Adverse Left Ventricular Remodeling Research Articles

Transcriptional regulation of macrophage inflammation in the heart failure with preserved ejection fraction

Abstract Funding Acknowledgements None. Introduction Heart failure with preserved ejection fraction (HFpEF) is a global public health problem with no effective treatment available. Pro-inflammatory cardiac macrophages are emerging as key determinants of adverse left ventricular remodeling; however, their role in HFpEF remains poorly understood. Mechanistically, the recruitment and activation of macrophages represent a key event in maladaptive myocardial remodeling in HFpEF patients. Evidence suggests that remodeling processes in HFpEF hearts are orchestrated and amplified by cardiac macrophages which regulate cardiomyocyte function, endothelial cell activation and fibroblast differentiation. Here we sought to determine the role of macrophage inflammation in experimental and human HFpEF. Methods Experiments were performed in rat cardiomyocytes (H9c2), human endothelial cells (HAECS), transgenic mice, and left ventricular (LV) myocardial samples from patients with HFpEF. H9c2 and HAECS treated with pro-inflammatory macrophage-like cells (RAW 264.7) conditional media in the presence or knockdown of a top-ranking activator of M1 type macrophages such as nuclear receptor corepressor 1 (NCOR1), were used to elucidate better the involvement of this gene in transcriptional regulation in vitro. The cardiac function of myeloid cell-specific NCOR1 knockout HFpEF mice undergoing a high-fat diet and L-NAME was investigated. LV myocardial samples were used to evaluate the pro-inflammatory activity of macrophages in human HFpEF tissues. Results Human and murine LV specimens showed upregulation of vascular adhesion molecules (ICAM1, ICAM2, E-selectin), recruitment of M1 macrophages to the myocardium, and decreased M2 macrophages. Notably, NCOR1 deletion in macrophages protected against diastolic dysfunction, exercise intolerance, and myocardial inflammation (TNF-a, IL6, IL-1b). Mechanistically, induction of metabolic stress by palmitic acid induced macrophage polarization, upregulation of NCOR1 and inflammatory genes in RAW cells. By contrast, Finally, NCOR1 depletion prevented pro-inflammatory transcriptional programs and secretion of TNF-a, IL6 and IL-1b in the macrophage secretome. Conclusion Targeting macrophage NCOR1 could represent a promising approach to blunt myocardial inflammation in HFpEF.

Cardiac Magnetic Resonance Evaluationof LV Remodeling Post-Myocardial Infarction: Prognosis, Monitoring and Trial Endpoints.

Adverse left ventricular remodeling (ALVR) and subsequent heart failure after myocardial infarction (MI) remain a major cause of patient morbidity and mortality worldwide. Overt inflammation has been identified as the common pathway underlying myocardial fibrosis and development of ALVR post-MI. With its ability to simultaneously provide information about cardiac structure, function, perfusion, and tissue characteristics, cardiac magnetic resonance (CMR) is well poised to inform prognosis and guide early surveillance and therapeutics in high-risk cohorts. Further, established and evolving CMR-derived biomarkers may serve as clinical endpoints in prospective trials evaluating the efficacy of novel anti-inflammatory and antifibrotic therapies. This review provides an overview of post-MI ALVR and illustrates how CMR may help clinical adoption of novel therapies via mechanistic or prognostic imaging markers.

Effects of the Low-Dose Colchicine Regimen on Left Ventricular Adverse Remodeling and Systolic Function in Acute Myocardial Infarction Patients with Anterior ST-Segment Elevation Undergoing Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial

Background: Inflammation in reperfusion injury results in adverse ventricular remodeling and reduced systolic function. The anti-inflammatory effects of colchicine have shown beneficial effects in cardiovascular disease. Objective: To determine the effects of low-dose colchicine on left ventricular (LV) adverse remodeling and systolic function in acute myocardial infarction with anterior ST-segment elevation (anterior STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Material and Methods: This prospective, randomized, double-blinded study randomly assigned anterior STEMI patients who underwent PPCI to receive either low-dose colchicine (1mg loading dose followed by 0.5mg daily) or a matching placebo for 30 days in addition to standard therapy. Outcomes included adverse LV remodeling and systolic function, determined by transthoracic echocardiography (TTE) in the first and third month. Result: Enrollment comprised 196 patients, with 92 patients in the colchicine group and 104 patients in the placebo group. Adverse LV remodeling and a decrease in systolic function were observed in both groups. No significant differences in LV remodeling were observed between the colchicine and placebo groups, as indicated by the change in LV end-systolic volume index (LVESVI) at the first month (16.5% vs. 18.25% [p=0.091]) and third month (19.5% vs. 21.5% [p=0.124]). Similar results were found in LV systolic function between the colchicine and placebo groups, with a reduction in LV ejection fraction (LVEF) observed in the first month (6.3% vs. 8.95% [p=0.083]) and third month (9.5% vs. 11.5% [p=0.163]). Diarrhea was the only reported side effect, occurring in 6.5% of patients in the colchicine group. Conclusion: Low-dose colchicine administration in anterior STEMI patients undergoing PPCI did not reduce LV adverse remodeling or systolic function. Keyword: Adverse Remodeling, Colchicine, Reperfusion Injury, STEMI, Systolic Function.

Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice.

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 μL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.

Left ventricular shape index and eccentricity index with ECG-gated Nitrogen-13 ammonia PET/CT in patients with myocardial infarction, ischemia, and normal perfusion

BackgroundLV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function. Methods and resultsOne hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05). ConclusionsShape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling.

Differential associations between abnormal cardiac left ventricular geometry types and cerebral white matter disease

ObjectivesReduced cardiac outflow due to left ventricular hypertrophy has been suggested as a potential risk factor for development of cerebral white matter disease. Our study aimed to examine the correlation between left ventricular geometry and white matter disease volume to establish a clearer understanding of their relationship, as it is currently not well-established. MethodsConsecutive patients from 2016 to 2021 who were ≥18 years and underwent echocardiography, cardiac MRI, and brain MRI within one year were included. Four categories of left ventricular geometry were defined based on left ventricular mass index and relative wall thickness on echocardiography. White matter disease volume was quantified using an automated algorithm applied to axial T2 FLAIR images and compared across left ventricular geometry categories. ResultsWe identified 112 patients of which 34.8 % had normal left ventricular geometry, 20.5 % had eccentric hypertrophy, 21.4 % had concentric remodeling, and 23.2 % had concentric hypertrophy. White matter disease volume was highest in patients with concentric hypertrophy and concentric remodeling, compared to eccentric hypertrophy and normal morphology with a trend-P value of 0.028. Patients with higher relative wall thickness had higher white matter disease volume (10.73 ± 10.29 cc vs 5.89 ± 6.46 cc, P = 0.003), compared to those with normal relative wall thickness. ConclusionOur results showed that abnormal left ventricular geometry is associated with higher white matter disease burden, particularly among those with abnormal relative wall thickness. Future studies are needed to explore causative relationships and potential therapeutic options that may mediate the adverse left ventricular remodeling and its effect in slowing white matter disease progression.

Predictive value of cardiac magnetic resonance imaging for adverse left ventricular remodeling after acute ST-segment elevation myocardial infarction

To assess the value of cardiac magnetic resonance (CMR) imaging for predicting adverse left ventricular remodeling in patients with ST-segment elevation myocardial infarction (STEMI). We retrospectively analyzed the clinical data and serial CMR (cine and LGE sequences) images of 86 STEMI patients within 1 week and 5 months after percutaneous coronary intervention (PCI), including 25 patients with adverse LV remodeling and 61 without adverse LV remodeling, defined as an increase of left ventricular end-systolic volume (LVESV) over 15% at the second CMR compared to the initial CMR. The CMR images were analyzed for LV volume, infarct characteristics, and global and infarct zone myocardial function. The independent predictors of adverse LV remodeling following STEMI were analyzed using univariate and multivariate Logistic regression methods. The initial CMR showed no significant differences in LV volume or LV ejection fraction (LVEF) between the two groups, but the infarct mass and microvascular obstructive (MVO) mass were significantly greater in adverse LV remodeling group (P < 0.05). Myocardial injury and cardiac function of the patients recovered over time in both groups. At the second CMR, the patients with adverse LV remodeling showed a significantly lower LVEF, a larger left ventricular end-systolic volume index (LVESVI) and a greater extent of infarct mass (P < 0.001) with lower global peak strains and strain rates in the radial, circumferential, and longitudinal directions (P < 0.05), infarct zone peak strains in the 3 directions, and infarct zone peak radial and circumferential strain rates (P < 0.05). The independent predictors for adverse LV remodeling following STEMI included the extent of infarct mass (AUC=0.793, 95% CI: 0.693-0.873; cut-off value: 30.67%), radial diastolic peak strain rate (AUC=0.645, 95% CI: 0.534-0.745; cut-off value: 0.58%), and RAAS inhibitor (AUC= 0.699, 95% CI: 0.590-0.793). The extent of infarct mass, peak radial diastolic strain rate, and RAAS inhibitor are independent predictors of adverse LV remodeling following STEMI.

Do False Tendons Prevent Adverse Left Ventricular Remodeling After Anterior Wall Myocardial Infarction? An Echocardiographic Strain Imaging Study

The role of muscular left ventricular (LV) false tendons (FTs) is poorly understood. To gain insight into their pathophysiologic significance, we adapted echocardiographic LV strain imaging software to measure LVFT longitudinal strain in subjects with normal left ventricles and in patients who sustained previous anterior wall myocardial infarction (AWMI). GE EchoPAC software was used to measure longitudinal strain in LVFTs ≥0.3 cm in diameter. Tendinous strain was measured in 11 patients with LVFTs confined to the left anterior descending artery territory (connecting the anteroseptum or anterior wall to the apex) ≥6 months after AWMI (myocardial infarction [MI]+FT+ group) and in 25 patients with normal hearts containing LVFTs (MI-FT+ group). We also compared the indexed LV end-diastolic volumes in the MI+FT+ group to that of 25 patients with previous AWMI without LVFTs (MI+FT- group). The mean LVFT strain in MI+FT+ group was 5.5 ± 6.2% and -28.9 ± 4.7% in the MI-FT+ group (p <0.0001). The indexed LV end-diastolic volume in the MI+FT+ group did not differ from the MI+FT- group (88.4 ± 17.8 vs 87.9 ± 17 ml/m2, p = 0.90). In conclusion, the negative strain (contraction) developed by LVFTs in the MI-FT+ group may help maintain normal LV size and shape by generating inward restraining forces. The development of positive strain (stretch) in LVFTs in patients in the MI+FT+ group suggests they become infarcted after AWMI. This implies that they are incapable of generating inward restraining forces that might otherwise mitigate adverse remodeling. Of note, LV volumes after AWMI do not differ whether or not LVFTs are present.

Mast Cells in Cardiac Remodeling: Focus on the Right Ventricle.

In response to various stressors, cardiac chambers undergo structural remodeling. Long-term exposure of the right ventricle (RV) to pressure or volume overload leads to its maladaptive remodeling, associated with RV failure and increased mortality. While left ventricular adverse remodeling is well understood and therapeutic options are available or emerging, RV remodeling remains underexplored, and no specific therapies are currently available. Accumulating evidence implicates the role of mast cells in RV remodeling. Mast cells produce and release numerous inflammatory mediators, growth factors and proteases that can adversely affect cardiac cells, thus contributing to cardiac remodeling. Recent experimental findings suggest that mast cells might represent a potential therapeutic target. This review examines the role of mast cells in cardiac remodeling, with a specific focus on RV remodeling, and explores the potential efficacy of therapeutic interventions targeting mast cells to mitigate adverse RV remodeling.

Patterns of left ventricular remodeling post-myocardial infarction, determinants, and outcome.

Left ventricular remodeling (LVR) after myocardial infarction (MI) can lead to heart failure, arrhythmia, and death. We aim to describe adverse LVR patterns at 6 months post-MI and their relationships with subsequent outcomes and to determine baseline. A multicenter cohort of 410 patients (median age 57 years, 87% male) with reperfused MI and at least 3 akinetic LV segments on admission was analyzed. All patients had transthoracic echocardiography performed 4 days and 6 months post-MI, and 214 also had cardiac magnetic resonance imaging performed on day 4. To predict LVR, machine learning methods were employed in order to handle many variables, some of which may have complex interactions. Six months post-MI, echocardiographic increases in LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were 14.1% [interquartile range 0.0, 32.0], 5.0% [- 14.0, 25.8], and 8.7% [0.0, 19.4], respectively. At 6 months, ≥ 15% or 20% increases in LVEDV were observed in 49% and 42% of patients, respectively, and 37% had an LVEF < 50%. The rate of death or new-onset HF at the end of 5-year follow-up was 8.8%. Baseline variables associated with adverse LVR were determined best by random forest analysis and included stroke volume, stroke work, necrosis size, LVEDV, LVEF, and LV afterload, the latter assessed by Ea or Ea/Ees. In contrast, baseline clinical and biological characteristics were poorly predictive of LVR. After adjustment for predictive baseline variables, LV dilation > 20% and 6-month LVEF < 50% were significantly associated with the risk of death and/or heart failure: hazard ratio (HR) 2.12 (95% confidence interval (CI) 1.05-4.43; p = 0.04) and HR 2.68 (95% CI 1.20-6.00; p = 0.016) respectively. Despite early reperfusion and cardioprotective therapy, adverse LVR remains frequent after acute MI and is associated with a risk of death and HF. A machine learning approach identified and prioritized early variables that are associated with adverse LVR and which were mainly hemodynamic, combining LV volumes, estimates of systolic function, and afterload.

Routine first-trimester pre-eclampsia screening and maternal left ventricular geometry.

Pre-eclampsia (PE) is a pregnancy complication associated with premature cardiovascular disease morbidity and mortality (i.e. before 60 years of age or in the first year postpartum). PE is associated with adverse left ventricular (LV) remodeling in the peri- and postpartum periods, an independent risk factor for cardiovascular disease. This study aimed to compare LV geometry by LV mass (LVM) and LVM index (LVMI) between participants with a high vs low screening risk for preterm PE in the first trimester. This was a prospective cohort study of singleton pregnancies between 11 + 0 and 13 + 6 weeks' gestation that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, from February 2019 until March 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm. Participants with a screening risk of ≥ 1 in 50 for preterm PE were classified as high risk and those with a screening risk of ≤ 1 in 500 were classified as low risk. All participants underwent two-dimensional and M-mode transthoracic echocardiography. A total of 128 participants in the first trimester of pregnancy were included in the analysis, with 57 (44.5%) participants screened as low risk and 71 (55.5%) participants as high risk for PE. The risk groups did not vary in maternal age and gestational age at assessment. Maternal body surface area and body mass index were significantly higher in the high-risk group (all P < 0.05). The high-risk participants were significantly more likely to be Afro-Caribbean, nulliparous and have a family history of hypertensive disease in pregnancy as well as other cardiovascular disease (all P < 0.05). In addition, mean arterial blood pressure (P < 0.001), mean heart rate (P < 0.001), median LVM (130.06 (interquartile range, 113.62-150.50) g vs 97.44 (81.68-114.16)g; P < 0.001) and mean LVMI (72.87 ± 12.2 g/m2 vs 57.54 ± 12.72 g/m2 ; P < 0.001) were significantly higher in the high-risk group. Consequently, those in the high-risk group were more likely to have abnormal LV geometry (37.1% vs 7.0%; P < 0.001). Early echocardiographic assessment in participants at high risk of preterm PE may unmask clinically healthy individuals who are at increased risk for future cardiovascular disease. Adverse cardiac remodeling in the first trimester of pregnancy may be an indicator of decreased cardiovascular reserve and subsequent dysfunctional cardiovascular adaptation in pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Kiosk 10R-TA-03 - Acute Sheetlet Mobility Predicts Adverse Left Ventricular Remodelling After STEMI

Kiosk 10R-TA-03 - Acute Sheetlet Mobility Predicts Adverse Left Ventricular Remodelling After STEMI

The predictive value of microvascular obstruction for adverse left ventricular remodeling after primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a prospective study

Objectives: Microvascular obstruction (MVO) is a specific cardiac magnetic resonance (CMR) imaging feature in patients with acute myocardial infarction. The purpose of this study was to elucidate the predictive value of MVO in left ventricular adverse remodeling after primary percutaneous coronary intervention (PCI) in patients with acute ST-elevation myocardial infarction (STEMI). Methods: A total of 167 patients with STEMI undergoing primary PCI in the Chinese PLA General Hospital from 2016 to 2020 were enrolled in this prospective cohort study, the average age of study patients was 57±10 years old, with 151 males (90.4%) and 16 females (9.6%). The patients were divided into the MVO group (n=81) and non-MVO group (n=86) according to the presence or absence of MVO on CMR imaging, respectively. The primary endpoint of the study was the occurrence of left ventricular adverse remodeling, which was defined as an increase in left ventricular end diastolic volume (LVEDV) by >20% at 6 months after primary PCI compared with the baseline. Patients who completed follow-up were diagnosed as left ventricular adverse remodeling or no left ventricular adverse remodeling according to CMR. The baseline data, perioperative data, and related data of end points were compared between the MVO group and non-MVO group. Finally, the predictive value of MVO in left ventricular adverse remodeling was calculated by receiver operating characteristic curve analysis. Results: In the baseline data, preoperative thrombolysis in myocardial infarction (TIMI) flow (χ2=13.74, P=0.003) and postoperative TIMI flow (χ2=14.87, P=0.001) were both obviously decreased in the MVO group. After 6 months of follow-up, the incidence of left ventricular adverse remodeling in the MVO group was significantly higher than that in the non-MVO group [37.0%(27/73) vs. 18.9%(14/74), χ2=5.96, P=0.015]. The left ventricular end systolic volume at 6 months post infarction in the MVO group was significantly larger than that in the non-MVO group [(94±32) vs. (68±20) ml, t=-5.98, P<0.001], as well as the LVEDV [(169±38) vs. (143±29) ml, t=-4.74, P<0.001]. Receiver operating characteristic curve showed that the area under the curve of MVO size for predicting left ventricular adverse remodeling was 0.637. Conclusion: The risk of left ventricular adverse remodeling is significantly increased in patients with MVO after primary PCI for acute STEMI.

Spatial transcriptomic analysis identifies a border zone with localized expression of brain natriuretic peptide in the inferobasal region of the left ventricle in patients with mitral valve prolapse

Abstract Background/Introduction Mitral valve prolapse (MVP) is a common cause of mitral regurgitation (MR), adverse left ventricular (LV) remodeling and arrhythmias. MVP induces mechanical stretch to the inferobasal (IB) myocardium and papillary muscles. The underlying regional and molecular pathology of MVP-induced LV remodeling remains incompletely understood. Purpose The aim was to characterize the molecular effects of mechanical stretch by comparing the regional gene expression of the IB region of LV with the interventricular septum in patients with MVP. Methods Myocardial biopsies were obtained from the IB LV (i.e. between papillary muscles) and the interventricular septum during mitral valve repair surgery for MVP-induced primary MR. The degree of cardiac fibrosis was detected and quantified by histology. We used spatial transcriptomics (ST) that - in contrast to traditional analyses of tissue homogenates - allows regional expressional analysis. Results Automated clustering of ST results correlated with histological staining of fibrosis in the IB and septal regions (R=0.97, P&amp;lt;0.0001), demonstrating good automated identification of fibrotic regions. The extent of fibrosis was similar between the inferobasal region and the septal control in the respective patients with MVP as determined by histological analysis and ST. The localized fibrotic areas of the inferobasal region showed decreased expression of cardiac myocytegenes such as RYR2, TNNI3, TNNC1 or TPM1, and increased expression of fibrous and EndMT markers such as COL3A1, BGN, SM22 or FN1. In the IB region, we identified a transition zone between healthy myocardium and fibrous tissue. This transition zone showed increased expression of the NPPB gene encoding brain natriuretic peptide (BNP), whereas NPPB was not increased in the septal region of the same patients. The upregulation of NPPB (6.4-fold, P=0.004) in the inferobasal region compared to the septal control was confirmed by qPCR in biopsies from patients with MVP. The identified transition zones were characterized by increased expression of genes such as IGFBP2 and LTBP2, which have been described to be associated with adverse LV remodeling in heart failure. Interestingly, the serum NT-proBNP levels (mean 276.8 ± 121.6 pg/ml) of the patients correlated with NPPB levels from the inferobasal region (R=0.76, P=0.01, N=9), whereas no correlation was found with NPPB levels from the septal control regions (R=0.17, P=0.65) of the same patients. Conclusions ST analysis in MVP identifies a transition zone of the inferobasal region of LV which is exposed to high mechanical stretch. This transition zone - but not the inferobasal fibrotic area nor the LV septum - is characterized by a specific increase in NBBP expression that correlates with increased NT-ProBNP serum concentrations. These special sequencing results indicate that mechanical stretch induces highly localized myocardial pathologies with systemic consequences.

Association of left ventricular geometry early after an acute coronary syndrome to long-term mortality

Abstract Background Markers of adverse left ventricular remodelling following myocardial infarction are associated with an increased risk of adverse events. Remodelling patterns can be classified using left ventricular mass index (LVMI) and relative wall thickness (RWT) into normal geometry, eccentric hypertrophy, concentric remodelling and concentric hypertrophy. In this analysis we evaluated the association between geometric classifications early after an acute coronary syndrome (ACS) and longer-term survival. Methods The Coronary Disease Cohort Study is a prospective multicentre observational cohort study. Between 2002-2010, 2140 ACS patients were recruited across New Zealand. Echocardiography and blood biomarker sampling were obtained at 1, 4 and 12 months of follow-up after ACS. Echocardiographic data from 1 month after ACS were analysed and patients classified into 4 groups based on geometry. The relationship between geometry and mortality at a median of 14 years follow up were evaluated using cox proportional hazards models after adjusting for demographics, clinical characteristics and biomarkers. Results Of 2140 patients, 401 (19%) had normal geometry, 747 (35%) concentric hypertrophy, 569 (26.5%) eccentric remodelling, 153 (7.1%) concentric remodelling, and 271 (12.7%) had incomplete data to classify. 874/2055 (43%) of participants had died at most recent follow up in 2022. Compared to those with normal geometry, the risk of death for patients with abnormal geometry was increased: concentric hypertrophy (hazard ratio [HR]:2.1; 95% confidence interval [CI]: 1.6 – 2.9); eccentric hypertrophy (HR: 1.7; 94% CI :1.3 – 2.4); concentric remodelling (HR: 1.7; 95% CI :1.1 – 2.6) after adjusting for baseline demographic, clinical, and biomarker covariates. Conclusion Abnormal left ventricular geometry documented one month after ACS portends an increased risk of death. Concentric hypertrophy carried the highest risk of death at long-term follow up.Unadjusted survival curves

Abstract 13478: Causes of Long-Term Mortality in Patients With Microvascular Obstruction Following ST-Segment Elevation Myocardial Infarction

Introduction: The presence of microvascular obstruction (MVO) following ST-segment elevation myocardial infarction (STEMI) portends a poor prognosis and is associated with adverse left-ventricular (LV) remodeling and an increase in mortality in the subsequent year of follow-up. However, the long-term effects of MVO on mortality have not been previously described. Methods: We analyzed the long-term follow-up and cardiac MRIs of 475 patients (Average age = 60 years, 76% male) for the presence (n=337) or absence (n=138) of MVO at a single institution following STEMI and successful reperfusion with primary percutaneous intervention (PCI). Causes of death were determined from the patient's electronic medical record or death certificate. Results: The infarct-related artery was more likely to be the LAD in patients with MVO and the RCA in patients without MVO. Patients with MVO had greater ischemic times (159 vs. 141 mins; p = 0.012) and were more likely to have TIMI 0 flow on presentation (71 vs 54%; p &lt;0.002). Patients with MVO had greater infarct size by cardiac enzymes resulting in greater LV end-diastolic volume index (LVEDVI) (80 vs.75 ml/m2), LV end-systolic volume index (LVESVI) (39 vs 30 ml/m2) and LV mass (146 vs 134 g) and reduced LVEF (48 vs 58 %; all p &lt; 0.01) by cardiac MRI performed 1-3 days following STEMI and PCI . During long-term follow-up a total of 56 patients with MVO died compared to 18 patients without MVO. Patients with MVO died sooner after STEMI (5.9 vs 7.8 years) and were more likely to die from cardiovascular causes such as progressive heart failure or sudden cardiac death (Table). LVEF before death was lower in the MVO group (46 vs 52%). Conclusions: There is significant long-term mortality associated with MVO following STEMI with the majority of patients dying from cardiovascular causes. In contrast, patients with STEMI without MVO rarely died from a cardiac etiology but from cancer and natural causes.

Left bundle branch pacing better preserves ventricular mechanical synchrony than right ventricular pacing: a two-centre study.

Left bundle branch pacing (LBBP) has been shown to better maintain electrical synchrony compared with right ventricular pacing (RVP), but little is known about its impact on mechanical synchrony. This study investigates whether LBBP better preserves left ventricular (LV) mechanical synchronicity and function compared with RVP. Sixty patients with pacing indication for bradycardia were included: LBBP (n = 31) and RVP (n = 29). Echocardiography was performed before and shortly after pacemaker implantation and at 1-year follow-up. The lateral wall-septal wall (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking, and septal strain patterns were also assessed. At baseline, LW-SW work difference was small and similar in two groups. SW was markedly decreased, while LW work remained mostly unchanged in RVP, resulting in a larger LW-SW work difference compared with LBBP (1253 ± 687 mmHg·% vs. 439 ± 408 mmHg·%, P < 0.01) at last follow-up. In addition, RVP more often induced septal flash or apical rocking and resulted in more advanced strain patterns compared with LBBP. At 1 year follow-up, LV ejection fraction (EF) and global longitudinal strain (GLS) were more decreased in RVP compared with LBBP (ΔLVEF: -7.4 ± 7.0% vs. 0.3 ± 4.1%; ΔLVGLS: -4.8 ± 4.0% vs. -1.4 ± 2.5%, both P < 0.01). In addition, ΔLW-SW work difference was independently correlated with LV adverse remodelling (r = 0.42, P < 0.01) and LV dysfunction (ΔLVEF: r = -0.61, P < 0.01 and ΔLVGLS: r = -0.38, P = 0.02). LBBP causes less LV mechanical dyssynchrony than RVP as it preserves a more physiologic electrical conduction. As a consequence, LBBP appears to preserve LV function better than RVP.

Remnant Cholesterol in Young Adulthood Is Associated With Left Ventricular Remodeling and Dysfunction in Middle Age: The CARDIA Study.

Recent studies have shown that remnant cholesterol (RC) is associated with incident heart failure; however, its association with left ventricular (LV) structure and function is unclear. We aimed to evaluate the association between RC levels in young adulthood and LV structure and function in middle age. We included 3321 participants from the CARDIA study (Coronary Artery Risk Development in Young Adults) at baseline. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus calculated low-density lipoprotein cholesterol, and the RC trajectories that followed a similar pattern of change over time were identified using the latent class growth mixture model. LV structure and function were assessed using echocardiography at CARDIA study year 25. Multivariable linear regression models were performed to assess the associations of both baseline and trajectories of RC levels with LV structure and function. Among 3321 participants, the mean age was 24.99±3.62 years: 1450 (43.90%) were male, and 1561 (47.00%) were Black. After multivariate adjustment, higher baseline RC (per SD in log-transformed) was associated with higher LV mass index (β=1.29; P=0.004), worse global longitudinal strain (β=0.19; P<0.001), worse global circumferential strain (β=0.16; P=0.014), lower septal e' (β=-0.26; P<0.001), lower lateral e' (β=-0.18; P=0.003), and higher E/e' (β=0.15; P=0.003). Three RC trajectories were identified during follow-up: low increasing (42.4%), moderate increasing (45.5%), and high increasing (12.1%). Similarly, compared with the low-increasing group, the high-increasing RC trajectory group was related to higher LV mass index, worse global longitudinal strain, lower septal e', lower lateral e', and higher E/e'. Elevated RC levels in young adulthood were related to adverse LV structural and functional alterations in midlife. Long-term trajectories of RC levels during young adulthood help identify individuals at a higher risk for adverse LV remodeling and dysfunction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

Genome-Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants.

BACKGROUND Pericardial adipose tissue (PAT) is the visceral adipose tissue compartment surrounding the heart. Experimental and observational research has suggested that greater PAT deposition might mediate cardiovascular disease, independent of general or subcutaneous adiposity. We characterize the genetic architecture of adiposity-adjusted PAT and identify causal associations between PAT and adverse cardiac magnetic resonance imaging measures of cardiac structure and function in 28 161 UK Biobank participants. METHODS AND RESULTS The PAT phenotype was extracted from cardiac magnetic resonance images using an automated image analysis tool previously developed and validated in this cohort. A genome-wide association study was performed with PAT area set as the phenotype, adjusting for age, sex, and other measures of obesity. Functional mapping and Bayesian colocalization were used to understand the biologic role of identified variants. Mendelian randomization analysis was used to examine potential causal links between genetically determined PAT and cardiac magnetic resonance-derived measures of left ventricular structure and function. We discovered 12 genome-wide significant variants, with 2 independent sentinel variants (rs6428792, P=4.20×10-9 and rs11992444, P=1.30×10-12) at 2 distinct genomic loci, that were mapped to 3 potentially causal genes: T-box transcription factor 15 (TBX15), tryptophanyl tRNA synthetase 2, mitochondrial (WARS2) and early B-cell factor-2 (EBF2) through functional annotation. Bayesian colocalization additionally suggested a role of RP4-712E4.1. Genetically predicted differences in adiposity-adjusted PAT were causally associated with adverse left ventricular remodeling. CONCLUSIONS This study provides insights into the genetic architecture determining differential PAT deposition, identifies causal links with left structural and functional parameters, and provides novel data about the pathophysiological importance of adiposity distribution.

Restoration of flow in the aorta: a novel therapeutic target in aortic valve intervention.

Aortic blood flow patterns are closely linked to the morphology and function of the left ventricle, aortic valve and aorta. These flow patterns demonstrate the exceptional adaptability of the cardiovascular system to maintain blood circulation under a broad range of haemodynamic workloads and can be altered in various pathophysiological states. For instance, normal ascending aortic systolic flow is predominantly laminar, whereas abnormal aortic systolic flow is associated with increased eccentricity, vorticity and flow reversal. These flow abnormalities result in reduced aortic conduit function and increased energy loss in the cardiovascular system. Emerging evidence details the association of these flow patterns with loss of aortic compliance, which leads to adverse left ventricular remodelling, poor tissue perfusion, and an increased risk of morbidity and death. In this Perspective article, we review the evidence for the link between aortic flow-related abnormalities and cardiovascular disease and how these changes in aortic flow patterns are emerging as a therapeutic target for aortic valve intervention in first-in-human studies.