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.

Coronary Microvascular Dysfunction

Coronary microvascular dysfunction (DMK) is a condition of patients who are accompanied by complaints of chest pain where the results of coronary angiography examination are normal and this is almost 49% with 60% of patients diagnosed with DMK. Another study said that about 40% of patients with DMK showed coronary flow reserve (CFR <2) of about 40% and the WISE study (Women's Ischaemia Syndrome Evaluation) showed that about 47% of patients with chest pain had normal coronary arteries. DMK can be divided into 4 groups; DMK with no coronary arterial disease (CAD) obstruction and myocardial disease, DMK with myocardial disease where this occurs due to remodeling of intramural coronary arteries, DMK with CAD (coronary arterial disease) or acute myocardial infarction with or without ST segment, iatrogenic typhoid DMK occurs after coronary recanalization caused by vasoconstriction and distal embolization. The mechanism of action of DMK can be caused by several factors, namely endothelial dysfunction, smooth muscle dysfunction, decreased diastolic perfusion time, damage to blood vessels and damage to the vascular and microvascular remodeling. And to enforce this DMK, there are several tests carried out in diagnosing the disease, some of which are invasive and non-invasive so that by enforcing the diagnosis of this disease, treatment for DMK can be done immediately and optimally.

Myocardial tissue phenotyping by radiomic features of native T1 maps and machine learning enhances disease detection and classification

Background Myocardial T1 mapping by cardiac magnetic resonance (CMR) is a useful technique to detect diffuse myocardial fibrosis, but a major limitation of T1 mapping is the significant overlap in native T1 values between health and disease. Purpose We explored whether radiomic features from T1 maps could enhance the diagnostic value of T1 mapping in distinguishing health from disease and classifying cardiac disease phenotypes. Methods In a total of 149 patients (n=30 with no evidence of heart disease, n=30 with LVH of various etiologies, n=61 with hypertrophic cardiomyopathy (HCM) and n=28 with cardiac amyloidosis) undergoing a CMR scan for various indications were included in this study. In addition to measuring native myocardial T1 values from T1 maps, we extracted a total of 843 radiomic features of myocardial texture and explored their value in disease classification. Results We first demonstrated that T1 mapping images are a rich source of extractable, quantifiable data. The first three principal components of the T1 radiomics were significantly and 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&lt;0.0001). After machine learning for feature selection, training with 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. amyloid). A subset of seven radiomic features outperformed mean native T1 values for classification between myocardial health vs. disease and HCM phenocopies (for normal: T1 AUC 0.549 vs. radiomics AUC 0.888, for LVH: T1 AUC 0.645 vs. radiomics AUC 0.790, for HCM T1 AUC 0.541 vs. radiomics AUC 0.638 and for amyloid T1 AUC 0.769 vs. radiomics AUC 0.840). Conclusions We have shown that specific imaging patterns in myocardial native T1 maps are linked to features of cardiac disease and we have provided for the first-time evidence that radiomic phenotyping can be used to enhance the diagnostic yield of native T1 mapping for myocardial disease detection and classification. FUNDunding Acknowledgement Type of funding sources: None.

Integrative Analyses of Genes Associated With Right Ventricular Cardiomyopathy Induced by Tricuspid Regurgitation

Tricuspid regurgitation (TR) induces right ventricular cardiomyopathy, a common heart disease, and eventually leads to severe heart failure and serious clinical complications. Accumulating evidence shows that long non-coding RNAs (lncRNAs) are involved in the pathological process of a variety of cardiovascular diseases. However, the regulatory mechanisms and functional roles of RNA interactions in TR-induced right ventricular cardiomyopathy are still unclear. Accordingly, we performed integrative analyses of genes associated with right ventricular cardiomyopathy induced by TR to study the roles of lncRNAs in the pathogenesis of this disease. In this study, we used high-throughput sequencing data of tissue samples from nine clinical cases of right ventricular myocardial cardiomyopathy induced by TR and nine controls with normal right ventricular myocardium from the Genotype-Tissue Expression database. We identified differentially expressed lncRNAs and constructed a protein-protein interaction and lncRNA-messenger RNA (mRNA) co-expression network. Furthermore, we determined hub lncRNA-mRNA modules related to right ventricular myocardial disease induced by TR and constructed a competitive endogenous RNA network for TR-induced right ventricular myocardial disease by integrating the interaction of lncRNA-miRNA-mRNA. In addition, we analyzed the immune infiltration using integrated data and the correlation of each immune-related gene with key genes of the integrated expression matrix. The present study identified 648 differentially expressed mRNAs, 201 differentially expressed miRNAs, and 163 differentially expressed lncRNAs. Protein-protein interaction network analysis confirmed that ADRA1A, AVPR1B, OPN4, IL-1B, IL-1A, CXCL4, ADCY2, CXCL12, GNB4, CCL20, CXCL8, and CXCL1 were hub genes. CTD-2314B22.3, hsa-miR-653-5p, and KIF17ceRNA; SRGAP3-AS2, hsa-miR-539-5p, and SHANK1; CERS6-AS1, hsa-miR-497-5p, and OPN4; INTS6-AS1, hsa-miR-4262, and NEURL1B; TTN-AS1, hsa-miR-376b-3p, and TRPM5; and DLX6-AS1, hsa-miR-346, and BIRC7 axes were obtained by constructing the ceRNA networks. Through the immune infiltration analysis, we found that the proportion of CD4 and CD8 T cells was about 20%, and the proportion of fibroblasts and endothelial cells was high. Our findings provide some insights into the mechanisms of RNA interaction in TR-induced right ventricular cardiomyopathy and suggest that lncRNAs are a potential therapeutic target for treating right ventricular myocardial disease induced by TR.

Native T1 mapping and extracellular volume fraction for differentiation of myocardial diseases from normal CMR controls in routine clinical practice

Background This study aimed to determine native T1 and extracellular volume fraction (ECV) in distinct types of myocardial disease, including amyloidosis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), myocarditis and coronary artery disease (CAD), compared to controls. Methods We retrospectively enrolled patients with distinct types of myocardial disease, CAD patients, and control group (no known heart disease and negative CMR study) who underwent 3.0 Tesla CMR with routine T1 mapping. The region of interest (ROI) was drawn in the myocardium of the mid left ventricular (LV) short axis slice and at the interventricular septum of mid LV slice. ECV was calculated by actual hematocrit (Hct) and synthetic Hct. T1 mapping and ECV was compared between myocardial disease and controls, and between CAD and controls. Diagnostic yield and cut-off values were assessed. Results A total of 1188 patients were enrolled. The average T1 values in the control group were 1304 ± 42 ms at septum, and 1294 ± 37 ms at mid LV slice. The average T1 values in patients with myocardial disease and CAD were significantly higher than in controls (1441 ± 72, 1349 ± 59, 1345 ± 59, 1355 ± 56, and 1328 ± 54 ms for septum of amyloidosis, DCM, HCM, myocarditis, and CAD). Native T1 of the mid LV level and ECV at septum and mid LV with actual and synthetic Hct of patients with myocardial disease or CAD were significantly higher than in controls. Conclusions Although native T1 and ECV of patients with cardiomyopathy and CAD were significantly higher than controls, the values overlapped. The greatest clinical utilization was found for the amyloidosis group.

Risk of Cardiac Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-Analysis

BackgroundWe performed a systematic review and meta-analysis to evaluate the risks of cardiac adverse events in solid tumor patients treated with monotherapy of immune checkpoint inhibitors (ICIs) or combined therapy of ICIs plus chemotherapy.MethodsEligible studies were selected through the following databases: PubMed, Embase and clinical trials (https://clinicaltrials.gov.) and included phase III/IV randomized controlled trials (RCTs) involving patients with the solid tumor treated with ICIs. The data was analyzed by using Review Manager (version5.3), Stata (version 15.1).ResultsAmong 2,551 studies, 25 clinical trials including 20,244 patients were qualified for the meta-analysis. Compared with PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy showed significant increase in grade 5 arrhythmology (OR 3.90, 95% CI: 1.08–14.06, p = 0.603). PD-1 inhibitor plus chemotherapy show significant increase in grades 1–5 myocardial disease (OR 5.09, 95% CI: 1.11–23.32, p = 1.000). Compared with chemotherapy, PD-1 inhibitor (nivolumab) or CTLA-4 inhibitor (ipilimumab), PD-1 inhibitor (nivolumab) plus CTLA-4 inhibitor (ipilimumab) combined therapy show significant increase in grades 1–5 arrhythmology (OR 2.49, 95% CI: 1.30–4.78, p = 0.289).ConclusionsOur meta-analysis demonstrated that PD-1 inhibitor plus CTLA-4 inhibitor can result in a higher risk of grade 5 arrhythmology in comparison with PD-1/CTLA-4 inhibitor alone, and a higher risk of grade 5 arrhythmology in comparison with chemotherapy. PD-1 inhibitor plus chemotherapy treatment could increase the risk of all-grade myocardial disease compared with chemotherapy. However, in most cases, there was no significant increase of risks of cardiovascular toxicity in PD-1/PD-L1 inhibitor monotherapy or PD-1/PD-L1 inhibitor plus chemotherapy compared with chemotherapy alone.

Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims

The contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD.