Higher Left Ventricular Mass Index Research Articles

Left ventricular mass index and prognosis of symptomatic severe aortic stenosis in women and men

Abstract Background Symptomatic severe aortic stenosis (AS) requires surgical (SAVR) or transcatheter aortic valve replacement (TAVR), and many patients are on the procedure waiting list. The diagnosis of severe AS is based on clinical and echocardiographic criteria, such as left ventricular ejection fraction (LVEF), aortic valve area (AVA), mean transvalvular gradient, and peak aortic jet velocity. However, there is a gap in knowledge regarding the influence of left ventricular mass on the prognosis of these patients, especially considering differences between women and men. Purpose To evaluate the influence of left ventricular mass index (LVMi) on the mortality of women and men with severe AS awaiting SAVR or TAVR. Methods A prospective study analysed the death rate in 531 outpatients with symptomatic severe AS with mean transvalvular gradient ≥40 mmHg, AVA ≤1.0 cm2, or peak aortic jet velocity ≥4.0m/s at echocardiography with the indication for TAVR or SAVR in the period from April 2020 to February 2024. Baseline data included analysis of clinical characteristics, echocardiographic variables, and the presence of coronary artery disease (CAD). Statistical analyses were performed using the Kaplan-Meier (K-M) and Cox proportional hazards methods to analyze mortality rates in women and men. Results The mean age was 74.7±11.6 years, with 283 (53.3%) men. Over a follow-up period of 2.67±1.22 years, death occurred in 165 (31.1%), 148 (86%) due to cardiovascular disease, and 152 (92%) had heart failure (HF) NYHA II to IV, 51 (9,6%) had angina, and syncope in 11 (2.1%) of the patients. Patients who died had lower LVEF (61.4%±8.9% vs. 58.8%±10.8%; p=0.008) and higher LVMi (125.3±32.5 g/m2 vs. 115.5±29.3 g/m2; p=0.001). Angina, syncope, hypertension, dyslipidemia, diabetes, smoking, atrial fibrillation, and CAD prevalence were similar in living patients and in those who died. Both groups had similar echocardiographic data, such as left atrial volume, mean transvalvular gradient, and peak jet velocity. TAVR and SAVR were done in 111 (20.9%) and 162 (30.5%) patients. Of these, 21 (18.9%) and 20 (12.4%) died during follow-up, respectively. Cumulative mortality of all patients was higher with LVMi >115 g/m2 compared to ≤115 g/m2 (p=0.008)(Figure). In women but not in men, cumulative mortality was higher with LVMi >115 g/m2 compared to ≤115 g/m2 (p=0.046). Cox multivariate analysis, adjusted for LVEF, LVMi, CAD, and age, showed LVMi as an independent variable for death [HR=1.50 (95%CI: 1.10-2.05); p=0.011]. LVEF [HR=0.97 (95%CI: 0.95-0.99); p=0.009] and LVMi [HR=1.75 (95%CI: 1.10-2.79); p=0.016] were independent variables for death in women, but not in men. Conclusion Women with higher LVMi and lower LVEF should have valve intervention prioritized.Figure

Autonomous cortisol secretion in patients with primary aldosteronism is associated with left ventricular hypertrophy and diastolic dysfunction

Abstract Background and Aims: Autonomous cortisol secretion (ACS) constitutes a significant portion of patients diagnosed with primary aldosteronism (PA) and is potentially linked to adverse cardiovascular outcomes. This study aimed to explore the impact of ACS on cardiac remodeling and diastolic dysfunction in PA patients. Methods We prospectively enrolled 567 PA patients from March 2000 to March 2023. ACS was defined as a cortisol level >1.8 μg/dL after a 1 mg dexamethasone suppression test (DST). Clinical, biochemical, and echocardiographic data were collected at baseline and during one-year follow-up after targeted treatments including adrenalectomy and mineralocorticoid receptor antagonist administration. Results In this prospective cohort, 21.5% of PA patients had concurrent ACS. PA patients with ACS were older and had a higher prevalence of diabetes. They also exhibited significantly higher left ventricular mass index (LVMI) and worse diastolic function (E/e'). Baseline post-1 mg DST cortisol levels positively correlated with baseline LVMI and E/e' in restricted cubic spline analysis. Multivariable linear regression analysis showed that ACS presence was significantly associated with higher LVMI and worse E/e' after adjusting for significant variables. Among patients who underwent adrenalectomy, both those with and without ACS showed significant improvements in LVMI and E/e'. Patients who received mineralocorticoid receptor antagonist treatment also showed significant improvement in E/e', irrespective of ACS presence. However, significant LVMI improvement was observed only in PA patients without ACS who received mineralocorticoid receptor antagonist treatment. Conclusions The presence of ACS in PA patients was associated with worse left ventricular hypertrophy and diastolic dysfunction. Adrenalectomy and mineralocorticoid receptor antagonist treatment partially reversed cardiac remodeling in PA patients with ACS.

Relationship between renin, aldosterone, aldosterone-to-renin ratio and left ventricular mass index in young adults

Abstract Background Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, especially in middle-aged and elderly populations. It is unclear if early changes in PA biomarkers can affect left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases. Aim To evaluate the relationship between PA biomarkers, namely renin concentration, aldosterone concentration and aldosterone-to-renin ratio (ARR), and LVMI in young adults. Methods The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27. Participants with PA biomarkers and LVMI measured by cardiac magnetic resonance imaging were included. Females who were on oral contraception were excluded due to its confounding effect on the ARR. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results Of 758 participants, 252 (33.2%) were females and the mean (SD) age was 26.7 (0.4) years. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m²; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusion An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function. One may speculate that an intervention trial in young adults with subclinical PA is warranted to determine the role of aldosterone blockade in preventing future cardiovascular diseases.

Association of inflammation with left ventricular mass index in patients with rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is an inflammatory autoimmune disease associated with cardiovascular organ damage. Purpose We explored the association of inflammatory markers with left ventricular (LV) mass index during 22 months of follow-up in patients with RA. Methods Eighty-three outpatients with RA (age 55±12 years, 71 % women) with indication for biological (b) or targeted synthetic (ts) disease modifying antirheumatic drug (DMARD) therapy were examined with echocardiography at baseline and after 22 months. LV mass was indexed for height in the allometric power of 2.7. Serum concentrations of the inflammatory markers, C-reactive protein (CRP), serum amyloid A (SAA) and calprotectin were measured by MALDI-TOF mass spectrometry. Results At baseline, 37% had hypertension, 6% diabetes, 21% obesity and 100% were using b/ts DMARDs. The inflammatory markers decreased during follow-up (all p<0.001), while the LV mass index did not change (33.1±8.1 g/m^2.7 vs. 33.5±7.3 g/m^2.7, p=0.57). The prevalence of hypertension, diabetes and obesity were unchanged at follow-up (p>0.05), but the percentage of patients using b/ts DMARDs had decreased to 83% (p<0.001). In multivariable analyses, higher CRP and SAA at baseline were associated with higher LV mass index at both baseline and follow-up independent of presence of obesity, hypertension, age, sex or treatment with b/ts DMARDs at follow-up (Table 1). Inflammatory markers at follow-up were not associated with LV mass index (Table 1), but use of b/ts DMARDs at follow-up were associated with lower LV mass index after adjusting for inflammatory markers, age, sex, presence of obesity and hypertension (Table 1). Conclusion Higher levels of inflammatory markers at baseline were associated with greater LV mass index in RA patients. The use of immunosuppressive treatment throughout the study period was associated with lower LV mass index at follow-up, pointing to a role of chronic inflammation in LV hypertrophy.

Chronic inflammation is associated with impaired cardiac structure and function in patients with inflammatory arthritis: the ARTCADIA Study

Abstract Background Inflammation as an underlying cause of cardiac dysfunction has been underscored in recent years. Patients with inflammatory arthritis (IA) are at risk of being exposed to a high degree of chronic and systemic inflammation. It is therefore important to investigate whether high inflammatory burden impacts cardiac structure and function in patients with IA. Purpose To examine the impact of long-term inflammation on measures of cardiac structure and function in individuals with rheumatoid arthritis (RA) and axial Spondyloarthritis (axSpA), collectively referred to as IA, in a large cohort. Methods In a prospective cohort study, outpatients with a diagnosis of IA were included over two years during their biannual rheumatological routine appointment. In total, 1,285 participants were included. Participants were evaluated at a cardiology research center where echocardiography was performed following a pre-defined protocol. To evaluate chronic inflammation, C-reactive protein (CRP) was averaged from clinical outpatient visits registered in a rheumatological database. Uni- and multivariable linear regressions were used to examine the relationship between echocardiographic measures and log-transformed CRP. Results Among the 1,285 participants, 903 (70%) were diagnosed with RA, 358 (28%) with axSpA, and 24 (2%) with other forms of IA. Mean age was 60 ± 13 years, 64% were female. The median number of outpatient visits was 30 (Interquartile range (IQR): 18 - 48), median disease duration was 12 (IQR: 6 - 20) years, and the median outpatient CRP was 5.7 (IQR: 3.7 – 9.8) mg/L. 519 (40%) patients had hypertension (HT), 113 (9%) diabetes mellitus (DM), 76 (5.9%) ischemic heart disease (IHD) and 35 (2.5%) heart failure (HF). Mean left ventricular (LV) ejection fraction was 54.6 ± 5.7%, mean numerical global longitudinal strain (GLS) was 17.8 ± 2.4%, mean LV mass index (LVMi) was 73 ± 18 g/m2 and mean tricuspid annular plane systolic excursion (TAPSE) was 2.5 ± 0.4 cm. In univariable analyses, higher levels of CRP were significantly associated with lower GLS, p < 0.001; higher E/e’, p = 0.001; higher LVMi, p < 0.001 and lower TAPSE, p = 0.005 (Figure). The associations remained significant after adjusting for clinical characteristics including disease duration, age, sex, blood pressure, body mass index, physical activity, pack-years of smoking, cholesterol, HT, DM, heart rate, atrial fibrillation, IHD and HF (p < 0.05 for all associations). We observed no significant interactions between the IA diagnosis and inflammation across the significant echocardiographic measures. Conclusion In a large cohort of patients with IA, increasing levels of chronic inflammation determined by outpatient CRP was associated with impaired measures of cardiac structure and function and remained significant after adjusting for clinical characteristics. The prognostic and clinical implication of these findings needs to be explored in future studies.Linear regression splines

Role of CT-derived global longitudinal strain in identifying left ventricular dysfunction in patients with severe aortic stenosis and preserved left ventricular ejection fraction

Abstract Introduction In patients with severe aortic stenosis, LVEF <50% is a current class 1 indication for aortic valve replacement. There are however studies showing increased mortality in patients with asymptomatic severe aortic stenosis and LVEF between 50-59% [1, 2]. Global longitudinal strain (GLS) has emerged as a more sensitive predictor of systolic dysfunction than ejection fraction in a wide number of cardiac diseases [3]. Purpose The aim of our study was to analyze left ventricular global longitudinal strain (GLS) by cardiac computed tomography (CT) in patients with severe aortic stenosis. We hypothesized that a larger portion of patients with LVEF 50-59% have signs of systolic dysfunction by GLS as compared to patients with LVEF ≥60%. Methods We identified 238 patients (median age 81, 51.3% females) with severe aortic stenosis, assessed by cardiac CT before undergoing transcatheter aortic valve replacement at Uppsala University hospital between 2016-2019. Patients in atrial fibrillation was excluded due to suboptimal image quality. Left ventricular mass index (LVMi), EF and peak GLS were calculated. The patients were divided into three groups based on LVEF (Reduced LVEF <50%, Low-Normal LVEF 50-59% and Normal LVEF ≥60%) and compared with each other regarding GLS, biomarkers and background variables. The cut off for significantly reduced GLS was set at <16%, in accordance with recently proposed criteria [4]. Results As expected GLS was significantly reduced in all patients with LVEF <50%. Among patients with Low-Normal LVEF, 62.3% had significantly reduced GLS as compared to only 3.8% patients with Normal LVEF >60% (p < 0.001). Median GLS in Low-Normal LVEF was 15.5% (IQR 14.1 - 17.4) as compared to 20.2% (IQR 18.4 - 21.9) in Normal LVEF (p < 0.001). Patients with Low-Normal LVEF had a significantly higher LV mass as compared to patients with Normal LVEF (median LVMi 85.8 g/m² vs. 75.8 g/m², p < 0.001). NT-pro-BNP was significantly higher in patients with Low-Normal LVEF compared to Normal LVEF (median 1130 vs. 664 ng/l, p = 0.003). Conclusions Almost two third of patients with severe aortic stenosis and lower range of normal LVEF (50-59%) had abnormally reduced GLS, reflecting systolic LV dysfunction, which was uncommon among those with LVEF >60%. Patients with LVEF 50-59% also presented with higher LV mass index and higher levels of NT-pro-BNP than patients with normal LVEF >60%, reflecting hypertrophic response of the myocardium to pressure overload which over time may lead to progressive myocardial decompensation. LVEF in the range of 50-59% might be an early sign of LV decompensation in severe aortic stenosis.

Left atrial parameters predict incident atrial fibrillation and flutter in patients with heart failure with reduced ejection fraction

Abstract Background Left atrial (LA) function parameters have shown prognostic value in relation to incidence of atrial fibrillation in the general population, but this remains to be investigated in patients with heart failure with reduced ejection fraction (HFrEF). Purpose This study aimed to investigate the relationship between LA function parameters and the risk of incident atrial fibrillation/atrial flutter (AF/AFL) in patients with HFrEF. Methods Subjects free of AF/AFL were retrospectively included from a HF clinic and followed using the Danish National Patient Registry. Cox proportional hazards regression was used to assess the prognostic value of LA function parameters. These included LA ejection fraction (LAEF), peak atrial longitudinal strain (PALS), peak atrial contractile strain (PACS) and LA conduit strain (LACS). In addition, multivariable Cox regression was performed to adjust for demographic and echocardiographic parameters, including LA volume index (LAVi). The LA function parameters that remained significant in adjusted analysis were examined using cubic splines, and cutoff values corresponding to a hazard ratio (HR) equal to 1 were derived from these. Results The total study population consisted of 435 subjects with a left ventricular ejection fraction (LVEF) ≤45% (mean age 65.6±11.7 years, male sex 70.1%) free from AF/AFL at baseline. During a median follow-up of 11.4 years [IQR: 10.8, 14.2], 111 (25.5%) developed AF/AFL. Subjects who met the outcome were generally older (69.0±8.8 years vs. 64.4±12.4, p<0.001), had lower baseline heart rate, and a higher prevalence of moderate or severe valve disease (12.6% vs. 3.1%, p<0.001). They also had higher LV mass index and LV internal diastolic diameter index, but similar LVEF. These subjects had larger LAVi (30 ml/m2 [IQR: 24, 38] vs. 26 ml/m2 [IQR: 20, 32], p<0.001), while LAEF (33±14.8% vs. 39±14.9%, p<0.001), PALS (20.3% [IQR: 16.2, 26.5] vs. 23.2% [IQR: 18.6, 29.6], p=0.001), and PACS (9.7% [IQR: 6.9, 13.5] vs. 12.0% [IQR: 7.8, 16.4], p=0.004) were all significantly lower. LACS was similar between groups. In univariable Cox regression, all LA parameters were significant predictors of the AF/AFL (LAEF: HR 0.98 per 1% increase, 95% CI 0.96-0.99, p=0.0002, PALS: HR 0.96 per 1% increase, 95% CI 0.94–0.98, p=0.0008, PACS: HR 0.95 per 1%, 95% CI 0.93–0.98, p=0.0024, LACS: HR 0.96, 95% per 1% increase CI 0.92–0.998, p=0.039. In adjusted analysis, however, only LAEF (HR 0.98, 95% CI 0.976-0.995, p=0.0087) and PACS (HR 0.96, 95% CI 0.993–0.999, p=0.044) remained significant. Splines were constructed for LAEF and PACS (Figure 1), and a cutoff for increased risk of AF/AFL at 38% for LAEF and 12% for PACS, respectively, were derived (Figure 2). Conclusion LAEF and PACS are associated with risk of incident AF/AFL in patients with HFrEF, independent of clinical and echocardiographic risk factors. Our results suggest an increased risk of AF/AFL at LAEF below 38% and PACS below 12%.Figure 1 SplinesFigure 2 Cumulative incident curves

Weight status change during four years and left ventricular hypertrophy in Chinese children

ObjectiveIt is well-established that overweight/obesity is a major risk factor for left ventricular hypertrophy (LVH) in childhood. However, it is still unclear if reversing from overweight/obesity to normal weight is associated with decreased LVH in children. This study aimed to examine the association between weight status change during four years and LVH among Chinese children based on a prospective cohort study.MethodsData were obtained from the Huantai Childhood Cardiovascular Health Cohort Study in China. A total of 1,178 children without LVH at baseline (mean age: 8.3 years) were included in this study. According to weight status [normal weight or overweight (including obesity)] at baseline (2017) and follow-up (2021), children were divided, based on sex- and age-adjusted body mass index (BMI), into four groups: persistent normal weight (normal weight at both baseline and follow-up), incident overweight (normal weight at baseline but overweight at follow-up), reversal to normal weight (overweight at baseline but normal weight at follow-up), persistent overweight (overweight at both baseline and follow-up).ResultsAfter adjustment for potential confounding factors, children with incident overweight (n = 114, 30.63 ± 4.74 g/m2.7) and those with persistent overweight (n = 363, 31.56 ± 6.24 g/m2.7) had higher left ventricular mass index (LVMI) at the end of the follow-up period than those with persistent normal weight (n = 632, 28.46 ± 7.64 g/m2.7), while those who reversed from overweight to normal weight had a non-significantly lower LVMI (n = 69, 28.51 ± 4.28 g/m2.7). Compared to children with persistent normal weight, those with persistent overweight [odds ratio (OR) = 5.14, 95% confidence interval (CI) = 3.33–7.95] and those with incident overweight (OR = 3.34, 95% CI = 1.77–6.30) had an increased risk of LVH. The risk of LVH tended to decrease, although not significantly, in those who reversed from overweight to normal weight (OR = 0.76, 95% CI = 0.22–2.55).ConclusionOur findings demonstrate a positive association between overweight and left ventricular mass in children and suggest that LVH in childhood could be attenuated by weight loss.

Carotid intima-media thickness, fibroblast growth factor 23, and mineral bone disorder in children with chronic kidney disease

BackgroundCarotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)—the earliest detectable serum abnormality associated with CKD-MBD—has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD.MethodsA cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored.ResultsWe recruited 42 children aged 2–18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05).ConclusionsFGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD.

Baseline characteristics and associated factors for hypertension in children with chronic kidney disease: results from the Korean Cohort Study for Outcome in Patients with Pediatric Chronic Kidney Disease study.

Hypertension is one of the most important complications of chronic kidney disease (CKD) as it exacerbates disease progression in children. The aim of this study is to identify characteristics and factors associated with hypertension in children with CKD. This is a cross-sectional study using baseline data from the 10-year ongoing cohort study named KNOW-PedCKD (Korean Cohort Study for Outcome in Patients with Pediatric Chronic Kidney Disease). We enrolled finally 378 patients aged <18 years at seven major pediatric nephrology centers in Republic of Korea. Blood pressure was measured and samples and clinical data were collected during the patients' annual hospital visits. We found that 30.7% of the patients had hypertension (n = 116); specifically, 16.4% (n = 62) had systolic hypertension, and 22.8% (n = 86) had diastolic hypertension. Multiple logistic regression analysis indicated that older age (odds ratio [OR], 1.13; p < 0.001), female sex (OR, 2.32; p = 0.002), a high left ventricular mass index (OR, 1.05; p < 0.001), and a high urine protein/creatinine ratio (OR, 1.12; p = 0.02) were significant associated factors for systolic or diastolic hypertension. This study analyzed the associated factors for hypertension in children with CKD. Hypertension is associated with various factors, including age, sex, heart status, and proteinuria. Therefore, clinicians should consider these factors during patient evaluations to improve health outcomes.

QRS prolongation is associated with associated with adverse cardiac remodeling in hypertrophic cardiomyopathy

BackgroundSignal-averaged electrocardiogram (SAECG) records myocardial depolarization, and can detect inhomogeneous/slow conduction in fibrotic myocardium, which promotes reentrant ventricular arrhythmias (VAs). Hypertrophic cardiomyopathy (HCM) is associated with a high prevalence of cardiac fibrosis and VAs, but abnormal SAECG has low predictive power for VAs. We hypothesized that HCM-specific structural/electrical remodeling underlies this result. MethodsWe tested our hypothesis by retrospectively studying HCM patients (n = 73) who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG and 12‑lead ECG. Patients were divided into 2 groups (normal-SAECG, abnormal-SAECG) based on filtered-QRS duration (fQRSd), root-mean-square-voltage (RMS40) and low-amplitude (<40 μV) signal of terminal 40 ms of filtered-QRS (late potentials). Abnormal SAECG was defined as fQRSd > 114 ms, RMS40 < 20 μV or LAS40 > 38 ms. ResultsAbnormal SAECG was seen in ~50 % of HCM patients (37/73). In the abnormal-SAECG group, 78 % (n = 29) only had prolonged fQRSd, and 22 % (n = 8) had prolonged fQRSd plus late potentials (RMS40 < 20 μV or LAS40 > 38 ms). Mean fQRSd and LAS40 were significantly higher in the abnormal-SAECG group. The abnormal-SAECG group had significantly larger LA size, lower global-LV longitudinal systolic strain/strain rate and early-diastolic strain rate by TTE; higher LV-mass index (LVMI) and LV-scar burden by CMR; higher prevalence of repolarization abnormalities on 12‑lead ECG. LVEF and adverse outcomes (VT/VF, heart failure, death) were similar in the 2 groups. Univariate analysis showed that fQRSd is positively correlated with LVMI, LV-scar mass, and negatively correlated with global-LV early diastolic strain rate. ConclusionsIn HCM, abnormal SAECG is associated with greater structural/electrical LV-remodeling, reflecting a severe global myopathy.

O99 RELATIONSHIP BETWEEN RENIN, ALDOSTERONE, ALDOSTERONE-TO-RENIN RATIO AND LEFT VENTRICULAR MASS INDEX IN YOUNG ADULTS

Background and Objective: Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, based on studies primarily conducted in middle-aged and elderly populations. It is unclear if the biomarkers of PA, including renin, aldosterone, and aldosterone-to-renin ratio (ARR), are associated with left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases, in young adults. Methods: The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27 years. Participants with elevated high-sensitivity C-reactive protein (&gt;10 mg/L) and females who were on oral contraception were excluded. LVMI was measured by cardiac magnetic resonance imaging. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results: Of 758 participants, 252 (33.2%) were females. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p&lt;0.001) and higher median ARR (21.0 vs 15.6; p&lt;0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m2; p&lt;0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusions: An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function.

Relationship Between Cardiac Structure and Function With Renal Function Trajectory and Outcomes in Patients With Heart Failure: Insights From the PARAGON-HF Trial.

Renal dysfunction is common and associated with a poor prognosis in patients with heart failure. However, the association of cardiac structure and function with decline in kidney function in this population is unknown. We aimed to assess the association between individual measures of cardiac structure and function with changes in renal function and renal outcomes in patients with heart failure with preserved ejection fraction. Patients enrolled in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) echocardiographic substudy were included. The association between each echocardiographic parameter (expressed in standardized units) and changes over time in estimated glomerular filtration rate was calculated with repeated-measures mixed-effect models. Multivariable Cox proportional hazards models were used to identify individual cardiac parameters associated with the composite renal outcome (≥50% decline in estimated glomerular filtration rate relative to baseline, development of end-stage renal disease, or death attributable to renal causes), after adjusting for covariates. Among 1097 patients (mean age 74±8 years and 53% women), over a median follow-up of 2.9 years, 28 composite renal events (0.9 per 100 person-years) occurred. Higher left ventricular (LV) mass index and higher E/average e' ratio were associated with significantly more profound annual decline in estimated glomerular filtration rate (for both, -0.4 [95% CI, -0.7 to -0.1] mL/min/1.73 m2/y per 1 higher SD). Higher LV mass index, LV end-diastolic volume index, right ventricular end-diastolic area, and a lower right ventricular fractional area change were each associated with a significantly higher risk for the composite renal outcome. In the PARAGON-HF echocardiographic substudy, higher LV mass and filling pressures were independently associated with more profound kidney function decline, and higher LV mass and volume, as well as impaired right ventricular structure and function, were each associated with renal events. Assessing these parameters may help identify patients with heart failure with preserved ejection fraction at higher risk for adverse renal events and indicate potential therapeutic targets. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Cognitive Outcomes in Young Adults with Primary Arterial Hypertension: The Role of Cardiovascular Risk Factors and Hypertension-Mediated Organ Damage.

Background and Objectives: We aimed to explore the association between cognitive performance and markers of hypertension-mediated organ damage (HMOD) in young adults with hypertension. Materials and Methods: A group of adults aged 16 to 45 years with primary arterial hypertension completed a battery of paper-pencil as well as computer-based neuropsychological tests across all major cognitive domains. They also underwent office and ambulatory 24 h blood pressure, intima-media thickness measurements, heart ultrasound, and laboratory analysis of their lipid profile, blood uric acid concentration, and urine albumin-creatinine ratio. Associations between cognitive test results and markers of HMOD were explored through correlation analysis and age-, sex-, and body mass index-adjusted linear regression modeling. Results: Seventy-six individuals (62, 81.6% male) aged 36.5 years (interquartile range 18.4 to 42.0 years) were enrolled. After adjusting for age, sex, and body mass index in linear regression models, worse categorical fluency was associated with higher left ventricular mass (βst = -0.264, p = 0.043) and worse performance in a task of sustained attention-with higher left ventricular mass index (βst = -0. 304, p = 0.016). Worse phonemic fluency was related to higher pulse pressure (βst = -0.241, p = 0.049) in the respective model. Better strategy use in the task of spatial working memory was linked to higher daytime mean diastolic blood pressure (βst = -0.343 p = 0.017). Conclusions: Performance among young adults with hypertension across selected cognitive domains was inversely associated with pulse pressure, markers of left ventricular damage, and directly associated with daytime diastolic blood pressure. Our study suggests that the previously reported relationship between cognitive and cardiovascular markers in hypertension exists earlier than in middle or late adulthood.

Association between physical activity and cardiovascular parameters in 7-year-old children: a Chinese cross-sectional study

IntroductionPhysical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children.MethodsFollow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children’s PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children.ResultsOverall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, β coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, β = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (β = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (β = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, β = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (β = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (β = -0.42, 95% CI: -0.78, -0.06).ConclusionsThis study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.

Importance of T1-Mapping Sequence in Patients with Hypertrophic Cardiomyopathy without Foci of Non-Ischemic Myocardial Injury in Late Gadolinium Enhancement Sequence.

The aim of this study was to assess the importance of T1-mapping sequences in the diagnosis of hypertrophic cardiomyopathy (HCM) in patients without foci of non-ischemic myocardial injury in classic cardiac magnetic resonance (CMR) sequences. Two groups were compared: 28 patients with HCM, without any foci of myocardial injury in the late gadolinium enhancement (LGE) sequence (HCM group), and 28 patients without cardiomyopathy (CON group). Classic CMR sequences and T1-mapping sequences were performed. The following parameters were assessed: T1 time of the whole left ventricular myocardium, T1 time of myocardium in the basal, middle and apical layers of the left ventricle, and T1 time in individual segments of the left ventricular myocardium. Myocardial extracellular volume (ECV) was assessed similarly. ECV was significantly higher in the HCM group than in the CON group, for the whole left ventricular myocardium, for the basal and apical layers of the left ventricle, and for segments 1-3, 8, and 13-16 of the left ventricle. Regression analysis showed that a higher left-ventricular mass index (LVMI), a higher body mass index and older age are factors independently associated with a higher ECV of the whole myocardium but only in the group with LVMI ≥ 131.84 g/m2. In patients with HCM without foci of non-ischemic myocardial injury, higher ECV values of the left ventricular myocardium are observed.

Type 2 diabetes mellitus and cardiovascular health: Evidence of causal relationships in a European ancestry population.

Type 2 diabetes mellitus (T2DM) is associated with increased cardiovascular disease (CVD) risk, but whether T2DM directly causes adverse cardiac remodelling is uncertain. We performed a comprehensive Mendelian randomization (MR) analysis to investigate the causal relevance of T2DM to CVD outcomes and cardiac structure/function. Bidirectional two-sample MR was conducted using summary-level data from European-ancestry genome-wide association studies. The T2DM GWAS data included 80154 cases and 853816 controls from the DIAGRAM consortium. Outcomes included coronary artery disease (CAD), myocardial infarction (MI), stroke, heart failure, atrial fibrillation, and various quantitative cardiac imaging traits assessed by magnetic resonance imaging. MR analysis revealed causal associations between genetic predisposition to T2DM and increased risk of CAD (odds ratio [OR] 1.104, 95% confidence interval [CI] 1.078-1.130, P=2.59e-16), MI (OR 1.129, 95% CI 1.094-1.166, P=6.02e-14) and stroke (OR 1.086, 95% CI 1.064-1.109, P=1.02e-14). These associations were validated in the FinnGen cohort (CAD: OR 1.117, 95% CI 1.075-1.158, P=1.56e-9; MI: OR 1.132, 95% CI 1.083-1.184, P=4.27e-8; stroke: OR 1.138, 95% CI 1.107-1.170, P=3.52e-20). Multivariable MR show consistent findings (CAD: OR 1.063, 95% CI 1.031-1.097, P=1.11e-4; MI: OR 1.088, 95% CI 1.042-1.135, P=1.12e-4; stroke: OR 1.066, 95% CI 1.032-1.101, P=1.18e-4) after adjusting for cardiometabolic traits. T2DM was causally associated with higher left ventricular mass index (β=0.473, 95% CI 0.193 to 0.752, P=0.001), lower indexed right atrial minimum (β=-0.048, 95% CI -0.073 to -0.022, P=2.1e-5), and maximum (β=-0.042, 95% CI -0.065 to -0.019, P=4.12e-5) areas. The effects on right atrial size remained significant after adjusting for risk factors (minimum area: β=-0.041, 95% CI -0.072 to -0.010, P=0.009; maximum area: β=-0.039, 95% CI -0.069 to -0.008, P=0.012). Both apolipoprotein A1 and SBP are important mediators in the causal relationship between T2DM and left ventricular mass index. No reverse causal associations were identified. Our MR study demonstrates that genetic liability to T2DM plays causal roles in CAD, MI, stroke, and cardiac structure changes including left ventricular hypertrophy and reduced right atrial dimensions. These findings provide genetic evidence supporting glycaemic control in T2DM to mitigate cardiovascular complications and adverse cardiac remodelling.

Sex differences in clinical characteristics and long-term clinical outcomes in Asian hospitalized heart failure patients.

Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. Between 2011 and 2020, a total of 12428 patients (6518 men and 5910 women, mean age 73.50±14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40±13.43 vs. 71.20±15.67years old, P<0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P<0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF>50%) than men (P<0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P<0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors. With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.

Insulin resistance may accelerate typical changes in heart function among type 1 diabetes patients, particularly in overweight patients: a preliminary study.

Type 1 diabetes (T1D) is a metabolic disease characterized by insulin deficiency and subsequent hyperglycemia. Cardiovascular diseases are the prime cause of mortality and morbidity among patients with T1D. Accumulating metabolic disturbances and accelerated cardiac fibrosis fuel the development of heart dysfunction. As insulin resistance (IR) is a risk factor for the development and worsened course of heart failure, this study aimed to assess its impact on heart function in patients with T1D. Adult participants were recruited prospectively. The inclusion criteria included a diagnosis of T1D. The exclusion criteria were other types of diabetes, symptoms/treatment of heart failure, AST and/or ALT exceeding the upper reference limit by ≥2x, hepatitis, alcoholism, metformin treatment, and pregnancy. The participants underwent a medical interview, physical examination, biochemical test, and echocardiography. The mean age in the study group was 38 ± 9.6 years, and the mean diabetes duration was 21.8 ± 11.3 years. The median BMI in the study cohort was 23.39 kg/m2. Patients with IR had significantly lower mitral E/A ratio and left ventricular and left atrial volume ratio (LVLAVR), higher LV mass index, and presented with altered mitral annular velocities. IR seems to accelerate the pattern of typical changes in heart function among patients with T1D, especially in the overweight subgroup.

LEFT VENTRICULAR REMODELING IN RELATION TO INTERACTION BETWEEN BLOOD PRESSURE AND SODIUM RENAL HANDLING AND INTAKE IN UNTREATED CHINESE PATIENTS

Objective: Whether or not renal sodium handling was associated with left ventricular remodeling independent of blood pressure (BP) is uncertain. Design and method: Consecutive untreated patients referred for ambulatory BP monitoring were recruited. Two-dimensional echocardiography was performed to measure left ventricular properties. Fractional excretion of lithium (FELi) and fractional distal reabsorption rate of sodium (FDRNa) were calculated as markers of proximal and distal sodium handling, respectively. Results: The 952 untreated patients (51.0% women; mean age, 50.8 years) included 614 (64.5%) ambulatory hypertension and 138 (14.5%) with left ventricular hypertrophy. FELi and FDRNa averaged 21.5% and 95.9%, respectively. In multivariable-adjusted analyses, per 1-SD increment in systolic/diastolic BP (+12.4/9.0 mm Hg) and reduction in FELi (-11.3%) and FDRNa (-2.4%) were associated with 0.19/0.19 and 0.19/0.20 mm higher interventricular septal wall thickness (IVS), respectively, 0.10/0.12 and 0.18/0.22 mm higher left ventricular posterior wall thickness (LVPW), respectively, and 2.99/2.68 and 2.17/1.95 g/m2 higher left ventricular mass index (LVMI), respectively. Associations of IVS and LVPW with FELi and FDRNa were tighter than with BP (P&lt;0.001), whereas the opposite trend was observed for LVMI (P&lt;0.001). There was significant (P&lt;0.045) interaction between urinary sodium excretion and FELi in relation to LVPW and LVMI. Only in tertile 1 of FELi, LVPW and LVMI were positively associated with urinary sodium excretion (P&lt;0.040). The interaction between urinary sodium excretion and FDRNa in relation to left ventricular structure was nonsignificant (P&gt;0.25). Conclusions: Renal sodium handling as assessed by FELi and FDRNa, were independently associated with left ventricular remodeling, particularly with ventricular wall thickening.