Abstract 14345: Cardiopulmonary Best Abstract Award: Improves Right Ventricular - Pulmonary Arterial Coupling and Right Ventricular Function in the Pulsar Study: A Phase 2, Double-blind, Placebo-controlled, Randomized Study to Compare the Efficacy and Safety of Sotatercept versus Placebo When Added to Standard of Care for the Treatment of Pulmonary Arterial Hypertension (PAH)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Vallerie McLaughlin ◽  
Mardi Gomberg-maitland ◽  
Solaiappan Manimaran ◽  
Jonathan Lu ◽  
Simon Gibbs ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Randomized Study ◽  
Pulmonary Arteries ◽  
Standard Of Care ◽  
Heart Catheterization ◽  
Right Heart ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Pulmonary Arterial ◽  
Rv Function

Background: The right ventricle (RV) and pulmonary arteries become uncoupled as RV function deteriorates in PAH, a consequence of pulmonary vascular remodeling which is ultimately fatal. Restoration of RV-PA coupling and RV function is a crucial aim of PAH treatment. Preclinically, sotatercept, a first-in-class fusion protein, has been shown to reverse right heart remodeling and improve right heart structure and function and acts by suppressing TGF-β signaling and rebalancing BMPR2 signaling. The PULSAR study (NCT03496207, EudraCT 2017-004738-27) released positive topline results earlier this year. Methods: The PULSAR study enrolled 106 patients with WHO Group 1 PAH and WHO functional classes (FC) II-III; age ≥18; pulmonary vascular resistance of ≥5 Wood units by right heart catheterization; stable PAH standard of care (SOC) therapy (all combinations allowed). Sotatercept was administered by SC injection every 21 days for a 24-week double-blind, placebo-controlled treatment period in 3 arms: placebo + SOC, 0.3 mg/kg sotatercept + SOC, 0.7 mg/kg sotatercept + SOC. 2D Doppler echocardiography was performed at baseline and 24 weeks and read in a central laboratory. RV-PA coupling was assessed by TAPSE/PASP. Results: Significant improvement was seen in LS mean (SE) change from baseline to week 24 in RV-PA coupling, RVFAC, RVEDA, RVESA, PASP, and RAP in both sotatercept dose level groups vs placebo. No changes were seen in TAPSE or, notably, in CO. For RV-PA coupling, all patients started below the 0.31 mm/mmHg prognostic threshold; both treatment arms improved above that threshold by 24 weeks while the placebo arm remained below. Conclusions: In the PULSAR study, treatment with sotatercept compared to placebo was associated with statistically significant improvements in RV-PA coupling and RV function. Sotatercept has the potential to be a new treatment option for PAH patients with consistent and encouraging effects on RV-PA coupling and RV function.

scholarly journals Effect of Riociguat and Sildenafil on Right Heart Remodeling and Function in Pressure Overload Induced Model of Pulmonary Arterial Banding

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Nabham Rai ◽  
Swathi Veeroju ◽  
Yves Schymura ◽  
Wiebke Janssen ◽  
Astrid Wietelmann ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Soluble Guanylate Cyclase ◽  
Pde5 Inhibitor ◽  
Pressure Overload ◽  
Pulmonary Vasculature ◽  
Heart Catheterization ◽  
High Morbidity ◽  
Right Heart ◽  
Pulmonary Arterial ◽  
Rv Function

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by remodeling of the pulmonary vasculature and a rise in right ventricular (RV) afterload. The increased RV afterload leads to right ventricular failure (RVF) which is the reason for the high morbidity and mortality in PAH patients. The objective was to evaluate the therapeutic efficacy and antiremodeling potential of the phosphodiesterase type 5 (PDE5) inhibitor sildenafil and the soluble guanylate cyclase stimulator riociguat in a model of pressure overload RV hypertrophy induced by pulmonary artery banding (PAB). Mice subjected to PAB, one week after surgery, were treated with either sildenafil (100 mg/kg/d, n=5), riociguat (30 mg/kg/d, n=5), or vehicle (n=5) for 14 days. RV function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometry. Both sildenafil and riociguat prevented the deterioration of RV function, as determined by a decrease in RV dilation and restoration of the RV ejection fraction (EF). Although both compounds did not decrease right heart mass and cellular hypertrophy, riociguat prevented RV fibrosis induced by PAB. Both compounds diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Treatment with either riociguat or sildenafil prevented the progression of pressure overload-induced RVF, representing a novel therapeutic approach.

The Influence of Pulmonary Hemodynamics on Right Ventricular Function in Pulmonary Hypertension

2013 ◽  
Author(s):  
Vitaly O. Kheyfets ◽  
Lourdes Rios ◽  
Triston Smith ◽  
Theodore Schroeder ◽  
Jeffrey Mueller ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Pulmonary Hypertension ◽  
Shear Stress ◽  
Right Ventricular ◽  
Pulmonary Arteries ◽  
Pulmonary Hemodynamics ◽  
Arterial Hemodynamics ◽  
Computational Fluid Dynamics Cfd ◽  
Pulmonary Arterial ◽  
Rv Function

Pulmonary arterial hypertension (PAH) is a degenerative disease that can lead to substantial morphometric remodeling of the pulmonary arteries. Previous studies have revealed coupling relationships between right ventricular (RV) function and pulmonary arterial hemodynamics. The objective of this study was to utilize computational fluid dynamics (CFD) to estimate spatially averaged Wall Shear Stress (WSS) for patients with PH and explore correlations between hemodynamics metrics and RV function.

Abstract 16661: Fluid Challenge During Right Heart Catheterization for Evaluation of Pulmonary Hypertension Identifies Patients With Decreased Right Ventricular Function

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Vineet A Agrawal ◽  
Amelia Muhs ◽  
Tufik Assad ◽  
Ivan M Robbins ◽  
John Newman ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Fluid Challenge ◽  
Right Heart Catheterization ◽  
Rank Test ◽  
Heart Catheterization ◽  
Stroke Work ◽  
Right Heart ◽  
Prognostic Implications ◽  
Rv Function

Introduction: Fluid challenge during right heart catheterization (RHC) identifies occult left heart diastolic dysfunction (Occ-DD) in 10-20% of patients initially diagnosed with pre-capillary pulmonary hypertension (PH). The prognostic implications of the response to fluid challenge are not known. Abnormal right ventricular (RV) function is a poor prognostic indicator in all forms of PH. Hypothesis: We hypothesized that fluid challenge during RHC identifies patients with worse RV function and survival. Methods: Consecutive patients referred for RHC with fluid challenge from 2009-2016 were studied. Occ-DD was defined by a resting pulmonary arterial wedge pressure (PAWP) < 15 mmHg, and a PAWP > 18 mmHg after 500cc fluid challenge. Resting DD was defined by resting PAWP > 15 mmHg. RV function was assessed by pulmonary artery pulsatility index (PAPi) or RV stroke work index (RVSWI). Statistical analysis was conducted using Kruskal Wallis test. Survival analysis was conducted by log rank test. Results: Of the 310 patients identified, 83% were female with a mean age of 54 + 14 years. The cohort consisted of 204 (66%) patients without DD, 30 (10%) with Occ-DD, and 76 (24%) with resting DD. Patients with Occ-DD were older (59 + 12 vs 51 + 14, p < 0.0001) with greater BMI (31 + 6 vs 28 + 7, p < 0.0001), but had similar prevalence of obesity, hypertension, diabetes mellitus, and coronary disease to all groups. Patients with Occ-DD had lower PAPi (7.8 + 0.4 vs 8.5 + 0.4, p < 0.0001), lower RVSWI (9.9 + 0.8 vs 17.8 + 0.7 mmHg*ml/m2, p < 0.0001) (Figure), and decreased survival (3.7 + 3.5 vs 4.9 + 3.5 years, p < 0.0001) compared to those without DD. After adjustment for RV function, survival was no longer different between groups. Conclusions: Patients with Occ-DD after fluid challenge during RHC have decreased survival due to worse RV function compared to patients without DD. These findings suggest important prognostic implications for fluid challenge in the evaluation of patients with PH.

scholarly journals Right ventricular dimension index by cardiac magnetic resonance for prognostication in connective tissue diseases and pulmonary hypertension

Rheumatology ◽  
2019 ◽  
Author(s):  
Nobuya Abe ◽  
Masaru Kato ◽  
Michihito Kono ◽  
Yuichiro Fujieda ◽  
Hiroshi Ohira ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Right Heart ◽  
Pulmonary Arterial ◽  
Dimension Index

Abstract Objectives Pulmonary hypertension (PH) in patients with CTD is a heterogeneous condition affected by left heart disease, chronic lung disease and thromboembolism as well as pulmonary vascular disease. Recent studies using cardiac magnetic resonance (CMR) have shown that right ventricular dysfunction is predictive for mortality in patients with PH, but limited to pulmonary arterial hypertension. This study aimed to analyse prognostic factors in PH-CTD. Methods This retrospective analysis comprised 84 CTD patients, including SSc, who underwent both CMR and right heart catheterization from 2008 to 2018. Demographics, laboratory findings, and haemodynamic and morphological parameters were extracted. The prognostic value of each parameter was evaluated by multivariate analysis using covariables derived from propensity score to control confounding factors. Results Of 84 patients, 65 had right heart catheterization-confirmed PH (54 pulmonary arterial hypertension, 11 non-pulmonary arterial hypertension). Nine out of these PH patients died during a median follow-up period of 25 months. In 65 patients with PH, right ventricular end-diastolic dimension index (RVEDDI) evaluated by CMR was independently associated with mortality (hazard ratio 1.24; 95% CI: 1.08–1.46; P = 0.003). In a receiver operating characteristic analysis, RVEDDI highly predicted mortality, with area under the curve of 0.87. The 0.5–2-year follow-up data revealed that RVEDDI in both survivors and non-survivors did not significantly change over the clinical course, leading to the possibility that an early determination of RVEDDI could predict the prognosis. Conclusion RVEDDI simply evaluated by CMR could serve as a significant predictor of mortality in PH-CTD. A further validation cohort study is needed to confirm its usability.

scholarly journals The Role of Four-Dimensional Automatic Right Ventricular Quantification Technology to Determine RV Function and Hemodynamics in Patients With Pulmonary Hypertension Compared With Right Heart Catheterization

2021 ◽  
Vol 8 ◽  
Author(s):  
Weichun Wu ◽  
Bingyang Liu ◽  
Min Huang ◽  
David H. Hsi ◽  
LiLi Niu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Image Quality ◽  
Right Ventricular ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Healthy Controls ◽  
Right Heart ◽  
Quality Image ◽  
Rv Function

Background: Four-dimensional automatic right ventricular quantification technology (4D auto-RVQ) is a new method that can simultaneously measure right ventricular (RV) structure and strain. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. The role of 4D auto-RVQ in determining RV function and hemodynamics is not clear. We assessed the 4D auto-RVQ to measure right heart structure, function, and hemodynamics in patients with pulmonary hypertension (PHTN) correlated with right heart catheterization (RHC).Methods: We enrolled a prospective cohort of 103 patients with PHTN and 25 healthy controls between September 2017 and December 2018. All patients with PHTN underwent echocardiography and RHC. Patients were included if they underwent two-dimensional (2D) and 4D auto-RVQ echocardiographic sequences on the same day as RHC. We analyzed RV functional indices using 2D and 4D auto-RVQ analyses. We divided patients with PHTN into three groups according to echocardiographic image quality as follows: high (n = 24), average (n = 48), and poor (n = 4). Hemodynamic parameters were measured using RHC, including mean right atrial pressure, mean pulmonary arterial pressure, RV cardiac index (RV-CI), and pulmonary vascular resistance.Results: There were significant differences in most 2D and 4D auto-RVQ parameters between patients with PHTN and healthy controls. Interobserver variability showed significant agreement with 4D auto-RVQ for most measurements except for 4D end-diastolic volume. Indices measured by auto 4D-RVQ in the high-quality image group had a good correlation with RHC but not in the average- and poor-quality image group. Mid-RV diameter showed the best predictive power for the right RV-CI [area under the curve (AUC) 0.935; 95% confidence interval (CI), 0.714–0.997; p &lt; 0.001]. RV end-systolic volume &gt;121.50 mL had a 71.43% sensitivity and a 100% specificity to predict right RV-CI (AUC, 0.890; 95% CI, 0.654–0.986; p &lt; 0.001).Conclusions: 4D auto-RVQ may be used to estimate RV function and some hemodynamic changes compared with RHC in PHTN patients with high image quality. Furthermore, a large sample of the study is needed to evaluate RV function by 4D auto-RVQ in PHTN patients with average image quality.

scholarly journals Surfing the right ventricular pressure waveform: methods to assess global, systolic and diastolic RV function from a clinical right heart catheterization

2020 ◽  
Vol 10 (1) ◽  
pp. 204589401985099 ◽  
Author(s):  
Rebecca R. Vanderpool ◽  
Reena Puri ◽  
Alexandra Osorio ◽  
Kelly Wickstrom ◽  
Ankit A. Desai ◽  
...  
Keyword(s):  
Stroke Volume ◽  
Right Ventricular ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Minimal Effect ◽  
Right Heart ◽  
End Diastolic Volume ◽  
Diastolic Stiffness ◽  
The Right ◽  
Rv Function

Right ventricular (RV) function strongly associates with mortality in patients with pulmonary arterial hypertension (PAH). Current methods to determine RV function require temporal measurements of pressure and volume. The aim of the study was to investigate the feasibility of using right heart catheterization (RHC) measurements to estimate systolic and diastolic RV function. RV pressure and volume points were fit to P = α(eβV-1) to assess diastolic stiffness coefficient (β) and end-diastolic elastance (Eed). Single-beat methods were used to assess RV contractility (Ees). The effects of a non-zero unstressed RV volume (V0), RHC-derived stroke volume (SVRHC), and normalization of the end-diastolic volume (EDV) on estimates of β, Eed, and Ees were tested using Bland–Altman analysis in an incident PAH cohort (n = 32) that had both a RHC and cardiac magnetic resonance (CMR) test. RHC-derived measures of RV function were used to detect the effect of prostacyclin therapy in an incident PAH cohort and the severity of PAH in prevalent PAH (n = 21). A non-zero V0 had a minimal effect on β with a small bias and limits of agreement (LOA). Stroke volume (SV) significantly influenced estimates of β and Ees with a large LOA. Normalization of EDV had minimal effect on both β and Eed. RHC-derived β and Eed increased due to the severity of PAH and decreased due to three months of prostacyclin therapy. It is feasible to detect therapeutic changes in specific stiffness and elastic properties of the RV from signal-beat pressure-volume loops by using RHC-derived SV and normalizing RV EDV.

scholarly journals Right Ventricular Function Predicts Adverse Clinical Outcomes in Patients With Chronic Thromboembolic Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Yidan Li ◽  
Lirong Liang ◽  
Dichen Guo ◽  
Yuanhua Yang ◽  
Juanni Gong ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Clinical Outcomes ◽  
Heart Function ◽  
Three Dimensional ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Heart Catheterization ◽  
Right Heart ◽  
Thromboembolic Pulmonary Hypertension ◽  
Rv Function

Background: Right ventricular (RV) function plays a vital role in the prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH). We used new machine learning (ML)-based fully automated software to quantify RV function using three-dimensional echocardiography (3DE) to predict adverse clinical outcomes in CTEPH patients.Methods: A total of 151 consecutive CTEPH patients were registered in this prospective study between April 2015 and July 2019. New ML-based methods were used for data management, and quantitative analysis of RV volume and ejection fraction (RVEF) was performed offline. RV structural and functional parameters were recorded using 3DE. CTEPH was diagnosed using right heart catheterization, and 62 patients underwent cardiac magnetic resonance to assess right heart function. Adverse clinical outcomes were defined as PH-related hospitalization with hemoptysis or increased RV failure, including conditions requiring balloon pulmonary angioplasty or pulmonary endarterectomy, as well as death.Results: The median follow-up time was 19.7 months (interquartile range, 0.5–54 months). Among the 151 CTEPH patients, 72 experienced adverse clinical outcomes. Multivariate Cox proportional-hazard analysis showed that ML-based 3DE analysis of RVEF was a predictor of adverse clinical outcomes (hazard ratio, 1.576; 95% confidence interval (CI), 1.046~2.372; P = 0.030).Conclusions: The new ML-based 3DE algorithm is a promising technique for rapid 3D quantification of RV function in CTEPH patients.

scholarly journals Right ventricular stroke work index in adult patients with pulmonary arterial hypertension: - a comparison between echocardiography and right heart catheterization

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R Jumatate ◽  
A Ingvarsson ◽  
G Smith ◽  
A Roijer ◽  
E Ostenfeld ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Right Heart Catheterization ◽  
Adult Patients ◽  
Heart Catheterization ◽  
Stroke Work ◽  
Work Index ◽  
Significant Difference ◽  
Stroke Work Index ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Swedish Society of Pulmonary Hypertension Background In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, constituting a negative prognostic factor.  In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) reflects right ventricular function and has been proposed to predict outcome in PAH. However, RVSWI assessed by echocardiography (ECHO) has not been thoroughly compared to measures with right heart catheterization (RHC) in adults. The aim of the present study was to therefore evaluate RVSWI derived by echocardiography (RVSWIECHO) vs. RHC (RVSWIRHC). Methods  Fifty-four consecutive treatment naïve adult patients with PAH, were retrospectively analysed. All patients performed echocardiography and RHC with a median time of 1 day [IQR 0-1 days]. RVSWIRHC was calculated as: (mean pulmonary arterial pressure (mPAP) – mean right atrial pressure (mRAP)) x stroke volume index (SVI)RHC. Four methods for RVSWIECHO were evaluated: RVSWIECHO-1 = Tricuspid regurgitant maximum pressure gradient (TRmaxPG) x SVIECHO, RVSWIECHO-2=(TRmaxPG-mRAPECHO) x SVIECHO, RVSWIECHO-3 = TR mean gradient (TRmPG) x SVIECHO and RVSWIECHO-4=(TRmPG–mRAPECHO) x SVIECHO. Vena cava inferior diameter and its collapsibility were used for estimation of mRAPECHO.. Pearson’s correlation coefficients were used and data was expressed as mean ± standard deviation. Results Mean RVSWIRHC was 1132 ± 352 mmHg*mL*m-2.  Mean RVSWIECHO-1-4 was: 1904 ± 568, 1732 ± 531, 1090 ± 366 and 918 ± 336 mmHg*mL*m-2, respectively. There was no significant difference between RVSWIRHC and RVSWIECHO-3 in mean values, although they exhibited the lowest correlation, but moderate (r = 0.66). The strongest correlation was demonstrated for  RVSWIECHO-2 (r = 0.78, p &lt; 0.001), followed by a moderate correlation for  RVSWIECHO-1 and RVSWIECHO-4 (r = 0.75 and r = 0.69, p &lt; 0.001). The absolute (relative) bias for RVSWIECHO-1 was  -772 ± 385 (-50 ± 20%) mmHg*mL*m-2, RVSWIECHO-2 -600 ± 339 (-41 ± 20%) mmHg*mL*m-2, RVSWIECHO-3 42 ± 286 (5 ± 25%) mmHg*mL*m-2 and for RVSWIECHO-4 214 ± 273 (23 ± 27%) mmHg*mL*m-2. Conclusion RVSWIECHO-3, using the mean tricuspid gradient and SVIECHO, showed no significant difference to RVSWIRHC, albeit a moderate correlation between the methods. RVSWIECHO-1, RVSWIECHO- 2 and RVSWIECHO-4 exhibited moderate to strong correlations to RVSWIRHC, but poor concordance between absolute values. The clinical utility of RVSWIECHO and RVSWIRHC in assessing RV function in relation to PAH prognosis, risk stratification and treatment response remains to be evaluated in a larger clinical context.

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