Right Ventricular Function Research Articles

Acute changes of right ventricular longitudinal strain after transcatheter edge-to-edge repair in patients with functional mitral regurgitation

Abstract Background Transcatheter edge-to-edge repair (TEER) is a valid therapeutic option in symptomatic patients with severe secondary mitral valve regurgitation (SMR) at high surgical risk. While right ventricular (RV) dysfunction is a predictor of poor outcomes in this context, TEER may lead to an improvement of RV function which portends a better outcome. Purpose The aim of this study was to investigate acute change in RV function and its prognostic implication after successful TEER in patients with severe SMR. Methods Patients with severe SMR who underwent TEER from 2013 to 2021 at our center were retrospectively screened. Only patients with successful procedure (MR ≤ grade 2) and adequate echocardiographic images for longitudinal strain assessment were enrolled. RV function was estimated at baseline and pre-discharge by echocardiographic evaluation; RV global longitudinal strain (RVGLS) and RV free wall longitudinal strain (RVFWLS) were assessed before and after TEER. Longitudinal strain improvement was defined as an increase of post procedural strain greater than median value variation. Population was then divided in two groups based on RVGLS significant improvement. The primary outcome was a composite of all-cause death, heart transplantation (HT) and left ventricular assist device (LVAD) implantation during follow-up, assessed with Kaplan-Maier curves and compared by log-rank test. Results A total of 61 patients were included. Mean age was 70±10 years, 89% patients were symptomatic with NYHA class 3-4, mean furosemide daily dose was 200±146 mg. Pre-TEER median left ventricle ejection fraction (LVEF) was 29% [IQR, 26; 35%], RV fractional area change (FAC) was 32% [IQR 26; 37%] and tricuspid anulus plan systolic excursion (TAPSE) was 17 mm [IQR 14; 20 mm]. Median RVGLS and RVFWLS at baseline were respectively -11% [IQR -13; -9%] and -14% [IQR -17; -11%]. After TEER a significant variation of RVGLS and RVFWLS was observed (RVGLS: -13% [IQR -15; -10%] p 0.012; RVFWLS: -16% [-19; - 13%] p 0.001). Moreover, a significant reduction in estimated systolic pulmonary artery pressure (sPAP) between baseline (45 mmHg [IQR 35; 55mmHg]) and post TEER (40 mmHg [IQR 30;45 mmHg] p <0.001) was observed. Median improvement of RVGLS was 1.3%. After mean follow up time of 55±7 months event rate for the combined primary endpoint was numerically lower in the improved RVGLS group, although the difference was not statistically significant (p 0.243). Interestingly, rate of HT was significantly lower in RVGLS-improved group (p 0.032). Conclusions This study showed significant pre-discharge improvement of RV longitudinal strain in patient with severe SMR after successful TEER. At follow-up this improvement did not affect the outcome in terms of freedom from composite endpoint of all-cause death, HT or LVAD implantation but events were numerically lower in patients with strain improvement. Further data on larger population are needed to confirm our observations.Table 1,2Figure 1,2

Right heart function in isolated severe tricuspid regurgitation. a new stratification approach by Speckle tracking echocardiography

Abstract Background Optimal management of severe tricuspid regurgitation (TR) remains controversial. While right ventricular (RV) systolic function is an established prognostic marker of outcomes, the potential role of right atrial (RA) function is unknown. Purpose to evaluate the clinical utility of combining RV and RA strain by Speckle-tracking echocardiography to assess RV and RA function for prediction of cardiovascular outcomes. Methods Consecutive patients with at least severe TR (severe, massive or torrential TR) evaluated in the Heart Valve Clinic were prospectively included following a comprehensive clinical protocol. Consecutive control subjects and patients with permanent atrial fibrillation were included for comparison. An independent cohort of patients was included for external validation. RA and RV mechanics analysis was performed using a novel, automated 2D strain analytical software. A combined endpoint of hospital admission due to heart failure (HF) or all-cause mortality was defined. Results 176 patients with at least severe TR, 20 AF patients and 20 control subjects were included in this study. Patients with TR showed lower RA reservoir strain (RASr) and RV-free wall longitudinal strain (RV-FWLS) compared to controls and to AF patients (p<0,001). After a median follow-up of 2,2 years (IQR: 12-41 months), 38% reached the combined endpoint. Reservoir RA strain (RASr) and RV-FWLS were predictors of outcomes independently of TR severity and RV dimensions in a multivariate Cox analysis (table, model 1). RA strain showed incremental value to RV strain. Conventional parameters of RV function were not predictive of events. RV-FWLS>-20% and RASr <10% identified patients with a higher event rate (p<0,001). The combination of abnormal values of RA and RV strain (STREI stratification) stratified 4 different groups of risk independently of TR severity, RV dimensions and clinical status (adj HR per stratum 1,89 (1,4-2,34), p<0,001) (table-model 2 and figure). Pre-defined cut-off values achieved similar prognostic performance in the validation cohort (n=50). Conclusion Clinical outcomes demonstrate that strain parameters are superior to conventional indices of RV function in patients with at least severe TR. The combination of RA and RV strain stratify better patients’ risk, reflecting a broader effect of TR on right heart chambers.STREI STRATIFICATION.Cox regression analysis

The effect of iron deficiency on RV function in acute decompensated heart failure patients

Abstract Background Iron deficiency is a major problem in heart failure (HF) patients. Although the negative impact of iron deficiency on left ventricular (LV) function is known, the effect on right ventricle function (RV) is unclear. In this study we aimed to investigate the effect of iron deficiency on RV function. Material and Methods A hundred patients hospitalized with acute decompensated HF (ADHF) regardless of LV ejection fraction (LVEF) were included in our study. The primary outcome was association between iron deficiency and TAPSE, RVEF, RV FAC, and RV TDI S’. The secondary outcome was impact of iron deficiency on RV free wall global longitudinal strain (GLS). Results The mean age of study population was 70±10 years-old and 64% were male. The prevalence of hypertension (HT), diabetes mellitus (DM), ischemic heart disease (IHD), chronic obstructive pulmonary disease (COPD) was 80%, 52%, 71%, and 18%, respectively. While the median LVEF was 35%, the proportion of patients with reduced EF (HFrEF), mildly-reduced EF (HFmrEF), and preserved EF (HFpEF) was 66%, 6% and 28%, respectively. On transthoracic echocardiography the median TAPSE was 16.4 mm, the mean FAC %37,2±7.8, the mean RV GLS %-16.4±5.1, and the mean RV TDI S’ was 10.6±2,9 cm per second. More than half of the patients (58%) had iron deficiency. There was no difference between patients with or without iron deficiency on neither demographics nor LVEF, RV FAC, RV TDI S’ and systolic pulmonary artery pressure (sPAP). The TAPSE (15.6 vs 17.2 mm, p = 0.05) and RV free wall GLS (-14.7% vs -18.2%, p = 0.005) was lower in HF patient with iron deficiency. Anemia was present in 56% of the patients and both TAPSE (15.3 vs 17.3 mm, p = 0.01) and RV GLS (-14.7% vs -18.6%, p = 0.01) were lower in patients with anemia. Conclusion RV dysfunction accompanying LV dysfunction adversely affects the prognosis. In patients with ADHF, iron deficiency causes subclinical RV dysfunction namely decreased RV free wall GLS before the right ventricle systolic functions parameters commonly used on echocardiography (RVEF, TAPSE, RV FAC, RV TDI S’) in daily practice deteriorate. In conclusion, screening for iron deficiency in HF patients facilitates early detection and treatment of iron deficiency which prevents RV dysfunction with iron replacement.Table 1Table 2

Catheter-directed therapies impact on intermediate-high- and high-risk pulmonary embolism patients

Abstract Introduction Intermediate-high- and high-risk pulmonary embolism (PE) patients treated with anticoagulation alone are associated with a considerable risk of circulatory collapse, death, or long-term pulmonary hypertension. Pulmonary Embolism Response Teams (PERT) have been created to deliver PE patients a better care. Catheter Directed Therapies (CDT), with mechanical thrombolysis and/or local fibrinolysis allow faster reperfusion and hemodynamic improvement without the systemic hemorrhagic effects of systemic fibrinolysis. The clinical evidence of its benefits is lacking. Objectives This analysis aims to describe the hemodynamics, morphological and perfusion improvement in intermediate-high- and high-risk acute PE patients submitted to CDT. Methods Prospective registry of consecutive intermediate-high- and high-risk PE patients submitted to CDT (mechanical thrombolysis with PenumbraÔ aspiration system and/or intrapulmonary local fibrinolysis with alteplase) in a single tertiary center. A multiparametric follow-up protocol was designed to evaluate echocardiographic, CT-scan, pulmonary angiogram, and right heart catheterization data at admission and at 3 months after CDT. The paired samples t-Test was used for the analysis of the variables. Results 26 PE patients (42.3% male, mean age 59 years old) were submitted to CDT (19% combined Penumbra and local fibrinolysis, 12% isolated Penumbra and 69% isolated local fibrinolysis). Baseline characteristics, laboratorial, imaging and procedure data are summarized in the figure 1. No major bleeding was seen during or after the procedure. 1 pulmonary artery dissection and 1 Penumbra burr partial avulsion occurred, both with conservative treatment with good result. 3 patients died during the follow-up (1 for oncologic disease, 1 for septic shock and 1 after discharge with undetermined cause). Of the remaining, 18 patients completed the 3-month follow-up protocol. At 3 months, a significant improvement was seen in the patients’ hemodynamics with 3.3mmHg mean drop of RA pressure (p 0.007), 16.1mmHg mean drop of systolic PA pressure (p <0.001), 8.0mmHg mean drop of mean PA pressure (p<0.001), 1.4L/min and 0.7L/min/m2 mean increases in cardiac output and index (p 0.003, p 0.001), and a tendency to a 0.8 Wood units decrease in the pulmonary vascular resistance (p 0.093). It was also seen an improvement in the perfusion defects with a mean drop of 7.9 points in the modified Miller index (p <0.001) and an improvement in the RV function with a mean decrease of 0.5 in the RV/LV ratio by CT-scan (p <0.001), a mean increase of 5.6mm in TAPSE (p <0.001) and a decrease of median NT-proBNP levels in 2866pg/ml (p <0.001). Conclusions In patients with intermediate-high- and high-risk PE, the use of CDT with mechanical thrombolysis and/or local fibrinolysis is safe and associated with improvement in hemodynamics, RV function and perfusion defects.Table 1.baseline characteristicsTable 2.results

Right ventricular-pulmonary artery coupling in the early stages of infarction could optimize patient risk stratification over five years

Abstract Background Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in heart failure (HF) patients. Myocardial infarction (MI) is often followed by unrecognized RV dysfunction, which can be associated with worse outcome. It is recently shown that the ratio between TAPSE and PASP (RV/PA) may depict cardiopulmonary hemodynamics better than the two parameters alone. Aim To evaluate the interactions between left ventricular (LV) and RV function in early phase of MI and to assess the prognostic significance of RV/PA coupling in patients with first MI during 5 years follow up. Methods The prospective study included 144 patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI. LV function analysis included: LV ejection fraction (EF), ratio between early diastolic velocity and tissue annular velocity (E/e) and global longitudinal strain (GLS). RV function and RV-PA interaction was expressed as ratio between TAPSE and PASP. During the five-year follow-up, major cardiovascular events and especially hospitalization for HF were analyzed. Results Progressive RV/PA uncoupling was associated with higher degree of LV impairment and dysfunction (EF p<0.001, E/e p=0.002, GLS p<0.001) and severity of mitral regurgitation (p=0.013). Lower baseline RV/PA coupling significantly reflects the frequency of hospitalizations for HF in the population of patients with first MI during five-year follow-up (0.62 v.s.0.51, p=0.021). After multivariate adjustment RV/PA remained an independent predictor of all major cardiac events (MACE) after five years (OR 14.0 [1.5–130.8], p=0.019). Conclusion A lower baseline RV-PA coupling, reflecting a higher degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with decline of LV function in early phase of MI, and is independently associated with worse prognosis after five years. The value of RV-PA ratio as an prognstic marker warrants further investigation.

Chronic kidney disease and survival of patients with tricuspid regurgitation

Abstract Introduction Chronic kidney disease (CKD) patients are under-represented in clinical trials examining transcatheter interventions for tricuspid regurgitation (TR). The purpose of the current analysis was to investigate how CKD modifies the association of severe TR with overall survival. Methods Consecutive echocardiographic reports linked to clinical data from the largest medical center in Israel (2007-2022) were reviewed. Patients were dichotomized into four mutually exclusive TR groups (none/trivial, mild, moderate and severe), following by stratification according to CKD stage classification. The primary outcome was all-cause mortality. Kaplan Meier, Multivariate Cox regression and interaction analysis models were applied. Results Final study population included 78,147 patients with a median age of 67 (IQR: 55-78 years), 2,989 (4%) of whom had severe TR. There were 19,910 (25%) patients with estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2, 14,359 (18%) with eGFR between 30-60 and 5,551 (7%) with eGFR <30. During a median follow-up period of 4 years (IQR: 1-7 years), 28,112 patients (36%) died. Kaplan-Meier survival analysis demonstrated an increased risk of death with both increasing severity of TR and/or CKD grade (log-rank p<.001 for both). Multivariate Cox analysis with adjustment for age, sex, left heart disease and pulmonary pressures demonstrated that compared to the none/trivial group, patients with severe TR were 38% more likely to die during follow up (95% CI 1.30-1.47, p<.001). The association of tricuspid regurgitation with poor survival was CKD-dependent, such that in the eGFR>60 group severe TR was associated with 19% increased risk of death, whereas among patients with eGFR<60 the risk was significantly higher and reached 34% in the same multivariate model (p for interaction <.001). Interestingly, the modification effect of CKD was mediated by RV function, such that the interaction analysis was no longer significant when RV function was incorporated into the multivariate model. Sub analysis limited to patients with isolated TR yielded consisted results. Conclusions While the association of severe TR with poor survival is consistent across all CKD groups, it is more pronounced among patients with advanced CKD. This association may be modulated through right ventricular function. When examining data and outcome of tricuspid clinical trials , special emphasis should be given to CKD status.Consort like figureHR modification by CKD

Artificial intelligence-driven echocardiographic classification identifies Brugada Syndrome patients at higher arrhythmic risk

Abstract Background Mounting evidence exists to support the hypothesis that patients with Brugada Syndrome (BrS) present morphological and structural anomalies localized to the right ventricle (RV), but this has not been investigated in a large cohort and the association with clinical outcomes are unknown. Purpose To investigate the role of echocardiography-derived RV parameters in a large, single-center cohort of patients with BrS. Methods We prospectively enrolled n=492 consecutive patients (379 males, 77%; age 46±14 years) with confirmed BrS who underwent an echocardiogram during their last visit at the outpatient clinic for inherited arrhythmogenic disorders. Comprehensive 2D and color Doppler echocardiographic evaluation was performed using the standard clinical protocol. Unsupervised clustering analysis using cluster package sorted body surface area-corrected morphological (RVOT linear dimensions and RV diastolic area) and functional measurements of RV (fractional area shortening [FAC], tricuspid annular plane systolic excursion [TAPSE]), blinded to other variables. We performed clustering with a hierarchical cluster algorithm (h-cluster) and the optimal number of clusters (k=2) was determined using fviz_nbclust-derived plots. Results All n=492 patients were classified into 2 stable clusters () with the best robustness. The Cluster 1 echocardiograms exhibited normal RV morphological and functional parameters. The Cluster 2 echocardiograms showed a dilatation of the RVOT (PLAX 17.2±2.1 vs. 15.6±2.1, p<0.001; PSAX 18.3±2.2 vs. 16.9±2.2, p<0.001) compared to Cluster 1, while the RV diastolic area was not different (9.9±1.5 vs. 9.9±1.6, p=0.801). Importantly, RV function as assessed by TAPSE was not different between the two groups, but Cluster 2 patients showed a significantly impaired radial contraction (RV FAC 40.1±3.4% vs. 48.6±3.8%, p<0.001). We then investigated the clinical characteristics of patients based on clusters. Patients in Cluster 1 were younger (43.2±12.8 years vs. 47.5±14.0 years, p<0.001) and had significantly less arrhythmic symptoms such as syncope (13% vs. 20%, p=0.046) and life-threatening arrhythmic events (2% vs. 7%, p=0.017). Importantly, no significant differences in terms of gender (77% males in both groups, p=1.000), pattern type (43% with spontaneous type 1 pattern in Cluster 1 vs. 47%, p=0.494) nor genetic status were observed. Multivariate logistic regression confirmed that at parity of age and arrhythmic syncope, Cluster 2 was independently associated with an increased incidence of life-threatening arrhythmic events (odds ratio 3.71, 95% confidence interval 1.31-10.53, p=0.039). Conclusions We constructed a novel, echocardiography-guided classification of patients with BrS using unsupervised clustering analysis. Our data suggest that RV structural abnormalities are associated with a higher incidence of life-threatening arrhythmic events in patients with BrS, independently of arrhythmic syncope or age.

Right ventricular pressure-strain-volume loop-derived myocardial work for the noninvasive assessment of volume overload-induced dysfunction in patients with secondary tricuspid regurgitation

Abstract Development of secondary tricuspid regurgitation (TR) is associated with poor outcomes in patients with left-sided cardiac diseases. Severe TR imposes substantial volume overload (VO) on the right ventricle (RV), inducing a vicious circle of progressive RV remodelling and dysfunction. Although previous studies have established the value of speckle tracking echocardiography (STE)-derived strain and pressure-strain loop-derived myocardial work indices, these metrics neglect chamber geometry, limiting their utility in conditions accompanied by VO. Accordingly, we aimed to (1) incorporate instantaneous RV volume into myocardial work calculation to define a method capable of detecting VO-induced RV dysfunction using 3D echocardiography (3DE) and (2) to test its prognostic power in patients with secondary TR. We enrolled 195 patients (age: 64±15 years, 69% male) with left-sided cardiac diseases and followed them for a median of 42 months. The primary endpoint was all-cause mortality. TR severity was graded according to current guidelines and we compared patients with significant (moderate+) TR (sTR, n=85) versus non-significant TR (nsTR, n=110). All patients underwent 3DE to measure left (LV), and RV volumes and ejection fractions (EF). A reference RV pressure curve was constructed using previously acquired right heart catheterization data and was individually adjusted by non-invasively estimated RV pressures. To obtain RV pressure-strain loops and global myocardial work index (GMWI), RV pressure and 3DE-derived RV circumferential strain tracings were concatenated. We further adjusted GMWI to instantaneous RV volumes (GMWIV) and constructed pressure-strain-volume loops (Figure 1). Twenty-three patients (11.8%) died during follow-up (16 out of 85 in the sTR group, and 7 out of 110 in the nsTR group). There were no differences in LV and RV volumes and EFs between the sTR and nsTR groups. Interestingly, patients with sTR had significantly higher values of GMWI (sTR vs. nsTR; 667 [438-879] vs. 567 [414-770] mmHg%, p=0.01), whereas GMWIV (292 [169-467] vs. 282 [170-399] mmHg%/mL, p=0.57) did not show difference. We compared patients with versus without adverse outcomes within the sTR group. Patients with sTR who died, presented with significantly lower volume-adjusted GMWIV values (dead vs. alive; 158 [122-332] vs. 312 [207-502] mmHg%/mL, p=0.02), while GMWI did not differ. By Cox regression analysis, GMWIV (hazard ratio [95% CI]: 0.997 [0.994-1.000], p<0.05) was a significant predictor of all-cause mortality in the entire population, whereas GMWI was not. By integrating RV volume into the pressure-strain relationship, our novel metric could detect the detrimental effects of VO on RV function with prognostic implications in patients with secondary TR. Our approach can be able to capture VO-induced subclinical RV dysfunction that conventional echocardiographic metrics could not unveil.Figure 1

Assessment of global and segmental strain in heterozygous APE1/Ref-1 transgenic mice using cardiac magnetic resonance imaging

Abstract Background Apurinic/apyrimidinic-endonuclease1(APE1/Ref-1) is a redox factor necessary for DNA binding and transcription regulator in ROS generation. The association between APE1/Ref-1 and heart failure(HF) has been observed in previous studies. Heterozygous APE1/Ref-1 transgenic mice displayed endothelial cell dysfunction with systemic hypertension. Global strain(GS) measures the myocardium's deformation along its axis and is known to be a sensitive marker of subclinical HF in hypertensive patients with preserved ejection fraction. Purpose This study aims to investigate the functional dynamics and GS of the heart in heterozygous APE1/Ref-1 mice to help identify the association between APE1/Ref-1 and early signs of HF and translate to clinical applications. Methods A study was conducted to assess the functional parameters of both the left ventricle(LV) and right ventricle (RV) and perform LV global and segmental strain analysis using cardiac magnetic resonance imaging(CMR) in heterozygous APE1/Ref-1 transgenic mice(n=4) and wild type mice (n=4) of age 10-12 weeks. A 7T CMR scanner and FSE T1 sequence were used to acquire short-axis views of mouse cardiac images. LV and RV functional parameters including ejection fraction(EF), stroke volume(SV), cardiac output, peak filling rate, peak emptying rate and strain indices including global circumferential strain, global radial strain, segmental circumferential strain, and segmental radial strain were calculated with a software dedicated to analyzing CMR images. Global LV and RV function was quantified both manually and using an AI-based algorithm of LV and RV segmentation. The strain analysis was performed using the strain medical image tracking toolbox module. Additionally, reproducibility testing was done to validate the accuracy of AI-driven calculations. Results We found that heterozygous APE1/Ref-1 mice displayed a decrease in SV(8.00±0.01ul vs 9.75±0.96ul, p=0.01) and LVEF(58.75±2.63% vs 66.50±2.89%, p=0.007) compared to controls while the functional parameters of RV were similar. Interestingly, the circumferential strain rate of LV was significantly reduced in APE1/Ref-1 mice compared to controls(p<0.001), particularly in the systolic phase. In addition, the study showed that manually-calculated and AI-derived indices were within an acceptable margin of error, rendering the AI system reproducible and reliable in calculating volumetric parameters and strain of the mice's hearts. Conclusions This study demonstrated that LV global circumferential strain rate, along with SV and LVEF decreased in heterozygous APE1/Ref-1 transgenic mice. These parameters could serve as markers for assessing early functional changes of mice hearts in a non-invasive manner. Volumetric and strain indices measured by AI-based analysis of mouse CMR images are reproducible parameters for cardiovascular research in small animals.LV strain analysis of mice CMRTable of volumetric parameters

By using the new hemodynamic definition of pulmonary hypertension in patients with left heart disease the prognostic value of different phenotypes might be lost

Abstract Background and aims In the 2022 ECS/ERS pulmonary hypertension (PH) guidelines the threshold for increased pulmonary vascular resistance (PVR) was lowered from 3 to 2 Wood Units (WU). Consequently, in patients with PH due to left heart disease, the proportions of patients with combined pre- and postcapillary PH (CpcPH) will increase while the proportion with isolated post-capillary PH (IpcPH) will decrease. In the present study we investigate in patients with left heart disease the impact of this revision in terms of hemodynamic profile, right ventricular (RV) function and prognostication. Methods. Two-hundred and two patients consecutively referred for heart transplant or heart failure work-up were included with right heart catheterization and echocardiography within 48 hours. RV dysfunction was graded using a novel echocardiographic score allocating one point each for (1) systolic pulmonary artery pressure (PAP) >40 mmHg, (2) reduced tricuspid annular plane systolic excursion (TAPSE<17 mm), (3) RV area dilatation, (4) moderate/severe tricuspid regurgitation and (5) reduced inferior cava collapsibility. For assessment of prognostication, we studied the end-point of all-cause mortality. Results. One-hundred and seventy-three patients (86%) had left ventricular ejection fraction <40%. Eighty-nine patients (44%) underwent heart transplantation and the median (25%; 75% percentile) follow-up time (years) was 1.8 (0.35; 6.7). Sixty patients (30%) had mean PAP<20 mmHg, thus no PH. Ninety-six patients (48%) had IpcPH using PVR 3 WU as threshold. Lowering the threshold to PVR 2 WU decreased the corresponding proportion to 24%. The degree of backward failure (PA wedge pressure), forward failure (cardiac index) or RV dysfunction (RVD score) did not significantly differ by the change in hemodynamic definition (Table). With the previous hemodynamic definition, the Kaplan-Meier curves demonstrated increased mortality in CpcPH patients compared with IpcPH (Figure B). Using the new definition this difference was not present (Figure B). Conclusions. The revised hemodynamic definition of PH significantly increases the proportion with CpcPH, but does not significantly alter the hemodynamic or RV function profiles in left heart disease patients with IpcPH or CpcPH phenotype. However, our findings indicate that by using the new hemodynamic definition of IpcPH and CpcPH phenotype the prognostic value of this hemodynamic classification might be lost.Table

Rimeporide, a first in class Na/H exchanger-1 inhibitor, ameliorates right ventricular dysfunction and pulmonary arterial hypertension in a SuHx model

Abstract Background Pulmonary arterial hypertension (PAH) is characterized by pulmonary vasoconstriction and vascular remodeling leading to right ventricular (RV) failure. Although RV function is the major prognostic factor in PAH, no RV-specific therapies exist. The Na+/H+ exchanger type 1 (NHE1) regulates the intra- and extracellular pH balance mainly through the 1:1 exchange of intracellular H+ with extracellular Na+. Increased NHE-1 activity is involved in several diseases, including hypoxic PAH. Inhibition of NHE-1 activity attenuates pulmonary vascular remodeling in rodents exposed to hypoxia but its potential direct contribution in RV remodeling remains unclear. Aim In the current study, we aimed to investigate the effect of NHE-1 inhibition by Rimeporide a preclinical hypoxic models of PH: Sugen5416/hypoxia. Methods Sugen/hypoxia model: PAH was induced in adult Sprague-Dawley rats with a single injection of SU5416 (20 mg/kg) followed by 3 weeks of hypoxia (10% O2; Sugen/Hypoxia model: SuHx) and then return to normoxia. Control rats were injected with equal volume of vehicle. At week 5 post-injection, control and SuHx rats were treated with rimeporide (100 mg/Kg daily in drinking water, n=10/group) or placebo (n=11/group) for 3 weeks. Echocardiography and blood sampling were performed. RV phenotype was monitored by echocardiography and hemodynamic analysis. Lung and heart were collected for histological and protein expression analysis, such as NHE-1 (target of Rimeporide). Results SuHx caused severe PAH and RV dysfunction. RV dysfunction was accompanied by an increase in RV hypertrophy and RV fibrosis and PA remodeling (increase in the arteriolar wall thickness and fibrosis). A marked increase in macrophages was found in lung and RV tissues but not in LV. Moreover, Western blot analysis showed that RV protein levels of NHE-1 was higher in SuHx rats than Normoxia rats. Treatment with Rimeporide reversed SuHx-induced PAH as well as RV dysfunction and blunted pulmonary and RV inflammation, RV NHE-1 protein expression. Conclusion Our results indicate that NHE-1 levels are increased in RV tissues from SuHx-induced PAH rats. Rimeporide, through NHE-1 inhibition, might be a potential new target for treatment of RV dysfunction and PAH.

Right ventricular diastolic adaptation to pressure overload in different rat strains

Abstract Background Different rat strains are used in various animal models of pulmonary hypertension and right ventricular (RV) failure. No systematic assessment has been performed to test differences in RV response to pressure overload between rat strains. Purpose We compared RV adaptation to pulmonary trunk banding (PTB) in Wistar, Sprague Dawley, and Fischer344 rats by hemodynamic profiling focusing on diastolic function. Methods Age-matched male rat weanlings were randomized to sham operation (Wistar sham, n=5; Sprague Dawley sham, n=4; Fischer344 sham, n=4) or PTB (Wistar PTB, n=8; Sprague Dawley PTB, n=8; Fischer344 PTB, n=8). RV function was evaluated after five weeks by echocardiography, cardiac MRI, and invasive pressure-volume measurements and RV remodelling assessed by histological analyses. Results At end of study, Fischer344 rats weighed 25 % less than Wistar and Sprague Dawley rats. PTB increased RV systolic pressures four-fold, and RV failure was evident by a decrease in cardiac index (Wistar PTB: 1.8±0.2 mL/s/m2 vs. Wistar sham: 3.9±0.2 mL/s/m2, p<0.0001; Sprague Dawley PTB: 1.7±0.1 mL/s/m2 vs. Sprague Dawley sham: 3.0±0.3 mL/s/m2, p=0.0029; Fischer344 PTB: 2.1±0.2 mL/s/m2 vs. Fischer344 sham: 3.8±0.3 mL/s/m2, p<0.0001). There was a 2.4-fold increase in RV end-systolic volume index in Wistar PTB and Sprague Dawley PTB compared with sham, while Fischer344 PTB rats were less affected with only a 2.0-fold increase in RV end-systolic volume index compared with Fischer344 sham. Diastolic and right atrial impairment were evident by increased end-diastolic elastance, filling pressure, and E/e’ in PTB rats compared with sham, again Fischer344 PTB the least affected. PTB increased RV fibrosis in all groups compared with sham, though Fischer344 PTB showed a trend towards a smaller increase in RV fibrosis (Fischer344 PTB: 9.2±0.4 % vs Wistar PTB: 10.7±0.2 %, p=0.0919). Conclusions PTB caused RV failure in all rats subjected to the procedure including signs of diastolic dysfunction. Despite similar increase in RV systolic pressure, Fischer344 PTB rats showed less RV dilatation and where more able to sustain diastolic function compared with Wistar and Sprague Dawley PTB rats. All three rat strains are suitable for PTB and studies of RV failure.

Early deterioration of right ventricular strain in patients undergoing transcatheter tricuspid valve intervention

Abstract Background Severe tricuspid regurgitation (TR) leads to volume overload and increased wall stress causing detrimental right ventricular (RV) remodelling and dysfunction and is associated with excess mortality. Transcatheter tricuspid valve interventions (TTVI) emerged to treat patients with severe TR and high surgical risk, but predictors of outcome remain largely unknown. RV free wall longitudinal strain (RVFWLS) is a sensitive parameter for RV dysfunction and has shown prognostic value in patients with functional TR treated conservatively. Periinterventional changes in RVFWLS and right atrial (RA) strain have not been evaluated in patients undergoing TTVI. Purpose To analyse the effect of transcatheter tricuspid valve annuloplasty (TTVA) and transcatheter edge-to-edge repair (TEER) on RVFWLS and RA strain, assessed by speckle tracking echocardiography, and their association with outcome. Methods We retrospectively analysed consecutive patients with severe TR that underwent TTVI at our centre between 2020 and 2022. 126 patients were included (n=48 underwent TTVA with the Cardioband system, n=78 underwent TEER with the PASCAL system). Established parameters for RV function (TAPSE, FAC) as well as RVFWLS and RA reservoir strain (RASR) were analysed at baseline and one month after TTVI. Results All patients (median age 80 years, 69% female, 79% in NYHA III/IV functional class) were at prohibitive surgical risk. RV function at baseline was slightly reduced according to FAC (34% [29-39]) and preserved according to TAPSE (18mm [15-20]), whereas RVFWLS (-18.6±5.7%) and RASR (10.0% [7.0-14.0]) were severely reduced in markedly dilated right heart chambers (RV basal 45mm [41-49], RA area 34 cm2 [28-41]). TR reduction following TTVI to TR grade ≤ 2 was achieved in 77%. Right heart chamber size significantly decreased after one month (RV basal 41mm [38-45], RA area 29cm2 [25-38], P<0.001), with no improvement of FAC (37% [30-40], P=0.668) or RASR (10% [7-13], P=0.143) but deterioration of RV longitudinal function (TAPSE 17mm [13-20], P=0.002; RFWLS -16.1±5.7%, P=0.001) compared to baseline. RVFWLS reduction occurred irrespective of the procedure performed (TEER [-9.2±41.4] vs. TTVA [-7.0±31.3], P=0.783). RVFWLS deterioration occurred in 63%, whereas it improved in 37% of patients. Symptomatic and clinical outcome did not differ in patients with deteriorated vs. improved RVFWLS (improvement of at least one NYHA class 61.9% vs. 58.3%, P=0.569, one-year mortality 13.7% vs. 12.3%, P=0.940, one-year heart failure rehospitalization 10.8% vs. 17.1%, P=0.701). Conclusion Deterioration of RVFWLS after TTVI possibly reflects the decreased wall stress due to TR and consecutive preload reduction. However, symptomatic and clinical outcomes did not differ in patients with deteriorated RVFWLS vs. patients with improved RVFWLS. Reduction of RA size after TTVI did not translate into improvement of RASR, indicating an already advanced pre-existing RA dysfunction.

Significant disagreements between conventional functional metrics and 3D echocardiography-derived ejection fraction in the detection of right ventricular systolic dysfunction

Abstract Background The conventional echocardiographic parameters of the right ventricular (RV) systolic function (e.g., tricuspid annular plane systolic excursion - TAPSE, fractional area change – FAC, free wall longitudinal strain – FWLS) only partially portray the complex functional characteristics of the RV; therefore, they may fail to capture the full spectrum of RV dysfunction and associated adverse clinical outcomes. 3D echocardiography-derived RV ejection fraction (RVEF) is a well-validated and reproducible parameter that overcomes these limitations. Purpose We aimed to investigate the discordance between TAPSE, FAC, FWLS and RVEF in RV systolic function grading and associated outcomes. Methods Two retrospective databases from different centers including consecutive patients with various cardiac diseases who underwent clinically indicated 2D and 3D echocardiography (n=750) were analysed. Patients were followed up for the occurrence of all-cause mortality. RVEF was measured by a single, commercially available 3D software package. Guideline-recommended cut-off values were used to indicate RV systolic dysfunction (TAPSE<17 mm, FAC<35%, FWLS>-20%). RVEF <45% served as the "ground truth" of RV dysfunction. Results Among patients with normal RVEF (n=511), 109 (21%) had reduced TAPSE, 168 (33%) had reduced FAC, and 42 (8%) had reduced FWLS. Among patients with reduced RVEF (n=239), 109 (46%) had normal TAPSE, 61 (26%) had normal FAC, and 98 (41%) had normal FWLS. Correspondingly, sensitivity and specificity for discrimination of RV systolic dysfunction (RVEF<45%) were 66% and 70% for TAPSE, 71% and 76% for FAC, and 89% and 69% for FWLS on ROC analysis, respectively (Figure 1). During the median follow-up time of 3.5 years, 112 patients (15%) died. Using univariable Cox regression, TAPSE (HR [95% CI]: 0.911 [0.881 - 0.942]), FAC (0.940 [0.924 - 0.957]), FWLS (1.101 [1.071 - 1.133], and RVEF (0.928 [0.913 - 0.944]) were all significant predictors of mortality (p<0.001). Interestingly, combining the conventional functional measures based on how many of them indicate dysfunction shows that outcomes are the worst if at least two parameters are impaired and gradually better if only one or none of them (Kaplan-Meier curves, Figure 2, log-rank p<0.001). Conclusion Guideline-recommended cut-off values of conventional echocardiographic parameters of RV systolic function are only modestly associated with RVEF-based assessment. Impaired values of FWLS show the closest association with the RVEF cut-off. Our results emphasize a multiparametric approach in the assessment of RV function, especially, if 3D echocardiography is not available.Figure 1.Figure 2.

Interleukin-22 deficiency exacerbates right ventricular remodeling during pressure overload

Abstract Background Fibrosis and remodeling of right ventricle (RV) are associated with prognosis in patients with RV failure. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, play roles in tissue protection and wound repair. We have previously shown that IL-22 plays an important role in cardiac remodeling after acute myocardial infarction; however, the role of IL-22 in RV fibrosis and remodeling remains elusive. Purpose We investigated the role of IL-22 in the pathogenesis of RV remodeling during pressure overload. Methods Pulmonary artery banding (PAB) is performed by placing a 6-0 suture around the pulmonary artery over a 24 G needle in wild type mice (C57BL/6J) and IL-22 knockout mice (IL-22 KO). Only mice with moderate pulmonary artery stenosis (peak pressure gradient across the pulmonary band: 25–40 mmHg at 1 week after surgery by echo Doppler) were included in the study protocol. Two weeks after PAB, RV function was measured by echocardiography and real-time PCR analysis was performed to measure IL-22, IL-22 receptor subunit alpha 1 (IL-22RA1), and IL-22 signaling inhibitor IL-22 binding protein (IL-22BP). Results 2 weeks after PAB, IL-22 KO mice showed markedly increased RV weight (IL-22 KO mice vs. wild-type mice; RV/LV+IVS: 0.48±0.05 vs 0.40±0.02, P=0.002). IL-22 KO mice exhibited significant RV enlargement and RV dysfunction 2 weeks after PAB. (IL-22 KO mice vs wild type mice; RVEDV: 10±2.3mm2 vs 12.9±3.1mm2, P=0.005, TAPSE: 10.8±1.8mm vs 9.5±1.7mm, P=0.04, FAC: 35.2±7.8% vs 23±6.0%, P<0.001). The expression of IL-22, IL-22RA1 and IL-22BP in the RV tended to increase 2 weeks after PAB (wild-type mice with PAB (n=3) vs. wild-type mice with sham; IL-22: 0.0023 vs 0.0028, P=0.18 IL-22RA1: 1.489 vs 1.773, P=0.175, IL-22BP: 0.025 vs 0.067, p=0.005). Conclusion These results suggest that IL-22 is involved in RV remodeling during RV pressure overload.

Retrospective analysis of confirmed cases of pulmonary veno-occlusive disease: a single tertiary referral center study

Abstract Background Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension that primarily results in intimal fibrosis of the pulmonary venules and veins, the venous lesions are often associated with changes in interlobular septa, lung parenchyma, and pulmonary arterioles and arteries. Purpose We sought to study the clinical characteristics of patients with confirmed PVOD at a single large referral center. Methods We retrospectively reviewed data from a total of 675 patients with pulmonary hypertension (identified by ICD codes or search of text) from 2017 and 2022 from a database obtained from electronic medical records at our institution. Patients with group 2 pulmonary hypertension were excluded. Only 29 cases were confirmed by histology or genetic testing. Results Out of the 29 patients confirmed with PVOD, 28 (96.5%) had a characteristic histology (lung biopsy (55.1%), explanted lung for transplant (27.5%) and autopsy (13.7%)) and 1 (3.4%) had a positive genetic test for EIF2AK4 biallelic mutation. The age at diagnosis was 53±16 years, 14 (48.2%) were men, 2 (6.8%) had systemic scleroderma, 2 (6.8%) had psoriasis, 2 (6.8%) were exposed to cytotoxic agents, 16 (55.1%) were smokers and 2 (6.8%) had a family history of pulmonary hypertension. All patients had computed tomography of the chest but only 12 (41.3%) had all 3 typical features found in PVOD (ground glass opacities, interlobular septal thickening, and lymphadenopathy). The most common feature was interlobular septal thickening in 26 (89.6%), followed by ground glass opacities present in 25 (86.2%) and lymphadenopathy in 12 (41.3%) of the patients. At diagnosis, mean pulmonary artery pressure was 45±15 mmHg and pulmonary vascular resistance was 9±6 WU. The median DLCO was 41 (34-58) %. On echocardiogram, 14 (48.2%) had severely enlarged right ventricle (RV), RV function was ≥moderately reduced in 17 (58.6%), RV systolic pressure was 63±20 mmHg and 6 (20.6%) had pericardial effusion. Out of 21 (72.4%) patients who received pulmonary vasodilators, 4 (13.7%) received single agent. 10 (34.4%) received 2 agents, 6 (20.6%) 3 agents, and 1 (3.4%) received 4 agents. 35.7% of these treated patients reported an improvement or initial worsening of symptoms with subsequent improvement afterwards. 18 (62%) patients with PVOD died, 12 (41.3%) had a lung transplant and 6 (20.6%) were still alive without the transplant until the day data was collected. Mean duration from diagnosis to death and lung transplantation was 446 ± 405 days and 274±479 days respectively. Conclusion PVOD is a rare and lethal cause of pulmonary hypertension. When suspected, a trial of medical therapy should be initiated carefully. The evaluation for lung transplant should be considered early given its high mortality.

Speckle tracking echocardiography detects subtle right ventricular systolic dysfunction in post Covid syndrome after mild severity Covid-19

Abstract Introduction Now that the global COVID-19 pandemic has come to an end, many patients seek medical help for its aftermath giving rise to post COVID syndrome. Post COVID syndrome describes individuals with a history of probable or confirmed COVID-19 infection, usually 3 months from the onset of infection with symptoms that last for at least 2 months and no alternative diagnosis can be explained. The affection of the right ventricular (RV) systolic function is a cornerstone in the pathogenesis underlying Post COVID syndrome. Many modalities were used to assess the RV with a widespread debate as to the most accurate one. However, echocardiography remains the modality of choice for the evaluation of RV systolic function, especially when using its novel features as myocardial deformation imaging by speckle tracking echocardiography (STE) to surpass the RV’s peculiar anatomy, retrosternal position and complex architecture. Purpose The aim was to assess RV systolic function by STE 3-6 months after recovery from mild severity COVID-19 disease and correlate these findings with Post COVID syndrome. Methods This study included 96 adults (above 18 years of age) who were classified into three equal groups; the first group recruited 32 subjects 3-6 months after recovery from mild severity COVID-19 disease without post COVID syndrome, the second group included 32 subjects 3-6 months after recovery from mild severity COVID-19 disease with post COVID syndrome and the third group recruited 32 gender-matched healthy subjects of similar ages without previous COVID-19 disease (control group). Each subject underwent a detailed transthoracic echocardiography including RV function assessment using 2D RV STE imaging. Results RV global longitudinal strain (GLS) and RV free wall longitudinal strain (FWLS) were significantly lower in patients after recovery from mild severity COVID-19 disease with post COVID syndrome (P-value= 0.010) in comparison to the other groups. There was a statistically significant negative correlation found between RV 2D STE parameters and RV end-diastolic dimension, systolic pulmonary artery pressure and RV myocardial performance index. Also, there was a statistically significant positive correlation found between RV 2D STE parameters and RV fractional area change, tricuspid annular plane systolic excursion and RV S'. The cardiac symptomatology in patients with post COVID syndrome was analyzed showing that the most common three symptoms were fatigue, palpitations and chest pain with a prevalence of 65.6%, 40.6% and 31% respectively. These three symptoms showed a significant negative relation with RV-GLS and RV-FWLS. Conclusion RV function assessed using STE occupied the lower normal ranges in patients recovering from mild severity COVID-19 disease, particularly those with post COVID syndrome. 2D STE may be used for the detection and follow-up of possible subtle long term RV dysfunction after mild severity COVID-19 disease.RV-GLS and RV-FWLS in the studied groupsRV-GLS and RV-FWLS using 2D STE

Comparison of milrinone versus dobutamine on invasive haemodynamics in patients with advanced heart failure on home inotropes

Abstract Background Home inotropic support is an established bridge to cardiac transplantation in patients with advanced heart failure. Milrinone, a phosphodiesterase 3 inhibitor, preferentially vasodilates pulmonary vasculature, thus is often chosen over dobutamine in patients with concomitant pulmonary hypertension. However, there is a paucity of data on the haemodynamic effects of milrinone in the pre-cardiac transplant population. Purpose We sought to examine the haemodynamic effects of milrinone vs. dobutamine out to 3 months in patients with advanced heart failure awaiting cardiac transplantation. Methods Patients in the home inotrope program at a quaternary referral centre from January 2000 to May 2022 were included. Retrospective analysis of echocardiographic and invasive haemodynamic studies via right heart catheterisation were performed at baseline (prior to commencement of inotrope), at 30 days (30D) and 3 months (3m). Results From a total of 119 patients, 57 were on milrinone and 62 on dobutamine. Non-ischaemic cardiomyopathies of various aetiologies accounted for 67%, while ischaemic cardiomyopathies accounted for 33%. Majority of patients were male (79%) with a mean age of 52±13 years. There was a significant increase in LVEF from 21±7% at baseline to 27±14% at 3m in those on dobutamine, p = 0.02. Similar increase in LVEF from 22±8% to 26±13% in the milrinone group did not reach significance, p = 0.43. Comparably, CI increased from 2.0±0.6L/min/m2 at baseline to 2.5±0.9L/min/m2 at 3m in the dobutamine cohort, p = 0.05, and from 2.0±0.7L/min/m2 at baseline to 2.3±0.6L/min/m2 at 3m in the milrinone cohort, p = 0.27. In the dobutamine cohort LVEDD was static from 68±14mm at baseline to 66±21mm at 3m, p = 0.78. LVEDD reduced from 67±11mm to 60± 9mm at 3m in the milrinone group, p = 0.09. Classification of mild right ventricular dysfunction increased from 7% to 18% after 30 days on milrinone, p= 0.2, compared to an increase from 10% to 16% in the dobutamine group, p = 0.47. Mean pulmonary artery pressure (mPAP) reduced from 34±11mmHg to 29±11mmHg at 3m in the milrinone group, p = 0.15. mPAP was static in the dobutamine group from 34±9mmHg at baseline to 34±10mmHg at 3m, p = 0.96. TPG in the milrinone group was 11.9±6.0mmHg to 12.9±6.3mmHg at 30D, with reduction at 3m to 9.6±6.3mmHg, p = 0.26. In the dobutamine group TPG remained static from 10.9±5.7mmHg at baseline to 11.4±5.1mmHg at 30D and 10.9±5.2 at 3m, p = 0.97. Wedge pressure (PCWP) reduced from 22±7mmHg at baseline to 21±7mmHg at 30D to 18±8mmHg at 3m in the milrinone group, p = 0.11. PCWP in the dobutamine group was static at 23±8mmHg at baseline to 24±5mmHg at 30D and 23±6mmHg at 3m, p = 0.92. Conclusion(s) Dobutamine demonstrated a significant increase in LVEF and CI out to 3 months, however milrinone demonstrated a larger improvement in RV function and greater reduction in cardiac and pulmonary pressures as compared to dobutamine. Larger studies are required to confirm these trends.Figure 1

Right ventricular dysfunction after therapy titration, but not at the time of index hospitalization, predicts prognosis in patients with new-onset acute heart failure

Abstract Introduction and aims The prognostic implications of right ventricular dysfunction (RVD) in patients with left ventricular (LV) disease has gained more attention over the last years. However, the role of RV function in new-onset acute heart failure (NoAHF) has only recently come into focus. The description of RVD is often confined to its longitudinal function. In the present study of patients with NoAHF, we aimed at (I) comparing the prognostic ability of RV longitudinal function with a novel echocardiographic RVD score and (II) to test the hypothesis that RVD conveys more prognostic information if it persists after titration of heart failure therapy. Methods Patients aged 18 to 70 years, admitted between 2015 and 2018 to a tertiary center with NoAHF were retrospectively included, provided that they did not have previous heart failure diagnosis or therapy and that complete echocardiograms were available at the time of index hospital admission and after titration of heart failure therapy. The RVD score allocates one point each for tricuspid annular plane systolic excursion (TAPSE) <17 mm (longitudinal dysfunction), right ventricular diastolic area index >11.5 (women) or >12.6 cm2/m2 (men) (RV dilatation), ≥moderate tricuspid regurgitation (RV deformation) and vena cava inferior collapsibility <50% (increased right atrial pressure). An RVD score ≥2 was defined as significant RVD. Patients were followed for the composite endpoint of death from all causes, heart transplantation or implantation of LV assist device until September 2022. Results Two-hundred and ten patients were followed for a median of 60 months. At index hospitalization, LV ejection fraction (LVEF) was 28±10%, TAPSE was 16±4 mm and 36% of the patients had a RVD score ≥2. Eighty-eight percent of the patients had LVEF<40%. At the end of the follow-up, 53 (25%) patients met the endpoint. At index hospitalization, there were no significant differences in any echocardiographic parameters between patients meeting and not meeting the endpoint. After titration of heart failure therapy, there were significant differences in LVEF (33% vs 46%, P<0.001), TAPSE (16 vs 19 mm, P = 0.001) and the proportion of patients with RVD score ≥2 (4% vs 36%, P<0.001). Figure 1 and 2 show Kaplan-Meier curves for survival free of composite endpoint in patients with and without RVD despite therapy titration, defined as TAPSE <17 mm or as RVD score ≥2. The unadjusted hazard ratio (95% CI) for TAPSE was 2.5 (1.5-4.4) and for RVD score 7.9 (4.4-14.0). Conclusions At index hospitalization, neither LVEF nor RV function can predict the prognosis in patients with NoAHF. However, the persistence or onset of RV dysfunction after titration of heart failure therapy does. A multiparametric echocardiographic RVD score might provide improved prognostic stratification when compared to TAPSE.Kaplan-Meier, TAPSE≥17mm vs <17mmKaplan-Meier, RVDS<2 vs ≥2

The effects of empagliflozin on right ventricular adaptation to pressure overload

Abstract Background Right ventricular (RV) failure is the prime cause of death in patients with pulmonary arterial hypertension. Novel treatment strategies that protect the RV are needed. Empagliflozin, a member of the new anti-diabetic sodium-glucose co-transporter-2 inhibitors, shows a cardioprotective effect on the left ventricle in clinical and preclinical studies, but its direct cardiac effects on the RV remain elusive. Purpose To investigate the effects of empagliflozin on RV dysfunction induced by pulmonary trunk banding (PTB). Methods Male Wistar rat weanlings (116±10 g) were randomized to PTB or sham surgery. One week after surgery, PTB animals were randomized to empagliflozin 20 mg/kg/day mixed in the chow (300 mg empagliflozin/kg chow) (PTB-empa, n=10) or standard chow (PTB-control, n=10). Sham rats (Sham, n=6) received standard chow. After five weeks, RV function was evaluated by clinically relevant methods including echocardiography, cardiac MRI, and invasive pressure-volume measurements. Results PTB increased RV end-systolic pressures four-fold and caused RV hypertrophy with a 55 % increase in RV/(left ventricle + septum) weight ratio in PTB-control rats compared with sham. RV failure was evident by a decrease in cardiac output (PTB-control: 1.07±0.06 mL/s vs sham: 2.06±0.24 mL/s, p=0.0136). PTB-empa rats had a slight but non-significant weight reduction and a 33 % increase in water intake compared with PTB-control, yet no differences in hematocrit or blood glucose were observed. Treatment with empagliflozin decreased RV end-systolic pressures by 11 % (PTB-empa: 81±3 mmHg vs PTB-control: 91±2 mmHg, p=0.0091) without any effects on RV cardiac output. This decrease in RV end-systolic pressure in PTB-empa rats was complemented by less decreased minimum dp/dt and less increased maximum dp/dt compared with PTB-control without changes in the ventriculo-arterial coupling (Ees/Ea) (PTB-empa: 0.58±0.08 vs PTB-control: 0.67±0.14, p=0.8170). Load-independent measures of RV systolic and diastolic function were not affected in PTB-empa rats compared with PTB-control. Conclusion PTB caused RV failure in all rats subjected to the procedure. Empagliflozin treatment showed promising effects in pressure overload induced RV failure by reducing end-systolic pressure. Our study supports that treatment with empagliflozin has no toxic or adverse effects on the failing RV. Further studies are needed to explore empagliflozin’s potential beneficial role against RV failure.