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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

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).)

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.)

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.)

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.)

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.)

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.)

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.)

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.

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.)

Background: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms., Methods: Patients with symptomatic-drug-refractory LVMCO were recruited for a randomized, blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical right ventricular pacing sites were assessed during an invasive hemodynamic study of multisite pacing. Patient-specific pacing-site and atrioventricular delays, defining PPoP, were selected on the basis of LVMCO gradient reduction and acceptable pacing parameters. Patients were randomized to 6 months of active PPoP or backup pacing in a crossover design. The primary outcome examined invasive gradient change with best-site pacing. Secondary outcomes assessed quality of life and exercise following randomization to PPoP., Results: A total of 17 patients were recruited; 16 of whom met primary end points. Baseline New York Heart Association was 3±0.6, despite optimal medical therapy. Hemodynamic effects were assessed during pacing at the right ventricular apex and at a mean of 8 LV sites. The gradients in all 16 patients fell with pacing, with maximum gradient reduction achieved via LV pacing in 14 (88%) patients and right ventricular apex in 2. The mean baseline gradient of 80±29 mm Hg fell to 31±21 mm Hg with best-site pacing, a 60% reduction ( P <0.0001). One cardiac vein perforation occurred in 1 case, and 15 subjects entered crossover; 2 withdrawals occurred during crossover. Of the 13 completing crossover, 9 (69%) chose active pacing in PPoP configuration as preferred setting. PPoP was associated with improved 6-minute walking test performance (328.5±99.9 versus 285.8±105.5 m; P =0.018); other outcome measures also indicated benefit with PPoP., Conclusions: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic patients with LVMCO., Registration: URL: https://clinicaltrials.gov/study; Unique Identifier: NCT03450252., Competing Interests: Prof Petersen provides Consultancy to Circle Cardiovascular Imaging Inc., Calgary, Alberta, Canada. Dr Lopes has received speaker fees from Sanofi, Alnylam, and Bristol Myers Squibb (BMS); and received a grant from BMS.

The function of the right ventricle (RV) is to drive the forward flow of blood to the pulmonary system for oxygenation before returning to the left ventricle. Due to the thin myocardium of the RV, its function is easily affected by decreased preload, contractile motion abnormalities, or increased afterload. While various etiologies can lead to changes in RV structure and function, sudden changes in RV afterload can cause acute RV failure which is associated with high mortality. Early detection and diagnosis of RV failure is imperative for guiding initial medical management. Echocardiographic findings of reduced tricuspid annular plane systolic excursion (<1.7) and RV wall motion (RV S' <10 cm/s) are quantitatively supportive of RV systolic dysfunction. Medical management commonly involves utilizing diuretics or fluids to optimize RV preload, while correcting the underlying insult to RV function. When medical management alone is insufficient, mechanical circulatory support (MCS) may be necessary. However, the utility of MCS for isolated RV failure remains poorly understood. This review outlines the differences in flow rates, effects on hemodynamics, and advantages/disadvantages of MCS devices such as intra-aortic balloon pump, Impella, centrifugal-flow right ventricular assist devices, extracorporeal membrane oxygenation, and includes a detailed review of the latest clinical trials and studies analyzing the effects of MCS devices in acute RV failure., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Purpose: The assessment of cardiac performance in septic new-borns is crucial for detecting hemodynamic instability and predicting outcome. The aim of the study is to assess myocardial performance in neonates with sepsis for the early identification of cardiac dysfunction., Patients and Methods: A case control study was carried out from September 2022 to May 2023 at the Neonatal Intensive care unit, Kasturba Medical College, Manipal. A total of 68 neonates were included in the study, with 33 females and 35 males. The study population was further subdivided into 3 groups namely preterm septic neonates (n = 21), term septic neonates (n = 10) and non-septic healthy controls (n = 37). The cardiac structure and function were assessed using conventional method, Tissue Doppler imaging (Sm) and speckle tracking echocardiography (GLS). The study was approved by the Institutional Ethics Committee at Kasturba Medical College, Manipal (approval number IEC: 90/2022). The CTRI registration number for the study is CTRI/2022/09/045437 and was approved on September 12, 2022. Prior to the neonate's enrolment, informed consent was obtained from their mothers or legal guardians., Results: Out of the total 68 neonates, 31 were cases and 37 were controls which included 33 females and 35 males. LV systolic function was not statistically significant between cases and controls. E/A ratio of the mitral valve was significantly lower in septic newborns than in healthy neonates. (1.01 ± 0.35 vs 1.18 ± 0.31, p < 0.05) preterm neonates showed significantly lower Lateral E' and RV E' velocities than term neonates. TAPSE was significantly lower in septic preterm neonates. (8.61 ± 1.28 vs. 10.7 ± 2.11, p < 0.05) No significant difference was noted in the Myocardial Performance Index between septic neonates and healthy neonates. LV Global Longitudinal Strain was slightly lower in preterm septic neonates than in term neonates with sepsis., Conclusion: Septic newborns are associated with LV diastolic dysfunction, RV systolic dysfunction and substantially higher pulmonary systolic pressures., (© 2024. The Author(s).)

To test the hypothesis that cine MRI-derived radiomics features of the cardiac blood pool can represent hemodynamic characteristics of pulmonary hypertension-heart failure with preserved ejection fraction (PH-HFpEF). Nineteen PH-HFpEF patients (9 male, 57.8 ± 14.7 years) and 19 healthy controls (13 male, 50.3 ± 13.6 years) were enrolled. All participants underwent a cardiac MRI scan. One hundred and seven radiomics features (7 classes) of the blood pool in the left and right ventricles/atrium (LV/RV/LA/RA) were extracted from 4-chamber cine (2D images) at the stages of systole, rapid filling, diastasis, and atrial contraction within a cardiac cycle. For PH-HFpEF patients, features acquired from LV/LA were related to the pulmonary capillary wedge pressure (PCWP); features acquired from RV/RA were related to the mean pulmonary artery pressure (mPAP) using the Pearson correlation coefficient (r). Logistic regression, receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to test the capability of radiomics features in discriminating 2 subject groups. Features acquired from different chambers at various periods present diverse properties in representing hemodynamic indices of PH-HFpEF. Multiple radiomics features blood pool were significantly related to PCWP and/or mPAP (r: 0.4-0.679, p < 0.05). In addition, multiple features of blood pools acquired at various time points within a cardiac cycle can efficiently discriminate PH-HFpEF from controls (individual AUC: 0.7-0.864). Cine MRI-derived radiomics features of the cardiac blood pool have the potential to characterize hemodynamic abnormalities in the context of PH-HFpEF., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Right heart output in heart failure can be compensated through increasing systemic venous pressure. We determined whether the magnitude of this "passive cardiac output" can predict LVAD outcomes., Methods: This was a retrospective review of 383 patients who received a continuous-flow LVAD at the University of Michigan between 2012 and 2021. Pre-LVAD cardiac output driven by venous pressure was determined by dividing right atrial pressure by mean pulmonary artery pressure, multiplied by total cardiac output. Normalization to body surface area led to the passive cardiac index (PasCI). The Youden J statistic was used to identify the PasCI threshold, which predicted LVAD death by 2 years., Results: Increased preoperative PasCI was associated with reduced survival (hazard ratio [HR], 2.27; P < .01), and increased risk of right ventricular failure (RVF) (HR, 3.46; P = .04). Youden analysis showed that a preoperative PasCI ≥0.5 (n = 226) predicted LVAD death (P = .10). Patients with PasCI ≥0.5 had poorer survival (P = .02), with a trend toward more heart failure readmission days (mean, 45.09 ± 67.64 vs 35.13 ± 45.02 days; P = .084) and increased gastrointestinal bleeding (29.2% vs 20.4%; P = .052). Additionally, of the 97 patients who experienced readmissions for heart failure, those with pre-LVAD implantation PasCI ≥0.5 were more likely to have more than 1 readmission (P = .05)., Conclusions: Although right heart output can be augmented by raising venous pressure, this negatively impacts end-organ function and increases heart failure readmission days. Patients with a pre-LVAD PasCI ≥0.5 have worse post-LVAD survival and increased RVF. Using the PasCI metric in isolation or incorporated into a predictive model may improve the management of LVAD candidates with RV dysfunction., (Copyright © 2023 The American Association for Thoracic Surgery. All rights reserved.)

In the Phase III PATENT-1 (NCT00810693) and CHEST-1 (NCT00855465) studies, riociguat demonstrated efficacy vs placebo in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Clinical effects were maintained at 2 years in the long-term extension studies PATENT-2 (NCT00863681) and CHEST-2 (NCT00910429). This post hoc analysis of hemodynamic data from PATENT-1 and CHEST-1 assessed whether riociguat improved right ventricular (RV) function parameters including stroke volume index (SVI), stroke volume, RV work index, and cardiac efficiency. REVEAL Risk Score (RRS) was calculated for patients stratified by SVI and right atrial pressure (RAP) at baseline and follow-up. The association between RV function parameters and SVI and RAP stratification with long-term outcomes was assessed. In PATENT-1 (n = 341) and CHEST-1 (n = 238), riociguat improved RV function parameters vs placebo (p < 0.05). At follow-up, there were significant differences in RRS between patients with favorable and unfavorable SVI and RAP, irrespective of treatment arm (p < 0.0001). Multiple RV function parameters at baseline and follow-up were associated with survival and clinical worsening-free survival (CWFS) in PATENT-2 (n = 396; p < 0.05) and CHEST-2 (n = 237). In PATENT-2, favorable SVI and RAP at follow-up only was associated with survival and CWFS (p < 0.05), while in CHEST-2, favorable SVI and RAP at baseline and follow-up were associated with survival and CWFS (p < 0.05). This post hoc analysis of PATENT and CHEST suggests that riociguat improves RV function in patients with PAH and CTEPH. [ABSTRACT FROM AUTHOR]

Background: Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure., Methods: We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves., Results: Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP., Conclusions: PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events., (© 2024. The Author(s).)

Objectives: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE., Design: All Swedish patients diagnosed with acute PE in 2005 ( n  = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 ( n  = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration., Results: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels., Conclusions: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Background: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology., Methods: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline., Results: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart., Conclusions: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function., (© 2024. The Author(s).)

Background: A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown., Objectives: This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA., Methods: This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR)., Results: A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188)., Conclusions: Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA., Competing Interests: Funding Support and Author Disclosures Dr J. von Stein has received lecture fees from Edwards Lifesciences. Dr Iliadis has received travel support from Abbott and Edwards Lifesciences; and has received consultant honoraria from Abbott and Edwards Lifesciences. Dr Kalbacher has received personal fees from Edwards Lifesciences, Abbott, and Pi-Cardio Ltd; and has received research grants and honoraria for consultation from Edwards Lifesciences. Dr Rudolph has received research grants and honoraria for consultation from Edwards Lifesciences. Dr Baldus has received honoraria for consultation from Abbott and Edwards Lifesciences. Dr Pfister has received speaker fees from Edwards Lifesciences and Abbott. Dr Körber has received travel support from JenaValve; and has received lecture fees from Edwards Lifesciences and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Right ventricular impairment is common among patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation (SMR). Adherence to guideline-directed medical therapy (GDMT) for heart failure is poor in these patients., Objectives: The aim of this study was to evaluate the impact of GDMT on long-term survival in this patient cohort., Methods: Within the EuroSMR (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation) international registry, we selected patients with SMR and right ventricular impairment (tricuspid annular plane systolic excursion ≤17 mm and/or echocardiographic right ventricular-to-pulmonary artery coupling <0.40 mm/mm Hg). Titrated guideline-directed medical therapy (GDMT tit ) was defined as a coprescription of 3 drug classes with at least one-half of the target dose at the latest follow-up. The primary outcome was all-cause mortality at 6 years., Results: Among 1,213 patients with SMR and right ventricular impairment, 852 had complete data on medical therapy. The 123 patients who were on GDMT tit showed a significantly higher long-term survival vs the 729 patients not on GDMT tit (61.8% vs 36.0%; P < 0.00001). Propensity score-matched analysis confirmed a significant association between GDMT tit and higher survival (61.0% vs 43.1%; P = 0.018). GDMT tit was an independent predictor of all-cause mortality (HR: 0.61; 95% CI: 0.39-0.93; P = 0.02 for patients on GDMT tit vs those not on GDMT tit ). Its association with better outcomes was confirmed among all subgroups analyzed., Conclusions: In patients with right ventricular impairment undergoing transcatheter edge-to-edge repair for SMR, titration of GDMT to at least one-half of the target dose is associated with a 40% lower risk of all-cause death up to 6 years and should be pursued independent of comorbidities., Competing Interests: Funding Support and Author Disclosures Dr Pfister is a consultant for Edwards Lifesciences; and has received speaker honoraria from Edwards Lifesciences and Abbott Vascular. Dr Iliadis is a consultant for Abbott and Edwards Lifesciences. Dr Kalbacher has received personal fees from Abbott, Edwards Lifesciences, and Pi-Cardia Ltd. Dr Metra has received consulting/speaker fees from Amgen, Livanova, Vifor Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards Lifesciences, and Roche Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure., Methods: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function., Results: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments., Conclusions: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction., Competing Interests: Disclosures None.

Background: The consequences of tricuspid regurgitation (TR) for right ventricular (RV) function and prognosis in pulmonary arterial hypertension (PAH) are poorly described and effects of tricuspid valve repair on the RV are difficult to predict., Methods: In 92 PAH patients with available cardiac magnetic resonance (CMR) studies, TR volume was calculated as the difference between RV stroke volume and forward stroke volume, i.e. pulmonary artery (PA) stroke volume. Survival was estimated from the time of the CMR scan to cardiopulmonary death or lung transplantation. In a subgroup, pressure-volume loop analysis including two-parallel elastances was applied to evaluate effective elastances, including net afterload (effective arterial elastance ( E a )), forward afterload (effective pulmonary arterial elastance ( E pa )) and backward afterload (effective tricuspid regurgitant elastance ( E TR )). The effects of tricuspid valve repair were simulated using the online software package Harvi., Results: 26% of PAH patients had a TR volume ≥30 mL. Greater TR volume was associated with increased N-terminal pro-brain natriuretic peptide (p=0.018), mean right atrial pressure (p<0.001) and RV end-systolic and -diastolic volume (both p<0.001). TR volume ≥30 mL was associated with a poor event-free survival (p=0.008). In comparison to E a , E pa correlated better with indices of RV dysfunction. Lower end-systolic elastance ( E es ) (p=0.002) and E TR (p=0.030), higher E pa (p=0.001) and reduced E es / E pa (p<0.001) were found in patients with a greater TR volume. Simulations predicted that tricuspid valve repair increases RV myocardial oxygen consumption in PAH patients with severe TR and low E es unless aggressive volume reduction is accomplished., Conclusions: In PAH, TR has prognostic significance and is associated with low RV contractility and RV-PA uncoupling. However, haemodynamic simulations showed detrimental consequences of tricuspid valve repair in PAH patients with low RV contractility., Competing Interests: Conflict of interest: H.J. Bogaard received research grants and lecture fees from Janssen Pharmaceuticals and MSD, and serves on an advisory board for Novartis. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD., Methods: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method., Results: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%., Conclusion: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity., (© 2024. The Author(s).)

Severe systemic right ventricular failure with tricuspid regurgitation is associated with poor prognosis. Here, we report a case of 49-year-old patient who experienced severe systemic right ventricular failure following atrial switch. We chose the surgical strategy for this challenging case using comprehensive four-dimensional imaging. The patient underwent tricuspid valve repair and cardiac resynchronization therapy and recovered with improved cardiac function and regulated tricuspid valve regurgitation., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The corresponding author K.I. has a following conflicts of interest associated with this manuscript: A Stock Option from Cardio Flow Design Inc., which delivers blood flow imaging tools.

Assessment of fetal ventricular function is mostly subjective, and currently, for the objective assessment left ventricular shortening fraction is obtained. However, this by itself is not very reliable. Hence, more tools that can provide an objective assessment are needed to increase the confidence of functional assessment. Speckle tracking imaging can provide one such tool. In this study we sought to establish the normative value of global longitudinal and circumferential strain for our fetal patients and for two major forms of congenital heart diseases, namely atrioventricular canal defects (AVC) and uncorrected dextro-transposition of the great arteries (dTGA) to act as a benchmark. The study was completed via a single center retrospective analysis on 72 fetal echocardiograms (26 normal, 15 dTGA, and 31 AVC). Tomtec Arena™ echocardiography analysis software was used for analysis. In normal fetuses, mean left ventricular (LV) global longitudinal strain (GLS) was - 22.6% (95% CI -24, -21.1) and mean right ventricular (RV) GLS was - 22.1% (95% CI -23.6, -20.6). In AVC patients LV GLS was-26.6% (95% CI -28,-25.3) and mean RV GLS was - 26.5% (95% CI -27.9,-25.2). In dTGA patients LV GLS was - 22.9% (95% CI of -24.8, -21) and RV GLS was - 21.3% (95% CI was - 23.4, -20.8). There was good intra-rater reliability though poor to fair inter-rater reliability. Notwithstanding its current limitations, strain imaging can provide useful information that can increase confidence of cardiac functional assessment in fetal patients. However, to be reliable across the board, further automation and standardization is required., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Echocardiographic studies indicate South Asian people have smaller ventricular volumes, lower mass and more concentric remodelling than White European people, but there are no data using cardiac MRI (CMR). We aimed to compare CMR quantified cardiac structure and function in White European and South Asian people., Methods: Healthy White European and South Asian participants in the UK Biobank Imaging CMR sub-study were identified by excluding those with a history of cardiovascular disease, hypertension, obesity or diabetes. Ethnic groups were matched by age and sex. Cardiac volumes, mass and feature tracking strain were compared., Results: 121 matched pairs (77 male/44 female, mean age 58 ± 8 years) of South Asian and White European participants were included. South Asian males and females had smaller absolute but not indexed left ventricular (LV) volumes, and smaller absolute and indexed right ventricular volumes, with lower absolute and indexed LV mass and lower LV mass:volume than White European participants. Although there were no differences in ventricular or atrial ejection fractions, LV global longitudinal strain was higher in South Asian females than White European females but not males, and global circumferential strain was higher in both male and South Asian females than White European females. Peak early diastolic strain rates were higher in South Asian versus White European males, but not different between South Asian and White European females., Conclusions: Contrary to echocardiographic studies, South Asian participants in the UK Biobank study had less concentric remodelling and higher global circumferential strain than White European subjects. These findings emphasise the importance of sex- and ethnic- specific normal ranges for cardiac volumes and function., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is commonly associated with unfavorable cardiovascular outcomes and remains the leading cause of mortality in individuals with end-stage renal disease (ESRD). Despite substantial knowledge about the impact of CKD on the left heart, the right heart, which holds significant clinical relevance, has often been overlooked and inadequately assessed in ESRD patients who have undergone kidney transplant (KTx). This study aimed to evaluate the effects of KTx on the right heart chambers in ESRD patients. 57 adult KTx candidates were enrolled in this prospective longitudinal study, while 49 of them were included in the final assessment. Patients underwent a comprehensive cardiac assessment, including conventional echocardiography, speckle tracking echocardiography, and three-dimensional heart modeling both before and after surgery. Echocardiographic assessments showed significant increases in right ventricular (RV) ejection fraction, RV fractional area change (RVFAC), tricuspid annular plain systolic excursion, RV fractional shortening, right atrial (RA) reservoir, conduit, and booster strains, and RV global longitudinal strain (RVGLS). Moreover, significant reductions in RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume, RV end-diastolic diameter (RVEDD) in mid-cavity view, systolic pulmonary artery pressure was observed (all P values < 0.05). However, no significant difference was found in S velocity, as well as RVEDD in basal and apex-to-annulus view. Moreover, pre-KTx measurements of RVGLS, RVEDD (apex-to-annulus diameter), RV fractional shortening, and S velocity were predictors of RVGLS after KTx. RA conduit strain was also identified as a predictor of RA conduit strain after KTx. Additionally, age, RVEDV, RVESV, RVFAC, and RA reservoir strain before KTx were identified as independent predictors of RA reservoir strain after KTx. The findings of this study demonstrate a significant improvement in right heart function following KTx. Furthermore, strain analysis can provide valuable insights for predicting right heart function after KTx., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated., Methods: This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study., Results: The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact., Conclusions: With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321)., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Cardiovascular magnetic resonance (CMR) has established itself as the gold standard for serial assessment of systemic right ventricular (RV) performance but due to the lack of standardized RV reference values for hypoplastic left heart syndrome (HLHS) patients, the interpretation of RV volumetric data in HLHS remains difficult. Therefore, this study aimed to close this gap by providing CMR reference values for the systemic RV in HLHS patients., Methods: CMR scans of 160 children, adolescents, and young adults (age range 2.2-25.2 years, 106 males) with HLHS were retrospectively evaluated. All patients were studied following total cavopulmonary connection. Short-axis stacks were used to measure RV end-diastolic and end-systolic volumes (RVEDV, RVESV), RV stroke volume (RVSV), RV ejection fraction (RVEF), and RV end-diastolic myocardial mass (RVEDMM). Univariable and multiple linear regression analyses were performed to assess associations between RV parameters and demographic and anthropometric characteristics. Following the results of the regression analysis, reference graphs and tables were created with the Lambda-Mu-Sigma method., Results: Multiple linear regression analysis showed strong associations between body height and RVEDV, RVESV as well as RVSV. Age was highly associated with RVEDMM. Therefore, percentile curves and tables were created with respect to body height (RVEDV, RVESV, RVSV) and age (RVEDMM). The influence of demographic and anthropometric parameters on RVEF was mild, thus no percentile curves and tables for RVEF are provided., Conclusion: We were able to define CMR reference values for RV volumetric variables for HLHS patients. These data might be useful for the assessment and interpretation of CMR scans in these patients and for research in this field., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To assess flow energy loss (EL) pattern inside the pulmonary circulation in adult patients with repaired tetralogy of Fallot (TOF), particularly in TOF with pulmonary stenosis (PS) and pulmonary regurgitation (PR), as a cardiac workload parameter and its relationship to symptoms and major adverse cardiovascular events (MACE)., Methods: Prospectively, 51 consecutive TOF adults after intracardiac repair, who underwent four-dimensional flow magnetic resonance imaging, were enrolled. All of them had significant PR (PR regurgitant fraction >25 %). TOF patients who had already reached the conventional criteria were excluded. We defined MACE as the following: 1) fatal arrhythmias, 2) sudden cardiac death, 3) surgical pulmonary valvular repair (PVR), 4) right heart failure (HF) needing diuretics and/or hospitalization within 2 years., Results: A total of 15 patients had MACE; 1) 10 patients underwent PVR within 2 years, 2) 2 patients had ventricular tachycardia, and 3) 6 patients developed right HF (overlapped). Right ventricular (RV) end diastolic volume index (EDVI), RV end systolic volume index (ESVI), average EL/cardiac output (CO), and diastolic EL/CO in patients with MACE were greater than ones without MACE. On a multivariate logistic analysis, the diastolic EL/CO ratio and RVEDVI had the highest odds with MACE in all TOF (odds ratio, 40.7 and 1.15. 95%CI, 1.83-905 and 1.02-13.0; p-value, 0.02 and 0.03). In sub-analysis within 29 patients with moderate PS with PR, and 10 patients with MACE showed higher diastolic EL/CO. Average and diastolic EL/CO negatively correlated with RV ejection fraction (EF) in this sub-analysis., Conclusions: High EL, particularly, high diastolic EL/CO, were the important factors for MACE in adult TOF. Higher diastolic EL/CO was also related to lower RV EF and deteriorated RV function in adult TOF with PS and PR. Right-sided EL can be a sensitive marker of excessive cardiac workload which integrates both afterload and preload in adult patients with TOF, beyond the RV size., Competing Interests: Declaration of competing interest The authors except for K.I. report no relationships that could be construed as a conflict of interest. K.I. has a stock option in Cardio Flow Design Inc., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: We assessed the safety profile of tricuspid transcatheter edge-to-edge repair (TEER) in patients with right ventricular (RV) dysfunction., Methods: We identified patients undergoing TEER to treat tricuspid regurgitation from June 2015 to October 2021 and assessed tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RVFAC). RV dysfunction was defined as TAPSE <17 mm and RVFAC <35%. The primary end point was 30-day mortality after TEER. We also investigated the change in the RV function in the early phase and clinical outcomes at 2 years., Results: The study participants (n=262) were at high surgical risk (EuroSCORE II, 6.2% [interquartile range, 4.0%-10.3%]). Among them, 44 patients met the criteria of RV dysfunction. Thirty-day mortality was 3.2% in patients with normal RV function and 2.3% in patients with RV dysfunction ( P =0.99). Tricuspid regurgitation reduction to ≤2+ was consistently achieved irrespective of RV dysfunction (76.5% versus 70.5%; P =0.44). TAPSE and RVFAC declined after TEER in patients with normal RV function (TAPSE, 19.0±4.7 to 17.9±4.5 mm; P =0.001; RVFAC, 46.2%±8.1% to 40.3%±9.7%; P <0.001). In contrast, those parameters were unchanged or tended to increase in patients with RV dysfunction (TAPSE, 13.2±2.3 to 15.3±4.7 mm; P =0.011; RVFAC, 29.6%±4.1% to 31.6%±8.3%; P =0.14). Two years after TEER, compared with patients with normal RV function, patients with RV dysfunction had significantly higher mortality (27.0% versus 56.3%; P <0.001)., Conclusions: TEER was safe and feasible to treat tricuspid regurgitation in patients with RV dysfunction. The decline in the RV function was observed in patients with normal RV function but not in patients with RV dysfunction., Competing Interests: Disclosures Dr Tanaka received a grant from the Japanese College of Cardiology and the Uehara Memorial Foundation and honoraria from Canon Medical Systems. Dr Nickenig received research funding from the Deutsche Forschungsgemeinschaft, the German Federal Ministry of Education and Research, Abbott, Edwards Lifesciences, Medtronic, and St. Jude Medical and honoraria for lectures or advisory boards from Abbott, Edwards Lifesciences, Medtronic, and St. Jude Medical. Dr Weber received lecture or proctoring fees from Abbott and Edwards Lifesciences. Dr Sugiura received honoraria for lectures from Abbott and Edwards Lifesciences. The other authors report no conflicts.

Introduction: Biventricular pacing (BiVp) improves outcomes in systolic heart failure patients with electrical dyssynchrony. BiVp is delivered from epicardial left ventricular (LV) and endocardial right ventricular (RV) electrodes. Acute electrical activation changes with different LV-RV stimulation offsets can help guide individually optimized BiVp programming. We sought to study the BiVp ventricular activation with different LV-RV offsets and compare with 12-lead ECG., Methods: In five patients with BiVp (63 ± 17-year-old, 80% male, LV ejection fraction 27 ± 6%), we evaluated acute ventricular epicardial activation, varying LV-RV offsets in 20 ms increments from -40 to 80 ms, using electrocardiographic imaging (ECGI) to obtain absolute ventricular electrical uncoupling (VEUabs, absolute difference in average LV and average RV activation time) and total activation time (TAT). For each patient, we calculated the correlation between ECGI and corresponding ECG (3D-QRS-area and QRS duration) with different LV-RV offsets., Results: The LV-RV offset to attain minimum VEUabs in individual patients ranged 20-60 ms. In all patients, a larger LV-RV offset was required to achieve minimum VEUabs (36 ± 17 ms) or 3D-QRS-area (40 ± 14 ms) than that for minimum TAT (-4 ± 9 ms) or QRS duration (-8 ± 11 ms). In individual patients, 3D-QRS-area correlated with VEUabs (r 0.65 ± 0.24) and QRS duration correlated with TAT (r 0.95 ± 0.02). Minimum VEUabs and minimum 3D-QRS-area were obtained by LV-RV offset within 20 ms of each other in all five patients., Conclusions: LV-RV electrical uncoupling, as assessed by ECGI, can be minimized by optimizing LV-RV stimulation offset. 3D-QRS-area is a surrogate to identify LV-RV offset that minimizes LV-RV uncoupling., (© 2024 Wiley Periodicals LLC.)

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH., (© 2024. The Author(s).)