Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study

PurposeMyocardial fibrosis in aortic stenosis (AS) is associated with worse survival following aortic valve replacement (AVR). We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. MethodsA total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement (LGE) and T1 mapping and global longitudinal strain (GLS) analysis. Collagen volume fraction (CVF) was measured in myocardial biopsies (71) that were sampled at the time of AVR. ResultsCVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19-33) vs 20.7% (15-30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=-0.303, p=0.013) and non-invasively (native T1; r=-0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. ConclusionOur data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

Reference Values of Native T1 at 3T Cardiac Magnetic Resonance—Standardization Considerations between Different Vendors

This study aimed at establishing native T1 reference values for a Canon Vantage Galan 3T system and comparing them with previously published values from different vendors. A total of 20 healthy volunteers (55% Women; 33.9 ± 11.1 years) underwent left ventricular T1 mapping at 3T MR. A MOLLI 5(3)3 sequence was used, acquiring three short-axis slices. Native T1 values are shown as means (±standard deviation) and Student’s independent samples t-test was used to test gender differences in T1 values. Pearson’s correlation coefficient analysis was used to compare two processes of T1 analysis. The results show a global native T1 mean value of 1124.9 ± 55.2 ms (exponential analysis), that of women being statistically higher than men (1163 ± 30.5 vs. 1077.9 ± 39.5 ms, respectively; p < 0.001). There were no specific tendencies for T1 times in different ventricular slices. We found a strong correlation (0.977, p < 0.001) with T1 times derived from parametric maps (1136.4 ± 60.2 ms). Native T1 reference values for a Canon 3T scanner were provided, and they are on par with those already reported from other vendors for a similar sequence. We also found a correlation between native T1 and gender, with higher values for women.

66 Heart and lung tissue characterization of COVID-19 pneumonia by T1 and T2 mapping magnetic resonance imaging

Aims Coronavirus disease 2019 (COVID-19) is a respiratory tract infection which can lead to systemic involvement including myocardial injury, severe respiratory failure and death. Magnetic resonance imaging (MRI) could potentially offer advantages in providing tissue characterization of lung parenchyma and heart muscle in COVID-19. The aim of the present study was to describe data on heart and lung MRI in a cohort of patients hospitalized due to COVID-19 pneumonia. Methods and results n = 11 patients hospitalized with COVID-19 pneumonia underwent a comprehensive MRI examinations including lung and heart tissue mapping, findings were compared to those of an age- and sex-matched cohort of n = 11 individuals. Lung native T1 and T2 mapping assessments were performed by drawing a circular region of interest (ROI) with diameter of 2 cm in the parenchyma visualized from the cardiac four chamber long axis-oriented slice; vessels and areas of pleural effusion were carefully excluded. Myocardial native T1 and T2 mapping were assessed by drawing a ROI within the midventricular left ventricular (LV) septum. No patients had previous history of cardiovascular disease (including known coronary artery disease, heart failure, cardiomyopathy, atrial fibrillation). As compared to controls, patients with COVID-19 had similar cardiac function, higher mid-septum myocardial native T1 (1028 ms vs. 985, P = 0.05) and significantly higher lung native T1 and T2 within affected areas (1375 ms vs. 1201 ms, P = 0.016 and 70 ms vs. 30 ms, P &lt; 0.001 respectively), whereas non-significant differences were observed between remote lung areas of patients and controls (1238 ms vs. 1152 ms, P = 0.088 and 29 ms vs. 33 ms, P = 0.797 respectively). No significant associations were observed between cardiac and lung mapping findings. Conclusions In our cohort of patients with COVID-19, T1 and T2 mapping lung MRI identified pneumonia related abnormalities as compared to healthy controls, likely representing oedema and ongoing inflammation at the lung site. Myocardial native T1 was elevated suggesting the presence of cardiac involvement. A comprehensive MRI examination can be potentially used to assess multiorgan involvement in COVID-19.

Machine learning of native T1 mapping radiomics for classification of hypertrophic cardiomyopathy phenotypes

We explored whether radiomic features from T1 maps by cardiac magnetic resonance (CMR) could enhance the diagnostic value of T1 mapping in distinguishing health from disease and classifying cardiac disease phenotypes. A total of 149 patients (n = 30 with no heart disease, n = 30 with LVH, n = 61 with hypertrophic cardiomyopathy (HCM) and n = 28 with cardiac amyloidosis) undergoing a CMR scan were included in this study. We extracted a total of 850 radiomic features and explored their value in disease classification. We applied principal component analysis and unsupervised clustering in exploratory analysis, and then machine learning for feature selection of the best radiomic features that maximized the diagnostic value for cardiac disease classification. The first three principal components of the T1 radiomics were distinctively correlated with cardiac disease type. Unsupervised hierarchical clustering of the population by myocardial T1 radiomics was significantly associated with myocardial disease type (chi2 = 55.98, p < 0.0001). After feature selection, internal validation and external testing, a model of T1 radiomics had good diagnostic performance (AUC 0.753) for multinomial classification of disease phenotype (normal vs. LVH vs. HCM vs. cardiac amyloid). A subset of six radiomic features outperformed mean native T1 values for classification between myocardial health vs. disease and HCM phenocopies (AUC of T1 vs. radiomics model, for normal: 0.549 vs. 0.888; for LVH: 0.645 vs. 0.790; for HCM 0.541 vs. 0.638; and for cardiac amyloid 0.769 vs. 0.840). We show that myocardial texture assessed by native T1 maps is linked to features of cardiac disease. Myocardial radiomic phenotyping could enhance the diagnostic yield of T1 mapping for myocardial disease detection and classification.

395 Diagnostic role of native T1 mapping compared to conventional magnetic resonance techniques in cardiac diseases: a real-life study

Aims T1 mapping is a validated technique in cardiac magnetic resonance (CMR), however in real-life clinical practice its effectiveness to diagnose myocardial disease is still unclear. To compare native T1 mapping to conventional late gadolinium enhancement (LGE) and T2-STIR techniques for the evaluation of a cohort of consecutive patients undergoing CMR for the suspicion of myocardial disease. Methods and results CMR was performed in 323 patients, 206 males (64%), mean age 54 ± 8 years, and in 27 age- and sex-matched healthy controls. LGE, T2-STIR, and pre- and post-contrast T1 mapping were acquired as suggested by the SCMR position paper. The CMR findings of global and regional T1 mapping were compared to the respective results of LGE and T2-STIR techniques. The main baseline indications for CMR were: suspicion of ARVC in 20%; non-ischaemic DCM in 19%; HCM in 16%; chest pain without obstructive coronary artery in 14% of patients (suspicion of MINOCA, Tako-tsubo or myocarditis); other indications (amyloidosis, scleroderma, previous myocardial infarction, pericarditis, LV non-compaction) in the remaining of cases. At T2-STIR images myocardial hyperintensity suggesting oedema was found in 41 patients (27%). LGE images were positive in 206 patients (64%). Native T1 mapping was abnormal in 171 (49%). In 206 patients (64%) a matching between LGE and native T1 was found (both positive in 132 and negative in 74). T1 was also abnormal in 32 out of 41 (78%) with oedema at T2-STIR. Overall, LGE and/or T2-STIR were abnormal in 209 patients, whereas native T1 in 154(52%). Conventional techniques and T1 mapping were concordant in 208 patients (64%). Conventional techniques were abnormal in 76 (24%) of patients with negative T1 mapping. Finally, in 39 patients T1 mapping was positive despite negative conventional techniques (12%). Among these latter 39 patients, only in 18 T2-STIR were acquired based on clinical decision. Then, the percentage of cases where T1 mapping could have an additive role would range between 6% and 12%. T1 mapping was particularly able in conditions with diffuse myocardial damage as cardiac amyloidosis, scleroderma and fabry disease (additive role in 42%). On contrast, T1 mapping was less effective in cardiac disease with regional distribution of myocardial damage as myocardial infarction, HCM, myocarditis (additive role in 1%). Conclusions T1 mapping may give additive information in 6–12% of patient but is less effective cardiac disease presenting with regional or segmental distribution of myocardial damage. Results of the present study suggest that conventional LGE/T2-STIR and T1 mapping are complementary techniques and should be used together in every CMR examination.

Is cardiac involvement prevalent in highly trained athletes after SARS-CoV-2 infection? A cardiac magnetic resonance study using sex-matched and age-matched controls

ObjectivesTo investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls.MethodsSARS-CoV-2 infection was diagnosed by PCR on swab tests or serum immunoglobulin G antibody tests prior to a comprehensive CMR examination. The CMR protocol contained sequences to assess structural, functional and tissue-specific data.ResultsOne hundred forty-seven athletes (94 male, median 23, IQR 20–28 years) after SARS-CoV-2 infection were included. Overall, 4.7% (n=7) of the athletes had alterations in their CMR as follows: late gadolinium enhancement (LGE) showing a non-ischaemic pattern with or without T2 elevation (n=3), slightly elevated native T1 values with or without elevated T2 values without pathological LGE (n=3) and pericardial involvement (n=1). Only two (1.4%) athletes presented with definite signs of myocarditis. We found pronounced sport adaptation in both athletes after SARS-CoV-2 infection and athlete controls. There was no difference between CMR parameters, including native T1 and T2 mapping, between athletes after SARS-CoV-2 infection and the matched athletic groups. Comparing athletes with different symptom severities showed that athletes with moderate symptoms had slightly greater T1 values than athletes with asymptomatic and mildly symptomatic infections (p<0.05). However, T1 mapping values remained below the cut-off point for most patients.ConclusionAmong 147 highly trained athletes after SARS-CoV-2 infection, cardiac involvement on CMR showed a modest frequency (4.7%), with definite signs of myocarditis present in only 1.4%. Comparing athletes after SARS-CoV-2 infection and healthy sex-matched and age-matched athletes showed no difference between CMR parameters, including native T1 and T2 values.

Prognostic value of right ventricular native T1 mapping in pulmonary arterial hypertension

Background Right ventricular function is an important prognostic marker for pulmonary arterial hypertension. Native T1 mapping using cardiovascular magnetic resonance imaging can characterize the myocardium, but accumulating evidence indicates that T1 values of the septum or ventricular insertion points do not have predictive potential in pulmonary arterial hypertension. We aimed to elucidate whether native T1 values of the right ventricular free wall (RVT1) can predict poor outcomes in patients with pulmonary arterial hypertension. Methods This retrospective study included 30 patients with pulmonary arterial hypertension (median age, 45 years; mean pulmonary artery pressure, 41±13 mmHg) and 16 healthy controls (median age, 43 years) who underwent native T1 mapping. RVT1 was obtained from the inferior right ventricular free wall during end systole. Results Patients with pulmonary arterial hypertension had significantly higher native RVT1 than did controls (1384±74 vs. 1217±57 ms, p<0.001). Compared with T1 values of the septum or ventricular insertion points, RVT1 correlated better with the effective right ventricular elastance index (R = −0.53, p = 0.003), ventricular-arterial uncoupling (R = 0.46, p = 0.013), and serum brain natriuretic peptide levels (R = 0.65, p<0.001). Moreover, the baseline RVT1 was an accurate predictor of the reduced right ventricular ejection fraction at the 12-month follow-up (delta -3%). RVT1 was independently associated with composite events of death or hospitalization from any cause (hazard ratio = 1.02, p = 0.002). Conclusions RVT1 was predictive of right ventricular performance and outcomes in patients with pulmonary arterial hypertension. Thus, native T1 mapping in the right ventricular free wall may be an effective prognostic method for pulmonary arterial hypertension.

Irisin as a Potential Biomarker Associated with Myocardial Injuries in Patients with Severe Hypothyroidism

Objective. Irisin, a novel myokine, has recently been considered to produce a cardioprotective effect. Potential biomarkers for myocardial injuries in patients with severe hypothyroidism have yet to be identified. We aimed to investigate whether serum irisin may serve as a promising biomarker for early detecting the myocardial injuries in patients with severe hypothyroidism. Methods. This cross-sectional study comprised 25 newly diagnosed drug-naive patients with severe primary hypothyroidism and 17 age- and sex-matched healthy controls. Circulating irisin levels and cardiac magnetic resonance (CMR) were evaluated in each participant. Left ventricular (LV) myocardial injuries were detected by CMR-based T1 mapping technique using a modified look-locker inversion recovery (MOLLI) sequence, which is quantified as native T1 values. Results. Compared with healthy controls, the severe hypothyroidism group had significantly lower levels of serum irisin, especially those with pericardial effusion ( P < 0.05 ). The severe hypothyroidism subjects exhibited lower peak filling rates (PFRs) and higher native myocardial T1 values than controls ( P < 0.05 ). Additionally, the ROC analysis displayed that the sensitivity and specificity of serum irisin for diagnosing pericardial effusion in patients with severe hypothyroidism were 73.3% and 100.0%, respectively. The AUC was 0.920 (0.861–1.000) ( P < 0.001 ). The cutoff value was 36.94 ng/mL. Moreover, the results in subgroup analysis revealed that the native T1 values of the low-irisin group were significantly higher than that of the high-irisin group ( P < 0.05 ). According to multivariate linear regression analysis, serum irisin concentrations were negatively and independently correlated with native myocardial T1 values after adjustment for age, sex, and other conventional confounding factors (β = −1.473, P < 0.05 ). Conclusions. Irisin may be a potential biomarker for predicting myocardial injuries in patients with severe hypothyroidism.

Adverse fibrosis remodeling and aortopulmonary collateral flow are associated with poor Fontan outcomes

Background The extent and significance in of cardiac remodeling in Fontan patients are unclear and were the subject of this study. Methods This retrospective cohort study compared cardiovascular magnetic resonance (CMR) imaging markers of cardiac function, myocardial fibrosis, and hemodynamics in young Fontan patients to controls. Results Fifty-five Fontan patients and 44 healthy controls were included (median age 14 years (range 7–17 years) vs 13 years (range 4–14 years), p = 0.057). Fontan patients had a higher indexed end-diastolic ventricular volume (EDVI 129 ml/m2 vs 93 ml/m2, p < 0.001), and lower ejection fraction (EF 45% vs 58%, p < 0.001), circumferential (CS − 23.5% vs − 30.8%, p < 0.001), radial (6.4% vs 8.2%, p < 0.001), and longitudinal strain (− 13.3% vs − 24.8%, p < 0.001). Compared to healthy controls, Fontan patients had higher extracellular volume fraction (ECV) (26.3% vs 20.6%, p < 0.001) and native T1 (1041 ms vs 986 ms, p < 0.001). Patients with a dominant right ventricle demonstrated larger ventricles (EDVI 146 ml/m2 vs 120 ml/m2, p = 0.03), lower EF (41% vs 47%, p = 0.008), worse CS (− 20.1% vs − 25.6%, p = 0.003), and a trend towards higher ECV (28.3% versus 24.1%, p = 0.09). Worse EF and CS correlated with longer cumulative bypass (R = − 0.36, p = 0.003 and R = 0.46, p < 0.001), cross-clamp (R = − 0.41, p = 0.001 and R = 0.40, p = 0.003) and circulatory arrest times (R = − 0.42, p < 0.001 and R = 0.27, p = 0.03). T1 correlated with aortopulmonary collateral (APC) flow (R = 0.36, p = 0.009) which, in the linear regression model, was independent of ventricular morphology (p = 0.9) and EDVI (p = 0.2). The composite outcome (cardiac readmission, cardiac reintervention, Fontan failure or any clinically significant arrhythmia) was associated with increased native T1 (1063 ms vs 1026 ms, p = 0.029) and EDVI (146 ml/m2 vs 118 ml/m2, p = 0.013), as well as decreased EF (42% vs 46%, p = 0.045) and worse CS (− 22% vs − 25%, p = 0.029). APC flow (HR 5.5 CI 1.9–16.2, p = 0.002) was independently associated with the composite outcome, independent of ventricular morphology (HR 0.71 CI 0.30–1.69 p = 0.44) and T1 (HR1.006 CI 1.0–1.13, p = 0.07). Conclusions Pediatric Fontan patients have ventricular dysfunction, altered myocardial mechanics and increased fibrotic remodeling. Cumulative exposure to cardiopulmonary bypass and increased aortopulmonary collateral flow are associated with myocardial dysfunction and fibrosis. Cardiac dysfunction, fibrosis, and collateral flow are associated with adverse outcomes.

Myocardial changes on 3T cardiovascular magnetic resonance imaging in response to haemodialysis with fluid removal

Background Mapping of left ventricular (LV) native T1 is a promising non-invasive, non-contrast imaging biomarker. Native myocardial T1 times are prolonged in patients requiring dialysis, but there are concerns that the dialysis process and fluctuating fluid status may confound results in this population. We aimed to assess the changes in cardiac parameters on 3T cardiovascular magnetic resonance (CMR) before and after haemodialysis, with a specific focus on native T1 mapping. Methods This is a single centre, prospective observational study in which maintenance haemodialysis patients underwent CMR before and after dialysis (both scans within 24 h). Weight measurement, bio-impedance body composition monitoring, haemodialysis details and fluid intake were recorded. CMR protocol included cine imaging and mapping native T1 and T2. Results Twenty-six participants (16 male, 65 ± 9 years) were included in the analysis. The median net ultrafiltration volume on dialysis was 2.3 L (IQR 1.8, 2.5), resulting in a median weight reduction at post-dialysis scan of 1.35 kg (IQR 1.0, 1.9), with a median reduction in over-hydration (as measured by bioimpedance) of 0.75 L (IQR 0.5, 1.4). Significant reductions were observed in LV end-diastolic volume (− 25 ml, p = 0.002), LV stroke volume (− 13 ml, p = 0.007), global T1 (21 ms, p = 0.02), global T2 (− 1.2 ms, p = 0.02) following dialysis. There was no change in LV mass (p = 0.35), LV ejection fraction (p = 0.13) or global longitudinal strain (p = 0.22). On linear regression there was no association between baseline over-hydration (as defined by bioimpedance) and global native T1 or global T2, nor was there an association between the change in over-hydration and the change in these parameters. Conclusions Acute changes in cardiac volumes and myocardial native T1 are detectable on 3T CMR following haemodialysis with fluid removal. The reduction in global T1 suggests that the abnormal native T1 observed in patients on haemodialysis is not entirely due to myocardial fibrosis.