Left Ventricular Extracellular Volume Research Articles

Abstract 14836: Left Ventricular Extracellular Volume on Computed Tomography is Useful for Predicting Reverse Remodeling After Catheter Ablation for Atrial Fibrillation

Introduction: In the CAMERA-MRI study, restoring sinus rhythm with catheter ablation (CA) for atrial fibrillation (AF) significantly improved left ventricular (LV) ejection fraction (EF), particularly in the absence of LV myocardial fibrosis, determined by magnetic resonance imaging (MRI). LV extracellular volume fraction (ECV) on MRI correlates with myocardial fibrosis. Recently analysis of LVECV on computed tomography (CT) has been feasible and LVECV on CT and MRI correlate well. Little is known about what predicts achieving LV reverse remodeling (LVRR) after CA. Hypothesis: LVECV on pre-ablation planning CT could predict LVRR after CA in patients with AF and reduced LVEF. Methods: One thousand three hundred twenty patients underwent CA for AF in our institutions from Apr 2014 to Aug 2022. Of these, 50 patients (4%) with LVEF under 50% on transthoracic echocardiography (TTE) were included. All patients underwent cardiac CT using 320-detector or 256-detector row CT before the CA. LVECV was measured by CT using non-contrast and late-phase cardiac images (Figure A). We defined LVRR as an LV end-systolic volume decrease of 15% or more, an increase in LVEF to 50% or more, or an absolute LVEF increase of 15% or more. We evaluated the utility of LVECV for the prediction of LVRR after CA. Results: LVRR was achieved in 31 patients (62%) after CA, and LVECV was significantly lower in them than in the others (31.3 ± 3.3% vs. 35.9 ± 6.6%, P < 0.01) (Figure B). On receiver operating characteristic curve analysis, the best cut-off of LVECV for the prediction of LVRR was 34.8%, and the sensitivity and specificity of LVECV for the prediction of RR were 90 and 68% (the area under the curve was 0.72, Figure C). On multivariate logistic regression analysis, LVECV less than or equal to 34.8% was the only significant predictor of LVRR. Conclusion: LVECV on CT is useful for predicting LVRR in patients with AF after CA.

The correlation of left atrial dysfunction and amyloid load in patients with immunoglobulin light-chain cardiac amyloidosis: a 3T cardiac magnetic resonance study.

To investigate the left atrial (LA) changes in immunoglobulin light-chain cardiac amyloidosis (AL-CA) patients with different risk stratifications and to explore the correlation between LA function and the degree of amyloid load using cardiac magnetic resonance (CMR) imaging. Forty-three AL-CA patients were retrospectively enrolled and were divided into low-to-moderate-risk group (n = 16, increased NT-proBNP or troponin I, or both normal) and high-risk group (n = 27, increased NT-proBNP and troponin I). 20 healthy individuals matched for age and gender were included. The function, myocardial deformation of left heart, and left ventricular (LV) tissue characterization among the three groups were compared. The correlation between LA function and LV tissue characterization was investigated. Compared with the controls, the AL-CA patients had a larger LA volume, lower left atrial emptying fraction (LAEF) and impaired left atrial strain (LAS). The high-risk group exhibited lower reservoir and booster function and increased LV extracellular volume (LV-ECV) than the low-to-moderate-risk group (p < 0.05). LV-ECV was significantly correlated with LAS and LAEF (all p < 0.05) but not LAEFconduit. The LAS and LAEF had a good diagnostic ability for risk stratification of AL-CA patients (area under the curve, 0.70 ~ 0.72). High-risk AL-CA patients showed more severe LA function impairment than low-to-moderate-risk AL-CA patients. LAS and LAEF were closely associated with LV-ECV in AL-CA patients, LAS and LAEF exhibited good capability to differentiate AL-CA patients of different risk stratifications. CMR-derived LAS and LAEF were correlated with amyloid load, allowing for differentiation of AL-CA patients at different risk stages.

Head-to-Head Comparison of T1 Mapping and Electroanatomical Voltage Mapping in Patients With Ventricular Arrhythmias

BackgroundElectroanatomical voltage mapping (EAVM) has been compared with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), which cannot delineate diffuse fibrosis. T1-mapping CMR overcomes the limitations of LGE-CMR, but it has not been directly compared against EAVM. ObjectivesThis study aims to assess the relationship between left ventricular (LV) endocardial voltage obtained by EAVM and extracellular volume (ECV) obtained by T1 mapping. MethodsThe study investigated patients who underwent endocardial EAVM for ventricular arrhythmias (CARTO 3, Biosense Webster) together with preprocedural contrast-enhanced T1 mapping (Ingenia 3T, Philips Healthcare). After image integration, EAVM datapoints were projected onto LGE-CMR and ECV-encoded images. Average values of unipolar voltage (UV), bipolar voltage (BV), LGE transmurality, and ECV were merged from corresponding cardiac segments (6 per slice) and pooled for analysis. ResultsThe analysis included data from 628 segments from 18 patients (57 ± 13 years of age, 17% females, LV ejection fraction 48% ± 14%, nonischemic/ischemic cardiomyopathy/controls: 8/6/4 patients). Based on the 95th and 5th percentile values obtained from the controls, ECV >33%, BV <2.9 mV, and UV <6.7 mV were considered abnormal. There was a significant inverse association between voltage and ECV, but only in segments with abnormal ECV. Increased ECV could predict abnormal BV and UV with acceptable accuracy (area under the curve of 0.78 [95% CI: 0.74-0.83] and 0.84 [95% CI: 0.79-0.88]). ConclusionsThis study found a significant inverse relationship between LV endocardial voltage and ECV. Real-time integration of T1 mapping may guide catheter mapping and may allow identification of areas of diffuse fibrosis potentially related to ventricular arrhythmias.

A new composite indicator consisting of left ventricular extracellular volume, N-terminal fragment of B-type natriuretic peptide, and left ventricular end-diastolic volume is useful for predicting reverse remodeling after catheter ablation for atrial fibrillation.

Recently, myocardial extracellular volume (ECV) analysis has been measurable on computed tomography (CT) using new software. We evaluated the use of cardiac CT to estimate the myocardial ECV of left ventricular (LV) myocardium (LVM) to predict reverse remodeling (RR) in cases of atrial fibrillation (AF) after catheter ablation (CA). Four hundred and seven patients underwent CA for AF in our institution from April 2014 to Feb 2021. Of these, 33 patients (8%) with an LVEF ≤ 50% and who had undergone CT were included in our study. We estimated the LVM ECV using commercial software to analyze the CT data. RR was defined as an improvement in LVEF to > 50% after CA. LVEF increased to > 50% in 24 patients (73%) after CA. In all 24 patients, LVM ECV, LV end-diastolic and end-systolic volumes (LVEDV and LVESV), and the n-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) were significantly lower than in the other nine patients (P = 0.0037, 0.0273, 0.0443, and < 0.0001). On receiver operating characteristic curve analysis, the best cut-off of ECV, LVEDV, LVESV and NT-proBNP for the prediction of RR were 37.73%, 120mL, 82mL, and 1267pg/mL, respectively. We newly defined the ENL (ECV, NT-proBNP, and LVEDV) score as the summed score for the presence or absence (1 or 0; maximum score = 3) of ECV, NT-proBNP, and LVEDV values less than or equal to each best cut-off value, and found that this score gave the highest area under the curve for the prediction of RR (0.9583, P < 0.0001). The ENL score may be useful for predicting RR in patients with AF undergoing CA.

The diagnostic value of multiparameter cardiovascular magnetic resonance for early detection of light-chain amyloidosis from hypertrophic cardiomyopathy patients.

Early-stage amyloidosis of the heart is prone to be underdiagnosed or misdiagnosed, increasing the risk of early heart failure and even death of the patient. To ensure timely intervention for cardiac light-chain amyloidosis (AL CA), it is vital to develop an effective tool for early identification of the disease. Recently, multiparameter cardiovascular magnetic resonance (CMR) has been used as a comprehensive tool to assess myocardial tissue characterization. We aimed to investigate the difference in left ventricular (LV) strain, native T1, extracellular volume (ECV), and late gadolinium enhancement (LGE) between AL CA patients, hypertrophic cardiomyopathy patients (HCM), and healthy control subjects (HA). Moreover, we explored the value of multiparameter CMR for differential diagnosis of the early-stage AL CA patients from HCM patients, who shared similar imaging characteristics under LGE imaging. A total of 38 AL CA patients, 16 HCM patients, and 17 HA people were prospectively recruited. All subjects underwent LGE imaging, Cine images, and T1 mapping on a 3T scanner. The LV LGE pattern was recorded as none, patchy or global. LV strain, native T1, and ECV were measured semi-automatically using dedicated CMR software. According to clinical and biochemical markers, all patients were classified as Mayo stage I/II and Mayo stage IIIa/IIIb. Univariable and multivariable logistic regression models were utilized to identify independent predictors of early-stage AL CA from HCM patients. Receiver operator characteristic (ROC) curve analysis and Youden's test were done to determine the accuracy of multiparameter CMR in diagnosing Mayo stage I/II AL CA and establish a cut-off value. For Mayo stage I/II AL CA patients, the global longitudinal strain (GLS) absolute value (11.9 ± 3.0 vs. 9.5 ± 1.8, P < 0.001) and the global circumferential strain (GCS) absolute value (19.0 ± 3.6 vs. 9.5 ± 1.8, P < 0.001) were significantly higher than in HCM patients. The native T1 (1334.9 ± 49.9 vs. 1318.2 ± 32.4 ms, P < 0.0001) and ECV values (37.8 ± 5.7 vs. 31.3 ± 2.5%, P < 0.0001) were higher than that of HCM patients. In multiparameter CMR models, GCS (2.097, 95% CI: 1.292-3.403, P = 0.003), GLS (1.468, 95% CI: 1.078-1.998, P = 0.015), and ECV (0.727, 95% CI: 0.569-0.929, P = 0.011) were the significant variables for the discrimination of the early-stage AL CA patients from HCM patients. ROC curve analysis and Youden's test were used on GCS, GLS, ECV, and pairwise parameters for differentiating between Mayo stage I/II AL CA and HCM patients, respectively. The combination of GLS, GCS, and ECV mapping could distinguish Mayo stage I/II AL amyloidosis patients from hypertrophic cardiomyopathy with excellent performance (AUC = 0.969, Youden index = 0.813). In early-stage AL CA patients with atypical LGE, who had similar imaging features as HCM patients, ECV mapping, GCS, and GLS were correlated with the clinical classification of the patients. The combination of GCS, GLS, and ECV could differentiate early-stage AL CA from HCM patients. Multiparameter CMR has the potential to provide an effective and quantitative tool for the early diagnosis of myocardial amyloidosis.

Natural history of myocardial fibrosis in dilated cardiomyopathy

Abstract Background It is commonly accepted that myocardial fibrosis (MF) is implicated in the pathology of dilated cardiomyopathy (DCM). However, MF is not a “fixed” abnormality but evolves over time. It is unknown what the natural history of MF is in optimally treated DCM patients. Methods This is a prospective, single-center, observational study. Between May 2019 and September 2020, 90 DCM (81 male, mean age 47.2±9.8 years, mean EF 34.5±12.2%) patients underwent cardiac magnetic resonance (CMR). All patients were optimally treated with heart failure approved medications (beta-blockers in 100%, ACE-I/ARNI/ARB – 98%, MRA – 95%). Both, replacement via late gadolinium enhancement (LGE) and interstitial via T1 mapping MF were assessed. Replacement MF was expressed as LGE mass and LGE extent, whereas interstitial MF as extracellular volume (ECV). Left ventricular (LV) matrix and cell volumes were calculated based on LV mass and ECV as: LV matrix volume = (LV mass/1.05 g/mL) × ECV and LV cell volume = (LV mass/1.05 g/mL) × (1 − ECV). After 12 months CMR studies with MF assessment were repeated. Results Overall, index LV end-diastolic and end-systolic volumes (LVEDvol, LVESvol) and LV mass significantly decreased, whereas EF increased during follow-up (Table 1). Both, LGE mass (8.7±8.1 vs. 8.6±7.7 g; p=0.6) and LGE extent (4.6±4.2 vs. 4.97±4.6%; p=0.14) were similar between two measurements. There was a trend towards ECV decrease between baseline and follow-up studies but it did not reach statistical significance (28.5±4.9 vs. 27.7±4.1%; p=0.09). LV matrix volume significantly decreased during follow-up (49.1±17.8 vs. 46.1±15.7 ml; p&amp;lt;0.05); however LV cell volume remained unchanged (123.1±35.6 vs. 119.7±39.6 ml; p=0.2). Conclusions Beneficial regression of LV volumes and improvement of systolic function is common in DCM over mid-term period (one year). Replacement fibrosis seems to be a “fixed” pathology without much room for improvement. On the other hand, interstitial fibrosis seems to be a subject for substantial change. Left ventricular cells compartment does not change over time. Two types of MF – replacement and interstitial behaved differently during follow-up. Interstitial MF is amenable for treatment, whereas replacement MF does not respond to currently available therapy. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was founded through the National Science Centre, Poland (grant number 2018/29/B/NZ5/02588) and the Department of Scientific Research and Structural Funds of Medical College, Jagiellonian University (grant number K/ZDS/007192)

Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease

ObjectivesThis study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). BackgroundEmpagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown. MethodsThis was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2. ResultsBaseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: –1.40%; 95% confidence interval [CI]: –2.60 to –0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: –1.5 ml/m2; 95% CI: –2.6 to –0.5 ml/m2; p = 0.006), with a trend toward reduction in iICV (adjusted difference: –1.7 ml/m2; 95% CI: –3.8 to 0.3 ml/m2; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2. ConclusionsIn individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970)

Abstract 17007: Cardiac Magnetic Resonance Assessment of Right Ventricular Remodeling After Anthracycline Therapy

Introduction: There are limited data characterizing the effect of anthracyclines on right ventricular (RV) structure and function. Hypothesis: The goal of this study was to test the effect of anthracyclines on RV myocardial remodeling using cardiac magnetic resonance (CMR). Methods: This was a prospective CMR and serum biomarker study of 27 women with breast cancer (BC) (51.8±8.9 years) who underwent a CMR prior, and up to 3-times after anthracycline therapy (240 mg/m 2 ). The primary measure of interest was the RV extracellular volume (ECV) and cardiomyocyte mass index (1-ECV). Additional measures of interest were the left ventricular (LV) ECV, and the LV and RV mass. Biomarkers included high-sensitive troponin T, and creatinine-kinase MB isoenzyme (CKMB). Results: Before anthracyclines, all subjects had normal LV ejection fraction (EF) (69.4±3.6%) and RVEF (55.6±9%). At 351-700 days after anthracyclines, the LVEF and LV mass index declined to 58±6% (P&lt;0.001) and 36±6g/m 2 (P&lt;0.001). Similarly, the RVEF and RV mass index also decreased, reaching 46.3±6.8% at (222-350] days (P&lt;0.001) and 8.13±2g/m 2 at (350-700] days (P&lt;0.001) after anthracycline, respectively (Figure 1). At (350-700] days after anthracycline, both LV and RV ECV increased by 0.037 to 0.36±0.04 (P=0.004) and by 0.12 to 0.40±0.07 (P&lt;0.001), respectively (Figure 2). In parallel, both the LV and RV cardiomyocyte mass also decreased after anthracyclines (Figure 2). Conclusions: In a prospective observational study among women with breast cancer, anthracyclines were associated with a decrease in the RV EF, an increase in the RV ECV and a decrease in the RV cardiomyocyte mass.

Abstract 17492: Chronic Treatment With a Mavacamten-Like Myosin-Modulator (MYK-581) Prevents Left-Atrial Remodeling, Decreases Cardiac Troponin Leakage, and Blunts Mortality in a Mini-Pig Model of Inherited Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is a progressive disease characterized by cardiac remodeling, impaired relaxation, left-atrial enlargement, and exertional intolerance. Direct myosin-inhibition with mavacamten can normalize contractility and improve exercise capacity in patients with obstructive HCM (oHCM). However, mavacamten also limits residual cross-bridges during diastole, and therefore, may offer cardiac benefits beyond obstruction relief. This in vivo study evaluated the chronic effects of MYK-581, a mavacamten surrogate, in a genetic large-animal model of HCM. Methods: Young cloned Yucatan mini-pigs with a heterozygous MYH7 R403Q mutation were randomly assigned to one of two arms: untreated-controls (CTRL, n = 29) or daily MYK-581 (n = 22; PO); wild-type pigs (WT) untreated served as disease-controls. After 14 weeks of treatment, pigs underwent in vivo cMR imaging, including T1 mapping and extracellular volume (ECV) assessments. In a subset of pigs, biomechanical studies were performed in skinned left-ventricular (LV) and left-atrial (LV) fibers. *, #: P&lt;0.05 vs. CTRL or WT. Results: In HCM pigs, MYK-581 treatment decreased mortality (9.0* vs. 37.9% in CTRL). MYK-581 blunted cTnT leakage, reducing both absolute values (21.2 ± 3.2* vs. 34.0 ± 4.3 ng/L in CTRL) and the incidence of cTnT &gt; 20 ng/L (36* vs. 81% in CTRL). Treated pigs had smaller LA volumes (16 ± 1* vs. 29 ± 4mL in CTRL) with lower LV T1-times and ECV (27 ± 1* vs. 32 ± 2% in CTRL). LA fibers from untreated HCM pigs showed biomechanical remodeling characteristic of chronic overload: increased maximal force (21.8 ± 1.5# vs. 14.7 ± 1.4 mN/mm2 in WT) and slowed cross-bridge formation rates (Ktr: 4.9 ± 0.4 # vs. 6.6 ± 0.6 s-1 in WT) consistent with a switch towards slow-myosin isoforms. MYK-581 prevented this remodeling (e.g., Ktr: 8.1 ± 1.3 s-1*), preserving normal LA (fast) myosin content. Conclusions: Chronic direct myosin attenuation with a mavacamten surrogate prevented left-atrial remodeling, a known prognostic indicator in HCM. Chronic treatment also reduced cardiac troponin leakage characteristic HCM, and, more importantly, decreased mortality. Taken together, these pre-clinical observations show potential salutary effects beyond obstruction relief in HCM.

The link between left ventricular extracellular volume determined by T1 myocardial mapping and gut microbiota composition in individuals with heart failure and preserved ejection fraction

Abstract Introduction Heart failure with preserved ejection fraction (HFpEF) represents a major challenge in modern cardiology. As described previously, in HFpEF comorbidities promote a systemic inflammatory state, leading to diffuse myocardial fibrosis resulting in myocardial stiffening. Gut dysbiosis which is considered as the novel source of chronic systemic inflammation has been actively investigated as the risk factor for the development and aggravation of cardiovascular diseases including heart failure. Cardiac magnetic resonance T1-mapping is a novel tool, which allows noninvasive quantification of the extracellular space and diffuse myocardial fibrosis. Moreover, the extracellular volume (ECV) fraction can be calculated, providing information on the relative expansion of the extracellular matrix, thus being a noninvasive alternative to myocardial biopsy studies. Purpose The research was aimed at investigating the correlation between the left ventricular ECV and gut microbial genera in patients with HFpEF. Methods 42 patients with confirmed HF-pEF (mediana and interquartile range of age 67 [64; 72] years, 47% men, body mass index &amp;lt;35 kg/m2 with no history of myocardial infarction or diabetes mellitus) were enrolled in the study. The patients underwent transthoracic echocardiography with Doppler study, HF-pEF was confirmed according to the recent ESC guidelines (based on E/e' ratio, N-terminal pro-B type natriuretic peptide &amp;gt;125 pg/ml and symptoms of heart failure). The intestinal microbiome was investigated using high-throughput sequencing of bacterial 16S rRNA gene. As the last step of research T1-myocardial mapping with the modified look-locker inversion-recovery protocol (MOLLI) sequence at 1.5 Tesla was performed to assess left ventricular extracellular volume fraction. Results The mean±std in ECV was 31.02±4.4%. The relative abundance (%) of the most prevalent phyla in gut microbiota was 48±22.5 for Firmicutes, 47.4±22.8 for Bacteroidetes and 1.5 [1.5; 2.5] for Proteobacteria. The analysis showed significant negative correlations between ECV and the following bacterial genera: Faecalibacterium (r=−0.35), Blautia (r=−0.43), Lachnoclostridium (r=−0.32). Moreover ECV positively correlated with Holdemania (r=0.4), Victivallis (r=0.38), Dehalobacterium (r=0.38), Enterococcus (r=0.33) and Catabacter (r=0.32). All correlation values with p&amp;lt;0.05. Conclusion We discovered both negative and positive significant correlations between ECV – the non-invasive marker of myocardial fibrosis and several bacterial genera, which may have negative impact on myocardial remodeling in HF-pEF. Funding Acknowledgement Type of funding source: None

Left atrial late gadolinium enhancement is associated with atrial fibrillation as detected by continuous monitoring

Abstract Background Left atrial late gadolinium enhancement (LA LGE) measured with cardiac magnetic resonance (CMR) imaging is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures. However, the prognostic value of LA LGE for incident AF remains unknown. Methods CMR including measurement of left ventricular (LV) and LA volumes and function, as well as LV extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received and implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. Results Patients were monitored for AF with implantable loop recorder during a median of 41 [36; 43] months. AF episodes lasting ≥6 minutes were detected in 32 patients (47%) and 16 patients (24%) experienced AF episodes lasting ≥5.5-hour. In Cox regression analyses adjusted for sex, age and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratio for time to AF episodes lasting ≥6 minutes and ≥5.5 hours were 1.40 (1.03, 1.89) per 10 cm2 increase (p=0.03) and 1.63 (1.11, 2.40) per 10 cm2 increase (p=0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. Conclusions Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Innovation Fund Denmark, The Research Foundation for the Capital Region of Denmark [no grant number]

Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders

ObjectivesThe authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population. BackgroundLA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown. MethodsCardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. ResultsPatients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm2 increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm2 increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. ConclusionsExtent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450)

Left Ventricular Extracellular Volume Expansion Is Not Associated with Atrial Fibrillation or Atrial Fibrillation-mediated Left Ventricular Systolic Dysfunction.

To determine whether left ventricular (LV) extracellular volume (ECV) expansion is associated with atrial fibrillation (AF) or AF-mediated LV systolic dysfunction (LVSD) while minimizing the influence of biologic and imaging methodologic confounders. This study examined the prevalence of LV ECV expansion in 137 patients with AF (mean age, 62 years ± 11 [standard deviation]; 92 male patients and 45 female patients; 83 paroxysmal and 54 persistent) who underwent preablation cardiovascular MRI. Biologic confounders were minimized by measuring the ECV fraction and excluding patients with severe LV hypertrophy, defined as wall thickness greater than 1.5 cm. Imaging confounders were minimized by using an arrhythmia-insensitive-rapid (AIR) cardiac T1 mapping pulse sequence. Other cardiac functional parameters, including LV ejection fraction (LVEF) and left atrial end-diastolic volume indexed to body surface area, were assessed using cine cardiovascular MRI. A substudy was conducted in 32 patients with no AF (mean age, 54 years ± 16) in sinus rhythm to establish control values and convert these values between the AIR sequence and literature-based modified Look-Locker inversion recovery (MOLLI) values. The mean ECV was not significantly different (P > .05) between patients with AF with a normal LVEF (24.5% ± 2.8; n = 107), patients with AF with LVSD (24.5% ± 2.5; n = 30), and patients with no AF (24.4% ± 3.8; n = 32), but there was a significant interaction between ECV and CHA2DS2-VASc score (P = .045). Compared with the literature data obtained from healthy control patients scanned using MOLLI, 99.3% of patients with AF had ECV below the fibrosis cutoff point (32.8% when converted from MOLLI T1 mapping to AIR T1 mapping), including a subset of patients with AF (n = 28) with low CHA2DS2-VASc score (0/1 for men/women). Study results suggest that an LV ECV expansion is not associated with AF or AF-mediated LVSD. Supplemental material is available for this article. © RSNA, 2020See also the commentary by Stillman in this issue.

Predictors of left ventricular remodelling in patients with dilated cardiomyopathy - a cardiovascular magnetic resonance study.

There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling. Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P=0.02). Baseline myocardial strain (P=0.39 global longitudinal strain), interstitial myocardial fibrosis (P=0.41), replacement myocardial fibrosis (P=0.25), and right ventricular contractile reserve (P=0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r=-0.22, P=0.23) or baseline LVEF (r=0.07, P=0.62). Men were more likely to experience adverse LV remodelling (P=0.01) but age (P=0.88) and disease-modifying heart failure medication (beta-blocker, P=0.28; angiotensin-converting enzyme inhibitor, P=0.92) did not predict follow-up LVEF. Substantial recovery of LV function occurs within 12 months in most patients with recent-onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.

Left ventricular extracellular volume expansion does not predict recurrence of atrial fibrillation following catheter ablation.

A recent study reported that diffuse left ventricular (LV) fibrosis is a predictor of atrial fibrillation (AF) recurrence following catheter ablation, by measuring postcontrast cardiac T1 (an error prone metric as per the 2017 Society for Cardiovascular Magnetic Resonance consensus statement) using an inversion-recovery pulse sequence (an error prone method in arrhythmia) in AF ablation candidates. The purpose of this study was to verify the prior study, by measuring extracellular volume (ECV) fraction (an accurate metric) using a saturation-recovery pulse sequence (accurate method in arrhythmia). This study examined 100 AF patients (mean age=62±11 years, 69 males and 31 females, 67 paroxysmal [pAF] and 33 persistent [peAF]) who underwent a preablation cardiovascular magnetic resonance (CMR) exam. LV ECV and left atrial (LA) and LV functional parameters were quantified using standard analysis methods. During an average follow-up period of 457±261 days with 4±3 rhythm checks per patient, 72 patients maintained sinus rhythm. Between those who maintained sinus rhythm (n=72) and those who reverted to AF (n=28), the only clinical characteristic that was significantly different was age (60 ± 12 years vs 66 ± 9years); for CMR metrics, neither mean LV ECV (25.1 ± 3.3%vs 24.7±3.7%), native LV T1 (1093.8 ± 73.5ms vs 1070.2 ± 115.9ms), left ventricular ejection fraction (54.1 ± 11.2%vs 55.7±7.1%), nor LA end diastolic volume/body surface area (42.4 ± 14.8mL/m2 vs 43.4±19.6mL/m2 ) were significantly different (P ≥ .23). According to Cox regression tests, none of the clinical and imaging variables predict AF recurrence. Neither LV ECV nor other CMR metrics predict recurrence of AF following catheter ablation.

T1-Mapping and extracellular volume estimates in pediatric subjects with Duchenne muscular dystrophy and healthy controls at 3T

BackgroundCardiovascular disease is the leading cause of death in patients with Duchenne muscular dystrophy (DMD)—a fatal X-linked genetic disorder. Late gadolinium enhancement (LGE) imaging is the current gold standard for detecting myocardial tissue remodeling, but it is often a late finding. Current research aims to investigate cardiovascular magnetic resonance (CMR) biomarkers, including native (pre-contrast) T1 and extracellular volume (ECV) to evaluate the early on-set of microstructural remodeling and to grade disease severity. To date, native T1 measurements in DMD have been reported predominantly at 1.5T. This study uses 3T CMR: (1) to characterize global and regional myocardial pre-contrast T1 differences between healthy controls and LGE + and LGE− boys with DMD; and (2) to report global and regional myocardial post-contrast T1 values and myocardial ECV estimates in boys with DMD, and (3) to identify left ventricular (LV) T1-mapping biomarkers capable of distinguishing between healthy controls and boys with DMD and detecting LGE status in DMD.MethodsBoys with DMD (N = 28, 13.2 ± 3.1 years) and healthy age-matched boys (N = 20, 13.4 ± 3.1 years) were prospectively enrolled and underwent a 3T CMR exam including standard functional imaging and T1 mapping using a modified Look-Locker inversion recovery (MOLLI) sequence. Pre-contrast T1 mapping was performed on all boys, but contrast was administered only to boys with DMD for post-contrast T1 and ECV mapping. Global and segmental myocardial regions of interest were contoured on mid LV T1 and ECV maps. ROI measurements were compared for pre-contrast myocardial T1 between boys with DMD and healthy controls, and for post-contrast myocardial T1 and ECV between LGE + and LGE− boys with DMD using a Wilcoxon rank-sum test. Results are reported as median and interquartile range (IQR). p-Values < 0.05 were considered significant. Receiver Operating Characteristic analysis was used to evaluate a binomial logistic classifier incorporating T1 mapping and LV function parameters in the tasks of distinguishing between healthy controls and boys with DMD, and detecting LGE status in DMD. The area under the curve is reported.ResultsBoys with DMD had significantly increased global native T1 [1332 (60) ms vs. 1289 (56) ms; p = 0.004] and increased within-slice standard deviation (SD) [100 (57) ms vs. 74 (27) ms; p = 0.001] compared to healthy controls. LGE− boys with DMD also demonstrated significantly increased lateral wall native T1 [1322 (68) ms vs. 1277 (58) ms; p = 0.001] compared to healthy controls. LGE + boys with DMD had decreased global myocardial post-contrast T1 [565 (113) ms vs 635 (126) ms; p = 0.04] and increased global myocardial ECV [32 (8) % vs. 28 (4) %; p = 0.02] compared to LGE− boys. In all classification tasks, T1-mapping biomarkers outperformed a conventional biomarker, LV ejection fraction. ECV was the best performing biomarker in the task of predicting LGE status (AUC = 0.95).ConclusionsBoys with DMD exhibit elevated native T1 compared to healthy, sex- and age-matched controls, even in the absence of LGE. Post-contrast T1 and ECV estimates from 3T CMR are also reported here for pediatric patients with DMD for the first time and can distinguish between LGE + from LGE− boys. In all classification tasks, T1-mapping biomarkers outperform a conventional biomarker, LVEF.

Biventricular tissue tracking demonstrating associations between left ventricular myocardial extracellular volume, pulmonary artery pressure, and reduced right ventricular ejection fraction in patients with systemic lupus erythematosus using cardiovascular MRI

To investigate the feasibility and prognostic value of biventricular strain analysis for patients with systemic lupus erythematosus (SLE) and relationship to left ventricular (LV) myocardial fibrosis, pulmonary hypertension (PAH), and right ventricular (RV) ejection fraction (RVEF). A total of 50 SLE patients (47 women; 34.4±12 years) and 15 controls (13 women; 32.9±8.6 years) were imaged via echocardiography and a 3 T magnetic resonance imaging (MRI). Pulmonary artery systolic pressure (sPAP) was assessed using echocardiography. Biventricular global circumferential strain (GCS), global longitudinal strain (GLS), global circumferential strain rate (GCSR), and global longitudinal strain rate (GLSR) as well as LV myocardial extracellular volume (ECV) were derived for each subject. Elevated LV ECV was significantly associated with LV GCS (beta -0.428, p=0.000), GLS (beta 0.404, p=0.000), GCSR (beta -0.350, p=0.006), GLSR (beta -0.445, p=0.000) and RV GCS (beta -0.373, p=0.000), and the presence of reduced RVEF was significantly associated with LV GCS (beta -0.338, p=0.002), GLS (beta -0.465, p=0.000) and RV GCS (beta -0.465, p=0.000). Raised sPAP was significantly associated with RV GLS (beta 0.445, p=0.000) and GCSR (beta -0.387, p=0.001). Moreover, there were significantly correlations between LV and RV strain and strain rate. Biventricular strain analysis may be a better prognostic tool for patients with SLE as it allows greater comprehensive analysis and more definitive treatment planning compared to separate assessment of LV or RV contractility.

P5274Characterization of cardiac involvement in patients with MELAS syndrome in comparison to HCM patients by conventional LGE imaging and novel T1-mapping

Abstract Background MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare clinical subtype of mitochondrial myopathy. Cardiovascular magnetic resonance (CMR) images of MELAS-patients at an advanced state of the disease often show characteristic patterns: septal pronounced left ventricular (LV) hypertrophy and distinct focal myocardial scars in late-gadolinium-enhancement (LGE) images. This specific pattern is different from those seen in patients with hypertrophic cardiomyopathy (HCM) due to sarcomere protein mutations. Besides LGE imaging another method for the assessment of myocardial integrity, T1-mapping, has been established recently. This is the first study comparing native and enhanced T1-mapping (T1-na/en) as well as extracellular volume (ECV) values in HCM and MELAS. Methods 12 patients with confirmed MELAS syndrome at different states of the disease, 13 HCM patients and 15 controls were included. All CMR studies were performed on a 1.5T MR scanner (Ingenia, Philips) using bSSFP cine sequences for the assessment of LV-function and MOLLI sequences for T1-na/en mapping. 15min after IV injection of 0.1mmol/kg BW Gadobutrol for LGE imaging, T1-en maps were acquired. For comparison of groups T1-na/en and ECV values in a basal short axis slice were used. Results Median and interquartile ranges of LV function, T1 and ECV are shown in the table. There was no difference in LV ejection fraction (LVEF) between the groups, but end-diastolic LV-mass was increased in HCM- and MELAS-patients vs. controls (p&lt;0.001, p=0.028). In MELAS-patients, myocardial fibrosis was detected in focal spots clearly defined in both septum and free lateral wall. In HCM patients there was a rather diffuse LGE pattern in the hypertrophic septum and the RV insertion points. Here T1-na/en and ECV significantly differed from those measured in healthy controls (p&lt;0.001, p&lt;0.001, p=0.002). In the MELAS group T1-na values were significantly higher compared to controls (p=0.004) and significantly lower compared to HCM patients (p=0.003). LV-function and mapping parameters of compared groups LV-EF, % LV-EDV, ml/m2 LV-mass, g/m2 T1-na, ms T1-en, ms ECV, % MELAS 57 (44–63) 86 (81–122) 80 (50–131) 969 (940–1033) 409 (381–465) 27 (24–35) HCM 60 (57–65) 50 (73–94) 94 (72–102) 1041 (1021–1074) 362 (346–430) 31 (28–36) Controls 61 (58–65) 72 (67–89) 53 (42–60) 937 (894–951) 464 (446–513) 26 (24–27) Conclusion Compared to healthy controls and HCM-patients, cardiac involvement in MELAS-patients is not only reliably visualized by conventional LGE imaging but also detected without the use of contrast agent by native T1-mapping. MELAS vs. HCM-patients show a different pattern of LGE and higher native T1 values, respectively.

Prognostic Significance of Left Ventricular Fibrosis Assessed by T1 Mapping in Patients with Atrial Fibrillation and Heart Failure

This study sought to investigate whether left ventricular (LV) fibrosis quantified by T1 mapping can be used as a biomarker to predict outcome in patients with atrial fibrillation (AF) and heart failure (HF). 108 patients with AF and HF were included in this study. They underwent cardiac magnetic resonance, including T1 mapping sequence to assess LV fibrosis between May 2014 to May 2016. Patients received catheter ablation for AF and pharmacological treatment for HF. The primary endpoint was a composite adverse outcome of cardiac death, subsequent HF or stroke, subsequent HF was the secondary endpoint. During follow up (median: 23 months, Q1-Q3: 11 to 28 months), 1 cardiac death, 12 strokes, and 42 HF episodes occurred. LV extracellular volume fraction (ECV) was predictive of composite adverse outcome and subsequent HF (all p < 0.001). In multivariable analysis, LV ECV was an independent predictor of composite adverse outcome (hazard ratio (HR): 1.258, 95% confidence interval (CI): 1.140–1.388, p < 0.001) and subsequent HF (HR: 1.223, 95% CI: 1.098–1.363, p < 0.001). LV fibrosis measured by T1 mapping indices significantly predicts composite adverse outcomes and subsequent HF in patients with AF and HF.

Determinants of Left Ventricular Dysfunction and Remodeling in Patients With Corrected Tetralogy of Fallot.

BackgroundThe aim of this study was to identify in asymptomatic patients with repaired tetralogy of Fallot the prevalence and determinants of impaired left‐sided cardiac function and adverse ventricular remodeling and the relation of left ventricular (LV) dysfunction and remodeling with cardiopulmonary exercise capacity.Methods and ResultsIn a cross‐sectional study, 103 patients with tetralogy of Fallot (median age, 16.3 years) in New York Heart Association class 1, with surgical repair at a median age of 1.1 years, and 63 age‐matched controls were studied. LV, right ventricular function and geometry, LV myocardial extracellular volume (n=57), and left atrial function were quantified with cardiac magnetic resonance. Peak oxygen consumption was measured by a standardized cardiopulmonary exercise test (n=70). Patients with tetralogy of Fallot had lower LV ejection fraction (P=0.001; 49% below age‐adjusted fifth percentile for controls), lower LV mass index (P=0.003), lower LV mass/volume ratio (P<0.01), and impaired left atrial function. Right ventricular mass/volume ratio was the best predictor for LV systolic dysfunction and for a lower LV mass/volume ratio. Compared with controls, LV extracellular volume was higher (P<0.001), particularly in female patients, and associated with subnormal peak oxygen consumption (P=0.037). A peak oxygen consumption below the third percentile reference level was more likely with decreasing LV ejection fraction (P=0.008), and lower LV mass index (P=0.024), but independent of right ventricular ejection fraction.ConclusionsIn New York Heart Association class 1 patients with tetralogy of Fallot, frequent impaired systolic and diastolic LV function, LV adverse remodeling with LV atrophy, a decreased mass/volume ratio, and extracellular matrix expansion suggest cardiomyopathic changes. The best predictor for LV systolic dysfunction was the right ventricular mass/volume ratio. The subnormal peak oxygen consumption indicates that monitoring of LV status may be important for long‐term prognosis.