the burden of diffuse myocardial fibrosis and arrhythmia

Abstract Background The pathophysiology of atrial fibrillation (AF) involves a continuum of structural, hemodynamic, and electrophysical remodeling that coexist in a complex interplay, often involving increased diffuse myocardial fibrosis. Purpose To examine whether low dose spironolactone can reduce the extent of diffuse fibrosis in the left atrium (LA) and left ventricle (LV), evaluated using post-contrast T1 myocardial relaxation time (T1 time) and myocardial strain derived from cardiac magnetic resonance imaging (CMR), in patients with paroxysmal and persistent AF. Methods CMR sub-study population of 100 individuals from INSPIRE-AF, an investigator-initiated, randomized, controlled, double-blind study (NCT02764619). Study participants with paroxysmal (n=49) and persistent (n=51) non-valvular AF and LV ejection fraction ≥45% were randomized to spironolactone 25 mg once daily (SPL-group, n=49) or placebo (PL-group, n=51) in addition to standard treatment. CMR scans were conducted at inclusion and after 12 months of treatment. LA and LV measures, including volumes, ejection fraction, and peak systolic longitudinal strain were assessed using cine CMR feature tracking. T1 times were estimated using a previously validated modified look-locker inversion-recovery sequence. Commercially available software (Circle, Calgary, Canada) was used. All participants were followed for recurrences of AF, and all recurrences were documented with a standard 12-lead electrocardiogram. The associations between changes in mean volume, strain, and T1 times were examined using multivariable linear regression, adjusted for baseline age, sex, and AF type. Results LV post-contrast T1 time increased significantly in the SPL group (mean increase in SPL=1,97 ms [95% CI: 0,169; 3,323] vs. PL=0,21 ms [95% CI: −0,67; 1,11], p=0,027 for difference). However, the mean change of post-contrast LA T1 time did not differ between groups. LV peak longitudinal strain was also significantly improved in the SPL group (mean decrease in SPL: 19,82% [95% CI: −0,85; 40,48] vs. PL: 14,15% [95% CI: −36,21; 7,92], p=0,047). Similarly, LA stroke volume corrected for body surface area increased in the SPL-group (mean SPL: 34,33 ml/m2 [95% CI: −2,17; 42,62] vs. PL: 8,46 ml/m2 [95% CI: −20,13; 5,94], p=0,013). All changes remained significant after adjusting for age, sex and systolic blood pressure. No difference was found in arrhythmia burden between groups (P=0,89). Conclusion Low dose spironolactone may reduce the burden of diffuse myocardial fibrosis in AF. However, there was no reduction in the burden of arrhythmia. Acknowledgement/Funding Region of Southern Denmark, University of Southern Denmark, Danish Heart Association

T1- and ECV-mapping in clinical routine at 3\u2009T: differences between MOLLI, ShMOLLI and SASHA

BackgroundT1 mapping sequences such as MOLLI, ShMOLLI and SASHA make use of different technical approaches, bearing strengths and weaknesses. It is well known that obtained T1 relaxation times differ between the sequence techniques as well as between different hardware. Yet, T1 quantification is a promising tool for myocardial tissue characterization, disregarding the absence of established reference values. The purpose of this study was to evaluate the feasibility of native and post-contrast T1 mapping methods as well as ECV maps and its diagnostic benefits in a clinical environment when scanning patients with various cardiac diseases at 3 T.MethodsNative and post-contrast T1 mapping data acquired on a 3 T full-body scanner using the three pulse sequences 5(3)3 MOLLI, ShMOLLI and SASHA in 19 patients with clinical indication for contrast enhanced MRI were compared. We analyzed global and segmental T1 relaxation times as well as respective extracellular volumes and compared the emerged differences between the used pulse sequences.ResultsT1 times acquired with MOLLI and ShMOLLI exhibited systematic T1 deviation compared to SASHA. Myocardial MOLLI T1 times were 19% lower and ShMOLLI T1 times 25% lower compared to SASHA. Native blood T1 times from MOLLI were 13% lower than SASHA, while post-contrast MOLLI T1-times were only 5% lower. ECV values exhibited comparably biased estimation with MOLLI and ShMOLLI compared to SASHA in good agreement with results reported in literature. Pathology-suspect segments were clearly differentiated from remote myocardium with all three sequences.ConclusionMyocardial T1 mapping yields systematically biased pre- and post-contrast T1 times depending on the applied pulse sequence. Additionally calculating ECV attenuates this bias, making MOLLI, ShMOLLI and SASHA better comparable. Therefore, myocardial T1 mapping is a powerful clinical tool for classification of soft tissue abnormalities in spite of the absence of established reference values.

Prognostic Role of T1 Mapping Parameters in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review

Introduction Diffuse myocardial fibrosis plays a key role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Cardiac magnetic resonance (CMR) parameters such as native myocardial T1 relaxation time and extracellular volume fraction (ECV) are evolving imaging-based biomarkers of myocardial fibrosis. Therefore, we performed a systematic review to synthesize the available data on the prognostic value of T1 and ECV in patients with HFpEF. Methods and Results We searched PubMed, Embase and Cochrane Central for relevant studies using predefined search criteria and endpoints. Studies with overlapping patient population were excluded. Four studies were included in the review (TABLE). All included studies were prospective, single-center observational cohorts. Of the 1507 participants, 62% were women, mean age was 74.7± 8.3 years, and mean left ventricular EF was 63.2 ± 9.3%. Two of the 4 studies reported outcomes in relation to native T1 value. Both of them found no significant association of T1 value with adverse cardiovascular outcomes. One study found that lower post contrast T1 times were significantly associated with adverse cardiac events (HR-0.99; 95% CI-0.98-0.99). Three studies reported outcomes in relation to ECV and all of them found that higher ECV was associated with increased risk for adverse cardiovascular events or mortality. Two of the studies also assessed histological ECV (by endomyocardial biopsy) and demonstrated strong correlation between histologically determined ECV and CMR quantification of ECV (R=0.494; P=0.037). Conclusion Estimation of ECV may provide important prognostic information in patients with HFpEF and has the potential to improve risk stratification.

FASt single-breathhold 2D multislice myocardial T1 mapping (FAST1) at 1.5T for full left ventricular coverage in three breathholds.

BackgroundConventional myocardial T1 mapping techniques such as modified Look–Locker inversion recovery (MOLLI) generate one T1 map per breathhold. T1 mapping with full left ventricular coverage may be desirable when spatial T1 variations are expected. This would require multiple breathholds, increasing patient discomfort and prolonging scan time.PurposeTo develop and characterize a novel FASt single‐breathhold 2D multislice myocardial T1 mapping (FAST1) technique for full left ventricular coverage.Study TypeProspective.Population/PhantomNumerical simulation, agarose/NiCl2 phantom, 9 healthy volunteers, and 17 patients.Field Strength/Sequence1.5T/FAST1.AssessmentTwo FAST1 approaches, FAST1‐BS and FAST1‐IR, were characterized and compared with standard 5‐(3)‐3 MOLLI in terms of accuracy, precision/spatial variability, and repeatability.Statistical TestsKruskal‐Wallis, Wilcoxon signed rank tests, intraclass correlation coefficient analysis, analysis of variance, Student's t‐tests, Pearson correlation analysis, and Bland–Altman analysis.ResultsIn simulation/phantom, FAST1‐BS, FAST1‐IR, and MOLLI had an accuracy (expressed as T1 error) of 0.2%/4%, 6%/9%, and 4%/7%, respectively, while FAST1‐BS and FAST1‐IR had a precision penalty of 1.7/1.5 and 1.5/1.4 in comparison with MOLLI, respectively. In healthy volunteers, FAST1‐BS/FAST1‐IR/MOLLI led to different native myocardial T1 times (1016 ± 27 msec/952 ±22 msec/987 ± 23 msec, P < 0.0001) and spatial variability (66 ± 10 msec/57 ± 8 msec/46 ± 7 msec, P < 0.001). There were no statistically significant differences between all techniques for T1 repeatability (P = 0.18). In vivo native and postcontrast myocardial T1 times in both healthy volunteers and patients using FAST1‐BS/FAST1‐IR were highly correlated with MOLLI (Pearson correlation coefficient ≥0.93).Data ConclusionFAST1 enables myocardial T1 mapping with full left ventricular coverage in three separated breathholds. In comparison with MOLLI, FAST1 yield a 5‐fold increase of spatial coverage, limited penalty of T1 precision/spatial variability, no significant difference of T1 repeatability, and highly correlated T1 times. FAST1‐IR provides improved T1 precision/spatial variability but reduced accuracy when compared with FAST1‐BS. Level of Evidence: 1 Technical Efficacy: Stage 3J. Magn. Reson. Imaging 2020;51:492–504.

Myocardial native-T1 times are elevated as a function of hypertrophy, HbA1c, and heart rate in diabetic adults without diffuse fibrosis

PurposeCardiac native-T1 times have correlated to extracellular volume fraction in patients with confirmed fibrosis. However, whether other factors that can occur either alongside or independently of fibrosis including increased intracellular water volume, altered magnetization transfer (MT), or glycation of hemoglobin, lengthen T1 times in the absence of fibrosis remains unclear. The current study examined whether native-T1 times are elevated in hypertrophic diabetics with elevated hemoglobin A1C (HbA1c) without diffuse fibrosis. MethodsNative-T1 times were quantified in 27 diabetic and 10 healthy adults using a modified Look-Locker imaging (MOLLI) sequence at 1.5 T. The MT ratio (MTR) was quantified using dual flip angle cine balanced steady-state free precession. Gadolinium (0.2 mmol/kg Gd-DTPA) was administered as a bolus and post-contrast T1-times were quantified after 15 min. Means were compared using a two-tailed student's t-test, while correlations were assessed using Pearson's correlations. ResultsWhile left ventricular volumes, ejection fraction, and cardiac output were similar between groups, left ventricular mass and mass-to-volume ratio (MVR) were significantly higher in diabetic adults. Mean ECV (0.25 ± 0.02 Healthy vs. 0.25 ± 0.03 Diabetic, P = 0.47) and MTR (125 ± 16% Healthy vs. 125 ± 9% Diabetic, P = 0.97) were similar, however native-T1 times were significantly higher in diabetics (1016 ± 21 ms Healthy vs. 1056 ± 31 ms Diabetic, P = 0.00051). Global native-T1 times correlated with MVR (ρ = 0.43, P = 0.008) and plasma HbA1c levels (ρ = 0.43, P = 0.0088) but not ECV (ρ = 0.06, P = 0.73). Septal native-T1 times correlated with septal wall thickness (ρ = 0.50, P = 0.001). ConclusionIn diabetic adults with normal ECV values, elevated native-T1 times may reflect increased intracellular water volume and changes secondary to increased hemoglobin glycation.

Myocardial extracellular volume fraction measurements with MOLLI 5(3)3 by cardiovascular MRI for the discrimination of healthy volunteers from dilated and hypertrophic cardiomyopathy patients

To investigate the diagnostic performance of myocardial native T1 time and the extracellular volume fraction (ECV) for differentiating dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) patients from healthy volunteers. Forty healthy volunteers, 57 DCM patients, and 30 HCM patients were enrolled, all of whom underwent cardiovascular magnetic resonance imaging (CMRI), including late gadolinium enhancement (LGE) and native and post-contrast T1 mapping acquired with the modified Look-Locker inversion recovery (MOLLI) sequence on a 1.5 T MRI system. ECV were calculated by native and post-contrast T1 times. Multivariate binary logistic regression analyses and receiver operating characteristic (ROC) curve analyses were used to assess the concordance with the clinical diagnosis of DCM and HCM. DCM and HCM patients had significantly higher myocardial native T1 times and ECVs than healthy volunteers (p<0.001). Multivariate logistic regression analyses showed that ECV was an independent predictor of DCM and HCM diagnosis (OR=1.556, p<0.001 and OR=1.847, p=0.001, respectively). ROC curve analysis indicated that ECV provided greater distinction between DCM patients and healthy volunteers than native T1 time (AUC: 0.889 versus 0.780, p=0.021). At the optimal cut-off value, ECV identified DCM and HCM patients with 80.7% and 83.3% sensitivity, 87.5% and 70% specificity, 90.2% and 67.6% positive predictive value, and 76.1% and 84.8% negative predictive value, respectively. The increased ECV in DCM and HCM patients reflects myocardial extracellular matrix expansion. Myocardial ECV provides good diagnostic performance for identifying DCM and HCM patients from healthy volunteers.

Abstract 17255: Standard 12-Lead Electrocardiogram Can Predict Diffuse Myocardial Fibrosis in Patients With Atrial Fibrillation

Background: The pathophysiology of atrial fibrillation (AF) involves a continuum of myocardial remodeling with increased diffuse fibrosis. Purpose: To examine whether the extent of diffuse fibrosis in the left atrium (LA) and left ventricle (LV), evaluated using the surrogate marker, post-contrast T1 myocardial relaxation time on cardiac magnetic resonance imaging (CMR), in patients with paroxysmal and persistent AF is associated with ECG markers obtained during sinus rhythm. Methods: This is a prespecified secondary analysis from the randomized controlled trial INSPIRE-AF (n=95) (ClinicalTrials.gov NCT02764619). Patients with paroxysmal and persistent AF underwent CMR. Post-contrast T1 times were quantified in 47 paroxysmal AF (mean age, 63 ±8 years), and 43 persistent AF (mean age, 54 ±7 years) patients using a previously validated modified look-locker inversion-recovery sequence. Standard resting 12-lead ECGs were analyzed using commercially available software. Results: Baseline characteristics were generally similarly distributed between AF groups. Mean LA T1 time was 492 +/- 72 ms and mean LV T1 time was 494 +/- 49 ms. P-wave area, P-wave terminal force, PR-interval, P-wave peak amplitude, and P-wave duration were unassociated with LA T1 time, and no significant interactions with AF type were detected. Similarly, neither R-wave duration, corrected QT interval (Bazett’s formula), nor QRS duration were associated with LV T1 time. P-wave terminal force in lead V1 did not differ between groups of investigation, but the joint mean value of -0.04 mm/s in the two groups is prominently different from normal controls. AF type significantly interacted with the association between R-wave duration and T1 time (P=0.03 for interaction), and between QRS duration and T1 time (P=0.009 for interaction). Specifically, R-wave duration and QRS duration were only significantly associated with T1 time among patients with persistent AF. Conclusions: Diffuse fibrosis in the LV, defined as post-contrast T1 time, was associated with R-wave duration and QRS duration in patients with persistent AF. Our findings suggest that surface 12-lead ECG obtained in sinus rhythm could provide predictive information regarding diffuse myocardial fibrosis.