Posterior Wall Thickness Research Articles

Systemic Immune Inflammatory Index as Predictor of Blood Pressure Variability in Newly Diagnosed Hypertensive Adults Aged 18–75

Background: Accumulating evidence from clinical trials, large registries, and meta-analyses of population studies shows that increased Blood Pressure Variability (BPV) is predictive of Cardiovascular (CV) outcomes, independently of the average Blood Pressure (BP) values. One of the mechanisms explaining the relationship between BPV and target organ damage is the inflammatory response. The Systemic Immune Inflammation Index (SII), which relies on peripheral blood cell counts, including platelets, neutrophils, and lymphocytes, has emerged as a predictor of prognosis and outcomes in various diseases. The aim of this study was to investigate the association of the SII with Ambulatory Blood Pressure Variability (ABPV) in newly diagnosed hypertensive patients. Methods: This study was designed as a cross-sectional observational study. A total of 1606 consecutive newly diagnosed Hypertension (HT) patients were included in the study. The population was evaluated across 3 different categories according to HT grades (5 groups), eligibility for antihypertensive therapy (2 groups) and ABPV levels (2 groups). Results: Significant differences were observed between ABPV groups in terms of Neutrophil to Lymphocyte ratio, Platelet to Lymphocyte ratio, glucose, SII, high-sensitive CRP, HT grade, Inter-Ventricular Septum, Posterior Wall thickness, and Left Ventricular Mass (p < 0.005). There was a significant relationship between SII and ABPV (r: 0.619, p < 0.05). At the cutoff value of 580.49, SII had 77% sensitivity and 71% specificity for ABPV > 14 (AUC: 0.788). Conclusions: SII may assist in developing an early treatment approach to minimize complications in patients with high ABPV who are at a higher risk of CV events.

Left atrial function in uraemic patients: Four-dimensional automatic left atrial quantitative technology study.

This study aimed to evaluate the utility of left atrial volume and function in uraemic patients using four-dimensional automatic left atrial quantification (4D auto LAQ) technology. Thirty-four undialysed uraemic patients (U-ND group), 60 dialysed uraemic patients (U-D group), and 32 healthy volunteers (N group) were enrolled in our current study. Conventional echocardiographic parameters were recorded, and left atrial volume and strain parameters were analysed to determine statistical differences among the three groups. The Pearson correlation coefficient was employed to assess the relationships between left atrial ejection fraction and left atrial strain parameters. Compared to the N group, uraemic patients often displayed left atrial enlargement and left ventricular hypertrophy. Significant increases were noted in left atrial diameter, interventricular septum thickness, left ventricular posterior wall thickness, E/e', diastolic blood pressure, systolic blood pressure, left atrial minimum volume, left atrial maximum volume, left atrial pre-atrial contraction volume, left atrial emptying volume and left atrial maximum volume index (P<0.05). Conversely, the e', E/A ratio and left atrial reservoir longitudinal strain were significantly decreased (P<0.05). However, no statistically significant differences were observed in the aforementioned parameters between the U-ND and U-D groups. The absolute values of left atrial conduit longitudinal strain and left atrial conduit circumferential strain, as well as left atrial passive ejection fraction, were notably lower in the U-D group compared to the N and U-ND groups, with statistically significant differences identified among the three groups (P<0.05). Uraemic patients exhibit marked left atrial enlargement and left ventricular hypertrophy, coupled with altered atrial function, particularly ductal dysfunction in the U-D group. The 4D auto LAQ technology proves advantageous in detecting these alterations, offering a promising tool for thorough cardiac assessment in this patient cohort.

Objective functional improvement and vital prognosis after TAVR in patients with low-gradient aortic stenosis. Development of a predictive score

Abstract Introduction Patients with low-gradient aortic stenosis (mean gradient &amp;lt; 40 mmHg) (LGAS) supose a clinical challenge because in these patients the degree of functional recovery after TAVR could be lower and their prognostic evolution more adverse. This is relevant for the optimal indication of TAVR, especially with the growing number of patients with a borderline indication due to comorbidities or advanced age with certain degree of frailty. Purpose To develop a clinical model to predict the response to TAVR in LGAS patients based in non invasive physiological parameters at baseline. Methods In a cohort of patients undergoing TAVR a prospective evaluation of multiple pathophysiological parameters was performed derived from pre- and post-TAVR assessment with echocardiography, computed tomography, and non-invasive arterial pulse wave analysis with the Sphygmocor XCEL system. Objective functional improvement 6 months after TAVR was assessed by the 6-minute walk test and NT-proBNP levels. Clinical follow-up was performed at 1 year. Results Of the 450 patients included, 310 showed high aortic gradient and 140 (31%) low gradient, with an objective functional improvement in 90% and 64% (p&amp;lt;0.001) respectively, and with 1-year mortality of 4% and 12% (p=0.001). In the LGAS group, 1-year mortality was 20% in the subgroup without functional improvement and 8% (p=0.001) in the subgroup showing functional improvement. In the LGAS group, the pathophysiological parameters predictive of functional improvement were the augmentation index75 ≥ 45% (OR 4, CI 95% 1.9–11.3; p=0.006), posterior wall thickness ≤ 12 mm (OR 3.2, CI 95% 1.4–8; p=0.01) and absence of atrial fibrillation (OR 2.7, CI 95% 1.5–8.4; p=0.01). To generate a simple integer-based point score for each predictive variable, each beta coefficient was divided by the absolute value of the smallest coefficient, multiplied by 5, and rounded to the nearest integer. The values were 7, 6 and 5 respectively. Among the low-gradient population, in 55 patients with 0-6 score points the functional improvement was only 29%, while in the remaining 85 patients with 7-18 score points the functional improvement was 86% (p&amp;lt;0.001). Conclusions LGAS patients account for a relatively high proportion of patients undergoing TAVR. They show less objective functional recovery, which is associated with a significantly higher mortality at follow-up. We have developed a score based on 3 variables (augmentation index75, posterior wall thickness and atrial fibrillation) that can help predict the functional and prognostic response to TAVR in these patients.

Echocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or diagnosed with fetal growth restriction (FGR) are at increased risk of neonatal mortality as well as cardiovascular disease later in life. Previous studies based on smaller cohorts (n&amp;lt;200) of newborns with SGA and FGR (n&amp;lt;200) have demonstrated structural and morphological alterations in the heart compared to infants born appropriate for gestational age (AGA). However, to our knowledge no previous study has systematically investigated the effect of SGA and FGR on echocardiographic parameters in the infant heart. Purpose To investigate whether echocardiographic parameters differ among infants born SGA or with FGR, in comparison to infants born AGA. Methods This study is a population-based cohort study of infants (n&amp;gt;25,000) offering postnatal cardiac examination including transthoracic echocardiography (TTE) between 2016-2018. We compared left ventricular (LV) TTE parameters in infants born SGA (birthweight ≥3rd and &amp;lt;10th percentile, n=2,106) and with FGR (birthweight &amp;lt;3rd percentile, n=972) with infants born AGA (birthweight ≥10th and &amp;lt;90th percentile, n=20,468) using a multiple linear regression analysis. We have investigated LV volumes, systolic function, diastolic function, and LV structure. All analyses were adjusted for sex, gestational age at birth, weight, length, and age at cardiac examination. Results Infants born SGA had higher heart rates compared with infants born AGA. Both infants born SGA and infants with FGR had significantly smaller LV dimensions including septal and posterior wall thicknesses (IVSd and LVPWd), and LV internal diameters (LVIDd and LVIDs). Infants born SGA had smaller end-diastolic and end-systolic volumes compared with infants born AGA (Table 1). Infants born SGA or with FGR had significantly higher mitral valve early peak velocities, compared with infants born AGA, and infants born SGA showed increased mitral valve atrial peak velocities indicating altered diastolic function (Table 1). Conclusion Infants born with inadequate intrauterine growth had smaller LV dimensions compared with infants born AGA, even when adjusting for infant size and age. Infants born SGA and with FGR both exhibited altered diastolic function. Longitudinal studies of children with inadequate intrauterine growth are needed to determine the impact on adult cardiac health.

Anemia in patients with chronic kidney disease and its association with cardiac abnormalities

Abstract Introduction Chronic kidney disease (CKD) is a pathology characterized by multisystemic comorbidities, predominantly associated with cardiovascular disease and anemia. However, the precise association between the degree of anemia and the development of cardiac abnormalities in patients with CKD undergoing hemodialysis remains unclear. Purpose To determine the association between the degree of anemia and cardiac abnormalities in patients with CKD receiving hemodialysis treatment. Methods A cross-sectional multicenter study that included individuals with CKD undergoing hemodialysis was conducted. Electronic medical records containing information regarding medical conditions and pertinent laboratory parameters was collected, and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the associated between the degree of anemia and echocardiographic parameters, with significant set at p &amp;lt;0.05. Results Ninety-nine individuals were included, with a median age of 48 years. The population was categorized based on hemoglobin (Hb) levels into non/mild anemia (Hb &amp;gt;10 mg/dL) and moderate/severe anemia (Hb &amp;lt;9.9 mg/dL) groups (table). Significant differences were observed in left ventricle (LV) posterior wall thickness (10mm in non/mild vs. 11mm in moderate/severe, p&amp;lt;0.015), left atrial (LA) volume (34 mL/m2 in non/mild vs. 39 mL/m2 in moderate/severe, p&amp;lt;0.007) and left ventricular ejection fraction (LVEF) (59% in non/mild vs. 55% in moderate/severe, p&amp;lt;0.025). Negative correlations (figure) were observed between Hb levels and LV mass index (r= -0.21, p= 0.03) and pulmonary artery systolic pressure (PASP)(r= -0.27, p= 0.006). Conclusion The degree of anemia demonstrated an association with cardiac abnormalities, as evidenced by alterations in echocardiographic parameters such as LVEF, LA volume and PSAP. This study underscores the importance of further prospective investigations to enhance early identification and stratification of anemia in patients with CKD aiming to mitigate further cardiac complications.Clinical demographics tableScatter plots with correlation graphs

Deep learning for fully automated echocardiographic measurements of left ventricular wall thickness and chamber dimensions in the parasternal long-axis view

Abstract Background Accurate quantification of left ventricular (LV) wall thickness and chamber dimensions in the echocardiographic parasternal long-axis view (PLAX) is crucial for clinical decisions in patients with heart disease. However, there is a need for more reproducible and time-efficient methods. Fully automated deep learning (DL)-based methods could address this need. Purpose To develop a DL-based method for fully automated measurements of LV wall thickness and chamber dimensions in PLAX, validate its performance in a large population cohort, and evaluate its capacity to differentiate between hypertensive and normotensive groups. Methods DL networks were trained on PLAX recordings from 207 subjects. The DL method performed cardiac segmentation, timing of end-systole and end-diastole, and measured LV wall thickness and chamber dimensions in PLAX. The model was validated in a large populational echocardiography dataset including a subset with test-retest evaluation. Agreement with expert reference measurements, test-retest reproducibility, and comparison of normotensive and hypertensive (defined as those on hypertensive medication or with systolic blood pressure &amp;gt;160 mmHg) groups were evaluated. Results In the populational study of 2047 subjects, the novel DL method demonstrated a feasibility of 97.6%. Strong agreement was observed between the automated DL method and expert readers in measuring end-diastolic septal thickness, posterior wall thickness, and LV diameter (bias 0.1 mm, 0.2 mm, and 2.2 mm, respectively, Figure 1). In a test-retest dataset (n=40, with 2 recordings per patient and 4 readers), the novel DL method displayed improved reproducibility compared to inter-reader measurements, with minimal detectable change for interventricular septal diameter 2.2 mm versus 2.6 mm, posterior wall diameter 1.2 mm versus 2.5 mm, and LV diameter 5.0 mm versus 6.3 mm (Figure 2). The DL method measured significantly wider septal diameter in the hypertensive group compared to normotensive group (p&amp;lt;0.001). Mean analysis time for wall thickness and chamber dimensions using the DL method was 1.2 seconds. Conclusion The novel DL method accurately measured LV wall thickness and chamber dimensions in the PLAX view, and demonstrated improved test-retest reproducibility compared to experienced echocardiographers. Additionally, it was able to detect significantly wider septal diameters in the hypertensive population. By providing fast and reliable measurements in retrospective data, and with potential for real-time measurements during image acquisition, this DL method has the potential to improve the yield, efficiency, and workflow in echocardiography.Bland-Altman posterior wall diameterTest-retest posterior wall diameter

Predicting cardiovascular death 1-year after transcatheter aortic valve implantation: an artificial-intelligence based risk model

Abstract Background Prediction of cardiovascular death after transcatheter aortic valve implantation (TAVI) remains difficult. Currently, more lower risk patients are considered for TAVI and predicting not only immediate survival, but more longer-term outcomes seems important. Most developed risk tools use standard statistical approaches and focus mainly on short-term (30 days post-TAVI) outcomes. Purpose The aim of this project was to identify important predictors for worse outcomes after aortic valve replacement using machine learning features. Furthermore, we want to develop and artificial intelligence (AI) -model to predict cardiovascular death 1 year after TAVI. Methods For our analysis we used 725 patients with severe AS that underwent TAVI between 2008 and 2022 and were included in a prospective single centre observational study. Leveraging an automated machine learning framework, we systematically evaluated various machine learning algorithms including Random Forest, AdaBoost, Neural Networks, Randomized Decision Trees and and Gradient Boosting. Results We constructed prediction models utilizing three feature subsets: the top 10 most important features, the top 15 most important features (Figure 1), and all available features (n=66). Our analyses yielded area under curve (AUC) values of 0.71, 0.83, and 0.92, respectively (Figure 2). The best model was obtained by Randomized Decision Trees. NYHA classification, left ventricular ejection fraction, Charlson comorbidity index, posterior wall thickness and myocardial infarction 90-days before TAVI appeared as the most influential predictors for cardiovascular death within one year after TAVI. Conclusions Our model was able to identify the most important features indicating high risk for patients undergoing TAVI. Using the 15-feature model, we were able to accurately predict cardiovascular death 1 year after TAVI. AI-models to predict risk can be used to better inform/select patients undergoing TAVI.

Validation of two simple scores to identify increased risk of transthyretin amyloid cardiomyopathy in heart failure with preserved ejection fraction

Abstract Background Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is an emerging underdiagnosed cause of heart failure (HF). 99mTc-3, 3-diphosphono-1,2-propanodicarboxylic acid (DPD) allows ATTR-CM diagnosis in the absence of histology. Recently two simple clinical scores to identify increased risk of ATTR-CM in patients with heart failure and preserved left ventricular ejection fraction have been developed and validated. Purpose To assess the prevalence of ATTR-CM in a Mediterranean cohort of patients at risk, and to externally validate the Mayo ATTR-CM and T-Amylo scores. We also explore its diagnostic accuracy improvement by adding N-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods Retrospective cohort study of consecutive patients with suspected cardiac amyloidosis referred to DPD between March 2017 and November 2020. Scans were reported using a visual grading system (0 to 3 increasingly; 2-3 positive) on planar images. Patients with clonal dyscrasia or those without rule-out tests (serum free light chain assay, and serum and urine protein electrophoresis with immunofixation) were excluded. Discrimination was obtained using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve based on the ATTR-CM score [High risk: score ≥ 6. Components: age (60-69 = 2 points; 70-79 = 3 points; ≥80 = 4 points), male sex = 2 points, hypertension = -1 point, ejection fraction &amp;lt;60% = 1 point, posterior wall thickness ≥12 mm = 1 point, relative wall thickness (septal + posterior wall thickness/left ventricular end diastolic diameter) &amp;gt;0.57 = 2 points], and T-amylo score [High risk: score &amp;gt; 6. Components: age ≥ 80 years = 1 point, interventricular septum thickness ≥16 mm = 2 points, low QRS interval voltage = 2 points, male gender = 3 points, and carpal tunnel syndrome = 3 points. Calibration was assessed with the Hosmer-Lemeshow goodness-of-fit test. Results A total of 200 patients were included with a mean age of 78.5 ± 11 years, 45.5% male, left ventricular ejection fraction 58% ± 12 and a median NT-proBNP of 2310 pg/mL (Table 1). 81 (40.5%) and 10 (5.0%) patients were categorized as a high-risk group due to ATTR-CM score value ≥6 and simplified T-Amylo score &amp;gt;6, respectively. Prevalence of ATTR-CM was 17.5%. The AUC for the Mayo ATTR-CM and T-Amylo scores in our cohort were 0.83 (95% CI 0.75-0.90) and 0.79 (95% CI 0.69-0.88) respectively, with an appropriated calibration (Figure 1). The addition of NT-proBNP to the scores did not increase the AUC (p=0.19 and p=0.08), with a Net Reclassification Improvement (NRI) of 0.055 (95% CI - 0.110 to 0.206) and 0.033 (95% CI - 0.113 to 0.224) respectively. Conclusion These two simple clinical scores are valid and reliable tools for ATTR-CM diagnosis in our Mediterranean cohort. Added to clinical suspicion, can improve the diagnostic workup for ATTR-CM, irrespective of NT-proBNP values.

Clinical and genetic profiles of patients with hereditary and wild type transthyretin amyloidosis: the transthyretin cardiac amyloidosis registry in the state of Sao Paulo, Brazil REACT-SP

Abstract Introduction Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. Purpose We designed the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo (REACT-SP), aiming to describe the demographic, genetic, clinical, and diagnostic test results and treatment of patients with ATTR. Methods We present data on physical signs and symptoms, cardiac and neurological assessments, and genetics in patients enrolled in the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil. Results Six hundred-forty-four patients were enrolled, 505 with the variant form (ATTRv) and 139 with wild-type (ATTRwt). Sixteen different mutations were detected, the most common being Val50Met (48.3%) and V142Ile (40.8%). Overall, more than half of the patients presented cardiological involvement, and the difference in this proportion between the ATTRv and ATTRwt groups was significant (43.9 vs. 89.9%; p&amp;lt;0.001). The neurological phenotype also differed between ATTRv and ATTRwt (56.8 vs. 31.7%; p&amp;lt;0.001). The mixed phenotype was found in 25.6% of the population, without a significant difference between the forms of amyloidosis. A group of patients remained asymptomatic (10.4%), with a lower proportion of asymptomatic ATTRwt patients. The median time between the onset of symptoms and diagnosis was 1,853 (IQR 1277–2997) days, which was longer in ATTRv patients than in ATTRwt patients (p&amp;lt;0.001). Sinus rhythm was reported in 74.2%, atrial fibrillation in 17.0%, low voltage in 28.6%, repolarization abnormalities in 39.8%, and pseudo infarction in 27.4%. Echocardiography showed median Left Ventricular Ejection Fraction (LVEF) was 60%, Interventricular Septum (IVS) 14 mm, Posterior Wall Thickness (PWT) 13 mm, Left Atrium (LA) 41 mm, Left Ventricular Diastolic Diameter (LVDD) 45 mm, Left Ventricular Systolic Diameter (LVSD) 30 mm, basal Right Ventricular Diastolic Diameter (RVDD) 35 mm and Left Ventricle (LV) longitudinal strain 9.1%. There was some degree of LV diastolic dysfunction in 38.4%, apical sparing in 31.3%, and thrombus or masses in 1.0%. Late Gadolinium Enhancement (LGE) was absent in 29% and was subendocardial in 35.5%, transmural in 13.7%, mesocardial in 13.7%, and epicardial in 8.2%. Conclusions This study details the clinical and genetic spectrum of patients with ATTR in São Paulo, Brazil. This preliminary analysis highlights the considerable phenotypic heterogeneity of neurological and cardiac manifestations in patients with variant and wild-type ATTR.

Modulation of p300 acetylation to protect against doxorubicin-induced cardiotoxicity

Abstract Background Doxorubicin (DOX) is a widely-used anti-neoplastic agent, but the most common adverse reaction to its use is cardiotoxicity(1). DOX acts by producing reactive oxygen species (ROSs) that cause DNA damage(1,2), which activates various proteins, including the tumour suppressor p53 and the acetyltransferase p300. When activated, p300 acetylates and increases the activity of p53 which leads to increased apoptotic activity(3). Cardiotoxicity results because the heart has limited mechanisms to dispose of ROSs(4), and because cardiomyocytes have a low turnover rate(5). Purpose We examined the p300 inhibitor Theracurmin (THR)(6,7) as a candidate to prevent DOX cardiotoxicity using an in-vivo mouse model, and sought to elucidate the underlying molecular mechanisms using in-vitro studies. Methods C57BL/6 mice were pre-treated with THR or vehicle (as control), then administered DOX or vehicle. Cardiac function was evaluated by echocardiography and cardiac catheterization. In vitro studies used cardiac fibroblasts (FBs) and cardiac endothelial cells (ECs) pre-treated with THR, then with DOX, as in the animal studies. Western blotting and rt-qPCR was used to quantify protein and mRNA levels of genes in the p53-p300 pathway or related to apoptosis, oxidative stress, and cell cycle control. Results DOX-treated mice showed significant decreases in left ventricular (LV) ejection fraction (LVEF, p=0.0004), fractional shortening (FS, p=0.0012), and a significant increase in end-systolic volume (ESV, p=0.0004). We also showed a significant decrease in anterior (LVAW;d, p=0.005) and posterior (LVPW;d, p=0.005) wall thickness of the LV in these mice. However, when mice were pre-treated with THR prior to DOX administration, we saw significant increases in LVEF (p=0.045) and LVPW;d (p=0.015), and a significant decrease in ESV (p=0.0047) compared to those that were not pre-treated. In-vitro analyses demonstrated a significant increase in cleaved caspase 3 protein expression in DOX-treated ECs (p=0.007), that was not prevented by THR pre-treatment. In DOX-treated FBs, we saw a reduction in AKT mRNA (p=0.017) and increases in BAX 9p=0.008), P21 (p=0.0001), and GADD45 (0.037) mRNA expression. In DOX-treated ECs, we also saw significant increases in BAX (p=0.015) and P21 (p=0.011) mRNA expression. These changes in mRNA expression were not reversed with THR pre-treatment in either cell type. Conclusion THR pre-treatment successfully mitigated functional deficits and structural deficits associated with DOX cardiotoxicity. In-vitro studies show that THR pre-treatment was not sufficient to significantly prevent changes in key molecular targets associated with apoptosis. Further studies are required to elucidate the mechanism behind the observed functional changes.Abstract OverviewAbstract Results

Predictive factors and gender insights into abnormal myocardial flow reserve in non-obstructive coronary artery disease: a CZT-SPECT analysis

Abstract Background Dynamic myocardial perfusion imaging (D-MPI) using cadmium-zinc-telluride (CZT) cardiac-dedicated SPECT has emerged as a valuable method for assessing coronary microcirculation, particularly compared to conventional SPECT. Additionally, gender-specific disparities in microvascular dysfunction require further investigation. Objective This study aims to identify predictive factors for abnormal myocardial flow reserve (MFR) in non-obstructive coronary artery disease (CAD) using CZT-SPECT, with a focus on gender differences in MFR dysfunction. Methods A retrospective analysis was conducted on clinical data from 393 patients presenting with symptoms of "chest pain and/or tightness," all of whom were confirmed to lack obstructive CAD by coronary angiography or CT angiography. MFR was measured using CZT-SPECT, with values ≥2.5 considered normal and values &amp;lt;2.5 considered abnormal. Results Of the patients, 49.1% (193/393) demonstrated abnormal MFR, with females representing 56.7% (223/393). Females with abnormal MFR exhibited higher averages in age, total cholesterol, LDL-C, creatinine, left atrial diameter, left ventricular posterior wall (LVPW) thickness in diastole, and E/e’ ratio (P &amp;lt; 0.05). Additionally, MDRD-eGFR and mitral annular septal velocity e’ were lower in the abnormal MFR cohort (P &amp;lt; 0.05). Multivariate logistic regression analysis identified elevated LDL-C levels (OR = 1.513, 95%CI: 1.122–2.041, P = 0.007) and increased LVPW thickness (OR = 1.717, 95%CI: 1.140–2.585, P = 0.010) as independent predictors of abnormal MFR in females. ROC analysis suggested optimal cutoff for LDL-C at 3.68 mmol/L (sensitivity 31%, specificity 84%, AUC = 0.586; 95%CI: 0.511–0.661) and LVPW thickness at 9.5 mm (sensitivity 62%, specificity 52%, AUC = 0.576; 95%CI: 0.501–0.652). A combined ROC analysis of LDL-C and LVPW thickness showed a sensitivity of 50% and specificity of 73% (AUC = 0.632, 95%CI: 0.559–0.705). In males, greater left ventricular end-diastolic diameter (LVEDD) was significantly associated with abnormal MFR (P = 0.014), with LVEDD identified as a predictor (OR = 1.130, 95%CI: 1.016–1.258, P = 0.025) and an optimal cutoff at 44.5 mm (sensitivity 88%, specificity 37%, AUC = 0.609; 95%CI: 0.524–0.694). No significant gender differences were observed in overall left ventricular resting myocardial blood flow (MBF) among patients with abnormal MFR (P = 0.072); however, female patients exhibited higher resting MBF in specific territories supplied by the left circumflex and right coronary arteries, and higher E/e’ ratios (P &amp;lt; 0.05). Furthermore, a negative correlation was found between resting MBF in the territory supplied by the right coronary artery and E/e’ in females (r = -0.210, P = 0.030). Conclusion Predictors of abnormal MFR in non-obstructive CAD show gender disparities, implicating an association with left ventricular diastolic function.

Obesity plays a key role in inducing myocardial and vascular dysfunction in a translational model of heart failure with preserved ejection fraction in rats

Abstract Background Exploring experimental models of heart failure with preserved ejection fraction (HFpEF) may help to understand the mechanisms leading to this challenging condition. Purpose In a translational model, we aimed to assess the relative contribution of hypertension and obesity in inducing structural, functional and hemodynamic changes associated to the HFpEF phenotype. Methods We investigated 3 groups of male 40 weeks old rats: control Wistar Kyoto (WKY, n=10), Spontaneous Hypertensive Rats (SHR, n=10) and SHR with obesity induced by consumption of cafeteria diet during 28 weeks (Ob-SHR, n=9). Animals were submitted to assessment of: body weight, systolic (SBP) and diastolic (DBP) blood pressure; in vivo structural and functional changes evaluated by high resolution Echocardiography including left atrial dimension (LA), left ventricle (LV) diastolic dimension (LVDD), LV posterior wall thickness (LVPW), LV wall relative thickness (LVWRT), LV ejection fraction (LVEF). Invasive hemodynamic evaluation assessed the intraventricular pressure curves obtaining LV end diastolic pressure (LVEDP) and calculation of LV diastolic time constant (Tau). After euthanasia, thoracic aorta was used for vascular function assessment by measuring the maximal cumulative concentration-effect curves of contraction to phenylephrine (PE), expressed as Emax (%). Protein expression of Intercellular Adhesion Molecule 1 (ICAM-1) was determined in myocardial tissue (% in relation to WKY). Results were expressed as mean ± SEM and effects of groups vs time were compared with mixed ANOVA. Results The results are shown in the table. We observed higher levels of SBP and DBP in SHR and Ob-SHR when compared to WKY, but with similar values between SHR and Ob-SHR groups. Regarding the structural LV changes, we observed LV remodeling and LA dilation in both SHR and Ob-SHR groups, but with no difference between both hypertensive groups. The Ob-SHR was the only group showing increased LVEDP in comparison to other groups. The Tau was also increased in the Ob-SHR animals. Concordantly, the Ob-SHR group showed increased expression of ICAM-1 (figure - A) that was concomitant to abnormal vascular response with increased contraction to PE (figure - B) as compared to SHR and WK groups. Conclusions In this translational model of HFpEF in rats, the structural changes related to LV remodeling were similar in SHR and Ob-SHR, probably reflecting comparable higher levels of blood pressure observed in both groups. In contrast, elevated EDP, a hallmark of HFpEF, was only seen in the Ob-SHR group and this was concomitant to diastolic dysfunction, endothelial inflammatory activation and altered vascular function. Our results indicate that obesity is a key factor inducing vascular and myocardial changes that triggers HFpEF phenotype in this model.

Epicardial adipose tissue and subclinical alterations in cardiac structure and function in early adulthood

Abstract Background Epicardial adipose tissue (EAT) is the visceral fat depot surrounding the heart and coronary arteries and shares the same microcirculation with myocardium. Under normal physiologic conditions EAT contains important cardioprotective properties such as cushioning the heart against mechanical stress, thermoregulation of the myocardium in hypothermia as well as balancing myocardial fatty acid homeostasis. Higher accumulation of EAT has been reported to independently associate with deleterious alterations in cardiac structure and function. However, majority of previously addressed study results are derived from older study population and in presence of cardiovascular diseases. Data on the associations of EAT and cardiac echocardiograpghically derived structural and functional parameters in a young and middle-aged population without prevalent cardiovascular disease is scarce. Purpose We aimed to address this knowledge gap by investigating the associations of echocardiographically measured EAT thickness and possible adverse subclinical alteration in cardiac structure and function in a population cohort of young and middle-aged adults. Methods This study participants were examined as part of the ongoing multi-centre longitudinal cohort, focusing on cardiovascular risk factors from childhood through adulthood. EAT thickness was measured by manual delineation from parasternal long-axis echocardiograms at end systole. Transthoracic and Doppler echocardiograpghy was performed and data on cardiac structural and functional parameters were derived comprehensively in accordance with EAE/ASE guidelines. Results In this study population (N=1677, men=770, women=897 ; age range 34-49 years) mean EAT thickness was 4.0 mm in whole population. In multivariable regression analysis models adjusted for age, sex, waist circumference and systolic blood pressure, significant independent associations of EAT and left atrial dimension (P&amp;lt;.0001) and various measures of left ventricular (LV) wall thickness such as LV mean wall thickness (P&amp;lt;.001), LV relative wall thickness (P&amp;lt;.001) as well as LV posterior wall thickness (P&amp;lt;.001) were observed. We found no significant associations between EAT thickness and cardiac functional and hemodynamic parameters after covariate adjustments in multivariable analysis models. Conclusion The findings of this study highlight that larger EAT thickness is associated with subclinical alteration in cardiac wall thicknesses in young and middle-aged adults. However, we found no associations between EAT thickness and cardiac functional parameters, which is perhaps due to the high cardiac adaptation properties in our relatively young study population. Therefore, further follow-ups is required to address long-term probable alterations in cardiac hemodynamics when the participants are older.

Metabolic dysfunction-associated steatotic liver disease-associated fibrosis and cardiac dysfunction in patients with type 2 diabetes.

Metabolic dysfunction-associated steatotic liver disease (MASLD), particularly in the presence of liver fibrosis, increases the risk of cardiovascular morbidity and mortality, but the nature of the cardio-hepatic interaction in the context type 2 diabetes mellitus (T2DM) is not fully understood. To evaluate the changes in cardiac morphology and function in patients with T2DM and MASLD-associated liver fibrosis. T2DM patients with MASLD underwent a medical evaluation that included an assessment of lifestyle, anthropometric measurements, vital signs, an extensive laboratory panel, and a standard echocardiography. Liver fibrosis was evaluated using two scores [Fibrosis-4 (FIB4) and Non-alcoholic fatty liver disease-Fibrosis Score (NFS)], and subjects were classified as having advanced fibrosis, no fibrosis, or an indeterminate risk. The correlations between structural and functional cardiac parameters and markers of liver fibrosis were evaluated through bivariate and multiple regression analyses. Statistical significance was set at P < 0.05. Data from 267 T2DM-MASLD subjects with complete assessment was analyzed. Patients with scores indicating advanced fibrosis exhibited higher interventricular septum and left ventricular (LV) posterior wall thickness, atrial diameters, LV end-systolic volume, LV mass index (LVMi), and epicardial adipose tissue thickness (EATT). Their mean ejection fraction (EF) was significantly lower (49.19% ± 5.62% vs 50.87% ± 5.14% vs 52.00% ± 3.25%; P = 0.003), and a smaller proportion had an EF ≥ 50% (49.40% vs 68.90% vs 84.21%; P = 0.0017). Their total and mid LV wall motion score indexes were higher (P < 0.05). Additionally, they had markers of diastolic dysfunction, with a higher E/e' ratio [9.64 ± 4.10 vs 8.44 (2.43-26.33) vs 7.35 ± 2.62; P = 0.026], and over 70% had lateral e' values < 10 cm/second, though without significant differences between groups. In multiple regression analyses, FIB4 correlated with left atrium diameter (LAD; β = 0.044; P < 0.05), and NFS with both LAD (β = 0.039; P < 0.05) and right atrium diameter (β = 0.041; P < 0.01), Moreover, LVMi correlated positively with age and EATT (β = 1.997; P = 0.0008), and negatively with serum sex-hormone binding protein (SHBP) concentrations (β = -0.280; P = 0.004). SHBP also correlated negatively with LAD (β = -0.036; P < 0.05). T2DM patients with markers of MASLD-related liver fibrosis exhibit lower EF and present indicators of diastolic dysfunction and cardiac hypertrophy. Additionally, LVMi and LAD correlated negatively with serum SHBP concentrations.

Developmental nicotine exposure alters cardiovascular structure and function in neonatal and juvenile rats.

Here we test the hypothesis that continuous nicotine exposure throughout pre- and postnatal development (developmental nicotine exposure, DNE) alters cardiovascular structure and function in neonatal and juvenile rats. Echocardiography showed that DNE reduced left ventricular mass, left ventricular outflow tract (LVOT) diameter, and posterior wall thickness, but only in females. Both male and female DNE rats had a lower end-systolic volume, higher ejection fraction, and increased fractional shortening, with unchanged stroke volume and cardiac output. Left ventricular single cardiac myocytes from male and female DNE animals exhibited increased calcium-evoked maximal tension with no effect on EC50. Tail-cuff plethysmography in awake rats showed that DNE males had lower systolic blood pressure and higher heart rate than control males. No significant changes in preload, afterload, or the in vitro renal artery response to vasodilators was observed. The results suggest that DNE enhances myocyte tension-generating capacity, possibly compensating for an unknown developmental insult, which may differ in males and females. While this adaptation maintains normal resting cardiac function, it may lead to reduced cardiac reserve, increased energy demand, and elevated oxidative stress, potentially compromising both short-and-long-term cardiovascular health in developing neonates.

Ductal stenting for retraining the left ventricle in patients with transposition of great arteries with intact ventricular septum: a single-centre experience.

Ductal stenting in late presenters with transposition of great arteries with intact ventricular septum retrains the left ventricle before arterial switch operation. However, the experience is limited for its efficacy and safety. This study aims to highlight the efficacy and safety of ductal stenting for retraining the left ventricle. Eight children with transposition of great arteries-intact ventricular septum and regressed left ventricle underwent ductal stenting. Serial echocardiographic measurements of left ventricle shape, mass, volume, free wall thickness, and function were done, and arterial switch operation was performed once the left ventricle was adequately prepared. Post-operative outcome in terms of duration of mechanical ventilation, ICU stay, and improvement in left ventricle function were monitored. The procedure was successful in all patients. Babies were divided into two groups on basis of age at ductal stenting (group 1 age less than 90 days and group 2 age more than 90 days) and were evaluated for the degree of left ventricle retraining as evidenced by echocardiographic parameters and post-operative variables. The left ventricle posterior wall thickness and mass index after ductal stenting increased significantly in both the groups. Postoperatively, one baby of group two expired after seven days due to severe left ventricle dysfunction. Rest babies had an uneventful post-operative ICU stay with no statistical difference in the duration of invasive mechanical ventilation or ICU stay. On six-month follow-up, all surviving babies were doing well with normal left ventricle function. Ductal stenting is a good alternative measure as compared to surgical procedures for left ventricle retraining in transposition of great arteries with regressed left ventricle.

Race, Sex, and Ejection Fraction-Based Differences in Transthyretin Amyloid Cardiomyopathy (ATTR-CM) Risk Prediction

Background: The early detection of transthyretin cardiac amyloidosis (ATTR-CM) is essential, with Tc-99m pyrophosphate scintigraphy (PYP scan) being a key diagnostic tool. Although a previously validated score has shown promise in predicting PYP scan positivity among patients with HFpEF, further evaluation in diverse cohorts is necessary. Objectives: To assess the effectiveness of the ATTR-CM score in predicting PYP scan positivity within our patient population. Methods: We analyzed patients referred for PYP with SPECT at the Cleveland Clinic from January 2012 to January 2020, all of whom had undergone echocardiography within the previous year. The ATTR-CM score was determined using the following criteria: Age (60–69, +2; 70–79, +3; ≥80, +4), sex (male, +2), hypertension (present, −1), left ventricular ejection fraction (LVEF &lt;60%, +1), posterior wall thickness (≥12 mm, +1), and relative wall thickness (&gt;0.57, +2). A score of ≥6 indicated high risk. Results: Among the 540 patients (32% female, 33% black), 27% had an LVEF &lt;40%. The score demonstrated good discrimination by AUC, with consistent performance across different racial groups, sexes, and LVEF categories. For scores ≥6, sensitivity was lower in women and black patients; however, lowering the cutoff to 5 markedly improved sensitivity. Conclusions: The ATTR-CM score displayed consistently good performance by AUC across our cohort, including patients with HFrEF. Nevertheless, its sensitivity was reduced in black patients and women. Efforts to scale ATTR-CM diagnosis tools should be mindful of demographic differences in risk prediction models.

Characteristics of gene expression in epicardial adipose tissue and subcutaneous adipose tissue in patients at risk for heart failure undergoing coronary artery bypass grafting

BackgroundEpicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9).ResultsThe study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e’mean, deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B.ConclusionsThe roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

The impact of ventricular remodeling on quality-of-life outcomes after Transcatheter aortic valve replacement

BackgroundAmong patients with aortic stenosis, ventricular remodeling by hypertrophy can limit the augmentation of flow with exertion, even after valve intervention. However, the effect of hypertrophy on quality of life (QoL) improvement has not been studied. We aimed to determine the effect of ventricular hypertrophy on QoL outcomes after transcatheter aortic valve replacement (TAVR). MethodsAll patients undergoing TAVR from 2011 to 2021 at our institution were included. Groups were divided into none/mild ventricular hypertrophy (non-remodeled, NR) and moderate/severe left ventricular hypertrophy (VH) according to guideline-recommended cut-offs for left ventricular (LV) wall thickness. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was utilized to assess QoL; primary outcome was KCCQ change <5 from baseline to 30 days and 1 year. ResultsWe analyzed 679 patients (NR: N = 389, VH: N = 290). Groups differed by septal thickness (1.12 cm vs. 1.44 cm, p < 0.001), posterior wall thickness (1.08 cm vs. 1.33 cm, p < 0.001), and LV internal diastolic diameter (4.34 cm vs. 4.19 cm, p = 0.006). The primary outcome was similar between NR and VH at 30 days (31.6 % vs. 28.6 %, p = 0.449) and 1 year (27.7 % vs. 21.5 %, p = 0.217). NR and VH experienced similar proportions of worsening, no change, or small, moderate, and large improvements in KCCQ score. Both groups experienced similar domain score changes and New York Heart Association class improvement. A subgroup analysis of VH patients did not reveal interaction with cavity size or stroke volume. ConclusionPatients with significant ventricular remodeling by hypertrophy and aortic stenosis have similar QoL changes after intervention compared to patients without significant remodeling.