Subclinical cardiac dysfunction and circulating markers of brain injury in older adults: The cardiovascular health study.

Background: The aim of this study was twofold: (1) to explore risk factors contributing to the progression of diabetic kidney disease (DKD) and the occurrence of renal and cardiovascular endpoint events in a real-world setting, and (2) to evaluate the effectiveness of Shenyuan Granules, a Chinese herbal medicine. Methods: This cohort study was performed on 298 DKD patients from June 2020 to June 2024. The patients were divided into risk groups based on Kidney Disease: Improving Global Outcomes (KDIGO) 2024 guidelines. Cox proportional hazards regression models were employed to identify the risk factors that contribute to renal and cardiovascular events. Propensity score matching (PSM) was used as the statistical method to compare 36 treatment-group patients, who were treated with Shenyuan Granules along with standard treatment, with 36 control-group patients, who received standard treatment alone. Furthermore, clinical biochemical indicators, traditional Chinese medicine (TCM) syndrome scores, and cardiovascular and renal endpoints of the two groups were assessed and compared. Results: This study helped identify the risk factors associated with renal and cardiovascular endpoint events in 298 DKD patients. The independent risk factors identified to be associated with renal endpoint events in DKD patients ( P < 0.05) were as follows: advanced age, elevated serum creatinine (Scr), elevated uric acid, elevated platelet lymphocyte ratio (PLR), abdominal aortic calcification (AAC), cardiac valve calcification (CVC), increased left ventricular mass index (LVMI), and left ventricular hypertrophy (LVH). However, the independent risk factors identified to be associated with cardiovascular endpoint events in DKD patients ( P < 0.05) were as follows: hypertension, AAC, CVC, increased LVMI, LVH, and left ventricle ejection fraction (LVEF) < 55.0%. According to the findings, Shenyuan Granules significantly improved TCM syndrome scores (83.3% and 44.4%, for treatment and control groups, respectively, with P < 0.05 each) in terms of key clinical indicators, including hemoglobin, estimated glomerular filtration rate (eGFR), Scr, 24-hour urinary protein, LVEF, and LVMI. Conclusion: Factors such as AAC, CVC, LVH, and increased LVMI can continue to deteriorate kidneys and increase the risk of cardiovascular diseases. However, Shenyuan Granules offer promising results in significantly improving renal and cardiac function and alleviating the clinical symptoms of DKD patients.

Impact of smoking on left and right ventricular systolic function and left ventricular mass in young healthy males: A two- and three-dimensional echocardiographic study

Transthyretin amyloidosis (ATTR) is a fatal disorder, thus early detection of cardiac involvement is crucial for improved clinical outcomes. This study investigated the utility of left ventricular (LV) speckle-tracking-derived mechanical dispersion as a potential marker for the assessment of cardiac amyloidosis (CA) in patients with ATTR and their first-degree relatives. This prospective, single-centre study enrolled 100 adults from 2020 to 2024 (ClinicalTrials NCT05814380). Participants underwent clinical assessment, genetic testing, and [99mTc]Tc-DPD SPECT/CT. Global longitudinal strain (GLS) and mechanical dispersion were evaluated using speckle-tracking echocardiography. Patients with ATTR CA exhibited significantly impaired GLS and increased mechanical dispersion (p < 0.001). Mechanical dispersion exhibited correlations with age, New York Heart Association class, LV mass index, E/E’, LV ejection fraction, GLS, levels of N-terminal pro-brain natriuretic peptide and Perugini grade (p < 0.05 for all). In univariable Cox regression, mechanical dispersion (Hazard ratio (HR) = 1.03, 95% confidence intervals (CI) 1.01–1.06, p = 0.004), normalised to heart rate mechanical dispersion (HR = 1.43, 95% CI 1.14–1.81, p = 0.002) were significant predictors of all-cause mortality. In our study increased mechanical dispersion was associated with advanced disease stages and mortality. These findings suggest that it may serve as a marker of ATTR CA.Registration: ClinicalTrials.gov Identifier: NCT05814380.

BackgroundBicuspid aortic valve (BAV) regurgitation and stenosis considerably alter post-valvular flow dynamics and impose additional energetic load on the left ventricle (LV). We therefore sought to determine whether 4D Flow MRI-derived ascending-aortic kinetic energy (KE) and viscous energy loss (EL), can differentiate BAV subtypes and healthy controls, and are associated with LV remodeling markers.MethodsSeventy-one participants (19 BAV without valve dysfunction, 17 with isolated aortic regurgitation (BAV-AR), 15 with isolated aortic stenosis (BAV-AS), and 20 healthy controls) underwent 3.0 T magnetic resonance imaging (MRI), including cine balanced SSFP and 4D‐Flow. Post valvular KE, viscous EL, and the dimensionless EL index were computed from the 4D Flow velocity fields. Global 3D LV strain metrics were derived via cine SSFP feature-tracking technique. Between‐group differences were assessed with one‐way ANOVA or Kruskal–Wallis tests, and associations were evaluated using Spearman’s rank correlation.ResultsAverage ascending aortic KE rose progressively from controls (3.3[2.3–4.3]) to uncomplicated BAV (6.7[5.3–9.1]), to BAV-AS (15.4[12.2–29.5]) and peaked in the BAV-AR (19.4[14.9–21.3], p < 0.001). Peak-systolic viscous EL was significantly elevated in both the stenotic (16.2 [9.1–24.4] mW) and regurgitant (11.4 [9.5–17.6] mW) groups compared to controls (4.1 [3.4–5.7] mW), but not in the uncomplicated BAV (6.4 [5.1–8.0] mW). Over the entire systole, viscous EL in the uncomplicated BAV (3.3 [2.5–4.1] mW) was also statistically increased compared to controls (1.7 [1.3–2.3] mW). KE correlated more strongly with regurgitation severity (rho = 0.50, p < 0.001), and EL with stenosis severity (rho = 0.48, p < 0.001). Aortic surgery referral was more closely associated with elevated KE (rho = 0.65, p < 0.001) and viscous EL (rho = 0.64, p < 0.001) than with aortic diameter (rho = 0.50, p < 0.001). Left ventricular Mass index and peak diastolic strain rate circumferential were correlated but more strongly with KE than viscous EL.Conclusions4D Flow MRI-derived post-valvular KE and viscous EL may serve as sensitive early biomarkers of LV dysfunction, and might outperform aortic diameter in risk stratification, and guide optimal intervention timing in BAV diseases while they need to be validated in broader populations.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12880-025-02026-z.

Early identification of abnormalities in vascular and cardiac structure offers an opportunity for intervention to reduce future cardiovascular disease (CVD). This study examined factors contributing to increased CVD risk from adolescence to young adulthood. Raine Study participants (n=716) classified as low- or high-CVD risk using cluster analysis at 17-years were re-studied at 27-years. Outcomes at 27-years were vascular stiffness assessed by pulse wave velocity (PWV), and left ventricular mass index (LVMI), left ventricular (LV), right ventricular (RV) and left atrial (LA) myocardial strain and respective ejection fractions (EF) assessed by cardiac magnetic resonance imaging. Outcomes were compared according to low- or high-risk classification at 17-years adjusting for sex and significant covariates at 27-years.At 27-years, individuals classified as high-risk at 17-years had significantly increased PWV (males: 6.6±0.12 vs 6.2±0.04 m/sec; females: 6.2±0.10 vs 5.6±0.04 m/sec) and LVMI (males: 75.2±2.1 vs 69.7±0.5 g/m2; females: 55.4±1.0 vs 52.1±0.4 g/m2) compared with low-risk individuals. Compared with low-risk individuals, LV global longitudinal strain in high-risk females (-16.7±0.4 vs -17.6±0.17 %, p=0.041) and LV global circumferential strain in males (-19.1±0.5 vs -20.5±0.2 %, p=0.013) and females (-21.3±0.4 vs -22.4±0.2 %, p=0.022) were attenuated. These differences were significant in regression analysis after adjusting for sex and contemporary risk factors. An unhealthy CVD risk profile in adolescence leads to structural vascular and cardiac changes in young adults predisposing them to future CVD. The results emphasize the importance of early public health measures to reduce the burden of cardiovascular and related lifestyle disorders.

Left ventricular myocardial work (LVMW) represents an innovative tool based on echocardiography designed to assess left ventricular (LV) performance in conjunction with LV pressure patterns. Although previous studies have compared differences in LVMW among patients with Fabry disease (FD), cardiac amyloidosis (CA), and hypertension at rest, there is limited research on the characteristics of LVMW in patients with FD during exercise. This study aims to explore the characteristics of LVMW at rest and during exercise in patients with FD and the value of LVMW combined with stress echocardiography for the early detection of impaired cardiac function in subclinical Fabry patients. This cross-sectional study included 54 participants, comprising 23 healthy individuals and 31 patients with FD. All participants underwent comprehensive two-dimensional echocardiography and semi-supine exercise stress echocardiography tests. At rest, individuals with FD exhibited markedly lower LV global longitudinal strain (LVGLS), LV global myocardial constructive work (LVGCW), LV global myocardial work efficiency (LVGWE), and LV global myocardial work index (LVGWI) compared to healthy controls. During exercise, LVGLS, LVGWI, LVGCW, and LV global wasted myocardial work (LVGWW) markedly increased in patients with FD and controls, while LVGWE decreased. However, across the four phases (rest, 25 W, peak, and recovery), patients with FD consistently demonstrated lower LVGLS, LVGWI, LVGWE, and LVGCW compared to controls. Moreover, the rise in LVGWI and LVGCW from the rest phase to the peak stage was markedly smaller in individuals with FD than in controls. A moderate correlation was found between LVGWI and LVGWE with LV mass index (LVMI) in individuals with FD (LVGWI: r = − 0.57, P < 0.05; LVGWE: r = − 0.68, P < 0.001). Additionally, individuals with FD with LV hypertrophy (LVH) exhibited lower LVGLS, LVGWE, and LVGCW from the rest to peak than those without LVH. Individuals with FD who had normal LVGLS at rest or those without LVH still showed markedly lower LVGWI than controls during the resting phase. Additionally, at peak exercise, LVGLS, LVGWI, and LVGCW were diminished significantly in the individuals with FD relative to the control cohort. ROC curve analysis in both resting and exercising states showed that LVGWI (rest: AUC 0.86, sensitivity 87%, specificity 74%; peak: AUC 0.94, sensitivity 71%, specificity 96%;) and LVGCW (rest: AUC 0.82, sensitivity 87%, specificity 70%; peak: AUC 0.92, sensitivity 84%, specificity 87%;) than LVGLS (resting: AUC 0.79, sensitivity 61%, specificity 87%; peak: AUC 0.88, sensitivity of 77%, and specificity of 87%) have a higher value in the diagnosis of FD. Patients with FD have markedly lower LVGWI, LVGWE, and LVGCW compared to the healthy controls, and these reductions are more prominent during exercise. Although LVGWI and LVGCW increase during exercise in patients with FD, the rate of increase is reduced, indicating impaired myocardial metabolism and energy utilization efficiency, especially in patients with FD with LVH. Additionally, LVMW combined with Stress Echocardiography allows early detection of impaired cardiac function in Fabry patients.

Adolescents with youth-onset type 2 diabetes (YO-T2D) have an increased risk for cardiometabolic complications. The impact of vertical sleeve gastrectomy (VSG) on fat distribution and cardiac morphology/function in YO-T2D is unknown. To evaluate changes in body composition, abdominal and cardiac fat depots, and cardiometabolic health in adolescents with YO-T2D undergoing VSG. Anthropometrics, labs and imaging were used to assess participants pre-surgery and 3-12 months post-surgery. MRI quantified pericardial (PAT), epicardial (EAT), subcutaneous (SAT) and visceral adipose tissue (VAT), hepatic fat fraction (HFF) and cardiac morphology/function. Mixed-effects models assessed longitudinal changes. By 12 months, weight decreased from 134.3 ± 5.1 to 103.3 ± 5.2 kg, VAT 1943 ± 148 to 1248 ± 150 cm3, HFF 23.2% ± 2.3% to 5.3% ± 2.3% and PAT and EAT by 27% and 33% (all p < 0.01). Homeostatic model assessment of insulin resistance (HOMA-IR) improved (7.8 ± 1.2 to 1.7 ± 1.2 [p < 0.01]). BMI, SAT, resting heart rate (RHR), left ventricular (LV) mass and cardiac output (CO) also decreased (all p < 0.05). VAT decreases correlated with decreases in HFF (r = 0.70, p = 0.01), HOMA-IR (r = 0.60, p = 0.04) and CO (r = 0.70, p = 0.03). HFF decreases correlated with decreases in BMI (r = 0.70, p = 0.03), HOMA-IR (r = 0.90, p < 0.001), RHR (r = 0.90, p = 0.002), CO (r = 0.80, p = 0.007) and LV mass (r = 0.70, p = 0.02). VSG reduces ectopic and regional fat and improves associated insulin sensitivity and cardiac health in adolescents with YO-T2D.

Biological aging varies across individuals and tissues, influencing chronic diseases, including heart failure (HF). Emerging proteome techniques enable quantification of organ-specific aging acceleration (OAA), but whether OAA relates to HF severity and differs by sex remains unclear. We aim to assess the sex-related association between OAA of heart, artery and kidneys and HF severity, and to investigate relevant cardiometabolic risk factors of organ aging. In 556 participants from the HELPFul cohort, we estimated predicted biological age for heart, artery, and kidneys using plasma proteomics and calculated OAA as the deviation from chronological age. Associations between OAA and HF stage, echocardiographic parameters, and cardiometabolic risk factors were evaluated using regression models. Composite indices, including triglyceride-glucose body mass index (TyG-BMI), c-reactive protein-triglyceride glucose index and triglyceride-to-HDL cholesterol ratio were assessed for associations with advanced OAA. Mean age was 63 ± 9years; 65% were women. Patients were classified as HF stage A (35%), B (29%) and C/D (36%). Heart OAA was significantly associated with advanced HF (Stage C/D) in both sexes (OR = 1.12, 95% CI 1.03 to 1.23 in women; OR = 1.18, 95% CI 1.05 to 1.32 in men), while artery OAA was linked to HF only in women (OR = 1.10, 95% CI 1.01 to 1.18). Multi-organ aging (≥ 2 organs with advanced OAA) conferred over three-fold higher odds of being in Stage C/D. Heart OAA correlated with impaired cardiac structure and function, particularly reduced ejection fraction in men and increased left ventricular mass index in both sexes. Diabetes emerged as the most relevant factor of artery and kidney OAA. TyG-BMI was significantly associated with advanced kidney OAA, only in women (z-scored OR = 1.88, 95% CI 1.45 to 2.45). Proteome-derived organ aging correlates with HF severity, with possible sex-related patterns. Diabetes and higher TyG-BMI are associated with faster organ aging, which may reflect shared aging mechanisms between metabolic dysfunction and HF.

BackgroundArterial stiffness is a major prognostic factor of cardiovascular (CV) morbi-mortality in kidney transplant (KT) patients. Preclinical studies have demonstrated that the vascular toxicity of calcineurin inhibitors (CNI) is mediated through the activation of the mineralocorticoid receptor (MR) in vascular smooth muscle cells. Additionally, the role of MR in contributing to arterial stiffness is well documented in non-transplanted individuals. This study aims to investigate the impact of MR antagonist treatment on the progression of arterial stiffness in KT patients on cyclosporine.MethodsThis is a randomized, open-label, single-center, cross-over trial involving 36 stable KT patients who have been transplanted for at least 1 year and are maintained on cyclosporine therapy. After a 4-week run-in period, participants will be randomly assigned to one of two groups. Group A will receive eplerenone at a dose of 50 mg daily for 6 months, followed by a 6-month period without treatment. There will be an 8-week washout phase between the treatment and non-treatment periods. Group B will start with 6 months without treatment, followed by the same 8-week washout phase, and then receive eplerenone for 6 months. The primary outcome is to assess the effect of 6 months of eplerenone on arterial stiffness, measured through pulse wave velocity (PWV) using the Sphygmocor® method at the start and end of each treatment period. Secondary outcomes will include changes in (1) central and peripheral blood pressure profiles, (2) intima-media thickness, (3) left ventricular mass, (4) biomarkers of oxidative stress and endothelial dysfunction, and (5) renal graft function markers, such as proteinuria and creatinine levels. Additionally, the incidence of hyperkalemia and episodes of acute renal failure will be monitored.DiscussionCNI are a key component of immunosuppressive therapy in KT patients. By limiting vascular toxicity through MR blockade, CV risk in these patients may be reduced.Trial registrationClinicalTrials.gov identifier: NCT04450953. EudraCT number 2019-004243-74.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13063-025-09187-w.

This study aimed to examine the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiac structure and cardiorenal function in older adults with hypertension and pre-heart failure. A total of 88 patients with hypertension and pre-heart failure who received care at the hospital between August 2022 and August 2024 were enrolled and randomly assigned to either a dapagliflozin group or a conventional treatment group. Changes in N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), estimated glomerular filtration rate (eGFR), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), left ventricular end-diastolic volume (LVEDV), ejection fraction(EF), left atrial volume index (LAVI), and left ventricular mass index (LVMI) were assessed and compared between the two groups before and after three months of treatment. No significant differences were observed in NT-proBNP, TnI, eGFR, IL-6, and hsCRP levels between the two groups before treatment. Additionally, there were no differences in PCT, TnI, and LVEDV between the groups at three months post-treatment. However, IL-6, hsCRP, and eGFR levels were significantly lower in the dapagliflozin group compared to the conventional treatment group at three months post-treatment (P < 0.05). Additionally, the LAVI was significantly lower in the dapagliflozin group relative to the conventional treatment group, with the difference being statistically significant (P < 0.05). These findings indicate that SGLT2i therapy may contribute to early myocardial remodeling and improvement in cardiorenal function in older adults with hypertension and pre-heart failure. Furthermore, prolonged SGLT2i administration appears to exert anti-inflammatory effects.

Assessing the myocardial mass at risk is essential in evaluating patients with coronary artery disease. This study aims to establish reference values for vessel-specific myocardial mass derived from coronary computed tomography angiography, providing a quantitative assessment of the myocardial mass subtended by each epicardial vessel. Left ventricular (LV) and vessel-specific myocardial mass were calculated from coronary computed tomography angiography using the Voronoi method in patients with stable coronary artery disease. Myocardial mass was quantified for each epicardial coronary artery with a diameter >1.5 mm. We included 948 patients with 9228 epicardial coronary artery branches. Mean age was 66±9 years. The cohort was predominantly male (77%); 66% had hypertension, and 22% had diabetes. Vessel-specific myocardial mass was calculated for 2767 main epicardial arteries (948 left anterior descending, 948 left circumflex, and 871 right coronary artery) and 6461 side branches (1888 diagonals, 1208 septals, 1422 obtuse marginals, 247 ramus intermedius, 850 right posterior descending, and 846 posterolateral branches). Median LV mass was 141 grams (interquartile range 118-166); women had smaller LV mass than men (106 [93-123] grams versus 150 [132-173] grams, P<0.001). On average, the left anterior descending subtended 42.5% [37.9-48.1] of LV mass, the left circumflex artery 28.8% [21.9-5.7], and the right coronary artery 26.4% [20.9-31.9]. Median LV mass subtended by the first septal, first diagonal, and first obtuse marginal were 8.9% [6.4-11.1], 7.9% [4.52-2.0], and 10.2% [4.52-12.0], respectively. This study quantified the myocardial mass subtended by each major artery in the coronary circulation. Understanding the vessel-specific mass at risk has significant clinical implications for personalizing revascularization strategies. This is a retrospective analysis of 5 prospectively conducted trials (P3: NCT03782688; P4: NCT05253677; PPG Global: NCT04789317; Euro-CRAFT: NCT05805462; INSIGHTFUL-FFR: NCT05437900). No additional registration was required.

We present the final report from the Fabry Outcome Survey (FOS) on long-term effectiveness and safety of agalsidase alfa in adults (≥18 years old). FOS was an international, multicentre, observational registry (NCT03289065), designed to enhance the understanding of Fabry disease and improve clinical management. Primary effectiveness endpoints were annualized change in estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI), and time to and age at composite morbidity event (comprising renal, cardiac or stroke events) and death. Safety outcomes were also assessed. FOS included data for 1864 adults (female/male, n = 907/957) who received agalsidase alfa only for a median (minimum, maximum) of 6.0 (0, 21.6) years, and 1613 untreated adults (female/male, n = 1235/378). At baseline, mean (standard deviation [SD]) eGFR was 94.01 (27.60) mL/min/1.73 m2 in treated adults; annualized changes in eGFR (slope [standard error; SE]) remained relatively stable in females and declined slightly in males (-1.07 [.12] vs. -2.17 [.12] mL/min/1.73 m2). At baseline, mean (SD) LVMI was 58.25 (25.01) g/m2.7 and LVMI (slope [SE]) remained stable (.34 [.16] vs. .38 [.15] g/m2.7/year in females and males, respectively). Time (median [95% confidence interval]) from treatment initiation to first composite event was longer for females than males (83.4 [65.7-98.0] vs. 56.3 [45.6-66.7] months); age (median [minimum, maximum]) at death was also higher for treated females than males (69.9 [32.5, 87.7] vs. 59.1 [26.2, 79.6] years). Agalsidase alfa was generally well tolerated. This report further supports the long-term effectiveness and safety of agalsidase alfa in adults with Fabry disease.

Left ventricular hypertrophy (LVH) can be identified through both electrocardiography (ECG) and echocardiography, with echocardiography recognized as the gold standard for the assessment of LVH. This imaging modality determines the presence of LVH by evaluating the left ventricular mass index (LVMI). For diagnostic purposes, LVH is defined in males as a left ventricular mass index greater than 115 g/m² and in females as greater than 95 g/m². Despite the high accuracy of echocardiography in diagnosing LVH, access to this examination is not universal across all healthcare facilities. Consequently, electrocardiography, a widely available, non-invasive, and cost-effective diagnostic tool, serves as an alternative for the diagnosis of LVH. Several criteria exist for the electrocardiographic assessment of LVH, including the Sokolow-Lyon and Cornell voltage criteria. However, the sensitivity of these electrocardiographic methods remains relatively low, with reported sensitivities of 17% for the Sokolow-Lyon criteria and 35% for the Cornell criteria. In left ventricular hypertrophy, the interstitium experiences changes characterized by fibrosis and other deposits. These alterations can reduce the expression of hypertrophic myocardial tension and limit the diagnostic capabilities of surface electrocardiograms. Additionally, several factors influence electrical tension, including variations in chest wall thickness, heart muscle activity, the distance of the electrode from the left ventricle, and lung activity. The presence of these limiting factors can increase the rate of false negatives in diagnosis. In 2017, Peguero and Lo Presti introduced novel criteria for the diagnosis of LVH, defined by evaluating the deepest S wave and summing it with the S wave in lead V4. According to these new criteria, LVH is identified as ≥ 2.8 mV in men and ≥ 2.3 mV in women. The Peguero-Lo Presti criteria demonstrate improved sensitivity when compared to traditional criteria such as Sokolow-Lyon and Cornell, offering enhanced diagnostic accuracy.

Introduction: Overweight has traditionally been considered an intermediate, relatively benign stage between normal weight and obesity; however, recent evidence suggests that it may already be associated with structural and functional cardiac alterations preceding overt cardiovascular disease. Early cardiac remodeling, defined as subclinical changes in left ventricular geometry, mass, and diastolic function, may represent the earliest manifestation of myocardial maladaptation in this population. Objective: The primary objective of this systematic review was to synthesize current evidence on early cardiac remodeling among overweight individuals (body mass index 25–29.9 kg/m²) compared with normal-weight controls. Secondary objectives included identifying the most sensitive imaging parameters for early detection, analyzing the modifying role of metabolic health and demographic variables, and evaluating the overall certainty of evidence. Methods: A comprehensive search was performed in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, ClinicalTrials.gov, and ICTRP for studies published between January 2015 and October 2025. Observational, cross-sectional, and interventional human studies assessing structural or functional cardiac changes in overweight individuals without pre-existing cardiovascular disease were eligible. Two reviewers independently screened titles, abstracts, and full texts, extracted data in duplicate, and assessed risk of bias using RoB 2, ROBINS-I, or QUADAS-2, with overall certainty rated by GRADE. Results and Discussion: 18 studies met inclusion criteria, encompassing 27,800 participants. Most studies reported that overweight individuals exhibited increased left ventricular mass index, concentric remodeling, higher left atrial volume index, and impaired myocardial strain or diastolic function compared with normal-weight subjects. These alterations persisted even after adjusting for blood pressure and metabolic factors, suggesting an independent effect of adiposity. Despite consistent findings across imaging modalities, heterogeneity in study design, populations, and definitions of overweight limited pooled synthesis. Certainty of evidence was graded as moderate for structural outcomes and low for functional outcomes. Conclusion: Overweight status is not metabolically or structurally innocuous. Evidence indicates that early cardiac remodeling can occur before the threshold of obesity, underscoring the importance of early risk assessment and lifestyle interventions. Standardized imaging criteria and longitudinal studies are needed to clarify reversibility and prognostic significance.

Isolated nocturnal hypertension (INH) is characterized by normal daytime blood pressure (BP) and elevated nighttime BP diagnosed by ambulatory BP monitoring (ABPM). In the present study, we aimed to evaluate the influence of nocturnal diastolic hypertension on left ventricular mass index (LVMI), renal resistive index (RRI), and inflammation in renal transplant recipients (RTR) with masked hypertension. We cross-sectionally analyzed the ABPM monitoring data in 250 RTRs from living related first and/or second degree or from deceased donors without the diagnosis of hypertension with stable allograft function from our renal transplant outpatient clinic. Daytime hypertensive as well as nocturnal systolic hypertensive patients were excluded, and 74 patients with isolated nocturnal diastolic hypertension (INDHT) (mean age: 39.2 ± 11.4 years, 58% male) were enrolled in the study. LVMI was calculated by conventional echocardiography. RRI was measured by doppler ultrasound. Patients were divided into two groups according to mean RRI values as group 1 (RRI < 0.67; n = 29) and group 2 (RRI ≥ 0.67; n = 45). The mean post-transplantation time, RRI, and LVMI were 34.9 ± 1.7 months, 0.67 ± 0.1, and 193.0 ± 115.5 g/m2, respectively. In correlation analysis, nocturnal diastolic BP was positively correlated with gender (p=0.039), post transplantation time (p=0.01), C-reactive protein (CRP) (p=0.04), neutrophil/lymphocyte ratio (p=0.01), RRI (p=0.01), and LVMI (p=0.033). RRI was significantly higher in males than in females (p=0.04). In subgroup analysis, patients in group 1 had lower serum ferritin (p=0.04), CRP (p=0.04), LVMI (p=0.01), nocturnal diastolic BP (p=0.01), and neutrophil/lymphocyte ratio (p=0.04) but higher serum albumin (p=0.03) levels. In multiple regression analysis; RRI (p=0.012) and LVMI (p=0.02) were detected as the predictors of nocturnal diastolic BP. INDHT has a significant influence on LVMI, RRI, and inflammation. Thus, INH could be an early predicting factor for graft function and cardiovascular outcome in RTRs.

Abstract Background Mavacamten, the first-in-class cardiac myosin inhibitor, is approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Previous cardiac magnetic resonance (CMR) imaging analyses in individual clinical trials indicated that mavacamten treatment was associated with positive cardiac structural remodelling. Purpose To evaluate cardiac structural remodelling and clinical correlations in a diverse population of patients with symptomatic obstructive HCM treated with mavacamten for 30 weeks, based on an integrated analysis of CMR data from randomized controlled trials (RCTs) conducted globally. Methods An integrated CMR analysis of double-blind RCTs was conducted using data from both the EXPLORER-HCM (NCT03470545; international) and EXPLORER CN trials. Changes from baseline to week 30 in CMR parameters were assessed by treatment group (MAVA-RCT and Placebo-RCT) in pooled patient populations. Clinical correlations were assessed between changes from baseline in CMR parameters (left ventricular mass index [LVMI] and left atrial volume index [LAVI]) and biomarker levels (N-terminal pro B-type natriuretic peptide [NT-proBNP] and troponin I). Trends were compared in patients who received 30 weeks of mavacamten treatment in the open label HORIZON-HCM study. Results Overall, 93 patients were pooled from the double-blind studies (MAVA-RCT: 56; Placebo-RCT: 37) and 17 patients were assessed from HORIZON-HCM. At baseline, for the MAVA-RCT vs Placebo-RCT group, mean age was 53.6 years vs 56.2 years, 71.4% vs 62.2% were male, 71.4% vs 54.1% were Asian and 28.6% vs 45.9% were White. Greater reductions from baseline were observed for MAVA-RCT than for Placebo-RCT in LVMI (mean difference [95% confidence interval (CI)]: −25.2 [−28.3, −16.3] g/m2), LAVI (mean difference [95% CI]: −15.6 [−18.2, −8.3] mL/m2), left ventricular (LV) maximum wall thickness (mean difference [95% CI]: −3.1 [−3.7, −2.0] mm), LV end-diastolic volume index (mean difference [95% CI]: −7.2 [−11.9, −3.3] mL/m2) and LV ejection fraction (mean difference [95% CI]: −4.1 [−6.6, −1.5]%) (Table). Similar reductions from baseline to week 30 were observed in mavacamten-treated patients in HORIZON-HCM. For the MAVA-RCT group, reductions from baseline to week 30 in LVMI were correlated with reductions in NT-proBNP (correlation coefficient: 0.48) and troponin I (correlation coefficient: 0.38) (Figure); correlations were also observed between reductions in LAVI and reductions in NT-proBNP (correlation coefficient: 0.28) and troponin I (correlation coefficient: 0.27). Conclusion This integrated analysis of CMR data from RCTs confirmed that mavacamten treatment over 30 weeks is associated with positive cardiac structural remodelling which correlates with improvements in clinical biomarkers in a diverse population of patients with symptomatic obstructive HCM.

Background: Obstructive sleep apnea (OSA) has been linked to increased cardiovascular risk, potentially contributing to adverse cardiac remodeling and arrhythmias through inflammation. However, its specific role in adverse cardicac remodeling and post-operative atrial fibrillation (POAF) in patients undergoing cardiac surgery remains understudied. Hypothesis: We hypothesized that OSA would be associated with adverse structural remodeling, elevated systemic inflammation, and a higher incidence of POAF in patients undergoing cardiac surgery. Methods: Sixty-five cardiac surgery patients (mean age 66 ± 8 years; 25% female) were included, with 13 having OSA and 52 without. Preoperative transthoracic echocardiography assessed cardiac structure and function, including left ventricular (LV) mass, wall thickness, and ejection fraction. Plasma proteomics using Olink proximity extension assays targeted inflammatory markers. POAF was defined as new-onset atrial fibrillation during hospitalization. Statistical comparisons used t-tests and chi-squared tests. Results: OSA and control groups were similar in age (66 ± 7 vs. 66 ± 9 years) and sex (15% vs. 27% female, p= 0.5). OSA patients had higher BMI (32.3 ± 5.2 vs. 28.9 ± 4.6 kg/m 2 , p= 0.035) and showed signs of adverse structural remodeling: increased interventricular septal thickness (1.17 ± 0.21 vs. 1.02 ± 0.21 cm, p= 0.017), posterior wall thickness (1.10 ± 0.19 vs. 0.99 ± 0.16 cm, p= 0.024), and LV mass (114 ± 27 vs. 90 ± 27 g, p= 0.005). Unexpectedly, POAF incidence was significantly lower in OSA patients (7.7% vs. 42%, p= 0.023). Proteomic profiling revealed no significant elevations in canonical inflammatory markers. In fact, CCL25 (8.30 ± 0.60 vs 7.91 ± 0.85, p= 0.0322) and hepatocyte growth factor (HGF) (13.08 ± 0.34 vs 12.93 ± 0.31, p= 0.0244) levels were significantly lower in the OSA group. Conclusions: OSA was associated with increased LV wall thickness and mass, consistent with adverse structural remodeling. Notably, these changes occurred without evidence of elevated systemic inflammation or an increased risk of POAF in our surgical cohort. These findings challenge the presumed link between OSA, inflammation, and post-operative atrial arrhythmias. They suggest that, at least in some surgical populations, OSA may not be accompanied by heightened inflammatory signaling. Further studies in larger and more diverse cohorts are warranted to better understand these complex relationships.

Resistant hypertension, defined as blood pressure &gt;130/80 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease including heart failure (HF) compared with those with more easily controlled hypertension. Many providers and patients alike are in desperate need of indicators that can help prevent and avoid symptomatic HF (Stage 3 AHA), or worse advanced HF (Stage 4 AHA). In early stages of HF in patients with Resistant Hypertension (RHTN) there have not been any investigations into biomarkers. We conducted a cross-sectional analysis of patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. In this study we analyzed data of patients with RHTN, and compared it with patients with hypertension (HTN). Demographics, body mass index, and blood pressure measurement were taken. Patients underwent blood samples, urine collection, and cardiac MRI assessment. We found that RHTN patients had higher fat free mass (FFM) (139.1 ± 29.3 vs 125.5 ± 23.4lbs, p = 0.0236). RHTN patients had a higher waist to hip ratio (W/H) (0.95 ± 0.1 vs 0.9 ± 0.05, p = 0.029). RHTN patients had lower levels of potassium present in their blood (3.9 ± 0.4 vs 4.3 ± 0.48mmol/L, p&lt;0.001). RHTN patients had higher Urinary Aldosterone (U-Aldo) (13.4μg ±10.1 vs 9.3μg ± 6.1, p = 0.01449). RHTN patients also had higher aldosterone renin ratio (14.7 ± 16.9 vs 7.2 ± 4.6, p &lt; 0.001). RHTN patients’ BNP and ANP were higher (41 ± 74.2 vs 19.4 ± 18.2, p = 0.007) (82.4 ± 54 vs 54.6 ± 32.6, p = 0.012). Among all of the Cardiac MRI measurements the most significant were the left ventricular mass (LVM) (169.5 ± 46.25 vs 125.6 ± 29.75, p &lt; 0.001), the LVM end diastolic (LVM ED) (162.4 ± 44.4 vs 120.8 ± 27.1, p &lt; 0.001), the LVM end systolic (LVM ES) ( 177.3 ± 49.7 vs 130.5 ± 32.8, p &lt; 0.001), the LVM posterior wall (LVPW) (10.3 ± 2.6 vs 8.1 ± 1.4, p&lt; 0.001), and IVS (12.5 ± 2.5 vs 10.1± 1.4, p&lt; 0.001). There was no difference in age, BMI, serum creatinine, urinary Sodium, and urinary potassium. When analyzed by gender or race there was no difference between groups. In summary, aldosterone renin ratio and urinary aldosterone are potential biomarkers for patients with RHTN on a high Na diet with stage 2 HF. Underlying mechanisms including hemodynamics and endocrine dysregulation need further investigation in patients with stage 2 HF.

Resistant hypertension (RHTN), defined as blood pressure (BP) above goal despite using ≥3 antihypertensive agents. Patients with resistant hypertension are at an increased risk of heart failure compared with those with more easily controlled hypertension. Early biomarkers for the prevention of symptomatic heart failure (stage 3 and 4) are needed. There has not been an evaluation of biomarkers in stage 2 heart failure (HF) in patients with Resistant Hypertension (RHTN) there have not been any investigations into biomarkers. We conducted a cross-sectional analysis of patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. In this study we analyzed data of patients with RHTN and stage 2 HF defined by structural changes assessed by cardiac MRI who had no history of HF, and compared it with patients with hypertension (HTN). We evaluated demographics, body mass index, and blood pressure levels. Patients also underwent biochemical evaluation of serum/plasma, 24-hr urine collection, and cardiac MRI assessment. Patients with RHTN and stage 2 HF had significantly higher 24-hr urinary cortisol levels (118.6 ±66.5 vs 86.7±31.5 mcg, p&lt;0.0022), higher BNP and ANP levels (41 ± 74.2 vs 19.4 ± 18.2, p = 0.007) (82.4 ± 54 vs 54.6 ± 32.6, p = 0.012). Among the pertinent cardiac MRI measurements the most significant were the left ventricular mass (LVM) (169.5 ± 46.25 vs 125.6 ± 29.75, p &lt; 0.001), the LVM end diastolic (LVM ED) (162.4 ± 44.4 vs 120.8 ± 27.1, p &lt; 0.001), the LVM end systolic (LVM ES) ( 177.3 ± 49.7 vs 130.5 ± 32.8, p &lt; 0.001), the LVM posterior wall (LVPW) (10.3 ± 2.6 vs 8.1 ± 1.4, p&lt; 0.001), and IVS (12.5 ± 2.5 vs 10.1± 1.4, p&lt; 0.001). There was no difference in age, BMI, serum creatinine, urinary sodium, and urinary potassium. When analyzed by gender or race there was no difference between groups. In summary, cortisol may play a role in the development of HF in patients with RHTN. Further studies are needed to elucidate underlying mechanisms.