Ventricular Mass Research Articles

Tissue characteristics of the athlete"s heart: differentiation of physiological and pathological hypertrophy using parametric T1 and T2 mapping

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Fund of Hungary Background Intensive physical exercise leads to structural and functional cardiac adaptation termed athlete’s heart. Cardiac magnetic resonance (CMR) has an important role in the differentiation of physiological adaptation and pathological conditions. Beside the precise measurement of the ventricular volumes, mass, and function, it provides tissue specific information. Recently, native T1 mapping technique has been applied as a non-contrast method to detect myocardial fibrosis. Previous studies suggested that native T1 mapping can identify myocardial pathology before other CMR imaging techniques. T2 mapping values are elevated in case of myocardial edema. Purpose The aim of our study was to investigate the differences in CMR characteristics especially the native T1 and T2 mapping values of highly trained healthy athletes, healthy controls and patients with hypertrophic cardiomyopathy (HCM). Methods A total of 43 healthy athletes (water polo, swimming, football, 22 ± 8 training hours/week), 27 non-athlete healthy control and 25 HCM patients were involved in the study. Our inclusion criteria were: age >18 years, in the athlete group >7 training hours per week . We evaluated the left ventricular (LV) end-systolic, end-diastolic (EDVi) and stroke volume (SVi) index, mass index (LVMi), ejection fraction (EF) and maximal end-diastolic wall thickness (EDWT). In a basal short axis slice the native T1 and T2 mapping values were evaluated. Results Athletes had significantly higher LV volumes compared to the control and HCM group (LVEDVi 114 ± 13 vs. 86 ± 11; 84 ± 15 ml/m2, LVSVi 64 ± 7 vs. 51 ± 7; 54 ± 10 ml/m2, respectively, p < 0.0001). HCM patients had the highest LVMi (72 ± 14 g/m2) and EDWT (18 ± 4 mm) compared to athletes and controls, athletes had higher LVMi (60 ± 11 vs. 42 ± 8 g/m2) and EDWT (10 ± 2 vs. 8 ± 1 mm) compared to the controls (p < 0.001). The native T1 mapping values differed significantly in the three groups, athletes had the lowest, HCM patients had the highest T1 values (athletes: 956 ± 19 ms, controls: 971 ± 20 ms, HCM patients: 993 ± 39 ms; p < 0.0001). There was no difference in the T2 mapping values between athletes and controls (44 ± 2 vs. 43 ± 2 ms), HCM patients had higher T2 values (45 ± 2 ms) compared to the other two groups (p < 0.01). Conclusion Intensive and regular training may lead to tissue specific changes of the myocardium. T1 and T2 mapping are potentially useful tools for differentiating between athlete"s heart and patients with hypertrophic cardiomyopathy. Abstract Figure. T1 mapping in HCM and athlete

Ivabradine plus conventional treatment vs conventional treatment alone in reducing the mean heart rate in heart transplant recipients: A randomized clinical trial.

The absence of afferent nerves for heart rate (HR) regulation leaves the transplanted heart under the influence of its internal and hormonal control. The HR of heart transplantation (HTx) recipients varies from to 90-110bpm, indicating a lack of vagal parasympathetic tone. We hypothesized that the reduction in mean HR using an If-channel antagonist (ivabradine) could be effective and safe in HTx recipients. The primary objective of this open-label randomized clinical trial was to compare the mean HR at 3, 6, 12, 18, 24, 30, and 36months after randomization between an ivabradine plus conventional treatment group (IG) and conventional treatment alone group (CG). The secondary objectives were reduction in mortality, graft dysfunction, and ventricular mass. All patients were randomized between 1 and 12months after HTx. Ivabradine started at randomization. Of the 35 patients, 54.28% were in the CG and 45.72% in the IG. There were no significant between-group differences in demographics. Over time, the HR differences between the groups became significant (P<.01). There were no significant between-group differences in mortality, graft dysfunction, and ventricular mass. We conclude that ivabradine could effectively and consistently reduce the HR in HTx recipients.

The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF)

A recent large cardiovascular outcome trial in patients with type 2 diabetes (T2DM) demonstrated excess heart failure hospitalization with saxagliptin. We sought to evaluate the impact of saxagliptin on cardiac structure and function using cardiac magnetic resonance imaging (CMR) in patients with T2DM without pre-existing heart failure. In this prospective study, patients with T2DM without heart failure were prescribed saxagliptin as part of routine guideline-directed management. Clinical assessment, CMR imaging and biomarkers were assessed in a blinded fashion and compared following 6months of continued treatment. The primary outcome was the change in left ventricular (LV) ejection fraction (LVEF) after 6months of therapy. Key secondary outcomes included changes in LV and right ventricular (RV) end-diastolic volume, ventricular mass, LV global strain and cardiac biomarkers [N terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP)] over 6 months. The cohort (n = 16) had a mean age of 59.9years with 69% being male. The mean hemoglobin A1c (HbA1c) was 8.3%. Mean baseline LVEF was 57% ± 3.4, with no significant change over 6months (- 0.2%, 95% CI - 2.5, 2.1, p = 0.86). Detailed CMR analyses that included LV/RV volumes, LV mass, and feature tracking-derived strain showed no significant change (all p > 0.50). NT-proBNP and hsCRP levels did not significantly change (p > 0.20). In this cohort of stable ambulatory patients with T2DM without heart failure, saxagliptin treatment was not associated with adverse ventricular remodeling over 6months as assessed using CMR and biomarkers.

Age- and Sex-Differences in Cardiac Characteristics Determined by Echocardiography in Masters Athletes.

BackgroundCardiac function and morphology are known to differ between men and women. Sex differences seen with echocardiography have not been studied systematically in masters athletes.PurposeTo evaluate sex differences in cardiac structure, function and left ventricular (LV) systolic global longitudinal strain among masters athletes.MethodsThis cross-sectional study comprises of 163 masters athletes (M = 109, 60 ± 12 years; F = 55, 57 ± 12 years, range 36–91 years) who participated at the 23rd World Masters Athletics Championship held in Málaga, Spain. All athletes underwent state-of-the-art echocardiography including cardiac function, morphology, strain and hemodynamic assessment.ResultsLeft ventricular mass was higher in male than in female athletes (174 ± 44 vs. 141 ± 36 g, p < 0.01) due to greater end-diastolic intraventricular septal, LV posterior wall and LV basal diameter. However, LV mass index did not differ between the groups. End-diastolic LV volume and right ventricular area, both indexed to body-surface-area, were greater in men than in women (52.8 ± 11.0 vs. 46.1 ± 8.5 ml/m2, p < 0.01, 9.5 ± 2.4 vs. 8.1 ± 1.7 cm2/m2, p < 0.01). In contrast, women had higher LV systolic global longitudinal strain (-20.2 ± 2.6 vs. -18.8 ± 2.6%, p < 0.01) and LV outflow tract flow velocity (75.1 ± 11.1 vs. 71.2 ± 11.1 cm/s, p = 0.04). Systolic and diastolic blood pressure, LV ejection fraction, and stroke volume index were not different between sexes.ConclusionCardiac sex differences are present even among masters athletes. Lifelong exercise training does not appear to exasperate morphological difference to a point of cardiac risk or dysfunction in both male and female athletes.

Right Ventricular Mass Quantification Using Cardiac CT and a Semiautomatic Three-Dimensional Hybrid Segmentation Approach: A Pilot Study.

ObjectiveTo evaluate the technical applicability of a semiautomatic three-dimensional (3D) hybrid CT segmentation method for the quantification of right ventricular mass in patients with cardiovascular disease.Materials and MethodsCardiac CT (270 cardiac phases) was used to quantify right ventricular mass using a semiautomatic 3D hybrid segmentation method in 195 patients with cardiovascular disease. Data from 270 cardiac phases were divided into subgroups based on the extent of the segmentation error (no error; ≤ 10% error; > 10% error [technical failure]), defined as discontinuous areas in the right ventricular myocardium. The reproducibility of the right ventricular mass quantification was assessed. In patients with no error or < 10% error, the right ventricular mass was compared and correlated between paired end-systolic and end-diastolic data. The error rate and right ventricular mass were compared based on right ventricular hypertrophy groups.ResultsThe quantification of right ventricular mass was technically applicable in 96.3% (260/270) of CT data, with no error in 54.4% (147/270) and ≤ 10% error in 41.9% (113/270) of cases. Technical failure was observed in 3.7% (10/270) of cases. The reproducibility of the quantification was high (intraclass correlation coefficient = 0.999, p < 0.001). The indexed mass was significantly greater at end-systole than at end-diastole (45.9 ± 22.1 g/m2 vs. 39.7 ± 20.2 g/m2, p < 0.001), and paired values were highly correlated (r = 0.96, p < 0.001). Fewer errors were observed in severe right ventricular hypertrophy and at the end-systolic phase. The indexed right ventricular mass was significantly higher in severe right ventricular hypertrophy (p < 0.02), except in the comparison of the end-diastolic data between no hypertrophy and mild hypertrophy groups (p > 0.1).ConclusionCT quantification of right ventricular mass using a semiautomatic 3D hybrid segmentation is technically applicable with high reproducibility in most patients with cardiovascular disease.

Motion tracking of left myocardium in cardiac cine magnetic resonance image based on displacement flow U-Net and variational autoencoder

The high morbidity and mortality of cardiovascular diseases (CVDs) seriously affects the quality of human life. How to asses cardiac function, assist in the diagnosis and treatment of clinical CVDs and evaluate prognosis is a problem to be solved urgently. In response to this issue, based on previous work of Cardiac Cine Magnetic Resonance (CCMR) image segmentation of the left myocardium (LVM), a robust and accurate LVM motion tracking method (DispFlow_UNet_Flow) with using the displacement flow UNet (DispFlow_UNet) and biomechanics-informed variational autoencoder (VAE) is proposed in this paper. The following are the main research contents: (1) building a compressed excitation residual U-net network to accurately segment LVM, calculating the ventricular volume and myocardial mass according to the segmentation results, and then evaluating the overall cardiac function; (2) reconstructing the dense displacement field (DDF) based on the proposed motion tracking method, and obtaining the LVM dense displacement field by combining the LVM segmentation mask; (3) contrasting and evaluating the motion tracking results by using the true displacement vector field of simulated data and clinical data sets. All the results show that the tracking algorithm proposed in this paper has high precision and generalization capability.

Структурно-функціональний стан лівого шлуночка у хворих з гіпертонічною хворобою та ревматоїдним артритом під впливом різних схем лікування

Hypertensive disease is one of the most common diseases in the world and the leading cause of death and disability from cardiovascular diseases among the population. Recent studies have indicated that patients with hypertension in combination with rheumatoid arthritis have a higher risk of cardiovascular complications and mortality. Ukrainian recommendations for the management of patients with hypertension for 2018 indicated that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are more effective in regressing left ventricular hypertrophy. The purpose of the study was to compare the effect of long-term therapy with valsartan in combination with indopamide and amlodipine on the structural and functional state of the left ventricular myocardium and the level of blood pressure in patients with arterial hypertension in combination with rheumatoid arthritis. Material and methods. The study included hypertensive patients in combination with rheumatoid arthritis. The patients were divided into 3 groups: the first group consisted of 17 patients with essential hypertension in combination with rheumatoid arthritis who took valsartan at a dose of 80 mg at home. The second group included 17 patients who were transferred to additional administration of the drug indapamide at a dose of 15 mg. The third group consisted of 18 patients whose dose of amlodipine was increased from 5 to 10 mg Results and discussion. In the daily blood pressure profile, the time-averaged values of systolic blood pressure and diastolic blood pressure were calculated for three-time intervals of 24 hours, day and night. Left ventricular remodeling was assessed by the relative left ventricular thickness - the ratio of the sum of the thickness of the interventricular septum and the thickness of the posterior wall to the final diastolic size of the left ventricular. The norms were considered to be an indicator of relative wall thickness &lt;0.45. When studying the analysis of the effect of 4-week monotherapy of valsartan at a dose of 80 mg / day on the level of blood pressure and daily blood pressure profile, we revealed a statistically significant decrease in blood pressure by -14.1±2.2 / -8.2±1.4 mm Hg. Art. (P &lt;0.01), mean daily values of systolic blood pressure (24) by 15.1±2.4 mm Hg. Art. (P &lt;0.001), diastolic blood pressure (24) on September 8±1.7 mm Hg. Art. (P &lt;0.001), day and night mean values and indicators of systolic blood pressure and diastolic blood pressure. Analysis of 24-week monotherapy with amlodipine (the average dose of which was 10 mg / day) in 15 patients revealed a decrease in blood pressure by 24.1±3.6 / 15.2±2.3 mm Hg. Art. (P &lt;0.01) and its normalization in 9 out of 15 patients (60%). According to the ABPM data, a significant decrease in systolic blood pressure and diastolic blood pressure was revealed within 24 hours, both in the daytime and at night. The target level of 24-hour AO was achieved in 6 (40%) patients. Valsartan therapy and their combination with indapamide led to regression of left ventricular hypertrophy in all patients, normalization of left ventricular geometry in 33% of patients. In 24 patients with concentric left ventricular hypertrophy, in (25%) left ventricular myocardial mass index and left ventricular geometry normalized, in 4 (17%) patients, left ventricular hypertrophy became eccentric, in 1 (4%) it turned into concentric remodeling, in 10 (54%) patients it remained without changes. Conclusion. Therefore, valsartan and its combination with indapamide in these patients led to regression of left ventricular hypertrophy, normalization of left ventricular geometry in 33% of patients, improvement of left ventricular diastolic function in 88.2%

Cardiac hemodynamic disorders in patients with active chronic viral hepatitis and the effectiveness of antiviral therapy

Aim. To study cardiac hemodynamic disorders in patients with chronic viral hepatitis (CVH) and evaluate the effectiveness of antiviral therapy (AVT).Material and methods. Seventy-nine patients with CVH (mean age, 38,6 years, disease duration, 4,7 years) were examined. The patients were divided into two groups: group 1 (n=42) — normal level of alanine aminotransferase (ALT), group 2 — ALT 3-10 times higher than normal (n=37). Fourteen patients with CVH underwent AVT. Control group consisted of 23 people. Doppler echocardiography was performed. Statistical processing was carried out using Statistica 10.0.Results. In patients with active hepatitis, atrial volume, end diastolic volume, left ventricular (LV) mass index, LV stroke volume increased, and the tricuspid (TC) annular systolic velocity decreased in comparison with the control and 1st groups. In patients with normal ALT levels, the left atrial volume index increased by 8% in comparison with control group. Concentric remodeling was the predominant variant of LV remodeling in patients with active hepatitis. In patients with active hepatitis, LV lateral wall, interventricular septal (IVS), and TC Em/Am ratio decreased. LV diastolic dysfunction was reported in 12 patients with active and 3 patients with inactive CVH. After AVT, left atrium (LA) volume, IVS thickness, LV mass decreased, while TC and mitral annular systolic velocity increased. The viral load has a relationship with mitral annular systolic velocity (r=0,91, p=0,001) and LV mass (r=0,64, p=0,05).Conclusion. In patients with active hepatitis, along with LV and LA dilatation and hypertrophy, a relative right atrial increase, a decrease in the right ventricular longitudinal systolic velocity, and the formation of biventricular diastolic dysfunction develop. In patients with inactive hepatitis, only the left atrial volume increased. The established correlations indicate possible LV damage. Antiviral therapy has a beneficial effect on the main structural and functional cardiac parameters.

Micro-computed tomography (micro-CT) for the assessment of myocardial disarray, fibrosis and ventricular mass in a feline model of hypertrophic cardiomyopathy

Micro-computed tomography (micro-CT) is a high-resolution imaging modality that provides accurate tissue characterization. Hypertrophic cardiomyopathy (HCM) occurs as a spontaneous disease in cats, and is characterized by myocardial hypertrophy, disarray and fibrosis, as in humans. While hypertrophy/mass (LVM) can be objectively measured, fibrosis and myocyte disarray are difficult to assess. We evaluated the accuracy of micro-CT for detection and quantification of myocardial disarray and fibrosis by direct comparison with histopathology. 29 cat hearts (12 normal and 17 HCM hearts) underwent micro-CT and pathologic examination. Myocyte orientation was assessed using structure tensor analysis by determination of helical angle (HA), fractional anisotropy (FA) and myocardial disarray index (MDI). Fibrosis was segmented and quantified based on comparison of gray-scale values in normal and fibrotic myocardium. LVM was obtained by determining myocardial volume. Myocardial segments with low FA, low MDI and disruption of normal HA transmural profile on micro-CT were associated with myocardial disarray on histopathology. FA was consistently lower in HCM than normal hearts. Assessment of fibrosis on micro-CT closely matched the histopathologic evaluation. LVM determined by micro-CT was higher in HCM than normal hearts. Micro-CT can be used to detect and quantify myocardial disarray and fibrosis and determine myocardial mass in HCM.

Diabetic Cardiomiopathy Progression is Triggered by miR122-5p and Involves Extracellular Matrix: A 5-Year Prospective Study

ObjectivesThe purpose of this study was to follow the long-term progression of diabetic cardiomyopathy by combining cardiac magnetic resonance (CMR) and molecular analysis. BackgroundThe evolution of diabetic cardiomyopathy to heart failure affects patients’morbidity and mortality. CMR is the gold standard to assess cardiac remodeling, but there is a lack of markers linked to the mechanism of diabetic cardiomyopathy progression. MethodsFive-year longitudinal study on patients with type 2 diabetes mellitus (T2DM) enrolled in the CECSID (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes) trial compared with nondiabetic age-matched controls. CMR with tagging together with metabolic and molecular assessments were performed at baseline and 5-year follow-up. ResultsA total of 79 men (age 64 ± 8 years) enrolled, comprising 59 men with T2DM compared with 20 nondiabetic age-matched controls. Longitudinal CMR with tagging showed an increase in ventricular mass (ΔLVMi = 13.47 ± 29.66 g/m2; p = 0.014) and a borderline increase in end-diastolic volume (ΔEDVi = 5.16 ± 14.71 ml/m2; p = 0.056) in men with T2DM. Cardiac strain worsened (Δσ = 1.52 ± 3.85%; p = 0.033) whereas torsion was unchanged (Δθ = 0.24 ± 4.04°; p = 0.737), revealing a loss of the adaptive equilibrium between strain and torsion. Contraction dynamics showed a decrease in the systolic time-to-peak (ΔTtP = −35.18 ± 28.81 ms; p < 0.001) and diastolic early recoil-rate (ΔRR = −20.01 ± 19.07 s-1; p < 0.001). The ejection fraction and metabolic parameters were unchanged. Circulating miR microarray revealed an up-regulation of miR122-5p. Network analysis predicted the matrix metalloproteinases (MMPs) MMP-16 and MMP-2 and their regulator (tissue inhibitors of metalloproteinases) as targets. In db/db mice we demonstrated that miR122-5p expression is associated with diabetic cardiomyopathy, that in the diabetic heart is overexpressed, and that, in vitro, it regulates MMP-2. Finally, we demonstrated that miR122-5p overexpression affects the extracellular matrix through MMP-2 modulation. ConclusionsWithin 5 years of diabetic cardiomyopathy onset, increasing cardiac hypertrophy is associated with progressive impairment in strain, depletion of the compensatory role of torsion, and changes in viscoelastic contraction dynamics. These changes are independent of glycemic control and paralleled by the up-regulation of specific microRNAs targeting the extracellular matrix. (Cardiovascular Effects of Chronic Sildenafil in Men With Type 2 Diabetes [CECSID]; NCT00692237)

Abstract 16754: Novel Characterization of Pulmonary Artery Bending, Rather Than Stenosis, Detects Increased Right Ventricular Afterload and is Associated With Increased Right Ventricular Mass in the Post-Arterial Switch Operation Heart

Introduction: Surgical treatment of transposition of great arteries involves the Arterial Switch Operation (ASO) and the LeCompte maneuver, where the pulmonary artery (PA) and its bifurcation are translocated anterior to the neoaortic root, creating relative PA stenosis and exaggerated PA bending. Assessment of branch PA dimensions can identify stenosis, however complex 3-dimensional bending without clear stenosis may contribute to elevated right ventricular (RV) afterload. Initial data suggest elevated RV afterload and RV mass are prevalent in these patients but the etiology and associated risk factors remain unclear. Hypothesis: In post-ASO patients, more extreme PA bending, as described by radius of curvature, will be associated with elevated RV afterload and RV mass independently of relative PA stenosis. Methods: Retrospective single-center analysis of 22 post-ASO patients was performed, representing native anatomy of D-TGA with (15, 68%) and without (7, 32%) intact ventricular septum, excluding those with PA stent, pulmonary hypertension, or other anatomical confounders. RV systolic pressure (RVSP) was recorded from echocardiography (11, 50%) or catheterization (11, 50%) and correlated to cardiac magnetic resonance (CMR) imaging measurements including: radius of curvature (Rcw) weighted to differential pulmonary blood flow and RV mass indexed to body surface area. Results: In ASO patients, receiver operating characteristic curve demonstrated Rcw, but not PA stenosis, moderately detected presence of elevated RVSP (&gt;40 mmHg) (respectively: AUC 0.84, p = 0.03 and AUC 0.49, p =0.60). Patients with elevated RV Mass had more extreme Rcw (when normalized to body surface area), but no difference in PA stenosis via Nakata index (respectively: p = 0.10, p = 0.02). Conclusions: Abnormal PA bending as described by Rcw is associated with increased RV afterload and RV Mass. Rcw may serve as a promising future clinical proxy to RV afterload.

Abstract 14773: Biventricular Conversion After Fontan Completion: A Preliminary Experience

Hypothesis: Biventricular conversion (BiVC) following takedown of Fontan circulation is feasible and results in improved hemodynamics. Methods: Retrospective analysis of patients who had takedown of Fontan circulation and conversion to BiV circulation at a single center from September 2007 to April 2020. Failing Fontan physiology was defined as Fontan circulation pressure &gt;15 mmHg. Results: There were 23 patients (median age: 10.0 (7.5-13.0) years); 15 (65%) had failing Fontan physiology and 8 (35%) underwent elective takedown of their Fontan circulation. Of the 15 patients with failing Fontan physiology, 4 had exercise intolerance or cyanosis, 3 had hepatic congestion or cirrhosis, 3 had end-organ damage and 1 patient had protein losing enteropathy; the rest 4 patients had no other sign of SVP complications. A subset of patients (n=6) underwent recruitment of the non-dominant ventricle prior to conversion. HLHS (p&lt;0.01) and sub-/aortic stenosis (p&lt;0.01) were more common in these patients. BiVC with or without staged ventricular recruitment led to a significant increase in indexed end-diastolic volume (p&lt;0.01), indexed end-systolic volume (p&lt;0.01) and ventricular mass (p&lt;0.01) of the non-dominant ventricle (14 RV, 9 LV). There were 1 (4%) early and 4 (17%) late deaths. All who underwent elective BiVC survived, while 2-year survival rate for patients with a failing Fontan circulation was 72.7% (95% CI: 37-90%) (Figure 1). The overall, 1-year reintervention free survival was 44.1% (95% CI: 21-65%). Left dominant atrioventricular canal defect (p&lt;0.01) and early year of BiVC (p=0.02) were significant predictors for mortality. Conclusions: BiVC is feasible in patients with failing Fontans, and has promising outcomes after elective takedown of Fontan circulation. A staged approach for ventricular recruitment does not seem inferior to primary BiVC. The optimal timing for BiVC in Fontan patients needs further evaluation.

Abstract 13834: Low Coronary Microvascular Vasodilator Capacity Relative to Myocardial Mass Predicts Cardiovascular Risk in Hypertensive Heart Disease

Introduction: Increased left ventricular (LV) mass and coronary microvascular disease (CMD) have been independently associated with risk of heart failure (HF) and mortality in hypertensive heart disease. Inability to match increased LV mass and corresponding metabolic demand with adequate perfusion may be important in the development of HF. Hypothesis: PET-derived coronary microvascular vasodilator capacity indexed to LV mass (stress P/M) is associated with LV structure (end-diastolic volume index, EDVi, and end-systolic volume index, ESVi), LV function (LVEF) and identifies patients at elevated risk for HF hospitalization and death. Methods: We studied a retrospective cohort of consecutive symptomatic patients with hypertension presenting for rest/stress myocardial perfusion PET with LVEF ≥ 40%, normal perfusion (summed stress score &lt; 3), and no prior CAD, cardiomyopathy, or HF. Stress P/M was defined as stress myocardial blood flow (MBF) divided by LV mass. CMD was defined by myocardial flow reserve (MFR = stress/rest MBF) ≤ 1.8. Associations between stress P/M and LV structure and function were assessed, and prognostic value for HF hospitalization and all-cause mortality was evaluated. Results: We studied 358 patients: mean age 62.7±12.3y, 72.4% female. Global stress MBF was negatively associated with LV mass (β=-0.023, P&lt;0.001). Lower stress P/M was independently associated with greater EDVi (β=-0.557, p&lt;0.001), greater ESVi (β=-0.943, p&lt;0.001), and lower LVEF (β=0.819, p&lt;0.001). A below-median stress P/M conferred increased risk of mortality or incident HF hospitalization (adjusted HR=1.73 [95% CI: 1.10-2.73], p=0.02) (Figure 1A) and conferred comparable risk to CMD in those with preserved MFR (Figure 1B). Conclusions: Coronary microvascular vasodilator capacity relative to myocardial mass integrates microvascular physiology with LV structure and function and refines risk of HF and all-cause death in hypertensive heart disease.

Abstract 14794: Cmr-derived Biventricular Global Function Index is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot

Introduction: Despite improvement in outcomes, patients with repaired tetralogy of Fallot (rTOF) are at risk for ventricular tachycardia and death. Cardiac magnetic resonance (CMR) derived global function index (GFI) is a new CMR parameter that integrates ventricular volume, mass, and function. This retrospective cohort study evaluated the utility of the biventricular global function index (BVGFI) for risk stratification in patients with rTOF. Methods: Patients with rTOF who had a CMR were followed for the occurrence of a composite outcome of death, resuscitated cardiac arrest, or sustained ventricular tachycardia (VT) were studied. GFI was calculated as the (ventricular stroke volume x 100) / (ventricular mean cavity volume + total ventricular myocardial volume). Ventricular mean cavity volume was defined as [(end-diastolic + end-systolic volume) /2]. BVGFI was calculated as the average of right and left GFI. Cox regression and CART analysis were used. Results: Of the 736 eligible patients (median age at CMR 25.4 years; median follow-up 28 months), 55 patients (7.4%) reached the composite outcome (41 deaths, 14 VT). Multivariable Cox regression identified BVGFI &lt;37, RV end-systolic volume index &gt;85 ml/m 2 , atrial tachycardia , and age at repair &gt;2.5 years as independent predictors of outcome with a model C-index of 0.86. RVEF &lt;40% , which is a known predictor of worse outcomes in previous studies, was not associated with the primary outcome when BVGFI is included in the analysis and only became significant when BVGFI was excluded from the model (C-index of 0.83). Similarly, CART analysis identified BVGFI as the only binary CMR parameter to identify patients at high-risk for adverse outcomes. Conclusions: We describe a novel CMR parameter that uses readily available parameters and is associated with adverse clinical outcome after adjusting for traditional CMR parameters in rTOF. BVGFI adds prognostic information and aids in risk stratification in the population.

Abstract 13944: Biracial Proteomic Profiling Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Individuals

Background: Increased left ventricular (LV) mass is associated with future adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect black individuals. To understand the mechanisms that drive disease, particularly in black individuals, we undertook a proteomic screen in a black cohort and compared it to a white cohort. Methods: We measured 1305 plasma proteins using an aptamer-based proteomic platform (SOMAscan™) in 1772 black participants in the Jackson Heart Study (JHS) with available baseline LV mass as assessed by 2D echocardiography, as well as 1600 free of HF with follow-up assessment of incident cases. Mean follow-up time was 11 years; 152 cases of incident HF hospitalization were identified. Models were adjusted for age, sex, body mass index, estimated glomerular filtration rate (as calculated by CKD-EPI equation), systolic blood pressure, hypertension treatment, presence of diabetes, total/HDL cholesterol, prevalent coronary disease, and current smoking status. Incident HF models were also adjusted for incident coronary heart disease. We then compared protein associations in JHS to those observed in whites from the Framingham Heart Study (FHS) to examine significant differences. Results: In JHS, there were 112 proteins associated with LV mass and 10 proteins associated with incident HF hospitalization with FDR &lt;5%. Several proteins showed expected associations with both LV mass and HF, including N-terminal pro-BNP (β = 0.04 [0.02, 0.05], p = 1.0 x 10 -8 , HR = 1.46 [1.20, 1.79], p = 0.0002). The strongest association with LV mass was more novel: leukotriene A4 hydrolase (LKHA4) (β = 0.05 [0.04, 0.06], p = 2.6 x 10 -15 ). Conversely, Fractalkine/CX3CL1 showed a novel association with incident HF (HR = 1.32 [1.14, 1.54], p = 0.0003). While proteins like Cystatin C and N-terminal pro-BNP showed consistent effects in FHS, LKHA4 and Fractalkine were significantly different. Conclusions: We identify several novel biological pathways specific to black individuals hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and Fractalkine. Further studies are needed to validate these results and elucidate the detailed underlying mechanisms.

Abstract 16026: Invasive Hemodynamic Assessment of Patients With Heart Failure With Preserved Ejection Fraction With Anemia and Iron Deficiency

Introduction: Anemia is associated with increased mortality, cardiovascular events, and decreased quality of life in patients with heart failure with preserved ejection fraction (HFpEF). Iron deficiency may contribute to disease severity independent of effects on red cell mass. The hemodynamic consequences of anemia and iron deficiency in HFpEF remain unclear. Methods: We analyzed a cohort of 313 consecutive subjects with HFpEF diagnosed by invasive hemodynamic assessment, and compared echocardiographic and hemodynamic characteristics of anemic versus non-anemic subjects. Anemia was defined as hemoglobin &lt;13 g/dL in men and &lt;12 g/dL in women. Iron deficiency was defined as ferritin &lt;100 ug/L. Results: Compared to patients without anemia, HFpEF patients with anemia displayed higher NT-proBNP, elevated pulmonary artery (PA) pressures at rest and at peak exercise, and lower oxygen consumption at peak exercise (Table). There was no difference in pulmonary capillary wedge pressure (PCWP). Patients with iron deficiency were more likely to be women. At rest, patients with iron deficiency displayed lower left ventricular (LV) mass, higher resting SVRI and lower cardiac index (CI), but there were not significant differences with exercise. Conclusions: Anemia in HFpEF is associated with greater evidence of congestion and more severe pulmonary hypertension, contributing to reduced exercise capacity. Iron deficiency in HFpEF is more common in women and associated with lower cardiac output at rest, but hemodynamics are otherwise similar. Further study is required to understand the mechanisms by which anemia and iron deficiency influence cardiac function and outcomes in HFpEF.

Abstract 15613: Evaluating the Heart Failure With Preserved Ejection Fraction (HFpEF) Phenotype Amongst Persons Living With HIV; a Miami Health System Analysis

Introduction: Current evidence suggests a 1 to 2-fold increased risk of heart failure among persons living with HIV (PWH), with possible underlying mechanisms including increased vascular stiffness, chronic inflammation and myocardial toxicity. This study evaluated the prevalence of HFpEF and differences in cardiovascular complications in PWH with and without HFpEF. Methods: Participants included 257 of 965 PWH at our Special Immunology Clinic at the Jackson Memorial and University of Miami Hospitals from 2017-19. Demographic, clinical, and laboratory information, were obtained from retrospective review of the electronic health records. HFpEF was confirmed by clinical and echocardiography findings, from which H2FpEF score was derived. Patients with an EF &lt;50% were excluded. Results: The prevalence of HFpEF was 0.7%, while the mean H2FpEF score was 3.3±1.4. Thus, on average the cohort had an intermediate probability of HFpEF. When comparing persons with compared with those without HFpEF, mean age (56.4 vs. 52.0 years) and proportion of women (57.1 vs.45.0%) did not significantly differ. Similarly, groups did not differ on mean CD4 count (665 vs. 568 cells/uL, p=0.40), % with undetectable Viral Load (85.7% vs. 71.6%, p=0.41), or antiretroviral therapy use (100.0% vs. 92.8%, p=0.46). Of note, the prevalence of coronary artery disease (CAD) (14.3% vs. 1.6%, p=0.009), myocardial infarction (28.6 vs. 1.8%, p&lt;0.001), abnormal stress testing (14.3% vs. 0.8%, p=0.001), PCI (14.3% vs. 0.9%, p=0.001), type II diabetes (57.1% vs. 16.0%, p=0.003), HbA1C (8.0±2.9% vs. 5.9±1.4%, p=0.004) and chronic kidney disease (57.1% vs. 10.2%, p&lt;0.001) were higher in PWH with HFpEF. Of note, the groups had comparable mean EF (55.0 vs. 56.0%, p=0.66), diastolic dysfunction (33.3% vs. 41.9%, p=0.68), left ventricular (LV) hypertrophy (28.6% vs. 20.9%, p=0.62) and LV mass index (86.4±30.8 vs. 79.1±23.2 g/m2, p=0.34). Conclusions: The overall prevalence was similar to that reported in persons 45 years of age or more in the general population. Risk markers for atherosclerotic disease were significantly higher in PWH with HFpEF. HIV disease severity did not appear to be associated with HFpEF prevalence. Further studies evaluating the pathophysiology of HFpEF in PWH are needed.

Abstract 14054: Soluble ACE2, Cardiac Biomarkers, Structure, Function and Events: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified to a have prominent role in SARS-COV-2 infection and is an important counter-regulator of renin-angiotensin system. But the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) remains unclear. We sought to identify the association of sACE2 with cardiac biomarkers, structure, function and events in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: sACE2 was measured in a subset of 497 patients from a case-control study of incident heart failure (HF) at visit 5 (2011-2013), mean age 78 (SD 5.4), 53% men and 27% black. We used linear regression to evaluate the associations of sACE2 with cardiac biomarkers (hs-cTnI, hs-cTnT, NT-proBNP) and echocardiographic parameters. We used Cox regression to evaluate associations of sACE2 with risk of HF hospitalization, global CVD events (CHD, ischemic stroke or HF hospitalization) and all-cause death. Results: Over a median follow up of 6.1 (4.6, 6.8) years, 282 global CVD events and 190 all-cause deaths occurred. sACE2 levels were higher in men, blacks, those with prevalent CVD, diabetes and hypertension. Higher sACE2 levels were associated with significantly higher hs-cTnI, hs-cTnT, NT-proBNP levels, greater left ventricular (LV) mass index, impaired diastolic function ( Table ) and increased risk for HF hospitalization (adjusted HR 1.32 per log unit increase, 95% CI 1.10-1.58), global CVD events (HR 1.34, 95% CI 1.13-1.60) and all-cause death (HR 1.26, 95% CI 1.01-1.57). Conclusions: In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, LV mass index, impaired diastolic function, CVD events and all-cause death. Future research is needed to elucidate the significance of sACE2 in development of CVD, not only in patients with SAR—COV2 infection, but the general population

Cardio-Protective Effects of Sodium-Glucose Co-Transporter 2 Inhibitors: Focus on Heart Failure.

Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal diseases, including heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large-scale clinical trials of patients with or without diabetes and either established cardiovascular disease (CV) or multiple CV risk factors. Herein we aim to focus on the role of SGLT2 inhibitors regarding the improvement in heart failure outcomes and the proposed mechanisms of action by which these drugs confer their beneficial effect. PubMed, Embase, and Google Scholar databases were searched to identify eligible articles that are comprehensively summarized and discussed in this study. The most commonly discussed mechanisms of action are diuresis and natriuresis, reduction in preload, afterload, and ventricular mass, as well as stimulation of erythropoietin production and improved myocardial energetics. SGLT2 inhibitors improve outcomes in patients with established heart failure (HF) and reduce the risk of death and HF admissions in patients with established chronic HF with reduced ejection fraction (HFrEF), either with or without diabetes. Potential key mechanisms that may explain the notable cardioprotective benefits of SGLT2 inhibitors have been outlined. These agents have recently received class Ia recommendation in specific groups of people with DM to lower the risk of hospitalization for HF and risk of death, while these benefits may also extend to people without diabetes. It remains to be seen whether they will also emerge as treatment approaches in the acute phase of CV episodes.

Endothelial cell premature senescence exacerbates pulmonary arterial hypertension through contact-mediated interaction with vascular smooth muscle cells

Abstract Introduction Pulmonary arterial hypertension (PAH) is characterized by remodelling and stenosis of the pulmonary arteries, ultimately leading to the right heart failure and death. Endothelial cell (EC) dysfunction is thought to play a central role in the pathogenesis of PAH by mediating the structural changes in pulmonary vasculatures. Various stresses promote premature senescence in EC, which may modify vascular disorders; however, the role of EC senescence in the development of PAH remains poorly understood. Purpose We aimed at investigating the potential role of EC premature senescence in the development of PAH. Methods We recently generated EC-specific progeroid mice in which ECs specifically undergo premature senescence by overexpressing the dominant-negative form of telomere repeat-binding factor 2 (published in Nat Commun 2020). These EC-specific progeroid mice were exposed to hypoxia (10% O2 for three weeks) to induce pulmonary hypertension. Also, we prepared premature senescent ECs using human pulmonary artery ECs (hPAECs) and explored their interaction with human pulmonary artery smooth muscle cells (hPASMCs) in two different conditions; direct and indirect interactions. For indirect coculture, hPASMCs were seeded onto the culture insert, while hPAECs were plated on the culture plate, and they were cocultured in the same well and medium so that secreted factors derived from senescent ECs could access to SMCs through the insert pores. For direct coculture, hPAECs were seeded onto the bottom side of the insert, while hPASMCs were cultured on the top side of the same insert, so that cell-to-cell contact could be made through the pores. Results After chronic hypoxia exposure, the EC-specific progeroid mice showed higher right ventricular systolic pressure and increased right ventricular mass as compared to wild-type (WT) mice, indicating exacerbated pulmonary hypertension. Histological analysis of the lung revealed a significantly enhanced muscularization in the small pulmonary arteries in EC-specific progeroid mice compared to WT mice. Mechanistically, we identified that direct coculture with premature senescent hPAECs enhanced proliferation and migration in hPASMCs, while no such effects were detected in indirect coculture condition. Conclusion To our knowledge, this is the first report that reveals a crucial role of EC premature senescence in the development of PAH. Our in vitro studies suggest that contact-mediated interaction between premature senescent ECs and SMCs is critically involved in its underlying mechanism. Therefore, EC premature senescence is a novel attractive pharmacotherapeutic target for the treatment of PAH. Funding Acknowledgement Type of funding source: None