Pulmonary Arterial Compliance Research Articles

Abstract 4124342: Invasive CPET-based hemodynamic correlates of abnormal peak VO 2 and V E /VCO 2 in HFpEF and pre-capillary Pulmonary Hypertension

Introduction: Pulmonary hypertension (PH) is a heterogeneous disease characterized by impaired gas exchange (CO 2 , O 2 ) in the pulmonary circulation, leading to dyspnea and exercise intolerance. We hypothesize that specific hemodynamic metrics correlate with poor gas exchange in PH phenotypes, which can be leveraged to define therapeutically relevant hemodynamic targets. Aim: This study aims to define hemodynamic correlates of poor gas exchange (peak VO 2 , V E /VCO 2 slope) in heart failure with preserved ejection fraction (HFpEF) and pre-capillary PH. Methods: We retrospectively analyzed 170 participants with invasive cardiopulmonary exercise testing: HFpEF (n=91), pre-capillary PH (n=54), and non-cardiac dyspnea (NCD, n=25). Linear regression models, adjusted for patient groups with interaction, were used to assess the association of peak VO 2 and V E /VCO 2 slope with predictors (pulmonary vascular resistance [PVR], distensibility, and pulmonary arterial compliance [PAC]). Results: In the order of NCD vs. HFpEF vs. pre-capillary PH, rest PAC (5.5±1.6 vs 3.8±1.7 vs 2.6±1.3 mL/mmHg), rest PVR (1.4±0.6 vs 3.2±2.0 vs 5.7±3.0 Woods unit), and distensibility (1.5±0.5 vs 0.8±0.4 vs 0.5±0.2 % per mmHg). In comparison to a non-significant correlation with rest PVR and distensibility, peak VO 2 (%predicted) showed significant correlation with rest PAC (p<0.01) with significantly positive slope of +6 in HFpEF and +10 in pre-capillary PH. Similarly, significant slopes were noted with rest PAC and V E /VCO 2 relationship (p<0.01) in HFpEF (-3) and pre-capillary PH (-4). Conclusion: Pulmonary arterial compliance (PAC) is the best correlate of poor gas exchange. Improving rest PAC by 1.0 mL/mmHg can lead to improvement in peak VO 2 predicted (+10% in pre-capillary PH, +6% in HFpEF), and V E /VCO 2 slope (-4 in pre-capillary PH, and -3 in HFpEF). In comparison to pre-capillary PH, more limited improvement in HFpEF is likely due to multi-organ dysfunction leading to exercise intolerance.

Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension

Abstract Background Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI. Purpose The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). Methods Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP. Results 794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient <0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table). Conclusions Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table

Enhanced diagnostic accuracy of cardiovascular magnetic resonance in identifying heart failure with preserved ejection fraction through assessment of right ventricular systolic dysfunction

Abstract Backgrounds Right ventricular maladaptive response to increased afterload affects exercise performance in heart failure with preserved ejection fraction (HFpEF). We investigated its role in the diagnosis of early stage of HFpEF with cardiac magnetic resonance (CMR) and invasive cardiopulmonary exercise testing (iCPET). Methods One hundred forty-five patients with suspected HFpEF were prospectively recruited from two centers and 113 of them completely underwent echocardiography, iCPET, and CMR. The diagnosis of HFpEF was based on the result of iCPET (pulmonary capillary wedge pressure > 15mmHg at resting and >25mmHg at peak exercise). Area under the curve (AUC) was determined by comparing HFpEF with non-HFpEF patients. Results Seventy-two HFpEF (68±10 years) and forty-one non-HFpEF (66±11 years) were identified. The resting pulmonary artery compliance was significantly reduced in HFpEF. CMR right ventricle longitudinal strain and left atrial reservoir strain had the highest diagnostic accuracy (AUCs 0.805 and 0.776, respectively). There is a sex disparity in the diagnosis accuracy of left atrial (LA) reservoir strain, with male patients exhibiting a significantly increased AUC (0.801) compared to females (AUC 0.559). Conclusions Right ventricular systolic dysfunction is an early indicator of HFpEF, accompanied by impaired LA filling. The diminished LA filling may be more prevalent in male patients, suggesting distinct early pathophysiological progressions between genders.

Efficacy and safety of the Aria pulmonary endovascular device in pulmonary hypertension

Abstract Background and aims A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and hemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH-LHD) and chronic lung disease (PH-CLD). Methods 8 patients with PH-LHD and 10 patients with PH-CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas-filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Hemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. Results No complications or investigational device-related serious adverse events occurred. Device activation in PH-LHD and PH-CLD patients decreased pulmonary arterial pulse pressure by 5.6±4.2mmHg (-12%; p=0.003) and 4.2±2.2mmHg (-11%; p<0.001), increased CPA by 0.4±0.2mL/mmHg (+23%; p=0.004) and 0.4±0.3mL/mmHg (+25%; p=0.001), and increased RV-PV coupling by 0.24±0.18 (+40%; p=0.012) and 0.11±0.07 (+21%; p=0.001), respectively. Conclusions Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV-PV coupling.Figure

Hemodynamic markers independent of pulmonary capillary wedge pressure can discriminate between pre and postcapillary exercise-induced pulmonary hypertension.

The discrimination between pre and postcapillary exercise-induced pulmonary hypertension relies on accurate measurement of pulmonary capillary wedge pressure, which can be unreliable. We found that exercise pulmonary artery compliance and right atrial pressure (AUC 0.88, 0.89, respectively) can differentiate subtypes of exercise-induced pulmonary hypertension in the absence of wedge pressure.

Association between right heart size and right ventricular output reserve in patients with pulmonary arterial hypertension

ObjectivesRight ventricular (RV) output reserve, defined as increase of cardiac output during exercise, is reduced in patients with pulmonary arterial hypertension (PAH). Aim of this study was to evaluate the association of right heart size measured by echocardiography and invasively measured RV function at rest and during exercise in PAH patients. MethodsAdult PAH-patients who received routine haemodynamic assessment at rest and during exercise by right heart catheterisation and echocardiographic measurement of right heart size (right atrial (RA) and RV area) were included in this study. Clinical, echocardiographic, laboratory, exercise and invasive haemodynamic parameters were retrospectively analysed. The primary endpoint was to assess the association between right heart size and right ventricular function. ResultsData from 215 PAH patients (age 58.9 ± 15.9 years, 63.3% female, 62.2% double or triple combination treatment) were analysed in this cross-sectional study. Cardiac index was significantly lower for patients with enlarged RA-area > 18 cm2 at rest, and at 25 and 50 W (all p < 0.001) and for patients with enlarged RV area > 20 cm2 at rest, 25, 50 and 75 W (all p < 0.001). Furthermore, pulmonary vascular resistance and mPAP/CO slope (all p < 0.001) were significantly higher and pulmonary arterial compliance (all p < 0.05) was significantly lower in patients with enlarged RA or RV area. RA and RV area correlated with TAPSE/sPAP (both p < 0.001, R − 0.570 and − 0.530). ConclusionThis study could underline that an enlargement of RA- and RV-area is associated with an impaired RV function at rest and during exercise in patients with PAH.

Dapagliflozin and Right Ventricular–Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction

Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown. To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF. Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction (CAMEO-DAPA) randomized clinical trial demonstrated improvement in PCWP at rest and exercise over 24 weeks with dapagliflozin compared with placebo with participants recruited between February 2021 and May 2022. This secondary analysis evaluates the effects of dapagliflozin on pulsatile pulmonary vascular load and RV-PA coupling using simultaneous echocardiography and high-fidelity invasive hemodynamic testing with exercise. This was a single-center study including patients with hemodynamically confirmed HFpEF with exercise PCWP of 25 mm Hg or greater. Dapagliflozin or placebo for 24 weeks. Pulsatile pulmonary vascular load (PA compliance and elastance) and right ventricular performance (PA pulsatility index, RV systolic velocity [s']/PA mean) during rest and exercise. Among 37 randomized participants (mean [SD] age, 67.4 [8.5] years; 25 female [65%]; mean [SD] body mass index, 34.9 [6.7]; calculated as weight in kilograms divided by height in meters squared), there was no effect of dapagliflozin on PA loading or RV-PA interaction at rest. However, with exercise, dapagliflozin improved PA compliance (placebo-corrected mean difference, 0.57 mL/mm Hg; 95% CI, 0.11-1.03 mL/mm Hg; P = .02) and decreased PA elastance (stiffness; -0.17 mm Hg/mL; 95% CI, -0.28 to -0.07 mm Hg/mL; P = .001). RV function during exercise improved, with increase in PA pulsatility index (0.33; 95% CI, 0.08-0.59; P = .01) and increase in exercise RV s' indexed to PA pressure (0.09 cm·s-1/mm Hg; 95% CI, 0.02-0.16 cm·s-1/mm Hg; P = .01). Improvements in pulsatile RV load and RV-PA coupling were correlated with reduction in right atrial (RA) pressure (PA elastance Pearson r = 0.55; P =.008; RV s'/PA elastance Pearson r = -0.60; P =.002) and PCWP (PA elastance Pearson r = 0.58; P <.001; RV s'/PA elastance Pearson r = -0.47; P = .02). Dapagliflozin increased resistance-compliance time (dapagliflozin, median [IQR] change, 0.06 [0.03-0.15] seconds; placebo, median [IQR] change, 0.01 [-0.02 to 0.05] seconds; P =.046), resulting in higher PA compliance for any exercise pulmonary vascular resistance. Results of this randomized clinical trial reveal that treatment with dapagliflozin for 24 weeks reduced pulsatile pulmonary vascular load and enhanced dynamic RV-PA interaction during exercise in patients with HFpEF, findings that are related to the magnitude of PCWP reduction. Benefits on dynamic right ventricular-pulmonary vascular coupling may partially explain the benefits of SGLT2 inhibitors in HFpEF. ClinicalTrials.gov Identifier: NCT04730947.

Clinical features, haemodynamics, and outcomes of heart failure with preserved ejection fraction in coarctation of aorta.

There are similarities in the pathogenesis of cardiac remodelling and dysfunction in heart failure with preserved ejection fraction (HFpEF) and coarctation of aorta (COA). We hypothesized that clinical HFpEF would be highly prevalent in adults with COA, and that the presence of HFpEF would increase the risk of mortality in this population. The aim of this study was to define the clinical features, haemodynamics, and prognostic implications of HFpEF in COA. Consecutive adults with repaired COA that underwent right heart catheterization were identified retrospectively. HFpEF was defined as heart failure symptoms (exertional dyspnoea or fatigue), preserved left ventricular ejection fraction ≥50%, and pulmonary artery wedge pressure at rest >15 mmHg. Of 99 COA patients, 32 (32%) had HFpEF. The correlates of HFpEF were obesity (adjusted odds ratio [OR] 4.15, 95% confidence interval [CI] 1.31-13.2), atrial fibrillation (adjusted OR 3.13, 95% CI 1.00-10.7), total arterial compliance index (adjusted OR 0.12, 95% CI 0.06-0.41 per 1 ml/mmHg*m2), and pulmonary artery compliance index (adjusted OR 0.36, 95% CI 0.15-0.56 per 1 ml/mmHg*m2). Of 99 patients, 24 (24%) died and 5 (5%) underwent heart transplant. The 10-year cumulative incidence of death/transplant was higher in COA patients with HFpEF compared with patients without HFpEF (39% vs. 12%, p = 0.001). The presence of HFpEF was associated with increased risk of death/transplant (adjusted hazard ratio 1.68, 95% CI 1.16-3.11). Heart failure with preserved ejection fraction is common in adults with COA and is associated with greater risk of death/transplant, emphasizing a pressing need for interventions to prevent and treat HFpEF in COA.

Reduced dynamic changes in pulmonary artery compliance during isometric handgrip exercise in patients with heart failure

Exercise intolerance is a debilitating symptom in heart failure (HF), adversely affecting both quality of life and long-term prognosis. Emerging evidence suggests that pulmonary artery (PA) compliance may be a contributing factor. This study aims to non-invasively assess PA compliance and its dynamic properties during isometric handgrip (HG) exercise in HF patients and healthy controls, using cardiovascular magnetic resonance (CMR). We prospectively enrolled 36 subjects, comprising 17 HF patients (NYHA class II and III) and 19 healthy controls. Participants performed an HG test, and we assessed changes in PA compliance and hemodynamic flow parameters using advanced CMR techniques. We also explored the relationship between CMR-derived PA compliance metrics and established clinical indicators, ensuring the validity of our findings through intra- and interobserver agreements. HF patients had significantly lower resting PA compliance compared to controls (28.9% vs. 50.1%, p < 0.01). During HG exercise, HF patients exhibited a dampened adaptability in PA compliance. Hemodynamic responses, including heart rate and blood pressure, were not significantly different between the groups. Further analyses revealed a significant correlation between changes in PA compliance and functional capacity, and an inverse relationship with NYHA class. Our study demonstrates a marked difference in PA vascular responses during HG exercise between HF patients and healthy controls. The compromised adaptability in PA compliance in HF patients is correlated with diminished functional capacity. These findings have significant clinical implications and may guide future interventional strategies in HF management.

Immature reticulocyte fraction: A novel biomarker of hemodynamic severity in pulmonary arterial hypertension.

Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease-related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p < 0.001), pulmonary vascular resistance (0.52, p = 0.001), and right atrial pressure (0.46, p = 0.005), and significant negative correlations with cardiac index (-0.43, p = 0.009), PA compliance (PAC) (-0.60, p < 0.001), stroke volume index (SVI) (-0.57, p < 0.001), and mixed venous oxygen saturation (-0.51, p = 0.003). IRF correlated with markers of iron deficiency (ID) and erythropoiesis. On multivariable linear regression, IRF was associated with elevated mPAP and reduced SVI and PAC independent of EPO levels, transferrin saturation, and soluble transferrin receptor levels. We identified IRF as a novel and potent biomarker of PAH hemodynamic severity, possibly related to its associations with erythropoiesis, ID, and tissue hypoxia.

Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes.

While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance. We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension). On the echocardiogram, TAPSE was divided by RV area in diastole (TAPSE/RVA-D) and systole (TAPSE/RVA-S). Analyses included correlations (Pearson and linear regression), receiver operating characteristic, and survival curves. On linear regression analysis, TAPSE/RVA metrics (versus TAPSE) had a stronger correlation with pulmonary artery compliance (r=0.48-0.54 versus 0.38) and peak VO2 percentage predicted (0.23-0.30 versus 0.18). Based on the receiver operating characteristic analysis, pulmonary artery compliance ≥3 mL/mm Hg was identified by TAPSE/RVA-D with an under the curve (AUC) of 0.79 (optimal cutoff ≥1.1) and by TAPSE/RVA-S with an AUC of 0.83 (optimal cutoff ≥1.5), but by TAPSE with only an AUC of 0.67. Similarly, to identify peak VO2 <50% predicted, AUC of 0.66 for TAPSE/RVA-D and AUC of 0.65 for TAPSE/RVA-S. Death or cardiovascular hospitalization at 12 months was associated with TAPSE/RVA-D ≥1.1 (HR, 0.38 [95% CI, 0.11-0.56]) and TAPSE/RVA-S ≥1.5 (HR, 0.44 [95% CI, 0.16-0.78]), while TAPSE was not associated with adverse outcomes (HR, 0.99 [95% CI, 0.53-1.94]). Among 31 subjects with available cardiac magnetic resonance imaging, RV ejection fraction was better correlated with novel metrics (TAPSE/RVA-D r=0.378 and TAPSE/RVA-S r=0.328) than TAPSE (r=0.082). In a broad cohort with suspected pulmonary hypertension, TAPSE divided by RV area was superior to TAPSE alone in correlations with pulmonary compliance and exercise capacity. As a prognostic marker of right heart function, TAPSE/RVA-D <1.1 and TAPSE/RVA-S <1.5 predicted adverse cardiovascular outcomes.

Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial

BackgroundPulmonary hypertension (PH) is a leading cause of death in patients with systemic sclerosis (SSc). An important component of SSc patient management is early detection and treatment of PH. Recently the threshold for the diagnosis of PH has been lowered to a mean pulmonary artery pressure (mPAP) threshold of > 20 mmHg on right heart catheterization (RHC). However, it is unknown if PH-specific therapy is beneficial in SSc patients with mildly elevated pressure (SSc-MEP, mPAP 21–24 mmHg).MethodsThe SEPVADIS trial is a randomized, double-blind, placebo-controlled phase 2 trial of sildenafil in SSc-MEP patients with a target enrollment of 30 patients from two academic sites in the United States. The primary outcome is change in six-minute walk distance after 16 weeks of treatment. Secondary endpoints include change in pulmonary arterial compliance by RHC and right ventricular function by cardiac magnetic resonance imaging at 16 weeks. Echocardiography, serum N-terminal probrain natriuretic peptide, and health-related quality of life is being measured at 16 and 52 weeks.DiscussionThe SEPVADIS trial will be the first randomized study of sildenafil in SSc-MEP patients. The results of this trial will be used to inform a phase 3 study to investigate the efficacy of treating patients with mild elevations in mPAP.Trial registrationClinicalTrials.gov Identifier NCT04797286.

Prognostic role of haemodynamics at follow-up in patients with pulmonary arterial hypertension: a challenge to current European Society of Cardiology/European Respiratory Society risk tools.

Haemodynamic variables like right atrial pressure (RAP), cardiac index (CI), stroke volume index (SVI) and mixed venous oxygen saturation (S vO2 ) predict survival in patients with pulmonary arterial hypertension (PAH). However, there is the need to identify further prognostic haemodynamic parameters as well as to redefine their role in PAH risk stratification compared to current risk tools and non-invasive parameters. This cohort study includes treatment-naïve patients assessed at baseline and after first-line PAH therapy with clinical, functional, exercise, laboratory and haemodynamic evaluations. Using a stepwise multivariate Cox regression analysis, independent prognostic haemodynamic parameters were identified and stratified according to cut-offs already defined in the European Society of Cardiology (ESC)/European Respiratory Society (ERS) risk table or defined based on the highest Chi-squared of the log-rank test. Their discriminatory power was tested for all-cause death and a combined end-point of death, hospitalisation and need of treatment escalation. 794 patients with PAH were enrolled. At first follow-up, RAP and pulmonary artery elastance were independently associated with death. Because of high correlations between haemodynamic parameters, different multivariable analyses were done identifying six other variables (pulmonary arterial compliance, cardiac efficiency, pulmonary vascular resistance, S vO2 , CI and SVI). Haemodynamic parameters were of no added prognostic value compared to ESC/ERS risk tools for the all-cause death end-point but they showed additional value to non-invasive parameters for the combined end-point and, when taken alone, had a discriminatory capacity comparable to ESC/ERS risk tools. Haemodynamics' discriminative ability for clinical worsening is comparable to current ESC/ERS risk tools and is of added value to non-invasive parameters.

Positive Vasoreactivity Testing in Pulmonary Arterial Hypertension: Therapeutic Consequences, Treatment Patterns, and Outcomes in the Modern Management Era.

Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8-60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

The impact of unilateral pulmonary artery stenosis on right ventricular to pulmonary arterial coupling in patients with transposition of the great arteries.

Unilateral pulmonary artery (PA) stenosis is common in the transposition of the great arteries (TGA) after arterial switch operation (ASO) but the effects on the right ventricle (RV) remain unclear. To assess the effects of unilateral PA stenosis on RV afterload and function in pediatric patients with TGA-ASO. In this retrospective study, eight TGA patients with unilateral PA stenosis underwent heart catheterization and cardiac magnetic resonance (CMR) imaging. RV pressures, RV afterload (arterial elastance [Ea]), PA compliance, RV contractility (end-systolic elastance [Ees]), RV-to-PA (RV-PA)coupling (Ees/Ea), and RV diastolic stiffness (end-diastolic elastance [Eed]) were analyzed and compared to normal values from the literature. In all TGA patients (mean age 12 ± 3 years), RV afterload (Ea) and RV pressures were increased whereas PA compliance was reduced. RV contractility (Ees) was decreased resulting in RV-PA uncoupling. RV diastolic stiffness (Eed) was increased. CMR-derivedRV volumes, mass, and ejection fraction were preserved. Unilateral PA stenosis results in an increased RV afterload in TGA patients after ASO. RV remodeling and function remain within normal limits when analyzed by CMR but RV pressure-volume loop analysis shows impaired RV diastolic stiffness and RV contractility leading to RV-PA uncoupling.

(857) - Improvements in Pulmonary Artery Compliance After Balloon Pulmonary Angioplasty Depend on Baseline Pulmonary Vascular Resistance

(857) - Improvements in Pulmonary Artery Compliance After Balloon Pulmonary Angioplasty Depend on Baseline Pulmonary Vascular Resistance

Insights Into Differences in Pulmonary Hemodynamics in Hispanic Patients With Pulmonary Arterial Hypertension.

Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes. A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center. Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates. This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts.

Role of hemolysis on pulmonary arterial compliance and right ventricular systolic function after cardiopulmonary bypass

BackgroundCardiopulmonary bypass (CPB) is associated with intravascular hemolysis which depletes endogenous nitric oxide (NO). The impact of hemolysis on pulmonary arterial compliance (PAC) and right ventricular systolic function has not been explored yet. We hypothesized that decreased NO availability is associated with worse PAC and right ventricular systolic function after CPB. MethodsThis is a secondary analysis of an observational cohort study in patients undergoing cardiac surgery with CPB at Massachusetts General Hospital, USA (2014–2015). We assessed PAC (stroke volume/pulmonary artery pulse pressure ratio), and right ventricular function index (RVFI) (systolic pulmonary arterial pressure/cardiac output), as well as NO consumption at 15 min, 4 h and 12 h after CPB. Patients were stratified by CPB duration. Further, we assessed the association between changes in NO consumption with PAC and RVFI between 15min and 4 h after CPB. ResultsPAC was lowest at 15min after CPB and improved over time (n = 50). RVFI was highest -worse right ventricular function- at CPB end and gradually decreased. Changes in hemolysis, PAC and RVFI differed over time by CPB duration. PAC inversely correlated with total pulmonary resistance (TPR). TPR and PAC positively and negatively correlated with RVFI, respectively. NO consumption between 15min and 4 h after CPB correlated with changes in PAC (−0.28 ml/mmHg, 95%CI −0.49 to −0.01, p = 0.012) and RVFI (0.14 mmHg*L−1*min, 95%CI 0.10 to 0.18, p < 0.001) after multivariable adjustments. ConclusionPAC and RVFI are worse at CPB end and improve over time. Depletion of endogenous NO may contribute to explain changes in PAC and RVFI after CPB.

Efficacy and safety of the Aria pulmonary endovascular device in pulmonary hypertension.

A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and haemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH-LHD) and chronic lung disease (PH-CLD). Eight patients with PH-LHD and 10 patients with PH-CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas-filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Haemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. No complications or investigational device-related serious adverse events occurred. Device activation in PH-LHD and PH-CLD patients decreased pulmonary arterial pulse pressure by 5.6 ± 4.2 mmHg (-12%; p = 0.003) and 4.2 ± 2.2 mmHg (-11%; p < 0.001), increased CPA by 0.4 ± 0.2 ml/mmHg (+23%; p = 0.004) and 0.4 ± 0.3 ml/mmHg (+25%; p = 0.001), and increased right ventricular-to-pulmonary vascular (RV-PV) coupling by 0.24 ± 0.18 (+40%; p = 0.012) and 0.11 ± 0.07 (+21%; p = 0.001), respectively. Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV-PV coupling.

Association of pulmonary hypertension with the outcome in patients undergoing edge-to-edge mitral valve repair

ObjectivesThe association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH.BackgroundPH is frequently found in patients with...