Left Ventricle Myocardium Research Articles

Abstract 11048: Serotonin Transporter Deficiency Leads to a Specific Fibrotic Pattern in Valvular and Myocardial Tissue

Introduction: Increased serotonin (5HT) levels can lead to heart valve disease. This mechanism is observed in patients with 5HT-secreting carcinoid tumors and after treatment with the diet drug Dexfenfluoramine, which acts as a 5HT receptor (HTR)-2B agonist and as an inhibitor of the 5HT transporter (SERT). SERT internalizes 5HT, limiting HTR signaling (Figure 1A). We showed that SERT reduction on human mitral valve (MV) contributes to the progression of MV regurgitation. We investigated the impact of SERT deficiency on cardiac substructures in a SERT-/- murine model. Methods: SERT-/- and wild type (WT) C57BL/6J mice (n≥8/group) were sacrificed at 16 weeks of age, after echocardiography (Fig. 1B). Cardiac substructures (left ventricle (LV) apex, MV leaflets, aortic valve (AV) leaflets and aortic-mitral (AM curtain) were isolated in three animals/group (Fig. 1E). Results: Ventricular dimensions were significantly larger in SERT-/- mice vs. WT at end-systole and end-diastole (Fig. 1C). Fractional shortening was significantly reduced in SERT-/- mice vs. WT. Pricosirius staining of collagen showed that SERT-/- mice had increased MV leaflet fibrosis, MV and AV sub-valvular fibrosis at leaflet attachment points (AM curtain, Fig. 1D), and epicardial fibrosis. PCR (Fig. 1F) showed significantly increased COL1A1 expression in the LV myocardium, MV, AV and AM curtain in SERT-/- mice vs. WT. Fibrosis marker alpha smooth muscle actin (αSMA) was significantly increased in the myocardium and AM curtain of SERT-/- mice, but not in the valve leaflets. HTR2B expression was significantly increased in the MV and AM curtain of SERT-/- mice. Conclusions: SERT-/- mice have decreased cardiac function, and cardiac fibrosis that is associated with HTR2B upregulation in the MV leaflets and valve leaflet attachment points. Our results support the hypothesis that decreased 5HT clearance by SERT downregulation may increase HTR2B signaling in the MV leading to remodeling and regurgitation.

Abstract 12273: Correlation Between Aortic Strain and Native T1 Value in Hypertrophic Cardiomyopathy

Introduction: Aortic stiffness is related to impairment of left ventricular (LV) function and LV remodeling. Myocardial ischemia and fibrosis in hypertrophic cardiomyopathy (HCM) cause ventricular arrhythmia and sudden cardiac death. Magnetic resonance imaging (MRI) can evaluate aortic stiffness and LV function noninvasively. Aortic strain shows the possibility for the assessment of the aortic status and T1 mapping allows the assessment of diffuse myocardial fibrosis. Hypothesis: We assessed the hypothesis that aortic strain is correlated with native T1 values in HCM patients. Methods: Thirty-six HCM patients (mean age : 64±2 years) and forty control subjects (mean age : 58±3 years) with no history of coronary artery disease were examined using a 3T MRI. Cross-sectional aortic areas of the descending aorta were measured and aortic strain was calculated as follows: aortic strain (%) = (maximum aorta area - minimum aorta area)/minimum aorta area х 100. Native T1 values were measured as an averaged T1 values in the septum of 3 short-axis slices of base-to-apex left ventricle myocardium. LV ejection fraction (LVEF), left atrium (LA) dimension and E/e’ were measured by echocardiography. Results: LVEF showed no significant differences between HCM patients and control subjects (66.2±1.1% vs. 64.5±1.0%, p=0.2488). LA dimension and E/e’ in HCM patients were significantly higher than control subjects (LA dimension: 38.3±1.1mm vs 34.9±0.85mm, p=0.0155, E/e’: 13.4±0.95 vs 9.2±0.42, p<0.0001). Native T1 values and aortic strain of the descending aorta in HCM patients were significantly lower than those in control subjects (native T1 values: 1254±8ms vs 1208±8ms, p<0.0001, aortic strain: 7.95±0.66% vs 12.92±1.27%, p=0.0012). Multiple linear regression analysis revealed that aortic strain was correlated with age (β=-0.370, p=0.0014) and native T1 values (β=-0.244, p=0.0448). Conclusions: In HCM patients, aortic strain of the descending aorta was significantly decreased compared to control subjects and correlated with native T1 values. Aortic strain may be a promising factor for myocardial fibrosis in HCM patients.

Abstract 10016: Potential of Stress T1 Mapping for Detection of Microvascular Dysfunction Without Contrast Agents

Introduction: Ischemia of hypertrophic myocardium due to microvascular dysfunction is related to worse prognosis in hypertrophic cardiomyopathy (HCM). Stress T1 mapping is a novel cardiac magnetic resonance (CMR) method without contrast agents to be able to assess myocardial blood flow. Hypothesis: We assessed the hypothesis that stress T1 mapping can detect microvascular dysfunction in HCM patients. Methods: Forty-one consecutive subjects without history of coronary artery disease (mean age : 60±3 years, 25 HCM patients, 10 concentric left ventricular hypertrophy (LVH) patients and 6 control subjects) underwent CMR at 3T including cine imaging, rest and adenosine stress T1 mapping, and late gadolinium enhancement (LGE). Native and stress T1 values were measured as an averaged T1 values in the septum of 3 short-axis slices of base-to-apex left ventricle myocardium and T1 reactivity (ΔT1) was calculated as follows: ΔT1 (%) = (T1stress - T1rest)/T1rest х 100. Thirteen HCM patients underwent phase-contrast imaging of coronary sinus flow during rest and adenosine stress to assess coronary flow reserve (CFR). Results: Native T1 values in HCM patients (1271±12ms) showed no significant differences compared with LVH (1225±13ms, p=0.0877) and control subjects (1243±8ms, p=0.534), but ΔT1 in HCM patients (4.00±0.36%) was significantly lower than that in control subjects (5.97±0.41%, p=0.0272), but not in LVH patients (4.95±0.29%, p=0.265, Figure 1). In HCM patients, native T1 values and ΔT1 showed no significant differences between LGE-positive (n=19) and LGE-negative (n=6) groups (native T1: 1274±15ms vs. 1260±20ms, p=0.632, ΔT1: 4.55±0.79% vs. 3.82±0.41%, p=0.394). A moderate positive correlation between ΔT1 and CFR was seen (β=0.697, p=0.0398). Conclusions: T1 reactivity (ΔT1) was reduced in HCM patients compared to control subjects. Stress T1 mapping is a promising CMR method for the assessment of microvascular dysfunction without contrast agents.

Abstract 12300: Impact of Catheter Contact Angle on Local Impedance Drop and Lesion Size Using the INTELLANAV STABLEPOINT Ablation Catheter: Insight From a Porcine Experimental Study

Background: Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on LI parameters were scarce. This study aimed to evaluate the influence of catheter contact angle on LI change and lesion size in a porcine experimental model. Methods: Lesions were created on porcine myocardial left ventricles by the LI and Contact force(CF)-sensing ablation catheter (INTELLANAV STABLEPOINT™). Radiofrequency ablation was performed with a power of 30 watts and a duration of 30 seconds. CF (0, 5, 10, 20, and 30g) and catheter contact angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise by catheter contact, LI drop by RF application, and lesion size (lesion width, surface width, and lesion depth) were evaluated. Results: The values of LI rise increased as CF increased. Regarding the difference of catheter angles, LI rise with 90° was lower than those with 30°. The LI drop also increased as CF increased in all contact angles. The LI drop with 90° was lower than those with 30° in CF 5, 10, 20, and 30 g, respectively. Maximum lesion width and surface width were smaller in 90° than those in 30°, whereas there were no differences in maximum lesion depth except for CF 5g. The approximate curves were well fitted with a quadratic equation in all angles on LI drop vs. maximum lesion width, and lesion depth. Conclusion: Under the same CF, the values of LI drop and lesion width in 90° were significantly lower than those in 30° despite lesion depths were not different among the three angles. LI drop correlates with lesion width and lesion depth at any angle, which may be a good predictor of lesion size.

Light-Weight Localization and Scale-Independent Multi-gate UNET Segmentation of Left and Right Ventricles in MRI Images.

Heart segmentation in cardiac magnetic resonance images is heavily used during the assessment of left ventricle global function. Automation of the segmentation is crucial to standardize the analysis. This study aims at developing a CNN-based framework to aid the clinical measurements of the left ventricle and right ventricle in cardiac magnetic resonance images. We propose a fully automated framework for localization and segmentation of the left ventricle and right ventricle in both short- and long-axis views from cardiac magnetic resonance images. The localization module utilizes a light-weight model that detects the region of interest and feeds it to the segmentation model. Also, we propose the Multi-Gate block as an extension to the UNet to boost the segmentation performance by aggregating multi-scale features. Comparison between our proposed method and the baseline UNet was performed to show the gain in the overall performance. The reliability of the model was assessed by testing the method against cardiac magnetic resonance images with different levels of noise and deformations. Heart localization accuracy was 0.59 and 1.75 pixels in both short- and long-axis views respectively. Left and right ventricle blood-pool segmentation Dice was (0.93, 0.90) in end-systole and (0.97, 0.95) in end-diastole. The left ventricle myocardium was segmented accurately with Dice of 0.91 and 0.90 in end-systole and end-diastole respectively. Left ventricle ejection fraction was found to be highly correlated with the gold standard with r = 0.987. Moreover, the proposed pipeline is fast, achieving 0.002 sec per image on average. Adding the Multi-Gate Dilated Inception Block has boosted the performance of UNet architecture and has shown generalization ability when tested on noisy and deformed cardiac magnetic resonance images. The proposed method has proven its wide applicability and reliability for heart detection when tested on different datasets.

Left ventricular strain-curve morphology to distinguish between constrictive pericarditis and restrictive cardiomyopathy.

AimsTo distinguish between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM) using cardiac magnetic resonance feature tracking (CMR‐FT) left ventricle (LV) diastolic time–strain curve patterns and myocardial strain.Methods and ResultsA total of 32 CP patients, 27 RCM patients, and 25 control subjects were examined by CMR‐FT and analysed for global strain, segmental strain, and LV time–strain curve patterns in the longitudinal, circumferential, and radial directions. Speckle tracking echocardiography (STE) strain imaging was performed in some cases. The peak global longitudinal strain (GLS) and global circumferential strain (GCS) of the RCM group were lower than those of the CP group. GLS [median (interquartile range) CP vs. RCM: −11.15 (−12.85, −9.35) vs. −6.5 (−8.75, −4.85), P < 0.001] and GCS (CP vs. RCM: −16.89 ± 5.11 vs. −13.37 ± 5.79, P < 0.001). In circumferential and radial directions, the strain ratios of the LV lateral/septal wall (LW/SW) of the CP group were significantly lower than those of the RCM group at the basal and mid segments. The CS ratio of LW/SW at the basal segment [CP vs. RCM: 0.95 (0.85, 1.25) vs. 1.43 (1.18, 1.89), P < 0.001] and mid segment [CP vs. RCM: 1.05 (0.92, 1.15) vs. 1.18 (1.06, 1.49), P = 0.026]. The RS ratio of LW/SW at the basal segment [CP vs. RCM: 0.97 (0.76, 1.37) vs. 1.55 (1.08, 2.31), P = 0.006] and mid segment [CP vs. RCM: 0.95 (0.70, 1.28) vs. 1.79 (1.32, 2.92), P < 0.001]. In the longitudinal and circumferential directions, the characteristic ‘plateau’ pattern of time–strain curves could be seen in the CP but not in the RCM during the diastole. The GCS ratio of 0–50%/50–75% diastolic period of the CP was higher than that of the RCM [CP vs. RCM: 17.01 (8.67, 23.75) vs. 5.38 (1.93, 11.24), P = 0.001], while the GCS ratio of 50–75%/75–100% diastolic period was lower than that of the RCM [CP vs. RCM: 0.36 (0.15, 1.67) vs. 1.12 (0.70, 5.58), P < 0.001]. The peak GLS (sensitivity, 85%; specificity, 78%) and the GCS ratio of 0–50%/50–75% diastolic period (sensitivity, 88%; specificity, 73%) had higher differential diagnosis value.ConclusionsThe CMR‐FT could distinctly differentiate CP from RCM based on LV myocardial strain and LV time–strain curve patterns. The characteristic ‘plateau’ pattern of the time–strain curve is specific for CP and not RCM and this curve can also be duplicated by STE.

MRI Radiomic Features of Radiation Induced Cardiac Toxicity and the Effects of c-GAS/STING Signaling

<h3>Purpose/Objective(s)</h3> The mechanism of late cardiac toxicity after radiation treatment is not well understood, and the ability to evaluate and predict this toxicity would be of great clinical value. We sought to identify radiomic features of cardiac MRI that were associated with cardiac toxicity after radiation treatment in wild type mice and a c-GAS/STING knockout model that has previously been shown to be resistant to radiation induced cardiac toxicity. <h3>Materials/Methods</h3> All protocols were approved by our institution's animal care and use committee. Cardiac irradiation was delivered to adult wild type C57BL/6 and commercially available <b>CGAS^−/-</b> strains using a precision small animal irradiator. At 28 and 84 days after treatment, cardiac MRI was acquired with retrospective gating. The heart was segmented using open-source software. Gabor edge features, which are directionally sensitive edge detectors, were extracted for each segmented voxel using an angle of 90° and bandwidth of √2, which roughly corresponds to the voxel spacing in the MR images. The Gabor edges strengths were summarized within heart and left ventricle using first order (mean, standard deviation, skewness, and kurtosis) features. Two-tailed T tests were used to compare features between radiation treatment versus sham treatment along with the 95% confidence intervals (CI) of the difference between the group means. <h3>Results</h3> A total of 42 MRI scans were analyzed and features in the left ventricle myocardium were found to be associated with irradiation. There were significant differences in Gabor skewness (<i>P</i> = 0.037, CI 0.015 to 0.46) and Gabor kurtosis (<i>P</i> = 0.034, CI 0.13 to 3.0) in irradiated compared to sham treated wild type mice. There was no significant difference in Gabor mean edges (<i>P</i> = 0.060, CI -4.1 to 0.091) or Gabor SD (<i>P</i> = 0.25, CI -4.3 to 1.2) after irradiation. In the radioresistant <i>CGAS^−/−</i>strain, only Gabor skewness showed a significant difference in irradiated versus sham treated mice (<i>P</i> = 0.007, CI 0.14 to 0.72). <h3>Conclusion</h3> We identified Cardiac MRI features that were associated with radiation induced damage. These may represent structural and/or functional changes in the left ventricle as a result of radiation induced inflammation and fibrosis. In this preliminary study, it is notable that only one of the two features associated with irradiation in wild type mice was significant in the radioresistant <i>CGAS^−/−</i>strain. Further studies are planned to determine how these imaging features correlate with inflammation, fibrosis, and functional impairment of the heart after radiation treatment. In addition to better understanding the physiology of radiation induced cardiac toxicity, MRI radiomic analysis after cardiac exposure to radiation could be explored for clinical application.

Lymphocytes telomere length and left ventricle heart functional state in emergency workers of Chernobyl accident who survived myocardial infarction

Abstract Background The reduction of lymphocytes telomeres length (TL) reflects aging and progression of atherosclerosis. TL shortening depends on multiple risk factors including ionizing radiation and chronic stress that were typical conditions for emergency workers (EW) of Chernobyl accident. Purpose To analyse the association between lymphocytes TL and myocardial functional state in EW survived myocardial infarction (MI). Methods We examined 48 EW aged 67.1±7.7 years. Ultrasound heart examination was performed using the Diagnostic Ultrasound System DS-N3 (Mindray). Determination of relative TL was performed using flow-FISH with Telomere PNA Kit/FITC (Dako Cytomation, Denmark) by laser flow cytometry (FACSCalibur, BD, USA). Results At the first stage of descriptive analysis we found that TL negatively correlated only with left ventricle (LV) end diastolic volume (EDV) and EDV normalised by body surface area (BSA) but not with other clinical and echocardiography indices. At the second stage the hierarchical cluster analysis was used to identify relatively homogeneous patient's groups according to given LT and EDV indexed by BSA (iEDV). The first one is characterized by significantly lesser TL (10.6±1.7 units) and higher iEDV (85.8±16.2 ml/m2) comparing with second cluster (14.7±1.6 units and 68.0±10.4 ml/m2). The patients belonged to 1st cluster (n=21) were differed from 2nd cluster persons (n=27) by greater magnitude of EDV (172.6±32.5 vs 140.2±27 ml, p=0.000), end systolic volume (85.4±33.0 vs 59.7±20 ml, p=0.002), end systolic volume normalized by BSA (42.5±16.1 vs 28.9±8.2 ml/m2, p=0.000), LV myocardium mass / BSA (145.2±27.1 vs 130.4±21.3 g/m2, p=0.040) and less value of ejection fraction (52.0±10.6 vs 57.8±8.4 per cent, p=0.038). Heart failure (HF) of NYHA class I was diagnosed in 47.4% cluster 1 patients and 66.7% cluster 2 ones (p&amp;gt;0.05) but HF NYHA class II on the contrary in 52.6% cluster 1 and 33.3% cluster 2 patients (p&amp;gt;0.05). Cluster 1 patients demonstrated normal geometry or concentric remodelling LV with frequency 9.5% vs 29.6% in cluster 2 ones (p&amp;gt;0.05). Concentric LV hypertrophy revealed in 23.8% and 44.4% of cluster 1 and 2 patients (p&amp;gt;0.05) but eccentric hypertrophy in 66.7% and 25.9% correspondingly (p&amp;lt;0.01). Conclusion Studied EW represent a heterogeneous group in terms of scattering the extreme values of TL and LV functional indices. The use of hierarchical cluster analysis made it possible to avoid the empirical way of dividing EW into more homogeneous groups and, with mathematical precision, to determine two clusters of patients. The first cluster, in comparison with the second, was characterized by a significantly shorter TL, large LV volumes and its mass, a decrease of ejection fraction, the presence of eccentric LV hypertrophy and more severe heart failure. The TL in EW who survived myocardial infarction is associated with a more severe clinical course of coronary heart disease and a decrease in LV myocardial function. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Academy of Medical Sciences of Ukraine Scatter diagram of TL, iEDV and clusters

Correlation arterial stiffness and central blood pressure with obstructive sleep apnea in patients with resistant arterial hypertension

Abstract The aim assess correlation the arterial stiffness in patients with resistant arterial hypertension (AH) and obstructive sleep apnea (OSA) Design 185 patients with AH were enrolled into the study. They were divided on 2 groups: OSA group – 148 patients were found to have OSA, indicated by at mean AHI of 38.1±2.5 h–1, and control group – 37 patients without OSA, mean AHI 3.02±0.25 h–1 (P&amp;lt;0.001). Patients of both groups were comparable on age, growth, total cholesterol level and office systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results Patients with RAH and OSA (mean apnea-hypopnea index (AHI) 36.5±2.7 event/h) in comparison with patients with RAH without OSA (mean AHI 3.4±0.2 event/h) had significantly higher body mass index (34.2±0.7 vs 31.6±0.7 kg/m2, P&amp;lt;0.05), uric acid level (6.7±0.1 vs 5.6±0.4 mg/dl, P&amp;lt;0,05), higher carotid-femoral pulse wave velocity (PWVcf) (12.1±0.5 vs 10.2 m/s, P&amp;lt;0,05) and central systolic blood pressure (CSBP) (143.8±2.7 vs 136.2±3.4 mm Hg, P&amp;lt;0,05). Patients of both groups had comparable office blood pressure (SBP 145.6±1.67 vs 138.4±3.66 mm Hg, P=0.057 and DBP 93.6+±1.18 vs 89.1±2.11 mm Hg, P=0.073), but significantly higher 24-h systolic and diastolic blood pressure. We suggest that in the study some patients with OSA had masked arterial hypertension. Daytime sleepiness in OSA patients was associated with structural remodeling of the left ventricle myocardium and more expressed arterial stiffness: ESS score was independently correlated with snoring duration (β=−0.008; P=0.021), interventricular septum thickness (β=0.023; P=0.026), LVMI (β=−0.037; P=0.039) and indexes of central pulse wave: ejection duration (ED) (β=−0.020; P&amp;lt;0.001) and subendocardial viability ratio (SEVR) (β=−0.224; P=0.012). Nocturnal hypoxemia in OSA patients was associated with increased aortic stiffness and higher central blood pressure: desaturation index was independently correlated with Aix (β=4.167; P=0.009), Aix75 (β=−3.929; P=0.006) and central DBP (β=0.151; P=0.004). Conclusion In patients with RH and OSA nocturnal hypoxemia correlation with increased aortic stiffness and higher central blood pressure. Funding Acknowledgement Type of funding sources: None.

Catheter contact angle influences local impedance drop during radiofrequency catheter ablation: insight from a porcine experimental study

Abstract Background Local impedance (LI) at a distal tip of the ablation catheter can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). LI decreases by RFCA, and a degree of LI drop is correlated with lesion size. However, data on the effects of catheter contact angle on lesion size and LI drop were scarce. This study aimed to evaluate the influence of catheter contact angle on lesion size and LI drop in a porcine experimental study. Methods Lesions were created on porcine myocardial left ventricles by the LI-sensing ablation catheter (IntellaNav MiFi OI®). Contact force (CF) was measured using pressure to current transducer (load cell). Radiofrequency ablation was performed with a power of 30 Watt and a duration of 30 seconds. CF (0g, 5g, 10g, 20g, and 30g) and catheter angle (30°, 45°, and 90°) were changed in each set (total 120 lesions, n=8 each). LI rise, LI drop by RF application, and lesion size (maximum lesion width, maximum surface width, and maximum lesion depth) were evaluated. Results There was no angular dependence in LI rise in all CF. The values of LI rise increased as CF increased. The LI drop also increased as CF increased in all contact angles. Regarding the difference of catheter angles, LI drop with 90° was lower than those with 30° and 45°in CF 10g, 20g, and 30g, respectively. Maximum lesion width and surface width were larger in 30° and 45° than those in 90°, whereas there were no differences in maximum lesion depth. Conclusion LI drop in 90° were significantly lower than those in 45° and 30°. Although lesion depths were not different among the three angles, the absolute values of LI drop were different. Caution should be exercised to comprehend the LI drop with catheter angles. Funding Acknowledgement Type of funding sources: None.

Development and preclinical evaluation of novel fluorinated ammonium salts for PET myocardial perfusion imaging

We previously presented the radiolabeled ammonium salt [11C]-dimethyl diphenylammonium trifluoromethanesulfonate ([11C]DMDPA) as a potential novel PET-MPI agent. The current study aimed to increase the clinical applicability of PET-MPI by designing and synthesizing fluorinated ammonium salt derivatives. Four fluorinated DMDPA derivatives and two quinolinium salt analogs were radiolabeled. The dynamic distribution in vivo, following injection of each derivative into male SD rats, was evaluated using small-animal dedicated PET/CT. Organ uptake after injection of [18F]fluoroethylquinolinium acetate ([18F]FEtQ) was examined ex vivo. Four fluorinated DMDPA derivatives were synthesized, two were labeled with fluorine-18: [18F]fluoroethyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FEMDPA) and [18F]fluorobuthyl-methyldiphenylammonium trifluoromethanesulfonate ([18F]FBMDPA). The other two were labeled using carbon-11: [11C]methyl-(3-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]3-F-DMDPA) and [11C]methyl-(4-fluorophenyl)-methylphenylammonium trifluoromethanesulfonate ([11C]4-F-DMDPA). All four DMDPA derivatives exhibited significantly lower heart/liver radioactivity uptake ratios (0.6, 0.4, 0.7 and 0.6, respectively) compared to that of [11C]DMDPA (1.2). Conversely, the two radiolabeled quinolinium salt derivatives, [11C]methylquinolinium iodide ([11C]MeQ) and [18F]FEtQ demonstrated improved heart/liver ratios (2.0 and 1.3, respectively) with clear visualization of the left ventricle myocardium. Renal clearance was the major route of elimination. Among the fluorinated quaternary ammonium salts tested, [18F]FEtQ yielded the best images. Further studies are in progress to elucidate the underlying mechanism of its cardiac uptake.

New Imaging Signatures of Cardiac Alterations in Ischaemic Heart Disease and Cerebrovascular Disease Using CMR Radiomics.

Background: Ischaemic heart disease (IHD) and cerebrovascular disease are two closely inter-related clinical entities. Cardiovascular magnetic resonance (CMR) radiomics may capture subtle cardiac changes associated with these two diseases providing new insights into the brain-heart interactions.Objective: To define the CMR radiomics signatures for IHD and cerebrovascular disease and study their incremental value for disease discrimination over conventional CMR indices.Methods: We analysed CMR images of UK Biobank's subjects with pre-existing IHD, ischaemic cerebrovascular disease, myocardial infarction (MI), and ischaemic stroke (IS) (n = 779, 267, 525, and 107, respectively). Each disease group was compared with an equal number of healthy controls. We extracted 446 shape, first-order, and texture radiomics features from three regions of interest (right ventricle, left ventricle, and left ventricular myocardium) in end-diastole and end-systole defined from segmentation of short-axis cine images. Systematic feature selection combined with machine learning (ML) algorithms (support vector machine and random forest) and 10-fold cross-validation tests were used to build the radiomics signature for each condition. We compared the discriminatory power achieved by the radiomics signature with conventional indices for each disease group, using the area under the curve (AUC), receiver operating characteristic (ROC) analysis, and paired t-test for statistical significance. A third model combining both radiomics and conventional indices was also evaluated.Results: In all the study groups, radiomics signatures provided a significantly better disease discrimination than conventional indices, as suggested by AUC (IHD:0.82 vs. 0.75; cerebrovascular disease: 0.79 vs. 0.77; MI: 0.87 vs. 0.79, and IS: 0.81 vs. 0.72). Similar results were observed with the combined models. In IHD and MI, LV shape radiomics were dominant. However, in IS and cerebrovascular disease, the combination of shape and intensity-based features improved the disease discrimination. A notable overlap of the radiomics signatures of IHD and cerebrovascular disease was also found.Conclusions: This study demonstrates the potential value of CMR radiomics over conventional indices in detecting subtle cardiac changes associated with chronic ischaemic processes involving the brain and heart, even in the presence of more heterogeneous clinical pictures. Radiomics analysis might also improve our understanding of the complex mechanisms behind the brain-heart interactions during ischaemia.

Morphology of Mitral Annular Disjunction in Mitral Valve Prolapse

Mitral annular disjunction (MAD) is an abnormal insertion of the hinge line of the posterior mitral leaflet on the atrial wall: the mitral annulus shows a separation or "disjunction" between the leaflet-atrial wall junction and the crest of the left ventricle myocardium. This anomaly is often observed in patients with myxomatous mitral valve prolapse. The anatomical substrate of MAD remains unclear for the following reasons: (1) most studies are focused on the association between MAD and arrhythmias, rather than on pathomorphological aspects of MAD; and (2) the complex anatomic architecture of the posterior mitral annulus is often simply described as the posterior segment of a fibrous ring. The aims of this paper are to review the pertinent normal anatomy of the mitral valve and to propose new hypotheses on the morphological nature of MAD.

Short-time total-body dynamic PET imaging performance in quantifying the kinetic metrics of 18F-FDG in healthy volunteers.

To investigate the performance of short-time dynamic imaging in quantifying kinetic metrics of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG). Dynamic total-body positron emission tomography (PET) imaging was performed in 11 healthy volunteers for 75min. The data were divided into 30-, 45- and 75-min groups. Nonlinear regression (NLR) generated constant rates (k1 to k3) and NLR-based Ki in various organs. The Patlak method calculated parametric Ki images to generate Patlak-based Ki values. Paired samples t-test or the Wilcoxon signed-rank test compared the kinetic metrics between the groups, depending on data normality. Deming regression and Bland-Altman analysis assessed the correlation and agreement between NLR- and Patlak-based Ki. A two-sided P < 0.05 was considered statistically significant. The 45- and 75-min groups were similar in NLR-based kinetic metrics. The relative difference ranges were as follows: k1, from 3.4% (P = 0.627) in the spleen to 57.9% (P = 0.130) in the white matter; k2, from 6.0% (P = 0.904) in the spleen to 60.7% (P = 0.235) in the left ventricle (LV) myocardium; k3, from 45.6% (P = 0.302) in the LV myocardium to 96.3% (P = 0.478) in the liver; Ki, from 14.0% (P = 0.488) in the liver to 77.8% (P = 0.067) in the kidney. Patlak-based Ki values were also similar between these groups in all organs, except the grey matter (9.6%, P = 0.029) and cerebellum (14.4%, P = 0.002). However, significant differences in kinetic metrics were found between the 30-min and 75-min groups in most organs both in NLR- and Patlak-based analyses. The NLR- and Patlak-based Ki values significantly correlated, with no bias in any of the organs. Dynamic imaging using a high-sensitivity total-body PET scanner for a shorter time of 45min could achieve relevant kinetic metrics of 18F-FDG as done by long-time imaging.

Postsystolic thickening is a potential new clinical sign of injured myocardium in marfan syndrome

The mechanisms leading to cardiac remodeling in Marfan syndrome (MFS) are a matter of debate since it could be either due to structural dysfunction of the myocardial extracellular matrix or to increased afterload caused by the dilated aorta. We aim to characterize the presence of abnormal myocardial function in MFS and to investigate its potential association with increased afterload. Aorta, left ventricle (LV) and the postsystolic thickening (PST) were analyzed in echocardiography in Fbn1C1039G/+ mice and in patients with MFS in comparison with wild type (WT) mice and healthy humans. PST was more frequent in MFS than in WT mice (p < 0.05). MFS mice with PST showed larger aorta than those without PST. Patients with MFS showed larger aorta, poorer LV function and a higher prevalence of PST (56%) than did the healthy controls (23%); p = 0.003. Blood pressure was similar. The higher prevalence of PST in an experimental murine model and in MFS patients, regardless of systemic arterial pressure, suggests an increased afterload on the LV myocardium. This finding supports the use of PST as an indicator of myocardial damage and encourage searching for novel early preventive therapy.

CineCT imaging platform for in-vivo and ex-vivo measurement of myocardial biomechanics post myocardial infarction and following intramyocardial delivery of theranostic hydrogel

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH) Purpose Myocardial infarction (MI) induces acute regional changes in myocardial strain and stiffness in the infarct and the remote areas of the left ventricle (LV), which lead to adverse changes in LV geometry and function. We hypothesize that cineCT imaging could evaluate these biomechanical changes along with the effects of intramyocardial delivery of theranostic hydrogels. Introduction We present an experimental platform to assess changes in the deformation of the LV myocardium using contrast cineCT (CCT) imaging of the beating porcine heart (active deformation) before and after acute MI and intramyocardial delivery of an imageable theranostic hydrogel. We then assess the acute effects of hydrogel delivery early post-MI on biomechanics (passive deformation) using an ex vivo perfused heart preparation. Methods Contrast cineCT imaging was performed using 64-slice CT on 5 Yorkshire pigs without MI (n = 3) or with MI (n = 2). MI pigs had serial imaging performed before and 1 hour after acute surgical coronary occlusion to induce anterolateral MI. One MI pig was also imaged 1 hour after intramyocardial injection of a novel imageable theranostic iodinated hydrogel within the MI region. Post euthanasia, excised hearts were flushed with chilled UW cardioplegic solution and mounted on a custom inflation apparatus for cineCT imaging during LV inflation by external pump. LV pressure was cycled between 10 and 60 mmHg at 35 bpm. Dilute iohexol was injected into aortic root and UW perfusate (15 ml, 1 ml/sec). CineCT image series were reconstructed, contrast enhanced, resampled to the LV long axis (Z), and exported as a series of 10 CT volumes covering 0-90% of the cardiac/inflation cycle. Volumes were registered incrementally using nonlinear image registration (BioImageSuite) and the calculated displacement at each time point was exported at a resolution of 1 mm. A custom Matlab program was used to fit the displacement field to local trilinear polynomials and then calculate the displacement gradients and 3D Lagrangian strains. To estimate the accuracy of this approach, cardiac volumes were also numerically deformed using a 10 pixel translation and 5% triaxial stretch. Results We successfully acquired serial in-vivo and ex-vivo 3D CineCT images for assessment of the active and passive LV myocardial deformation and tracked deformation through the full cardiac/inflation cycle (Figure 2). Numerical deformation tests showed average tracking errors of &amp;lt; 0.2 mm (1/4 pixel) in the X,Y,Z directions of the volume. These resulted in Lagrangian strain errors of &amp;lt; 0.47% for the in-plane strains EXX and EYY (radial and circumferential plane) and &amp;lt; 0.5% for EZZ (long axis). Conclusions We have developed a novel CineCT imaging platform that allows for high resolution in-vivo and ex-vivo measurement of myocardial biomechanics post-MI and following intramyocardial delivery of imageable theranostic hydrogels, which may improve early active and passive biomechanics.

Analysis of risk factors for prognostically unfavorable MI features as determined by cardiac MRI with contrast enhancement

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): A.L. Myasnikov Institute of Clinical Cardiology, Russian Cardiology Research and Production Complex, Ministry of Health of Russia, Moscow, Russia Background A growing number of publications describe the role of cardiac MRI in STEMI prognostic assessment. Infarct size, microvascular obstruction (MVO) and myocardial heterogeneity are among the most prognostically significant MRI parameters in MI. Primary PCI (pPCI) is the current standard of STEMI treatment. The impact of clinical factors on the development of MVO, myocardial heterogeneity and infarct size remains insufficiently investigated. Purpose To investigate the impact of certain medical history aspects, clinical and laboratory parameters on the most prognostically significant MRI measures of acute MI (MVO, infarct size, myocardial heterogeneity). Methods The study included 52 patients with first STEMI within &amp;lt;48 hours of onset. All patients urgently underwent coronary angiography with pPCI of infarct-related arteries (IRA). On Days 3-7 contrast-enhanced cardiac MRI was done. Tissue analysis of scans was performed using CVI 42 software evaluating infarct size, MVO, myocardial heterogeneity, and left ventricle (LV) ejection fraction (EF). Results 85% patients were men, with mean age of 59.09 ± 7.7 years. All patients underwent pPCI for reperfusion. The median time from symptom onset to pPCI was 3 hours. We analyzed the influence clinical and laboratory factors impacting cardiovascular prognosis on the development of MVO, infarct size, and myocardial heterogeneity. Odds ratios demonstrated no significant relationship between arterial hypertension (OR 2.10, CI 0.57-7.79 р=0,2), smoking (OR 1.01 CI 0.32-3.20, р=0.9), obesity defined as BMI &amp;gt;30 kg/m2) (OR 0.83 CI 0,50-1.39, р=0.16) and MVO development. However, diabetes mellitus had significant effect on MVO development (OR 4.34 CI 1.34-14.03, р=0.01). With regards to laboratory parameters, relationship between hs-Troponin elevation &amp;gt; &amp;gt;8400 pg/mL and MVO occurrence (OR 7.00, CI 0.79 – 61.74, р=0.04). Correlation analysis demonstrated association between myocardial heterogeneity and BNP (r 0.612, р&amp;lt;0.0001), as well as advanced age (r 0,544, р&amp;lt;0,0001). Inverse correlation was found between myocardial heterogeneity and LV EF (r -0.461, р=0.0006). We also analyzed the factors associated with infarct size and found correlation between this parameter and BNP levels (r 0,553, p = 0,0003), as well as MVO magnitude (r 0,383, p = 0,005). Inverse correlation was found between infarct size and history of hypertension (r -0.380, p = 0.0054) Conclusions Type 2 diabetes mellitus, was found to be an independent predictor of microvascular obstruction on MRI. Elevation of hs-Troponin &amp;gt;8400 pg/mL was found to be associated with MVO development. Correlation data analysis demonstrated that high BNP may indicate higher infarct size and myocardial heterogeneity values (r 0.612, р&amp;lt;0.0001).

Left ventricle motion estimation for cine MR images using sparse representation with shape constraint.

To propose a left ventricle (LV) motion estimation method based on sparse representation, in order to handle the spatial-varying intensity distortions caused by tissue deformation. For each myocardial landmark, an adaptive dictionary was generated by learning transformations from a training dataset. Then the landmark was tracked using sparse representation. Next, a point distribution model was applied to the overall tracking results. Finally, the dense displacement field of the LV myocardium was estimated based on the correspondence between each landmark. Using the dense displacement field estimated, the circumferential strain was calculated to assess the myocardial function. The performance of the proposed method was quantified by the average perpendicular distance (APD), the Dice metric, and the mean symmetric contour distance (SCD). Comparing to the state-of-the-art techniques, the smallest value of APD and SCD, and the highest value of Dice can be obtained using the proposed method, for three public cardiac datasets. Moreover, the mean value of strain difference between the proposed method and the commercial software Medis Suite MR was -0.01, while the intraclass correlation coefficient between these two methods was 0.91. The proposed method could estimate the dense displacement field of the LV accurately, which outperforms other state-of-the-art techniques. The circumferential strain derived from the proposed method was in excellent agreement with that derived from the Medis Suite MR software, while segmental strain abnormalities were detected for most of the subjects with heart diseases, which indicates the potential of the proposed method for clinical usage.

Unveiling Complexity and Multipotentiality of Early Heart Fields.

[Figure: see text].

Incidental Detection of Ischemic Myocardium on 68Ga-FAPI PET/CT.

Recent studies using Ga-68-labeled fibroblast activation protein inhibitors (FAPI) PET have shown strong association between focal uptake of FAPI in myocardium and presence of coronary artery disease. We present an interesting case of a 76-year-old female with breast cancer with incidental uptake on FAPI PET in apex and septal wall of left ventricle myocardium correlating with findings of ischemia on dobutamine stress myocardial perfusion imaging and anatomical stenosis on coronary angiography.