Left Ventricular Research Articles

Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis.

Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA. Consecutive ATTR-CA patients (n=100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD SPECT/CT imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n=50; high DPD uptake: >5.4, n=50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r=0.366,p<0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r=0.316,p=0.002), LV diastolic function (E/e' average: r=0.304, p=0.013), NT-proBNP (r=0.332,p<0.001), troponin T (r=0.233,p=0.022), 6-minute walk distance (6MWD: r=-0.222,p=0.033) and National Amyloidosis Centre (NAC) stage (r=0.294,p=0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: p=0.012, RV-FW-LS: p=0.036), LV diastolic function (E/e' average: p=0.035), cardiac biomarkers (NT-proBNP: p=0.012, troponin T: p=0.044), exercise capacity (6MWD: p=0.035) and disease stage (NAC stage I: p=0.045, III: p=0.006), and experienced adverse outcomes compared to the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95%CI:1.439-5.737), p=0.003; DPD retention index: adjusted HR 1.221 (95%CI: 1.078-1.383), p=0.002]. In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA.

Right atrial strain measured by 2D speckle-tracking echocardiography is associated with poor cardiac outcomes in patients with heart failure.

Right heart failure (HF) is a poor prognostic factor in patients with HF. The right atrial (RA) function has attracted less attention than the right ventricular (RV) function. The association of RA reservoir strain evaluated by 2D speckle-tracking echocardiography (2DSTE) with clinical outcomes in patients with HF remains unclear. We prospectively enrolled patients with HF admitted to our hospital. We measured the RA, RV, left atrial (LA), and left ventricular (LV) strain using 2DSTE before discharge. The RA reservoir strain (RASr) was measured in the global right atrium. The primary endpoints were cardiac death and worsening of HF requiring rehospitalization or intravenous diuretics. Among 226 patients with HF, 72 primary endpoints were recorded during a median follow-up period of 1081days. Kaplan-Meier analysis showed a higher cardiac event rate in the low RASr group than in the high RASr group (P = 0.0089). Multivariate Cox hazard analysis showed that RASr was independently associated with cardiac events after adjusting for confounding factors [hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.51-0.96; P = 0.0347]. Decreased RASr could be a feasible marker of cardiac events in patients with HF.

Impact of kidney transplantation vs. dialysis waiting for deceased donor on left ventricular diastolic dysfunction.

Left ventricular (LV) diastolic dysfunction is frequently observed in patients with end-stage kidney disease (ESKD) and a significant risk factor for the development of cardiovascular events in those patients. We hypothesized that the ratio of early diastolic peak mitral flow velocity to early mitral annulus velocity (E/e' ratio), the widely used non-invasive LV diastolic dysfunction index, would show improvements following kidney transplantation (KT). A total of 192 KT recipients who underwent echocardiography before KT and 2 years after KT were included this analysis. Moreover, 137 patients with ESKD on dialysis, waiting for deceased donor were included as a control group. Multiple linear regression analysis was used to identify the factors related to changes in the E/e' ratio. The median duration between conducting the two echocardiographies was 809 days for the KT recipients and 798 days for the controls. The mean E/e' ratio showed a significant decrease in KT recipients (10.9 vs. 9.8, respectively; p=0.002), but not in the controls (11.7 vs. 11.9, respectively; p=0.605). In multiple linear regression, KT (standardized β (SB) = -0.156; p=0.009) and administration of β blocker (BB) at enrollment (SB = -0.130; p==0.034) and at 2 years (SB=0.206, p=0.001) were significant predictors of the change in the E/e' ratio. LV diastolic dysfunction showed a noticeable improvement in the patients after KT compared to those on the waiting list and undergoing dialysis. Further studies, including patients with volume status and major cardiovascular events, may be helpful for validating these findings.

Evaluation of fetal heart size, morphology and function with fetal growth restriction using fetal HQ.

Fetal growth restriction (FGR) is associated with various perinatal complications. Limited research has focused on the fetal heart in the context of FGR. This study aimed to investigate the application value of fetal heart quantification (HQ) technology in evaluating the size, morphology, and function of the heart in FGR. A total of 31 fetuses diagnosed with FGR in our hospital from April 2022 to May 2024 were included, alongside another 31 normal fetuses matched for gestational age as the control group. Ultrasound Doppler parameters of the middle cerebral artery (MCA), umbilical artery (UA), venous catheter, and fetal HQ parameters were collected for comparative analysis, and perinatal data were followed up. Fetuses with FGR exhibited significant differences in various parameters of the MCA and UA compared to the control group (P < 0.05). The four-chamber view end-diastolic transverse width, end-diastolic area, left ventricular (LV) end-diastolic area, end-systolic area, end-systolic length, end-diastolic volume, end-systolic volume, and right ventricular (RV) end-systolic area in the FGR group were significantly lower than those in the control group (P < 0.05). In the 24-segment analysis, the LV fractional shortening in the FGR group was greater than in the control group at segments 12 to 14, while the end-diastolic diameter (ED) at segments 5 to 13 of the LV and segments 1 to 14 of the RV were smaller than those in the control group, with statistical significance (P < 0.05). Analysis of each subgroup indicated that fractional shortening (FS) in the early-onset group was significantly greater than in the late-onset group at RV segments 2 to 8. LV-ED at segments 1 to 15 and RV-ED at segments 1 to 16 were significantly smaller in the early-onset group than in the control group, and LV ED segments 20 to 21 were significantly smaller in the early-onset group compared to the late-onset group (P < 0.05). FS in the mild group was significantly larger than in the normal group at LV segments 10 to 16. The severe group exhibited significantly smaller LV segment 2 to 11 ED and the mild group showed smaller RV segments 1 to 13 compared to the control group (P < 0.05). Fetal HQ is a promising technique for evaluating the cardiac function, size, and morphology in cases of FGR.

Left ventricular myocardial deformation in patients on maintenance haemodialysis

Background Patients with chronic kidney disease (CKD) undergoing maintenance haemodialysis (MHD) develop several abnormalities of left ventricular (LV) structure and function. Speckle-tracking echocardiography permits compressive assessment of LV myocardial deformation. Previous studies involving CKD patients have shown a significant reduction in LV global longitudinal strain (GLS) with strong prognostic implications. However, the other components of LV deformation have not been fully elucidated. Methods A total of 90 CKD patients undergoing MHD (mean age 41.3 ± 12.5 years, 80% men) were compared with 45 apparently healthy age- and gender-matched controls. Results The CKD patients had a high prevalence (77.8% patients) of LV hypertrophy. They also had a significantly elevated ratio of early diastolic mitral inflow velocity to annular velocity (12.1 ± 4.6 vs. 7.1 ± 1.5, p < .001) indicating a high prevalence of LV diastolic dysfunction. LV ejection fraction (LVEF) was the same between the two groups, but the CKD patients had significantly impaired LVGLS (−17.8 ± 3.9 vs. −20.8 ± 2.6, p < .001), global circumferential strain (−14.0 ± 3.5 vs. −16.1 ± 3.4, p = .001), LV apical rotation (6.6 ± 4.7° vs. 8.8 ± 4.0°, p = .008) and LV twist (12.8 ± 6.1° vs. 15.0 ± 6.0°, p = .037). There was no difference in the global radial strain between the two groups. Conclusions The present study shows that CKD patients on MHD have significantly impaired LV longitudinal and circumferential mechanics despite preserved LVEF. The prognostic implications of reduced LVGLS have already been demonstrated previously. Future studies are needed to assess the prognostic implications of abnormal LV circumferential mechanics as well as their reversibility following renal transplant.

Electrocardiographic strain and relationship with LV remodelling and clinical outcomes in patients with aortic stenosis undergoing transcatheter aortic valve implantation.

Left ventricular (LV) remodelling and fibrosis is known to occur in patients with aortic stenosis (AS) and is linked to post-intervention outcomes. These myocardial changes may be detected upon the routine 12-lead electrocardiogram by the presence of a LV strain pattern (LVS-ECG). Although LVS-ECG has been related to excessive cardiovascular morbidity and mortality in multiple patient populations, there is currently a dearth of data upon its impact in patients undergoing transcatheter aortic valve implantation (TAVI). The aim of the current study was to investigate the prevalence, predictors and prognostic value of LVS-ECG. Between 2012 and 2019, 640 consecutive patients underwent TAVI at Haukeland University Hospital, Bergen. Of these, 600 patients with severe AS were included in the TAVI-NOR study. Patients with known bundle branch block (n=85) or permanent pacing (n=25) were excluded, leaving 490 patients (mean age 81±6years, 52% females) eligible for the analyses. LVS-ECG was defined as down-sloping, convex ST-segment depression with asymmetric T-wave inversion in V5 or V6. LVS-ECG was present in 25.7% patients. Higher levels of NT-proBNP (OR 1.96; 95% CI:1.08-3.55, p=0.028), LVEF<50% (OR 3.14; 95% CI:1.61-6.13, p=0.001), increase in LV mass index per SD (32g/m2) (OR 1.37; 95 CI:1.06-1.76, p=0.014), and the presence of LV hypertrophy on ECG (OR 3.23; 95% CI:1.97-5.32, p<0.001) were independent predictors of LVS-ECG in the multivariable-adjusted analysis. Although all-cause mortality was significantly higher in patients with LVS-ECG compared to those without (54.8% vs 44.2%, p=0.041), the presence of LVS-ECG did not predict all-cause mortality during a median follow-up of 64±24 months (HR 1.05; 95% CI:0.79-1.39, p=0.742). Patients with LVEF <50% and concomitant LVS-ECG had a worse prognosis than those with LVEF >50% and no LVS-ECG (p<0.001). LVS-ECG may represent a simple marker of structural and functional LV remodelling that signals a propensity to excess mortality during long-term follow-up after TAVI, as it is strongly associated with other prognosticators such as reduced LVEF and increased levels of NT-proBNP.

CardiLect: A combined cross-species lectin histochemistry protocol for the automated analysis of cardiac remodelling.

Cardiac remodelling, a crucial aspect of heart failure, is commonly investigated in preclinical models by quantifying cardiomyocyte cross-sectional area (CSA) and microvascular density (MVD) via histological methods, such as immunohistochemistry. To achieve this, optimized protocols are needed, and the species specificity is dependent on the antibody used. Lectin histochemistry offers several advantages compared to antibody-based immunohistochemistry, including as cost-effectiveness and cross-species applicability. Direct comparisons between the two methods are lacking from the literature. In this study, we compared antibody- and lectin-based methods for the histological assessment of cardiomyocyte CSA (with the use of anti-laminin and wheat germ agglutinin [WGA]) and microvascular density (utilizing anti-CD31 and isolectin B4 [ILB4]) using different embedding and antigen/carbohydrate retrieval techniques. Here, we describe a detailed, easy-to-use combined lectin histochemistry protocol (WGA and ILB4, 'CardiLect' protocol) for the histological assessment of cardiac remodelling. The lectin-based approach has been evaluated on a cross-species basis, and its efficacy has been demonstrated in zebrafish, rodents, large animals and human samples. We provide an ImageJ script ('CardiLect Analyser') for automated image analysis, validated in a preclinical heart failure model by correlating histological parameters with echocardiographic findings. CSA showed a significant positive correlation with left ventricular (LV) mass (P=0.0098, rS=0.7545) and significant negative correlation with markers of systolic function, such as ejection fraction (EF) (P=0.0402, rS=-0.6364). Microvascular density showed significant negative correlation with LV mass (P=0.0055, rS=-0.7622) and significant positive correlation with EF (P=0.0106, rS=0.7203). The described combined lectin histochemistry protocol with the provided ImageJ script is an easy-to-use, cost-effective, cross-species approach for the histological assessment of cardiac remodelling.

Abstract 4132838: Coronary Collaterals Provide Cardioprotection in Hemorrhagic ST-elevation MI (STEMI)

Introduction: Development of intramyocardial hemorrhage (IMH) in acute STEMI following reperfusion is estimated to affect 35-50% of patients. IMH is a lethal event as it contributes to larger MI size, compromised myocardial salvage, adverse left ventricular (LV) remodeling, lower LVEF, and consequential major adverse CV events post-MI. Whether coronary collateral circulation reduces the deleterious effects of IMH has not been investigated. Hypothesis: We hypothesized that coronary collaterals could reduce the extent of post-reperfusion IMH volume and offer cardioprotection to hemorrhagic MI patients. Methods: MIRON-CL (NCT05898425) recruited and studied STEMI patients (n=294) reperfused via PCI. Pre-PCI coronary angiography allowed for assessment of collateral vessels using the Rentrop grading system, from Grade 0 (no collaterals) to Grade III (complete collateral filling). Post-PCI cardiac MRI, performed 3 days later, was used to determine area affected (extent of myocardial edema) from T2 maps, extent of IMH from T2* maps and MI size from LGE as %LV. Statistical analyses were used to examine relationships between collateral grades, MI size, IMH, and area affected. Results: 124 patients were hemorrhagic and 170 were non-hemorrhagic. Patients with no collaterals (Grade 0; CL-) exhibited significantly higher IMH volumes (7.41 ± 5.33% LV) compared to those with collaterals (Grade I: 5.23 ± 3.21% LV, Grade II: 3.11 ± 2.78% LV, Grade III: 2.05 ± 1.89% LV; p&lt;0.001). Total area affected post-PCI was larger in CL- (37.62 ± 15.32% LV) compared to CL+ (21.48 ± 13.21% LV, p&lt;0.001). Presence of collateral circulation (Grade&gt;0 combined; CL+) was correlated with smaller MI sizes (CL-: 38.66 ± 14.63% LV vs. CL+: 19.84 ± 13.72% LV, p&lt;0.001) and reduced MVO volumes (CL-: 8.07 ± 6.60% LV vs. CL+: 2.17 ± 2.35% LV, p&lt;0.001). Patients with no collaterals had a significantly higher adj. risk of IMH (OR: 5.71, 95% CI: 3.16-10.33, p&lt;0.0001). Conclusion: Coronary collaterals reduce post-reperfusion IMH volume in STEMI patients and provide significant cardioprotection: reductions in area affected, MVO and MI size. Insight into collateral grade offers opportunities to improve risk stratification and management of revascularized STEMI patients.

Abstract 4135861: Lipoprotein(a) and Its Impact on Left Ventricular Remodeling Over a Decade: The Multi-Ethnic Study of Atherosclerosis

Background: Lipoprotein (a) (Lp[a]) is associated with an increased risk of cardiovascular disease and mortality, as well as heart failure and myocardial fibrosis. However, the link between Lp(a) and cardiac remodeling as a pathway to adverse cardiac outcomes remains unknown. Objectives: This study investigated the relationship between Lp(a) levels and longitudinal changes in the left ventricular (LV) remodeling over a decade among individuals without a previous history of cardiovascular disease. Methods: 2,366 Multi-Ethnic Study of Atherosclerosis (MESA) participants who underwent cardiac MRI at Visit 1 (2000-02) and Visit 5 (2010-12) and had available Lp(a) at baseline were examined. Lp(a) was analyzed as a continuous and a categorical variable based on quartiles (Q1[&lt;7.6 mg/dL], Q2[7.6-16.7 mg/dL], Q3[16.8-38.8 mg/dL], Q4[&gt;38.8 mg/dL]). Multivariable linear regression analysis was used to examine the association of Lp(a) with changes in cardiac MRI measures of LV remodeling ( Table ). Results: Participants had a mean age 60±9 years and 53% were women. Over 10-year follow-up, LV indexed volumes decreased, while LV indexed mass and mass to volume ratio increased across all the Lp(a) quartiles. However, LV ejection fraction only decreased in the third and fourth Lp(a) quartiles. Lp(a) examined as a continuous variable was associated with an increase in LV end-systolic indexed volume (per log-unit Lp[a]; β 0.32 mL/m 2 ; P = 0.01), LV indexed mass (per log-unit Lp[a]; β 0.38 g/m 2 ; P = 0.02), and a decrease in LV ejection fraction (per log-unit Lp[a]; β -0.29 %; P = 0.02) over 10 years after adjusting for sociodemographic and traditional cardiovascular risk factors ( Table ). Similarly, the fourth Lp(a) quartile was associated with an increase in LV end-systolic indexed volume (β 1.07 mL/m 2 ; P = 0.01), LV indexed mass (β 1.17 g/m 2 ; P = 0.02) and a decrease in LV ejection fraction (β -1.01 %; P = 0.01) compared to the first Lp(a) quartile after controlling for risk factors. The observed associations remained significant after further adjusting for aortic valve calcium score at Visit 1 ( Table - Model 3), and baseline coronary artery calcium score and interim myocardial infarction ( Table - Model 4). Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, higher Lp(a) levels were independently associated with an increase in LV end-systolic volume and LV mass as well as a decrease in LV ejection fraction over the span of a decade.

Abstract 4138589: Prognostic implications of Biventricular systolic and diastolic strain in diabetes without coronary artery diseases.

Background: 2D-speckle-tracking echocardiography (2D-STE) has emerged as useful to assess subclinical myocardial dysfunction, however its utility in diabetes milletus (DM) has been limited to the evaluation of left ventricular (LV) longitudinal systolic function. Aim: To assess the differences and prognostic implications of left (LV) and right (RV)ventricular systolic and diastolic strain parameters in DM. Methods: Of the initial 1721 DM patients screened for this study only 513 consecutive patients with DM were eligible and retrospectively enrolled, and 2D-STE strain (longitudinal, circumferential and radial) parameters assessed on the 2D-TTE images. All patients were prospectively followed for development of new outcome/cardiac events which included hospitalization for acute HF, CVS-related death, heart transplantation, and also diabetic complications. The 2D-STE analysis was used to measure the peak LV (longitudinal, radial and circumferential) and RV (longitudinal and radial) strain parameters. The long-term outcomes were evaluated for all-cause CVS outcomes and recurrent hospitalization. Results: For the 513 eligible patients [mean age: 51±8; 62 % male sex], 263 reached the combined endpoint during a mean follow-up of 1.4±0.6years. Conventional TTE was performed in all subjects and reviewed. Both LV and RV strain parameters were significantly impaired compared to normal standard references (p&lt;.0001), where RV was more impaired than LV strain parameters. Th e best performance parameters predictive of CVS events were RV systolic and diastolic strain than global LV longitudinal systolic and diastolic strain. The strongest association between the degree of myocardial dysfunction and CVS risk was more evident for RV strain (free wall &gt; global strain) and lesser extend to LV strain. More myocardial strain impairments were demonstrated in those with higher left atrial volume index, impaired diastolic function, lower strain values ( LV, RV), and reduced tricuspid annular plane systolic excursion, p&lt;.001). RV strain and to a lesser extend LV strain impairment were independent predictors of combined outcomes after multiple adjustments using different models. Conclusion: Patients with Diabetes, RV and LV strain parameters are stronger (RV&gt;LV strain) predictors of outcome than other conventional parameters and should be included for regular clinical screening DM patients as these parameters provide a stronger prognostic stratification

Abstract 4117594: Fetal Synthetic Glucocorticoid (sGC) Exposure Results in Later Life Cardiac Dysfunction and Ventricular Remodeling in Male Baboon Offspring

The “theory of developmental origins of health and disease” posits that stress in critical developmental periods will program life-course health and may affect cardiovascular (CV) health. Mothers at risk for premature delivery receive synthetic glucocorticoids (sGC) to enhance fetal lung maturation and manage fetal respiratory distress, but sGC exposure is linked to long-term CV dysfunction in offspring. Four groups of male baboons were studied: sGC exposed in utero at middle age (sGC-MA, 13.8±0.2Y), older sGC exposed in utero (sGC-O, 17.1±0.4Y), middle age unexposed (CTR-MA, 13.5±0.6Y), and older, unexposed baboons (CTR-O, 17.4±0.4Y). Gated, breath-hold, cine cardiac magnetic resonance imaging was performed at 3 Tesla (Siemens TIM Trio) to assess left ventricular (LV) function and myocardial strain, analyzed using cvi42® software. Mitochondrial electron transport chain (ETC) complex activity was analyzed using LV tissue from sGC-O and CTR-O euthanized baboons. Protein quantification was used to measure mitochondrial function and RNA-seq assessed differential gene expression and gene ontology (GO) enrichment. Unpaired t-tests were used. Data are reported as mean ± SD. Stroke volume and ejection fraction were similar in the elderly groups (4 sGC-O, 8 CTR-O). However, higher end-systolic and end-diastolic sphericity indexes (SI) and shorter LV axis lengths indicated remodeling. Also, global longitudinal and radial strains were reduced (both p&lt;0.04) in sGC-O vs. CTR-O. Reduced LV cardiac output (p=0.005) was found in 5 sGC-MA animals vs 4 sGC-O animals, but not in 5 CTR-MA vs 8 CTR-O. In sGC-MA vs sGC-O, but not CTR-MA vs CTR-O, significant increases in SI (p=0.001), radial strain (p=0.02), and longitudinal (p=0.03) strain were found, but LV axis length (p=0.03) was reduced. LV mitochondrial analysis in 4 sGC-O vs 4 CTR-O myocardial samples revealed 33.5% less ETC activity (p=0.002) and 19.8% less complex I expression (p=0.048) in sGC. LV RNA-seq identified 63 upregulated and 20 downregulated genes in the sGC-O samples. GO pathway enrichment included changes in heart contraction, wounding responses, and leukocyte regulation pathways. These findings indicate that fetal sGC exposure developmentally programs offspring with LV remodeling and long-term cardiac and gene expression changes in male baboons, the closest available experimental nonhuman primate species to man. Future studies on females will probe sexual dimorphism in developmental programming.

Abstract 4136016: Higher aircraft noise exposure associates with worse heart structure and function

Introduction: Aircraft noise is a concern for communities living near airports, but its impact on heart structure and function is unknown. Methods: Night-time (L night ) and weighted 24-hour day (L den ) aircraft noise levels were provided by the UK Civil Aviation Authority for 2011 (Fig.1). Health data came from UK Biobank (UKB) participants living near four UK major airports (Heathrow, Gatwick, Manchester, and Birmingham) who had cardiovascular magnetic resonance (CMR) imaging starting from 2014 and self-reported no hearing difficulties. Generalized linear models investigated the associations between aircraft noise exposure and CMR metrics (derived using a validated convolutional neural network to ensure consistent image segmentations), after adjustment for demographics, socio-economic, lifestyle, and environmental covariates. Mediation by cardiovascular (CV) risk factors was also explored. Downstream associations between CMR metrics and major adverse cardiac events (MACE) were tested in a separate prospective UKB subcohort (n=26,658) to understand the potential clinical impact of noise-associated heart remodeling. Results: Of 3,635 UKB participants included, 3% experienced higher aircraft noise L night (≥45decibels) and 8% higher L den (≥50decibels). Participants exposed to higher L night had 7% [95% confidence interval: 4–10%] higher left ventricular (LV) mass and 4% [2–5%] thicker LV walls with a normal septal:lateral wall thickness ratio (Fig.2 A1). This LV concentric remodeling is relevant since 7% higher LV mass associates with 32% higher odds of MACE. They also had worse LV myocardial dynamics (Fig.2 A2) (e.g., 8% [4–12%] lower global circumferential strain which associates with 37% higher odds of MACE). Overall, a hypothetical individual experiencing the typical CMR abnormalities associated with higher L night exposure may have 5-times higher odds of MACE. Body mass index and hypertension appeared to mediate 20-50% of the observed associations. Findings were similar in those exposed to higher L den (Fig.2 B1-2). Participants who did not move home during follow-up and were continuously exposed to higher aircraft noise levels had the worst CMR phenotype. Conclusion: Higher aircraft noise exposure associates with adverse LV remodeling, potentially due to noise increasing the risk of obesity and hypertension. Findings are consistent with the existing literature on aircraft noise and CV disease, and need to be considered by policymakers and the aviation industry.

Abstract 4148070: Clonal Hematopoeisis of Indeterminate Potential and Risk of Autopsy-defined Sudden Cardiac Death

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with an increased risk of coronary artery disease (CAD) and cardiovascular (CV) mortality. Whether CHIP may affect myocardium beyond promoting CAD, or its potential association with sudden cardiac death (SCD), the most feared manifestation of CV disease, is unknown. Research Questions/Hypothesis: We hypothesize that CHIP-mutant macrophages infiltrate the myocardium and are associated with autopsy-defined arrhythmic death. Goals/Aims: (1) determine rate of CHIP at time of death in an unselected, countywide study of all incident sudden deaths; (2) evaluate whether CHIP-mutant macrophages infiltrate into myocardium; and (3) evaluate potential association of CHIP with autopsy-confirmed arrhythmic causes among countywide sudden deaths Methods/Approach: We used autopsy to adjudicate arrhythmic from non-arrhythmic (PE, stroke, overdose, tamponade) causes in 1,148 sudden deaths and 141 trauma control deaths in San Francisco County from 2011-23. DNA was extracted from frozen blood samples collected at time of death from 399 consented cases. Sequencing of 22 CHIP-associated genes was performed to ~2000x mean target coverage. All pathogenic/likely pathogenic CHIP variants at &gt;2% variant allele frequency (VAF) were considered CHIP+. DNA was then isolated from left ventricular (LV) tissue sampled at autopsy in all CHIP+ blood cases and sequenced as above. Results: Of 399 consented cases, 70 blood samples (17.5%) were CHIP+ (range 2%-39.6%; mean age 70.6 years vs. 58.1 years for CHIP-). The most frequent mutant genes were DNMT3A, TET2, and ASXL1. Proportion of arrhythmic causes among sudden deaths was similar for CHIP+ vs. CHIP- cases (36 of 70 [52%] vs. 171 of 329 [51%]). Sequencing of available LV tissue from 61 CHIP+ blood cases revealed 67% (n=41) harbored the same CHIP mutation identified in blood at &gt;0.2% VAF (range 0.2%-4.3%). Proportion of arrhythmic causes among sudden deaths was significantly higher in cases where both blood and LV were CHIP+ (24 of 41 [58.5%] vs. 5 of 19 [26.3%] CHIP+ blood/CHIP- LV, p=0.02). Conclusions: Prevalence of CHIP positivity at sudden death is similar to published studies and correlated with age. CHIP+ status in myocardial tissue but not peripheral blood was associated with arrhythmic causes of sudden death, suggesting a direct tissue effect of CHIP-mutant macrophages.

Abstract 4141497: Left ventricular diastolic function by echocardiography is related to extracellular volume and is an independent predictor of mortality in patients with aortic regurgitation

Background: Cardiac catheterization along with cardiac biopsy studies have shown the presence of abnormally increased left ventricular (LV) chamber stiffness in patients with severe aortic regurgitation (AR) and its significant correlation with interstitial fibrosis. LV diastolic dysfunction (DD) is associated with increased mortality in several patient populations. However, there is a paucity of data on the association of DD with mortality in patients with AR. Hypotheses: 1 - LV DD is related to extracellular volume (ECV), imaging marker of interstitial fibrosis, by cardiac magnetic resonance imaging (CMR) 2 - LV DD by echocardiography is associated with mortality in patients with AR Methods: We studied patients with moderate or greater AR who underwent echocardiographic and CMR imaging within 12 months. We excluded patients with concomitant valve disease, prior valve intervention, cardiomyopathy deemed unrelated to AR, congenital heart disease and terminal conditions. The primary outcome was all-cause death. CMR was used to obtain LV volumes, EF and mass, AR severity, scar extent by delayed hyperenhancement, and ECV. DD was assessed by comprehensive echocardiography. Results: The study included 323 patients. Mean age was 61.9 ± 16.0 years and 22% were female. Median follow-up was 3.8 years, during which 65 patients died and 172 had aortic valve replacement. Median LV EF was 56 (47-65) %, AR volume on CMR was 40 (30-61) mL, and AR fraction was 40 (33-47) %. ECV progressively increased with higher grades of LV DD (Figure 1). Table 1 shows the univariate associations with mortality in the study. On multivariable analysis based on the Lasso variable selection process, Euroscore, Charlson comorbidity index, DD grade, and RAP were associated with total mortality. Conclusion: ECV by CMR progressively increases with higher grades of DD by echocardiography, and DD is independently associated with mortality in patients with AR.

Abstract 4145884: Left ventricular 3D-sphericity is associated with 92 genetic loci

Introduction: Left ventricular (LV) sphericity is a measure of the degree to which the LV blood pool resembles a sphere. Analyses of cardiovascular magnetic resonance imaging (MRI) in the MESA cohort have shown that LV sphericity is an important mode of variation in cardiac structure that is associated with ischemia, heart failure, and atrial fibrillation. A recent genome-wide association study (GWAS) of a two-dimensional estimate of sphericity in 38,000 UK Biobank participants identified 4 genetic loci (near PDZRN3, HLA, PLN, and ANGPT1). Genetic contributions to three-dimensional (3D) sphericity remain unknown. Aims: To measure 3D sphericity from cardiovascular MRI at scale and characterize the genetic contributions to 3D sphericity. Methods: Deep learning models were constructed to perform semantic segmentation in the short- and long-axis view from cardiovascular MRI in UK Biobank. These models were applied to all participants with MRI. Poisson surface reconstruction was used to build 3D meshes of the left ventricle. Sphericity was estimated at end-systole and end-diastole as the area of a perfect sphere with the same volume as the left ventricle, divided by the estimated surface area from the mesh. Heritability was estimated with ldsc; GWAS was conducted with REGENIE. Results: Sphericity was estimated in 68,978 individuals, of whom 3,096 were excluded due to atrial fibrillation or atrial dysfunction, and 2,686 were excluded during genetic quality control; 63,196 participants were included in the GWAS. Ldsc heritability was 29.7% for sphericity in diastole and 26.0% for sphericity in systole. 49 genetic loci were associated with 3D sphericity in diastole as were 64 in systole (92 distinct loci). 46 of these loci were unique to sphericity and not found for other LV traits, including loci near the genes encoding calsequestrin 2, troponin T2, palladin, supervillin, and angiopoietins 1 and 2. Shared loci included those near RXFP4, encoding a relaxin-family peptide receptor, and MICU2 (previously implicated in cardiac relaxation). Conclusion: Left ventricular sphericity is heritable, with genetic underpinnings distinct from standard LV measurements.

Abstract 4136694: Impact of left ventricular support devices on myocardial and pulmonary recovery in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation

Background: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is used to treat cardiogenic shock. However, retrograde arterial perfusion from the femoral artery can increase left ventricular (LV) afterload, resulting in LV distention which may hamper myocardial recovery and worsen pulmonary congestion. An intra-aortic balloon pump (IABP) can mitigate LV afterload, and Impella (Abiomed, Danvers, MA) can directly unload LV pressure. This study aimed to evaluate the efficacy of LV support devices during VA-ECMO in patients with cardiogenic shock. Methods: We retrospectively collected data from 213 consecutive patients treated with VA-ECMO due to cariogenic shock at our institution between January 2013 and December 2023. Patients were categorized as either receiving VA-ECMO alone or VA-ECMO with an LV support device. The LV support device was characterized as VA-ECMO with IABP or Impella. Data were analyzed for mortality, weaning from VA-ECMO, and changes in pulmonary congestion using the congestion score index (CSI), which is a semi-quantitative approach to pulmonary congestion based on a 6-zone evaluation of chest radiography, scoring each zone from 0 (no congestion) to 3 (intense pulmonary edema). Results: In this study, 95 patients received VA-ECMO alone, whereas 118 patients received an LV support device (101 VA-ECMO with IABP and 17 VA-ECMO with Impella). LV support devices improved weaning from VA-ECMO (odds ratio, 3.09 [95% confidence interval (CI), 1.75–5.55]; p&lt;0.0001) whereas there was no difference in IABP versus Impella cohorts. Compared with VA-ECMO alone, patients with VA-ECMO with an LV support device had better survival at 30 days (OR, 3.04 [95% CI, 1.73–5.43]; p&lt;0.0001). The rate of survival to discharge was better in VA-ECMO with an LV support device versus VA-ECMO alone (hazard ratio, 2.51 [95% CI, 1.72–3.65]; p&lt;0.0001). The evaluation of pulmonary congestion using the CSI revealed that congestion significantly improved in VA-ECMO with Impella (changes of CSI: 1.86 to 1.36) but not in VA-ECMO with IABP (1.80 to 1.96) and VA-ECMO alone (1.94 to 2.14). Conclusion: An LV support device may be associated with reduced mortality and increased success in weaning off VA-ECMO in patients with cardiogenic shock. Impella may be particularly effective in reducing pulmonary congestion.

Abstract 4131736: Myocardial Work in Patients with Systemic Arterial Hypertension: Correlation with Left Ventricular Mass and Aortic Strain Lidia Capotosto 1,2 , Enrico Mangieri 2 , Gaetano Tanzilli 2 , Giuseppe Placanica 2 , Attilio Placanica 2 , Fabio Miraldi 2 , Antonio Vitarelli 1,21 Department of Echocardiography, Cardiodiagnostica CS, Rome, Italy, 2 Department of Cardiology and Cardiac Surgery, Sapienza

Background: Myocardial work (MW) is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure-strain loops and has been validated against invasively derived pressure-volume measurements. The purpose of the present study was to analyze whether systemic arterial hypertension is associated with abnormal left ventricular (LV) function assessed by myocardial work and how these changes are related to left ventricular hypertrophy (LVH) and aortic strain. Methods: We examined 86 hypertensive (mean age, 66±14 years, 51% male) and 86 sex- and age-matched healthy controls (mean age, 64±15 years, 53% male). Hypertensive patients were divided into two groups: patients without LVH (group-A) and patients with LVH (group-B, LVMI&gt;115g/m2 men, LVMI&gt;95g/m2 women). All of them had preserved LV ejection fraction. Global LV longitudinal strain (GLS) was calculated by speckle tracking echocardiography. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Corrected circumferential aortic strain (Ao-S) was calculated in the ascending aorta by two-dimensional speckle tracking echocardiography as global aortic strain /pulse pressure. Data analysis was performed offline (GE EchoPAC). Results: GWI and GCW were increased in group-A compared to controls (p&lt;0.05) and decreased in group-B (p=0.04). GWW was increased in group-A(p=0.02) and group-B(p&lt;0.001). GWE was decreased in group-A(p&lt;0.01) and group-B(p&lt;0.005). There was a positive correlation between GWE and Ao-S(r=0.51,p=0.03). GWE was independently associated with GLS(β=0.26,p=0.034), LV mass(β=0.31,p=0.02) and Ao-S(β=0.37,p=0.01) in the whole hypertensive population. At the receiver operating characteristic (ROC) analysis, optimal cutoff values of GWI, GLS, Ao-S, GWE and (GWE+Ao-S) discriminating LV hypertrophy were 0.7329, 0.7613, 0.8011, 0.8442 and 0.8986, respectively. Conclusions: Decreased GWE in systemic hypertension was related to aortic strain and occurred even in the absence of LV hypertrophy. Additional assessment of aortic strain improved the ability of myocardial work variables to differentiate patients with LVH, patients without LVH, and control subjects.

Abstract 4121970: Early to Mid-Gestational Testosterone Excess Sex-specifically Reprograms Cardiac Transcriptome and Metabolome Profiles of Sheep Fetuses

Exposure of sheep to excess testosterone (T) from days 30-90 of gestation (term 147 days) perturbs maternal systemic lipidome in late gestation, induces fetal growth restriction and sexually dimorphic perturbation in the cardiac left ventricular (LV) transcriptome in gestational (GD) day 90 fetuses culminating in cardiometabolic dysfunction in adult female offspring. We hypothesized that the detrimental impact of prenatal T excess on fetal cardiac transcriptome is a programmed event that will persist even after cessation of excess T exposure and will be accompanied by changes in fetal metabolome. Pregnant ewes were injected with 100 mg intramuscular T propionate or vehicle (C), twice weekly from GD 30-90. On GD120±5, 30 days after cessation of T treatment fetal weights were recorded, left ventricle (LV) tissue and fetal plasma processed for transcriptomics by RNA sequencing and metabolomics analysis (Female C (FC) n=6, T (FT) n=7; Male C (MC) n=6, T (MT) n=7). LV transcriptome-based pathways enrichment analysis revealed 1) downregulation of pathways associated with oxidative phosphorylation, citric acid cycle, pyruvate metabolism; 2) upregulation of TGF-β signaling pathway in T fetuses compared to C (p&lt;0.05, FDR&lt;0.1); 3) selective downregulation of the glycolytic pathway in MT relative to MC as opposed to downregulation of mitochondria-related pathways in FT vs FC (p&lt;0.05, FDR&lt;0.1). LV lipidomics analyses found glycerophospholipids and sphingolipids as main class lipid metabolites to be enriched in FT relative to FC fetuses (p&lt;0.05, ER&gt;1). Fetal systemic lipidome main class metabolites enriched (p&lt;0.05, ER&gt;2) in T vs C fetuses included 1) sphingomyelins in both sexes 2) fatty acyls metabolites only in MT vs MC as opposed to glycerophospholipids only in FT vs FC. LV polar metabolites enriched (p&lt;0.05, ER&gt;2) included 1) arginine&amp;proline metabolism pathways in T vs C in both sexes 2) nicotinate and nicotinamide metabolism only in MT vs MC (p&lt;0.05, ER&gt;3), and porphyrin, riboflavin metabolism and N-glycan biosynthesis pathways only in FT vs FC. Systemic polar metabolites enriched (p&lt;0.05, ER&gt;2) included 1) D-amino acid metabolism pathways in T vs. C, 2) valine, leucine, and isoleucine pathways only in FT vs FC and glycerophospholipid and sphingolipid metabolism only in MT vs MC. These results suggest persistence of sex-specific perturbation in fetal transcriptome and systemic and cardiac metabolome in late gestational fetuses exposed to prenatal T excess.

Abstract 4134305: Intraoperative indicators depending on QRS morphology are required to narrow QRS width during CRT implantation

Introduction: Various indicators to detect the most delayed electrical or mechanical activation site of left ventricular (LV) have been studied using intracardiac electrocardiogram or speckle tracking echocardiogram to narrow QRS width in patients with cardiac resynchronization therapy (CRT). Hypothesis: Unusual intraoperative indicators are required to narrow QRS width in patients with non-LBBB (left bundle branch block) during CRT implantation. Methods: Nineteen patients (14 men, 71±12yrs, 7 with left bundle branch block: LBBB / 10 non-LBBB / 2 pacing-depend, 6 ischemic cardiomyopathy, LVEF 29.6±8.9%, QRS 152±28ms) underwent CRT implantation. Q-LV (an interval from QRS onset to LV potential), RV-LV (from RV to LV), RVp-LV (from RV pacing to LV), and S-QRS (from LV pacing stimulation to QRS onset) were measured in multi-sites of coronary sinus (CS) veins using a 5 mm spacing 2Fr 8-polar catheters. Q-peak strain (an interval from QRS onset to peak radial strain) was evaluated by speckle tracking echocardiogram in each LV segment during sinus rhythm (SR) and RVp. QRS narrowing was defined as the difference between the QRS interval during SR (or RVp) and the QRS interval with biventricular pacing. Results: Parameters were evaluated in 17±7 (8-32) sites of 1.9±0.9 (1-4) CS branches in each patient. In LBBB patients, longer Q-LV during SR, extended RV-LV during SR, and lengthy Q-peak strain during SR were associated with QRS narrowing. Shorter S-QRS during LVP and longer RVP-LV during RVP were related to QRS narrowing in non-LBBB patients. (Table) Conclusion: Suitable indicators depending on QRS morphology are required for QRS narrowing in CRT implantation. The parameters using speckle tracking echocardiogram to detect mechanical LV delay sites might not be useful in patients with non-LBBB.

Abstract 4143219: Pressure-Volume Analysis by Three-Dimensional Echocardiography: A Novel Method to Estimate Left Ventricular Efficiency

Background: Left ventricular (LV) efficiency is a key pathophysiological marker in heart failure (HF). LV pressure curve estimation and three-dimensional (3D) volumes via echocardiography allows for non-invasive pressure-volume (PV) analysis and calculation of an index of efficiency (Figure 1). Aim: Validate efficiency index by 3D echocardiography by comparing it to invasive measurements and efficiency derived from Positron Emission Tomography (PET) metabolism. Methods: Two experimental models were utilized - one with canines (n=21) and another with sheep (n=12). In canines, echocardiography provided 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting the time axis of a reference pressure curve to the valve events and its amplitude to measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Invasive pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Non-invasive and invasive efficiency indices, calculated as the ratio of stroke work to total mechanical energy (Figure 1), were compared during baseline, right ventricular pacing, aortic constriction and dobutamine infusion. Twelve sheep implanted with a pacemaker underwent 8 weeks of rapid dyssynchronous DDD pacing to induce dilated HF. LV efficiency index was calculated as in Figure 1, using measurements from a PV-catheter calibrated to end-diastolic volume by cardiac MRI, and compared to efficiency calculated as stroke work divided by total LV glucose metabolism via PET/CT. Recordings were performed during AAI and DDD pacing, at baseline (n=3) and following 8 weeks pacing-induced HF (n=12). Results: In canines, non-invasive and invasive efficiency indices showed excellent agreement (r=0.95, p&lt;0.0001; mean difference 0.4%, SD 3.4%) (Figure 2). In sheep, the efficiency index showed similar decline compared to efficiency by PET/CT after induction of HF and after switching from AAI to DDD pacing (p&lt;0.05 for all interventions). Overall correlation between the methods was moderate (r=0.67, p=0.0001) but excellent in animals with longitudinal data (r=0.89, p=0.0001) (Figure 3). Conclusions: Efficiency index by 3D echocardiography is accurate and reflects changes in efficiency measured by PET/CT. It may thus be of interest for clinical use.