Left Ventricular Structural Changes Research Articles

Cardiac remodeling in rheumatoid arthritis: assessing the influence of anti-CCP and rheumatoid factor

Abstract Background Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF), markers of Rheumatoid Arthritis (RA) activity, are associated with adverse cardiovascular outcomes, suggesting a potential link between RA and cardiac remodeling. Purpose Our study aimed to explore the correlation between antibody levels (anti-CCP and RF) and left ventricular (LV) remodeling in RA patients without known heart disease. Additionally, it sought to identify other disease-related factors that correlate with LV remodeling. Methods A cross-sectional study of 124 RA patients aged ≥ 18 years, classified per the 2010 ACR/EULAR criteria, collected blood samples for CRP, and antibody levels (RF ≥ 20 IU/ml and anti-CCP ≥ 5 IU/ml via ELISA). Transthoracic echocardiography (TTE) was conducted using a linear method in a long-axis parasternal 2D window. Sixty-two patients exhibited LV remodeling and were matched with 62 patients without it. Echocardiographic variables included were those to calculate the relative wall thickness (RWT, cut-off value 0.42) and left ventricular mass index (LVMI, cut-off values of 43-95 g/m2 in women and 49-115 g/m2 in men) along with left ventricular end diastolic (LVIDd), and systolic volumes (LVIDs), and left ventricular ejection fraction (LVEF). Statistical analyses employed the Chi-square test, Student's t-test, or Mann-Whitney U test as applicable, with correlations assessed using Spearman's rho, an analysis was conducted on the area under the curve (AUC) and a significance level of p ≤ 0.05. Results The most common type of LV alteration in our study was concentric remodeling (74.2%). A statistically significant difference was observed in the levels of Anti-CCP titers 193.85 IU/ml (p < .001), RF IgM 200.00 IU/ml (p < .001) and IgA 185.5 IU/ml (p < .001) in patients with LV remodeling. Anti-CCP and RF IgA antibody levels exhibited a moderate correlation with the presence of LV remodeling, with rho 0.387 (p < .001) and rho 0.344 (p < .001), respectively. The RWT showed a moderate correlation with anti-CCP titers with rho 0.298 (p .001). AUC analysis anti-CCP titers demonstrated better diagnostic performance for the existence of cardiac remodeling (0.722, 95% CI 0.628-0.816, p < .001), RF IgA (0.696, 95% CI 0.602-790, p < .001) and IgM (0.650, 95% CI 0.563-755, p .002). Conclusion In summary, among RA patients without heart failure (HF), LV remodeling and elevated RWT correlate with antibody levels independently of traditional cardiovascular risk factors. Patients with altered LV geometry exhibit higher antibody titers, highlighting the need for RA-related biomarkers that correlate with changes in LV structure and function Recognizing association between autoimmunity and HF development holds significant implications for both prevention and treatment strategies in RA patients.

Maternal hypertensive disorders of pregnancy and electrocardiographic findings among newborns: The Copenhagen Baby Heart Study.

Maternal preeclampsia is associated with both congenital heart defects and changes in left ventricular structure and function in the offspring. Whether preeclampsia and gestational hypertension also affect the offspring's cardiac conduction system is unknown. This study assesses whether infants exposed to maternal hypertensive disorders of pregnancy (HDPs) exhibit changes in their electrocardiogram (ECG) compared with infants unexposed to HDPs. This population-based cohort study included newborns from the Copenhagen Baby Heart Study who had an ECG performed within 30 days of birth and had available obstetric information. ECG parameters of newborns exposed to maternal HDPs were compared with those of unexposed newborns using linear regression. Our study cohort included 11,826 newborns, including 441 exposed to maternal preeclampsia and 320 exposed to gestational hypertension. Infants exposed to preeclampsia had prolonged QRS durations (adjusted mean difference 0.6 ms, 95% confidence interval [CI] 0.04, 1.16) and lower maximum amplitudes of the R-wave in V1 (adjusted mean difference, linear scale 0.95, 95% CI 0.90, 1.00), compared with unexposed infants. Exposure to maternal preeclampsia was not associated with changes in other ECG parameters. Exposure to gestational hypertension was associated with increased QT interval durations (QTc Bazett, adjusted mean difference 2.48 ms, 95% CI -0.23, 5.20; QTc Fridericia, adjusted mean difference 2.32 ms, 95% CI -0.19, 4.83). Our findings suggest that the newborn cardiac conduction system is affected by exposure to maternal preeclampsia. This could reflect the previously described thickening of the left ventricular myocardium in infants exposed to preeclampsia.

NT-proBNP and Cardiac Troponin I, but Not Cardiac Troponin T, Are Associated With 7-Year Changes in Cardiac Structure and Function in Older Adults: The ARIC Study.

Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized. Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest. Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P>0.05). Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors.AQ.

Racial Differences in Age-Related Changes in Left Ventricular Structural and Functional Echocardiographic Measurements Among Healthy Japanese and American Participants - A Subanalysis of the World Alliance Society of Echocardiography Normal Values Study.

Age-related changes in left ventricular (LV) structure and function lower the threshold for the onset of heart failure with preserved ejection fraction (HFpEF). LV parameters change also with race; however, the racial differences in age-related changes in LV parameters with and without adjustment for body mass index (BMI), heart rate (HR), and blood pressure (BP) remain unclear. We performed a subanalysis of the World Alliance Society of Echocardiography Normal Values Study, an international cross-sectional study that examined normal echocardiographic values in 15 countries. The age-related changes in 2-dimensional echocardiographic derived parameters including LV size, systolic function, and mass, were compared between healthy Japanese (n=227) and healthy White (n=98) and Black (n=69) American participants. In men, age-related changes in all parameters did not differ significantly among races. However, compared with Japanese women, White American women had a smaller body surface area (BSA)-indexed LV volume, BSA-indexed LV internal dimension at end-systole, BSA-indexed LV stroke volume, and LV mass index to BSA, and a larger LV ejection fraction with age, even after adjusting for BMI, HR, and BP. Age-related changes in LV structure and function, which are important for the pathophysiology of HFpEF, may differ by race. Therefore, future studies examining echocardiographic reference values for each age group in each race are needed.

Heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and has a prevalence that is expected to rise with the growing ageing population. HFpEF is associated with significant morbidity and mortality. Specific HFpEF risk factors include age, diabetes, hypertension, obesity and atrial fibrillation. Haemodynamic contributions to HFpEF include changes in left ventricular structure, diastolic and systolic dysfunction, left atrial myopathy, pulmonary hypertension, right ventricular dysfunction, chronotropic incompetence, and vascular dysfunction. Inflammation, fibrosis, impaired nitric oxide signalling, sarcomere dysfunction, and mitochondrial and metabolic defects contribute to the cellular and molecular changes observed in HFpEF. HFpEF impacts multiple organ systems beyond the heart, including the skeletal muscle, peripheral vasculature, lungs, kidneys and brain. The diagnosis of HFpEF can bemade in individuals with signs and symptoms of heart failure with abnormality in natriuretic peptide levels or evidence of cardiopulmonary congestion, facilitated by the use of HFpEF risk scores and additional imaging and testing with the exclusion of HFpEF mimics. Management includes initiation of guideline-directed medical therapy and management of comorbidities. Given the significant impact of HFpEF on quality of life, future research efforts should include a particular focus on how patients can live better with this disease.

99mTc-HFAPi SPECT imaging predicts left ventricular remodeling after acute myocardial infarction

BackgroundDespite improved treatments for acute myocardial infarction (AMI), myocardial fibrosis remains a key driver of adverse left ventricular (LV) remodeling and increased mortality. Fibroblast activation and proliferation significantly contribute to this process by enhancing cardiac fibrosis, which can lead to detrimental changes in LV structure. This study evaluates the effectiveness of 99mTc-labeled fibroblast activation protein inhibitor (99mTc-HFAPi) SPECT imaging in predicting LV remodeling over 12 months in post-AMI patients. MethodsA cohort of 58 AMI patients (46 males, median age 61 [53, 67] years) underwent baseline 99mTc-HFAPi imaging (5 ± 2 days post-MI), perfusion imaging (6 ± 2 days post-MI), and echocardiography (2 ± 2 days post-MI). Additionally, 15 patients had follow-up 99mTc-HFAPi and perfusion imaging, while 30 patients had follow-up echocardiography. Myocardial 99mTc-HFAPi activity was assessed at the patient level. LV remodeling was defined as a ≥10% increase in LV end-diastolic diameter (LVEDD) or LV end-systolic diameter (LVESD) from baseline to follow-up echocardiography. ResultsAMI patients displayed localized but non-uniform 99mTc-HFAPi uptake, exceeding perfusion defects. Baseline 99mTc-HFAPi activity exhibited significant correlations with BNPmax, LDHmax, cTNImax, and WBCmax, inversely correlating with LVEF. After 12 months, 11 patients (36.66%) experienced LV remodeling. Univariate regression analysis demonstrated an association between baseline 99mTc-HFAPi uptake extent and LV remodeling (OR = 2.14, 95%CI, 1.04, 4.39, P = 0.038). Conclusions99mTc-HFAPi SPECT imaging holds promise in predicting LV remodeling post-MI, providing valuable insights for patient management and prognosis.

Cardiac Reverse Remodeling Mediated by HeartMate 3 Left Ventricular Assist Device: Comparison to Older Generation Devices.

Currently, the fully magnetically levitated left ventricular assist device (LVAD) HeartMate 3 (HM3) is the only commercially available device for advanced heart failure (HF) patients. However, the left ventricular (LV) functional and structural changes following mechanical unloading and circulatory support (MCS) with the HM3 have not been investigated. We compared the reverse remodeling induced by the HM3 to older generation continuous-flow LVADs. Chronic HF patients (n = 405) undergoing MCS with HeartWare Ventricular Assist Device (HVAD, n = 115), HM3 (n = 186), and HeartMate II (HM2, n = 104) at four programs were included. Echocardiograms were obtained preimplant and at 1, 3, 6, and 12 months following LVAD implantation. There were no differences in the postimplant serial LV ejection fraction (LVEF) between the devices. The postimplant LV internal diastolic diameter (LVIDd) was significantly lower for HM2 at 3 and 6 months compared with HVAD and HM3. The proportion of patients achieving "cardiac reverse remodeling responder" status (defined as LVEF improvement to ≥40% and LVIDD ≤5.9 cm) was 11.9%, and was similar between devices. HeartMate 3 appears to result in similar cardiac reverse remodeling as older generation CF-LVADs, suggesting that the fully magnetically levitated device technology could provide an effective platform to further study and promote cardiac reverse remodeling.

Left ventricular strain changes at high altitude in rats: a cardiac magnetic resonance tissue tracking imaging study

BackgroundLong-term exposure to a high altitude environment with low pressure and low oxygen could cause abnormalities in the structure and function of the heart. Myocardial strain is a sensitive indicator for assessing myocardial dysfunction, monitoring myocardial strain is of great significance for the early diagnosis and treatment of high altitude heart-related diseases. This study applies cardiac magnetic resonance tissue tracking technology (CMR-TT) to evaluate the changes in left ventricular myocardial function and structure in rats in high altitude environment.Methods6-week-old male rats were randomized into plateau hypoxia rats (plateau group, n = 21) as the experimental group and plain rats (plain group, n = 10) as the control group. plateau group rats were transported from Chengdu (altitude: 360 m), a city in a plateau located in southwestern China, to the Qinghai-Tibet Plateau (altitude: 3850 m), Yushu, China, and then fed for 12 weeks there, while plain group rats were fed in Chengdu(altitude: 360 m), China. Using 7.0 T cardiac magnetic resonance (CMR) to evaluate the left ventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV), as well as myocardial strain parameters including the peak global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). The rats were euthanized and a myocardial biopsy was obtained after the magnetic resonance imaging scan.ResultsThe plateau rats showed more lower left ventricular GLS and GRS (P < 0.05) than the plain rats. However, there was no statistically significant difference in left ventricular EDV, ESV, SV, EF and GCS compared to the plain rats (P > 0.05).ConclusionsAfter 12 weeks of exposure to high altitude low-pressure hypoxia environment, the left ventricular global strain was partially decreased and myocardium is damaged, while the whole heart ejection fraction was still preserved, the myocardial strain was more sensitive than the ejection fraction in monitoring cardiac function.

The effect of long-term soccer training on left ventricular structure and function in elite male youth soccer players.

Cardiac adaptations in elite, male adolescent youth soccer players have been demonstrated in relation to training status. The time course of these adaptations and the delineation of the influence of volatile growth phases from the training effect on these adaptations remain unclear. Consequently, the aims of the study were to evaluate the impact of 3 years of elite-level soccer training on changes in left ventricular (LV) structure and function in a group of highly trained elite youth male soccer players (SP) as they transitioned through the pre-to-adolescent phase of their growth. Twenty-two male youth SP from the highest Level of English Premier League Academy U-12 teams were evaluated once a year for three soccer seasons as the players progressed from the U-12 to U-14 teams. Fifteen recreationally active control participants (CON) were also evaluated over the same 3-year period. Two-dimensional transthoracic echocardiography was used to quantify LV structure and function. After adjusting for the influence of growth and maturation, training-induced increases in Years 2 and 3 were noted for: LV end diastolic volume (LVEDV; p = 0.02) and LV end systolic volume (LVESV; p = 0.02) in the SP compared to CON. Training-induced decrements were noted for LV ejection fraction (LVEF; p = 0.006) and TDI-S' (p < 0.001). An increase in training volume (Years 2 and 3) were aligned with LV volumetric adaptations and decrements in systolic function in the SP that were independent from the influence of rapid somatic growth. Decrements in systolic function were suggestive of a functional reserve for exercise.

Transcatheter aortic valve replacement in heart failure.

Patients with severe aortic stenosis (AS) may develop heart failure (HF), the presence of which has traditionally been deemed as a final stage in AS progression with poor outcomes. The use of transcatheter aortic valve replacement (TAVR) has become the preferred therapy for most patients with AS and concomitant HF. With its instant afterload reduction, TAVR offers patients with HF significant haemodynamic benefits, with corresponding changes in left ventricular structure and improved mortality and quality of life. The prognostic covariates and optimal timing of TAVR in patients with less than severe AS remain unclear. The purpose of this review is to describe the association between TAVR and outcomes in patients with HF, particularly in the setting of left ventricular systolic dysfunction, acute HF, and right ventricular systolic dysfunction, and to highlight areas for future research.

Insights into the effects of Friedreich ataxia on the left ventricle using T1 mapping and late gadolinium enhancement.

The left ventricular (LV) changes which occur in Friedreich ataxia (FRDA) are incompletely understood. Cardiac magnetic resonance (CMR) imaging was performed using a 1.5T scanner in subjects with FRDA who are homozygous for an expansion of an intron 1 GAA repeat in the FXN gene. Standard measurements were performed of LV mass (LVM), LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF). Native T1 relaxation time and the extracellular volume fraction (ECV) were utilised as markers of left ventricular (LV) diffuse myocardial fibrosis and late gadolinium enhancement (LGE) was utilised as a marker of LV replacement fibrosis. FRDA genetic severity was assessed using the shorter FXN GAA repeat length (GAA1). There were 93 subjects with FRDA (63 adults, 30 children, 54% males), 9 of whom had a reduced LVEF (<55%). A LVEDV below the normal range was present in 39%, a LVM above the normal range in 22%, and an increased LVM/LVEDV ratio in 89% subjects. In adults with a normal LVEF, there was an independent positive correlation of LVM with GAA1, and a negative correlation with age, but no similar relationships were seen in children. GAA1 was positively correlated with native T1 time in both adults and children, and with ECV in adults, all these associations independent of LVM and LVEDV. LGE was present in 21% of subjects, including both adults and children, and subjects with and without a reduced LVEF. None of GAA1, LVM or LVEDV were predictors of LGE. An association between diffuse interstitial LV myocardial fibrosis and genetic severity in FRDA was present independently of FRDA-related LV structural changes. Localised replacement fibrosis was found in a minority of subjects with FRDA and was not associated with LV structural change or FRDA genetic severity in subjects with a normal LVEF.

Correlation Between Left Ventricular Structural and Functional Changes and Coronary Artery Disease in Hypertensive Patients (Speckle Tracking Echocardiographic Study)

Correlation Between Left Ventricular Structural and Functional Changes and Coronary Artery Disease in Hypertensive Patients (Speckle Tracking Echocardiographic Study)

Impact of atrial fibrillation burden on longitudinal changes in left ventricular structure and function: a post-hoc analysis of a randomized clinical trial

Abstract Background Atrial fibrillation (AF) is a well-established risk factor for heart failure (HF), stroke, and left ventricular (LV) dysfunction. However, only limited longitudinal data exist regarding the impact of AF burden on left ventricular (LV) structure and function. Purpose The aim of this study was to investigate the association between AF burden and longitudinal changes in LV structure and function in an older patient population with cardiac risk factors. Methods This study was a post-hoc analysis of a randomized clinical trial, which investigated whether AF screening with implantable loop recorders (ILRs) and subsequent initiation of anticoagulation could prevent stroke in high-risk individuals. As a substudy, a group of participants had extensive transthoracic echocardiography performed at baseline and a re-examination after ILR end-of-life. We included participants with available ILR data and echocardiographic data from both baseline and follow-up. We excluded participants with ongoing AF during the baseline echocardiogram. AF episodes were adjudicated by two cardiologists and AF burden was calculated as the percentage of time spent in AF during the total ILR monitoring period. Univariable and multivariable linear regression models were used to investigate the association between AF burden and changes in echocardiographic measures. The multivariable model was adjusted for age, sex, systolic blood pressure, diabetes, smoking status, previously acute myocardial infarction, previous coronary artery bypass grafting, prevalent HF, body mass index, estimated glomerular filtration rate, number of days monitored by ILR, and the number of days between the two echocardiographic examinations. Both models included adjustment for the baseline value of the echocardiographic measure. Results The study population consisted of 640 participants with available baseline and follow-up echocardiograms. Mean age was 73.6 years (±3.4 years) and 278 (43.4%) were women. AF was documented in 188 (29.4%) participants during a median ILR monitoring period of 3.2 years (IQR 2.9-3.4 years). The mean timespan between the echocardiographic examinations was median 5.0 (IQR 4.6-5.2) years. Among participants with AF, the median AF burden was 0.098% (IQR 0.026-0.758%). Over the course of echocardiographic follow-up, mean ∆GLS was -0.59% (±3.49%), mean ∆LVEF was -1.44% (±8.5%), and mean ∆E/e’ was -1.12(±3.23) in those with AF. Increasing AF burden was significantly associated with an accelerated decline in absolute global longitudinal strain in both univariable (ß= -0.12, p=0.002) and multivariable (ß= -0.11, p=0.003) models (Table 1/Figure 1). Conclusions In an older at-risk population, AF was frequent, and increasing AF burden was found to be independently associated with an accelerated decline in LV function. These findings support AF as an independent risk factor in the development of HF.

Maternal hypertensive disorders of pregnancy and electrocardiographic findings in newborns

Abstract Background Hypertensive disorders of pregnancy (HDP) - preeclampsia in particular - are important causes of pregnancy complications and death for both the mother and her offspring. Preeclampsia is also associated with both congenital heart defects (CHDs) in the offspring and subtle changes in left ventricular structure and function in the offspring. However, whether preeclampsia also affects the newborn’s cardiac conduction system is unknown. Purpose To assess whether newborns born after pregnancies complicated by HDP exhibit changes in their electrocardiogram (ECG) compared with newborns born after pregnancies without HDP. Methods This population-based cohort study included newborns, who had ECG data obtained within 30 days of birth. Information on maternal preeclampsia (ICD-10 codes DO14-14.2 and DO15-15.9) and maternal gestational hypertension (ICD-10 codes DO13-13.9) was retrieved from an obstetric database. ECG parameters of interest included heart rate, PR interval, QRS axis, QRS duration, uncorrected and corrected QT intervals, maximum R- and S-wave amplitudes in V1 and V6, respectively. ECG parameters of exposed and non-exposed newborns were compared using summary statistics and linear regression, adjusting for sex, gestational age at delivery and length, weight and age at examination. Sensitivity analyses were conducted with adjustments for maternal smoking, parity, age, and multiple pregnancies and the analyses were repeated after excluding neonates and mothers with CHD, newborns exposed to pre-gestational diabetes and children born preterm (&amp;lt;37 weeks’ gestation). Results Our study cohort included 11,826 newborns; 441 were exposed to maternal preeclampsia and 320 were exposed to maternal gestational hypertension (table). Newborns born to mothers with preeclampsia had significantly prolonged QRS duration compared to neonates born after pregnancies without HDP (adjusted mean difference of 0.6 ms, 95% CI [0.04 – 1.16], p=0.04). The maximum amplitude of the R-wave in the V1-recording was significantly lower in newborns born to mothers with preeclampsia by 5% (linear scale: 0.95, 95% CI [0.9 – 0.996], p=0.03). These associations persisted after adjustment for additional covariates and restrictions on the study population. Gestational hypertension was not associated with significant differences in any of the investigated ECG parameters. Conclusion The cardiac conduction was affected in children born to mothers with preeclampsia compared with newborns born after pregnancies without HDP, including prolonged QRS duration and lower amplitude of the R-wave in V1 in the ECG. These findings could be an indicator of thickening of the left ventricular myocardium in newborns of mothers with preeclampsia. The potential clinical implications of these changes – short or long-term – are unknown and require further investigation.Table

Abstract 16721: Concentrations of Troponin I but Not Cardiac Troponin T Are Associated With 7-year Changes in Left Ventricular Structure and Function in Older Adults: The Atherosclerosis Risk in Community (ARIC) Study

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are strongly associated with incident heart failure (HF) and left ventricular (LV) remodeling. Their associations with longitudinal changes in cardiac structure and function are less clear. Methods: Among 1,908 participants in the Atherosclerosis Risk in Communities (ARIC) study who were free of coronary disease, HF, or atrial fibrillation and had echocardiography at study Visits 5 (2011-2013) and 7 (2017-2019), we assessed the associations of log-transformed hs-cTnT and hs-cTnI at Visit 5 with absolute changes in LV structure and function between Visit 5 and 7 (median of 6.6 [IQR 6.1-7.0] years) using multivariable linear regression with the exposures modeled as restricted cubic spline models. Models were adjusted for age, sex, race, BMI, diabetes, hypertension and eGFR at Visit 5, blood pressure and heart rate at both visits. Results: At Visit 5, the mean age (years) was 74 (SD 4), 60% were female, 24% reported Black race and the median (p25-p75) concentrations of hs-cTnT and hs-cTnI were 9 (6-13) ng/L and 2.7 (1.9-4.0) ng/L respectively. In adjusted models, higher hs-cTnI concentration was associated with 7-year decline in LV systolic function (ejection fraction, global longitudinal and circumferential strain; Figure ). In contrast, hs-cTnT was not consistently associated with changes in cardiac function. Changes in hs-cTnI, but not hs-cTnT, were also associated with greater increases in left atrial volume. Neither were associated with changes in LV mass or volume. Conclusions: Higher hs-cTnI, but not hs-cTnT, concentrations are associated with greater declines in LV function over ~7 years in late life independent of traditional cardiovascular risk factors. These findings support previous findings of cTnI to be more cardiac specific than cTnT.

Abstract 14700: Associations of Left Ventricular Structure With Cumulative Systolic Blood Pressure Load: A Report From Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study

Background: Recent studies have identified cumulative systolic blood pressure load to be associated with increased risk of adverse cardiovascular disease (CVD) outcomes. Similarly, associations between left ventricular (LV) structure and CVD events have long been recognized. Purpose: The purpose of this study was to assess the association between cumulative systolic blood pressure (CuSBP) load and LV structure in women with suspected ischemia with no obstructive coronary arteries (INOCA). Methods: Women enrolled in the Women’s Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) study (NCT00832702) underwent cardiac magnetic resonance imaging (CMRI) for LV structure and those (n= 225) who had at least 2 blood pressure (BP) measures recorded at a single site before their baseline CMRI were included in this analysis. Cumulative systolic BP (CuSBP) was defined as systolic BP (SBP) ≥ 130 divided by all SBP readings and each mean value multiplied by the years. LV remodeling index was defined as the ratio between LV mass and LV end diastolic volume (LVEDV). Results: The mean age was 55±10 years, body mass index (BMI) 26.3 ± 5.5 kg/m 2 , 36% had a history of hypertension, number of BP medications was mean 2.7 ± 1.6 [median 2 (range 0, 8)], and SBP and DBP were 126 ± 15 and 66 ± 10 mmHg respectively. Age, BMI and history of hypertension were significantly associated with higher CuSBP load. In univariate analyses, LV end diastolic volume and LV end systolic volume decreased, and LV remodeling index increased across CuSBP quartiles while LV mass index did not significantly differ among the quartiles (Figure 1) . In multivariable regression analysis, the association between CuSBP and LV mass index and LV remodeling index remained significant. Conclusions: Among women with suspected INOCA, higher CuSBP load was associated with greater LV mass index and concentric LV remodeling independent of age. Changes in LV volumes may represent age-related changes in LV structure.

Abstract 14093: Effects of Continuous Accelerated Pacing on Cardiac Structure and Function in Patients With Heart Failure With Preserved Ejection Fraction: Insights From the MyPACE Randomized Clinical Trial

Introduction: Heart failure with a preserved ejection fraction of 50% or higher (HFpEF) is prevalent and has few evidence-based therapies. In a trial of HFpEF patients with specialized pacemakers, treatment with an accelerated personalized pacing rate averaging 75 bpm (myPACE) markedly improved quality of life, NT-proBNP, physical activity, and atrial fibrillation burden compared with the standard lower rate setting of 60bpm (usual care). Methods: Provider-initiated echocardiographic studies obtained before and after the trial were assessed for changes in left ventricular (LV) structure and function amongst participants who continued their pacing assignment. The analytic approach aimed to detect differences in standard and advanced echocardiographic parameters within and between study arms. Results: Of the 100 trial participants, 16 patients in the myPACE arm and 20 in the usual care arm had a qualifying set of echocardiograms with a mean±SD time of 3.7±2.0 years apart. Heart rates were expectedly higher among myPACE patients after the trial (in bpm: myPACE 75±6 vs. usual care 65±7, p&lt;0.001). Sustained exposure to moderately accelerated pacing resulted in a reduced septal wall thickness (myPACE 1.07±0.05mm vs usual care 1.23±0.04, p=0.008) and a lower LV mass to systolic volume ratio (myPACE 1.52±0.09 vs. usual care 1.84±0.05, p=0.038) accompanied by a small reduction in LV ejection fraction (in %: myPACE 55±1 vs usual care 60±1, p=0.015). These changes were paralleled by marked improvements in heart failure-related quality of life (MLHFQ points: myPACE 17±21 vs usual care 28±22, p&lt;0.001). Markers of diastolic function and LV performance were not affected. Conclusions: Exposure to continuous accelerated pacing in HFpEF is associated with a reduced LV wall thickness and a lower mass to systolic volume ratio and ejection fraction that remained within normal limits.

Speckle tracking tissue motion mitral annulus displacement to assess early changes in the left ventricle and its association with lung function in patients with chronic obstructive pulmonary disease.

To evaluate the early changes in left ventricular (LV) in patients with chronic obstructive pulmonary disease (COPD) by measuring tissue motion mitral annulus displacement (TMAD) and three-dimensional (3D) parameters using speckle tracking imaging (STI), and to explore its correlation with lung function. Forty two COPD patients (GOLD I, GOLD II, GOLD III) and 30 healthy individuals (control group) were included. STI was used to assess the changes in LV structure and systolic function. Receiver operating characteristic (ROC) curves were drawn, and correlations among TMAD parameters, LV systolic function, structural, pulmonary artery systolic pressure (PASP), and lung function were analyzed. Compared to the control group, COPD patients were able to undergo LV remodeling, with a decrease in the absolute value of global longitudinal strain (GLS) and TMAD, but no significant modification of LVEF. Correlation analysis showed that TMAD was positively related to the absolute value of GLS (r > 0.51, P < 0.01) and predicted forced expiratory volume in the first second (FEV1%) (r > 0.56, P < 0.01), and negatively to PASP (r < -0.52, P < 0.01). The LV posterior wall thickness (LVPWd), relative wall thickness (RWT), end-diastolic volume (LVEDV) and PASP negatively correlated with FEV1%. The LV geometric changes and systolic function impairment in COPD patients were found to correlate with airflow restriction (FEV1%). TMAD aided in detection of early changes in LV systolic function in COPD patients. It negatively correlated with PASP and positively with FEV1%. Moreover, it was more convenient than GLS.

Cardiomyocyte and endothelial cells play distinct roles in the tumour necrosis factor (TNF)-dependent atrial responses and increased atrial fibrillation vulnerability induced by endurance exercise training in mice.

Endurance exercise is associated with an increased risk of atrial fibrillation (AF). We previously established that adverse atrial remodelling and AF susceptibility induced by intense exercise in mice require the mechanosensitive and pro-inflammatory cytokine tumour necrosis factor (TNF). The cellular and mechanistic basis for these TNF-mediated effects is unknown. We studied the impact of Tnf excision, in either atrial cardiomyocytes or endothelial cells (using Cre-recombinase expression controlled by Nppa or Tie2 promoters, respectively), on the cardiac responses to six weeks of intense swim exercise training. TNF ablation, in either cell type, had no impact on the changes in heart rate, autonomic tone, or left ventricular structure and function induced by exercise training. Tnf excision in atrial cardiomyocytes did, however, prevent atrial hypertrophy, fibrosis, and macrophage infiltration as well as conduction slowing and increased AF susceptibility arising from exercise training. In contrast, endothelial-specific excision only reduced the training-induced atrial hypertrophy. Consistent with these cell-specific effects of Tnf excision, inducing TNF loss from atrial cardiomyocytes prevented activation of p38MAPKinase, a strain-dependent downstream mediator of TNF signalling, without affecting the atrial stretch as assessed by atrial pressures induced by exercise. Despite TNF's established role in innate immune responses and inflammation, neither acute nor chronic exercise training caused measurable NLRP3 inflammasome activation. Our findings demonstrate that adverse atrial remodelling and AF vulnerability induced by intense exercise require TNF in atrial cardiomyocytes whereas the impact of endothelial-derived TNF is limited to hypertrophy modulation. The implications of the cell autonomous effects of TNF and crosstalk between cells in the atria are discussed.

Erratum: Elevated bile acids are associated with left ventricular structural changes in biliary atresia.

Erratum: Elevated bile acids are associated with left ventricular structural changes in biliary atresia.