RV-PA Coupling Research Articles

RIGHT VENTRICULAR - PULMONARY VASCULAR COUPLING DURING EXERCISE IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION OR PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE

<h3>BACKGROUND</h3> Pulmonary hypertension (PH) is a state of high afterload to the right ventricle (RV), which is described as afterload sensitive. The purpose of this study was to examine the effect of exercise on the relationship between RV systolic performance [measured as end-systolic elastance (Ees)], and RV afterload [measured as pulmonary arterial (PA) elastance (Ea)] between 2 groups of patients with pulmonary arterial hypertension (PAH) or PH due to left heart disease (PH-LHD). <h3>METHODS AND RESULTS</h3> Patients with suspected PH underwent right heart catheterization with cycle-ergometry and classified by their exercise hemodynamic responses: 1) Normal 2) PAH and 3) PH-LHD. RV, right atrium (RA), and PA pressures were recorded continuously and analyzed offline. As our lab previously reported, RV Ees and PA Ea were calculated using the single-beat method, and Ees:Ea ratio expresses RV-PA coupling. Ees:Ea is defined as uncoupled if < 0.8. Results were analyzed at semi-upright rest and exercise. Data is presented as Mean ± SD or Median [25th – 75th Percentiles]. We included 40 patients (35%Female; 58±15 years); exercise hemodynamic classification comprised 18 Normal, 11 PAH, and 11 PH-LHD. At rest Ea and Ees were significantly elevated in PAH (0.45[0.38-0.98], p=0.002 and 0.85[0.65-1.20], p=0.003) and PH-LHD (0.51[0.32-0.67], p=0.001 and 0.74[0.39-1.20], p=0.017) vs. Normal (0.22[0.17-0.27] and 0.41[0.29-0.54]). Ea increased significantly with exercise in PAH (0.60[0.51-1.36], p=0.003) and PH-LHD (0.59[0.37-0.91], p=0.002) compared to Normal (0.29[0.21-0.36]). Exercise was associated with a significant decline in Ees:Ea ratio in PH-LHD (∆-0.23±0.72, p=0.022). Ees:Ea ratio was uncoupled at rest/exercise in 6% of the Normal group, 55% of the PAH group and 36% of the PH-LHD group. Figure 1 illustrates the trend to Ees:Ea uncoupling if Ea increased by more than 0.2mmHg/mL. Compared to patients with preserved Ees:Ea coupling, patients with PH and Ees:Ea uncoupling with exercise demonstrated significantly higher increases in RA pressures (∆9±5mmHg vs ∆4±3mmHg, p=0.012) and more impaired stroke volume indexed to body surface area (∆3±9mL/m2 vs ∆12±8mL/m2 p=0.032). <h3>CONCLUSION</h3> During exercise, RV afterload increases in patients with PAH and PH-LHD. In both PH groups, the proportion of patients with Ees:Ea uncoupling was high, and the decline in Ees:Ea ratio reached statistical significance in PH-LHD. Uncoupling of the Ees:Ea ratio occurred with larger increases in Ea and was associated with evidence of impaired RV systolic and diastolic function with exercise. Limiting the increase in Ea with exercise and/or preservation of Ees:Ea coupling may optimize RV function in PH patients.

Right Ventricular-Pulmonary Arterial Coupling in Repaired Tetralogy of Fallot.

We assessed right ventricular (RV)-pulmonary arterial (PA) coupling in patients with repaired tetralogy of Fallot (TOF). Sixty patients (34 males) aged 18.6 ± 8.3years at 14.8 ± 7.4years after repair and 60 controls were studied. Two-dimensional, tissue Doppler and speckle tracking echocardiography and colour flow mapping were performed to assess RV end-systolic (ESA) and -diastolic areas, tricuspid valve Doppler and myocardial velocities, left ventricular (LV) and RV deformation and pulmonary (PR), tricuspid regurgitation (TR), respectively. The ratios of RV area change to ESA and peak tricuspid annular systolic (s) velocity to RV ESA indexed to body surface area reflected RV-PA coupling. Patients had greater RV areas and reduced tricuspid annular and myocardial velocities, LV and RV myocardial mechanics compared to controls (all p < 0.05). Both RV area change/ESA ratio and peak tricuspid annular s velocity/indexed RV ESA ratio were reduced in patients (all p < 0.001). Sixty-one and 100% of patients had, respectively, RV area change/ESA ratio and peak tricuspid annular s velocity/indexed RV ESA ratio < -2SD of controls. Indices of RV-PA coupling correlated positively with tricuspid myocardial velocities, LV and RV deformation and inversely with PR and TR (all p < 0.05). Multivariate analysis showed RV systolic strain rate, PR and TR as independent predictors of both RV-PA coupling indices, whilst age, gender and LV systolic strain were also predictors of peak tricuspid annular s velocity/indexed RV ESA ratio (all p < 0.05). In conclusion, RV-PA coupling is impaired and is associated with RV and LV mechanics and severity of PR and TR in patients with repaired TOF.

Age-changes in right ventricular function-pulmonary circulation coupling: from pediatric to adult stage in 1899 healthy subjects. The RIGHT Heart International NETwork (RIGHT-NET).

The present study analyzes age-specific changes in RV function and RV-PA coupling in a large cohort of apparently healthy subjects with a wide age-range, to identify reference values and to study the influence of clinical and echocardiographic cofactors. 1899 Consecutive healthy subjects underwent a standardized transthoracic echocardiographic examination. Tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) were measured. Ventriculo-arterial coupling was then inferred from the TAPSE/SPAP ratio. A quantile regression analysis was used to estimate quantiles 0.05, 0.10, 0.50 (median), 0.90, and 0.95 of TAPSE, SPAP and TAPSE/SPAP. The association between age and each of these values was determined. The mean age of the group was 45.2 ± 18.5years (range 1 to 102years), 971 were males. SPAP increased with age, whereas TAPSE and TAPSE/SPAP ratio decreased. Upon multivariate modeling, the most significant positive associations for TAPSE were body surface area (BSA) driven by the pediatric group, stroke volume (SV), E/A and negatively heart rate and E/e' ratio. SPAP was positively associated with increasing age, SV, E/A, E/e' and negatively with BSA. TAPSE/SPAP ratio was negatively associated with age, female sex, and E/e' and positively with BSA. A preserved relationship between TAPSE and SPAP was found across the different age groups. TAPSE, SPAP and TAPSE/SPAP demonstrate important trends and associations with advancing age, impaired diastolic function, affected by female sex and BSA However the relationship between TAPSE and SPAP is relatively well preserved across the age spectrum.

Right Ventricular Function and Its Coupling With Pulmonary Circulation in Precapillary Pulmonary Hypertension: A Three-Dimensional Echocardiographic Study.

Objective: To assess right ventricular (RV) function and RV-pulmonary arterial (PA) coupling by three-dimensions echocardiography and investigate the ability of RV-PA coupling to predict adverse clinical outcomes in patients with precapillary pulmonary hypertension (PH).Methods: We retrospectively collected a longitudinal cohort of 203 consecutive precapillary PH patients. RV volume, RV ejection fraction (RVEF), and RV longitudinal strain (RVLS) were quantitatively determined offline by 3D echocardiography. RV-PA coupling parameters including the RVEF/PA systolic pressure (PASP) ratio, pulmonary arterial compliance (PAC), and total pulmonary resistance (TPR) were recorded.Results: Over a median follow-up period of 20.9 months (interquartile range, 0.1–67.4 months), 87 (42.9%) of 203 patients experienced adverse clinical outcomes. With increasing World Health Organization functional class (WHO-FC), significant trends were observed in increasing RV volume, decreasing RVEF, and worsening RVLS. RV arterial coupling (RVAC) and PAC were lower and TPR was higher for WHO-FC III+IV than WHO-FC I or II. The RVEF/PASP ratio showed a significant correlation with RVLS. RVAC had a stronger correlation with the RVEF/PASP ratio than other indices. Multivariate Cox proportional-hazard analysis identified a lower 3D RVEF and worse RVLS as strong predictors of adverse clinical events. RVAC, TPR, and PAC had varying degrees of predictive value, with optimal cutoff values of 0.74, 11.64, and 1.18, respectively.Conclusions: Precapillary-PH with RV-PA uncoupling as expressed by a RVEF/PASP ratio <0.44 was associated with adverse clinical outcomes. PAC decreased and TPR increased with increasing WHO-FC, with TPR showing better independent predictive value.

Right ventricular-arterial coupling - A new perspective for right ventricle evaluation in heart failure patients undergoing cardiac resynchronization therapy.

Right ventricular - arterial (RV-PA) coupling can be estimated by echocardiography using the ratio between (TAPSE) and pulmonary arterial systolic pressure (PASP). TAPSE/PASP ratio proved to be a prognostic parameter in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the significance of RV-PA coupling in patients with HFrEF undergoing cardiac resynchronization therapy (CRT). Patients undergoing CRT in our center between January 2017 and November 2019 were eligible. Response to CRT was defined by a reduction of more than 15% of left ventricle systolic volume (LVESV) one year after CRT. Primary endpoint was a composite of HF hospitalizations and death during follow-up. 54 patients (Age 64.0±13.8years; 58% male; left ventricular ejection fraction (LVEF) 28.4±1.3%) were prospectively included. After a mean follow-up of 31±12.9months, the primary endpoint had occurred in 18 (33.3%) patients. A lower TAPSE/PASP ratio was associated with baseline worse HF symptoms, lower LVEF and long-term less LV reverse remodeling (P<.05). After one year CRT improved RV systolic function (TAPSE, RV global longitudinal strain, P<.05), but not TAPSE/PASP ratio (P=.4). The ratio TAPSE/PASP (AUC=0.834)≥0.58mm/mmHg showed good sensitivity (90%) and specificity (81.8%) for predicting response to CRT while a ratio <0.58mm/mmHg was associated with a higher risk of death and HF hospitalizations during the follow-up (HR 5.37 95%CI [1.6-18], P<.001). RV-PA coupling evaluation using TAPSE/PASP ratio predicts CRT response. A lower TAPSE/PASP ratio is associated with a higher risk of adverse cardiovascular events.

Pulmonary Arterial Remodeling Is Related to the Risk Stratification and Right Ventricular-Pulmonary Arterial Coupling in Patients With Pulmonary Arterial Hypertension.

BackgroundPulmonary arterial (PA) stiffness has an essential contribution to the right ventricular (RV) failure pathogenesis. A comprehensive and multiparameter risk assessment allows predicting mortality and guiding treatment decisions in PA hypertension (PAH). We characterize PA remodeling with intravascular ultrasound (IVUS) in prevalent and stable patients with PAH according to the ESC/ERS risk table and analyze the RV-PA coupling consequences.MethodsTen control subjects and 20 prevalent PAH adult patients underwent right heart catheterization (RHC) with simultaneous IVUS study. We estimated cardiac index (CI), pulmonary vascular resistance, and compliance (PVR, PAC) by standard formulas. From IVUS and RHC data, PA diameter, wall thickness/luminal diameter ratio, and indexes of stiffness (pulsatility, compliance, distensibility, incremental elastic modulus - Einc-, and the stiffness index β) were measured. We evaluated RV-PA coupling by the ratio of tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure (TAPSE/sPAP). The individual average risk was calculated by assigning a score of 1 (low-risk -LR-), 2 (intermediate-risk -IR-), and 3 (high-risk -HR-) for each of seven variables (functional class, six-minute walking test, brain natriuretic peptide, right atrial area and pressure, CI, and PA oxygen saturation) and rounding the average value to the nearest integer.ResultsAll PA segments interrogated showed increased vessel diameter, wall cross-sectional area (WCSA), and stiffness in patients with PAH compared to control subjects. 45% corresponded to LR, and 55% corresponded to IR PAH patients. The different measurements of PA stiffness showed significant correlations with TAPSE/sPAP (r = 0.6 to 0.76) in PAH patients. The IR group had higher PA stiffness and lower relative WCSA than LR patients (P < 0.05), and it is associated with a lower PAC and TAPSE/sPAP (P < 0.05).ConclusionIn prevalent PAH patients, the severity of proximal PA remodeling is related to the risk stratification and associated with PAC and RV-PA coupling impairment beyond the indirect effect of the mean PA pressure. The concomitant assessment of IVUS and hemodynamic parameters at diagnosis and follow-up of PAH patients could be a feasible and safe tool for risk stratification and treatment response of the PA vasculopathy during serial hemodynamic measurements.

Right Ventricular–Pulmonary Arterial Coupling in Secondary Tricuspid Regurgitation

Chronic pressure-overload induces right ventricular (RV) adaptation to maintain RV-pulmonary arterial (PA) coupling. RV remodeling is frequently associated with secondary tricuspid regurgitation (TR) which may accelerate uncoupling. Our aim is to determine whether the non-invasive analysis of RV-PA coupling could improve risk stratification in patients with secondary TR. A total of 1,149 patients (median age 72[IQR, 63 to 79] years, 51% men) with moderate or severe secondary TR were included. RV-PA coupling was estimated using the ratio between two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). The risk of all-cause mortality across different values of TAPSE/PASP was analyzed with a spline analysis. The cut-off value of TAPSE/PASP to identify RV-PA uncoupling was based on the spline curve analysis. At the time of significant secondary TR diagnosis the median TAPSE/PASP was 0.35 (IQR, 0.25 to 0.49) mm/mm Hg. A total of 470 patients (41%) demonstrated RV-PA uncoupling (<0.31 mm/mm Hg). Patients with RV-PA uncoupling presented more frequently with heart failure symptoms had larger RV and left ventricular dimensions, and more severe TR compared to those with RV-PA coupling. During a median follow-up of 51 (IQR, 17 to 86) months, 586 patients (51%) died. The cumulative 5-year survival rate was lower in patients with RV-PA uncoupling compared to their counterparts (37% vs 64%, p < 0.001). After correcting for potential confounders, RV-PA uncoupling was the only echocardiographic parameter independently associated with all-cause mortality (HR 1.462; 95% CI 1.192 to 1.793; p < 0.001). In conclusion, RV-PA uncoupling in patients with secondary TR is independently associated with poor prognosis and may improve risk stratification.

Right ventricular load and contractility in HIV-associated pulmonary hypertension.

BackgroundPeople living with human immunodeficiency virus (PLWH) are at risk of developing pulmonary hypertension (PH) and right ventricular (RV) dysfunction, but understanding of the relationship of RV function to afterload (RV-PA coupling) is limited. We evaluated the clinical and hemodynamic characteristics of human immunodeficiency virus (HIV)-associated PH.MethodsWe performed a retrospective review of patients with a diagnosis of HIV undergoing right heart catheterization (RHC) from 2000–2016 in a tertiary care center. Inclusion criteria were diagnosis of HIV, age ≥ 18 years and availability of RHC data. PH was classified as either pulmonary arterial hypertension (PAH; mean pulmonary arterial pressure [mPAP] ≥ 25mmHg with pulmonary artery wedge pressure [PAWP] ≤ 15mmHg) or pulmonary venous hypertension (PVH; mPAP ≥ 25mmHg with PAWP > 15). We collected demographics, CD4 cell count, HIV viral load, RHC and echocardiographic data. The single beat method was used to calculate RV-PA coupling from RHC.ResultsSixty-two PLWH with a clinical likelihood for PH underwent RHC. Thirty-two (52%) met PH criteria (15 with PAH, 17 with PVH). Average time from diagnosis of HIV to diagnosis of PH was 11 years. Eleven of 15 individuals with PAH were on antiretroviral therapy (ART) while all 17 patients with PVH were on ART. Compared to PLWH without PH, those with PH had an increased likelihood of having a detectable HIV viral load and lower CD4 cell counts. PLWH with PAH or PVH had increased RV afterload with normal RV contractility, and preserved RV-PA coupling.ConclusionPLWH with PH (PAH or PVH) were more likely to have a detectable HIV viral load and lower CD4 count at the time of RHC. PLWH with PAH or PVH had increased RV afterload, normal RV contractility, with preserved RV-PA coupling suggestive of an early onset, mild, and compensated form of PH. These results should be confirmed in larger studies.

Preoperative right ventricular overwork is a major determinant of residual pulmonary arterial hypertension in patients with repaired arterial septal defect

Abstract Funding Acknowledgements Type of funding sources: None. Background The haemodynamic effect of atrial septal defect (ASD) is a chronic volume overload of the right heart and pulmonary vasculature. Pulmonary overcirculation is generally compensated for by the right ventricular (RV) and pulmonary arterial (PA) reserve. However, in a subset of patients, prolonged pulmonary overcirculation insidiously induces obstructive pulmonary vasculopathy, which results in postoperative residual pulmonary arterial hypertension (PAH) after ASD closure. Postoperative PAH is a major concern because it is closely associated with poor outcomes and impaired quality of life. However, to date, no clinically robust predictors of postoperative residual PAH have been clearly identified. Purpose This study sought to assess the haemodynamic characteristics of ASD patients in terms of mechano-energetic parameters and to identify the predictors of postoperative residual PAH in these patients. Methods A total of 120 ASD patients (age: 58 ± 17 years) and 46 normal controls were recruited. As previously reported, the simplified RV contraction pressure index (sRVCPI) was calculated as an index of RV external work by multiplying the tricuspid annular plane systolic excursion (TAPSE) by the pressure gradient between the RV and right atrium. RV- PA coupling was evaluated using TAPSE divided by PA systolic pressure as an index of the RV length-force relationship. These parameters were measured both at baseline and 6 months after ASD closure. Results As expected, baseline sRVCPI was significantly greater in patients with ASD than in controls (775 ± 298 vs. 335 ± 180 mm Hg • mm, P &amp;lt; 0.01), which indicated significant "RV overwork". As a result, RV-PA coupling in ASD patients was significantly impaired compared to that in controls (0.9 ± 0.8 vs. 3.5 ± 1.7 mm/mm Hg, P &amp;lt; 0.01). All 120 ASD patients underwent transcatheter or surgical shunt closure; 15 of them had residual PAH after closure. After 6 months, RV-PA coupling index significantly improved in patients without residual PAH, from 0.96 ± 0.81 to 1.27 ± 1.24 mm/mm Hg (P = 0.02). Furthermore, RV load was markedly reduced, with sRVCPI falling from 691 ± 258 to 434 ± 217 mm Hg • mm, P &amp;lt; 0.01). However, in patients with residual PAH, RV-PA coupling index deteriorated from 0.64 ± 0.23 to 0.53 ± 0.12 mm/mm Hg (P &amp;lt; 0.01). As a result, RV overload was not significantly relieved (sRVCPI; from 971 ± 382 to 783 ± 166 mm Hg • mm, P = 0.22). In a multivariate analysis, baseline pulmonary vascular resistance (hazard ratio 1.009; P &amp;lt; 0.01) and preoperative sRVPCI (hazard ratio 1.003; P &amp;lt; 0.01) revealed to be independent predictors of residual PAH. Conclusion In terms of mechano-energetic function, preoperative "RV overwork" can be used as a robust predictor of an impaired RV-PA relationship in ASD patients. Moreover, periodic assessment of sRVPCI may contribute to the better management for patients with unrepaired ASD. Abstract Figure.

Intermittent outpatient administration of levosimendan improves right ventricular-pulmonary arterial coupling in ambulatory patients with advanced heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background Intermittent infusions of levosimendan in an outpatient setting have been associated with improved symptoms and reduced hospitalizations in patients with advanced heart failure (HF). Little is known on the potential effect of intermittent levosimendan infusions on right ventricle (RV)-pulmonary arterial (PA) coupling in ambulatory patients with advanced HF. Purpose Aim of the present study was to explore the effects of intermittent levosimendan infusions on the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PAPs), an echocardiographic measure of RV/PA coupling, in ambulatory patients with advanced HF, and on left ventricular arterial coupling (VAC), expressed as the relationship between arterial elastance (Ea) and ventricular elastance (Ees). Methods 17 ambulatory patients with advanced HF treated with intermittent levosimendan (6-hour intravenous infusion, 0.2 ug/kg/min without bolus) received baseline clinical, biochemical and echocardiographic evaluation and changes in TAPSE/PAPs ratio were assessed from baseline to 48 hours after the infusion, based on the pharmacokinetic profile of levosimendan. VAC, expressed as Ea/Ees ratio, was obtained by a calculator (iElastance) designed for non-invasive single beat measure of end-systolic Ees and Ea according to Chen"s method. Results After 48 hours from levosimendan infusion, there was a significant improvement of TAPSE/PAPs ratio (p = 0.04), stroke voume (SV) (p = 0.05) and cardiac output (CO)(p = 0.04). We observed a significant reduction of Ea (p = 0.007) and of Ees (p = 0.01) and a non significant improvement of VAC (p = 0.4)(Tab.1). Conclusion. Our results show that an intermittent 6-hour levosimendan infusion at 0.2 ug/kg/min improves after 48 hours RV-PA coupling, SV, CO, Ea and Ees in ambulatory patients with advanced HF. Further studies including more patients are necessary to confirm these preliminary findings. Tab.1 Baseline 48h afterlevosimendan infusion p value NT-proBNP (pg/mL) 5607 ± 4300 3868 ± 3856 &amp;lt;0.001 LVEF (%) 24.1 ± 7.7 25.7 ± 7.3 0.5 SV (mL) 36.8 ± 12.4 46.1 ± 14.8 0.05 CO (L/min)36.8 ± 12.4 2.6 ± 0.7 3.2 ± 0.9 0.05 TAPSE/PAPs (mm/mmHg) 0.38 ± 0.13 0.49 ± 0.16 0.04 Ea (mmHg/mL/m2) 2.9 ± 0.9 2.1 ± 0.6 0.007 Ees (mmHg/mL/m2) 1.3 ± 0.4 1.0 ± 0.2 0.01 VAC 2.2 ± 0.6 2.0 ± 0.4 0.4

Echocardiographic evaluation of pulmonary hypertension, right ventricular function, and right ventricular-pulmonary arterial coupling in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients are at increased risk for developing cardiovascular disease, including right heart failure. The evaluation of right ventricle (RV) using the relationship between tricuspid annular plane systolic excursion (TAPSE) and right ventricular systolic pressure (RVSP) is of clinical prognostic relevance. Mild echocardiographic pulmonary hypertension (ePH) has been associated with worse RV function. The aim of this study was to evaluate RV function as measured by TAPSE to RVSP ratio in rheumatoid arthritis patients compared to matched healthy controls. A case-control study with 67 RA patients aged 40 to 75 years that fulfilled the 2010 ACR/EULAR criteria and 45 matching controls was included. A transthoracic echocardiogram was performed to all patients. TAPSE was measured as the distance traveled from end-diastole to end-systole. RVSP was calculated using the modified Bernoulli equation. Comparisons were done using Chi-square and Mann-Whitney's U test or Student's t test. Patients with RA had significantly reduced ventricular function (TAPSE 23 [21-25] vs 25 [23-26], p = 0.033) and TAPSE/RVSP ratio was significantly lower in RA-patients than controls (TAPSE to RVSP ratio 0.809 [0.67-1.01] vs 0.933 [0.79-1.11], p = 0.009). RA-patients with mild ePH had similar RV function, evaluated by TAPSE, in comparison to RA-patients with normal RVSP. RA-patients had worse RV function measured by TAPSE and worse TAPSE/RVSP ratio than controls. Also, RA-patients with mild ePH had reduced right ventricular-pulmonary arterial coupling in comparison with patients with RA and normal RVSP. These echocardiographic findings could justify aggressive treatment for these patients and assess their evolution. Key Points • Right ventricular (RV) function and RV coupling with the pulmonary artery (RV-PA coupling) were worse in patients with RA in comparison to healthy controls. • Values of right ventricular systolic pressure (RVSP) were similar between RA-patients and non-RA controls. • Prevalence of normal RVSP, mild echocardiographic pulmonary hypertension (ePH), and pulmonary hypertension was similar between RA-patients and non-RA matched controls •Patients with RA and mild ePH had reduced RV-PA coupling in comparison with RA-patients with normal RVSP.

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching. Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared. Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24). These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.

Right ventricular dysfunction in critically ill COVID-19 ARDS

AimsComprehensive echocardiography assessment of right ventricular (RV) impairment has not been reported in critically ill patients with COVID-19. We detail the specific phenotype and clinical associations of RV impairment in COVID-19 acute respiratory distress syndrome (ARDS). MethodsTransthoracic echocardiography (TTE) measures of RV function were collected in critically unwell patients for associations with clinical, ventilatory and laboratory data. ResultsNinety patients (25.6% female), mean age 52.0 ± 10.8 years, veno-venous extracorporeal membrane oxygenation (VVECMO) (42.2%) were studied. A significantly higher proportion of patients were identified as having RV dysfunction by RV fractional area change (FAC) (72.0%,95% confidence interval (CI) 61.0–81.0) and RV velocity time integral (VTI) (86.4%, 95 CI 77.3–93.2) than by tricuspid annular plane systolic excursion (TAPSE) (23.8%, 95 CI 16.0–33.9), RVS’ (11.9%, 95% CI 6.6–20.5) or RV free wall strain (FWS) (35.3%, 95% CI 23.6–49.0). RV VTI correlated strongly with RV FAC (p ≤ 0.01). Multivariate regression demonstrated independent associations of RV FAC with NTpro-BNP and PVR. RV-PA coupling correlated with PVR (univariate p < 0.01), as well as RVEDAi (p < 0.01), and RVESAi (p < 0.01), and was associated with P/F ratio (p 0.026), PEEP (p 0.025), and ALT (p 0.028). ConclusionsSevere COVID-19 ARDS is associated with a specific phenotype of RV radial impairment with sparing of longitudinal function. Clinicians should avoid interpretation of RV health purely on long-axis parameters in these patients. RV-PA coupling potentially provides important additional information above standard measures of RV performance in this cohort.

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)

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.

Abstract 15011: Association of Pulmonary Hemodynamics and Right Ventricular Function With Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Higher pulmonary artery systolic pressure (PASP) and right ventricular (RV) dysfunction are associated with higher risk of heart failure (HF) and mortality. Whether higher PASP and lower RV function are associated with risk of atrial fibrillation (AF) is unclear. Hypothesis: Higher PASP, higher pulmonary vascular resistance (PVR), and lower RV function are associated with incident AF after accounting for left atrial (LA) size and function, and left ventricular (LV) systolic and diastolic function. Methods: ARIC participants free of prevalent coronary heart disease (CHD), HF, AF, and with LA volume index (LAVi) &lt;34ml/m 2 and average E/e’ ratio &lt;14 in 2011-13 were included. We measured PASP, PVR, RV fractional area change (RVFAC), and RV-PA coupling (defined as RVFAC/PASP ratio) from 2D-echocardiograms. Incident AF (through 2018) was ascertained from hospital discharge codes and death certificates. We used Cox proportional hazards regression in our analysis. Results: We included 1915 participants (mean age 75 years, 69% female, 24% black) of whom 176 developed AF over a median follow-up of 6.3 years. PASP, PVR, and RV-PA coupling were significantly associated with incident AF after adjusting for measures of LA and LV structural and functional remodeling. RVFAC was not significantly associated with incident AF. Conclusions: In persons without CHD, HF, and LA enlargement, higher PASP and lower RV-PA coupling are associated with higher risk of AF after accounting for LA and LV structural and functional remodeling. This finding, which suggests a possible etiological role of RV remodeling for AF, needs further confirmation.

Right ventricle to pulmonary artery coupling improves early after transcatheter aortic valve implantation and this is related to improved left atrial function

Abstract Background Transcatheter aortic valve implantation (TAVI) improves not only left heart remodeling but also has an upstream effect on the right ventricle and pulmonary vasculature. Right ventricle (RV) to pulmonary artery (PA) coupling, a parameter which integrates RV systolic performance at a given degree of afterload, was associated with all-cause mortality in these patients (pts). Our aim was to evaluate the short-term effect of TAVI on RV-PA coupling and the main determinants of RV-PA coupling in pts with aortic stenosis (AS) undergoing transfemoral TAVI. Methods We have prospectively enrolled 102 consecutive pts (76±8 years, 57 men) with severe AS undergoing TAVI. All pts underwent a comprehensive echocardiogram both before and 30 days after TAVI, including speckle tracking echocardiography (STE) for myocardial deformation analysis. Peak values of global longitudinal left ventricular strain (GLS), left atrial strain (LAε, reservoir function), and late diastolic LA strain rate (ASr, contractile function) were measured. The ratio of tricuspid annular plane systolic excursion (TAPSE) to PA systolic pressure (PASP) was used as an estimate of RV-PA coupling. Results Compared with baseline, there was a significant increase in LV ejection fraction after TAVI (54±12% vs 50±13%, p=0.04), a significant reduction in LV mass (147±35 vs 171±44 g/m2, p&amp;lt;0.001) and increase in absolute GLS values (14±3% vs 12±5%, p=0.007). Indexed LA volumes decreased (49±19 vs 55±19 ml/m2, p=0.03) while both global LAε and ASr improved significantly after TAVI (16±8% vs 13±7%, p=0.01 and −1.2±0.6 vs −0.9±0.6%, p=0.01). A significant improvement of TAPSE/PASP values (0.069±0.026 vs 0.057±0.025 cm/mm Hg, p&amp;lt;0.001) was found after TAVI, indicating an enhanced RV-PA coupling. In multivariable regression analysis global LAε was independently related to RV-PA coupling, both before and after TAVI (R=0.54, p=0.003 and R= 0.39, p&amp;lt;0.001). The increase in RV-PA coupling was significantly related to the increase in LAε (p=0.005). Conclusions Our results confirm that relief of aortic valve obstruction by TAVI has beneficial effects on the RV-PA coupling, that occur early after intervention. This is accompanied by a significant improvement in LV and LA deformation. Moreover, there is a significant correlation between LA function and RV-PA coupling both before and after TAVI. Enhanced RV-PA coupling after TAVI is related to improved LA strain, suggesting the contribution of LA function in modulating right heart function in this setting. Funding Acknowledgement Type of funding source: None

Right ventricular pulmonary vascular coupling in secondary tricuspid regurgitation: a pressure volume loop study

Abstract Introduction The severity of secondary tricuspid regurgitation (sTR) predicts outcome of patients with left heart failure with reduced ejection fraction (HFrEF). In these patients sTR predominantly occurs as a result of secondary pulmonary hypertension (PH). However, more than 46% of patients with severe PH have only mild or none sTR. In this study we tested the hypothesis that intrinsic right ventricular (RV) contractility adaptation to the pulmonary arterial (PA) vascular load (RV-PA-coupling) is associated with the presence and severity of sTR. Methods In 110 patients with HFrEF (a post-hoc analysis of the Magdeburger CRT Responder Trial, DRKS00011133) we quantified the RV intrinsic contractility response (end-systolic elastance, Ees) to pulmonary vascular afterload (arterial elastance, Ea) and its coupling ratio (RV-PA coupling ratio: Ees/Ea) by the RV pressure-volume loop catheter technique at baseline, and combined it with echocardiography-derived parameter of sTR presence and severity and RV function. Results Echocardiography at baseline demonstrated no or trace TR (TR0) in 67 patients (61%), mild TR (TR1) in 23 (21%), moderate TR (TR2) in 11 (10%), and severe TR (TR3) in 9 (8%). The transition from TR0 to TR1 was characterized by a pronounced drop of the RV-PA coupling ratio (TR0: Ees/Ea= 0.88, 0.67–1.1 vs. TR1: Ees/Ea= 0.48, 0.3–0.83, p&amp;lt;0.001), caused by a non-adaptive, non-rising Ees (0.24 mmHg/ml, 0.34–0.44 vs. 0.3 mmHg/ml, 0.21–0.46, p=0.8, respectively, p&amp;lt;0.001). We observed a further but only marginal drop of Ees/Ea from TR1 to TR3 (p=0.008) caused by an additional small non-significant decrease of Ees and increase of Ea. Interestingly, other afterload parameter, such as PA-pressure, wedge pressure (PCWP), PA compliance, and PA resistance (PVR), and parameters of RV function, such as tricuspid annular plane systolic excursion (TAPSE) and fractional area shortening (FAC) followed the same course of a pronounced drop from TR0 to TR1, succeeded by an only marginal change from TR1 to TR3. In contrast, the progressive RV-PA un-coupling from TR0 to TR3 was accompanied by a more or less continuously increase of RV size and volume load (end-diastolic (ED) area in 4 chamber view, ED-RV outflow tract diameter, size of tricuspid annulus). In the binary logistic regression analysis, the decrease of RV-PA coupling ratio Ees/Ea (OR 0.14, CI 0.001–0.165) and PA compliance (OR 0.44, CI 0.25–0.79) were independently associated with the transition from TR0 to TR1–3. Conclusion The presence and severity of secondary TR in patients with HFREF is independently associated with a progressive RV-PA uncoupling. Most importantly, already the transition from none TR to mild TR is characterized by a significant and pronounced increase of pulmonary vascular afterload, a non-adaptive RV contractility response, and resulting RV-PA un-coupling. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boston Scientific

Evaluation of right ventricle pulmonary artery coupling on right ventricular function in post operative tetralogy of Fallot patients underwent for pulmonary valve replacement

BackgroundTo evaluate RV-PA coupling in post operative TOF patients with ventricular dilatation underwent for PVR and investigate the correlation between ventricular functions measuring Ea/Emax ratio using cardio magnetic resonance and the effect of surgical type at primary repair of TOF on coupling.MethodRV-PA coupling was measured noninvasively by Ea/Emax ratio from CMRI and ECHO. From CMRI results the patients were divided in two groups, RV-PA coupling and RV-PA uncoupling. Ea/Emax ≤1 was considered for coupling patients and Ea/Emax > 1 for uncoupling patients.ResultsNinety patients were uncoupled (Ea/Emax: 1.55 ± 0.46) and 45 were coupled (Ea/Emax: 0.81 ± 0.15). Out of 75 TAP repaired patients 60 were uncoupled RV-PV. In addition, higher pro-BNP is an important factor for uncoupled RV-PV (P = 0.001). CMR evaluation for right ventricular function between uncoupling and coupling were RVEDVi (196.65 ± 63.57 vs. 154.28 ± 50.07, P = 0.001), RVESVi (121.19 ± 51.47 vs. 83.94 ± 20.43, P = 0.001), RVSVi (67.19 ± 19.87 vs. 106.31 ± 33.44, P = 0.001), and RVEF (40.90 ± 8.73 vs. 54.63 ± 4.76, P = 0.001). The increased RVEDVi, RVESVi and RVSVi and decreased RVEF have significant correlation with Ea/Emax. Ea/Emax was also found positively correlated with RVEDVi (P = < 0.05, r = 0.35), RVESVi (P = < 0.001, r = 0.41) and negatively correlated with RVSVi (P = < 0.05, r = 0.22) and RVEF (P = < 0.05, r = 0.78).ConclusionsUnfavorable RV-PA coupling is present in post operative TOF patients and it is affected by several factors. Our results explain a new concept of RV-PA interactions as a contributing mechanism for the observed decline in RV function.

Association between right-sided cardiac function and ultrasound-based pulmonary congestion on acutely decompensated heart failure: findings from a pooled analysis of four cohort studies.

Right ventricular (RV) dysfunction and RV-pulmonary artery (PA) uncoupling are associated with the development of pulmonary congestion during exercise. However, there is limited information regarding the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated heart failure (HF). We performed an individual patient meta-analysis from four cohort studies of hospitalized patients with HF who had available lung ultrasound (B-lines) data on admission and/or at discharge. RV function was assessed by tricuspid annular plane systolic excursion (TAPSE), RV-PA coupling was defined as the ratio of TAPSE to PA systolic pressure (PASP). Admission and discharge cohort included 319 patients (75.8 ± 10.1years, 46% women) and 221 patients (77.9 ± 9.0years, 47% women), respectively. Overall, higher TAPSE was associated with higher ejection fraction, lower PASP, b-type natriuretic peptide and B-line counts. By multivariable analysis, worse RV function or RV-PA coupling was associated with higher B-line counts on admission and at discharge, and with a less reduction in B-line counts from admission to discharge. Higher B-line counts at discharge were associated with a higher risk of the composite of all-cause mortality and/or HF re-hospitalization [adjusted-HR 1.13 (1.09-1.16), p < 0.001]. Furthermore, the absolute risk increase related to high B-line counts at discharge was higher in patients with lower TAPSE. In patients with acutely decompensated HF, impaired RV function and RV-PA coupling were associated with severe pulmonary congestion on admission, and less resolution of pulmonary congestion during hospital stay. Worse prognosis related to residual pulmonary congestion was enhanced in patients with RV dysfunction. TAPSE, tricuspid annular plane systolic excursion; PASP, pulmonary artery systolic pressure.

P1309RIGHT VENTRICULAR-PULMONARY ARTERIAL UNCOUPLING IN PATIENTS ON CHRONIC HEMODIALYSIS WITH SEVERE RIGHT VENTRICULAR REMODELING

Abstract Background and Aims Patients on chronic hemodialysis (HD) may present right ventricular (RV) dysfunction and increased pulmonary artery pressure (PA). The aim of the current study is to describe the RV-PA coupling in chronic patients on HD. Method This study explored the adequacy of RV-PA coupling in 41 patients on HD. They underwent a comprehensive transthoracic Doppler echocardiography, and were stratified in accordance with the severity of RV remodeling defined by the presence of RV dilation (tricuspid annulus ≥40 mm) and RV systolic dysfunction (tricuspid annulus systolic excursion plane [TAPSE] &amp;lt;17 mm). RV-PA coupling was estimated by the TAPSE to PA systolic pressure (TAPSE:PASP) ratio. Results Three groups of patients were identified: No RV remodeling (Group 1, n=26), mild-to-moderate RV remodeling (Group 2, n=11) and severe RV remodeling (Group 3, n=4). Compared to patients from Groups 1 and 2, patients from Group 3 exhibited significant lower TAPSE values (p&amp;lt;0.001), a tendency to higher PASP values (p=0.054) and significant lower TAPSE:PASP ratio values (p=0.012). C-reactive protein levels and were directly correlated with PASP (r=0.405, p=0.017) and inversely with TAPSE (r=-0.311, p=0.041) and the TAPSE:PASP ratio (r= -0.392, p=0.015) in all patients. These echocardiographic parameters were not correlated with other biochemical, hemodynamic or anthropometric parameters. Conclusion These findings suggest that RV-PA coupling is markedly decreased in HD patients with severe RV remodeling. The role of systemic inflammation in RV remodeling and RV-PA uncoupling in HD patients warrants further studies.