RV-PA Coupling Research Articles

Abstract 4142768: Association Between Right Ventricular-Pulmonary Arterial Coupling and Outcomes in Patients with Heart Failure with Preserved Ejection Fraction

Introduction: Right ventricle (RV)-pulmonary artery (PA) coupling reflects functional adaptation of RV to afterload. Impaired RV-PA coupling is associated with worse outcomes in patients with pulmonary hypertension. However, the association between RV-PA coupling and outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not well established. Objective: To assess the association between RV-PA coupling and outcomes in patients with HFpEF and determine an optimal cutpoint of the TAPSE/RVSP ratio for prediction of adverse events. Methods: Participants with a diagnosis of HFpEF were enrolled at the University of Toledo Medical Center from March 2012 and were followed until August 2023. The ratio of tricuspid annular plain systolic excursion (TAPSE) to right ventricular systolic pressure (RVSP) on echocardiogram was used as a measure of RV-PA coupling. The primary endpoint was death or heart failure hospitalization. ROC analysis was performed to determine an optimal cutpoint point for TAPSE/RVSP. Cox proportional hazards regression model was used to assess the association between TAPSE/RVSP and outcomes. Results: 83 participants (age 68.69 ± 10.72, 67.5% female) with HFpEF and available echocardiogram data were enrolled in the study. The median TAPSE/RVSP was 0.41. Death or heart failure hospitalization occurred in 51 (56.6%) individuals. Using ROC curve analysis, we identified the optimal cutpoint of TAPSE/RVSP of 0.31 which had a sensitivity of 57% and specificity of 88% for predicting mortality (AUC 0.756, 0.622-0.889). TAPSE/RVSP less than 0.31 was associated with higher risk of death or heart failure (HF) hospitalization (HR=2.61, CI=1.28-5.33, p= 0.008), death (HR=3.40, CI=1.34-8.64, p= 0.01), and HF hospitalization (HR=2.45, CI=1.06-5.68, p= 0.03). Conclusion: Worse RV-PA coupling was associated with worse outcomes in individuals with HFpEF. The TAPSE/RVSP cutpoint of <0.31 had a good specificity for prediction of adverse events including death or HF hospitalization.

Abstract 4135001: Right Ventricular Function and Right Ventricular-Pulmonary Arterial Adaptations in Aging Older Adults

Background: Compared to our understanding of left ventricular (LV) dysfunction in cardiac aging, there is far less depiction of right heart function, especially right ventricular (RV) remodelling in response to pulmonary arterial (PA) changes with aging. Given the importance of cardio-respiratory function in declining aerobic capacity with age, identifying sensitive metrics of RV function would complete our understanding of RV and RV-PA conduit adaptations in aging. Methods: Community older adults without cardiovascular disease underwent prospective cardiac magnetic resonance (CMR) imaging that measured RV volumes (RV end-diastolic volume, EDV; end-systolic volume, ESV), RV function (RV ejection fraction, RVEF; RV global longitudinal strain, GLS) and RV-PA coupling (end-systolic elastance to arterial elastance, computed as ratio of LV stroke volume, SV to RVESV). A RV-PA coupling threshold of >1.5 (based on prior literature) implies effective RV adaptation Aerobic capacity (VO 2 ) was calculated. Multivariable regression adjusted for significant covariates. Results: We studied 251 participants (54.5% female, 70.78±9.07 years) with normal LV and RV function (mean LVEF, 65.13±7.51 %, RVEF, 64.25±6.98 %). RV-PA threshold of <1.5 defined poorer RV structure and function with lower RVEF (56.6 ± 3.95 vs. 67.5 ± 5.25, p < 0.001), RVGLS (28.13± 4.55 vs. 32.8 ± 5.1, p = 0.0065) and higher RVEDV index (73.2 ± 15.15 vs. 63.34 ± 12.03, p < 0.001), compared to those with RVPA > 1.5. Predictors of better RVGLS were female sex (β=0.189, adj. p=0.019), independent of systolic and diastolic blood pressure while predictors of RVESV were female sex (β=-0.433, adj. p<0.00), age (β=-0.195, adj. p<0.001) and body mass index (β=0.264, adj. p<0.001). Overall, women had better RVEF and RVGLS but lower RVSV and VO 2 (30.1±4,5 vs 37.7±5.1, ml/kg/min) compared to men (all p<0.001) (Table 1). Lower VO 2 among women compared to men was accompanied by higher RV-PA (2.1±0.7 vs 1.8±0.7, p<0.001). Female sex (β=0.233, 95% CI [0.158, 0.506, adj. p<0.001) was independently associated with RV-PA coupling on multivariable analyses. Conclusions: Novel CMR-derived right heart parameters defined RV function and RV adaptations as depicted by RV-PA interactions in older adults. Superior RV functions and RV-PA coupling in women may represent hemodynamic adaptations in women, despite lower aerobic capacities.

Abstract 4118444: Right Ventricular Contractile Reserve and Right Ventricular-Pulmonary Arterial Coupling Are Impaired in Long-Term Survivors of Childhood Cancers

Background: Childhood cancer survivors are at risk of right ventricular (RV) dysfunction in relation to cardiac toxicity due to chemotherapy and radiation therapy. This study tested the hypothesis that RV contractile reserve and RV-pulmonary arterial (PA) coupling are altered in long-term survivors of childhood cancers. Methods: Thirty survivors (60% men) aged 24.3 ± 5.2 years at 15.3 ± 6.3 years after completion of chemotherapy and thirty healthy control subjects (47% men) were studied. Resting and submaximal supine bicycle stress echocardiography was performed for assessment of RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), left ventricular (LV) and RV longitudinal strain, mitral and tricuspid annular velocities and myocardial acceleration during isovolumic contraction (IVA). The slope of the RV force-frequency relationship was derived from the change in IVA with the change in heart rate during exercise (△IVA/△heart rate), while RV-PA coupling was determined by the ratio between TAPSE and pulmonary arterial acceleration time indexed to RV ejection time (PAATi). Results: At rest, tricuspid annular systolic velocity and RV systolic strain were significantly lower in survivors ( P < 0.05 for both), while RV FAC, TAPSE and IVA were similar between the two groups ( P > 0.05 for all). During submaximal exercise testing, all RV systolic functional indices were significantly lower in survivors than controls ( P < 0.05 for all). The slope of the RV force-frequency relationship was significantly flatter in survivors compared to controls (0.038 ± 0.002 vs 0.059 ± 0.003 m/sec 2 beats/min, P < 0.001). For RV-PA coupling, TAPSE/PAATi was similar between survivors and controls at baseline but became significantly lower in survivors during submaximal exercise ( P = 0.002). Conclusions: The RV contractile reserve and RV-PA coupling are impaired during exercise in long-term survivors of childhood cancers. Future studies aimed at determining the clinical and prognostic significance of these impairments are warranted.

Evolution and prognostic relevance of right ventricular morphofunctional parameters in patients undergoing isolated tricuspid valve surgery

Abstract Background Right ventricular (RV) function is key in evolution after isolated tricuspid valve surgery (ITVS). Right ventricular-pulmonary artery coupling (RV-PA coupling), determined with echocardiography as the ratio TAPSE/sPAP, has merged as a relevant functional parameter in many clinical scenarios. Purpose Our aim is to evaluate the prognostic relevance of RV-PA coupling in patients undergoing ITVS. Methods We carried out a retrospective study involving all the patients undergoing ITVS at our tertiary centre. Several RV function measurements were assessed from the baseline echocardiogram (TAPSE, fractional area change (FAC), systolic pulmonary artery pressure (sPAP), tricuspid annulus tissue Doppler velocity (RVS´) and free-wall global longitudinal strain (FW-GLS)) and RV-PA coupling was calculated. Association between RV morphofunctional variables and mortality during one year follow-up was determined. Results 45 patients were included (68 years-old, 51,1% female). The most common TR etiology was functional (51.1%) and 42.2% had previous left-sided valvular surgery. The median Tri-Score was 2 (1-4) points and the most frequent procedure was biological valve replacement (65%). Baseline echocardiographic parameters were as follows: basal 52 (48 – 53.5) mm, mid 40 (36-45.5) mm and longitudinal 73 (68-80) RV diameters, TAPSE 18.1 (15.5-20.7) mm, RVS´ 10.1 (9-12.5) cm/s, FAC 0.5 (0.43-0.57), sPAP 35 (31.5-37.5) mmHg, and FW-GLS - 21.1 (17.2-25) %. During the follow-up 8 (18%) patients died. Solely TAPSE (16 vs 19, p= 0.047) and RV-PA coupling (0.35 vs 0.5; p= 0.035) showed significant differences in mortality among RV echocardiographic parameters. An RV-PA coupling <0.375 mm/mmHg appeared to be the best mortality predictor (RR 1.45; p= 0.04) one year after the intervention (Figure). Conclusions In our series RV-PA coupling has proved to be the best echocardiographic prognostic factor in ITVS, so it could be considered a relevant parameter in risk stratification previous to this surgery. Figure. Kaplan Meier curves of mortality after ITVS by RV-PA coupling.Figure

Prognostic implication of right ventricular - pulmonary arterial coupling in patients with non-valvular atrial fibrillation

Abstract Background The clinical importance of right ventricular (RV) - pulmonary arterial (PA) coupling has been reported in various cardiac diseases such as right heart failure, pulmonary hypertension, and valvular dysfunction. However, there is limited data on patients with non-valvular atrial fibrillation (AF). We aim to investigate whether RV-PA uncoupling affects the clinical outcome in patients with non-valvular AF. Methods A total of 807 consecutive patients with non-valvular AF who underwent echocardiography (mean age 70 ± 12 years, 39% female) were included. We excluded patients with significant (at least moderate degree) valvular diseases, left ventricular ejection fraction (LVEF) <50%, cardiac implantable electronic devices, previous cardiac surgery, and poor echocardiographic image for RV analysis. RV-PA coupling was assessed by the ratio of RV global longitudinal strain (GLS) to PA systolic pressure (PASP), and decreased RV-PA coupling was defined as less than 0.52 %/mmHg based on on the receiver operating characteristic analysis. The primary outcome was the composite of all-cause death and hospitalization for heart failure. Results Over a mean of 4.7 ± 3.5 years of follow-up, 178 (22%) patients had experienced primary outcomes. Among them, 107 (13%) patients were hospitalized for HF and 90 (11%) patients died. Patients with decreased RV-PA coupling were older (73 ± 11 vs. 68 ± 12 years, p<0.001), had a higher prevalence of females (51 vs. 33%, p<0.001) and diabetes (33 vs. 23%, p=0.003), lower left ventricular ejection fraction (60 ± 5 vs. 61 ± 5%, p=0.011), higher E/e’ (14 ± 5 vs. 11 ± 4, p<0.001), larger left atrial volume index (78 ± 37 vs. 62 ± 22 ml/m2, p<0.001) and larger RV end-systolic area (11 ± 4 vs. 10 ± 3 cm2/m2, p=0.001) compared to those with preserved RV-PA coupling. In multivariate Cox regression analysis, decreased RV-PA coupling was associated with worse clinical outcomes even after adjusting for age, diabetes, E/e’, and RV end-systolic area (Hazard ratio [HR] 1.50, 95% Confidence interval [CI] 1.09 – 2.07, p=0.014) (Figure 1). Conclusions In patients with non-valvular AF, RV-PA coupling was associated with clinical outcome, suggesting that it may provide additional information for predicting future cardiovascular risk in this population.

Impact of right ventricular - pulmonary arterial coupling on mortality after transcatheter aortic valve implantation in patients with aortic stenosis

Abstract Background Aortic stenosis (AS) leads to left ventricle (LV) pressure overload. In more advanced stages of the disease, this pressure, which is transmitted through the pulmonary vasculature, may result in right ventricle (RV) remodeling and eventual dilatation and disfunction. RV failure is associated with impair prognosis, even after relief of the obstruction. The interplay of pulmonary arterial (PA) pressure and RV function can be assess using RV-PA coupling index; in a compensate state RV function is coupled with pulmonary pressure, and this function has a proper response to an increase in pulmonary afterload; in contrast, when RV function uncouples with pulmonary pressure it means that RV function can no longer sustain PA afterload, leading to a decompensate state. RV-PA uncoupling has already been associated with poor prognosis in other heart conditions, such as heart failure or pulmonary hypertension; however, there is still not much evidence on how RV-PA uncoupling prior transcatheter aortic valve implantation (TAVI) impacts on mortality. Purpose Assess the impact of RV-PA uncoupling on all-cause mortality after TAVI in patients with aortic stenosis. Methods In a prospective TAVI registry, patients were included if they had an adequate echocardiographic evaluation prior TAVI. All-cause mortality after the procedure was analyzed in two subgroups, according to their RV-PA coupling status. RV-PA was assess using tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP). The cut-off value was 0.39, consistent with other studies. Hazard ratios (HR) are calculated by univariate and multivariate Cox proportional hazard model. Multivariate adjustment included baseline characteristics – including age, gender, hypertension, diabetes, dyslipidemia, atrial fibrillation, and serum albumin –, and Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) and European System for Cardiac Operative Risk Evaluation (EUROSCORE) II. Results A total of 1190 patients underwent TAVI from January 2011 to December 2023; 315 patients were eligible, with mean age 82,24 years (± 8,0), 52% being women, and a mean EUROSCORE II score of 4.0 (± 9,3). The RV-PA cut-off value of 0.39 stratified patients into groups of RV-PA coupling (n = 194/63,6 %) or uncoupling (n = 121/38,4 %). During follow-up time (35,94 months ±25,6), patients with unpaired coupling had a 64% more risk of all-cause mortality in univariate analysis and, after adjusting for the parameters above, a 58% increased risk in multivariate analysis. Table. Conclusions Patients with significant aortic stenosis who had an impair RV-PA coupling prior TAVI had a significant increased risk of all-cause mortality. This suggests the need to incorporate this parameter to our right-side hemodynamics evaluation prior the procedure. Broader experience to determine its application and cut-off value are still needed.

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p<0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p<0-001), obesity (17.1 vs 20.7%; p<0.001) and diabetes (9.4 vs 22.1%; p<0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p<0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

Endarterectomy in CTEPH: hemodynamic improvement and RV-PA coupling

Abstract Introduction Pulmonary artery endarterectomy (PAE) remains the gold standard in treating chronic thromboembolic pulmonary hypertension (CTEPH). Reducing the thrombotic burden and mechanical obstruction of the pulmonary artery (PA) leads to significant hemodynamic improvement, allowing for favorable right ventricular (RV) remodeling. Methods Single center retrospective study, including 30 pts submitted to PEA over a 7-year period. Hemodynamic assessment was performed by right heart catheterization (RHC) before PEA, immediately after and at 6-month follow-up (FUP). Echocardiographic assessment of RV function was acquired at baseline and 6m FUP. Mean absolute differences were calculated before and after PEA. Differences between groups were assessed with ANOVA analysis and ROC curve analysis allowed us to define a cut-off point in mPAP reduction to predict favorable RV remodeling. Results We included 30 pts with a mean age of 57,9 ± 13 years old and slight predominance of female sex (57%). Regarding risk assessment with the 4 strata tool at baseline, 23% of pts were high risk, 20% intermediate high, 27% intermediate low and 6% at low risk. Pulmonary hemodynamics improved immediately after PEA, as indicated by a mean reduction of 28,3 ±17 mmHg in mPAP; 44,4±27,6mmHg in sPAP; 8±3,4 Wu in PVR and an increase in CO of 0,5±1 l/min. This improvement was sustained at 6-m post PEA assessment, with a mean reduction of 31,5 ±26,7 mmHg in mPAP; 48,3±41,2mmHg in sPAP; 6,3±6,2Wu in PVR and a 0,5±1 l/min increase in CO. Regarding RV remodeling at 6m post PEA, an increase of 0.15±0.2mm/mmHg in TAPSE/PSAP ratio and 3±2,8cm/s in Tricuspid S’ were recorded. RV/PA uncoupling, defined as TAPSE/PSAP <0,31 mm/mmHg, was evident in 73% of pts at baseline, 25% of which recovered at 6m follow-up. There were no significant differences between groups, according to the 4 strata risk assessment at baseline, regarding pulmonary hemodynamics and RV remodeling. Through ROC curve analysis, we were able to define a cut-off point of 37mmHg in immediate mPAP post-op reduction to predict RV-RA coupling normalization at 6-m FUP (sensitivity 70%, specificity 89%). Conclusions PEA remains a cornerstone of CTEPH treatment. It’s impact on improving pulmonary hemodynamics is immediate and maintained at 6-month FUP. This improvement may be expected regardless of risk assessment at baseline. Reducing RV afterload allows favorable remodeling and an immediate post operative reduction of mPAP > 37mmHg may predict normalization of RV-PA coupling.

Exercise Doppler echocardiography to detect early changes in the right ventricular-pulmonary circulation unit after pulmonary embolism

Abstract Introduction After pulmonary embolism (PE), patients frequently complain about reduced exercise capacity and dyspnea on exertion, even without pulmonary hypertension (PH). The underlying condition is often chronic thromboembolic disease, which is caused by residual pulmonary obstruction with preserved resting pulmonary haemodynamics. The symptoms are the consequences of the increased dead space ventilation, exercise-induced PH and right ventricular (RV) dysfunction. We aimed to assess the pathologic differences in the echocardiographic parameters of the RV- pulmonary circulation unit among patients with previous PE and the healthy control group. Furthermore, an objective was to compare the hemodynamic response to stress after different treatment strategies (thrombolysis vs. heparin administration). Methods 21 patients after PE (mean age 58,5±12,1 years; 53% men) have been included in the study. All of them were effectively anticoagulated for at least three months, and none had any signs of PH on echocardiography at rest. The control group included 20 healthy volunteers (mean age 56,9±11,5 years; 55% men). Each patient underwent resting and exercise stress echocardiography on a semi-recumbent bicycle ergometer according to a standardised protocol until the maximally tolerated workload. Echocardiography was performed at rest, at 50 Watt workload and during peak stress. The measurements focused on the RV's systolic function (TAPSE), the estimated pulmonary artery systolic pressure (PASP), and the Doppler measurements in the RV and left ventricular outflow tracts. Pulmonary vascular resistance (PVR) and RV-pulmonary artery coupling (RV-PA) were calculated from the echocardiographic parameters. Results The post-PE group had significantly higher PASP (39,2 ±16,6 vs. 27,7±12,5 mmHg; p<0,05) and PVR (1,5±0,4 vs. 1,1±0,3 Wood Units; p<0,05) at peak stress, than the controls. 55% of post-PE patients remained symptomatic, but there were no significant differences between the symptomatic and asymptomatic groups regarding TAPSE, PASP, RV-PA coupling and PVR. 30% of post-PE patients had thrombolysis. In the patients where thrombolysis was performed, the coupling at peak stress was significantly higher than in heparin-treated patients (1,4±0,1 vs 0,9±0,4 mm/mmHg, p<0,05). Conclusion Post-PE patients without resting PH have higher PVR and PASP than the healthy control group, even after at least 3 months of adequate therapy. Post-PE patients treated with thrombolysis may have more preserved RV-PA coupling than the heparin-treated patients.

Novel CMR-assessed right ventricular-pulmonary artery coupling index independently associates with exercise capacity and clinical risk in pulmonary arterial hypertension

Abstract Background We defined a novel noninvasive right ventricle (RV)–pulmonary artery (PA) coupling index as the ratio of cardiovascular magnetic resonance (CMR)-assessed RV direct flow (RVDF) and PA pulse wave velocity (PWV), and investigated its associations with exercise capacity and clinical risk in pulmonary arterial hypertension (PAH). Method 43 PAH patients (mean age 46±12 years, M:F 7:36) and 60 healthy volunteers (mean age 46±13 years, M:F 11:48) underwent CMR and cardiopulmonary exercise test (CPET) within one week. From cine CMR, RV ejection fraction (EF) and RV end-diastolic volume (RVEDV) were calculated using volumetric analysis; and tricuspid annular plane systolic excursion (TAPSE), feature tracking. PAPWV was the ratio of early systolic DPA flow and DPA area measured from instantaneous phase and magnitude through plane 2D flow CMR images across the pulmonary trunk, respectively. RVDF was the 4D flow CMR-assessed blood volume entering and exiting the RV in one cardiac cycle, indexed to RVEDV. RV-PA coupling was RVDF/PAPWV. Based on CPET-assessed peak oxygen consumption (PVO2), all 103 participants were stratified into two groups: PVO2>15 ml/kg/min; and PVO2≤15 ml/kg/min. Based on the REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) 2.0 score, the 43 PAH patients were stratified into low risk (score ≤6) and intermediate to high risk (score >6) groups. Results RVDF/PAPWV was significantly lower in PAH vs. controls (7.9 vs. 20.4 %/(m/s), P<0.001); and in PAH patients with intermediate to high risk vs. low risk (4.6 vs. 9.4 %/(m/s), P=0.001). On multivariable analyses, RVDF/PAPWV was an independent predictor of PVO2≤15 ml/kg/min (=0.302, P=0.001) among all participants, and of REVEAL 2.0 score >6 (=0.621, P=0.009) among PAH patients. Compared to RVEF and TAPSE, RVDF/PAPWV had numerically higher discrimination (p values non-significant based on Delong test) for PVO2≤15 ml/kg/min (AUC=0.914 vs. 0.872, 0.843); and among PAH patients, REVEAL 2.0 score >6 (AUC=0.851 vs. 0.723 and 0.728) (Figure). Conclusion CMR-derived noninvasive RVDF/PAPWV independently associates with exercise capacity and PAH clinical risk, supporting its utility as an imaging marker of disease progression and therapeutic response.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=<0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=<0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

The ventilatory efficiency parameters outperform peak oxygen consumption in monitoring the therapy effects on the right ventricular load in patients with hypertrophic cardiomyopathy

Abstract Aim We sought the cardiopulmonary exercise testing (CPET) parameter that is the most reflective of right ventricular (RV) load and its coupling with pulmonary artery (PA) in patients diagnosed with hypertrophic cardiomyopathy (HCM) undergoing medical therapy. Methods CPET on recumbent bike was performed in adult patients with symptomatic non-obstructive HCM with NYHA class I–III, during phase II, randomised, open-label multicentre study, before and after diverse medical treatment for 16 weeks. Endpoints were the changes in: 1) peak oxygen consumption (peak VO2); 2) minute ventilation (VE)/carbon-dioxide (CO2) production slope during the whole CPET; 3) VE/VCO2 slope before anaerobic threshold (AT); 4) VE/VCO2 slope after AT; 5) VE/VCO2 nadir; 6) VE/VCO2 at AT; and 7) VE/VCO2 intercept. Standard ehocardiography at rest was performed concomitantly with CPET to assess tricuspid annular plane systolic excursion (TAPSE), pulmonary artery systolic pressure (PASP), severity of mitral regurgitation (MR) and TAPSE/PASP ratio as a measure of RV-PA coupling. Results Of 115 screened patients, 61 (mean age 52 years [SD 14], 43% women) met the study inclusion criteria and underwent CPET. On regression analysis, among all CPET end-point variables, the best independent predictor of the change in PASP, TAPSE and MR severity after 16 weeks of medical treatment was VE/VCO2 below AT (B=-0.28, -0.01,-0.11; SE=0.10, 0.05, 0.01; CI=-0.48 to -0.08, -0.22 to -0.01; -0.02 to 0.01; p=0.007, 0.035, 0.004, respectively), whereas the best predictor of TAPSE/PASP ratio was intercept of the VE/VCO2 curve (B=0.014, CI=0.01to 0.03, p=0.005). Conclusion The changes in VE/VCO2 slope below anaerobic threshold, and intercept of the VE/VCO2 curve outperform peak VO2 in the monitoring of therapy effects on the right heart load and RV-PV coupling in patients with hypertrophic cardiomyopathy.

Right ventricular to pulmonary artery coupling credicts poor outcomes after interatrial shunting in heart failure

Abstract Background Left atrial decompression is under investigation for heart failure (HF) with the potential to improve symptoms and potentially clinical outcomes. However, heterogeneous outcomes have been observed in randomized controlled studies. Purpose This study aimed to explore whether right ventricular (RV) -pulmonary artery (PA) coupling, as assessed from the tricuspid annular plane systolic excursion (TAPSE) /systolic PA pressure ratio, can be useful in predicting outcomes after implantation of the interatrial shunting device. Methods A total of 106 HF patients, n=62 with reduced ejection fraction (HFrEF), n=44 with preserved ejection fraction (HFpEF), were prospectively enrolled in the PRELIEVE registry with the Atrial Flow Regulator (AFR) implantation. Serious adverse events included cardiovascular mortality and HF worsening (W). Results Serious adverse events (SAEs) occurred in a total of 19 (18%) patients. There were no differences in baseline comorbidities, KCCQ scores, the 6-minute walking distance between patients with and without SAEs (Table). Patients with SAEs showed higher systolic pulmonary arterial pressure, NT-proBNP, serum creatinine and lower TAPSE/PASP ratio. Incidence of SAEs was higher in patients within the first TAPSE/PASP vs the third tertile (59% vs 12%, p=0.026), respectively. A TAPSE/PASP of <0.55 was identified to bear the most optimal sensitivity to predict the event (AUC=0.683, CI95% (0.533-0.833). Conclusion The reduced TAPSE/PASP ratio was associated with higher rates of serious adverse events in patients with heart failure undergoing controlled inter-atrial shunting. The hypothesis generating finding that reduced RV-PA coupling may identify potential clinical non-responders to left atrial decompression should be further prospectively validated.

Prognostic role of right ventricular-pulmonary artery coupling assessed by TAPSE/PASP ratio in patients with heart failure and mildly reduced ejection fraction

Abstract Background The development of right ventricular (RV)-pulmonary arterial (PA) coupling has resulted in a novel and comprehensive index for evaluating RV function in relation to the underlying RV afterload. In patients with heart failure (HF), it is acknowledged that RV-PA uncoupling are features that are associated with poor outcome. The RV-PA coupling index can be readily assessed non-invasively using the ratio of two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). However, few studies have defined the prognostic impact of the TAPSE/PASP ratio in patients with HF and mildly reduced EF (HFmrEF). Methods From the prospective cohort study of 1,410 hospitalized HF patients (age 68+/-15, men 62%) between August 2015 and September 2019, this study enrolled 191 HFmrEF (i.e., left ventricular ejection fraction (LVEF) 41–49%) patients whose TAPSE and PASP were measured during hospitalization and discharged alive. We studied the prognostic impact of TAPSE/PASP ratio on HFmrEF patients using by cut-off value obtained from receiver operating characteristic (ROC) analysis. The primary and secondary endpoints was defined as the all-cause death and HF re-hospitalization after discharge, respectively. Results During median follow-up of 38 [23–52] months, 48 patients (25%) died. The deceased patients had a significantly older (median 75 vs. 71 years, p<0.05), higher rate of ischemic heart disease (50% vs. 23%, p<0.05), elevated brain natriuretic peptide levels (325 vs. 159 pg/ml, p<0.05) and lower rate of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (65% vs. 80%, p<0.05) at discharge. In the ROC analysis, the cut-off value of TAPSE/PASP ratio for mortality was 0.46. Patients with TAPSE/PASP ≤0.46 had a significantly higher all-cause mortality (log-rank p<0.05) and had a tendency of higher rate of HF re-hospitalization than patients with TAPSE/PASP >0.46 (log-rank p=0.06) (Figure). Using multivariate analysis, the lower TAPSE/PASP ratio had an independent predictive value of prognosis in patients with HFmrEF (hazard ratio 2.16, 95% confidence interval; 1.08–3.92, p<0.05) (Table). Conclusion The TAPSE/PASP ratio has a significant prognostic value in patients with HFmrEF. The RV-PA uncoupling assessed by TAPSE/PASP ratio might be useful for risk assessment in patients with HFmrEF.

Right ventricular to pulmonary artery coupling in chronic thromboembolic pulmonary hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is characterized by increased pulmonary vascular resistance (PVR) and pressure and right ventricular (RV) dysfunction. We aimed to evaluate the correlation of RV to pulmonary artery coupling, measured as the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio, and invasive hemodynamic measurements, and to assess the changes in this ratio following CTEPH treatment. MethodsWe conducted a retrospective cohort study of CTEPH patients treated at Aarhus University Hospital with pulmonary angioplasty (BPA), pulmonary endarterectomy (PEA), and or medical therapy only. Patients underwent transthoracic echocardiography and right heart catheterization at baseline and follow-up. The primary endpoint was the association between TAPSE/PASP and PVR. Secondary endpoints included other hemodynamic and functional parameters. ResultsThe study included 139 patients. Mean TAPSE/PASP at baseline was 0.22 [0.16, 0.29] mm/mmHg. An exponential decay correlation was found between TAPSE/PASP and PVR (correlation coefficient − 0.67, p < 0.001). The TAPSE/PASP ratio improved from 0.23 [0.18; 0.29] to 0.33 [0.26; 0.46] mm/mmHg, p < 0.0001, following BPA, and from 0.20 [0.15;0.27] to 0.35 [0.21;0.41] mm/mmHg, p = 0.0007 following PEA, indicating enhanced RV to pulmonary artery coupling. ConclusionIn patients with CTEPH, the echocardiographic TAPSE/PASP ratio as a measure of RV-PA coupling correlates well with invasively measured pulmonary vascular resistance. The TAPSE/PASP ratio improved after BPA or PEA treatments suggesting a potential use for monitoring patient outcomes. Further prospective studies are warranted to establish the prognostic value of the TAPSE/PASP ratio and ability to guide treatment decisions.

Tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio in chronic thromboembolic pulmonary hypertension improves with balloon pulmonary angioplasty.

Right ventricle (RV)-to-pulmonary artery (PA) coupling measured by the ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) is a meaningful prognostic marker in pulmonary hypertension (PH). It's unclear if balloon pulmonary angioplasty (BPA) treatment of chronic thromboembolic pulmonary hypertension (CTEPH) alters RV-PA coupling measured by TAPSE/PASP. We reviewed CTEPH patients treated with BPA at our institution who had a transthoracic echocardiogram (TTE) before BPA and a follow-up TTE at any point during BPA. TAPSE was obtained from the initial and lattermost TTE; hemodynamics were obtained before each BPA session. Between March 2015 to October 2023, there were 228 patients treated with BPA. After excluding post-PTE patients and those without PH, 67 were included. Initial TAPSE/PASP was 0.39 ± 0.21 mm/mmHg. Using previously defined TAPSE/PASP tertiles in PH (<0.19, 0.19-0.32, >0.32 mm/mmHg), there were 6 patients (9%) in low, 30 (45%) in middle, and 31 (46%) in the high tertiles at baseline. The lower TAPSE/PASP tertiles had more severe baseline hemodynamics (p < 0.001) compared to the high TAPSE/PASP cohort. At follow-up, TAPSE/PASP improved to 0.47 ± 0.20 mm/mmHg (p = 0.023), with 2 (3%), 13 (19%), and 52 (78%) patients in the low, middle, high TAPSE/PASP tertiles, respectively. As patients progress through BPA sessions, the TAPSE/PASP ratio increases, possibly reflecting improved RV mechanics and RV-PA coupling. TAPSE/PASP ratio as a marker of RV-PA coupling can improve with BPA treatment and may be an important measure to follow during treatment of CTEPH.

Prognostic Value of Echocardiographic Coupling Metrics in Systemic Sclerosis–Associated Pulmonary Vascular Disease

Ineffective right ventricular (RV) adaptation to increasing pulmonary arterial (PA) afterload in pulmonary vascular disease (PVD) significantly contributes to morbidity and mortality. Pulmonary vascular disease in systemic sclerosis (SSc) arises through various mechanisms, yet detecting abnormal contractile response remains challenging. Here we examine whether echocardiographic RV-PA coupling metrics correlate with invasive pressure-volume (PV) loops, enhancing the prediction of adverse clinical outcomes in SSc-PVD patients. Prospectively enrolled patients with SSc-PVD with paired echocardiogram and PV loops were included. Linear regression and receiver-operating curve analysis were used to assess the relationship between tricuspid annular plane systolic excursion/PA systolic pressure (PASP), fractional area change/PASP, tissue Doppler velocityS'/PASP, and RV free wall strain (RVFWS)/PASP and coupling thresholds defined by end-systolic to end-arterial elastance (Ees/Ea), obtained by the multibeat method. The contribution of right atrial strain (RAS) to RV-PA coupling parameters was also investigated. Kaplan-Meier analysis was used to identify the relationship between coupling ratios and composite outcomes including clinical worsening, lung transplant, and death. Forty-two patients with SSc were studied, 91% female, with a mean age of 59±12years and varying degrees of PVD: mean pulmonary artery pressure 29.5±12.8mm Hg, PVR 4.7±4.2 WU, and PCWP 10.3±4.1mm Hg. Echocardiographic coupling metrics including tricuspid annular plane systolic excursion/PASP, fractional area change/PASP, tissue Doppler velocity S'/PASP, RVFWSglobal and RVFWSbasal/PASP, and RASreservoir/PASP were linearly associated with Ees/Ea. At cut points obtained through receiver-operating curve analysis, all ratios were predictive of RV-PA uncoupling, defined by Ees/Ea, and composite outcomes. Additionally, RASreservoir/RVFWS correlated with Ees/Ea even after adjustment for PASP, suggesting that diminished RAS further impacts RV performance and coupling. Echocardiographic RV-PA coupling ratios strongly correlate with invasive Ees/Ea and predict adverse clinical outcomes in SSc patients across the spectrum of PVD. Further, we demonstrate how RAS impacts RV performance. These findings may refine risk stratification and prognostication in this at-risk cohort.

Pulmonary hypertension in ischemic heart failure: a pilot study

Aim. To evaluate the role of cardiopulmonary system assessment in a group of patients with pulmonary hypertension (PH) associated with ischemic heart failure (HF) with the right ventricular-pulmonary arterial (RV-PA) coupling.Material and methods. Forty stable patients were examined. The patients were divided into 3 groups depending on the left ventricle ejection fraction (LVEF). PH was established by using expert transthoracic echocardiography. RV-PA coupling was calculated by 2 following ways: as tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio and as TAPSE´Pulmonary Artery Aceleration Time (pACT) multiplication.Results. The patients included in the study were mainly men (73,8%), functional class PH II-III (95,2%), stage IIB CHF (62%). The highest values of TAPSE (18,6±3 mm) and RV-PA coupling (0,64±0,42 mm/mm Hg) were found in the patients with preserved LVEF. In the general cohort, high level of NT-proBNP corresponds to reduced values of RVPA coupling (rs=-0,563) and TAPSE (rs=-0,666; p&lt;0,01). The severity of PH directly affects the level of NT-proBNP (p&lt;0,01). As the stage of HF and PH functional class increases, the indicators of PASP, inferior vena cava diameter and NT-proBNP level significantly increase, as well as TAPSE and RV-PA coupling decrease (p&lt;0,05). Different calculating methods of RV-PA coupling has a strong correlation (rs=0,832; p&lt;0,01).Conclusion. The right heart and RV-PA coupling assessment in patients with ischemic HF of origin is of significant value for the early diagnosis of PH and timely clinical decision-making.

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.

Relevance of the TAS'/PASP Ratio as a Predictor of Outcomes in Patients with Heart Failure with a Reduced Ejection Fraction.

There is evidence that right ventricular (RV) contractile function, especially its coupling with the pulmonary circulation, has an important prognostic value in patients with left ventricular dysfunction. This study aimed to identify the best echocardiographic parameters of RV function and pulmonary artery systolic pressure (PASP) alone or in the form of the index of right ventricular-pulmonary artery coupling (RV-PA coupling) to determine the best predictor of 1-year major adverse cardiovascular events (MACE), which were defined as cardiovascular death and cardiac decompensation in heart failure patients with reduced ejection fraction (HFrEF). The study enrolled 191 HFrEF patients (mean age 62.28 ± 12.79 years, 74% males, mean left ventricular ejection fraction (LVEF) 25.53 ± 6.87%). All patients underwent clinical, laboratory, and transthoracic echocardiographic (TTE) evaluation, focusing on assessing RV function and non-invasive parameters of RV-PA coupling. RV function was evaluated using fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), and peak tricuspid annular systolic velocity (TAS'). PASP was estimated by peak tricuspid regurgitation velocity (TRVmax) and corrected by assumed right atrial pressure relative to the dimension and collapsibility of the inferior vena cava. The TAPSE/PASP and TAS'/PASP ratios were taken as an index of RV-PA coupling. During the follow-up (mean period of 340 ± 84 days), 58.1% of patients met the composite endpoint. The independent predictors of one-year outcome were shown to be advanced age, atrial fibrillation, indexed left atrial systolic volume (LAVI), LVEF, TAPSE/PASP, and TAS'/PASP. TAS'/PASP emerged as the strongest independent predictor of prognosis, with a hazard ratio (HR) of 0.67 (0.531-0.840), p < 0.001. Reconstructing the ROC curve 0.8 (0.723-0.859), p < 0.001, we obtained a threshold value of TAS'/PASP ≤ 0.19 (cm/s/mm Hg) (sensitivity 74.0, specificity 75.2). Patients with TAS'/RVSP ≤ 0.19 have a worse prognosis (Log Rank p < 0.001). This study confirmed previously known independent predictors of adverse outcomes in patients with HfrEF-advanced age, atrial fibrillation, LAVI, and LVEF-but non-invasive parameters of RV-PA coupling TAPSE/PASP and TAS'/PASP improved risk stratification in patients with HFrEF. Variable TAS'/PASP has been shown to be the most powerful, independent predictor of one-year outcome.