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Background: Since hyperthyroidism could be associated with right ventricular dysfunction, this study intended to investigate right ventricular (RV) function using strain echocardiography in hyperthyroid patients both at rest and in maximum-stress conditions. Methods: This cross-sectional study was conducted at Rajaie Cardiovascular Medical and Research Center, Tehran, Iran, from January 2019 to January 2020. All study participants completed a maximum treadmill exercise test, as well as a complete two-dimensional echocardiogram at rest and the peak of stress test. The data were analyzed using SPSS statistical software. The independent samples t test and Mann–Whitney U test were used for numerical, and the Chi square test was used for nominal variables. P

Aims: Chronic hypoxia causes detrimental structural alterations in the lung, which may cause pulmonary hypertension and are partially mediated by the endothelium. While its relevance for the development of hypoxia-associated lung diseases is well known, determinants controlling the initial adaptation of the lung endothelium to hypoxia remain largely unexplored., Methods and Results: We revealed that hypoxia activates the transcription factor nuclear factor of activated T-cells 5 (NFAT5) and studied its regulatory function in murine lung endothelial cells (MLECs). EC-specific knockout of Nfat5 (Nfat5(EC)-/-) in mice exposed to normobaric hypoxia (10% O2) for 21 days promoted vascular fibrosis and aggravated the increase in pulmonary right ventricular systolic pressure as well as right ventricular dysfunction as compared with control mice. Microarray- and single-cell RNA-sequencing-based analyses revealed an impaired growth factor-, energy-, and protein-metabolism-associated gene expression in Nfat5-deficient MLEC after exposure to hypoxia for 7 days. Specifically, loss of NFAT5 boosted the expression and release of platelet-derived growth factor B (Pdgfb)-a hypoxia-inducible factor 1 alpha (HIF1α)-regulated driver of vascular smooth muscle cell (VSMC) growth-in capillary MLEC of hypoxia-exposed Nfat5(EC)-/- mice, which was accompanied by intensified VSMC coverage of distal pulmonary arteries., Conclusion: Collectively, our study shows that early and transient subpopulation-specific responses of MLEC to hypoxia may determine the degree of organ dysfunction in later stages. In this context, NFAT5 acts as a protective transcription factor required to rapidly adjust the endothelial transcriptome to cope with hypoxia. Specifically, NFAT5 restricts HIF1α-mediated Pdgfb expression and consequently limits muscularization and resistance of the pulmonary vasculature., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH., Methods: Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance., Results: A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression., Conclusions: Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets., Competing Interests: Drs Pi, Suresh, Hemnes, Bravo, Rayner, Shojaie, Leary, and Gharib have received research funding from the National Institutes of Health. Dr Hemnes has done consulting work for GossamerBio, United Therapeutics, Janssen, Merck, and Tenax Therapeutics. She is a stockholder (negligible value) in Tenax Therapeutics. Dr Rayner received research funding from Bayer Pharmaceuticals and United Therapeutics. Dr Leary has received grants and research support from the CHEST Foundation, the American Heart Association, Bayer, Janssen, and Acceleron/Merck. He has been a grant review consultant for Bayer and has adjudicated clinical end points for Sumitomo Pharma. He is on the scientific leadership council for the Pulmonary Hypertension Association and the medical advisory board for Team PHenomenal Hope. The other authors report no conflicts.

Sonography, in particular echocardiography, is essential in the assessment of volume status and hemodynamics in critically ill patients. Examination of the left ventricle, in addition to assessing ventricular function, provides valuable information, including the "kissing papillary muscle sign," which may indicate fluid responsiveness. Examination of the right ventricle is also important because it is sensitive to both volume and pressure overload. Assessment of diastolic function and measurement of inferior vena cava width and variability provide clues to left and right ventricular preload, respectively. Measurement of stroke volume and cardiac output allows further assessment of hemodynamics and also permits determination of stroke volume variability., (© 2024. The Author(s).)

Background: Accurate quantification of right ventricular (RV) volumes and function is crucial for the management of congenital heart diseases., Aims: We aimed to assess the feasibility and accuracy of bedside analysis using new RV quantification software from three-dimensional transthoracic echocardiography in children with or without congenital heart disease, and to compare measurements with cardiac magnetic resonance imaging., Methods: We included paediatric patients with congenital heart disease (106 patients) responsible for RV volume overload and a control group (30 patients). All patients underwent three-dimensional transthoracic echocardiography using a Vivid E95 ultrasound system. RV end-diastolic and end-systolic volumes and RV ejection fraction were obtained using RV quantification software. Measurements were compared between RV quantification and cardiac magnetic resonance imaging in 27 patients., Results: Bedside RV quantification analysis was feasible in 133 patients (97.8%). Manual contour adjustment was necessary in 126 patients (93%). The mean time of analysis was 62±42s. RV end-diastolic and end-systolic volumes were larger in the congenital heart disease group than the control group: median 85.0 (interquartile range 29.5) mL/m 2 vs 55.0 (interquartile range 20.5) mL/m 2 for RV end-diastolic volume and 42.5 (interquartile range 15.3) mL/m 2 vs 29.0 (interquartile range 11.8) mL/m 2 for RV end-systolic volume, respectively. Good agreement for RV end-diastolic and end-systolic volumes and RV ejection fraction was found between RV quantification and magnetic resonance imaging measurements. RV quantification software underestimated RV end-diastolic volume/body surface area by 3mL/m 2 and RV ejection fraction by 2.1%, and overestimated RV end-systolic volume/body surface area by 0.2mL/m 2 ., Conclusions: We found good feasibility and accuracy of bedside RV quantification analysis from three-dimensional transthoracic echocardiography in children with or without congenital heart disease. RV quantification could be a reliable and non-invasive method for RV assessment in daily practice, facilitating appropriate management and follow-up care., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Pectus excavatum, the most frequent malformation of the chest wall, has been related to cardiac compression and exercise intolerance. Cardiac outcomes after minimally invasive repair of pectus excavatum with retrosternal implants, particularly after removal (> 2 years postoperative) are generally unknown. We evaluated stress echocardiography outcomes before repair and after bar removal. This study comprised a retrospective cohort of patients with diagnosis of isolated pectus excavatum who underwent stress echocardiography before minimally invasive repair with retrosternal implants, and after bar removal. The diastolic function was evaluated by means of the trans tricuspid flow and tissue doppler imaging. The compression of the atrioventricular groove was assessed using the trans tricuspid gradient and the tricuspid area. We included 43 patients, with a mean age of 15.7 ± 4.0 years (91% male). After bar removal, 83% of patients referred improvement of exercise capacity. Furthermore, we found a significant improvement in right ventricular filling patterns, including a better E/A ratio profile during exercise (p = 0.001), lower filling pressures both at rest (p < 0.0001) and during exercise (p = 0.031), and lower rates of resting paradoxical septal motion [70% vs. 20%, p = 0.0007]. The trans tricuspid mean gradient during exercise was significantly lower after bar removal (p < 0.0001). In this study involving patients with minimally invasive repair of pectus excavatum, we demonstrated a beneficial impact of such intervention after bar removal, with significant improvements related to the right ventricular function, as well as signs of relief of cardiac compression., Competing Interests: Declarations IRB and informed consent The protocol of this retrospective study was approved by the Ethics Committee (CEICyT, approval number 0-1095, date 15/03/2023), and all patients provided informed written consent for anonymous use of data. Central message Cardiac outcomes after pectus bar removal remain controversial. Using stress echocardiography, we identified improvement in right ventricular function and signs of relief in cardiac compression after bar removal. Perspective We identified a significant improvement in right ventricular diastolic and systolic function as well as signs of cardiac decompression, and improved exercise capacity after bar removal of minimally invasive repair of pectus excavatum. The compression of the atrioventricular groove, reflected by the presence of an incremented tricuspid gradient, was significantly lower after bar removal. Competing interests Marcelo Martinez-Ferro: ownership interest in Pampamed SRL, Gaston Rodriguez-Granillo: consultant of Fundacion INICIAR, Caristo Diagnostics, MultiplAI Health, and RDCom. None of the other authors have conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: The ratio between tricuspid annular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (PASP) has been shown to be a reliable, non-invasive surrogate of the right ventricular-pulmonary artery (RV-PA) coupling. The present study analysed the association between TAPSE/PASP and response to cardiac resynchronization therapy (CRT) and the prognostic role of RV-PA in patients undergoing CRT implantation. The primary endpoints were: the association between baseline TAPSE/PASP and CRT response/cardiovascular and all-cause death., Methods and Results: All patients having undergone CRT implantation in our Center from 2016 to 2020 were included in our retrospective analysis. The RV-PA coupling was assessed by echocardiography at baseline and 1 year follow up in CRT recipients. The cut-off value of TAPSE/PASP resulted from ROC curve analysis (i.e.<0.33 mm/mmHg). A total of 229 patients (age 69.9 ± 10.1 years; 77.7% men) were included. During a mean follow-up of 44.2 ± 17.9 months, 40 (17.5%) patients died. The baseline value of TAPSE/PASP was not significantly associated with CRT response. Patients with a more impaired TAPSE/PASP ratio had significantly worse survival rates. On multivariate Cox regression, only TAPSE/PASP ratio and estimated glomerular filtration rate were independently associated with all-cause death. Finally, the TAPSE/PASP ratio significantly increased after CRT implantation in the group of "responders" whereas it did not change in 'non-responders'., Conclusions: The baseline value of TAPSE/PASP ratio was not associated with CRT response. However, the TAPSE/PASP ratio was a strong predictor of both all-cause and cardiovascular death in CRT recipients., Competing Interests: Declarations Competing interests The authors report no relationships that could be construed as a conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Echocardiographic evaluation of the cardiopulmonary unit is difficult in case of tricuspid regurgitation (TR) and combined echocardiographic parameters could be useful. This study aimed to assess the variation of simple and combined echocardiographic parameters analysing the cardiopulmonary unit according to the severity of TR. TR was graded according to Hahn's classification in 179 patients. Classical morphological, function and load parameters analysing right ventricle were assessed. Combined parameters of function and load; morphology and load; and morphology-load-function index were calculated. We used ROC curve analysis to analyze the diagnostic value of echocardiographic parameters to predict potential high or low surgical risk of mortality according to TRISCORE in 82 patients. Simple parameters were significatively different among groups with a nonlinear progression between the 5 levels of severity of TR. Combined parameters were also significatively different among groups. Among them, myomechanical index (MMI = RV-RA mean pressure gradient x RVFWS/indexed RAED area × 10 -2 ) and morphology-load-function index (MLF = RVED length/area x TR TVI x RVFWS) had a linear progression between the 5 groups and had the best predictive value for TRISCORE high and low risk. Combined parameters are relevant to evaluate cardiopulmonary unit in patients with various degrees of TR, especially when combining morphology, function, and load parameters, and are potentially interesting in their prognostic assessment, as shown by the good predictive value for TRISCORE risk., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Existing evidence of the effect of spinal anesthesia (SA) on cardiac systolic function is scarce and inconclusive. This study aimed to evaluate the effects induced by a single injection of SA for elective vascular surgery on left (LV) and right (RV) ventricular systolic performance using transthoracic echocardiography (TTE). A prospective study. Single-center study, university hospital. Adult patients undergoing elective vascular surgery with SA. During patients' evaluations fluid administration was targeted using arterial waveform monitoring. All patients underwent TTE studies before and after SA induction for the assessment of indices reflective of LV and RV systolic function. Blood samples were drawn to measure troponin and brain natriuretic peptide (BNP) levels. A total of 62 patients (88.7% males, 71.00 ± 9.42 years) were included in the study. The primary outcome was the difference before and after SA in LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE). In total population, LVEF significantly increased after SA 53.07% [16.51]vs 53.86% [13.28]; p < 0.001). End-systolic volume (ESV, 69.50 [51.50] vs. 65.00 [29.50] ml; p < 0.001) decreased while stroke volume (SV) insignificantly increased (70.51 ± 16.70 vs. 73.00 ± 18.76 ml; p = 0.131) during SA. TAPSE remained unchanged (2.23 [0.56] vs. 2.25 [0.69] mm; p = 0.558). In patients with impaired compared to those with preserved LV systolic function, the changes evidenced in LVEF (7.49 ± 4.15 vs. 0.59 ± 2.79; p < 0.001), ESV (-18.13 ± 18.20 vs-1.53 ± 9.09; p < 0.001) and SV (8.71 ± 11.96 vs-1.43 ± 11.89; p = 0.002) were greater. This study provides evidence that SA in patients undergoing elective vascular surgery improved LV systolic function, while changes in RV systolic function are minimal., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The right ventricle and its stress response is perhaps the most important arbiter of survival in patients with pulmonary hypertension of many causes. The physiology of the cardiopulmonary unit and definition of right heart failure proposed in the 2018 World Symposium on Pulmonary Hypertension have proven useful constructs in subsequent years. Here, we review updated knowledge of basic mechanisms that drive right ventricular function in health and disease, and which may be useful for therapeutic intervention in the future. We further contextualise new knowledge on assessment of right ventricular function with a focus on metrics readily available to clinicians and updated understanding of the roles of the right atrium and tricuspid regurgitation. Typical right ventricular phenotypes in relevant forms of pulmonary vascular disease are reviewed and recent studies of pharmacological interventions on chronic right ventricular failure are discussed. Finally, unanswered questions and future directions are proposed., Competing Interests: Conflict of interest: A.R. Hemnes reports grants from NIH/NHLBI, consultancy fees from Bayer, Gossamer Bio, Merck, Janssen, United Therapeutics and Tenax, participation on a data safety monitoring board or advisory board with NIH/NHLBI, leadership roles with Nashville Ballet and Pulmonary Vascular Research Institute, and stock (or stock options) with Tenax Therapeutics. D.S. Celermajer has no potential conflicts of interest to disclose. M. D'Alto reports consultancy fees and payment or honoraria for lectures, presentations, manuscript writing or educational events from Merck Sharp and Dhome, Dompé, AOP and Janssen, and support for attending meetings from Dompé, AOP and Janssen. F. Haddad reports grants from Johnson & Johnson, and consultancy fees from Merck. P.M. Hassoun reports grants from NIH/NHLBI (R01 R01HL114910), and participation on a data safety monitoring board or advisory board with MSD and ARIA-CV. K.W. Prins reports grants from NHLBI (R01 HL158795 and 162927) and Bayer (PHAB grant), and consultancy fees from Edwards. R. Naeije reports consultancy fees from AOP Orphan Pharma, Johnson & Johnson, United Therapeutics and Lung Biotechnology, payment or honoraria for lectures, presentations, manuscript writing or educational events from AOP Orphan Pharma, support for attending meetings from AOP Orphan Pharma, and participation on a data safety monitoring board or advisory board with Johnson & Johnson, AOP Orphan Pharma and United Therapeutics. A. Vonk Noordegraaf reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Actelion and Johnson & Johnson., (Copyright ©The authors 2024.)

Background: Hypertension (HTN) and diabetes mellitus (DM) are two common comorbidities of heart failure with reduced ejection fraction (HFrEF), each of which can cause right ventricular (RV) dysfunction. The aim of this study was to investigate the impact of DM on RV dysfunction and ventricular interdependence in hypertensive HFrEF patients via cardiac magnetic resonance imaging (MRI) feature tracking., Methods: This study included 249 patients with HFrEF: 77 HFrEF controls, 97 with hypertensive HFrEF (HTN-HFrEF [DM-]) and 75 with hypertensive HFrEF and comorbid DM (HTN-HFrEF [DM+]). The cardiac MRI-derived biventricular global radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were obtained and compared among the groups. Multivariable linear regression and mediation analyses were used to evaluate the effects of DM and left ventricular (LV) strain on RV strain., Results: The biventricular GLS and GLS of segments 8, 9 and 14 of the interventricular septum (IVS) decreased gradually from the HFrEF control group to the HTN-HFrEF (DM-) group to the HTN-HFrEF (DM+) group (all P < 0.05). Patients with DM had even lower biventricular GCS and IVS strains in all directions in specific segments than did those without DM and the HFrEF controls (all P < 0.05). DM was independently associated with impaired RVGLS and RVGCS (both P < 0.05) in hypertensive HFrEF patients. The difference in RVGLS between the hypertensive HFrEF subgroups was partly mediated by LVGLS [β = 0.80, 95% CI (0.39-1.31)], and that of RVGCS was partly mediated by LVGCS [β = 0.28, 95% CI (0.01-0.62)]., Conclusions: In hypertensive HFrEF patients, comorbid DM may have aggravated RV dysfunction and was an independent determinant of impaired RV strain. RV dysfunction might be directly affected by DM and partially mediated by LV strain through unfavorable ventricular independence., (© 2024. The Author(s).)

Introduction: The indications for concominant tricuspid valve surgery in patients undergoing mitral valve surgery for rheumatic reasons are limited. The aim of our study was to investigate the effects of severe pulmonary hypertension and low TAPSE values on early-term mortality and morbidity in patients undergoing mitral valve replacement., Methods: The data of all patients who underwent mitral valve replacement between January 2013 and August 2020 were examined retrospectively. Patients were divided into 2 groups according to pulmonary artery pressure (PAP ≥ 50 and PAP < 50). The group with PAP > 50 was then divided into 2 subgroups according to TAPSE (1.5 ≥ or < 1.5) values. The early-term mortality and morbidity rates of these groups were compared., Results: Seventy-nine patients who underwent mitral valve replacement were included in the study. Fifty-four (68%) of them were female, and 25 (32%) were male. During the preoperative period, the TAPSE was 16.8 ± 3.0 mm, and the PAP was 52.1 ± 14.1 mmHg. There were 53 patients with PAP > 50 and 26 patients with PAP < 50. In the PAP > 50 group, the rates of tricuspid regurgitation (p < 0.001), blood transfusion (p < 0.001), intensive care unit stay (p < 0.001), need for CPAP (p = 0.043), reintubation (p = 0.048), acute renal failure (p = 0.028), and mortality (p = 0.026) were found to be significantly different., Conclusion: In conclusion, we believe that in patients with mitral valve pathology, early referral for surgical intervention, before the pulmonary pressures significantly increase and right ventricular function deteriorates, can enhance survival outcomes., (© 2024. The Author(s).)

Objective: To explore the cardiac structural and functional changes in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF)., Methods: This retrospective study included 336 OSAHS patients with HFpEF. They were divided into Groups A (without an AF history and no AF episodes during cardiac color ultrasound examination), B (an AF history but no AF episodes), and C (an AF history and AF episodes). They all received cardiac color ultrasound examinations. Cardiac structural and functional changes in ultrasonic cardiograms were compared between the three groups., Results: Compared with Groups A and B, Group C showed increased left atrial diameter (LAD), left atrial volume (LAV), right ventricular diameter at end-diastole (RV-D1), right ventricular diameter at end-systole (RV-D2), right ventricular outflow tract diameter (RVOT2), right atrial diameter at end-diastole (RA-D1), right atrial diameter at end-systole (RA-D2), and right atrial area (RAA) (p < 0.05). Compared with Group A, Group C showed decreased fractional shortening (FS), left ventricular ejection fraction (LVEF), deceleration time (DT), isovolumic relaxation time (IVRT), E/E' ratio, and peak filling velocity (FPV), as well as increased E and E' (p < 0.01). Compared with Group B, Group C showed decreased FS and increased E and FPV (p < 0.01)., Conclusion: In OSAHS patients with HFpEF and AF, cardiac remodeling and AF incidence are increased with the severity of OSAHS. OSAHS patients with HFpEF combined with AF have a significantly higher abnormality rate in right heart structural indices rather than left heart, mainly in the right atrium., (© 2024. The Author(s).)

Pulmonary hypertension (PH) is highly prevalent in patients with interstitial lung disease (ILD) and is associated with increased morbidity and mortality. Widely available noninvasive screening tools are warranted to identify patients at risk for PH, especially severe PH, that could be managed at expert centres. This review summarises current evidence on noninvasive diagnostic modalities and prediction models for the timely detection of PH in patients with ILD. It critically evaluates these approaches and discusses future perspectives in the field. A comprehensive literature search was carried out in PubMed and Scopus, identifying 39 articles that fulfilled inclusion criteria. There is currently no single noninvasive test capable of accurately detecting and diagnosing PH in ILD patients. Estimated right ventricular pressure (RVSP) on Doppler echocardiography remains the single most predictive factor of PH, with other indirect echocardiographic markers increasing its diagnostic accuracy. However, RVSP can be difficult to estimate in patients due to suboptimal views from extensive lung disease. The majority of existing composite scores, including variables obtained from chest computed tomography, pulmonary function tests and cardiopulmonary exercise tests, were derived from retrospective studies, whilst lacking validation in external cohorts. Only two available scores, one based on a stepwise echocardiographic approach and the other on functional parameters, predicted the presence of PH with sufficient accuracy and used a validation cohort. Although several methodological limitations prohibit their generalisability, their use may help physicians to detect PH earlier. Further research on the potential of artificial intelligence may guide a more tailored approach, for timely PH diagnosis., Competing Interests: Conflict of interest: A. Arvanitaki, M.A. Gatzoulis and C. McCabe declare no conflicts of interest relevant to this work. ​G.P. Diller has received honoraria and travel grants from Janssen Global. L.C. Price has received consultancy fees from Janssen and educational support and conference support from Janssen and Ferrer. S.J. Wort has received consultancy fees from Janssen, Acceleron, MSD, Ferrer and Bayer, honoraria from Janssen, Acceleron, MSD, Ferrer and Bayer, as well as travel and research grants from Janssen and Ferrer., (Copyright ©The authors 2024.)

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age of 13.4 ± 2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ± 25 mmHg at rest to 130 ± 40 mmHg at peak exercise ( P < 0.001), whereas RV fractional area change (RV-FAC) and RV-free wall longitudinal strain (RVFW-S l ) worsened (35.2 vs. 27%, P = 0.09 and -16.6 vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity exercise, RVsp was positively associated with stroke volume and O 2 pulse ( P < 0.1). At high-intensity exercise, RV-FAC, RVFW-S l , and left ventricular longitudinal strain were positively associated with oxygen uptake and O 2 pulse ( P < 0.1), whereas stroke volume decreased toward peak ( P = 0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV to pulmonary artery (RV-PA) uncoupling, worsening of interventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population. NEW & NOTEWORTHY In children with pulmonary arterial hypertension, there is a marked increase in pulmonary artery pressure during physical activity, but this is not the underlying mechanism that limits exercise. Instead, right ventricle-to-pulmonary artery uncoupling occurs at the transition from moderate to high-intensity exercise and correlates with lower peak oxygen uptake. This highlights the more complex underlying pathological responses and the need for multiparametric assessment of cardiac function reserve in these patients when feasible.

Women with primary mitral insufficiency have a smaller regurgitant volume at the same regurgitant fraction than men. We hypothesized that normalizing regurgitant volume with left ventricular end-diastolic volume or allometric scaling would eliminate the difference in regurgitant volume between women and men. The study cohort consisted of 101 patients with mitral valve prolapse undergoing cardiac MRI. Descriptive statistics and linear regression were performed to assess differences between sexes. Of the 101 patients, 46 (46%) were women. Women had a significantly smaller left and right ventricular end-diastolic volume, end-systolic volume, and stroke volume. While there was no difference in regurgitant fraction between women and men (34 ± 13% vs. 35 ± 14%; p = 0.71), women had a significantly smaller regurgitant volume (36 ± 18 ml vs. 49 ± 26 ml; p = 0.005). The slope-intercept relationship between regurgitant fraction and regurgitant volume revealed unique slopes and y-intercept values for men and women (p-value < 0.0001). Normalizing regurgitant volume to left ventricular end-diastolic volume (RVol/LVEDV), body surface area 1.5 (RVol/BSA 1.5 ) and height 2.7 (RVol/height 2.7 ) all had essentially identical slope-intercept relationships with regurgitant fraction for men and women, but RVol/LVEDV had the smallest effect size. In mitral insufficiency secondary to mitral valve prolapse women have a significantly smaller regurgitant volume than men despite no difference in regurgitant fraction. The significant difference in regurgitant volume between women and men is secondary to women having a smaller left ventricular end-diastolic volume., (© 2024. The Author(s).)

Background: Branch pulmonary artery (PA) stenosis is one of the most common indications for percutaneous interventions in patients with transposition of the great arteries (TGA), tetralogy of Fallot (ToF), and truncus arteriosus (TA). However, the effects of percutaneous branch PA interventions on exercise capacity remains largely unknown. In addition, there is no consensus about the optimal timing of the intervention for asymptomatic patients according to international guidelines. This trial aims to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with TGA, ToF, and TA. In addition, it aims to assess the effects on RV function and to define early markers for RV adaptation and RV dysfunction to improve timing of these interventions., Methods: This is a randomized multicenter interventional trial. TGA, ToF, and TA patients ≥ 8 years with a class IIa indication for percutaneous branch PA intervention according to international guidelines are eligible to participate. Patients will be randomized into the intervention group or the control group (conservative management for 6 months). All patients will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and cardiopulmonary exercise testing at baseline, 6 months, and 2-4 years follow-up. Quality of life (QoL) questionnaires will be obtained at baseline, 2 weeks post intervention or a similar range for the control group, and 6 months follow-up. The primary outcome is exercise capacity expressed as maximum oxygen uptake (peak VO 2 as percentage of predicted). A total of 56 patients (intervention group n = 28, control group n = 28) is required to demonstrate a 14% increase in maximum oxygen uptake (peak VO 2 as percentage of predicted) in the interventional group compared to the control group (power 80%, overall type 1 error controlled at 5%). Secondary outcomes include various parameters for RV systolic function, RV functionality, RV remodeling, procedural success, complications, lung perfusion, and QoL., Discussion: This trial will investigate the effects of percutaneous branch PA interventions on exercise capacity in patients with TGA, ToF, and TA and will identify early markers for RV adaptation and RV dysfunction to improve timing of the interventions., Trial Registration: ClinicalTrials.gov NCT05809310. Registered on March 15, 2023., (© 2024. The Author(s).)

The goal of this study was to determine the potential for right ventricular (RV) and left ventricular (LV) strain to predict cardiopulmonary complications of COVID-19. We identified 276 patients with COVID-19 who underwent transthoracic echocardiography within 30 days of COVID-19 diagnosis at our institution. Patients were excluded if they had a history of any primary outcomes before COVID-19 diagnosis or insufficient imaging. LV global longitudinal strain (GLS) and RV GLS were obtained using 2-dimensional speckle-tracking echocardiography. Primary outcomes were death, pulmonary embolism, congestive heart failure (CHF), cardiomyopathy, pulmonary fibrosis, pulmonary hypertension, acute respiratory distress syndrome (ARDS), and myocardial infarction (MI) occurring after COVID-19 diagnosis. In the final analysis of 163 patients, mean RV GLS and LV GLS were reduced, and 43.6% developed at least one primary outcome. There were significant differences in LV GLS distribution in terms of CHF, cardiomyopathy, and MI in bivariate analysis. However, LV GLS was not significantly associated with CHF after adjusting for LV ejection fraction and RV fractional area change, nor with MI after adjusting for troponin T. RV GLS was significantly associated with ARDS after adjusting for other variables. In the risk stratification of patients with COVID-19, strain imaging can provide incremental prognostic information, as worsened RV GLS is associated with the development of ARDS., (© 2024. The Author(s).)

Background: Patients with d-transposition of the great arteries (d-TGA) who have undergone an arterial switch operation (ASO) can develop right ventricular outflow tract (RVOT) dysfunction with pulmonary regurgitation (PR) or stenosis. In these patients, treatment may include transcatheter pulmonary valve replacement (TPVR). Coronary compression is a contraindication occurring in 5% of typical TPVR cases. After ASO, there are various anatomical considerations that can confound TPVR, including potential coronary artery compression. Our goal is to understand feasibility of TPVR in patients following ASO., Methods: This was a retrospective multicenter cohort study of patients with RVOT dysfunction after ASO who underwent cardiac catheterization with intention to perform TPVR from 2008 to 2020., Results: Across nine centers, 33 patients met inclusion criteria. TPVR was successful in 22 patients (66%), 19 receiving a Melody valve and 3 a SAPIEN valve. RVOT stenosis in isolation or with PR dictated need for TPVR in nearly all patients. One serious adverse event occurred with valve embolization. After TPVR, the RVOT peak gradient decreased from 43 to 9 mm Hg (p < 0.001); PR was trivial/none in all but one patient, in whom it was mild. Coronary compression prohibiting TPVR occurred in eight patients (24%) and two patients (6%) had severe aortic regurgitation from aortic root deformation precluding TPVR. Seven patients underwent RVOT reintervention a median of 5.3 years post-TPVR., Conclusions: TPVR in patients with d-TGA after ASO is feasible, but in this cohort, coronary compression or aortic root distortion precluded TPVR in one-third of patients. The rate of RVOT reintervention after TPVR was higher in this cohort of ASO patients than in prior studies., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Transthoracic echocardiography is usually the first non-invasive imaging modality for the detection of Loeffler endocarditis at thrombotic stage. In the recent decade 3D echocardiography and deformation imaging already proved as a helpful tool for the monitoring of left and right ventricular heart disease., Case Presentation: The present case illustrates the diagnostic role of 3D echocardiography and deformation imaging in the acute stage of right sided Loeffler endocarditis in a 70-year-old Western European (German) woman. This case proves that myocardial involvement due to inflammation can be detected at subclinical stages by speckle tracking echocardiography. Acute deterioration of left and right ventricular function and the early response to prednisolone therapy can objectively be monitored. In addition, alterations of effective stroke volume can quantitatively be assessed by 3D right ventricular volumetry with exclusion of thrombus formation in the volume measurements., Conclusion: This case underlines the importance of 3D echocardiography and deformation imaging as a helpful diagnostic tool in disease management in the acute phase of Loeffler endocarditis at thrombotic stage., (© 2024. The Author(s).)

Background: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA-PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important., Purpose: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA-PAI patients without PH., Study Type: Retrospective., Population: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non-PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex- and age-matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography., Field Strength/sequence: 3 T/Cine imaging sequence with a steady-state free precession readout., Assessment: Cardiac MRI-derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA-PAI patients with and without PH., Statistical Tests: Student's t test, one-way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P-value of <0.05 was considered statistically significant., Results: Although the TA-PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non-PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non-PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA-PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non-PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non-PH 14.8 ± 3.9%) than those without PH., Data Conclusion: Right ventricular dysfunction was detected in the TA-PAI patients without PH. MR-feature tracking may be an effective method for detecting early cardiac damage in the TA-PAI patients without PH., Level of Evidence: 3 TECHNICAL EFFICACY: Stage 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Cardiac magnetic resonance (CMR) feature-tracking (FT) has an important diagnostic role in non-ischemic dilated cardiomyopathy (NIDCM). To date, the relationship between whole-heart myocardial mechanics by CMR and early primary outcomes in NIDCM has not been elucidated. patients with NIDCM were eligible for this study. CMR-FT was used to analyze whole-heart myocardial mechanics. The primary outcomes were a composite of heart failure (HF) death, heart transplantation (HT), and hospitalization for HF worsening (WHF) after 1-year since diagnosis. 98 patients were included. During a 1-year follow-up, a worse prognosis occurred in 32 patients (30 hospitalizations for WHF, 8 deaths, and 3 HT). The left ventricular (LV) global longitudinal systolic strain (GLS), left ventricular global circumferential strain (LV GCS), strains of right ventricle and both atria were significantly reduced in patients with events vs. those without (GLS - 8.0 ± 3.4 vs. - 12.1 ± 4.5, p < 0.001; GCS - 13.0 ± 6.4 vs. - 18.3 ± 7.1, p < 0.001; right ventricular (RV) GLS - 12.1 ± 4.9 vs. - 17.4 ± 6.4, p < 0.001; left atrial longitudinal strain 7.5 ± 3.8 vs. 15.1 ± 12.3, p < 0.001; right atrial longitudinal strain 11.0 ± 6.7 vs. 17.2 ± 8.0, p < 0.001). Left ventricular ejection fraction (LVEF) was significantly higher in patients with better prognosis (22.7 ± 8.7 vs. 33.56 ± 10.4, p < 0.001). Multivariate regression analysis revealed LV GLS as an independent predictor of a worse prognosis (OR 0.787, CI 95% 0.697-0.890, p < 0.001). reduction of LV GLS showed the strongest predictive value for the composite outcome of WHF, HT, and HF death., (© 2024. The Author(s).)

While Maternal Diabetes Mellitus (DM) is well known to affect the size and function of multiple fetal organ systems, effects on developing heart chamber function remain difficult to assess. We sought to determine the independent impact of maternal DM on fetal cardiac function in middle pregnancy. We prospectively recruited mothers with all categories of DM and non-diabetic healthy controls (NDC). Echocardiograms were optimized for chamber quantification and strain analysis. Left atrial area (LAA), LA strain (LAS), right atrial strain (RAS), global longitudinal ventricular strain (GLS) and Right ventricular free wall strain (RV FWS) were evaluated by 2 blinded operators. After excluding 9 mothers with poor fetal image quality, images from 104 mothers with DM and 47 NDC were analyzed. Mothers with DM and NDCs were well matched for age, blood pressure, smoking prevalence, and gestational age. Fetal heart rate (FHR) was significantly higher in fetuses of mothers with DM compared to NDC (147 ± 10 bpm vs. 144 ± 8, p = 0.04). LAA in fetuses of mothers with DM trended towards being larger in size (1.68 ± 0.4cm 2 vs. 1.56 ± 0.4cm 2 , p = 0.08). Fetal septal diameters were larger in maternal DM compared to NDC (2.7 ± 0.5 cm vs. 2.5 ± 0.5 cm, p = 0.001). GLS was similar between the groups. Fetal LAS was lower in maternal DM (28.8 ± 8.8% vs. 33.3 ± 10.4%, p = 0.007) and was independently associated with maternal DM after adjusting for GLS and FHR. Fetal RAS was lower in maternal DM (27.7 ± 10.4% vs. 31.8 ± 10.3%, p = 0.007), however only determinates were estimated fetal weight and RV FWS. Maternal DM independently impairs fetal LA function in mid pregnancy. These early functional changes in the developing heart warrant future studies investigating impact on cardiovascular health., (© 2024. The Author(s).)

We sought to couple current cardiac magnetic resonance (CMR) thresholds of right ventricular (RV) size and function with longitudinal trajectories of RV recovery, after pulmonary valve replacement (PVR). We aimed to identify optimal timing of PVR and couple CMR-based metrics with contemporaneous echocardiographic metrics. From June 2002 to January 2019, 174 patients with severe pulmonary regurgitation and peak RV outflow tract gradient <30 mm Hg underwent PVR at Cleveland Clinic. Mean age was 35 ± 16 years and 60 (34%) had concomitant tricuspid valve surgery. RV end diastolic area index (RVEDAi) and function metrics were measured by offline image review on preoperative and 794 postoperative echocardiograms. Contemporaneous RV end diastolic volume index (RVEDVi) was assessed on CMR and correlated to RVEDAi. Multiphase nonlinear mixed-effects models were used to analyze the longitudinal change in RV size and function after PVR. RVEDAi was correlated with RVEDVi (P < 0.0001, r = 0.59). RVEDAi decreased slowly over 10 years following PVR. An inflection point at 24 cm 2 /m 2 was noted at 1 year post-PVR and was associated with failure of RV reverse remodeling and RVEDVi ≥150 mL/m 2 . Compared to patients with preoperative RVEDVi ≥150 mL/m 2 , patients with RVEDVi <150 mL/m 2 had accelerated recovery of longitudinal trajectories of RV size and function metrics on echocardiograms. Reverse remodeling of RV following PVR is an ongoing process. Current accepted threshold values for PVR are associated with greatest RV recovery, suggesting that earlier PVR is warranted. Echocardiography can potentially be utilized in lieu of CMR for surveillance and interventional triage., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives . The aim was to demonstrate a reliable ex vivo method to test the function of the whole heart. Design . Pigs of varying sizes (44-80 kg) were exposed to dose response of adrenaline. Blood pressures and cardiac output were measured. The explanted hearts were tested in a novel ex vivo system to see if we could replicate the in vivo values at maximal adrenaline stimulation. The perfusion solution was STEEN Solution™ with erythrocytes and continuous infusion of essential drugs. In contrast to normal body circulation which is sequential, the heart evaluation system is divided into left and right heart circuits which are operating in parallel, making it possible to test the right and left heart individually or as a whole. The system provides coronary flow measurements. The nonlinear dynamic resistances are constructed to stabilize systolic and diastolic pressures in a broad range and independently from cardiac output. It is important for the functional evaluation to avoid pumping help for the heart; therefore, atrial vortexes are constructed to minimize pump flow directionality and energy from entering atria. Results. Ex vivo evaluation was able to match the maximal in vivo effect of adrenaline on cardiac output and blood pressures. After 2 h of evaluation, the blood gases and lactate were normal and free haemoglobin was zero. Autopsy of the hearts showed no macroscopic pathology. Conclusions. The system is able to give a reliable functional evaluation of the heart ex vivo .

Background: Children with repaired tetralogy of Fallot (rToF) often have pulmonary regurgitation with right ventricular (RV) dilatation and dysfunction, whereas less is known about the effect on the left ventricle (LV). The aim was to investigate LV haemodynamic variables derived from non-invasive pressure-volume loops in children with rToF and how they compare to controls and previous research on adults., Materials and Methods: Ten children with rToF and pulmonary regurgitation (12 years [10-13], 6 males) and 10 age- and sex-matched healthy controls (12 years [10-14], 6 males) underwent brachial blood pressure in conjunction with cardiac magnetic resonance imaging. Pressure-volume loops were derived by brachial blood pressure together with LV volumes throughout the cardiac cycle in short-axis cine images yielding several haemodynamic variables, including arterial elastance. The RV endocardial border was delineated in end-diastole and end-systole., Results: Children with rToF and pulmonary regurgitation had larger RV end-diastolic volume (136 [114-156]) than controls (100 [94-112] ml/m 2 ; p  = 0.0015) and smaller LV end-diastolic volume (83 [58-91] ml/m 2 ) than controls (101 [92-110] ml/m 2 ; p  = 0.002). Arterial elastance was higher in children with rToF (1.5 [1.3-2.7] mmHg/ml) than in controls (1.1 [1.0-1.5] mmHg/ml; p  = 0.02). Heart rate was higher in children with rToF (77 [74-81] bpm) than in controls (69 [65-75] bpm; p  = 0.027)., Conclusion: Children with rToF had higher arterial elastance and heart rate than controls, likely due to increased sympathetic tone to compensate for impaired LV filling following pulmonary regurgitation. If this contributes to increased risk of adverse cardiovascular and cerebrovascular events remains to be studied.

Background: A relatively common complication of COVID -19 infection is arrhythmia. There is limited information about myocardial deformation and heart rate variability (HRV) in symptomatic post COVID patients presented by ventricular arrhythmia., Aim of the Study: Our goal was to assess 2D-ventricular strain and heart rate variability indices (evaluated by ambulatory ECG monitoring) in post-COVID-19 patients suffering from ventricular arrhythmia., Methods: The current observational case-control study performed on 60 patients one month after they had recovered from the COVID-19 infection. Thirty healthy volunteers served as the control group. Each participant had a full medical history review, blood tests, a 12-lead surface electrocardiogram (ECG), 24-h ambulatory ECG monitoring, and an echo-Doppler examination to evaluate the left ventricular (LV) dimensions, tissue Doppler velocities, and 2D-speckle tracking echocardiography (2D-STE) for both the LV and right ventricular (RV) strain., Results: Symptomatic post-COVID patients with monomorphic premature ventricular contractions (PVCs) showed a substantial impairment of LV/RV systolic and diastolic functions, LV/RV myocardial performance (MPI) with reduced indices of HRV. Patients with higher versus lower ventricular burden had poorer functional status, higher levels of inflammatory biomarkers and reduced parameters of HRV (New York Heart Association (NYHA) class: 2.1 ± 0.9 vs. 1.5 ± 0.6, p < 0.001, C-reactive protein (CRP): 13.3 ± 4.1 vs. 8.3 ± 5.9 mg/L, p < 0.0001, low frequency/high frequency (LF/HF): 3.6 ± 2.4 vs. 2.2 ± 1.2, p < 0.002, the root mean square of the difference between successive normal intervals (rMSSD): 21.8 ± 4.7 vs. 29.3 ± 14.9 ms, p < 0.039 and the standard deviation of the RR interval (SDNN): 69.8 ± 19.1 vs.108.8 ± 37.4 ms, p < 0.0001). The ventricular burden positively correlated with neutrophil/lymphocyte ratio (NLR) (r = 0.33, p < 0.001), CRP (r = 0.60, p < 0.0001), while it negatively correlated with LV-global longitudinal strain (GLS) (r = -0.38, p < 0.0001), and RV-GLS (r = -0.37, p < 0.0001)., Conclusions: Patients with post-COVID symptoms presented by ventricular arrhythmia had poor functional status. Patients with post-COVID symptoms and ventricular arrhythmia had subclinical myocardial damage, evidenced by speckle tracking echocardiography while having apparently preserved LV systolic function. The burden of ventricular arrhythmia in post-COVID patients significantly correlated with increased inflammatory biomarkers and reduced biventricular strain., (© 2024. The Author(s).)

Background: Patients with concomitant type 2 diabetes mellitus (T2DM) and aortic regurgitation (AR) can present with right ventricular (RV) dysfunction. The current study aimed to evaluate the impact of AR on RV impairment and the importance of ventricular interdependence using cardiac magnetic resonance feature tracking (CMR‑FT) in patients with T2DM., Methods: This study included 229 patients with T2DM (AR-), 88 patients with T2DM (AR+), and 122 healthy controls. The biventricular global radial strain (GRS), global circumferential strain (GCS), and global longitudinal peak strain (GLS) were calculated with CMR‑FT and compared among the healthy control, T2DM (AR-), and T2DM (AR+) groups. The RV regional strains at the basal, mid, and apical cavities between the T2DM (AR+) group and subgroups with different AR degrees were compared. Backward stepwise multivariate linear regression analyses were performed to determine the effects of AR and left ventricular (LV) strains on RV strains., Results: The RV GLS, LV GRS, LV GCS, LV GLS, interventricular septal (IVS) GRS and IVS GCS were decreased gradually from the controls through the T2DM (AR-) group to the T2DM (AR+) group. The IVS GLS of the T2DM (AR-) and T2DM (AR+) groups was lower than that of the control group. AR was independently associated with LV GRS, LV GCS, LV GLS, RV GCS, and RV GLS. If AR and LV GLSs were included in the regression analyses, AR and LV GLS were independently associated with RV GLS., Conclusion: AR can exacerbate RV dysfunction in patients with T2DM, which may be associated with the superimposed strain injury of the left ventricle and interventricular septum. The RV longitudinal and circumferential strains are important indicators of cardiac injury in T2DM and AR. The unfavorable LV-RV interdependence supports that while focusing on improving LV function, RV dysfunction should be monitored and treated in order to slow the progression of the disease and the onset of adverse outcomes., (© 2024. The Author(s).)

Aims: Physiological activation of the heart using algorithms to minimize right ventricular pacing (RVPm) may be an effective strategy to reduce adverse events in patients requiring anti-bradycardia therapies. This systematic review and meta-analysis aimed to evaluate current evidence on clinical outcomes for patients treated with RVPm algorithms compared to dual-chamber pacing (DDD)., Methods and Results: We conducted a systematic search of the PubMed database. The predefined endpoints were the occurrence of persistent/permanent atrial fibrillation (PerAF), cardiovascular (CV) hospitalization, all-cause death, and adverse symptoms. We also aimed to explore the differential effects of algorithms in studies enrolling a high percentage of atrioventricular block (AVB) patients. Eight studies (7229 patients) were included in the analysis. Compared to DDD pacing, patients using RVPm algorithms showed a lower risk of PerAF [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.57-0.97] and CV hospitalization (OR 0.77, 95% CI 0.61-0.97). No significant difference was found for all-cause death (OR 1.01, 95% CI 0.78-1.30) or adverse symptoms (OR 1.03, 95% CI 0.81-1.29). No significant interaction was found between the use of the RVPm strategy and studies enrolling a high percentage of AVB patients. The pooled mean RVP percentage for RVPm algorithms was 7.96% (95% CI 3.13-20.25), as compared with 45.11% (95% CI 26.64-76.38) of DDD pacing., Conclusion: Algorithms for RVPm may be effective in reducing the risk of PerAF and CV hospitalization in patients requiring anti-bradycardia therapies, without an increased risk of adverse symptoms. These results are also consistent for studies enrolling a high percentage of AVB patients., Competing Interests: Conflict of interest: G.B. reports small speaker fees from Bayer, Boehringer Ingelheim, Boston, BMS, Daiichi, Sanofi, and Janssen, outside the submitted work. The other authors do not have conflict of interests to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI). However, the best timing for prognostic assessment remains uncertain. Our aim was to determine the impact of RV longitudinal function parameters and RV-PA coupling on mortality in patients undergoing TAVI.  Retrospective, single center, analysis including patients with AS who underwent TAVI between 2007 and 2021. Echocardiographic evaluation was performed before, shortly after the procedure, and during follow-up. RV-PA uncoupling was defined as a TAPSE/PASP ratio<0.55 (severe RV uncoupling was defined as TAPSE/PASP ratio<0.32. The effect of RV parameters on all-cause mortality up to 12 months was assessed.  Among the 577 patients included, pre-procedural TAPSE/PASP ratio data were available for 205. RV-PA uncoupling was present in 113 patients (55.1%), with severe uncoupling observed in 31 (15.1%). Within the first 12 months after TAVI, 51 patients (9%) died. Severe RV-PA uncoupling was associated with mortality in univariable Cox regression; however, this association was lost after adjusting for EuroSCORE II. A significant association was found between the TAPSE/PASP ratio (per 0.1-unit increase) after the procedure and the primary endpoint (HR: 0.73; 95% CI: 0.56, 0.97; p=0.029). Higher postprocedural PASP (HR: 1.04; 95% CI: 1.02, 1.06; p<0.001 was also associated with all-cause mortality.  V-PA uncoupling and PASP after TAVI are associated with all-cause mortality in patients and may be valuable for patient selection and for planning post-procedural care., (© 2024. The Author(s).)

The aim of this cross-sectional study was to investigate the relationship of left atrioventricular coupling index (LACI) and right atrioventricular coupling index (RACI) with demographics, clinical data, cardiovascular magnetic resonance findings, and cardiac complications (heart failure, arrhythmias, and pulmonary hypertension) in a cohort of patients with beta-thalassemia major (β-TM). We evaluated 292 β-TM patients (151 females, 36.72 ± 11.76 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. Moreover, we assessed 32 sex- and age-matched healthy controls (12 females, mean age 40.78 ± 14.35 years). LACI was determined by calculating the ratio of the left atrium end-diastolic volume to the left ventricle end-diastolic volume, while RACI was defined by calculating the ratio of the right atrium end-diastolic volume to the right ventricle end-diastolic volume. Compared to healthy control, β-TM demonstrated increased LACI (22.99 ± 13.58% vs. 16.05 ± 5.28%; p < 0.0001) and RACI (27.84 ± 10.30% vs. 17.06 ± 5.03%; p < 0.0001). Aging, diabetes, splenectomy, and the presence of late gadolinium enhancement (LGE) showed a significant positive association with both LACI and RACI. In stepwise regression analysis, the presence of LGE was found to be an independent predictor of both impaired LACI and RACI (β coefficient = 0.244, p < 0.0001 and β coefficient = 0.218, p = 0.003; respectively). LACI and RACI were not correlated with myocardial iron overload. Patients with cardiac complications had significantly higher LACI and RACI than patients without cardiac complications. In patients with β-TM, LACI and RACI were significantly associated with the presence of LV LGE. In addition, patients with cardiac complications had impaired LACI and RACI., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The value of cardiovascular magnetic resonance (CMR) in assessing and predicting acute right ventricular (RV) dysfunction in patients with anterior ST-segment elevation myocardial infarction (STEMI) remains ascertained. Eighty eight patients with anterior STEMI were prospectively recruited and underwent CMR examinations within one week following the coronary intervention. Patients with RV ejection fraction (RVEF) less than 2 standard deviations below the average at the center (RVEF ≤ 45.0%) were defined as having RV dysfunction. The size of infarction, segmental wall motion, and T1 and T2 mapping values of global myocardium and the interventricular septum (IVS) were measured. Predictive performance was calculated using receiver-operating characteristic curve analysis and logistic regression test. Twenty two patients presented with RV dysfunction. The RV dysfunction group had a larger IVS infarct extent (54.28 ± 10.35 vs 33.95 ± 15.09%, P < 0.001) and lower left ventricle stroke volume index (33.93 ± 7.96 vs 42.46 ± 8.14 ml/m 2 , P < 0.001) compared to the non-RV dysfunction group. IVS infarct extent at 48.8% best predicted the presence of RV dysfunction with an area under the curve of 0.864. Left ventricular stroke volume index (LVSVI) and IVS infarct extent were selected by stepwise multivariable logistic regression analysis. Lower LVSVI (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.79 to 0.99; P = 0.044) and higher IVS infarct extent (OR 1.16; 95% CI 1.05 to 1.33; P = 0.01) were found to be independent predictors for RV dysfunction. In patients with anterior STEMI, those with larger IVS infarct extent and worse LV function are more likely to be associated with RV dysfunction., (© 2024. The Author(s).)

The right ventricle (RV) differs developmentally, anatomically and functionally from the left ventricle (LV). Therefore, characteristics of LV adaptation to chronic pressure overload cannot easily be extrapolated to the RV. Mitochondrial abnormalities are considered a crucial contributor in heart failure (HF), but have never been compared directly between RV and LV tissues and cardiomyocytes. To identify ventricle-specific mitochondrial molecular and functional signatures, we established rat models with two slowly developing disease stages (compensated and decompensated) in response to pulmonary artery banding (PAB) or ascending aortic banding (AOB). Genome-wide transcriptomic and proteomic analyses were used to identify differentially expressed mitochondrial genes and proteins and were accompanied by a detailed characterization of mitochondrial function and morphology. Two clearly distinguishable disease stages, which culminated in a comparable systolic impairment of the respective ventricle, were observed. Mitochondrial respiration was similarly impaired at the decompensated stage, while respiratory chain activity or mitochondrial biogenesis were more severely deteriorated in the failing LV. Bioinformatics analyses of the RNA-seq. and proteomic data sets identified specifically deregulated mitochondrial components and pathways. Although the top regulated mitochondrial genes and proteins differed between the RV and LV, the overall changes in tissue and cardiomyocyte gene expression were highly similar. In conclusion, mitochondrial dysfuntion contributes to disease progression in right and left heart failure. Ventricle-specific differences in mitochondrial gene and protein expression are mostly related to the extent of observed changes, suggesting that despite developmental, anatomical and functional differences mitochondrial adaptations to chronic pressure overload are comparable in both ventricles., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Prior studies have indicated an impact of cardiac muscle viscoelasticity on systolic and diastolic functions. However, the studies of ventricular free wall viscoelasticity, particularly for that of right ventricles (RV), are limited. Moreover, investigations on ventricular passive viscoelasticity have been restricted to large animals and there is a lack of data on rodent species. To fill this knowledge gap, this study aims to develop a biaxial tester that induces high-speed physiological deformations to characterize the passive viscoelasticity of rat RVs., Methods: The biaxial testing system was fabricated so that planar deformation of rat ventricle tissues at physiological strain rates was possible. The testing system was validated using isotropic polydimethylsiloxane (PDMS) sheets. Next, viscoelastic measurements were performed in healthy rat RV free walls by equibiaxial cyclic sinusoidal loadings and stress relaxation., Results: The biaxial tester's consistency, accuracy, and stability was confirmed from the PDMS samples measurements. Moreover, significant viscoelastic alterations of the RV were found between sub-physiological (0.1 Hz) and physiological frequencies (1-8 Hz). From hysteresis loop analysis, we found as the frequency increased, the elasticity and viscosity were increased in both directions. Interestingly, the ratio of storage energy to dissipated energy (W d /W s ) remained constant at 0.1-5 Hz. We did not observe marked differences in healthy RV viscoelasticity between longitudinal and circumferential directions., Conclusion: This work provides a new experimental tool to quantify the passive, biaxial viscoelasticity of ventricle free walls in both small and large animals. The dynamic mechanical tests showed frequency-dependent elastic and viscous behaviors of healthy rat RVs. But the ratio of dissipated energy to stored energy was maintained between frequencies. These findings offer novel baseline information on the passive viscoelasticity of healthy RVs in adult rats., (© 2024. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Ventricular remodeling leads to fibrotic changes in systemic right ventricles (RV). Native T1 mapping provides a quantitative measure in myocardial tissue characterization. The aim of our study was to correlate native T1 values of the systemic RV to function and volumetric data. Native T1 maps were generated with a single breath hold Modified Look-Locker Inversion-recovery pulse (MOLLI) sequence was acquired in the mid-ventricular short axis. Regions of interest (ROI) were drawn in both ventricular free walls, the interventricular septum (IVS), superior insertion point (SIP) and inferior insertion point (IIP) to obtain native T1 values. T1 values were compared to CMR ventricular volumes and function using Spearman correlation. The median age was 36 years (IQR 27-48 years). There were elevated mean native left ventricular (LV) T1 and IIP T1 values at 1122 ± 171 ms and 1117 ± 96 ms, respectively. RV dysfunction was associated with elevated IIP T1 (p = 0.007). Significant moderate negative correlations were seen between RV T1 and LV ejection fraction (LVEF) (r= -0.63, p = 0.01), between RV: IVS T1 ratio and LVEF (r= -0.68, p = 0.006), between LVEF and SIP: IVS T1 ratios (r= -0.54, p = 0.04), and RVEF and IIP T1 (r= -0.59, p = 0.02). Fibrosis measured by native T1 mapping in the systemic RV is most prominent in the LV wall and septal insertion point and correlates with decreased function. T1 values can be used in non-invasive imaging assessment of the RV, but further studies with larger cohorts are needed to assess ability to risk stratify and guide therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The detailed hemodynamics after patent ductus arteriosus (PDA) ligation in preterm infants remain unknown. We aimed to clarify the effect of surgical ligation on left ventricular (LV) and right ventricular (RV) volume and function., Methods: Echocardiography was performed in 41 preterm infants (median gestational age: 25 weeks) before and after PDA ligation. Global longitudinal strain was determined using three-dimensional speckle-tracking echocardiography. These values were compared with those in 36 preterm infants without PDA (non-PDA)., Results: Preoperatively, the PDA group had greater end-diastolic volume (EDV) and cardiac output (CO) in both ventricles, a higher LV ejection fraction (LVEF) (53% vs 44%) and LV global longitudinal strain, and a lower RVEF (47% vs 52%) than the non-PDA group. At 4-8 h postoperatively, the two groups had a similar LVEDV and RVEDV. However, the PDA group had a lower EF and CO in both ventricles than the non-PDA group. At 24-48 h postoperatively, the RVEF was increased, but the LVEF remained decreased, and LVCO was increased., Conclusions: PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery. Three-dimensional echocardiography may be beneficial to understand the status of both ventricles., Impact: Preterm infants are at high risk of hemodynamic compromise following a sudden change in loading conditions after PDA ligation. Three-dimensional echocardiography enables quantitative and serial evaluation of ventricular function and volume in preterm infants with PDA. PDA induces biventricular loading and functional abnormalities in preterm infants, and they dramatically change after surgery., (© 2024. The Author(s).)

Right ventricular (RV) function is an important prognostic indicator for pulmonary arterial hypertension (PAH), a vasculopathy that primarily and disproportionally affects women with distinct pre- and postmenopausal clinical outcomes. However, most animal studies have overlooked the impact of sex and ovarian hormones on RV remodeling in PAH. Here, we combined invasive measurements of RV hemodynamics and morphology with computational models of RV biomechanics in sugen-hypoxia (SuHx)-treated male, ovary-intact female, and ovariectomized female rats. Despite similar pressure overload levels, SuHx induced increases in end-diastolic elastance and passive myocardial stiffening, notably in male SuHx animals, corresponding to elevated diastolic intracellular calcium. Increases in end-systolic chamber elastance were largely explained by myocardial hypertrophy in male and ovary-intact female rats, whereas ovariectomized females exhibited contractility recruitment via calcium transient augmentation. Ovary-intact female rats primarily responded with hypertrophy, showing fewer myocardial mechanical alterations and less stiffening. These findings highlight sex-related RV remodeling differences in rats, affecting systolic and diastolic RV function in PAH. NEW & NOTEWORTHY Combining hemodynamic and morphological measurements from male, female, and ovariectomized female pulmonary arterial hypertension (PAH) rats revealed distinct adaptation mechanisms despite similar pressure overload. Males showed the most diastolic stiffening. Ovariectomized females had enhanced myocyte contractility and calcium transient upregulation. Ovary-intact females primarily responded with hypertrophy, experiencing milder passive myocardial stiffening and no changes in myocyte shortening. These findings suggest potential sex-specific pathways in right ventricular (RV) adaptation to PAH, with implications for targeted interventions.

Brugada syndrome (BrS) is a cardiac electrophysiological disease with unknown etiology, associated with sudden cardiac death. Symptomatic patients are treated with implanted cardiac defibrillator, but no risk stratification strategy is effective in patients that are at low to medium arrhythmic risk. Cardiac computational modeling is an emerging tool that can be used to verify the hypotheses of pathogenesis and inspire new risk stratification strategies. However, to obtain reliable results computational models must be validated with consistent experimental data. We reviewed the main electrophysiological and structural variables from BrS clinical studies to assess which data could be used to validate a computational approach. Activation delay in the epicardial right ventricular outflow tract is a consistent finding, as well as increased fibrosis and subclinical alterations of right ventricular functional and morphological parameters. The comparison between other electrophysiological variables is hindered by methodological differences between studies, which we commented. We conclude by presenting a recent theory unifying electrophysiological and structural substrate in BrS and illustrate how computational modeling could help translation to risk stratification., (© 2024 Wiley Periodicals LLC.)

Introduction: Right ventricular (RV) dysfunction is a significant negative prognostic indicator in human dilated cardiomyopathy (DCM). Many RV indices are weight-dependent, and there is a lack of reference values for the right heart in giant breed dogs (over 50 kg), including Great Danes (GDs). This study aimed to compare indices of RV function in echocardiographically normal GDs, those with preclinical DCM (PC-DCM), and those with DCM and congestive heart failure (DCM-CHF)., Animals: A total of 116 client-owned adult GDs: 74 normal, 31 with PC-DCM, and 11 with DCM-CHF., Methods: A retrospective, single-center cohort study assessed RV function using free-wall RV longitudinal strain (RVLS), strain rate, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and pulsed-wave tissue Doppler imaging-derived systolic myocardial velocity of the lateral tricuspid annulus (TDI S'). Relationships between DCM status and RV function indices were analyzed., Results: RV function, measured by TAPSE (P=0.001), FAC (P<0.001), and TDI S' (P<0.001), decreased in dogs with PC-DCM and DCM-CHF compared to healthy dogs, with FAC being lower in DCM-CHF compared to PC-DCM (P=0.048). RVLS impairment was more significant in the DCM-CHF group than in the PC-DCM group (P=0.048). RVLS had the highest area under the curve (0.899) for differentiating between normal and DCM-CHF dogs., Conclusion: As DCM progresses, echocardiographic variables of RV function, including TAPSE, FAC, TDI S', RVLS, and strain rate, worsen, indicating impaired RV systolic function in GDs affected by DCM., Competing Interests: Conflict of Interest Statement None of the authors have any conflict of interest of relevance for this manuscript, which are not declared in the acknowledgments., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The risk stratification of pulmonary arterial hypertension proposed by the European Society of Cardiology /European Respiratory Society guidelines in 2015 and 2022 included two to three echocardiographic indicators. However, the specific value of echocardiography in risk stratification of pre-capillary pulmonary hypertension (pcPH) has not been efficiently demonstrated. Given the complex geometry of the right ventricular (RV) and influencing factors of echocardiographic parameter, there is no single echocardiographic parameter that reliably informs about PH status. We hypothesize that a multi-parameter comprehensive index can more accurately evaluate the severity of the pcPH. The purpose of this study was to develop and validate an echocardiographic risk score model to better assist clinical identifying high risk of pcPH during initial diagnosis and follow-up., Methods: We studied 197 consecutive patients with pcPH. A multivariable echocardiographic model was constructed to predict the high risk of pcPH in the training set. Points were assigned to significant risk factors in the final model based on β-coefficients. We validated the model internally and externally., Results: The echocardiographic score was constructed by multivariable logistic regression, which showed that pericardial effusion, right atrial (RA) area, RV outflow tract proximal diameter (RVOT-Prox), the velocity time integral of the right ventricular outflow tract (TVI RVOT ) and S' were predictors of high risk of pcPH. The area under curve (AUC) of the training set of the scoring model was 0.882 (95%CI: 0.809-0.956, p < 0.0001). External validation was tested in a test dataset of 77 patients. The AUC of the external validation set was 0.852. A 10-point score risk score was generated, with scores ranging from 0 to 10 in the training cohort. The estimate risk of high risk of pcPH ranged from 25.1 to 94.6%., Conclusions: The echocardiographic risk score using five echocardiographic parameters could be comprehensive and useful to predict the high risk of pcPH for initial assessment and follow-up., (© 2024. The Author(s).)

Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.

Background: Pulmonary arterial hypertension (PAH) is characterised by poor exercise tolerance. The contribution of right ventricular (RV) diastolic function to the augmentation of cardiac output during exercise is not known. This study leverages pressure-volume ( P - V ) loop analysis to characterise the impact of RV diastology on poor flow augmentation during exercise in PAH., Methods: RV P - V loops were measured in 41 PAH patients at rest and during supine bike exercise. Patients were stratified by median change in cardiac index (CI) during exercise into two groups: high and low CI reserve. Indices of diastolic function (end-diastolic elastance ( E ed )) and ventricular interdependence (left ventricular transmural pressure (LVTMP)) were compared at matched exercise stages., Results: Compared to patients with high CI reserve, those with low reserve exhibited lower exercise stroke volume (36 versus 49 mL·m -2 ; p=0.0001), with higher associated exercise afterload (effective arterial elastance ( E a ) 1.76 versus 0.90 mmHg·mL -1 ; p<0.0001), RV stiffness ( E ed 0.68 versus 0.26 mmHg·mL -1 ; p=0.003) and right-sided pressures (right atrial pressure 14 versus 8 mmHg; p=0.002). Higher right-sided pressures led to significantly lower LV filling among the low CI reserve subjects (LVTMP -4.6 versus 3.2 mmHg; p=0.0001). Interestingly, low exercise flow reserve correlated significantly with high afterload and RV stiffness, but not with RV contractility nor RV-PA coupling., Conclusions: Patients with poor exercise CI reserve exhibit poor exercise RV afterload, stiffness and right-sided filling pressures that depress LV filling and stroke work. High afterload and RV stiffness were the best correlates to low flow reserve in PAH. Exercise unmasked significant pathophysiological PAH differences unapparent at rest., Competing Interests: Conflict of interest: T.M. Kolb serves a fiduciary role for Oxywear, Inc., activities unrelated to the current work. R.J. Tedford reports no direct conflicts of interest related to this manuscript. He is the co-chair of the PH due to left heart disease task force for the 7th World Symposium on Pulmonary Hypertension and Deputy Editor for the Journal of Heart and Lung Transplantation. He reports general disclosures to include consulting relationships with Abbott, Acorai, Aria CV Inc., Acceleron/Merck, Alleviant, Boston Scientific, Cytokinetics, Edwards LifeSciences, Gradient, Lexicon Pharmaceuticals, Medtronic and United Therapeutics. R.J. Tedford serves on a steering committee for Merck, Edwards and Abbott, as well as a research advisory board for Abiomed. He also does haemodynamic core laboratory work for Merck. P.M. Hassoun serves on a scientific steering committee for MSD and on a scientific advisory board for Aria CV, activities unrelated to the current work. The other authors have no relevant financial disclosures., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Aims: Recommendations on cardiac resynchronization therapy (CRT) in patients with atrial fibrillation or flutter (AF) are based on less robust evidence than those in sinus rhythm (SR). We aimed to assess the efficacy of CRT upgrade in the BUDAPEST-CRT Upgrade trial population by their baseline rhythm., Methods and Results: Heart failure patients with reduced ejection fraction (HFrEF) and previously implanted pacemaker (PM) or implantable cardioverter defibrillator (ICD) and ≥20% right ventricular (RV) pacing burden were randomized to CRT with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145). Primary [HF hospitalization (HFH), all-cause mortality, or <15% reduction of left ventricular end-systolic volume] and secondary outcomes were investigated. At enrolment, 131 (36%) patients had AF, who had an increased risk for HFH as compared with those with SR [adjusted hazard ratio (aHR) 2.99; 95% confidence interval (CI) 1.26-7.13; P = 0.013]. The effect of CRT-D upgrade was similar in patients with AF as in those with SR [AF adjusted odds ratio (aOR) 0.06; 95% CI 0.02-0.17; P < 0.001; SR aOR 0.13; 95% CI 0.07-0.27; P < 0.001; interaction P = 0.29] during the mean follow-up time of 12.4 months. Also, it decreased the risk of HFH or all-cause mortality (aHR 0.33; 95% CI 0.16-0.70; P = 0.003; interaction P = 0.17) and improved the echocardiographic response (left ventricular end-diastolic volume difference -49.21 mL; 95% CI -69.10 to -29.32; P < 0.001; interaction P = 0.21)., Conclusion: In HFrEF patients with AF and PM/ICD with high RV pacing burden, CRT-D upgrade decreased the risk of HFH and improved reverse remodelling when compared with ICD, similar to that seen in patients in SR., Competing Interests: Conflict of interest: B.M. reports grants from Boston Scientific, NRDIF Hungary, and National Heart Program during the conduct of the study; personal fees from Biotronik, Abbott, AstraZeneca, Novartis, and Boehringer Ingelheim; and grants from Medtronic outside the submitted work. I.O. reports lecture and advisory fees from Abbott, Biotronik, Boston Scientific, Medtronic, and Vitatron and travel grants from Abbott, Biotronik, Boston Scientific, and Medtronic. Attila K. reports grants from Bolyai Research Scholarship and FK ‘OTKA’ Research Grant from NKFIH outside the submitted work, stock from CardioSight, Inc. and stock option from Argus Cognitive, Inc. outside the submitted work, and personal fees from Argus Cognitive, Inc. and CardioSight Hungary LLC outside the submitted work. G.D. reports research grants to institution from Medtronic and Biotronik and lecture and advisory fees from Medtronic, Biotronik, and Abbott. C.F. reports support from the Semmelweis University, grants from Medtronic, consulting fees from Medtronic and Biotronik Hungary, and payment or honoraria for lectureures from Johnson and Johnson Co., Abbott Laboratories and Boehringer Ingelheim RCV GmbH and Co. L.G. reports support for the present manuscript from Vitatron Medical, Boston Scientific, Abbott Laboratories, Medtronic Hungary, and Biotronik Hungary; consulting fees from Medtronic Hungary and Abbott Hungary; honoraria; travel grants; participation on a data safety monitoring board or advisory board; and role in other board and committee (FESC, FEHRA, President of the Scientific Committee of the Hungarian Society of Cardiology, Past President of the Working Group on Cardiac Arrhythmias and Pacing, and EHRA Scientific Programme Board). Annamária K. reports grants from Bolyai Research Scholarship outside the submitted work; consulting fees from Medtronic; honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Biotronik, and Novartis; payment for expert testimony from Boehringer Ingelheim and Boston Scientific; travel grants from AstraZeneca and Novartis; participation on a data safety monitoring board or advisory board for Boehringer Ingelheim and Boston Scientific; and role in other board and committee (committee member of Hungarian Society of Cardiology and secretary of the Working Group on Cardiac Arrhythmias and Pacing, Hungarian Society of Cardiology). S.D.S. reports grants to institution from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, BMS, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI and consulting fees outside the scope of the current work from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProthera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, Akros, and Valo. R.H. reports institutional grants from Abbott, Biotronik, and Slovak Research and Development Agency; honoraria from Abbott and Medtronic; and travel grants from the European Society of Cardiology and Pfizer. He is also the president of the Slovak Heart Rhythm Association. E.M. reports grants from Novartis, Boehringer Ingelheim, and Biotronik Hungary. V.K. reports grants from Boston Scientific, ZOLL, Biotronik, Spire Inc., and NIH, consulting fees from Biotronik and Zoll, and payment or honoraria for lectures from Abbott Medical and Medtronic. The other authors declare no conflict of interest for this contribution., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Exercise imaging using current modalities can be challenging. This was patient focused study to establish the feasibility and reproducibility of exercise-cardiovascular magnetic resonance imaging (EX-CMR) acquired during continuous in-scanner exercise in asymptomatic patients with primary mitral regurgitation (MR)., Methods: This was a prospective, feasibility study. Biventricular volumes/function, aortic flow volume, MR volume (MR-Rvol) and regurgitant fraction (MR-RF) were assessed at rest and during low- (Low-EX) and moderate-intensity exercise (Mod-EX) in asymptomatic patients with primary MR., Results: Twenty-five patients completed EX-CMR without complications. Whilst there were no significant changes in the left ventricular (LV) volumes, there was a significant increase in the LVEF (rest 63 ± 5% vs. Mod-EX 68 ± 6%;p = 0.01). There was a significant reduction in the right ventricular (RV) end-systolic volume (rest 68 ml(60-75) vs. Mod-EX 46 ml(39-59);p < 0.001) and a significant increase in the RV ejection fraction (rest 55 ± 5% vs. Mod-EX 65 ± 8%;p < 0.001). Whilst overall, there were no significant group changes in the MR-Rvol and MR-RF, individual responses were variable, with MR-Rvol increasing by ≥ 15 ml in 4(16%) patients and decreasing by ≥ 15 ml in 9(36%) of patients. The intra- and inter-observer reproducibility of LV volumes and aortic flow measurements were excellent, including at Mod-EX., Conclusion: EX-CMR is feasible and reproducible in patients with primary MR. During exercise, there is an increase in the LV and RV ejection fraction, reduction in the RV end-systolic volume and a variable response of MR-Rvol and MR-RF. Understanding the individual variability in MR-Rvol and MR-RF during physiological exercise may be clinically important., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Longitudinal right ventricular free wall strain (RVFWS) has been identified as an independent prognostic marker in patients with pulmonary hypertension. Little is known however about the prognostic value of RVFWS in patients with sickle cell (SC) disease, particularly during exercise. We therefore examined the prognostic significance of RVFWS both at rest and with exercise in patients with SC disease and normal resting systolic pulmonary artery pressure (SPAP). Consecutive patients with SC disease referred for bicycle ergometer stress echocardiography (SE) were enrolled ftom July 2019 to January 2021. All patients had measurable tricuspid regurgitation velocity (TRV). Conventional echocardiography parameters, left ventricular global longitudinal strain (LVGLS), RVFWS, and ventriculoarterial coupling indices (TAPSE/SPAP and RVFWS/SPAP) were assessed at rest and peak exercise. Repeat SE was performed at a median follow-up of 2 years. The cohort consisted of 87 patients (mean age was 31 ± 11 years, 66% females). All patients had normal resting TRV < 2.8 m/s, RVFWS and LVGLS at baseline. There were 23 (26%) patients who had peak stress RVFWS < 20%. They had higher resting and peak stress TRV and SPAP, but lower resting and peak stress TAPSE/SPAP, RVFWS/SPAP, and LVGLS as well as lower peak stress cardiac output when compared to patients with peak stress RVFWS ≥ 20% (p < 0.05). Patients with baseline peak stress RVFWS < 20% had a significant decrease in exercise performance at follow-up (7.5 ± 2.7 min at baseline vs. 5.5 ± 2.8 min at follow-up, p < 0.001). In the multivariate analysis, baseline peak stress RVFWS was the only independent predictor of poorer exercise performance at follow-up [odds ratio 8.2 (1.2, 56.0), p = 0.033]. Among patients with SC disease who underwent bicycle ergometer SE, a decreased baseline value of RVFWS at peak stress predicted poorer exercise time at follow-up., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)