Global Longitudinal Strain Research Articles

Usefulness of left ventricular mechanical dyssynchrony for predicting atrial fibrillation and adverse outcomes following first atrial fibrillation event

Abstract Background Left ventricular mechanical dyssynchrony (LVMD) has shown to predict many cardiovascular outcomes including ventricular arrhythmias. Our hypothesis is that LVMD can reveal early atrial dysfunction. Purpose The aim of this study was to investigate whether LVMD can be used to predict atrial fibrillation (AF) and adverse outcomes following first AF event in individuals from the general population. Methods A total of 3785 individuals (mean age 55±17 years, 57% women) from the general population free of AF, heart failure (HF) and prior stroke had an echocardiographic examination performed including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or HF after the diagnosis of AF. Results During a median follow-up of 5 years (interquartile range, 4.4-6.2 years), 142 (4%) individuals were diagnosed with AF, and of these 22 (15%) individuals developed HF or stroke. LVMD was a univariable predictor of AF (per 10ms increase: HR 1.03; 95% CI (1.02-1.05), p<0.001, Figure). The association remained significant even after multivariable adjustment for age, sex, body mass index, diabetes, hypertension, heart rate, previous ischaemic heart disease, systolic blood pressure, diastolic blood pressure, smoking, left ventricular ejection fraction, global longitudinal strain, left atrial volume index (LAVI), and E/e’ (per 10ms increase: HR 1.02; 95% CI (1.00-1.04), p=0.042). LVMD also predicted complicated AF, and the association remained significant even after multivariable adjustment (per 10ms increase: HR 1.05; 95% CI (1.01-1.09), p=0.026). Furthermore, LVMD provided incremental prognostic information over the LAVI with regard to predicting AF (Harrell’s C-statistics 0.66 vs. 0.70, p=0.012). Conclusion In a low-risk general population, LVMD provides prognostic information on the risk of AF. Additionally, LVMD can identify individuals with complicated AF defined as occurrence of either stroke or HF following the diagnosis of incident AF. Furthermore, LVMD provides incremental prognostic information over the LAVI in predicting AF.

Hypoperfused myocardium and systolic function in patients with AMI undergoing complete revascularization

Abstract Background and Aim Coronary revascularization is the standard treatment for acute myocardial infarction (AMI), while the restoration of epicardial flow is non-parallel to myocardial reperfusion. This study sought to investigate the dynamic of myocardial perfusion and its association with left ventricular (LV) systolic function in AMI patients undergoing complete revascularization. Methods AMI patients who underwent complete revascularization were prospectively enrolled, and hybrid positron emission tomography/magnetic resonance (PET/MR) was performed at 2 months and 1 year. Hypoperfused myocardium was defined as myocardium with reduced perfusion and normal metabolism. Results Forty-five patients (59.80 ± 10.68 years, 80.0% male) were enrolled, and hypoperfused myocardium (median: 12% of LV) was detected in 21 (46.7%) patients 2 months post-AMI. Patients with hypoperfused myocardium (Group A) had significantly higher hypersensitive C-reactive protein (hs-CRP) (p = 0.016) and lower T2 value (p = 0.010) than those without (Group B). In the follow-up PET/MR at 1 year, significant LV ejection fraction improvement was observed in Group A (56.39 ± 9.76% vs. 54.58 ± 10.39%, p = 0.016) but not in Group B (51.63 ± 13.09% vs. 50.79 ± 16.95%, p = 0.615). Six (31.6%) patients in Group A showed recovery of perfusion, of which there were more females (p = 0.025), fewer diabetics (p = 0.044), or overweight (p = 0.035), with better global longitudinal strain (GLS) (p = 0.005). Conclusions Myocardial hypoperfusion is not rare and evolves over time in AMI patients undergoing complete revascularization, of which the reversal is probably associated with improved LV systolic function.Structured Graphical AbstractRepresentative PET/MR image of 2 separat

Unsupervised machine learning identifies distinct phenotypes in cardiac complications of pediatric patients treated with anthracyclines

BackgroundAnthracyclines are essential in pediatric cancer treatment, but patients are at risk cancer therapy-related cardiac dysfunction (CTRCD). Standardized definitions by the International Cardio-Oncology Society (IC-OS) aim to enhance precision in risk assessment.ObjectivesCategorize distinct phenotypes among pediatric patients undergoing anthracycline chemotherapy using unsupervised machine learning.MethodsPediatric cancer patients undergoing anthracycline chemotherapy at our institution were retrospectively included. Clinical and echocardiographic data at baseline, along with follow-up data, were collected from patient records. Unsupervised machine learning was performed, involving dimensionality reduction using principal component analysis and K-means clustering to identify different phenotypic clusters. Identified phenogroups were analyzed for associations with CTRCD, defined following contemporary IC-OS definitions, and hypertensive response.ResultsA total of 187 patients (63.1% male, median age 15.5 years [10.4–18.7]) were included and received anthracycline chemotherapy with a median treatment duration of 0.66 years [0.35–1.92]. Median follow-up duration was 2.78 years [1.31–4.21]. Four phenogroups were identified with following distribution: Cluster 0 (32.6%, n = 61), Cluster 1 (13.9%, n = 26), Cluster 2 (24.6%, n = 46), and Cluster 3 (28.9%, n = 54). Cluster 0 showed the highest risk of moderate CTRCD (HR: 3.10 [95% CI: 1.18–8.16], P = 0.022) compared to other clusters. Cluster 3 demonstrated a protective effect against hypertensive response (HR: 0.30 [95% CI: 0.13– 0.67], P = 0.003) after excluding baseline hypertensive patients. Longitudinal assessments revealed differences in global longitudinal strain and systolic blood pressure among phenogroups.ConclusionsUnsupervised machine learning identified distinct phenogroups among pediatric cancer patients undergoing anthracycline chemotherapy, offering potential for personalized risk assessment.

The condition of myocardium reserves score from a cloud-based analytics platform of Holter ECG data indicates better cardiometabolic function in heart failure

Abstract Introduction Cardiometabolic dysregulation, particularly type 2 diabetes mellitus (T2DM), is associated with subtle myocardial pathologies, even in individuals without known cardiovascular disease. These subclinical changes, often undetectable by standard electrocardiogram (ECG) analytics, can offer valuable insights into the relationship between metabolic health and cardiac function. Novel ECG markers, developed through machine learning and artificial intelligence (AI), may provide the sensitivity needed to detect such changes. Aim This study aims to evaluate novel composite cardiac parameters from an analytics platform in the context of heart failure (HF), seeking to understand their relationship to cardiometabolic dysregulation. Methods Data from the MyoVasc study, a prospective cohort on HF, were analysed. Participants underwent extensive clinical phenotyping, including a Holter ECG assessment. Holter ECG data was processed based on machine learning and AI models on a cloud-based analytics platform (Cardiolyse, Helsinki, Finland), generating both traditional and proprietary ECG, and heart rate variability cardiac health markers. LASSO-penalized logistic regression adjusted for sex and age was performed to select the marker most strongly associated with T2DM. The identified marker was then evaluated in relation to cardiac function and structure as well as HF-related outcome. Results A total of 953 subjects (mean±SD age 64.6±10.5 years; 35.7% women) were included in the analyses. Symptomatic HF stage C/D was present in 54.8% (n=522) of subjects and diabetes mellitus in 22.4% (n=213). The Condition of Myocardium Reserves Score (CMRS) was the novel composite cardiac parameter selected based on its relationship with T2DM. In a Poisson regression model with robust variance adjusted for sex and age, a lower score was associated with T2DM (Prevalence ratio per SD 1.24, 95% confidence interval [1.14;1.36], P=0.0002). In multivariable linear regressions adjusted for traditional cardiovascular risk factors, comorbidities, and medication, a higher CMRS was associated with better global longitudinal strain (β per SD –0.82 [–1.11;–0.53], P<0.0001), diastolic function (left ventricular E/e’; β per SD –0.04 [–0.06;–0.01], P=0.0059) and systolic function (LV ejection fraction; β per SD 2.06 [1.46;2.67], P<0.0001). A lower CMRS independently predicted all-cause death (Hazard ratio per SD 1.25 [1.09;1.45], P=0.0020) and worsening of HF (HR per SD 1.44 [1.21;1.72], P<0.0001) in Cox regression analysis adjusted for the same confounders. Conclusion The Condition of Myocardium Reserves Score exhibited a strong association with cardiometabolic dysregulation. A higher CMRS indicated preserved cardiac function, while a lower score independently predicted increased risk of all-cause death and worsening HF. This novel score offers potential as a non-invasive tool for assessing cardiometabolic health and stratifying risk in patients with HF.

Comparison of different non-invasive estimates of right ventriculo-arterial coupling as outcome predictors in dilated cardiomyopathy

Abstract Right ventriculo-arterial coupling (RVAC) has emerged as an outcome predictor in pulmonary hypertension, but its role in left-sided HF remains to be clarified. Different non-invasive estimates for RVAC have been proposed, but a direct comparison of their prognostic ability is lacking. We sought to evaluate RVAC non-invasively using five different methods in a cohort of patients with dilated cardiomyopathy (DCM) and to assess their prognostic role. We enrolled 121 consecutive patients with non-ischemic DCM in sinus rhythm, who underwent comprehensive echocardiography, including speckle-tracking and 3D analysis. They were prospectively followed for 19±11 months for a composite endpoint of death, nonfatal cardiac arrest and hospitalization. RVAC was measured using five non-invasive estimates: (1) as the tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio; (2) as the right ventricular (RV) global longitudinal strain (RV-GLS)/PASP ratio; (3) as the longitudinal strain of the RV free wall (LS-RVFW)/PASP ratio; (4) as the 3D RV ejection fraction (RVEF)/PASP ratio; and (5) as the 3D RV stroke volume (SV)/3D RV end-systolic volume (ESV) ratio. Mean age in the study cohort was 59±14 years and the majority (74%) were men. 55 patients (46%) reached the endpoint: there were 27 deaths, 5 nonfatal cardiac arrests and 23 readmissions for heart failure. Patients with adverse outcome had lower TAPSE/PASP (0.42±0.23 vs. 0.62±0.33, p<0.001), lower RVEF/PASP (0.96±0.49 vs. 1.47±0.67, p<0.001), lower RV SV/ESV (0.57±0.20 vs. 0.93±0.29, p<0.001) and higher RV-GLS/PASP (-0.25±0.20 vs. -0.38±0.23, p=0.002) and LS-RVFW/PASP (-0.28±0.30 vs. -0.51±0.33, p<0.001), reflecting greater ventriculo-vascular decoupling. In univariate Cox regression, all three RVAC indices were outcome predictors: HR=0.09 [95% CI, 0.02-0.37], p=0.001 for TAPSE/PASP, HR=13.67 [95% CI, 2.77-67.48], p=0.001 for RV-GLS/PASP, HR=8.72 [95% CI, 3.24-23.45], p<0.001 for LS-RVFW/PASP, HR=0.27 [95% CI, 0.14-0.50], p<0.001 for RVEF/PASP, HR=0.004 [95% CI, 0.001-0.019], p<0.001 for RV SV/ESV. In ROC analysis, the SV/ESV ratio had the highest AUC (AUC=0.88, p<0.001), a value lower than 0.74 having 86% sensitivity and 77% specificity for event prediction. After adjustment for age, NYHA class, left ventricular ejection fraction, and maximal left atrial volume, all coupling indices remained independent predictors of outcome: HR=1.90 [95% CI, 1.01-3.57], p=0.047 for TAPSE/PASP, HR=2.15 [95% CI, 1.17-3.96], p=0.01 for RV-GLS/PASP, HR=2.48 [95% CI, 1.34-4.60], p=0.004 for LS-RVFW/PASP, HR=3.19 [95% CI, 1.19-8.52], p=0.02 for RVEF/PASP, HR=7.50 [95% CI, 3.47-16.22], p<0.001 for RV SV/ESV. In DCM, RVAC is significantly more impaired in patients with major adverse events. Non-invasive RVAC was an independent predictor of adverse outcome irrespective of the formula used for estimation, but 3D RV SV/ESV ratio had the greatest prognostic power.

Early detection of cardiac dysfunction using shear wave imaging: insights into reduced cardiorespiratory fitness in childhood cancer survivors

Abstract Background Diastolic dysfunction is thought to be the earliest cardiotoxic sequel after cancer therapy among childhood cancer survivors. Despite many survivors do exhibit reduced cardiorespiratory fitness (CRF) potentially due to cardiotoxicity, current echocardiographic parameters fail to detect hidden diastolic dysfunction early after therapy (1). High frame rate (HFR) shear wave imaging (SWI) is a novel tool that could give insights about myocardial stiffness, which is a key determining factor of diastolic function. Purpose We aimed at testing the ability of SWI to detect early alterations in myocardial stiffness among childhood cancer survivors and its relation with the reduced CRF. Methods Fifty childhood cancer survivors (mean 20 ±3 years) who received chemo-and/or- radiotherapy (mean time after treatment: 4 ±3 years) and thirty-two matched healthy volunteers (HV) were recruited. Conventional as well as HFR echocardiographic images (ca. 1200 frames/second) were acquired at rest using a modified commercial echocardiography machine. All participants underwent an incremental, symptom-limited cardiopulmonary exercise test on a treadmill measuring peak oxygen consumption (VO2 peak). HFR data were analysed offline. An anatomical M mode was drawn along the ventricular septum, and tissue Doppler acceleration maps were extracted to measure SW velocities after mitral valve closure (MVC) (Figure 1). Results Among cancer survivors, left ventricular ejection fraction (LVEF) and global longitudinal strain were significantly lower compared to HV (56 % ±4 vs 59 % ±4, and 17.6 % ±1.6 vs 19.1 % ±1.2, respectively; p <0.001). However, both LVEF and GLS were within the normal range and none of them correlated with the peak VO2 (Figure 2A&B). None of the echocardiographic diastolic parameters (e.g. mitral E, E/e’, left atrial volume or TR jet velocity) showed significant difference between both groups (P > 0.05). The mean SW velocities were significantly higher in cancer survivors compared to HV (3.9 ±0.6 m/s vs 3.2 ±0.3 m/s respectively; p <0.001). Interestingly, SW velocities among cancer survivors showed moderate significant negative correlation with the VO2 peak (r= -0.590, p <0.001) indicating increasing myocardial stiffness as the cardiorespiratory fitness declined (Figure 2C). Conclusions Our data indicate that myocardial stiffness in cancer survivors is significantly increased. We hypothesize that this increased stiffness may at least in part explain the significantly reduced cardiorespiratory fitness in this population. Echocardiographic shear wave elastography appears as a promising non-invasive tool for early detection of diastolic dysfunction in follow-up of childhood cancer survivors.Figure 1.Figure 2.

Deep learning detection of subclinical cardiovascular dysfunction in type 2 diabetes through retinal photography

Abstract Background Type 2 diabetes (T2D) is associated with excess atherosclerotic coronary disease and heart failure risk, with several cardiac abnormalities described in asymptomatic patients. Routine digital retinal photography performed for screening of diabetic retinopathy (DR) has the potential to identify patients with underlying cardiovascular disease (CVD). We aimed to determine whether features extracted from digital retinal photographs could detect subclinical cardiovascular dysfunction in asymptomatic people with T2D. Methods We prospectively enrolled adults with T2D and no history or symptoms of CVD to undergo extensive phenotyping with multiparametric stress perfusion cardiac MRI and CT coronary artery calcium scoring. Digital retinal photographs acquired for routine diabetic eye screening and performed within one year of cardiac evaluation were interrogated for retinopathy grading and using four deep learning (DL) models (Xception, Inception, EfficientNet, and MobileNet) to capture complex patterns within the retinal vasculature. Each subject had four retinal photographs (two of each eye) for DL analysis. Cardiac image analysis was performed blinded to participant details and independent of retinal images. Subjects with and without DR were compared. Participants were divided into training (80%) and validation datasets (20%) prior to DL analysis. DL models employed to predict from retinal images: presence or absence of coronary artery calcium on non-contrast CT, myocardial perfusion reserve <2.5, left ventricular (LV) global longitudinal strain <16%, absolute stress and rest myocardial blood flood (mL/g/min) used as continuous variables. AUC was used to assess the ability of DL models to discriminate between those without and without subclinical CVD. Results An initial 254 subjects (comprising 1,016 retinal photographs) were included in the analysis: 212 (83%) with no DR, 42 (17%) with grade 1 (mild background) DR. Key cardiac imaging parameters in subjects with and without DR are displayed in Table 1. The groups were well matched for age, sex, body mass index and blood pressure. Overall, those with grade 1 DR had higher atheroma burden, evidence of increased LV filling pressures (E/e’) and poorer systolic function, but no differences in stress and rest myocardial blood flow or myocardial perfusion reserve. However, all four DL models failed to achieve sufficient discrimination of any of the evaluated cardiac imaging parameters, with the majority achieving AUC scores below 50% for all cardiac parameters. Conclusion Asymptomatic adults with grade 1 DR exhibit more subclinical atherosclerosis and cardiovascular dysfunction than those without DR. However, DL transfer models could not discriminate between subjects with and without cardiovascular disease. Further work is needed to better define whether retinal screening may be used to identify those people with T2D most at risk of underlying cardiovascular disease.Subjects demographics

Prognostic value of cardiac magnetic resonance global circumferential strain assessed by feature tracking techniques in asymptomatic patients with significant aortic regurgitation

Abstract Introduction Cardiac magnetic resonance feature tracking (CMR-FT) deformation techniques have gained significant interest in recent years. They provide a comprehensive evaluation of myocardial function and improve the reproducibility of echocardiography strain techniques. Purpose The aim of this study was to evaluate whether CMR-FT deformation parameters play a role predicting worse clinical evolution in patients with chronic significant aortic regurgitation (AR) not meeting guidelines intervention criteria. Methods We included 85 patients with significant AR (moderate, moderate/severe, and severe) referred for CMR. Only asymptomatic patients with preserved left ventricle ejection fraction (LVEF) were considered for inclusion. Other concomitant myocardiopathies were excluded. Conventional functional left chambers parameters as well as myocardial deformation were evaluated, including global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS). A composite clinical major outcome was assessed, including admission heart failure admission, need for aortic valvule replacement and all-cause mortality. Results The mean age of the sample was 62 years old. One third of the patients were females. Other clinical baseline characteristics were not significantly different between groups when compared with Chi-squared and T-test statistical analysis. Mean follow-up was 42 months (±31). 21 patients presented with the composited outcome previously described. End-diastolic and end-systolic volumes did not differ between groups. Mean end-diastolic volume (EDV) was 196 ± 6.1 mL and mean end-systolic volume (ESV) was 88 ± 3.4 mL. Mean values of CMR-FT GLS, GCS and GRS were -14.1%, 22.8% and -16.9% respectively. GCS was selected as the best predictor for the combined endpoint point, with and area under the ROC curve of 0.67. A GCS value <-17% was selected as the optimal cut-off point. This value predicted events as is shown in Kaplan-Meier curves (HR 3.6, CI 95% 1.42 - 9.02, p = 0.007). A multivariate analysis showed that this association was independent of left ventricle (LV) ejection fraction, LV volumes and left atrial (LA) volume. Conclusion CMR-FT deformation parameters are impaired in significant AR patients even if intervention criteria are not met. A value of GCS < -17% in this population could predict a worse clinical evolution and emerges as a promising new tool helping clinical decision making in this challenging population.Kaplan-Meier curve free-event survival

Cardiovascular (reverse) remodelling induced by pregnancy: looking at the right side of the heart

Abstract Introduction Many studies have focused on pregnancy-induced left ventricular remodelling, overlooking the changes in right cardiac chambers. Purpose To characterize the right cardiovascular (CV) remodelling and reverse remodelling (RR) induced by pregnancy and postpartum, respectively, and the impact of CV risk (CVR) factors on these processes. Methods This prospective cohort was recruited at two tertiary centers from 2019 to 2022, including 51 healthy and 79 obese and/or hypertensive and/or with gestational diabetes and/or smoking habits pregnant women (cardiovascular risk [CVR] group). Women were evaluated by transthoracic echocardiography at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy, as well as one-month (PP1), six-months (PP2), and one-year postpartum (PP3). Generalized linear mixed-effects models were used for the analysis of right CV remodelling and RR and to evaluate the impact of CVR factors on these processes. Results This study included 130 pregnant women, 60.8% primiparous, with a median age of 33 years. Despite all echocardiographic results being within the normality range, we describe the progression of right heart adaptations throughout pregnancy and postpartum (Table 1), namely: 1) Similar enlargement of the right atrium (RA) and right ventricle (RV) dimensions throughout pregnancy, recovering at PP2 except for RA in the CVR group; 2) Preserved RV systolic function throughout pregnancy in both groups, while the postpartum hemodynamic normalization triggers a reduction of (TAPSE) and tricuspid S' wave velocity; 3) Reduced RA strain in both groups during pregnancy, more evident in CVR group, which had a slower postpartum recovery; 4) Preserved RV global longitudinal strain (GLS) throughout follow-up time, being significantly reduced in 3T of CVR group and recovering at PP2; 5) Reduction of tricuspid E/A ratio from 1T to 3T in both groups with an early recovery at PP1, being these values significantly higher in the healthy group, and 6) Steady pulmonary artery systolic pressure (PASP) values throughout follow-up time, showing consistently higher values in the CVR group. Conclusion This study describes the subclinical right cardiac functional and structural changes within the physiological range, which recover 6 months after delivery. CVR factors impact the magnitude of the subclinical RV diastolic function changes, PASP and myocardial deformation (strain) without any impact on classic RV systolic function.

Prognostic implication of right ventricular - pulmonary arterial coupling in patients with non-valvular atrial fibrillation

Abstract Background The clinical importance of right ventricular (RV) - pulmonary arterial (PA) coupling has been reported in various cardiac diseases such as right heart failure, pulmonary hypertension, and valvular dysfunction. However, there is limited data on patients with non-valvular atrial fibrillation (AF). We aim to investigate whether RV-PA uncoupling affects the clinical outcome in patients with non-valvular AF. Methods A total of 807 consecutive patients with non-valvular AF who underwent echocardiography (mean age 70 ± 12 years, 39% female) were included. We excluded patients with significant (at least moderate degree) valvular diseases, left ventricular ejection fraction (LVEF) <50%, cardiac implantable electronic devices, previous cardiac surgery, and poor echocardiographic image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) to PA systolic pressure (PASP), and decreased RV-PA coupling was defined as less than 0.52 %/mmHg based on on the receiver operating characteristic analysis. The primary outcome was the composite of all-cause death and hospitalization for heart failure. Results Over a mean of 4.7 ± 3.5 years of follow-up, 178 (22%) patients had experienced primary outcomes. Among them, 107 (13%) patients were hospitalized for HF and 90 (11%) patients died. Patients with decreased RV-PA coupling were older (73 ± 11 vs. 68 ± 12 years, p<0.001), had a higher prevalence of females (51 vs. 33%, p<0.001) and diabetes (33 vs. 23%, p=0.003), lower left ventricular ejection fraction (60 ± 5 vs. 61 ± 5%, p=0.011), higher E/e’ (14 ± 5 vs. 11 ± 4, p<0.001), larger left atrial volume index (78 ± 37 vs. 62 ± 22 ml/m2, p<0.001) and larger RV end-systolic area (11 ± 4 vs. 10 ± 3 cm2/m2, p=0.001) compared to those with preserved RV-PA coupling. In multivariate Cox regression analysis, decreased RV-PA coupling was associated with worse clinical outcomes even after adjusting for age, diabetes, E/e’, and RV end-systolic area (Hazard ratio [HR] 1.50, 95% Confidence interval [CI] 1.09 – 2.07, p=0.014) (Figure 1). Conclusions In patients with non-valvular AF, RV-PA coupling was associated with clinical outcome, suggesting that it may provide additional information for predicting future cardiovascular risk in this population.

Lipoprotein(a) levels and LPA genotypes are not associated with echocardiographic measures of left ventricular structure and function in the general population

Abstract Background Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for myocardial infarction and aortic valve stenosis, and elevated Lp(a) levels are associated with increased risk of heart failure. While part of this heart failure risk is mediated through atherosclerotic and valvular disease, other pathological pathways may also contribute to the association between Lp(a) and heart failure. Purpose To assess if Lp(a) levels and corresponding LPA genotypes are associated with echocardiographic measures of left ventricular structure and function in the general population. Methods We included 3,427 participants from an observational general population study who underwent protocol echocardiography between 2011-15 and had an available measurement of Lp(a) and LPA genotypes. Lp(a) was measured in 1991-94 and 2001-03 using well-validated assays with the most recent measurement used for the present analysis. Participants were divided into groups based on quartiles of Lp(a) with the top quartile further stratified to capture those above the 90th percentile. For genetic analysis, participants were grouped based on kringle IV type 2 [KIV-2] repeat corresponding to plasma Lp(a) percentile groups. Linear regression models were used to estimate β-coefficients for echocardiographic measures associated with Lp(a) levels and genotypes, while logistic regression models were used to estimate odds ratios for cardiac dysfunction or remodeling. All models were adjusted for age and sex. Results Mean age was 63±14 years and 44% were male. Median plasma Lp(a) was 18 mg/dL [IQR 10-40], median number of KIV-2 repeats were 36 [30-40], 102 (3%) were rs3798220 minor allele carriers and 467 (14%) were rs10455872 carriers. Mean left ventricular ejection fraction [LVEF] was 56.0±6.6% and we had 99% power to detect an absolute LVEF difference of 2% between those with Lp(a) levels above the 90th percentile (corresponding to >75 mg/dL) compared with those below the 25th percentile (<10 mg/dL). Mean absolute global longitudinal strain (GLS) was 19.2±2.7% and we had 99% power to detect an absolute difference of 1%. However, we found no statistically significant differences in echocardiographic measures according to Lp(a) levels or LPA genotypes (Table 1). The prevalence of impaired LVEF was 16%, and we had <20% power to detect an odds ratio of 1.2 for those with Lp(a) above the 90th percentile compared with those below the 25th percentile. We found no significant associations between odds for cardiac dysfunction or left ventricular hypertrophy and Lp(a) levels or LPA genotypes (Table 2). Conclusion Elevated Lp(a) levels and corresponding LPA genotypes were not associated with echocardiographic measures of left ventricular structure and function in this general population cohort. While we did not have sufficient power to detect associations between Lp(a) and cardiac dysfunction, our findings do not support a substantial effect of Lp(a).

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

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

Association of type-D personality and left-ventricular remodelling in patients treated with primary percutaneous intervention after ST-segment elevation myocardial infarction

BackgroundType-D personality is an established predisposing factor for various diseases. Type-D traits have been shown to pose a 26% increased risk of coronary artery disease after controlling for other confounding factors. Significant associations have been reported between type-D personality traits and dyslipidaemia, impaired endothelial function, coronary heart disease (CAD), acute myocardial infarction, and other adverse cardiovascular events.ObjectiveTo assess the association between type-D personality and left-ventricular adverse remodelling in patients treated with percutaneous coronary intervention following index ST-segment elevation myocardial infarction.MethodsAll patients hospitalized and treated with percutaneous coronary intervention (PCI) after their index ST-segment elevation myocardial infarction (STEMI) between 1 January 2022 to 31 December 2023 were prospectively enrolled. Type-D personality traits in the study population were determined at baseline using type-D Scale-14 (DS14) instrument, whereas any positive change in left ventricular end diastolic volume (LVEDV) ≥ 20% at follow up period of 12-months from baseline was defined as left-ventricular adverse remodelling (LVAR). Univariate and multivariate analysis was done to establish the independent predictors of LVAR. The area under receiver-operating characteristic curve (AUROC) was employed to assess the sensitivity and specificity of the identified independent predictors.ResultsA total of 124 patients were enrolled in the study. The mean age of the study population was 67 ± 10 years and the overall incidence of LVAR was found to be 25%. Multivariate regression analysis revealed that type-D personality is a significant independent predictor of LVAR \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:(OR:2.51;95\\%CI:1.16-5.77;p=0.03)$$\\end{document} apart from the already established independent predictors Killip Class\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:(OR:7.30;95\\%CI:3.03-17.55;p<0.0001)$$\\end{document}, baseline Global Longitudinal strain (GLS)\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:(OR:2.69;95\\%CI:1.19-6.61;p=0.01)$$\\end{document}, and 3-vessel CAD\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:(OR:2.27;95CI:1.10-5.33;p=0.04)$$\\end{document}. In ROC curve analysis type-D personality as an independent predictor of LVAR achieved a sensitivity of 41.4% and a specificity of 87.1%, p < 0.02.ConclusionType-D personality trait is a significant independent predictor of LVAR in patients treated with PCI after their index-STEMI.

Incremental value of biventricular strain in patients with severe aortic stenosis

Abstract Background Left ventricular global longitudinal (LVGLS) and right ventricular free wall strain (RVFWS) demonstrated separately prognostic value in patients with severe aortic stenosis (AS). However, studies evaluating combined assessment of LVGLS and RVFWS have shown contradictory results. Aim To explore the prognostic value of combining LVGLS and RVFWS in a large group of severe AS patients referred for transcatheter aortic valve implantation. Methods Patients were classified into three groups: preserved (LVGLS ≥15% AND RVFWS &amp;gt;20%), single-ventricle impaired (LVGLS &amp;lt;15% OR RVFWS ≤20%), or biventricular impaired strain group (LVGLS &amp;lt;15% AND RVFWS ≤20%). Cut-off values were based on previously published data and spline analyses. Endpoint was all-cause mortality. Results Of the 712 patients included (age 80±7 years, 53% men), 248 (35%) died. The single-ventricle impaired and biventricular impaired (vs. preserved) strain groups showed significantly lower 5-year survival rates (68%and 55%vs.77%, respectively, p&amp;lt;0.001; Figure 1). On multivariable analysis, single-ventricle impaired (HR 1.762; 95%CI:1.114-2.788; p=0.015) and biventricular impaired strain groups (HR1.920; 95%CI:1.134-3.250; p=0.015) were independently associated with all-cause mortality. These findings were confirmed by sensitivity analysis in patients with preserved LV ejection fraction (Figure 2). Conclusions In patients with severe AS, biventricular strain allows better risk stratification, even if LV ejection fraction is preserved.

Prevalence of stage B heart failure in healthy adults and people with type 2 diabetes

Abstract Introduction People with Type 2 Diabetes (T2D) are at increased risk of heart failure, and as such are classified as having Stage A Heart Failure (SAHF). Those with additional evidence of raised filling pressures, biochemical or structural cardiac changes, without heart failure symptoms, are deemed to have Stage B heart failure (SBHF). Identifying patients with SBHF may help determine those at highest risk of disease progression. Purpose The aim of this work was to assess the prevalence of SBHF in a cohort of asymptomatic healthy volunteers and people with T2D characterised according to current American Heart Association/American College Cardiology/Heart Failure Society of America. Methods A single-centre, prospectively recruited cohort of middle-aged asymptomatic adults with T2D and healthy volunteers, with no history or signs of cardiovascular disease, underwent comprehensive cardiac phenotyping with transthoracic echocardiography and circulating brain natriuretic peptide. Healthy volunteers with risk factors for heart failure, including hypertension and obesity, were excluded from analysis. Prevalence of SBHF was determined by comparing cardiovascular data to proposed standards, left ventricular ejection fraction and global longitudinal strain parameters were omitted from analysis due to data availability. Results We included 383 T2Ds (diabetes duration 9(5,15) years) and 65 healthy volunteers (Table 1); 91% of those with T2D and 65% of healthy volunteers met ≥1 criteria for SBHF (Table 2). Median number of SBHF criteria met in the T2D cohort was 3 (2,4); in particular, a large proportion of the cohort met defined cut offs for relative wall thickness (70.6%), lateral e’ (62.2%), septal e’ (54.1%) and LV wall thickness (47.4%). Of the 65 healthy volunteers, median number of SBHF criteria met was 1 (0,2.5). In healthy volunteers, SBHF was most commonly defined by lateral e’ (40.0%), septal e’ (38.3%), relative wall thickness (32.2%), left atrial volume indexed (22.4%) and serum brain natriuretic peptide (23.3%). Of note, brain natriuretic peptide levels met current SBHF parameters in 18.8% of healthy volunteers and 9.9% people with T2D, which may be attributable to the exclusion of obesity in the healthy volunteer group. Conclusion Using currently proposed standards, a high proportion of middle-aged asymptomatic people with T2D, and healthy volunteers without any risk factors for heart failure, would be categorised as having SBHF. These data strongly suggest that the majority of the proposed parameters for the definition of SBHF are not specific for a UK population and if applied will incorrectly classify many asymptomatic people at high risk of developing heart failure.

Improving exercise cardiac reserve assessment using a novel cardiopulmonary and echocardiography testing protocol (CPET-ESE) based on individualised exercise intensity domains

Abstract Background Functional exercise stress echocardiography (ESE) is used to quantify changes in cardiac reserve and can improve early cardiac dysfunction diagnosis and follow-up.[1.2] Current ESE protocols do not account for individual variations in fitness and heart rate response, leading to difficulties in defining normal reference values.[2,3] Physiologically defined exercise intensity domains could be implemented as part of combined cardiopulmonary and ESE testing (CPET-ESE) to address this problem. Purpose We propose that using exercise intensity domains as part of CPET-ESE will result in cardiac reserve values not influenced by individual cardiorespiratory fitness or physical activity (PA) levels. We also hypothesise by matching work-rates and heart rates (HR), respectively, cardiac reserve will be higher in those exercising at the higher exercise intensity domain. Methods A total of 45 healthy adults (mean age 43.8 ± 14.2, range 18-65 y) underwent a CPET followed by a CPET-ESE consisting of two 6-minute stages: 1. Moderate intensity (MOD) at 90% of the work-rate at the gas exchange threshold (GET) and 2. High intensity (HIGH) at 40% of the difference between GET and peak. Global left ventricular and right ventricular free wall (LV and RV) longitudinal strain (Sl), RV fractional area change (RV-FAC), peak LV and RV TDI derived systolic (S’) and diastolic velocities (E’) were measured at each step, including rest. HIGH steps were matched 1-to-n with MOD steps from other participants based on work-rate and HR, respectively. Questionnaire derived PA was classified as low, moderate, and high active. Cardiorespiratory fitness was measured as peak oxygen uptake relative to body mass (mL·kg-1·min-1). Results After adjusting for age and sex, neither higher PA nor peak VO2 were associated with higher cardiac function parameters at either intensity (Table 1). Higher peak VO2 was associated with higher work-rate for HIGH only, while higher PA was associated with lower HR for MOD only (interaction term p&amp;lt;0.05). When paired by matching HR and work-rate, respectively, HIGH was associated with higher cardiac function parameters compared to MOD (all except for LV-S’ and RV-FAC when HR matched, Table 2), despite those matched from HIGH being older, less physically active and having lower peak VO2 (p&amp;lt;0.05 for all). Conclusions Current ESE protocols, which define submaximal exercise intensity using arbitrary work-rate or HR targets,[3] do not account for the complex differences in exercise response between healthy individuals. Cardiac function augmentation during exercise is likely a response to VO2 kinetics and this is not accurately described by either HR or work-rate alone. We derived normal reference values for cardiac reserve from implementing physiologically defined exercise intensity domains within the combined CPET-ESE testing frameworks. These values could be more appropriately used when comparing diverse clinical populations using CPET-ESE.

Patients vaccinated against COVID-19 present better coronary flow, myocardial work and NTproNP levels than non-vaccinated at 4 months post COVID infection

Abstract Introduction COVID-19 affected patients present impaired subclinical markers of cardiovascular and endothelial function post resolution of infection. Whether vaccination impedes impairment of myocardial and vascular function has not been clarified. Purpose We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function in vaccinated and non-vaccinated subjects at four months after the infection. Methods We recruited 60 vaccinated and 60 non-vaccinated patients with similar clinical characteristics, who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four months after a confirmed COVID-19 infection. We measured (i) perfused boundary region (PBR) of the sublingual arterial (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) NTproBNP blood levels. Results Among vaccinated patients 54,2% had mild disease, 33,3% had moderate disease and 12,5% had severe disease, while among non-vaccinated 29,1% had mild disease, 32,9% had moderate disease and 38% had severe disease(p&amp;lt;0.05). At four months, vaccinated patients presented with higher LVGLS, GCW values and CFR compared to non-vaccinated (p&amp;gt;0.05 table), while GWI, GWW and GWE were similar between the two groups(p&amp;gt;0.5). Moreover, in vaccinated patients RVGLS and RV FWLS were significantly higher than in non-vaccinated patients (p&amp;gt;0.05). Also, NTproBNP leves were significantly lower in vaccinated than in non-vaccinated patients (p&amp;lt;0.05). At four months, in vaccinated patients , we observed a marginally lower brachial and central systolic blood pressure compared with non-vaccinated (p=0.045, p=0.048 respectively.) Vaccinated patients displayed similar FMD and PWV values compared to non-vaccinated (p&amp;gt;0.05 for all the comparisons). Conclusion Patients vaccinated against COVID-19 suffered from milder disease resulting to better cardiac function and lower NTproNP levels than non-vaccinated 4 months post COVID infection.

Left atrial longitudinal strain behavior in patients with cryptogenic stroke - a case control study

Abstract Background A significant percentage of ischemic strokes classified as cryptogenic stroke (CS) where the definition is varied according to the type of classification used. Left atrial (LA) function has a role in determining the possible cardio-embolic source of stroke. Using speckle tracking transthoracic echocardiography (TTE) we can detect the early changes in left atrial function by measuring left atrial longitudinal strain (LALS). Aim To evaluate the left atrial stain in patients with a cryptogenic stroke as compared to a healthy papulation. Method and results We recruited 50 cryptogenic ischemic stroke patients with mean age of 44.7 years and 50 % were male who treated consecutively as for first CS, and 50 age-and sex-matched healthy stroke-free controls. Using Speckle tracking TTE analysis we measured the global , passive and active longitudinal LA strain corresponding to the reservoir (LASRES), conduit(LASCD), and contractile function(LASCT),respectively in addition to standard other LA parameters and filling pressure parameters of Left ventricle(LV) in both group. Data were compared using t-test and Mann-Whitney test. Cryptogenic stroke patients as compared with controls had significantly reduced value of all components of LALS [Mean value of LASRES, LASCD and LASCT in CS group versus control group were 25.15±6.79 versus 43.95±4.62 (P-value &amp;lt;0.01), 14.41±3.53 versus 25.68±3.30 (P- value &amp;lt;0.01), 10.73±3.35 versus 18.28±1.60 (P-value &amp;lt;0.01) respectively] (Figure 1 and Figure 2). There were no significant differences in means of LA area and LA volume index in both groups (P value &amp;gt;0.05). Between parameters of LV filling pressures, it was noticed that early diastolic transmitral flow velocity (E) and early diastolic velocity at annulus (E’) were statistically lower in CS patients as compared to control group (P-value &amp;lt;0.01). In addition, the Cluster and Discriminant analysis used confirmed that LASRES, LASCD and LASCT were significantly lower in value in cryptogenic stroke patients in comparison to Control group which can be used to detect early LA dysfunction. Conclusion LA longitudinal strain in all components were significantly impaired in patients with CS. Measuring LALS parameters can be useful in determining early LA dysfunction in cryptogenic stroke patients.Figure 1-left atrial strain components.Figure 2 -left atrial strain component.

Prognostic impact of left ventricular myocardial work in patients undergoing surgery for primary mitral regurgitation

Abstract Background Although left ventricular ejection fraction (LVEF) is widely used as a parameter for the assessment of LV systolic function, LVEF can overestimate LV systolic function in patients with severe mitral regurgitation (MR) due to its high load-dependency. Echocardiography-based, left ventricular myocardial work (LVMW) can assess LV function by incorporating LV afterload. Purpose This study aims to evaluate the prognostic value of LVMW indices in patients with primary MR undergoing mitral valve surgery. Methods Individuals who underwent mitral valve surgery for severe primary MR were included. All patients underwent transthoracic echocardiography before surgery. LVMW was derived from a vendor-specific package which integrates LV global longitudinal strain with sphygmomanometric blood pressure to construct pressure-strain loops during the cardiac cycle. (Figure 1) For the LVMW indices, previously-established normal values were used as thresholds. The primary endpoint was all-cause mortality after mitral valve surgery. Results A total of 309 patients (mean age 63 ± 12 years, 68% male) with severe, primary MR who underwent surgery, were included. The mean LV global work index (LVGWI) was 1977 ± 537 mmHg% and 132 (43%) patients had impaired LVGWI (≤ 1900 mmHg%). During a median follow-up of 5.0 years (interquartile range, 2.5-8.9), 27 (8.7%) patients died after mitral valve surgery. Patients with impaired LVGWI or LV GLS (≤ 20%) had lower survival rates compared to the group with preserved LVGWI (p &amp;lt;0.01) or LVGLS (p = 0.02), whereas there was no significant difference in the survival rate between patients with LVEF ≤ 60% and &amp;gt; 60%. (Figure 2) Furthermore, LVGWI ≤ 1900 mmHg% demonstrated incremental prognostic value over LVGLS (p = 0.049) for all-cause mortality. Conclusions In patients with severe, primary MR who underwent surgery, impaired pre-operative LVGWI was associated with a higher mortality risk. In addition, impaired LVGWI had incremental prognostic value over LVGLS. Based on these findings, LVMW is a promising parameter for predicting postoperative outcome and determining the optimal timing of valve surgery in patients with severe, primary MR.Fig1.Echo-derived Myocardial workFig2.Kaplan-Meier curves

Impact of cardiovascular risk factors in cardiac (reverse) remodelling induced by pregnancy

Abstract Introduction Haemodynamic overload during pregnancy induces cardiac remodelling, characterised by cardiac hypertrophy and chamber enlargement, associated with deterioration of diastolic function, despite preservation of the systolic function. After delivery, the woman's heart undergoes reverse remodelling(RR), and myocardial function and structure normalise to their pre-gravid state. The impact of cardiovascular risk factors(CRF) in cardiac remodelling and RR, namely, on cardiac function and structure, is variable and remains to be clarified. Purpose To characterise cardiac remodelling and RR during pregnancy and postpartum, respectively, and to investigate CRF's impact in these processes. Methods This prospective cohort study included volunteer pregnant women (healthy [H group] or obese and/or hypertensive and/or with gestational diabetes [CRF group]) recruited in two tertiary centres between 2019 and 2022. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T,10-15 weeks, baseline], 3rd trimester [3T,30-35 weeks, peak of cardiac remodelling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Blood samples were collected in each evaluation moment to quantify plasma troponin I (cTnI), procollagen I COOH-terminal propeptide (PICP), ST2/IL33-receptor, C-reactive protein (CRP) and relaxin-2 by ELISA. Generalised linear mixed-effects models were used to evaluate the extent of RR and its potential predictors. Results We included 130 pregnant women with a median age of 33 [30,36] years, 41.5% with at least one CRF. As shown in Table 1, pregnant women developed cardiac hypertrophy with significant atrial and ventricular enlargement from 1T to 3T in both groups. A significant rise in filling pressures was also documented. During postpartum, a significant regression of cardiac hypertrophy and dilation was verified in the two study groups, accompanied by a significant decrease of E/e’ as soon as 1 month after delivery. These cardiac anatomical and functional adaptations induced by pregnancy were accompanied by a significant reduction in plasma cTnI, PICP, ST2/IL33-receptor, CRP and relaxin-2 levels from 3T to 6-months after delivery. Compared to the healthy pregnant women, the CRF group showed higher relative wall thickness (RWT) for all time points of the follow-up period, with similar values of indexed cardiac mass and volumes. Pregnant women with CRF revealed higher E/e’, contrasting with lower ejection fraction and worse global longitudinal strain. Conclusion The significant cardiac reverse remodelling occurred as soon as 1 month after delivery, returning to basal values 6 months postpartum, supported by a significant reduction of levels of plasma biomarkers related to myocardial injury, repair, fibrosis, and inflammation. Pregnant women with CRF showed higher RWT, impaired relaxation and subclinical LV dysfunction when compared with healthy women at all time points of the study.