Ventricular Volume Research Articles

Population pharmacokinetic study of the effect of polymorphisms in the ABCB1 and CES1 genes on the pharmacokinetics of dabigatran

PurposeThe impact of genetic polymorphisms in the ABCB1 and CES1 genes on dabigatran plasma concentrations remains a subject of debate, and the purpose of this study was to quantitatively assess the effects of genetic polymorphisms on dabigatran esters in healthy Chinese subjects employed a population pharmacokinetic (PopPK) approach.MethodsIn total, 1,926 pharmacokinetic (PK) samples from 123 healthy individuals who were given 150 mg of dabigatran orally during a fasting state or postprandially were analyzed using the PopPK model. A two-compartment model with first-order absorption was found to adequately describe the PK data.ResultsThe results showed that covariates food intake and ABCB1 SNP rs4148738 were shown to have statistically significant impacts. Specifically, in postprandial administration increased lag time (ALAG) and clearance (CL) by 2.65% and 0.51%, respectively, and decreased absorption rate constant (KA) by 0.24%. Additionally, in subjects with CT genotype ABCB1 (rs4148738), the central ventricular volume of distribution (V2) was increased by 0.38%.ConclusionIn summary, the PopPK model developed in this study was robust and effectively characterized the pharmacokinetics of dabigatran in healthy Chinese adults, demonstrating that both food and ABCB1 genetic variation significantly influence the absorption and plasma concentration levels of dabigatran.

Evaluation of fetal heart size, morphology and function with fetal growth restriction using fetal HQ.

Fetal growth restriction (FGR) is associated with various perinatal complications. Limited research has focused on the fetal heart in the context of FGR. This study aimed to investigate the application value of fetal heart quantification (HQ) technology in evaluating the size, morphology, and function of the heart in FGR. A total of 31 fetuses diagnosed with FGR in our hospital from April 2022 to May 2024 were included, alongside another 31 normal fetuses matched for gestational age as the control group. Ultrasound Doppler parameters of the middle cerebral artery (MCA), umbilical artery (UA), venous catheter, and fetal HQ parameters were collected for comparative analysis, and perinatal data were followed up. Fetuses with FGR exhibited significant differences in various parameters of the MCA and UA compared to the control group (P < 0.05). The four-chamber view end-diastolic transverse width, end-diastolic area, left ventricular (LV) end-diastolic area, end-systolic area, end-systolic length, end-diastolic volume, end-systolic volume, and right ventricular (RV) end-systolic area in the FGR group were significantly lower than those in the control group (P < 0.05). In the 24-segment analysis, the LV fractional shortening in the FGR group was greater than in the control group at segments 12 to 14, while the end-diastolic diameter (ED) at segments 5 to 13 of the LV and segments 1 to 14 of the RV were smaller than those in the control group, with statistical significance (P < 0.05). Analysis of each subgroup indicated that fractional shortening (FS) in the early-onset group was significantly greater than in the late-onset group at RV segments 2 to 8. LV-ED at segments 1 to 15 and RV-ED at segments 1 to 16 were significantly smaller in the early-onset group than in the control group, and LV ED segments 20 to 21 were significantly smaller in the early-onset group compared to the late-onset group (P < 0.05). FS in the mild group was significantly larger than in the normal group at LV segments 10 to 16. The severe group exhibited significantly smaller LV segment 2 to 11 ED and the mild group showed smaller RV segments 1 to 13 compared to the control group (P < 0.05). Fetal HQ is a promising technique for evaluating the cardiac function, size, and morphology in cases of FGR.

Anatomical Characteristics of Cervicomedullary Compression on MRI Scans in Children with Achondroplasia

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.1–3.6] years) and compared with scans from 37 children without achondroplasia (median age 1.5 [0–3.9] years). Mann–Whitney U testing was used for between-group comparisons. Foramen magnum diameter and area were significantly smaller in children with achondroplasia compared with the reference group (mean 10.0 vs. 16.1 mm [p &lt; 0.001] and 109.0 vs. 160.8 mm2 [p = 0.005], respectively). The tentorial angle was also steeper in children with achondroplasia (mean 47.6 vs. 38.1 degrees; p &lt; 0.001), while the clivus was significantly shorter (mean 23.5 vs. 30.3 mm; p &lt; 0.001). Significant differences were also observed in myelon area, occipital angle, fourth ventricle, intracranial cerebrospinal fluid and supratentorial ventricular volumes, and the volume of brainstem protruding beyond the posterior fossa (all p &lt; 0.05). MRI analysis of brain structures may provide a standardized value to indicate decompression surgery in children with achondroplasia.

Associations Between Plasma Levels of NLRP3 Protein, Interleukin-1 Beta and Features of Acute ST-Elevation Myocardial Infarction

Background. Phenotyping inflammation in ST-elevation myocardial infarction (STEMI) is a challenge for modern cardiology. NLRP3 inflammasome is a proven predictor of adverse outcomes in cardiovascular disease, but its specificity in stratifying inflammatory activity in patients with myocardial infarction (MI) has not been demonstrated. The aim of this paper is to describe the levels of NLRP3 protein and IL-1β concentrations and their changes in dynamics and associations with clinical, laboratory and instrumental characteristics of patients with STEMI. Methods. A total of 45 patients with STEMI were enrolled. Concentrations of NLRP3 and IL-1β were evaluated in arterial and venous EDTA blood from the infarct-related coronary and peripheral arteries and veins on days 1, 3 and 7 after MI. Results and Conclusions. The concentrations of markers were higher on the first day after MI with a maximum decrease on the third day. The levels of both markers in venous plasma correlated with those in arterial blood, allowing their routine determination in venous plasma on the first day after MI. IL-1β levels correlated directly with the wall motion index and inversely with left ventricular ejection fraction and stroke volume, which characterize the potential contribution to adverse myocardial remodeling. There were two multidirectional trends in changes in NLRP3 and IL-1β levels during hospitalization. Initially higher levels with a gradual decrease by day 7 were associated with a longer duration of myocardial ischemia and higher plasma troponin I levels. Further evaluation of the long-term outcomes of MI will allow identifying inflammatory factors that input to the development of secondary major adverse cardiac events and will provide a new step in the understanding of inflammatory phenotyping.

Abstract 4125026: Effect Of Pressure-Controlled Intermittent Coronary Sinus Occlusion On Echocardiographic Features In Patients With STEMI: A Systematic Review And Meta-Analysis With Trial Squential Analysis

Introduction: Primary percutaneous coronary intervention (pPCI) is the treatment of choice for patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, pPCI is still associated with poorer outcomes particularly left ventricular dysfunction. Pressure-controlled intermittent coronary sinus occlusion (PiCSO) is a novel therapeutic approach proposed to improve myocardial perfusion and its function in patients with STEMI. Therefore, we performed this meta-analysis to evaluate the effects of PiCSO on left ventricular function in STEMI patients. Methods: We performed a comprehensive search on PubMed, Scopus, and Web of Science. Our primary endpoints were left ventricular ejection fraction (LVEF%), left ventricular end diastolic volume (LVEDV), and left ventricular end systolic volume (LVESV). The secondary endpoint was infarct size. We performed Trial Squential Analysis (TSA), and we pooled our continuous data as mean difference (MD) and 95% confidence interval (CI) in the fixed effects model. Results: A total of four studies, with 335 patients, were included in the analysis. Our pooled analysis showed that PiCSO significantly increased LVEF% compared to pPCI (MD = 3.52, 95% CI [1.05, 6.00], P= 0.005). However, there was no significant difference between the two groups in terms of LVESV and LVEDV (MD = -1.1, 95% CI [-9.28, 7.08], P= 0.79; MD = -1.69, 95% CI [-9.14, 5.76], P= 0.66, respectively). With regard to infarct size, a significant reduction was observed in PiCSO group compared to pPCI (MD = -4.26, 95% CI [-7.39, -1.14], P= 0.007). The TSA curve crossed the conventional boundary for statistical significance, indicating that the available evidence reach the predetermined threshold. Conclusions: Our meta-analysis revealed that PiCSO could mitigate left ventricular dysfunction in STEMI patients by improving LVEF% and reducing infarct size. Nevertheless, PiCSO failed to show a positive impact on LVESV and LVEDV. Further large-scale studies are warranted to draw a definitive conclusion.

Abstract 4129182: Transendocardial Stem Cell Therapy Improves Cardiac Parameters in Chronic Ischemic Heart Failure: A Meta-analysis of Randomized Controlled Trials

Introduction: Despite recent advances in therapy, chronic ischemic heart failure remains a significant cause of morbidity and mortality worldwide. Stem cell (SC) therapy has recently emerged as a potential therapeutic approach, yet its efficacy remains debatable. We aimed to systematically review and meta-analyze the current evidence to evaluate its effectiveness. Methods: A comprehensive literature search was conducted across the following databases: PubMed, Embase, and Cochrane, from inspection to April 2024. We identified RCTs with a blinded study design, done on patients diagnosed with chronic ischemic HFrEF, and utilized mesenchymal stem cells as an intervention in comparison to placebo/sham intervention using percutaneous endomyocardial catheter systems. Meta-analysis was conducted using RevMan v5.4 to calculate the odds ratio (OR) at 95% confidence intervals (CI) and a p-value of 0.05. I 2 was indicated for the assessment of heterogeneity. Sensitivity analysis was done in case of heterogeneity between studies. Results: A total of twenty studies were included in our meta-analysis. The overall change in left ventricular end-systolic volume (LVESV) and stress SPECT significantly favored the stem cell group (pooled effect size -7.59, 95% CI [-12.28 to -2.89], P=0.002), and (pooled effect size -5.33, 95% CI [-6.73 to -3.93], P=0.00001), respectively. Initially, the change in left ventricular end-diastolic volume (LVEDV) did not favor either group. However, sensitivity analysis which excluded one study at a time, reduced heterogeneity (P=0.01, I 2 =54%) and showed a significant effect favoring the stem cell group (pooled effect size -3.87, 95% CI [-6.77 to -0.97], P=0.009). However, the overall changes in left ventricular ejection fraction (LVEF) did not favor either of the two groups (pooled effect size 0.08, 95% CI [-0.1 to 0.26], P=0.39). Similarly, the overall change in myocardial oxygen consumption (MVO2) did not favor either group (pooled effect size 0.66, 95% CI [-0.1 to 1.32], P=0.05). Conclusion: Transendocardial SC therapy demonstrates promising results by significantly improving specific cardiac parameters. While the therapy shows potential, particularly after sensitivity adjustments, its impact on other critical measures like LVEF and MVO2 remains inconclusive. These findings highlight the need for further investigation to fully understand and enhance the therapeutic potential of stem cell interventions in heart failure management.

Abstract 4119195: Proteomic Analysis of Primary Angioplasty in Acute Myocardial Infarction: Implications for Left Ventricular Remodelling and Recovery of Function

Introduction: Acute myocardial infarction (AMI) is a leading global cause of mortality. Following primary percutaneous coronary intervention (PCI), 25% require hospitalisation for symptomatic heart failure. Further understanding of the molecular pathogenesis and the temporal relationship of the protein profile associated with ischaemic insult and subsequent cardiac remodelling is required to improve risk stratification following AMI. Methods: 20 patients with AMI presenting to Royal Free Hospital in London were recruited for proteomic analysis (O link Proximity Extension Immunoassay) at presentation and at 24 and 72 hours following primary PCI. All underwent initial CMR on admission and at 6 month follow up to assess for myocardial oedema, left ventricular volumes and function and assessment of scar. Results: Proteomic biomarkers that increased on discharge following AMI were: IGFBP2 (8% increase, p=0.001), MMP-10 (5% increase, p=0.001), TIMP4 (14.4% increase, p&lt;0.001), CSF-1 (3.4% increase, p&lt;0.001), CHI3L1 (15% increase, p&lt;0.001), ST2 (19% increase, p=0.001), TGF-alpha (17% increase, p=0.001), IL6 (38% increase, p&lt;0.001), and NT-proBNP (93% increase, p&lt;0.001). The only biomarker that significantly decreased was IGFBP-1 (24% decrease, p=0.003). Notably, increased post-PCI biomarkers correlated with reduced infarct size at follow-up, including CCL23 (R=-0.6, p=0.016), IL6 (R=-0.051, p=0.04), NT-proBNP (R=-0.72, p=0.002). High biomarkers at initial presentation associated with reduced left ventricular end diastolic volume (LVEDV) were CSF-1 (R=-0.64, p=0.03) and CCL23 (R=-0.76, p=0.006). Discussion: Following AMI, we observed increase in proteins implicated in inflammation, angiogenesis and tissue repair. IGFBP1 as a stress hormone significantly decreased after PCI. Markers that showed linear association with reduced cardiac preload measured by LVEDV were linked with angiogenesis promotion and resolution of inflammation.

Abstract 4135289: Renal Blood Perfusion is Closely Related to Right Ventricular Volume Overload in Congestive Heart Failure

Background: Cardiorenal syndrome (CRS) involves a bidirectional relationship where dysfunction in one organ exacerbates the other. A key factor in this interaction is the impact of right ventricular (RV) volume overload on renal blood flow, which is vital for the progression and management of heart failure (HF). Objective: This study aims to explore and quantify the relationship between right ventricular volume overload, i.e, echocardiographic assessments of right ventricular diameter (RVD), and the time-to-peak (TTP) of renal blood flow in patients with HF measured by 99mTc-DTPA renal scintigraphy. Methods: This single-center study included 304 stable, ambulatory HF patients admitted between October 2017 and August 2022. HF was diagnosed based on the 2016 ESC guidelines. Echocardiographic parameters, including RVD, and TTP of renal blood flow measured by 99mTc-DTPA renal scintigraphy, were collected. Statistical analysis was conducted using SPSS and R software, with Spearman correlation analysis used to assess the relationship between echocardiographic parameters and TTP. Results: The study showed there was a significant correlation between RVD and TTP (rs=0.535, P &lt;0.001), indicating that RV volume overload is closely related to impaired renal perfusion. The median TTP among the study population was 27.25 seconds (IQR: 21-39 seconds). Corrected for body surface area (BSA), RVD was found to be significantly higher in patients with heart failure with reduced ejection fraction (HFrEF) compared to heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) (HFrEF: 20.62 mm/m 2 , HFmrEF: 18.72 mm/m 2 , HFpEF: 18.09 mm/m 2 ; p &lt; 0.001). Furthermore, right atrial diameter (RAD) corrected for BSA (RAD/BSA) demonstrated the strongest correlation with TTP in the HFrEF subgroup (rs=0.602, p&lt;0.001). Conclusions: Our findings highlight the significant impact of right ventricular volume overload on renal perfusion, providing valuable insights into the pathophysiology of CRS. These results suggest that therapeutic strategies aimed at reducing RV overload could enhance renal perfusion and improve overall outcomes in HF patients.

Abstract 4135465: Efficacy of SGLT-2 inhibitors combined with percutaneous coronary intervention on clinical and echocardiographic parameters in patients with acute myocardial infarction: A systematic review and meta-analysis

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular outcomes in heart failure (HF) patients and may mitigate symptom progression in myocardial infarction (MI). However, their efficacy in acute MI patients undergoing percutaneous coronary intervention (PCI) is unclear. This study aims to evaluate whether SGLT2i combined with PCI improves clinical and echocardiographic outcomes. Methods: A comprehensive search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from inception till May 2024. The study was conducted adhering to the PRISMA guidelines. The clinical benefit of PCI plus SGLT2i was assessed through risk reduction of acute kidney injury (AKI), CV death (CVD), hospitalization due to HF (hHF), all-cause mortality (ACM), and revascularization. Echocardiographic outcomes assessed were change in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (LVEDV). Results were presented as risk ratios (RR) along with their 95% CI for dichotomous data while weighted mean difference (WMD) were reported for continuous outcomes. The data was aggregated using a random effects model. Results: Our analysis included eleven records comprising 6,411 participants. The results indicated that PCI plus SGLT2i significantly reduced the risk of AKI (RR: 0.66, 95% CI: [0.52, 0.83], p&lt;0.01) and ACM (RR: 0.54, 95% CI: [0.4, 0.7], p&lt;0.01) compared to PCI alone. However, the reduction in risk for CVD was not statistically significant (RR: 0.56, 95% CI: [0.2, 1.1], p=0.09), as was the case for hHF (RR: 0.65, 95% CI: [0.3, 1], p=0.07). Additionally, there was no significant difference in the risk of revascularization between the two groups (RR: 2.9, 95% CI: [0.62, 14.39], p=0.17). PCI plus SGLT2i was also significantly associated with an increase in LVEF (WMD: 2.73, 95% CI: [1.09, 4.36], p&lt;0.01) and decrease in LVEDV (WMD: -8.0, 95% CI: [-13.17, -2.90], p&lt;0.02). Conclusion: Our study demonstrates that SGLT2i administration in MI patients undergoing PCI leads to improved renal and mortality outcomes, along with enhanced cardiac function. These benefits are hypothesized to result from kidney-mediated natriuretic effects, improved blood flow regulation, reduced endothelial dysfunction, and decreased arterial stiffness, which optimize cardiac function. We recommend future studies with larger sample sizes and longer follow-ups to assess the long-term benefits of SGLT2i combined with PCI.

Abstract 4134668: Title: Mandibular advancement device versus CPAP on cardiovascular health and quality of life in OSA a pre-specified 12 months follow up of outcomes

Background: Obstructive sleep apnoea (OSA) is a significant cause of hypertension. ACC/AHA Guidelines recommended screening and treatment of OSA in patients with hypertension; however, evidence comparing mandibular advancement devices (MAD) to continuous positive airway pressure (CPAP) on cardiovascular health is lacking. We present the complete 12 months follow-up data on the comparative effectiveness of MAD versus CPAP in ambulatory BP reduction, QoL, cardiac arrhythmia, and myocardial remodelling. Method: In a randomized, non-inferiority trial (margin 1.5 mmHg), 321 participants, aged over 40, with hypertension and high cardiovascular risk were recruited. Of these, 220 participants with OSA (apnoea–hypopnea index ≥15 events/h) were randomized to either MAD or CPAP (1:1). Pre-specified secondary outcomes include: ambulatory BP, quality of life (QoL) (sleep-specific: ESS, SAQLI, FOSQ; non-sleep-specific: SF-36, EQ-5D), ambulatory ECG monitoring, and cardiac MRI. Results: A total of 89 (80.9% of 110) participants from MAD, and 91 (82.7% of 110) participants from CPAP completed 12 months follow-up. The median daily usage was 5.5 hours for MAD and 4.9 hours for CPAP. The between-group difference in 24h mean BP from baseline to 12 months was - 0.57 mmHg (95% confidence interval: (-2.53 to 1.39, non-inferiority P &lt; 0.001). Compared with the CPAP group, MAD group demonstrated a larger reduction in all the 24h with the most pronounced differences observed in the asleep BP parameters (Table 1). Both the MAD and CPAP improved QoL (Table 2). CPAP had greater improvement in FOSQ from sleep-specific questionnaires (P=0.038), and social QoL in SF-36 from non-sleep-specificl questionnaires (P=0.013). The ambulatory ECG monitoring (MAD: 2.8 ± 1.0 days, CPAP: 2.3 ± 1.1 days) showed no between-group differences in % atrial fibrillation(P=0.209), % ventricular ectopic isolated count (P=0.790) and % supraventricular ectopic isolated count (P= 0.333). The cardiac MRI sub-study (101 participants : MAD= 45, CPAP= 56) showed CPAP had greater improvement in right ventricular stroke volume (P=0.023) and MAD had greater improvement in circumferential strain favours the MAD group (P=0.015) (Table 3). Conclusion: At 12 months , MAD was non-inferior to CPAP for reducing 24h mean arterial BP. MAD showed greater reduction in 24h BPs, especially during asleep. While both the MAD and CPAP are effective in improving QoL, CPAP is more effective in improving FOSQ and social QoL (SF-36).

Meta-analysis of the effects of different exercise modes on cardiac function and peak oxygen uptake in patients with type 2 diabetes mellitus

BackgroundThe benefits of exercise for primary and secondary prevention of cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM). However, the effects of exercise on cardiac structure and function require clarification.MethodsA literature search for clinical studies reporting on the effects of exercise on cardiac structure, cardiac function, and VO2peak in T2DM patients was conducted. PubMed, Embase, EBSCO, Web of Science, and China National Knowledge Infrastructure were systematically searched for original articles published from January 2000 to July 2023. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed by exercise mode (high-intensity interval training [HIIT] or moderate-intensity continuous training [MICT]) and intervention duration (&amp;gt;6 or ≤6 months).ResultsCompared to usual care, both HIIT and MICT significantly affected left ventricular end-diastolic volume (MD: 19.44, 95% CI: 13.72 to 25.17, p &amp;lt; 0.00001; I2 = 42%; MD: 13.90, 95% CI: 7.64 to 20.16, p &amp;lt; 0.0001; I2 = 0%), but only HIIT significantly affected left ventricular mass (MD: 17.04 g, 95% CI: 5.45 to 28.62, p = 0.004; I2 = 0%). HIIT significantly improved left ventricular ejection fraction (MD: 5.52, 95% CI: 2.31 to 8.73, p = 0.0008; I2 = 0%), as did MICT in the ≤6 months subgroup (MD: 1.36, 95% CI: 0.61 to 2.10, p = 0.0004; I2 = 0%). Neither significantly affected systolic tissue velocity. HIIT significantly improved VO2peak (MD: 8.04, 95% CI: 6.26 to 9.83, p &amp;lt; 0.00001; I2 = 0%), as did MICT in the ≤6 months subgroup (MD: 3.33, 95% CI: 2.39 to 4.27, p &amp;lt; 0.00001; I2 = 0%).ConclusionExercise significantly improved cardiac structure, systolic function, and VO2peak, but did not significantly affect diastolic function in T2DM patients. HIIT seemed to be superior to MICT at improving VO2peak and left ventricular ejection fraction in T2DM patients.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, PROSPERO registration no.: CRD4242018087376

Abstract 4138373: Machine learning identifies clinically distinct phenotypes in patients with aortic regurgitation.

Background: Aortic regurgitation (AR) is a prevalent valve disease with a long latent period to symptoms. Recent data has suggested the role of novel markers of myocardial overload in assessing onset of decompensation. Method: We sought to evaluate the role of unsupervised cluster analyses in identifying different clinical clusters, including clinical status, and a large number of echocardiographic variables including left ventricular (LV) volumes, and their association with mortality. Patients with ≥moderate-severe chronic AR identified using echocardiography at Mayo Clinic, Rochester were retrospectively analyzed. Primary outcome was all-cause mortality censored at aortic valve surgery/last follow-up. Uniform Manifold Approximation and Projection (UMAP) with K -means algorithm was used to cluster patients using clinical and, echocardiographic variables at the time of presentation. Missing data were imputed with the Multiple Imputation by Chained Equations (MICE) method. A supervised approach trained on the training set was used to find cluster membership in a hold-out validation set. Log-rank tests were used to assess differences in mortality rates between the clusters, both in the training and validation sets. Results: Three distinct clusters were identified among 1100 patients (log-rank P for survival &lt;0.001). Cluster 1 (n=337), which included younger males with severe AR but fewer symptoms, showed the best survival, 75.6% (69.5, 82.3). Cluster 2 (n=235), older and more females with elevated filling pressures, showed intermediate survival of 64.2 % (56.8, 72.5). Cluster 3 (n=253), characterized by severe symptomatic AR, demonstrated the lowest survival of 45.3 % (34.4, 59.8) at 5 years. Similar clusters were formed in the internal validation cohort. Conclusion: Distinct clusters with variable echocardiographic features and mortality differences exist within patients with chronic ≥moderate-severe AR. Recognizing these clusters can refine individual risk stratification and clinical decision-making after verification in future prospective studies.

Abstract 4119052: Redefining the phenotypic continuum of cardiovascular disease using machine learning

Background: Current approaches that define cardiovascular disease rely on assignment of traditional diagnostic labels which may not reflect the natural continuum of phenotypic expression, influenced by genetic and environmental modifiers, or adequately identify groups with shared molecular mechanisms. Machine learning can leverage advances in genetic and imaging characterisation to reclassify phenotypic diversity along a continuum, from health to disease. Research Aims: Our study aims to build a tree-like classification of cardiovascular phenotypes in the community where branches represent subjects with shared features, ordered by their severity. Using dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) as exemplar conditions with opposing phenotypes, we aim to demonstrate the interaction between genetic and environmental modifiers of disease expression. Methods: We analysed cardiovascular magnetic resonance (CMR) imaging, electrocardiogram (ECG), biomarkers and clinical data from participants in the UK Biobank. Using unsupervised learning of multiparametric data, we built a tree of phenotypic expression. We projected the risk of DCM and HCM cases, and associated rare and common variant risk, onto the tree structure. Results: Ten main branches were discovered, using data from 41,525 participants (51.7 % female, median age 65 yrs [IQR: 58, 70]). The extremities of branches 1 and 6 were enriched for DCM cases (p &lt;0.05) and participants with reduced ejection fraction and high left ventricular volumes (p &lt;0.05). Compared with subjects at the tree centre, distal participants in branch 1 had increased blood pressure (BP) and body mass index (BMI), whilst those in branch 6 were more likely to have high HbA1c levels and carry a pathogenic DCM variant (p &lt;0.05). The extremity of branch 5 was enriched for HCM cases, rare sarcomeric variants (p = 0.004) and high polygenic risk (p &lt;0.001). Whilst the ends of branches 3 and 9 had high polygenic risk for HCM, they were less likely to have elevated BP and BMI, and had reduced likelihood of HCM expression, compared with branch 5. A phenomapping model was trained to accurately project unseen subjects onto the tree (R 2 0.98). Conclusions: We present a tree-like continuum of cardiovascular phenotypes, providing a novel framework for mechanistic discovery and exploration of genotype-phenotype associations. Phenomapping of unseen subjects enables personalised estimation of genetic and cardiovascular risk.

Abstract 4119210: Differential Proteomic Expression of IGFßP-1 and IGFßP-2 in Primary Angioplasty for Acute Myocardial Infarction

Introduction: Insulin growth factor (IGF) binding protein-1 and 2 (IGFBP-1 and 2) are implicated in acute myocardial infarction (AMI) and have been suggested as predictors of mortality and development of heart failure. The IGF axis has been shown to play roles in cell proliferation and apoptosis. We analysed the serum IGFBP-1 and 2 levels in AMI before and after percutaneous coronary intervention (PCI) and correlated this with cardiac magnetic resonance (CMR) imaging to better establish their significance as biomarkers in AMI. Methods: Patients with AMI who presented to Royal Free Hospital, London, were recruited for proteomic analysis (O link Proximity Extension Immunoassay) at presentation, 24h and 72h following primary PCI. All underwent both admission and follow-up CMR at 6 months to assess for myocardial oedema, left ventricular volumes and function, and assessment of scar. Results: Proteomic evaluation in 20 AMI patients (male 95%; median age 59) revealed significant reduction in the average IGFBP-1 values at discharge compared with presentation, from 5.93 to 4.52 (24% reduction, p=0.003). Conversely, the average IGFBP-2 values at discharge significantly increased from 7.66 to 8.29 (8% increase, p=0.001). Higher discharge IGFBP-2 value was also correlated with increased indexed left ventricle end diastolic volume (LVEDV) at 6-month follow-up (R=0.54, p=0.032). Discussion: IGFBP-1 and 2 showed significant change following intervention for AMI. IGFBP-1 is a stress hormone, which is directly and indirectly activated by cytokines, dysglycaemia and vasopressin activation. Its subsequent reduction following PCI in AMI indicates relative resolution of inflammation, but this was not correlated with changes in infarct size or LV function at follow-up. IGFBP-2 showed significant upregulation, and higher values at discharge were significantly correlated with increased LDEDV at follow-up, suggesting adverse clinical outcomes within this setting. This data suggests differential roles of IGFBP-1 and 2 in the pathogenesis of AMI.

Abstract 4136900: Left-to-right ventricular volume ratio as a predictor of cardiovascular events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The left ventricle (LV) and right ventricle (RV) are closely connected anatomically and functionally. Therefore, relative volume alterations signify pathologic disequilibrium even when within the normal range for chamber volumes. We aimed to define the prognostic value of volumetric imbalance between the LV and RV in the general population. Methods: The study sample consisted of 4073 asymptomatic participants from the Multi-Ethnic Study of Atherosclerosis who had a cardiac MRI at baseline. The left to right ventricular volume ratio (LRVR) was defined as LV volume/RV volume at end diastole. LRVR was categorized into balanced reference category 0.8-1.3, low (RV predominance) &lt;0.8, and high (LV predominance) &gt;1.3. Multivariable cox regression models were used to study the association between LRVR and heart failure (HF), atrial fibrillation (AF), and death. Results: The mean age of participants was 61.3±10 years, with 52% females. Participants were followed for a median of 17.8 years for HF, 16.7 years for AF, and 17.1 years for death. During follow up, 239 (5.9%) participants developed HF, 772 (19%) developed AF, and 906 (22.2%) died. When compared with the reference balanced LRVR group, those with high LRVR had increased risk of HF (HR 2.55; 95% CI 1.7-3.8; p &lt;0.01), AF (HR 1.57; 95% CI: 1.2-2.06; p&lt;0.01), and death (HR 1.63; 95% CI: 1.29-2.07; p&lt;0.01) after adjusting for demographics and traditional cardiovascular risk factors. Participants with low LRVR had increased risk of HF (HR 1.88; 95% CI 1.1-3.2; p=0.02) and death (HR 1.51; 95% CI 1.12-2.04; p&lt;0.01) in crude models. Adjusting for risk factors maintained increased risk of HF and death, but statistical significance was lost. Low LRVR was not associated with increased risk of AF. In a subgroup of participants with both absolute RV and LV volumes within normal ranges, high LRVR was still associated with increased risk of HF, AF, and death after adjusting for risk factors. Conclusion: In healthy asymptomatic participants at baseline, LV volume exceeding RV volume by at least 30% is associated with increased risk of HF, AF, and death. This relationship is independent of cardiovascular risk factors and absolute dilatation of either ventricle.

Stem cell therapy for non-ischemic dilated cardiomyopathy: a systematic review and meta-analysis

BackgroundStem cell therapy is the transplantation of human cells to aid the healing of damaged or wounded tissues and cells. Only a few small-scale trials have been conducted to investigate stem cell therapy for non-ischemic dilated cardiomyopathy (DCM). We aimed to perform a systematic review and meta-analysis to assess the efficacy and safety of stem cell therapy for DCM.MethodsA comprehensive search of the databases of PubMed, Embase, Web of Science Core Collection, Cochrane Library, and ProQuest was conducted from their inception to June 30, 2024, to access randomized controlled trials (RCTs) that were centered on stem cell therapy for DCM. The primary outcome was left ventricular ejection fraction (LVEF), and the secondary outcomes included left ventricular end-diastolic dimension (LVEDD), left ventricular end-diastolic volume (LVEDV), 6-min walk test (6MWT), NYHA functional classification, quality of life (QoL) such as Minnesota Living with Heart Failure Questionnaire (MLHFQ) and Kansas City Cardiomyopathy Questionnaire (KCCQ), N-terminal pro-brain natriuretic peptide (NT-proBNP), and VO2 peak. Moreover, major adverse cardiovascular events (MACEs) were also recorded. The Cochrane risk-of-bias assessment tool was used to evaluate the quality of the included RCTs, and the certainty of the evidence was assessed using the GRADE method. Sensitivity analysis was taken into consideration to determine the stability of the results. This review was registered with PROSPERO (CRD42024568912).ResultsEleven RCTs involving 637 participants were included in the quantitative analysis. The results indicated that there was a significant increase in mean LVEF (MD = 4.84, 95% CI 3.25–6.42, P < 0.00001) and considerable decrease in LVEDV (MD = − 29.51, 95% CI − 58.07 to − 0.95, P = 0.04) and NT-proBNP (MD = − 737.55, 95% CI − 904.28 to − 570.82, P < 0.00001) in DCM patients treated with stem cell therapy compared with controls. Stem cell therapy was also related to the improvement in functional capacity, as evaluated by 6MWT (MD = 44.32, 95% CI 34.70 − 53.94, P < 0.00001) and NYHA functional classification (MD = − 0.63, 95% CI − 0.96 to − 0.30, P = 0.0002). It also had positive effects on improving QoL, including significantly decreasing MLHFQ score (MD = − 16.60, 95% CI − 26.57 to − 6.63, P = 0.001) and increasing the KCCQ score (MD = 14.76, 95% CI 7.76 − 21.76, P < 0.0001). No significant differences were observed in LVEDD, VO2 peak, and MACEs between the two groups. The GRADE analysis revealed that the evidence was graded from low to moderate. Sensitivity analysis of the results suggested that the results were stable.ConclusionThe systematic review and meta-analysis indicates that stem cell therapy may be an effective and safe approach to improve cardiac function and quality of life in DCM patients. Nevertheless, given the limitations of existing studies, larger well-designed RCTs are required to confirm and support our findings.

Comprehensive Morphometric Analysis to Identify Key Neuroimaging Biomarkers for the Diagnosis of Adult Hydrocephalus Using Artificial Intelligence.

Hydrocephalus involves abnormal cerebrospinal fluid accumulation in brain ventricles. Early and accurate diagnosis is crucial for timely intervention and preventing progressive neurological deterioration. The aim of this study was to identify key neuroimaging biomarkers for the diagnosis of hydrocephalus using artificial intelligence to develop practical and accurate diagnostic tools for neurosurgeons. Fifteen 1-dimensional (1-D) neuroimaging parameters and ventricular volume of adult patients with non-normal pressure hydrocephalus and healthy subjects were measured using manual image processing, and 10 morphometric indices were also calculated. The data set was analyzed using 8 machine, ensemble, and deep learning classifiers to predict hydrocephalus. SHapley Additive exPlanations (SHAP) feature importance analysis identified key neuroimaging diagnostic biomarkers. Gradient Boosting achieved the highest performance, with an accuracy of 0.94 and an area under the curve of 0.97. SHAP analysis identified ventricular volume as the most important parameter. Given the challenges of measuring volume for clinicians, we identified key 1-D morphometric biomarkers that are easily measurable yet provide similar classifier performance. The results showed that the frontal-temporal horn ratio, modified Evan index, modified cella media index, sagittal maximum lateral ventricle height, and coronal posterior callosal angle are key 1-D diagnostic biomarkers. Notably, higher modified Evan index, modified cella media index, and sagittal maximum lateral ventricle height, and lower frontal-temporal horn ratio and coronal posterior callosal angle values were associated with hydrocephalus prediction. The results also elucidated the relationships between these key 1-D morphometric parameters and ventricular volume, providing potential diagnostic insights. This study highlights the importance of a multifaceted diagnostic approach incorporating 5 easily measurable 1-D neuroimaging biomarkers for neurosurgeons to differentiate non-normal pressure hydrocephalus from healthy subjects. Incorporating our artificial intelligence model, interpreted through SHAP analysis, into routine clinical workflows may transform the diagnostic landscape for hydrocephalus by standardizing diagnosis and overcoming the limitations of visual evaluations, particularly in early stages and challenging cases.

Exploring cardiovascular involvement in IgG4-related disease: a case series approach with cardiovascular magnetic resonance

BackgroundIgG4-related disease (IgG4-RD) is a relapsing–remitting, fibroinflammatory, multisystem disorder. Cardiovascular involvement from IgG4-RD has not been systematically characterised. In this study, we sought to evaluate consecutive patients with IgG4-RD using...

Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk.

Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR). Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed. Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter. This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.

The Impact of Different Revascularization Strategies Implemented in Acute Myocardial Infarction on the Recovery of Left Ventricular Functional and Deformational Parameters

Background: Despite well-established therapeutic techniques, such as direct revascularization through percutaneous coronary intervention (PCI), acute myocardial infarction (AMI) remains a leading cause of mortality and morbidity. Objectives: To determine if two-dimensional speckle tracking echocardiography (STE) deformation parameters and the early recovery of left ventricular (LV) functions are affected by the timing of PCI in AMI. Methods: A total of 200 cases with newly-onset acute myocardial infarction (AMI) who had a baseline left ventricular ejection fraction (LVEF) higher than 40% and received effective therapy with percutaneous coronary intervention (PCI) were included in this investigation. cases were categorized as either ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI). cases were grouped into four groups according to the time between presentation and PCI. Using standard echocardiography and two-dimensional (2D) ST-elevation STE, individuals were re-evaluated three months later to find out if remodeling had taken place or if the LV function had returned. Results: Of the 200 AMI patients, including 140 males (70%), improvement in global longitudinal strain (GLS) and harmed longitudinal strain (HLS) were better in STEMI and NSTEMI patients received urgent revascularization with PCI (groups I and III) versus patients with pharmacoinvasive strategy or routine invasive strategy (Groups II and IV) (P &lt; 0.05) while there was an insignificant difference between group I and III (P = 0.79). Of the 200 patients, 47 patients (23.5%) presented signs of LV remodeling at 3 months follow up. Age, smoking history, hypertension, dyslipidemia, Killip class, peak creatine phosphokinase - MB level, baseline left ventricular end diastolic volume (LVEDV), HLS, and harmed longitudinal strain rate (HLSR) were all factors that were found to be significantly associated with left ventricular remodeling (P&lt;0.05) in the univariate logistic regression analysis. The following factors were identified as independent predictors of left ventricular remodeling in multivariate logistic regression analysis: damaged left ventricular ejection fraction (EF) and end-systolic volume, peak troponin I, Killip class, culprit left anterior descending (LAD), 2 and 3-vessel coronary artery disease (CAD), and wall motion score index (WMSI). Conclusion: Earlier PCI in AMI helps earlier improvement in myocardial strain parameters. HLS and HLSR are excellent predictors for LV remodeling and may do better than global parameters.