Left Ventricular Myocardium Research Articles

Abstract 9874: Correlation of Left Ventricular Strain Derived From Rb-82 ECG-Gated PET Myocardial Perfusion Imaging vs 2D Echocardiography

Introduction: Global longitudinal strain (GLS) by two-dimensional (2D) transthoracic echocardiography (TTE) is a robust index for identifying early left ventricular (LV) myocardial dysfunction. Positron emission tomography (PET) myocardial perfusion imaging (MPI) is widely used in the assessment of ischemic heart disease (IHD) but has not been used for strain analysis. Hypothesis: Longitudinal, radial, and circumferential myocardial strain measures at rest and at pharmacologic stress by Rb-82 ECG-gated PET MPI are correlated to those measured by resting 2D TTE. Methods: We developed a novel PET MPI method to track the LV myocardium throughout the cardiac cycle processed in the Emory Cardiac Toolbox, to measure LV strain from longitudinal, radial, and circumferential direction at regadenoson-stress and at rest. We retrospectively identified 80 patients who underwent Rb-82 PET MPI and also had TTE with strain analysis within 3 months. The agreement between LV strain and LVEF derived from PET MPI and resting TTE was assessed with Bland-Altman analysis, Pearson’s correlation, and the concordance correlation coefficient (CCC). Results: PET MPI derived measurements of longitudinal (Figure 1A-1B: Bland-Altman analysis; 1C-1D: Pearson’s correlations), circumferential (Figure 1E-1F: Pearson’s correlations) and radial (Figure 1G-1H: Pearson’s correlations) strain measures at rest and stress were strongly correlated to resting TTE derived GLS (p<.001). LVEF showed strong correlations at stress (0.83, p<.001) and rest (0.80, p<.001). Inter-observer agreements of PET MPI strain measures showed high correlation between 2 independent observers for all 3 directions (p<.001). Conclusions: LV strain measures by PET MPI using a novel automated technique correlated strongly with GLS by TTE. PET MPI measures are highly reproducible. Strain by PET MPI should be investigated further to establish its value in routine clinical practice.

Abstract 13312: Can the Extent of Late Gadolinium Enhancement on Cardiac Magnetic Resonance Be Predicted by the 12-Lead Electrocardiogram?

Background: In hypertrophic cardiomyopathy (HCM), late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) is an in vivo marker of replacement fibrosis with a continuous relationship between amount of LGE and both risk for sudden death and development of endstage disease. Cost and accessibility can limit routine utilization of CMR. In contrast, electrocardiogram (ECG) is an inexpensive readily available test and identifies patients with myocardial scarring in ischemic heart disease. Its ability to identify presence and extent of LGE in HCM is unknown. Methods: 1983 consecutive HCM patients were included; 62% male, average wall thickness 18 ± 3mm, and 36% with resting LV outflow tract obstruction ≥ 30mmHg. ECGs were analyzed for LV hypertrophy, T wave abnormalities, ST-segment depression or elevations, abnormal Q waves, conduction disease, atrial enlargement and QTc prolongation. Extent of LGE was quantified and expressed as a proportion of total LV myocardium. Results: 822 (41%) had no LGE, while 1161 (59%) had LGE, including 687 (35%) with <5%, 299 (15%) with 5-9%, 92 (5%) with 10-14%, and 83 (4%) with ≥ 15%. Compared to no LGE, Patients with LGE were more likely to have pathologic T wave inversions (55% vs. 36%, p<0.01), positive T waves in aVR (34% vs. 20%, p<0.01), and ST-depressions (29% vs. 21%, p<0.01), with no difference in LV hypertrophy, bundle branch block, pathologic Q waves, first degree AV block, QTc prolongation ≥ 480ms, or ST-elevations (p>0.05). Notably, as extent of LGE increased there was a corresponding progressive increase in the prevalence of both positive T waves in aVR (20% in no LGE to 42% in ≥ 15% LGE, p<0.01) and pathologic T wave inversions (36% in no LGE to 61% in ≥ 15% LGE, p<0.01) but with no incremental differences in ST depressions (p>0.05). In contrast, 43% of patients with LGE did not have either positive T waves in aVR or pathologic T wave inversions, including 34% with ≥ 15% LGE. Conclusion: Most ECG findings including pathologic Q waves have no relation to presence or extent of LGE. While positive T waves in aVR and pathologic T wave inversions are associated with LGE, they have limited sensitivity. These finding support that routinely evaluated ECG abnormalities do not predict presence or extent of scarring in HCM.

Abstract 11065: Stress T1 Mapping Demonstrates Coronary Microcirculatory Dysfunction in Both Nonhypertrophied and Hypertrophied Myocardium of Hypertrophic Cardiomyopathy

Introduction: Coronary microcirculatory dysfunction (CMD) in hypertrophic cardiomyopathy (HCM) is associated with clinical deterioration. We have shown that stress T1 mapping could detect CMD of hypertrophied interventricular septum (IVS). However, CMD in nonhypertrophied left ventricular free wall (LVFW) has not been fully elucidated. Hypothesis: We assessed the hypothesis that regional CMD in LVFW of HCM can be detected using stress T1 mapping. Methods: We evaluated 36 consecutive subjects (26 HCM patients and 10 control subjects, mean age: 61±3 years) who underwent CMR at 3T. Cine imaging, rest and adenosine stress T1 mapping, late gadolinium enhancement (LGE) and phase-contrast imaging of coronary sinus flow were performed. The T1 values at rest and after adenosine stress were measured as an averaged T values of 3 short-axis slices of LV myocardium and T1 reactivity (ΔT1) was calculated as follows: ΔT1 (%) = (T1stress - T1rest)/T1rest х 100. Coronary flow reserve (CFR) was measured coronary sinus blood flow during adenosine stress divided by that at rest. Results: The T1 values at rest were significantly higher in HCM than control (1245±9ms vs. 1196±11ms, p=0.0027), and the T1 values after adenosine stress significantly increased in both groups (HCM: 1285±10ms, p=0.0018 vs. rest, control: 1244±9ms, p=0.0128 vs. rest, Figure 1). Both IVS and LVFW demonstrated significantly lower ΔT1 in HCM than control (IVS: 3.95±0.35% vs. 5.68±0.41%, p=0.0163, LVFW: 4.80±0.39% vs. 6.75±0.65%, p=0.0163, Figure 2). CFR in HCM significantly decreased than that in control (2.48±0.40 % vs. 5.97±1.31 %, p=0.0051). Multiple regression analysis revealed that ΔT1 of both IVS and LVFW was correlated with CFR (β=0.527, p=0.0026, β=0.445, p=0.0325). Conclusions: T1 reactivity significantly decreased in both nonhypertrophied and hypertrophied myocardium of HCM compared to control. Stress T1 mapping have the advantage of being able to estimate regional CMD in addition to global CMD.

Abstract 14605: Deleterious Effects of Type 2 Diabetes on the Myocardium of Patients With Aortic Stenosis

Introduction: Type 2 diabetes (T2D) may induce myocardial alterations and is associated with an increased risk of heart failure. T2D is often associated to LV pressure overload, as encountered in aortic stenosis (AS). Hypothesis: We hypothesized that T2D has deleterious effects on LV remodelling and function in patients with severe AS and we explored some underlying mechanisms. Methods: Non diabetic and T2D patients with severe AS, referred for aortic valve replacement, were included. Patients with atrial fibrillation, LV ejection fraction (LVEF) <50%, significant coronaropathy or other valvulopathy were excluded. Before surgery, patients underwent blood tests and a complete echocardiography. During surgery, a LV myocardium biopsy was obtained for histological analysis. Results: We included 82 patients, including 33 T2D. Hypertension and dyslipidaemia were more frequent in T2D patients. Severity of the AS was similar between the two groups. Echocardiography revealed that T2D was associated with a more pronounced LV hypertrophy (mass LV 3D/hight 2.7 ; p=0.03) and systolic dysfunction (Global Longitudinal Strain (GLS) 15±3 vs 18±2 %; p<0.01). In addition, LV ventricular filling pressure was more often increased in T2D patients (50% of T2D vs 26% of non-diabetics; p=0.03). Circulating levels of leptin and endothelin 1 were significantly higher in T2D. Interestingly leptin level correlates with diastolic function (left atrial strain; r=-0.25, p=0.01) and Endothelin 1 with LV mass (r=0.27, p<0.001) and GLS. Histologic analysis revealed an enhanced cardiomyocyte hypertrophy in T2D biopsies but similar degrees of fibrosis. Proximity ligation assay displayed a significant decreased proximity between the IP3-receptor and the mitochondrial porin VDAC in T2D hearts suggesting a reduced reticulum-mitochondria Ca 2+ transfer. Conclusions: T2D is associated with an increased LV remodelling and dysfunction in patients with a severe AS as well as an increased circulating level of leptin and endothelin-1. Our results also suggest a potential role of reticulum-mitochondria Ca 2+ uncoupling.

Abstract 13272: Diabetic Cardiomyopathy as a Coronary Artery Disease Mimic: A Case Report

A 49-year-old female presented with complaints of angina and dyspnea on exertion for last 4 months, which caused significant limitation of ordinary physical activity. She had poorly controlled diabetes mellitus type 2 with HbA1C of 10.3%. EKG showed complete LBBB with QRS duration of 180 milliseconds. Echocardiogram was consistent with dilated left ventricle and global hypokinesia of left ventricle with ejection fraction of 25-30%. There was marked reduction in GLS (GLPS average of -7.0%). She underwent coronary angiogram which revealed normal epicardial coronary arteries. 99m Tc-sestamibi SPECT myocardial perfusion imaging (MPI) at rest, demonstrated moderate to severe ischemia involving apical, antero-septal, adjacent anterior wall and adjacent basal 2/3 rd of inferior wall segments of LV myocardium (involving approx.~73% of RCA territory and 57% of LAD territory at 50% uptake threshold). There was wall motion abnormality in above mentioned segments on ECG gated SPECT and estimated LVEF with QGS was ~29±5%. She has been started on anti-ischemic measures, guideline directed therapy for HFrEF and comprehensive diabetes care. Diabetic cardiomyopathy is myocardial dysfunction with normal epicardial coronary arteries and absence of other cardiovascular diseases. It is characterized by myocardial fibrosis and associated systolic dysfunction preceded by diastolic dysfunction. Cardiac insulin resistance leads to advanced glycation end products, microvascular dysfunction etc. Perfusion defects observed during MPI in patients with LBBB may be due to CAD, microvascular dysfunction, or artifacts. In the setting of LBBB, isolated anteroseptal defect has low probability of CAD but presence of perfusion defects in RCA territory and apical region increases probability of ischemic events.In this case, there was ischemia with systolic dysfunction in the absence of any overt clinical coronary artery disease and no other identifiable cause.

Identification of fibrosis in hypertrophic cardiomyopathy: a radiomic study on cardiac magnetic resonance cine imaging

ObjectivesHypertrophic cardiomyopathy (HCM) often requires repeated enhanced cardiac magnetic resonance (CMR) imaging to detect fibrosis. We aimed to develop a practical model based on cine imaging to help identify patients with high risk of fibrosis and screen out patients without fibrosis to avoid unnecessary injection of contrast.MethodsA total of 273 patients with HCM were divided into training and test sets at a ratio of 7:3. Logistic regression analysis was used to find predictive image features to construct CMR model. Radiomic features were derived from the maximal wall thickness (MWT) slice and entire left ventricular (LV) myocardium. Extreme gradient boosting was used to build radiomic models. Integrated models were established by fusing image features and radiomic models. The model performance was validated in the test set and assessed by ROC and calibration curve and decision curve analysis (DCA).ResultsWe established five prediction models, including CMR, R1 (based on the MWT slice), R2 (based on the entire LV myocardium), and two integrated models (ICMR+R1 and ICMR+R2). In the test set, ICMR+R2 model had an excellent AUC value (0.898), diagnostic accuracy (89.02%), sensitivity (92.54%), and F1 score (93.23%) in identifying patients with positive late gadolinium enhancement. The calibration plots and DCA indicated that ICMR+R2 model was well-calibrated and presented a better net benefit than other models.ConclusionsA predictive model that fused image and radiomic features from the entire LV myocardium had good diagnostic performance, robustness, and clinical utility.Key Points• Hypertrophic cardiomyopathy is prone to fibrosis, requiring patients to undergo repeated enhanced cardiac magnetic resonance imaging to detect fibrosis over their lifetime follow-up.• A predictive model based on the entire left ventricular myocardium outperformed a model based on a slice of the maximal wall thickness.• A predictive model that fused image and radiomic features from the entire left ventricular myocardium had excellent diagnostic performance, robustness, and clinical utility.

Two cases of left ventricular apical aneurysm associated with severe aortic stenosis: case report

BackgroundLeft ventricular (LV) apical aneurysm associated with aortic valve stenosis (AS) is very rare. We herein report two cases of this entity.Case presentationCase 1 was a 75-year-old woman admitted for surgery for severe AS and enlargement of the ascending aorta. Preoperative routine echocardiography and cardiac computed tomography (CT) revealed an unexpected local aneurysm of the LV apex. The patient underwent aortic valve replacement (AVR), LV aneurysm resection, and ascending aorta replacement. Case 2 was a 71-year-old woman diagnosed with severe AS. Preoperative cardiac CT detected LV apical aneurysm that could not be detected by echocardiography. Cardiac catheterization showed a coronary ventricular fistula. The patient underwent AVR and LV aneurysm resection. Given that neither of the two cases had a history of myocardial infarction or obstructive hypertrophic cardiomyopathy, the cause of the local aneurysm of the LV apex was thought to be relative ischemia at the apex due to myocardial hypertrophy and LV pressure overload due to long-term AS. In addition, a coronary artery fistula was suggested to be involved in the relative ischemia of the apex in Case 2.ConclusionsEchocardiography alone is not sufficient to exclude apical aneurysm, and cardiac CT may be useful. Regarding the surgical indication, it is necessary to consider further cases in the future.

Characterization of Vascular Patterns Associated with Endothelial Glycocalyx Damage in Early- and Late-Onset Preeclampsia.

This paper provides an assessment of molecular and functional changes in blood vessels, and a description of vascular patterns during preeclampsia (PE). Patients with normal pregnancy, and pregnancy complicated by PE at earlier (20-34 weeks) and later terms (≥34 weeks) underwent a 24 h monitoring of blood pressure, central hemodynamics, arterial stiffness, and myocardial function. The blood levels of the structural components of endothelial glycocalyx (eGC): syndecan-1 (SDC 1), heparan sulfate proteoglycan 2 (HSPG2), and hyaluronic acid (HA) were determined. In early-onset PE, the vascular pattern comprised changes in all structural components of eGCs, including transmembrane proteoglycans levels, and severe disorders of central hemodynamics, arterial stiffness, and myocardial changes, probably leading to more severe course of PE and the formation of morphological grounds for cardiovascular disorders. The vascular pattern in late-onset PE, including changes in HA levels, central hemodynamics, and myocardial function, may be a signal of potential cardiovascular disorder. PE may change adaptive hemodynamic responses to a pathological reaction affecting both arterial elasticity and the left ventricular myocardium, with its subsequent hypertrophy and decompensation, leading to a delayed development of cardiovascular disorders after PE. Further clinical studies of these indicators will possibly identify predictors of PE and long-term consequences of the disease.

THE CORRELATION OF LEFT VENTRICULAR MECHANICAL DISPERSION AND LEFT VENTRICULAR EJECTION FRACTION WITH QT DISPERSION IN END-STAGE RENAL DISEASE PATIENTS ON HEMODIALYSIS BEFORE AND AFTER DIALYSIS

Background: Ventricular arrhythmias (VA) is common in dialytic patients. Left Ventricular Mechanical Dispersion (LVMD) could provide an inhomogeneous of left ventricular myocardium contraction lead to VA. Reduced Left Ventricular Ejection Fraction (LVEF) and QT Dispersion (QTd) are well-known VA predictors in dialytic patients. This study aimed to determine the relationship between LVMD and LVEF on QT dispersion in ESRD patients before and after dialysis. Methods: This cross-sectional study was conducted in November 2021 - February 2022. All study subjects who met the inclusion criteria underwent history taking and physical examination including age, sex, body weight, body height, electrocardiography, echocardiography, and routine laboratory studies. Results: Among 43 subjects, 24 (55.8%) were male, with mean age of 51,14±11,6 was conducted in this study. The most common comorbidities were hypertension (79%) and diabetes mellitus (44.19%). Pre-dialysis LVMD mean was 28.99±15.98 ms and significantly decrease to 24.16±15.77 ms after dialysis (p<0.05). There was insignificant decrease in the QTd value before dialysis with a mean 61.72±25.93 ms to 54.60±21.26 ms. There was no difference in the mean LVEF before dialysis (57.19±5.17%) and after dialysis (57.54±5.04%). There are no correlation between LVEF, LVMD and QTd variables before and after dialysis. Conclusion: There was a significant decrease of LVMD after dialysis period, but there was no significant difference in the LVEF and QTd parameters. No correlation was found between QTd parameters, LVMD, or LVEF in ESRD patients on HD both before and after dialysis.

PSAT006 Two Cases of Pheochromocytoma Associated Takotsubo Syndrome- Importance of Early Recognition and Treatment

Abstract Introduction Pheochromocytoma is a rare catecholamine producing adrenal medullary tumor that classically presents with hypertension. Takutsubo cardiomyopathy (TC) is a rare but increasingly recognized presentation of pheochromocytoma. We present two cases of TC likely caused by pheochromocytoma. Case 1 A 60 y/o male who presented with acute onset nausea, vomiting and abdominal pain. Systolic BP was 150-160 mm Hg, and diastolic BP was 100 mmHg. Troponin was elevated (4.15 ng/ml; nl = 0-0.04). An echocardiogram showed a reduced left ventricular ejection fraction (LVEF) of 15-20% (nl = 50-75%), a mildly dilated left ventricle, and apical ballooning suggestive of TC. Coronary arteries were normal on cardiac catheterization. CT scan identified a 5.3×5.6×5.7 cm adrenal mass of 50 HU pre-contrast. Further evaluation revealed markedly elevated plasma metanephrine concentration of 858 pg/ml (nl<57) and normetanpehrine concentration of 1729 pg/ml (<148). His presentation was strongly suggestive of pheochromocytoma associated TC. He was prepared for surgery with doxazosin 2 mg twice daily followed by metoprolol succinate and metyrosine up to 500 mg/d. Final pathology revealed a 5.3 cm left pheochromocytoma with negative surgical margins. Germline genetic testing was negative for pheochromocytoma/paraganglioma pathogenic gene mutations, and an MIBG scan did not reveal metastatic disease. Echocardiogram one month after adrenalectomy showed a marked improvement in LVEF to 55-60% with no regional wall motion abnormalities, and plasma metanephrine concentrations normalized. Case 2 A 61 y/o female smoker with type 2 diabetes mellitus, hypertension, Graves disease and obesity presented with sudden onset of nausea followed by chest discomfort, bilateral shoulder discomfort and shortness of breath. Troponin was 0.6 ng/ml (nl = 0-0.04), EKG showed ST elevations in leads I, 2, V5 V6 with hyperacute T waves. Coronary arteries were normal on catheterization. She required intubation, and systolic BP ranged from 110 to 200 mm Hg. On echocardiogram the LVEF was 35% to 40% (nl = 50-75), and there was diffuse hypokinesis of the mid to apical LV myocardium with hypercontractility of the LV base, suggestive of TC. The plasma metanephrine concentration was 3.31 nmol/l (nl= 0-0.49), and normetanephrine concentration was 5.02 nmol/l (nl= 0-0.89). CT imaging revealed a 2.9 cm left adrenal mass. She underwent successful left adrenalectomy after preparation with alpha, beta blockade and metyrosine. Germline genetic testing was negative for pheochromocytoma/paraganglioma pathogenic gene mutations . Echocardiogram nine months post-adrenalectomy showed normal EF of 50-55% and resolution of apical hypokinesis. Discussion We present two pheochromocytoma patients presenting with TC that reversed following appropriate pheochromocytoma management. Few case series report the association of pheochromocytoma and TC. These patients usually present acutely without prodromal stressors commonly found with classic TC. Conclusion In the setting of TC, pheochromocytoma should be considered. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The clinical case of non-compact left ventricular myocardium in combination with restrictive cardiomyopathy

In this paper the information about a comparatively rare form of cardiomyopathy – noncompaction of the left ventricular myocardium is showed. As a result of genetical changes on the early stages of embryogenesis a disability of myocardial fibres develops, and two-layer myocardial structure is formed: thin compact layer and remaining more voluminous non-compact layer with significant trabeculation and deep intratrabecular cavities communicated with ventricular cavity. Mutations in genes which encode sarcomeric, structural and regulatory proteins and proteins, which are responsible for ion channels functioning, are considered to be one of the main reasons of non-compact myocardium. There is a theory that considers a non-compact myocardium as a result of an exposure of various factors during lifetime – so-called non-embryonal (acquired) noncompaction myocardium. “Non-embryonal” hypothesis views non-compact myocardium as a sign of functional maladaptation, possible stage in cardiomyopathy development. By way of illustration the clinical case of 32-year-old female patient is presented in the article. The noncompaction of the left ventricular myocardium in conjunction with restrictive cardiomyopathy was first diagnosed in her. The diagnosis was confirmed by main diagnostic methods for this pathology such as echocardiography and MRI of a heart. This clinical observation is interesting due to formation of disease patterns by two rare combined pathological conditions: noncompaction of the myocardium syndrome and restrictive cardiomyopathy. Changes of heart hemodynamics occurs in interaction between these pathologies. Diastolic filling of left ventricular decreases as a result of restrictive cardiomyopathy, which leads to decreasing of its myocardium load. Therefore, systolic disfunction, which is specific to non-compact myocardium, doesn’t occur. Generally, prognosis for this patient is poor due to presence of two serious pathologies.

Landscape of RNA-binding proteins in diagnostic utility, immune cell infiltration and PANoptosis features of heart failure.

Objective: Heart failure remains a global public health problem linked to rising morbidity and mortality. RNA-binding proteins (RBPs) are crucial regulators in post-transcriptionally determining gene expression. Our study aimed to comprehensively elucidate the diagnostic utility and biological roles of RBPs in heart failure. Methods: Genomic data of human failing and nonfailing left ventricular myocardium specimens were retrieved from the GEO datasets. Heart failure-specific RBPs were screened with differential expression analyses, and RBP-based subtypes were clustered with consensus clustering approach. GSEA was implemented for comparing KEGG pathways across subtypes. RBP-based subtype-related genes were screened with WGCNA. Afterwards, characteristic genes were selected through integrating LASSO and SVM-RFE approaches. A nomogram based on characteristic genes was established and verified through calibration curve, decision curve and clinical impact curve analyses. The abundance of immune cell types was estimated with CIBERSORT approach. Results: Heart failure-specific RBPs were determined, which were remarkably linked to RNA metabolism process. Three RBP-based subtypes (namely C1, C2, C3) were established, characterized by distinct pathway activities and PANoptosis gene levels. C2 subtype presented the highest abundance of immune cells, followed by C1 and C3. Afterwards, ten characteristic genes were selected, which enabled to reliably diagnose heart failure risk. The characteristic gene-based nomogram enabled to accurately predict risk of heart failure, with the excellent clinical utility. Additionally, characteristic genes correlated to immune cell infiltration and PANoptosis genes. Conclusion: Our findings comprehensively described the roles of RBPs in heart failure. Further research is required for verifying the effectiveness of RBP-based subtypes and characteristic genes in heart failure.

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

Long-term epigenetic and metabolomic changes in the mouse ventricular myocardium after exertional heat stroke.

Evidence from human epidemiological studies suggests that exertional heat stroke (EHS) results in an elevated risk of long-term cardiovascular and systemic disease. Previous results using a preclinical mouse model of EHS demonstrated severe metabolic imbalances in ventricular myocardium developing at 9-14 days of recovery. Whether this resolves over time is unknown. We hypothesized that the long-term effects of EHS on the heart reflect retained maladaptive epigenetic responses. In this study, we evaluated genome-wide DNA methylation, RNA-Seq, and metabolomic profiles of the left ventricular myocardium in female C57BL/6 mice, 30 days after EHS (exercise in 37.5°C; n = 7-8), compared with exercise controls. EHS mice ran to loss of consciousness, reaching core temperatures of 42.4 ± 0.2°C. All mice recovered quickly. After 30 days, the left ventricles were rapidly frozen for DNA methyl sequencing, RNA-Seq, and untargeted metabolomics. Ventricular DNA from EHS mice revealed >13,000 differentially methylated cytosines (DMCs) and >900 differentially methylated regions (DMRs; ≥5 DMCs with ≤300 bp between each CpG). Pathway analysis using DMRs revealed alterations in genes regulating basic cell functions, DNA binding, transcription, and metabolism. Metabolomics and mRNA expression revealed modest changes that are consistent with a return to homeostasis. Methylation status did not predict RNA expression or metabolic state at 30 days. We conclude that EHS induces a sustained DNA methylation memory lasting over 30 days of recovery, but ventricular gene expression and metabolism return to a relative homeostasis at rest. Such long-lasting alterations to the DNA methylation landscape could alter responsiveness to environmental or clinical challenges later in life.

Cardiac magnetic resonance radiomics for prediction of incident heart failure: a feasibility study in the UK Biobank Imaging cohort

Abstract Background Cardiac magnetic resonance (CMR) radiomics is a novel image quantification technique with the potential to improve image-based disease diagnosis and prediction. Purpose In this proof-of-concept study, we aimed to evaluate the utility of CMR radiomics in the prediction of incident heart failure (HF). Methods We studied 32,121 UK Biobank participants with CMR. Incident HF was defined from linked Hospital Episode Statistics. To create a balanced cohort, we identified as comparators an equal number of randomly selected subjects who did not develop the outcome of interest during this period. Radiomics shape, first-order and texture features were extracted from short-axis cine images (left and right ventricle, left ventricular myocardium) using the Pyradiomics toolbox. Vascular risk factors (VRFs) were considered as additional predictors. Feature selection was conducted using the sequential forward selection technique and modelling was performed using Support Vector Machine (SVM) methods with 5-fold cross-validation. Models were developed using 1) VRFs alone, 2) radiomics alone, and 3) VRFs and radiomics. We determined model performance using receiver operating characteristic (ROC) curve and area under the curve (AUC) scores. Results Over average follow-up time of 3.7 (±1.3) years, 209 participants experienced incident HF. Among vascular risk factors, age, body size, hypertension, diabetes, high cholesterol were chosen for the incident HF predictive model (Accuracy: 0.66, AUC: 0.73) by the SVM methods. The model based on radiomics features reached a marginal improvement compared to vascular risk factors alone (Accuracy: 0.71, AUC: 0.75). The combination of VRFs and radiomics features significantly improved the performance of the model to predict incident HF compared to VRFs alone (Accuracy: 0.77; AUC: 0.83; p&amp;lt;0.05) Conclusion We demonstrate the feasibility of CMR radomics features to predict incident HF and illustrate their added value over vascular risk factors. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding.

A 2D-speckle tracking analysis in patients undergoing trastuzumab in non-metastatic breast cancer

Abstract Background Trastuzumab (TZ) is widely used for his key role in HER2 positive breast cancer. However, the most concerning cardiovascular complication is cardiotoxicity. Many studies have highlighted the importance of screening for subclinical myocardial dysfunction using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, there are only few studies investigating a possible atrial damage. Purpose Aim of this study is to analyze the modification of GLS and peak atrial systolic longitudinal strain (PALS) in patients undergoing therapy with TZ in a follow-up period of 12 months. The eventual fluctuation of left atrial function under chemotherapy was evaluated and the correlation between subclinical atrial disfunction and early left ventricular impairment was investigated. Methods 105 women affected by breast cancer treated with TZ were enrolled. Each patient underwent a complete echocardiography at baseline and every 3 months. 37 patients (35%) were excluded from the left atrial function analysis while LV function evaluation was performed in 83 patients (21%). Exclusion criteria were poor quality imaging and lack of a complete follow up with consequent missing data. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software in order to analyze both atrial and left ventricular function. Subclinical LV disfunction was defined as a GLS reduction of ≥15% compared to the baseline value. Left atrial impairment was arbitrary defined as a PALS reduction of ≥25% compared to the initial value. Finally, trends of GLS and PALS during 12 months-follow up periods were analyzed. Additionally, we explored if diabetes and renal impairment were associated with more prevalent atrial subclinical disfunction as demonstrated in previous studies. Results A total of 49% patients developed subclinical LV dysfunction. Similarly, 48% patients showed a left atrial impairment. Interestingly a significant (p=0.0001) reduction in GLS was observed during the follow-up, particularly in the first six months of treatment. PALS showed a similar trend with a significant decrease during the whole 12 months-follow up (p=0.0001) and mostly in the first 6 months. 6 patients presented a diagnosis of diabetes at baseline, and presented lower PALS compared to the non-diabetic counterpart (37.6±9.9% vs 48.7±12.2%, p=0.03). 2 patients presented a significant renal impairment (eGFR ≤30 ml/min). Similarly, these patients presented a lower PALS at baseline (32±7 and 48±7; p=0.05). Conclusions In patients treated with Trastuzumab development of left atrial impairment is frequent and PALS modifications follow a similar pattern to GLS variations during the treatment, suggesting a possible cardiotoxic effect of such therapy on both atrial and left ventricular myocardium and physiology. Funding Acknowledgement Type of funding sources: None.

Influence of the SGLT2 inhibitor empagliflozin on post myocardial infarction rat hearts

Abstract Studies have shown that inhibition of the sodium glucose transporter protein 2 (SGLT2) reduces cardiovascular death in patients with heart failure and reduced ejection fraction. However, the mechanisms involved in the benefits of SGLT2 inhibitors are poorly understood. Objective To evaluate the effects of empagliflozin (EMP) on normal and post-myocardial infarction (MI) rat hearts. Methods Male Wistar rats (n=80) were assigned into four groups: Sham; Sham treated with EMP (Sham-EMP); myocardial infarction (MI); and MI treated with EMP (MI-EMP). EMP added to rat chow (5 mg/kg/day) was initiated 10 days after MI induction and maintained for 12 weeks. Echocardiogram was performed at the end of the experimental period. Markers of oxidative stress, energy metabolism, and respiratory complex activity were analyzed in left ventricular myocardium. Statistical analysis: ANOVA. Results Histological evaluation showed that EMP did not change infarct size. Cardiac structural and functional parameters did not differ between MI-EMP and MI groups. Myocardial oxidative stress, evaluated by lipid hydroperoxide concentration, was lower in MI-EMP than MI group (Sham 143±26; Sham-EMP 123±20; MI 183±29; MI-EMP 137±11 nmol/g tissue). Glutathione peroxidase was lower in the infarcted groups and did not differ between MI-EMP and MI (Sham 37.6±6.14; Sham-EMP 40.8±10.1; MI 27.7±6.61; MI-EMP 26.5±6.80 μmol/g tissue). Activity of the energy metabolism enzymes lactate dehydrogenase (Sham 45.2±6.65; Sham-EMP 41.1±9.33; MI 58.4±14.4; MI-EMP 55.7±10.1 nmol/mg protein) and citrate synthase (Sham 30.4±4.25; Sham-EMP 37.2±4.85; MI 45.8±8.47; MI-EMP 46.5±9.95 nmol/mg protein) was higher, and β-hydroxyacyl-CoA dehydrogenase (Sham 24.0±3.12; Sham-EMP 20.4±4.84; MI 16.9±4.81; MI-EMP 14.4±4.58 nmol/mg protein) lower in the infarcted groups with no differences between MI-EMP and MI. Respiratory complexes I and II, and ATP synthase did not differ between the infarcted groups. Conclusion Empagliflozin reduces myocardial oxidative stress independent of changes in antioxidant enzymes activity, energy metabolism, and respiratory complex activity in the myocardium of infarcted rats. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Fapesp, CNPq

Left ventricular myocardial tissue characteristics and function among healthy subjects with varying atherosclerotic cardiovascular disease risk

Abstract The Atherosclerotic Cardiovascular Disease Risk (ASCVD) score by pooled cohort equation is a reliable predictor for future ASCVD events and is used to guide primary prevention in asymptomatic aging subjects. ASCVD risk is associated with burden of coronary artery disease as measured from computed tomography angiography. Purpose We aim to investigate the association between ASCVD risk and cardiac magnetic resonance (CMR) derived left ventricular (LV) myocardial tissue characteristics (T1 values) and LV systolic and diastolic ventricular function in a large cohort of healthy subjects. Methods We selected all healthy subjects who underwent CMR from the UK-Biobank cohort study. We collected patient characteristics, cardiovascular risk factors, blood pressure at CMR, medication use and cholesterol levels. We used AI-CMRQC, our quality-controlled tool for analysis of cardiovascular function metrics from CMR using artificial intelligence [1,2], to automatically extract septal T1 values from native T1 maps and LV ejection fraction (EF), peak ejection and early filling rates (PER, PEFR), peak systolic longitudinal strain and diastolic strain-rate, mitral valve annular plane systolic excursion and diastolic peak velocity from cine long and short axis acquisitions. Subjects were stratified for low (&amp;lt;7.5%), intermediate (7.5–21%) and high (&amp;gt;21%) ASCVD risk. One-way repeated measures ANOVA was used to examine the association between cardiovascular metrics and ASCVD risk groups. Results 12,493 healthy subjects were included (females n=6,000). Mean age was 62.7±7.5 years, 3.2% had diabetes, 12.5% received treatment for hypertension and 23% smoked. ASCVD risk score could be calculated in 9,487 subjects. Mean ASCVD risk was 12.7±9%. 38% of subjects had low, 43% intermediate and 19% high ASCVD risk. T1 values fell across the incremental ASCVD groups (low: 943±51 ms, intermediate: 921±47 ms, high: 918±50 ms, P&amp;lt;0.001). Indexed LV PEFR (low: 188±45 ml/ms·m2, intermediate: 170±48 ml/ms·m2, high: 147±45 ml/ms·m2, P&amp;lt;0.001), diastolic longitudinal strain rate (low: 1.25±0.36, intermediate: 1.20±0.37, high: 1.17±0.36, P&amp;lt;0.001) also fell consistently with incremental risk. A statistically significant, but clinically less relevant decrease was seen for LVEF (low: 59±6%, intermediate 58±6%, high: 57±6% p&amp;lt;0.001) and longitudinal systolic strain (low: 21±3.5%, intermediate: 21±3.4%, high: 21±3.5%). Conclusion Increasing ASCVD risk was associated with lower native T1 values and decreasing metrics of diastolic and systolic LV function. The fall in T1 might suggest fibrofatty replacement in the LV myocardium in patients with incremental ASCVD risk that could contribute to the observed deterioration of LV function. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIHR MedTech cooperation awarded to Guy's and ST Thomas NHS Foundation Trust

Late gadolinium enhancement patterns in severe symptomatic high-gradient aortic stenosis

Abstract Background Left ventricular (LV) remodeling in patients with severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response and may involve reparative/replacement fibrosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for detecting focal myocardial fibrosis through late gadolinium enhancement (LGE). However, myocardial fibrosis prevalence and distribution is quite variable among series. Our goal was to assess LGE prevalence and distribution pattern in severe symptomatic high-gradient AS. Methodology Single-center prospective cohort of 132 patients with severe symptomatic high-gradient AS (mean age 73±11 years; 48% male, mean valvular transaortic gradient 60±20 mmHg; mean aortic valve area 0.7±0.2 cm2/m2; mean LV ejection fraction by 2D echocardiogram 58±9%), all with normal flow (except one) undergoing surgical aortic valve replacement. Those with previous history of acute myocardial infarction, ischemic cardiomyopathy or other cardiomyopathy were excluded. All patients performed 1.5T CMR assessment with LV myocardium tissue characterization prior to surgery. Segmental LGE presence was assessed by two independent operators and classified according to the AHA 16 segment model, using 5-standard deviations from remote myocardium as the signal intensity cut-off for LGE identification and quantification. Results Overall, 96 patients (74%) had non-ischemic LGE (median LGE mass 3.2 g [IQR 0.2–8.3] g; median percentage of LGE myocardial mass 2.5% [IQR 0.1–6.1]%); 22 patients [17%] with exclusively junctional LGE); in one patient an incidental ischemic scar (subendocardial distribution) was identified. No cases of subepicardial distribution were found. Intramyocardial LGE was most frequently observed in basal and mid-anterior and inferior interventricular septum – see Figure 1. In these segments, LGE was most often junctional at right-ventricular insertion points (54%), followed by mid-wall LGE (32%) or both sites involvement (14%). Conclusion LGE is frequent in symptomatic high-gradient AS patients with preserved left ventricular ejection fraction, most often presenting as junctional enhancement in basal/mid-anterior and inferior interventricular septum. Future studies may address whether distinct LGE patterns may impact patient prognosis. Funding Acknowledgement Type of funding sources: None.

Cardiac MRI segmentation with sparse annotations: Ensembling deep learning uncertainty and shape priors.

The performance of deep learning for cardiac magnetic resonance imaging (MRI) segmentation is oftentimes degraded when using small datasets and sparse annotations for training or adapting a pre-trained model to previously unseen datasets. Here, we developed and evaluated an approach to addressing some of these issues to facilitate broader use of deep learning for short-axis cardiac MRI segmentation. We developed a globally optimal label fusion (GOLF) algorithm that enforced spatial smoothness to generate consensus segmentation from segmentation predictions provided by a deep learning ensemble algorithm. The GOLF consensus was entered into an uncertainty-guided coupled continuous kernel cut (ugCCKC) algorithm that employed normalized cut, image-grid continuous regularization, and "nesting" and circular shape priors of the left ventricular myocardium (LVM) and cavity (LVC). In addition, the uncertainty measurements derived from the segmentation predictions were used to constrain the similarity of GOLF and final segmentation. We optimized ugCCKC through upper bound relaxation, for which we developed an efficient coupled continuous max-flow algorithm implemented in an iterative manner. We showed that GOLF yielded average symmetric surface distance (ASSD) 0.2-0.8mm lower than an averaging method with higher or similar Dice similarity coefficient (DSC). We also demonstrated that ugCCKC incorporating the shape priors improved DSC by 0.01-0.05 and reduced ASSD by 0.1-0.9mm. In addition, we integrated GOLF and ugCCKC into a deep learning ensemble algorithm by refining the segmentation of an unannotated dataset and using the refined segmentation to update the trained models. With the proposed framework, we demonstrated the capability of using relatively small datasets (5-10 subjects) with sparse (5-25% slices labeled) annotations to train a deep learning algorithm, while achieving DSC of 0.871-0.893 for LVM and 0.933-0.959 for LVC on the LVQuan dataset, and these were 0.844-0.871 for LVM and 0.923-0.931 for LVC on the ACDC dataset. Furthermore, we showed that the proposed approach can be adapted to substantially alleviate the domain shift issue. Moreover, we calculated a number of commonly used LV function measurements using the derived segmentation and observed strong correlations (Pearson r=0.77-1.00, p<0.001) between algorithm and manual LV function analyses. These results suggest that the developed approaches can be used to facilitate broader application of deep learning in research and clinical cardiac MR imaging workflow.