Left Ventricular Concentric Remodeling Research Articles

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.

Left ventricular hypertrophy, wall thickness, and histological myocyte alteration in end-stage heart failure: a call for a standard definition

Abstract Objective This study aimed to examine the relationship between different left ventricular hypertrophy (LVH) classification criteria according to the American Society of Echocardiography (ASE), and anatomical measurement of LV wall thickness (LVWT) and histological evidence of myocyte hypertrophy. Methods Data from 146 consecutive patients (47 years; 75% were male) who have undergone heart transplantation were analysed. Fixed ventricles were dissected and measured in weight after both atria, great vessels, and epicardial fat were removed. The fixed biventricular weight was calculated as 87% of total weight (the effect of fixed formalin reduced the total weight by 3%). Anatomical LVWT was measured with a ruler at LV free wall where maximal thickness is located. A comprehensive echocardiogram was performed in all patients before heart transplantation. LVM and relative wall thickness (RWT) (2 PWT/LVEDD) were measured by M-mode echocardiography in parasternal long-axis view. Patients were considered to have LVH when the LVM index exceeds 95 g/m2 in women and exceeds 115 g/m2 in men. Patients were considered to have concentric LVH when RWT > 0.42. LVWT was measured using 2D echocardiography perpendicular to the LV long axis. Results Of 146 explanted hearts, dilated cardiomyopathy (CM), cardiac amyloid, and hypertrophic CM were diagnosed in 53 (47%), 1 (1%), and 8 (5%) patients, respectively. Anatomic ventricular mass correlated with echocardiographic LVM (r=0.5, p < 0.01). Anatomic LVWT modestly correlated with echocardiographic LVWT (r=0.2, p=0.01). Of 146 patients, echocardiographic normal LV geometry, concentric LV remodelling, concentric LVH, and eccentric LVH were present in 22 (15%), 6 (4%), 14 (10%), and 104 (71%), respectively. Increased LVWT (≥ 13 mm) assessed by 2-D echocardiography was present in normal LV geometry (5%), concentric LV remodelling (5%), concentric LVH (57%), and eccentric LVH (33%) (p <0.001) in those classified by ASE guidelines. Anatomic LVWT (≥ 13 mm) was present in normal LV geometry (14%), concentric LV remodelling 5%), concentric LVH (14%), and eccentric LVH (80%) (p <0.001) in those classified by ASE guidelines. Histological myocyte hypertrophy was present in normal LV geometry (12%), concentric LV remodelling (2%), concentric LVH (11%), and eccentric LVH (70%) (p <0.001) in those classified by ASE guidelines. Conclusions 2D-derived echocardiographic increased LVWT in patients with LVH defined by increased LVM index was present in approximately 30-50%. Furthermore, anatomical increased LVWT in those with LVH classified by ASE guidelines was present in a varying range of 10-70%. Patients with concentric LVH had a low prevalence of histological myocyte hypertrophy (approximately 10%). Inconsistencies in classification methods reveal the need for more robust LVH terminologies and definition that is consistent across cardiac imaging and anatomico-pathological examination, particularly in patients with CM.

A comparative analysis of conventional echocardiographic findings among different heart failure stages and phenotypes: insights from the national echocardiographic society registry

Abstract Background The contemporary conceptualization of heart failure (HF) encompasses four developmental stages (at risk for HF, pre-HF, symptomatic HF, and advanced HF) and three distinct HF phenotypes categorized by left ventricular ejection fraction (LVEF) (HFpEF, HFmrEF, HFrEF). However, there is a need for a more comprehensive understanding of echocardiographic similarities and differences among pre-HF stages and various HF phenotypes. Material and Methods Our national echocardiographic society conducted a multicenter HF screening initiative. General practitioners in 13 primary care centers utilized the original mobile phone app to determine referrals for transthoracic echocardiography and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing in individuals without a prior HF diagnosis. The 2021 ESC guidelines' algorithms were used to diagnose HF phenotypes and 2016 EACVI/ASA recommendation² to assess diastolic function. This study defined "heart stress" (elevated NT-proBNP in asymptomatic individuals with risk factors, regardless of structural heart disease or cardiac dysfunction) and "patients at risk for HF" (normal NTproBNP and at least one HF risk factor). All patients were categorized into six groups: (I) no HF, no risk, (II) at risk for HF, (III) heart stress, (IV) HFpEF, (V) HFmrEF, and (VI) HFrEF. Echocardiographic findings were compared among groups (II) to (VI), using ANOVA, Kruskal-Wallis and Chi-squared test, when needed. Results In a cohort of 930 outpatients (mean age 66±11 years, 61% female), 34.2% were diagnosed with HF, 22.3% experienced heart stress, 37.8% were at risk for HF, and 12.8% had neither HF nor risk factors (Figure). While NT pro BNP showed progressive increase, LVEF showed a progressive decline across the groups, reaching its lowest in HFrEF patients (Table). Simultaneously, left ventricular mass index (LVMi), left atrial volume index (LAVi), and maximal velocity of tricuspid regurgitation (TR Vmax) significantly increased in a stepwise manner. Variations in predominant LV geometry were significant across groups (p<0.001): normal LV geometry in those without HF (60.8%), concentric LV remodeling in at-risk patients (38.6%), normal LV geometry in heart stress (49%), concentric LV hypertrophy (LVH) in HFpEF (27.7%), eccentric LVH in HFmrEF (42.3%), and both concentric and eccentric LVH in HFrEF (43.3% each). Diastolic dysfunction increased prevalence across the groups (12.9% vs 24.7% vs 37.6% vs 19.6% vs 51.1%, p<0.001). Remarkably, HFmrEF group had the highest proportion of undetermined diastolic function (14.7% vs 23.1% vs 27.9% vs 50% vs 26.7%, p<0.001). Conclusions The mobile phone app used in primary care setting allowed identification of significant number of individuals in the pre-HF stages, warranting further investigation. Distinct echocardiographic differences in pre-HF stages and HF phenotypes provide valuable insights for early detection and tailored treatments.

Clustering analysis based on clinically available data for improving risk stratification and outcome prediction of hypertension

Abstract Background Hypertension (HTN) is a heterogeneous condition with several factors contributing to adverse outcomes. Machine learning can harness complex data to unveil outcome predictors and guide prevention. Purpose To use clustering analysis on clinical data to identify HTN risk profiles and their associations with cardiovascular abnormalities and clinical outcomes. Methods A cohort of 14,840 UK Biobank hypertensive participants without pre-existing heart failure (HF) who underwent cardiovascular magnetic resonance (CMR) assessment was examined using K-means clustering on 79 clinical attributes. The clusters’ association with incident HF, mortality, atrial fibrillation (AF), and major adverse cardiovascular events (MACE) were evaluated, alongside imaging characteristics, with mediation analysis probing the role of imaging in risk differentiation. All post-hoc analyses were adjusted for vascular risk factors (VRFs), including diabetes, hypercholesterolaemia, previous myocardial infarction. Results Three distinct clusters differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles were identified. Cluster 1 (lowest risk), predominantly females, exhibited the most favourable metabolic profile and outcomes. Cluster 2 (highest risk), predominantly males, had the most adverse metabolic and cardiovascular profiles, and the highest risk of all adverse outcomes, especially AF and HF (hazard ratio (HR) 1.80 [1.45–2.25] and 1.85 [1.39–2.46]; p <0.005). This group was associated with more eccentric LV hypertrophy (LVH), overall poorer left atrial emptying function (LAEF), bi-ventricular systolic function and LV mechanics, and higher systemic vascular resistance (Figure 1). Cluster 3 (intermediate risk) was a more heterogeneous group with the highest burden of diabetes and adiposity and a moderate rise in AF and MACE risk (HR 1.61 [1.12-2.32] and 1.30 [1.07-1.58]; p <0.05). This cluster was associated with concentric LV remodelling and better indices of cardiac mechanics, but greater impairment in LA booster pump function (active LAEF) than Cluster 2 (Figure 1). Cluster 2's effect on MACE was mostly mediated through LV mass increase (proportion mediated, 67%), followed by changes (reducing) in LV global longitudinal strain (33%), and ejection fraction (25.4%). The indirect effect of CMR changes in the association between cluster 3 and MACE was much smaller with the highest proportion of the effects mediated through increased myocardial wall thickness (26%) but not LV mass, and changes in all the components of LA function. Conclusions Clinical data clustering provides insight into distinct HTN risk profiles, each with specific imaging characteristics and clinical trajectories, hinting at different pathophysiological mechanisms. Enhanced phenotyping can facilitate tailored interventions based on the disease subtype and improve clinical outcomes.Figure 1.

Interarm systolic blood pressure difference is associated with left ventricular concentricity and concentric remodeling.

Interarm systolic blood pressure difference (IASD) values >15 mmHg (IASD > 15) are associated with increased cardiovascular risk, yet the underlying mechanisms remain unclear. This report evaluated whether IASD >15, assessed by different protocols [sequential or simultaneous; based on one or several blood pressure (BP) readings], was associated with adverse left ventricular (LV) remodeling. This cross-sectional study evaluated 605 individuals who underwent clinical and echocardiography evaluation and three pairs of simultaneous arm BP readings. IASD was estimated by seven distinct protocols (three simultaneous and four sequential BP measurements criteria). The cohort had a mean age of 53.5 ± 15.4 years, with 51% being women, 23% with LV hypertrophy, 14% with LV concentricity, 69% with normal geometry, 8% with concentric remodeling, 17% with eccentric hypertrophy and 6% with concentric hypertrophy. Multivariable logistic regression revealed that IASD >15 defined by simultaneous measures of the last two pairs of BP readings (IASDsim2) and sequential arm BP readings (right-left-right arm sequence; IASDseq3) were related to LV concentricity (odds ratio [95% CI] = 3.24 [1.02-10.28], P = 0.046 and 2.56 [1.09-6.00], P = 0.030, respectively) and LV concentric remodeling (odds ratio [95% CI] = 4.12 [1.08-15.78], P = 0.039 and 4.16 [1.61-10.76], P = 0.003, respectively). Conversely, IASD >15 defined by any criteria showed no association with LV hypertrophy. Individuals with IASD >15 defined by IASDsim2 and IASDseq3 are associated with adverse LV remodeling, namely LV concentricity and LV concentric remodeling. These findings suggest that both criteria might be potentially used to preferentially assess abnormal IASD in the setting of clinical practice.

Left Ventricular Concentric Remodeling In Deployed Post 9/11 Veterans And Effects On Exercise Performance.

Left Ventricular Concentric Remodeling In Deployed Post 9/11 Veterans And Effects On Exercise Performance.

Associations between visceral and liver fat and cardiac structure and function: a UK Biobank study.

Different fat depots have connected to cardiovascular health. We assessed the associations of abdominal magnetic resonance-quantified visceral adipose tissue (VAT) and liver fat (proton density fat fraction, PDFF) with cardiac magnetic resonance (CMR)-measured cardiac structure and function, and considered potential mechanism. Our study encompassed 10,920 participants from the UK Biobank. We utilized multiple linear regression and multiple mediation analyses to estimate the connections between VAT or PDFF and CMR metrics. Elevated VAT or PDFF exhibited associations with adverse left ventricular (LV) structure (increased wall thickness, concentric LV remodeling), impaired LV function (lower LV global functional index, absolute value of LV global longitudinal strain), and diminished left atrial volumes and stroke volume (all p-values were significant）. Upon stratifying participants based on VAT and PDFF combinations, all groups, except the low VAT-low PDFF group, were linked to unfavorable cardiac remodeling metrics. The high VAT-high PDFF group displayed the most pronounced cardiac alterations. Multiple mediation analyses were employed to investigate potential mediating roles of systolic blood pressure (SBP), diabetes, dyslipidemia and blood biomarkers (lipidemia, transaminases) in the adipose-CMR relationship. The findings suggested that VAT or PDFF was related to SBP, diabetes, dyslipidemia, lipid profile, liver function, and glucose. Several potential mediating pathways were identified, primarily through SBP and triglyceride-glucose index, which only partially explained the adipose-CMR relationship. We established the independent associations of VAT and PDFF with unhealthy cardiac structure and function. Furthermore, it identifies SBP and insulin resistance as important mediating factors.

Sex-related disparities in aortic stenosis from disease awareness to treatment: a state-of-the-art review.

This state-of-the-art review aimed to synthesize evidence from various sex-stratified studies on aortic stenosis (AS), focusing on the difference in clinical presentation, anatomical characteristics, pathophysiology, and management of AS. In comparison to men, women with AS are present at later stages, are older, more symptomatic, frailer, and exhibit higher operative risk [Society of Thoracic Surgeons (STS) score]. Women tend to have smaller aortic valve (AV) areas and left ventricular (LV) outflow tract, leading to lower stroke volumes (SVs) than men and have a higher prevalence of paradoxical, low-flow, low-gradient AS. In women, chronic pressure overload due to AS results in concentric LV remodelling and hypertrophy, characterized by reduced LV cavities, higher filling pressures, lower wall stress, and more diastolic dysfunction. Conversely, men exhibit more dilated eccentric LV remodelling and hypertrophy. AVs in women are less calcified but more fibrotic. Moreover, women are often underdiagnosed, have severity underestimated, and experience delays or receive fewer referrals for AV replacement (AVR). However, women tend to benefit from transcatheter AVR (TAVR) with a long-term survival advantage over men, although the incidence of vascular complications and bleeding events in 30 days after TAVR is higher in women. Surgical AVR (SAVR) in women has high operative risk, is technically demanding and has poorer outcomes with increased mortality at 30 days compared to men. According to the STS score and EuroSCORE, the female sex itself is considered a risk factor for SAVR. Therefore, addressing sex-related disparities in AS and increasing awareness among physicians promises improved diagnosis and treatment, facilitating equitable care and the development of sex-specific personalized medicine.

P135 FITNESS INFLUENCES THE RELATIONSHIP BETWEEN EXERCISE BLOOD PRESSURE AND LEFT VENTRICULAR STRUCTURE: EVIDENCE FROM THE EXERCISE STRESS TEST COLLABORATION (EXERTION) STUDY

Background. A hypertensive response to exercise is associated with left ventricular (LV) remodelling, a principal sign of hypertensive heart disease. Fitness may modify this relationship, making clinical interpretation of peak exercise systolic blood pressure (SBP) challenging. This study examines the influence of fitness on the relationship between peak exercise SBP and LV structure. Methods. Cardiovascular structure and function (LV mass index (LVMI), LV relative wall thickness (RWT), cardiac output (CO) and total peripheral resistance (TPR)) were assessed at rest by echocardiography on 4,309 individuals (aged 58.6±12.7 years,52.0% male). SBP was measured at peak treadmill exercise, and fitness (exercise duration (minutes)) was grouped into thirds. Multiple regression analysis was conducted with fitness as an interaction term with peak exercise SBP, adjusted for age, sex, pre-exercise SBP, and cardiovascular disease (CVD) history. Results. Peak exercise SBP was similar across low (180±26.5mmHg), moderate (181±26.3mmHg) and high (182±24.5mmHg) fitness groups. Fitness modified the relationship between exercise SBP and LVMI; each 5mmHg increase in exercise SBP was associated with LVMI in moderate [0.27(0.10–0.43) and high [0.25(0.06–0.43)] fitness groups, which was not observed among those with low fitness [-0.05(-0.22–0.12)]. RWT increased with higher peak exercise SBP at all fitness levels (all p<0.001), with higher values among those with low fitness. Prevalence of LV concentric remodelling was highest in those with low fitness (29.9%) and lowest in those with high fitness (10.8%). A lower CO and higher TPR were observed in the low fitness group (7.5±2.5L/min and 14.3±5.1mmHg min/L) compared to those with high fitness (10.9±3.1L/min and 9.2±2.09mmHg min/L). Conclusion. Whilst a small effect, fitness modified the peak exercise SBP-LV structure relationship, such that for similar peak exercise SBP, those with low fitness exhibit a more adverse LV remodelling, with lower CO and higher TPR, compared to those with higher fitness. Considering fitness when interpreting SBP and cardiac imaging results from exercise stress testing may be relevant in identifying CVD risk and optimal patient management.

Myocardial ischemia in patients with mild-to-moderate aortic stenosis: Interaction with cardiac remodeling and adverse events

BackgroundThe association between aortic valve stenosis (AVS) and myocardial perfusion abnormalities has been incompletely characterized. We sought to assess the predictors of myocardial ischemia in patients with mild-to-moderate AVS, and its relationship with long-term prognosis. MethodsEighty-nine patients with mild-to-moderate AVS (peak velocity between 2.6 and 4.0 m/second and aortic valve area > .6 cm2/m2), preserved left ventricular (LV) function, and either normal coronary arteries (28 patients) or non-obstructive coronary artery disease (<50% stenosis; 61 patients) were individuated. Myocardial perfusion imaging was performed using a cadmium–zinc–telluride camera, and the summed difference score (SDS) was computed. The presence of either LV hypertrophy (LVH) (LV mass index [LVMI] > 115 g/m2 [males] or 95 g/m2 [females]) or concentric LV remodeling (relative wall thickness: >.42) was determined at two-dimensional echocardiography. ResultsForty (45%) and 49 (55%) patients had mild and moderate AVS, respectively. Fifty (56%), 17 (19%), and 22 (25%) patients had normal LV geometry, concentric LV remodeling, and LVH, respectively. An interaction between LV remodeling and inducible ischemia was revealed with progressively higher values of SDS in patients with normal LV geometry (3 ± 3), concentric remodeling (4 ± 2), and LVH (7 ± 2) (P < .001).Accordingly, a moderate correlation existed between LVMI and SDS values (R: .67; P < .001). After a median follow-up of 84 ± 47 months, 27 adverse events were recorded, including 19 AV replacements and 8 deaths. On multivariable analysis, the presence of LVH (hazard ratio [HR]: 6.46; 95% confidence interval [CI]: 2.09–20.00; P = .001) and a higher SDS (HR: 1.41; 95% CI: 1.15–1.75; P = .001) were the two independent predictors of AE. ConclusionsIn patients with mild-to-moderate AVS, myocardial ischemia correlates with the severity of adverse LV remodeling. Patients with LVH and ischemia are at increased risk of AE.

Sex Differences in Outcomes of Adults with Repaired Coarctation of Aorta and Concomitant Aortic Valve Disease

BackgroundAortic valve disease is common in adults with coarctation of aorta. However, no systematic comparative analyses have been performed of the clinical course of aortic valve disease for male vs female patients in this population. The purpose of this study was to compare cardiac remodelling, onset of symptoms, and incidence of aortic valve replacement (AVR) for male vs female patients. MethodsA retrospective study was conducted of adults with repaired coarctation of aorta and ≥ moderate aortic stenosis and/or aortic regurgitation. Cardiac remodelling (left ventricular [LV], left atrial, right ventricular [RV], and right atrial structure and function) and symptomatic and/or functional class were determined at the baseline encounter. Development of new-onset symptoms and the incidence of AVR were ascertained for the period from baseline to last encounter. ResultsWe identified 214 patients (121 male [57%], 93 female [43%]). Although both groups had a similar aortic valve gradient, aortic valve area indexed to body surface area, aortic regurgitation severity, and functional status at baseline, female patients had more LV concentric hypertrophy and remodelling, left atrial hypertension and dysfunction, elevated RV systolic pressure, and RV systolic dysfunction. Of 151 patients without symptoms at baseline,102 (72%) developed symptoms. Female sex was independently associated with new-onset symptoms (adjusted hazard ratio 1.14, [95% confidence interval 1.05-1.23]). Of 214 patients, 191 (89%) underwent AVR. Female sex was not associated with AVR upon multivariable analysis. However, LV concentric hypertrophy and remodelling (both of which were more common in female patients) were associated with new-onset symptoms and AVR. ConclusionsFemale patients, compared to male patients, had more-advanced cardiac remodelling, and more-rapid onset of symptoms, but a similar risk of AVR.

Plasma and Myocardial miRNomes Similarities and Differences during Cardiac Remodelling and Reverse Remodelling in a Murine Model of Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome characterised by multiple risk factors touching various organs outside the heart. Using a murine HFpEF model, we studied cardiac reverse remodelling (RR) after stopping the causing metabolic-hypertensive stress (MHS; Angiotensin II [AngII] and a high-fat diet [HFD]) after 28 days and introducing voluntary exercise (VE) for four more weeks. We measured the effects of MHS and RR on the plasma and myocardial microRNA (miR) profile (miRNome) to characterise better cardiac and non-cardiac responses to HFpEF-inducing risk factors and their reversibility. AngII alone, the HFD or the MHS caused cardiac hypertrophy (CH), left ventricular (LV) concentric remodelling and left atrial enlargement in females. Only AngII and the MHS, but not HFD, did in males. After RR, CH, LV concentric remodelling and atrial enlargement were normalised. Among the 25 most abundant circulating miRs, 10 were modulated by MHS. Plasma miRNomes from AngII, HFD or MHS mice shared 31 common significantly modulated miRs (24 upregulated and 7 downregulated), suggesting that the response of organs producing the bulk of those circulating miRs was similar even for seemingly different stress. In the LV, 19 out of 25 most expressed miRs were modulated. RR restored normality for the plasma miRNome but not for the LV miRNome, which remained mostly unchanged. Our results suggest that abnormalities persist in the myocardium of the HFpEF mice and that the normalisation of circulatory markers may be falsely reassuring after recovery.

Sex differences in clinical profile, left ventricular remodeling and cardiovascular outcomes among diabetic patients with heart failure and reduced ejection fraction: a cardiac-MRI-based study

BackgroundHeart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM.MethodsA total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes.ResultsWomen were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men.ConclusionsAmong patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

Left ventricular concentric remodeling in COPD patients: A cross-sectional observational study

ObjectiveTo investigate the association between left ventricular structure and disease severity in COPD patients. MethodsTwenty-eight COPD patients were stratified according to the disease severity, using the BODE index, into Lower (n=17) and Higher (n=11) groups, composed of patients with lower severity (BODE <5) and higher severity (BODE ≥5), respectively. Left ventricle (LV) was assessed by 2D-echocardiography. BODE index was calculated using body mass index (BMI); forced expiratory volume in the first second (FEV1, %); modified Medical Research Council (mMRC) and distance walked during 6-minute walk test (6MWD). ResultsPatients in the Higher group showed lower oxygen arterial saturation (p=0.02), FEV1 (p<0.01) and 6MWD (p=0.02) and higher value of relative posterior wall thickness (RWT) compared to Lower group (p=0.02). There were significant associations between LV end-systolic diameter (LVESD) and BODE index (r=−0.38, p=0.04), LV end-diastolic diameter (LVEDD) and FEV1 (r=0.44, p=0.02), LVEDD and BMI (r=0.45, p=0.02), LVESD and BMI (r=0.54, p=0.003) and interventricular septal thickness and 6MWD (r=−0.39, p=0.04). ConclusionsMore severe COPD patients, BODE score ≥5, may have higher RWT, featuring a possible higher concentric remodeling of LV in this group. Besides that, a greater disease severity may be related to LV chamber size reduction.

Association of body adiposity with left ventricular concentric remodeling and diastolic dysfunction

AbstractBackgroundObesity is a significant risk factor for heart failure with preserved ejection fraction (HFpEF). In this study, we explore the relationships between body mass index (BMI) and adipose tissue compartments such as visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), with respect to left ventricular (LV) structure and function in subjects with preserved LV systolic function.MethodsBetween January and December 2020, this retrospective study included 749 participants who exhibited preserved LV systolic function and underwent transthoracic echocardiography along with abdominal computed tomography. LV structural and functional variables as well as EAT, VAT, and SAT thickness were evaluated using echocardiography and computed tomography.ResultsSAT decreased, while VAT and EAT progressively increased with age. There were significant correlations between BMI and various adipose tissues, with the strongest correlation observed with SAT (r = .491, p &lt; .001) compared to VAT (r = .371, p &lt; .001) or EAT (r = .135, p &lt; .001). However, EAT demonstrated the most substantial association with decreased LV end‐diastolic dimension, LV end‐systolic dimension, and septal mitral annular velocity and increased relative wall thickness (all p &lt; .05), while VAT and SAT did not show significant associations with LV remodeling and functional parameters after adjusting for clinical variables.ConclusionEAT is the most critical adipose tissue influencing LV geometric and functional changes, compared with VAT or SAT. Thick EAT is associated small LV chamber size, concentric remodeling, and relaxation abnormalities.

Association of Cardiovascular Fibrosis, Remodeling, and Dysfunction With Frailty, Prefrailty, and Functional Performance: The Multi-Ethnic Study of Atherosclerosis.

Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remains unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA). As part of the MESA study, 3 045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010 and 2012. Of these, 1 743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up exam: 2016-2018) which were used to generate a binary combined frail/prefrail versus robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction). Participants were 66 ± 8 years, 52% female at the time of imaging, and 29.4% were classified as frail or prefrail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (odds ratio [OR] 1.89, p = .008; Coef. -52.9, p < .001), increased ECV (OR 1.10, p = .002; Coef. -4.0, p = .001), and worsening left atrial strain rate at early diastole (OR 1.56, p ≤ .001; Coef. -22.75, p = .027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m). All associations with 6MWT performance were attenuated with adjustments for risk factors whereas ECV and LA strain rate remained independently associated with frailty. These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis, and physical frailty.

Cardiomyocyte Specific MLK3 Deletion Opposes LV Dysfunction and Cardiac Fetal Gene Re-Expression

Study Objective: To determine the cardiac myocyte (CM) and blood pressure-independent effects of Mixed lineage kinase 3 (MLK3) in the regulation of left ventricular (LV) function at baseline and in response to pathological stress. Background: MLK3 functions as a direct substrate effector of cGMP-dependent protein kinase 1α (PKG1α). Whole-body MLK3 deletion in mice increases cardiac dysfunction and remodeling after pressure overload and prevents the therapeutic effect of cGMP augmentation on LV function. However, MLK3 deletion also causes hypertension, which may confound these findings. Hypothesis: MLK3 opposes LV dysfunction through a blood pressure-independent function in the cardiac myocyte (CM). Methods: We generated mice harboring LoxP sites flanking the MAP3K11 gene encoding MLK3 (MLK3fl/fl) and crossed them with αMHC-Cre transgenic mice, enabling constitutive postnatal cardiac myocyte-specific MLK3 deletion (CMKO). Male and female 3- and 6-month-old MLK3 CMKO and control MLK3 intact (MLK3fl/fl Cre-) littermates were studied in the basal state. We also performed transaortic constriction (TAC) or sham surgery for 4 weeks on 3-month-old male mice. We assessed LV structure and function by organ mass, echocardiography, pressure volume loop analysis, qPCR, and immunoblot. In basal and TAC studies, we used age-matched αMHC-Cre x MLK3+/+ (non-floxed) mice as additional controls. Results: MLK3 gene excision in CMs was confirmed by PCR. By 6 months of age, MLK3 CMKO mice displayed: progressive reduction in LV ejection fraction; increase in LV internal diameter; and LV hypertrophy, indicating LV dysfunction and pathological remodeling, compared with littermate controls or with αMHC-Cre x MLK3+/+ non-floxed mice. This effect was more prominent in females than in males. LV fetal gene expression did not differ between genotypes at 3 months. At 6 months of age, however, the fetal genes nppa, RCAN, and CTGF were significantly upregulated in both male and female MLK3 CMKO mice, compared with MLK3 intact, indicating pathological remodeling. After 4-week TAC, MLK3 CMKO LVs developed more severe reduction in LV systolic function compared with MLK3 intact littermates as assayed by echocardiographic measures of LV ejection fraction; and invasive hemodynamic indices of preload recruitable stroke work, maximum LV pressure and LV developed pressure. The MLK3 CMKO LVs also demonstrated a more eccentric remodeling phenotype in which LV mass/tibia length, LV end diastolic and end systolic diameters increased more severely in CMKO mice, with corresponding reduced LV wall thicknesses. Finally, lung mass/tibia length was elevated in the MLK3 CMKO TAC mice compared to MLK3 intact TAC littermates, indicating overt heart failure. Conclusion: (1) MLK3 functions as a tonic inhibitor of LV dysfunction and pathological remodeling through a role in the CM, possibly through sex-specific mechanisms. (2) Intact MLK3 is required for normal LV compensation and concentric remodeling in response to pressure overload. These findings have important clinical implications, as drugs which activate PKG1 in heart failure improve outcomes but are limited by excess hypotension. As a myocardial PKG1 substrate which opposes pathological LV remodeling through blood pressure-independent mechanisms, MLK3 may represent a candidate therapeutic target for heart failure. NIH 1R01HL162919. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Features of structural and geometric cardiac remodeling in patients with diabetes mellitus depending on chronic kidney disease stages

Objective. To study the features of structural and geometric cardiac remodeling in patients with diabetes mellitus (DM) depending on the stage of chronic kidney disease (CKD). Materials and methods. We examined 499 patients (127 men and 322 women) with type 1 DM (133 people) and type 2 DM (316 people) aged 62 [52;69] years. The comparison group consisted of 65 randomly selected volunteering individuals (54 women and 11 men) without disorders of carbohydrate metabolism and kidney damage aged 59 [46;66] years. The laboratory examination of the patients included the measurement of serum creatinine, eGFR according to the CKD-EPI equation. An echocardiographic investigation was performed to study structural and geometric heart parameters. Left ventricular hypertrophy (LVH) was diagnosed when the left ventricular myocardial mass index (LVMI) exceeded 115 g/m2 in men and 95 g/m2 in women. Results. LVH was detected in 57.7 % of patients with DM, while in the comparison group – in 35.4 %. The frequency of LVH increased with a decrease in eGFR and was diagnosed in 100 % of cases with CKD 5. In patients with DM, the left ventricular concentric remodeling significantly predominated (29.2%). Multiple linear regression analysis demonstrated the influence of age (ß=0.30, p=0.01) and serum creatinine (ß = 0.15, p &lt; 0.0001) on the LVMI, independent of other factors, which confirms their independent pathogenetic significance. Conclusion. Thus, patients with DM regardless of the CKD stage have structural and functional changes in the LV myocardium. Regardless of the nitrogen-excretion function of the kidneys, the predominant pattern of LV remodeling is concentric. The study of the features of structural and functional restructuring of the left heart in patients with diabetes should be taken into account in determining the cardiovascular prognosis.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68–77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82–1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3–6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

Increased aortic pressures and pulsatile afterload components promote concentric left ventricular remodeling in adults with transposition of the great arteries and arterial switch operation

BackgroundFunctional abnormalities of the ascending aorta (AA) have been mainly reported in young patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA). ObjectivesTo compare systolic, diastolic brachial and central blood pressures (bSBP, bDBP, cSBP, cDBP), aortic biomechanical parameters, and left ventricular (LV) afterload criteria in adult ASO patients with healthy controls and to assess their relationships with LV remodeling and aortic size. Materials and methodsForty-one prospectively enrolled patients (16.8 to 35.8 years) and 41 age- and sex-matched healthy volunteers underwent cardiac MRI to assess LV remodeling with simultaneous brachial BP estimation. After MRI, carotid-femoral tonometry was performed to measure pulse wave velocity (cfPWV), cSBP and cDBP for further calculation of pulse pressure (cPP), AA distensibility (AAD), and AA and LV elastance (AAE, LVE). ResultsbSBP, bDBP, cSBP,cDBP and cPP were all significantly higher in ASO group than in controls: cSBP (116.5 ± 13.8 vs 106.1 ± 12.0, p < 0.001), cDBP (72.5 ± 6.9 vs 67.1 ± 9.4, p = 0.002), cPP (44.0 ± 12.1 vs 39.1 ± 8.9, p = 0.003) and not related to aortic size. AAD were decreased in ASO patients vs controls (4.70 ± 2.72 vs 6.69 ± 2.16, p < 0.001).LV mass was correlated with bSBP, cSBP, cPP (ρ = 0.48; p < 0.001), while concentric LV remodeling was correlated with AAE (ρ = 0.60, p < 0.001) and LVE (ρ = 0.32, p = 0.04), but not with distensibility. ConclusionEven without reaching arterial hypertension, aortic sBP and PP are increased in the adult TGA population after ASO, altering the pulsatile components of afterload and contributing to LV concentric remodeling.