Left Ventricle Research Articles

Assessment of cardiopulmonary exercise capacity in suspected heart failure with preserved ejection fraction: impact of coronary flow velocity reserve and body fat

Abstract Background and objectives Heart failure with preserved ejection fraction (HFpEF) has various pathophysiology including coronary microvascular dysfunction (CMD), obesity, and frailty. In the present study, we aimed to assess the cardiopulmonary exercise capacity according to coronary microvascular function and body composition in patients with suspected HFpEF. Methods Patients with chest symptoms with non-obstructive coronary artery disease (<50% stenosis) and preserved left ventricle (LV) ejection fraction (≥50%) were enrolled. LV end-diastolic pressure was measured during coronary angiography. All patients underwent body composition analysis, adenosine stress echocardiography with the evaluation of coronary blood flow, and cardiopulmonary exercise test assessing maximal oxygen consumption (VO2max). Coronary flow velocity reserve (CFvR) was defined as the ratio of peak to baseline mean diastolic velocity of coronary blood flow. Association between VO2max and CFvR as well as body composition was assessed. Results Of the 106 patients (mean age 63.5), 54 (50.9%) were women, 52.4% had hypertension, and 28.6% had diabetes. Baseline LV end-diastolic pressure was 15.3 ± 5.5 mmHg. Median Heart Failure Association-PEFF score was 3, while medial e’ velocity was 6.7 ± 2.0 cm/s and E/e’ was 9.6 (7.6 – 12.0). Mean diastolic velocity of coronary blood flow was 0.17 [interquartile range (IQR) 0.13 – 0.23] m/sec at baseline, while it increased to 0.46 [IQR 0.38 – 0.57] m/sec at peak, resulting in CFvR of 2.75 [IQR 2.10 – 3.67]. Eighteen (17.1%) patients had CMD (CFvR <2.0). VO2max was 23.1 ± 5.4 mL/kg/min with lower value in women (21.7 ± 4.8 vs. 24.5 ± 5.6 mL/kg/min, p = 0.007). CFvR was directly related to VO2max (r = 0.350, p <0.001). In body composition, skeletal muscle mass index, percent body fat, and visceral fat area were associated with VO2max. In multivariable analysis, age, visceral fat area or percent body fat, and CFvR were linearly correlated with VO2max, and estimated VO2max was well correlated with measured VO2max. Conclusions Cardiopulmonary exercise capacity represented by VO2max was correlated with CFvR and body composition including skeletal muscle mass index, percent body fat, and visceral fat area in patients with suspected HFpEF. VO2max could be estimated by CFvR and fat component in the body.

Normal values and reference ranges for quantitative assessment of myocardial first-pass perfusion by spectral computed tomography. From the Cadami-Spectral study

Abstract Background Spectral computed tomography (SCT) can generate iodine concentration maps according to the tissue iodine uptake, serving as a surrogate marker of organ perfusion. Thus, assessment of the iodine distribution maps derived from SCT allows to detect deviations in normal myocardial perfusion. As of present, reference ranges for the iodine concentration in each myocardial segment of the left ventricle (LV) derived from the first-pass perfusion have not been published. Purpose To provide normal values of first pass perfusion in individuals without coronary artery disease (CAD). Additionally, we explored whether these values could vary according to gender, contrast dosing or the cardiac cycle phase assessed. Methods From October 2021 to January 2024, we retrospectively identified patients who underwent a CT Cardiac Angiography (CTCA) and had no evidence of CAD or structural heart disease. Subjects were scanned using a dual-layer SCT, following a standard local protocol which included a weight-based contrast medium dosing of 0.8 mL/Kg. Iodine density maps were reconstructed using the MCA filter at a phase of 78%. An additional sample of 18 subjects who received a dosing of contrast of 1 mL/Kg and 16 cases scanned using a systolic acquisition and reconstructed at phase of 35% were also included. Spectral reconstructions were combined with tissue segmentation to obtain the spatial distribution of iodine along the myocardium. Mean, median and standard deviations values of density of iodine (mg/ml) were quantified for each segment following the AHA-17 segment model. Results Perfusion data from 80 woman (median age: 60 [IQR: 54-65.6] years) and 47 males (median age: 47 [IQR: 43 – 54] years) were analysed. Despite receiving higher dose of contrast (67.9 vs 59.8 mL; p < 0.05), male subjects exhibited lower iodine density values in the myocardium compared to females (median concentration per segment 1.58 vs 2.01 mg/dL, p<0.001; figure 1). Notably, the volume of the LV myocardium was higher in male than in women (143 mL vs 92 mL, p<0.001). These differences could be partially explained in a mixed model considering the ratio contrast dose/myocardium volume (b = 1.500, p < 0.001). Higher contrast dosing (1 mL/Kg vs 0.8 mL/kg) correlated with higher iodine density values in the myocardium (2.03 vs 1.83 mg/dL, respectively; p = 0.023). No differences were noted when comparing reconstructions at systole vs diastole (1.86 vs 1.80 mg/dL, respectively; p = 0.484). Reference range values of each myocardial segment are listed in table 1. Conclusions Significant gender discrepancies are detected in the analysis of first-pass myocardial perfusion. These variations can be partially explained by differences in the LV myocardium volume. Our findings provide applicable reference ranges of the iodine concentration in myocardium at first pass perfusion in controls without coronary or structural heart disease.

TAVI for treating severe aortic valve disease in cardiogenic shock: a single centre experience

Abstract Introduction Recent evidence shows the safety and efficacy of TAVI in patients with aortic valve disease (AVD) presenting in cardiogenic shock (CS). However, there is limited data regarding CS management in the cardiac intensive care unit (CICU) and its outcomes. We aimed to describe the CS features, pre-TAVI management and short-term clinical outcomes of a cohort of CS patients (pts) submitted to TAVI. Methods Single-centre retrospective registry of consecutive pts with AVD undergoing TAVI in CS, from January 2020 to October 2023. CS was defined as pre-procedural hypotension/hypoperfusion requiring vasoactive drugs or mechanical circulatory support (MCS) devices. The severity of CS was defined according to the SCAI classification. Procedural related outcomes according to the VARC-3 criteria and 30-day mortality were assessed. Results A total of 16 pts (1% of our global TAVI cohort, 62% male, mean age 79±5 years) meet the inclusion criteria. The majority (n=13) presented severe aortic stenosis, two had degenerated aortic bioprosthesis with severe regurgitation and one had native valve severe regurgitation. 6 pts (38%) had isolated left ventricle (LV) dysfunction and 10 (62%) had biventricular dysfunction. The admission LVEF was 33±8% and the mean transaortic gradient for those with aortic stenosis was 46±13mmHg. The EuroSCORE II estimated for a single non-CABG emergency procedure was 37±15%. All patients were refused for surgical treatment upon Heart Team discussion. At admission, 12 (75%) patients presented in CS SCAI-C, 1 (6%) in SCAI-D and 3 (19%) in SCAI-E. These last 3 patients presented in cardiac arrest upon admission to the CICU (time to ROSC from 2 to 15 minutes). The peak lactate level at 48 hours was 3.4 mmol/L [2.1-5.1] and the highest Vasoactive-Inotropic Score (VIS) during admission was 21 [11-45]. None of the patients needed MCS pre-TAVI. 5 (31%) patients required invasive mechanical ventilation and 5 (31%) renal replacement therapy. Median time between CICU admission and transfemoral TAVI was 2.5 days [IQR 1-7]. Procedural success was 100%, with 57% receiving a balloon-expandable and 43% a self-expandable valve. Post-TAVI CICU length of stay was 6 days [IQR 5-9]. Most common procedural complication were the need for permanent pacemaker implantation (n=2, 12%) and access-related bleeding (n=2, 12%). Hospital length-of-stay was 20±15 days. Thirty-day mortality was 12% (n=2). Conclusion In this cohort of CS patients selected for TAVI treatment, procedural success was achieved in all cases. While complications were similar to the general TAVI population, in-hospital mortality remained high but very acceptable. These results suggest that, if correctly selected, aortic valve disease patients in CS represent a niche for whom brief stabilization and urgent percutaneous valve treatment might impact their dismal prognosis.

Impact of right ventricular - pulmonary arterial coupling on mortality after transcatheter aortic valve implantation in patients with aortic stenosis

Abstract Background Aortic stenosis (AS) leads to left ventricle (LV) pressure overload. In more advanced stages of the disease, this pressure, which is transmitted through the pulmonary vasculature, may result in right ventricle (RV) remodeling and eventual dilatation and disfunction. RV failure is associated with impair prognosis, even after relief of the obstruction. The interplay of pulmonary arterial (PA) pressure and RV function can be assess using RV-PA coupling index; in a compensate state RV function is coupled with pulmonary pressure, and this function has a proper response to an increase in pulmonary afterload; in contrast, when RV function uncouples with pulmonary pressure it means that RV function can no longer sustain PA afterload, leading to a decompensate state. RV-PA uncoupling has already been associated with poor prognosis in other heart conditions, such as heart failure or pulmonary hypertension; however, there is still not much evidence on how RV-PA uncoupling prior transcatheter aortic valve implantation (TAVI) impacts on mortality. Purpose Assess the impact of RV-PA uncoupling on all-cause mortality after TAVI in patients with aortic stenosis. Methods In a prospective TAVI registry, patients were included if they had an adequate echocardiographic evaluation prior TAVI. All-cause mortality after the procedure was analyzed in two subgroups, according to their RV-PA coupling status. RV-PA was assess using tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP). The cut-off value was 0.39, consistent with other studies. Hazard ratios (HR) are calculated by univariate and multivariate Cox proportional hazard model. Multivariate adjustment included baseline characteristics – including age, gender, hypertension, diabetes, dyslipidemia, atrial fibrillation, and serum albumin –, and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) and European System for Cardiac Operative Risk Evaluation (EUROSCORE) II. Results A total of 1190 patients underwent TAVI from January 2011 to December 2023; 315 patients were eligible, with mean age 82,24 years (± 8,0), 52% being women, and a mean EUROSCORE II score of 4.0 (± 9,3). The RV-PA cut-off value of 0.39 stratified patients into groups of RV-PA coupling (n = 194/63,6 %) or uncoupling (n = 121/38,4 %). During follow-up time (35,94 months ±25,6), patients with unpaired coupling had a 64% more risk of all-cause mortality in univariate analysis and, after adjusting for the parameters above, a 58% increased risk in multivariate analysis. Table. Conclusions Patients with significant aortic stenosis who had an impair RV-PA coupling prior TAVI had a significant increased risk of all-cause mortality. This suggests the need to incorporate this parameter to our right-side hemodynamics evaluation prior the procedure. Broader experience to determine its application and cut-off value are still needed.

Diagnostic performance of semi-quantitative echocardiographic evaluation in patients with aortic regurgitation: implications for clinical practice

Abstract Background In current practice, screening for severe aortic regurgitation (AR) relies on qualitative and semi-quantitative echocardiographic parameters. No information is given on the diagnostic performance of each of these parameters. Objectives The purpose of this study was to investigate the diagnostic performance of semi-quantitative echocardiographic parameters in discriminating moderate from severe AR. Methods This single-center retrospective cohort study included 102 consecutive patients with chronic isolated moderate or severe AR. Patients were divided between severe and moderate AR using a combination of left ventricle (LV) dilatation, Proximal Isovelocity Surface Area (PISA) echocardiographic method and cardiovascular magnetic resonance (CMR). Receiver operator characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of vena contracta width (VC), pressure half-time (PHT) and diastolic flow reversal in descending aorta (DFR). Results Threshold value VC > 6mm provided a low sensitivity (40.4%) and an excellent 88.9% specificity for the diagnosis of severe AR. For PHT, the value < 200ms provided a poor sensitivity (2.0%) and an excellent 100% specificity. For DFR, the value ≥ 0.2m/s provided a low sensitivity (37.8%) and a good 78.6% specificity. These 3 parameters have a good positive predictive value (PPV) > 80% and a poor negative predictive value (NPV) < 40%. The area under the curve for the diagnosis of severe AR was 0.72, 0.72 and 0.59 for VC, PHT and DFR, respectively. Conclusion Our study demonstrates that the semi-quantitative parameters VC, PHT and DFR are highly specific but poorly sensitive for diagnosing severe chronic AR. They can rule in severe AR but in presence of intermediate values, they are insufficient to rule out severe AR.Venn diagramDiagnostic performance

Worse ischemic symptoms and cardiac function in women with suspected ischemia with no obstructive coronary artery disease and adverse pregnancy outcomes history

Abstract Background Adverse pregnancy outcomes (APO) are associated with increased maternal risk of cardiovascular disease (CVD) and mortality. Ischemia with no obstructive coronary artery disease (INOCA) is predominant in women, however the association of APO history with INOCA is poorly understood. Purpose To compare clinical characteristics, symptoms, cardiac structure and function and coronary microvascular dysfunction in women suspected to have INOCA with or without a history of APO. Methods Women’s Ischemia Syndrome Evaluation (WISE) CVD (NCT00832702) and WISE pre-HFpEF (NCT02582021) prospective cohorts of women with suspected INOCA were merged and utilized to determine among women with at least 1 prior pregnancy whether a history of APO was associated with ischemic symptoms, and to characterize CMRI measured left ventricle (LV) structure and function, myocardial deformation (systolic and diastolic strain) and coronary microvascular dysfunction on invasive coronary functional testing (CFT). Self-reported APO was defined as hypertensive disorder of pregnancy (HDP), gestational diabetes, preterm birth (<37-week gestation), low birth weight (<5lbs). Results In a cohort of 469 women with suspected INOCA, (mean average age 55 [SD 10.2] years) and at least 1 prior pregnancy, 138 (29%) had history of at least 1 APO. Among women with history of APO, 78 reported HDP, 50 gestational diabetes, 27 pre-term birth, 8 low birth weight. Women with a history of APO were younger, had higher rates of hypertension and diabetes, higher BMI and lower SAQ and DASI scores compared to those with no history of APO (Table). LV ejection fraction (EF) was lower and early diastolic strain rate/LVEDP was higher in women with APO history compared to those without APO history. Conclusion(s) In cohort of women with INOCA, history of APO was highly prevalent. Despite younger age, women with history of APO had higher rates of CVD risk factors, worse ischemic symptoms and functional capacity, lower EF, and higher filling pressures. Our findings suggest a potential for APO history to better identify women with worse prognosis that warrants further investigation and aggressive management.

Improvement in cardiac function but not structure in adults born preterm following a prescribed moderate to high intensity exercise intervention: a randomized clinical trial

Abstract Background People born preterm (<37 weeks’ gestation) have a potentially adverse cardiac phenotype that progresses with blood pressure elevation and may explain their increased risk of early heart failure and cardiovascular-related mortality. It remains unknown whether lifestyle or pharmacological interventions lead to beneficial left ventricle (LV) and right ventricle (RV) structural and/or functional changes in preterm-born adults. Purpose To determine whether preterm-born adults with elevated and stage 1 hypertension exhibit similar cardiac remodelling following a 16-week aerobic exercise intervention as their term-born peers with comparable blood pressures. Methods We conducted an open, parallel, two-arm superiority randomised controlled (1:1) trial in n=203 adults aged 18-35 years old with elevated or stage 1 hypertension. Participants were randomised to a 16-week aerobic exercise intervention targeting three, 60-minute supervised sessions per week at 60-80% peak heart rate (exercise intervention) or sign-posted to educational materials (controls). In a pre-specified cardiovascular magnetic resonance imaging (CMR) sub-study in n=100 individuals, CMR was performed before and after the 16-week intervention. Group differences in outcome variables after the intervention were examined using ANCOVA adjusting for baseline outcome variables, sex, and age. Interactions between birth category and intervention effect were investigated by including an interaction term in the intervention ANCOVA analyses. Results One hundred participants completed CMR scans at baseline and after the 16-week intervention, with n=47 in the exercise intervention group (n=26 term-born; n=21 preterm-born) and n=53 controls (n=32 term-born; n=21 preterm-born). Cardiac structural measures in preterm-born adults did not change following the intervention. However, term-born adults in the exercise intervention group decreased LV mass to end-diastolic volume ratio (adjusted mean difference: -0.03, 95% CI: -0.06,-0.01, interaction term p=0.027) and increased RV stroke volume (adjusted mean difference: 5.53mL/m2, 95% CI: 2.60,8.47, interaction term p=0.076) versus controls. Preterm-born adults in the exercise intervention group increased LV basal- and mid-ventricular circumferential strain versus controls (adjusted mean difference: -1.33%, 95% CI: -2.07,-0.60, interaction term p=0.057 and adjusted mean difference: -1.54%, 95% CI: -2.46,-0.63, interaction term p=0.046, respectively), which was not observed in term-born adults. Similarly, preterm-born adults improved RV longitudinal strain versus controls (adjusted mean difference: -0.51%, 95% CI: -1.49,0.46, interaction term p=0.053), which was also not observed in term-born adults. Conclusions Aerobic exercise training improves myocardial function but not cardiac structure in preterm-born adults. Modified exercise protocols or combination with pharmacological intervention may lead to additional cardiac remodelling benefits.

Cardiac MRI traits linked to cardiomyopathy mutations in phenotype naive carriers

Abstract Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are prevalent forms of cardiomyopathies, characterised by changes in cardiac structure and function, associated with an increased risk of atrial fibrillation (AF), heart failure (HF), and sudden cardiac death (SCD). Due to these potential life-threatening consequences close monitoring of genetic mutation carriers of HCM and DCM, is important. However, disease onset in these subjects is highly variable, with a substantial subset of people only developing disease late-in-life, or not at all, making risk stratification challenging. We set out to identify cardiac MRI (CMR) based imaging biomarkers of HCM and DCM carriership in phenotype naïve individuals, which were benchmarked against associations with AF and HF. CMR and whole genome sequencing (n: 42,723) data were sourced from a UK biobank sample free of heart failure at the time of CMR measurements. A previously validated deep learning(DL) network was used to derive 22 CMR traits(1). Adjusted cox regression models were used to determine the CMR associations with the onset of heart failure and atrial fibrillation, providing empirical validation of the DL CMR network. Univariable and multivariable generalised linear models were employed to identify associations with genetic carriership conditional on cardiac risk factors. 14 and 19 CMR measurements were associated with the time until HF (274 cases), AF (704 cases), respectively. These variables included left-ventricle (LV) ejection fraction (EF), LV end systolic volume (ESV), Right-ventricular (RV) EF and right atrial (RA) EF. Using WGS data we identified 154 people with an HCM mutation and 220 with a DCM mutation, where HCM carriership associated with five and DCM with four CMR traits. This included RA-EF (OR 1.26 95%CI 1.10; 1.45), and RV-EF (OR 1.41 95%CI 1.23;1,63) for HCM, and LV-EF (OR 0.72 95%CI 0.62; 0.84), and RV stroke volume (OR 0.75 95CI 0.62; 0.91) for DCM. By combining deep learning of CMR with large sample size WGS we were able to identify cardiac imaging biomarkers of HCM and DCM carriership in apparently healthy subjects. This could prove relevant for early identification and monitoring of phenotype naïve people.

Prognostic value of combined myocardial performance index in patients with acute ST-elevation myocardial infarction

Abstract Background Myocardial performance index (MPI) also known as Tei index is a unique echocardiographic parameter which can estimate both systolic and diastolic performances of left and right ventricles. We previously suggested the echocardiographic parameter combined MPI (CMPI) as a new predictor of the prognosis of acute ST-elevation myocardial infarction (STEMI). The CMPI is the sum of left ventricular (LV) MPI and right ventricular (RV) MPI (CMPI = LV MPI + RV MPI). We supposed that CMPI might be a better predictor in STEMI, because it reflects both ventricular systolic and diastolic functions. Objectives The purpose of this study is to assess the prognostic value of a new echocardiographic parameter CMPI in STEMI patients calculated in acute phase. Methods 240 STEMI patients who underwent primary PCI have been included in the study. Echocardiography (EchoCG) was performed, and LV MPI and RV MPI were assessed within 24 hours after the symptom onset, prior to primary PCI. The MPI was calculated as the sum of isovolumic contraction time (ICT) and isovolumic relaxation time (IRT), divided by the ejection time (ET): MPI = (ICT + IRP) / ET. 50 % of the patients had anterior STEMI. 30 patients (12.5%) had concomitant RV myocardial infarction (MI). Patients were divided into two groups: Group 1 – CMPI > 0.9 (110 patients), Group 2 – CMPI ≤ 0.9 (130 patients). Baseline demographic and clinical characteristics were similar in both groups. Also, there were no differences in LV MI localization and concomitant RV MI between the groups. Primary endpoints were in-hospital and the one-year cardiovascular mortality rates. The secondary endpoint was the one-year heart failure hospitalization rate. Results In Group 1 the in-hospital mortality rate was 9.1%, and 3.1% in Group 2 (p = 0.0489). One-year cardiovascular mortality rate was 12.7% in and 5.4%, respectively (p = 0.0465). One-year heart failure hospitalization was also significantly lower in Group 2 (22.7% vs. 12.3%, p = 0.0332). Conclusion CMPI can be offered as a new predictor for the in-hospital and one-year cardiovascular mortality and one-year heart failure hospitalization rate in patients with acute STEMI.

Right ventricular outflow tract arrhythmias in patients with obstructive sleep apnea- electrophysiological insights

Abstract Background Obstructive sleep apnea (OSA) was associated with atrial fibrillation and heart failure. Furthermore, the arrhythmic sudden death during sleep in patients with OSA raises serious concerns. Non-ischemic ventricular arrhythmias arise frequently from the right ventricular outflow tract (RVOT). The involvement of obstructive sleep apnea in the genesis of arrhythmia (premature ventricular contraction or tachycardia) originating specifically in the RVOT is not yet coherently established. Purpose This study aims to demonstrate the possible relationship between untreated obstructive sleep apnea and the occurrence of RVOT arrhythmia and to follow the electrophysiological features and outcomes after radiofrequency catheter ablation (RFA) in patients carrying this double burden. Methods One-hundred-twelve (112) consecutive asymptomatic and symptomatic patients admitted with RVOT arrhythmia ((PVCs and VTs) underwent a sleep study (polysomnography). Apnea was set out as the cessation of breathing and hypopnea was defined as shallow, slow, and restricted breathing occurring in episodes of ten seconds or more. The patients had normal left and right ventricle ejection fractions and no structural cardiovascular disease or other known extracardiac arrhythmia predisposing conditions. No significantly elevated systolic pressure in the pulmonary artery was assessed at echocardiography. Every patient was investigated by electrophysiologic study (EPS) and RFA of the clinical ventricular arrhythmia was immediately performed. Practicing and former professional athletes were excluded. Results Seventy-eight (69 %) of the included patients had an apnea-hypopnea index > 10/h. The included patients had the following characteristics: mean age 52 ± 8 years, 62% males, 81% had a BMI >30kg/m². The cardiac electrophysiologic study did not induce sustained VTs. The distribution of the PVCs and non-sustained VTs evidenced a predilection for the superior, septal and anterior (68%) and also superior and anterolateral aspects of the RVOT (23%). Radiofrequency catheter ablation (RFA) guided by activation mapping, precocity (the site of earliest activation > 30 ms before the setting of the QRS complex) and pace-mapping were performed in all patients. Immediate success was obtained in 98 patients (88%). After a mean follow-up of 24± 6 months, 28 patients (28%) from the success arm had a recurrence of the PVCs or the non-sustained VTs, 22 patients (22%) with and 6 patients (6%) without sleep apnea. Conclusions RVOT arrhythmia genesis and relapse after successful RFA seem highly associated with sleep apnea. Furthermore, patients with sleep apnea are more prone to have recurrent arrhythmias after radiofrequency catheter ablation in the absence of appropriate control of OSA.

Echocardiographic left and right ventricular strain reference values and their associated characteristics in a healthy adult population from the ELSA-Brasil Study

Abstract Background/Introduction Impaired left ventricular (LV) systolic function is a well-known predictor of cardiovascular morbidity and mortality. Global longitudinal strain (GLS) analysis has been shown a robust measure to detect early systolic dysfunction and a prognostic parameter beyond traditional echocardiographic systolic parameters. Standard reference values for echocardiography measures have been established by echocardiography societies. However, these data may not accurately represent diverse world populations. Purpose We aimed to describe, from a Brazilian multiethnic population, age and sex-specific reference values for left (LV) and right ventricles (RV) GLS in a sample free of cardiovascular disease and risk factors, and to describe the impact of these risk factors according to GLS distribution. Methods ELSA-Brasil is a prospective cohort to investigate cardiovascular disease and diabetes including 15,105 participants aged 35 to 74 years. A predefined representative randomly selected sample with echocardiographic exam was included. We categorized the sample in tertiles according to severity of LV and RV systolic function measured by GLS, and applied trend tests across ordered groups to illustrate the association between GLS and demographic characteristics and echocardiographic measures of cardiac structure and function. Results In the study population (n=527), the mean age was 50.2 years and 59% were women. The overall mean value of LVGLS was -19.0 ± 2.4%, while the mean value of RVFWLS was -28.35 ± 3.06%. Women had higher absolute values of LV and RV GLS compared to men. Conclusion Our study provided the reference ranges for LV and RV GLS in a large middle-aged healthy Brazilian sample, with sex-differences reflected on these values.Central FigureTable 1:Tertiles of LVGLS and RVFWLS

Mapping renal impairment and cardiac structure and function: observation and genetic insights from 30,000 cardiac magnetic resonance images

Abstract Background The elevated risk of heart failure in kidney dysfunction is well-identified. However, the early alteration of renal impairment on cardiac structure and function, as well as genetic susceptibility associations have not been well reported. We sought to map the early effects of kidney dysfunction on cardiac remodeling with the cardiac magnetic resonance images (MRI) and identify share genetic correlation in community population. Methods Of 29,592 subjects underwent MRI test were recruited from the population-based UK Biobank study from 2006-2010. Renal function was assessed by historical identified chronic kidney disease (CKD), log-transfrom estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRCysC) or serum creatine (eGFRSCr) and urine albumin-to-creatinine ratio (uACR). Multivariable generalized linear regression was used to analyse the association of 4 different kidney function indexes with six cardiac MRI-derived traits: left atria and ventricle, right atria and ventricle, and ascending and descending aortas. Genetic correlation between renal function decline and cardiac traits were evaluated by Mendelian randomization (MR). Results The mean (SD) age of subjects was 54.9 (7.5) years, and 51.1% were women. Observational and MR analysis showed a reliable relationship of lower level of eGFRCysC with reduced biventricular end systolic volume, biventricular ventricular end diastolic volume and left ventricular mass, and lower level of eGFRSCr with reduced left ventricular cardiac output. Conclusions Our study indicates the observational and genetic correlation between kidney function decline and cardiac measurements. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics.Renal function decline & Cardiac Imaging

Cardiac morphology and function in patients with primary biliary cholangitis (PBC) without cirrhosis

Abstract Background Primary biliary cholangitis (PBC) is a chronic, autoimmune liver disease causing destruction of the small intralobular bile ducts in the liver. PBC patients can also develop extrahepatic manifestations. Though patients with PBC have often elevated levels of serum lipids, data concerning cardiac involvement is inconsistent and cardiovascular changes may be underdiagnosed. Purpose The purpose of the study was to assess cardiac morphology and function in patients with PBC without cirrhosis and comparison with control subjects. Methods We studied 52 females with PBC, and included in the analysis 22 females without cirrhosis, who were compared to 44 healthy female controls matched for age (53.4 ± 9.2 and 51 ± 8.3 yrs., respectively, p =0.312). Transthoracic echocardiography (TTE) was performed with the analysis of the left ventricular (LV) global longitudinal strain (GLS) and myocardial work. Additionally, impedance cardiography was conducted, with the analysis of the autonomic function using BRS (baroreceptor sensitivity), HRV (heart rate variability) and BPV (blood pressure variability). Results Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) differed between PBC and control group (128 ± 17 mmHg vs. 116 ± 11 mmHg, p=0.007 and 78± 12 mmHg vs. 75 ± 8 mmHg, p=0.024, and 73.5 ± 12 bpm vs. 71 ± 8 bpm , p=0.024, respectively). PBC group had larger diameter of the cardiac chambers when adjusted for body surface area (BSA), including left atrium (LA/BSA) and right ventricle (RV/BSA), as well as left ventricular mass (LWMI) and relative wall thickness (RWT), with no difference in the left ventricular end diastolic diameter (LVEDD/BSA). LV ejection fraction (EF) measured by bi-plane Simpson method was higher in PBC group. LV diastolic function parameters (E/A, E/e’) differed in patients with PBC when compared with controls, however, without signs of diastolic dysfunction. LV GLS indices (GLSAVG, GLSLAX, GLS4C, GLS2C) were significantly higher in PBC group, as well as global myocardial work indexes: global myocardial work (GWI) and global constructive work (GCW). Non-invasive autonomic assessment showed lower BPV in patients with PBC without cirrhosis, but no differences in baroreceptor sensitivity and HRV. Impedance cardiography did not show differences between both groups. Conclusion Our study shows that PBC patients without cirrhosis are characterized by remodeling and functional changes of the heart, when compared to age-matched controls. These changes could imply hyperkinetic circulation even before the development of cirrhosis in PBC patients.

Association of visceral adipose tissue with echocardiographic abnormalities in type 2 diabetes patients

Abstract Introduction Ectopic deposition of adipose tissue, particularly visceral adipose tissue (VAT) has been identified as a significant contributor to cardiometabolic complications among individuals with type 2 diabetes (T2D). An increase in VAT has been suggested to cause cardiac dysfunction, which may lead to echocardiographic abnormalities such as alterations in speckle-tracking and left ventricular ejection fraction (LVEF). However, this relationship has not been fully elucidated. Purpose This study aims to determine the association between VAT and echocardiographic abnormalities in patients with T2D. Methods A cross-sectional study in a tertiary hospital which included 195 individuals with T2D, the diagnosis of autoimmune diabetes was excluded. VAT was measured using electrical bioimpedance (BIA), and cardiac function was determined using echocardiography. A Spearman rank correlation analysis was conducted to evaluate the association between VAT and echocardiographic parameters, with significance set at p < 0.05. Results Within our cohort, the median age was 57 years, with 37% men. Based on the third quartile (P75) cutoff (5 liters for men, 3.75 liters for women), the population was categorized into P1-75 and P75-100 (Table). There were significant differences in LVEF (61% in P1-75 vs. 58% in P75-100, p = 0.041), left ventricular global longitudinal strain (LV GLS) (P1-75: -20.3%, P75-100: -19.2%, p = 0.012), and conduit phase of left atrial strain (LAScd) (P1-75: 25%, P75-100: 20%, p = 0.046). Positive correlations (Figure) were observed between VAT and indexed LV mass (r = 0.171, p = 0.020), basal diameter of the right ventricle (r = 0.308, p = 0.001), and LV GLS (r = 0.197, p = 0.006). Additionally, negative correlations were observed between VAT and LVEF (r = -0.342, p = <0.001) and right ventricular fractional area change (r = - 0.227, p= 0.001). Conclusion Increased VAT was associated with cardiac dysfunction, as indicated by altered LV GLS and LAScd. This study underscores the relevance of VAT in influencing both functional and structural changes in the left and right ventricles. It also highlights the significance of monitoring VAT for comprehensive cardiovascular risk assessment in T2D patients.Clinical demographics tableScatter plots with correlation graphs

A Case of A Middle-Aged Woman with Cor Triatriatum Dexter and Sick Sinus Syndrome: Comprehensive Cardiovascular Evaluation

This case study discusses a 51-year-old woman with a complex cardiovascular condition, cor triatriatum dexter, complicated by sick sinus syndrome. The patient presented with a history of bradycardia, dizziness, and amaurosis, and was admitted to the emergency department due to numbness in her right limb. Diagnostic examinations, including computed tomography (CT) and cardiac color-ultrasound screening, revealed cor triatriatum dexter along with an enlarged left atrium and ventricle. Additional findings included the absence of the inferior vena cava and polysplenic syndrome. Based on these results, double-chamber pacemaker surgery was recommended, supported by cardiac and thoracic-abdominal CT angiography and three-dimensional vascular reconstruction. This case underscores the importance of comprehensive examinations in identifying associated cardiovascular abnormalities.

Direct comparison of mechanical circulatory support devices in porcine model of acute myocardial infarction complicated by ventricular septal defect and cardiogenic shock

Abstract Introduction Despite urgent clinical need, until now optimal strategy for mechanical circulatory support in acute myocardial infarction (AMI) complicated by ventricular septal defect (VSD) and cardiogenic shock has not been determined. Purpose The aim of our study was to compare hemodynamic effects of intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO) and Impella CP in the animal model of AMI complicated by VSD and cardiogenic shock. Methods Under general anesthesia and mechanical ventilation in pigs (sus scrofa domestica), using partial sternotomy, AMI was induced by ligation of left anterior descending. VSD was simulated by insertion of 25F cannulas into the left and right ventricles and their extracorporeal connection by 3/8 tubes generating left-to-right shunt. The hemodynamic effect of ECMO (2 L/min), IABP, and Impella CP (2 L/min) was evaluated by the measurement of the left ventricular end-diastolic pressure (LVEDP), mean arterial pressure (MAP), carotid flow (CAR) as a surrogate of total circulatory output, and VSD flow. Data are presented as mean (SD), P < 0.05 was considered statistically significant. Results Eleven animals were used, one died after induction of AMI, ten pigs completed all study procedures. Baseline (no mechanical support) LVEDP was 13.8 (3.0) mmHg, MAP 54.5 (11.0) mmHg, CAR 290.9 (37.3) mL/min, and VSD 1174.0 (499.3) mL/min (Table 1). IABP significantly improved all parameters in comparison to Baseline (Table 1). ECMO significantly improved MAP and CAR not only in comparison to Baseline but also in comparison to IABP and Impella; on the other hand, ECMO increased VSD flow (Table 1). Impella significantly improved all parameters with the largest effect on LVEDP and VSD flow (Table 1). Conclusions All tested devices improved the key hemodynamic parameters of MAP and CAR, however each to different extent. Individual devices influenced differently LVEDP and VSD flow. The results of this study may help in selection of optimal therapeutic strategy in AMI complicated by VSD and cardiogenic shock.Table 1.Hemodynamic outcomes.

Scan-rescan variability of AI-enabled cardiac functional assessment from cine CMR

Abstract Background/Introduction Cine cardiovascular magnetic resonance (CMR) is the gold-standard technique for the assessment of cardiac function and structure. Manual analysis of cine CMR to estimate structural and functional biomarkers is costly and time-consuming, motivating the use of artificial intelligence (AI) for automation. However, the scan-rescan repeatability of AI derived biomarkers remains unknown. Purpose Measure the repeatability of AI-based cine CMR biomarkers in scan-rescan data. Methods 92 scan-rescan short-axis cine CMR were acquired from volunteers on the same day (i.e. 184 in total) and annotated with ground truth (GT) manual segmentations of the left and right ventricle (LV, RV) blood pools, and LV myocardium at end-diastole (ED) and end-systole (ES). AI segmentations and subsequent biomarker estimates were produced using the AI-CMR-QC tool described in [1]. Segmentation performance was assessed with Dice score, pixelwise sensitivity and specificity, and Hausdorff distance. Scan-rescan differences in cardiac biomarkers for each subject were used to assess repeatability. Repeatability of LV ejection fraction (EF) based classification (LVEF<40 = abnormal, 40>LVEF>50 = mildly reduced, LVEF>50 = normal) [2] was also estimated from scan-rescan data. Results The segmentation model obtained high Dice scores (> 88% for LV and RV blood pools, >83% for LV myocardium). The summary of scan-rescan biomarker differences in Fig. 1(a) highlights that biomarker repeatability is generally better in GT segmentations, with lower differences between the two scans. While performance is satisfactory, a more in-depth analysis reveals that in some pairs of scans there are inconsistencies in the segmentations, leading to fluctuations in the calculation of blood pool volumes, which affects the repeatability of the computed biomarkers, as seen in Fig. 2(b). For instance, significant changes in LVEF between pairs of scans can arise from inconsistencies in the segmentation of the LV in basal slices, as shown in Fig. 2(a). This has consequences in the classification of subjects based on LVEF, as shown in Fig. 1(b). Only two subjects belonged to the mildly reduced LVEF class, however, when comparing predicted scan and rescan LVEF, both sensitivity and specificity decrease, suggesting inconsistency in the biomarker estimation. Conclusion(s) While we have demonstrated successful AI cardiac segmentation and biomarker estimation based on conventional performance metrics, additional refinement is necessary to enhance reliability and consistency. Further work is needed to obtain a better delineation of the valve plane, which would help addressing the inconsistencies at the LV basal slice. An automated segmentation and analysis pipeline for cine CMR is vital to support overworked clinicians, however, demonstrably repeatable performance, particularly when looking at therapy response, will have a significant impact on patient care and clinical outcomes.Repeatability of GT and AI biomarkersRepeatability of GT and AI segmentations

A Genome-Wide Association Study (GWAS) of Takotsubo syndrome

Abstract Background Takotsubo syndrome (TS) is an acute cardiac condition of unknown etiology characterized by transient regional systolic dysfunction of the left and/or right ventricle. Several studies have suggested the importance of genetics; however, studies are limited and have presented conflicting results. Purpose To identify potential genetic risk variants associated with TS. Methods A case-control GWAS in three steps; I) A discovery study with Swedish takotsubo cases (n=260) and age- and sex-matched controls without heart disease from the UK Biobank (n=3034), II) A replication study of Swedish takotsubo cases (n=250) and sex- and age-matched Swedish controls without myocardial infarction from the Swedish coronary angiography and angioplasty register (n=229), III) A Meta-analysis of study I-II with extended controls from the UK-biobank (n=5161). Genotyping was performed using the Axiom® UK Biobank Genotyping Array including 820 000 single nucleotide polymorphisms (SNPs). After applying filters and QC control around 480 000 SNPs remained with a Bonferroni corrected p-value 1*10^-7, minor allele frequency (MAF 1.5-2%), Hardy-Weinberg (HWE) 10^-6. QC, filtering and analysis were performed in PLINK 1.9 and R v 4.0. Results In the discovery (I) 1490 SNP:s fulfilled a significance level of <10^-4, of which 36 SNP:s replicated (II) with a significance level of <10^-2, 11 reached a significance level of 10^-7 in the meta-analysis (III). One of the 36 SNP:s, rs1614887, replicated (II) with a significance level of 10^-3. This SNP is an intron variant in the butyrophilin subfamily 2 member A2 gene, a glycoprotein receptor involved in lipid, fatty-acid and sterol metabolism highly expressed in the heart. Of the 11 SNP:s with a significance level of 10^-7 in the meta-analysis (III) several risk variants were associated with psoriasis. Conclusions This is the largest GWAS of takotsubo syndrome performed so far, identifying one candidate gene and several potential risk variants. Further research of genetic risk variants in TS is warranted.

The potential protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients after one year of observation

Abstract Introduction Despite the widespread use of anthracyclines (ANT) and anti-HER2 agents as trastuzumab (TZB) in chemotherapy schemes, it is known the potential cardiotoxic effects that can limit the intensity and duration of treatments. The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus. Purpose We aimed to study if dapagliflozin could exerts cardioprotective effects in anthracycline, carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction (LVEF), global longitudinal strain (GLS) of both left and right ventricle, E/A ratio, E/e’ ratio, left atrium diameter, BNP/NT-pro-BNP and troponin I. Methods 32 diabetic patients were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function as well as chemotherapeutic agents ). Our patients who were diagnosed with cancer at our medical center, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Results In the first year of observation patients treated with dapagliflozin didn’t show any deterioration of LV GLS (¬19.8±2.8 vs ¬19.3±4.1%, p=0.403) There was no change in LVEF (57.8±4.9% vs 59±6.8%) and GLS of right ventricle (20.3±2.8% vs 20.0±3.6%). Conversely, patients treated with placebo, presented a significant impairment of LV GLS (¬20.8±2.1% vs ¬18.5±2.2%, p=0,001) while a borderline deterioration of EF was noticed after treatment with placebo(60±5.4 vs 56.7±6.7%, p=0,045). Conclusions At the best of our knowledge, our study is the first to investigate the prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in diabetic patients receiving anthracycline or trastuzumab,carflilzomib therapies. Treatment with dapagliflozin prevented deterioration of myocardial function and preserved ejection fraction

Microcirculatory resistance after primary percutaneous coronary intervention predicts residual myocardial damage: a post hoc analysis from the CLEVER-ACS trial

Abstract Introduction Coronary microvascular dysfunction has been associated with adverse cardiovascular events following acute myocardial infarction. This study evaluates the role of the angiography-derived index of microcirculatory resistance (angio-IMR) in predicting myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Material and Methods In this post hoc analysis of the Controlled Level Everolimus in Acute Coronary Syndromes (CLEVER-ACS) trial, the associations between post-PCI angio-IMR of infarct-related coronary arteries (IRAs) and infarct size, microvascular obstruction (MVO), and left ventricle ejection fraction (LVEF) at 30 days as assessed with cardiac magnetic resonance (CMR) imaging were investigated. High post-PCI angio-IMR value was defined as a value >40 U. In non-IRAs angio-IMR was measured before the IRA-PCI. Results A total of 52 IRAs and 94 non-IRAs of 52 patients were included in the analysis. Post-PCI Angio-IMR was 41.5 (IQR 28.5–55.7) U in IRAs and pre-PCI Angio-IMR was 43.7 (31.7–54.0) U in non-IRAs (p = 0.70). Patients with high post-PCI angio-IMR (52%) exhibited a larger myocardial infarct size (36.0 [23.0–52.5] g vs. 14.5 [6.50–26.5] g, p < 0.001) and a lower LVEF (46.5 [39.5–49.5] % vs. 55.0 [48.0–61.4] %, p = 0.002) at 30 days as compared to those with low post-PCI angio-IMR values. Post-PCI angio-IMR correlated with myocardial infarct size (r = 0.45, p = 0.001) and extent of MVO (r = 0.40, p = 0.004) at 30 days. Post-PCI angio-IMR predicted myocardial infarct size (AUC = 0.78 [0.65–0.92], p = 0.001) and extent of MVO (AUC = 0.74 [0.60–0.89], p = 0.009) at 30 days. Conclusion In patients with STEMI undergoing PCI, post-PCI angio-IMR was identified as independent predictor of myocardial infarct size and extent of MVO at 30 days. The assessment of post-PCI angio-IMR values may represent a novel tool for early risk stratification of patients with STEMI.Central illustration