Ventricular-pulmonary Arterial 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.

Right Ventricular-Pulmonary Arterial Uncoupling as a Predictor of Invasive Hemodynamics and Normotensive Shock in Acute Pulmonary Embolism

Right ventricular-pulmonary arterial (RV-PA) coupling describes the relationship between RV contractility and its afterload and is estimated as the ratio of the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) via echocardiography. Whether TAPSE/PASP is reflective of invasive hemodynamics or occult shock in acute pulmonary embolism (PE) is unknown. This was a single-center retrospective study over a 3-year period of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization with echocardiograms performed within 24 hours prior to the procedure.Seventy patients (81% intermediate-risk) had complete invasive hemodynamic profiles and echocardiograms with TAPSE/PASP calculated. The optimal cutoff for TAPSE/PASP as a predictor of a reduced cardiac index (CI≤ 2.2 L/min/m2) was 0.34 mm/mmHg with an AUC of 0.97 and sensitivity, specificity, positive predictive value, and negative predictive value of 97.3%, 90.9%, 92.3% and 96.8%, respectively. Every 0.1 mm/mmHg decrease in TAPSE/PASP was associated with a 0.24 L/min/m2 decrease in the CI. This relationship was similar when restricted to intermediate-risk PE. The TAPSE/PASP ratio was predictive of normotensive shock with an OR 2.63 (95% CI: 1.42, 4.76, p=0.002) per unit decrease in the ratio.In conclusion, patients with acute PE undergoing mechanical thrombectomy, TAPSE/PASP was a strong predictor of a reduced CI and normotensive shock. This means of non-invasive point-of-care assessment of hemodynamics may have added value in PE risk stratification.

Right ventricular-pulmonary artery coupling and clinical outcomes after mitral transcatheter edge-to-edge repair: A meta-analysis

Abstract Introduction Mitral transcatheter edge-to-edge repair (TEER) has gained prominence in the realm of cardiovascular care, as it has been proven to improve patient prognosis and quality of life. While the primary focus of such interventions is the mitral valve itself, understanding the broader impact of right ventricular function and pulmonary artery dynamics is crucial for a comprehensive assessment of clinical efficacy and patient outcomes. A newly recognized index, right ventricular-pulmonary artery (RV-PA) coupling, reflects the RV's ability to handle pulmonary afterload and is associated with adverse outcomes. Purpose This meta-analysis consolidates findings from diverse studies to systematically evaluate the association between RV-PA coupling parameters and the success of mitral TEER. Methods We conducted a systematic literature search for studies assessing RV-PA coupling indices at baseline in patients undergoing mitral TEER. We recorded the year of publication, method of RV-PA assessment, and the proposed cutoffs. The primary outcome of interest was the combined primary endpoint of included studies at maximal follow-up and the adjusted hazard ratios of RV-PA uncoupling were extracted if they were available. Secondary outcomes included mortality and post-operative mitral regurgitation at follow-up. Pooling of the hazard ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being significant. Results We identified a total of 316 studies, of which 8 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All but one study utilized the Tricuspid Annular Plane Systolic Excursion/Pulmonary artery systolic pressure (TAPSE/PASP) as the method of RV-PA assessment. According to the results of the meta-analysis, the presence of baseline RV-PA uncoupling was associated with a 2.3-fold increased risk of facing the combined primary endpoint at maximal follow-up (Figure, Panel A). All-cause mortality was also approximately 2.2-fold higher in cases of RV-PA uncoupling (Figure, Panel B). Finally, post-operative MR was 1.4-fold higher in cases of RV-PA uncoupling (Figure, Panel C). Significant between-study heterogeneity was detected in all the examined endpoints. Conclusion: This meta-analysis indicates that RV-PA uncoupling at baseline represents an important prognostic marker in patients undergoing mitral TEER.Figure

The role of cardiopulmonary rehabilitation in the recovery of right ventricular function and right ventricular-pulmonary artery coupling in convalescent COVID-19 patients

Abstract Introduction Coronavirus disease-19 (COVID-19) is predominantly a respiratory disease, but simultaneous cardiovascular impairment has been documented, even in the post-acute phase. Subclinical right ventricular (RV) dysfunction is often described and mainly attributed to parenchymal lung damage (ARDS) or pulmonary vascular complications such as pulmonary embolism. Cardiopulmonary rehabilitation programs play an integral part in the long-term management of chronic cardiovascular and pulmonary diseases and lately have been proven useful in managing post-COVID-19 sequelae. Purpose The aim of this study is to assess the impact of a post-COVID-19 rehabilitation program in the recovery of right ventricular function and right ventricular-pulmonary artery coupling in convalescent COVID-19 patients. Methods 40 convalescent COVID-19 patients were evaluated one and three months after the acute phase of the disease. 30 subjects participated in a 3-month cardiopulmonary rehabilitation program (study group) and 10 did not (control group). Right ventricular function echocardiographic parameters (right ventricular global longitudinal strain (RVGLS) and pulmonary artery systolic pressure (PASP)) were evaluated and right ventricular-arterial coupling (RVAC) was estimated via the RVGLS/PASP ratio. Results A total of 40 patients were included in this study, of whom 30 underwent cardiopulmonary rehabilitation. There were no major differences in the prevalence of cardiovascular risk factors between the two groups. When examining right ventricular parameters at baseline, RVGLS (Rehabilitation: -23.1 (4.1) % vs. No rehabilitation: -23.0 (4.7) %, p=0.94) and PASP (Rehabilitation: 28 (6) mmHg vs. No rehabilitation: 25 (4) mmHg, p=0.08) did not differ statistically between the two groups. RVAC was also similar at baseline (Rehabilitation: -0.96 (0.28) %/mmHg vs. No rehabilitation: -0.86 (0.27) %/mmHg, p=0.30). At follow-up, patients who underwent cardiopulmonary rehabilitation exhibited a significant improvement in RVGLS (from Τ0: -23.1 (4.2) % to T1: -24.3 (4) %, p<0.001), PASP (from T0: 28 (6) mmHg to T1: 27 (5) mmHg, p=0.016), and RVAC (from T0: -0.86 (0.27) %/mmHg to T1: -0.93 (0.26) %/mmHg, p<0.001). In the no rehabilitation group, RVGLS (from T0: -23.0 (4.7) % to T1: -23.2 (4.4) %, p=0.19), PASP (from T0: 25 (4) mmHg to T1: 25 (4) mmHg, p=0.17), and RVAC (from T0: -0.96 (0.28) %/mmHg to T1: -0.96 (0.27) %/mmHg, p=0.60) were not significantly altered at follow-up. We detected a statistically significant interaction of intervention with RVGLS (p=0.024) and RVAC (p=0.012) (Figure 1). Conclusion Subclinical right ventricular dysfunction is present in convalescent COVID-19 patients. Cardiopulmonary rehabilitation can accelerate the improvement of RVAC by mediating both the RV afterload reduction (PASP) and improving RV function.Figure 1

Prognostic value of right ventricular-pulmonary arterial coupling indices in patients with moderate to severe mitral stenosis

Abstract Background Right ventricular-pulmonary arterial (RV-PA) coupling represents the relationship of RV contractility and RV afterload. The ability of RV to adapt to changes in RV afterload (i.e. increased pulmonary arterial (PA) loading) has prognostic implications in various cardiovascular diseases such as heart failure and pulmonary arterial hypertension. RV-PA uncoupling occurs when RV contractility cannot match RV afterload, resulting in right heart dysfunction. However, RV-PA coupling has not been investigated in mitral stenosis patients. Purpose To evaluate the prognostic significance of various non-invasive RV-PA coupling parameters (TAPSE/PASP and RVFWLS/PASP) in patients with moderate to severe mitral stenosis. Methods This was a single-center retrospective study of 237 patients with moderate or severe mitral stenosis enrolled between January 2010 to December 2022. Baseline clinical and echocardiographic parameters were collected. RV free wall longitudinal strain (RVFWLS) was subsequently analyzed using TOMTEC software. Echocardiography-derived RV-PA coupling parameters were collected, including TAPSE/PASP and RVFWLS/PASP. The primary endpoint was a composite outcome of all-cause mortality, heart failure hospitalization and valve intervention (percutaneous transvenous mitral commissurotomy and surgical intervention). RV parameters were analyzed separately to avoid collinearity. Results A total of 237 patients were included in the study. The patients had a mean age was 66.56 ± 13.61 years-old and were predominantly female (67.9%). The median follow-up duration was 4.54 years (IQR 1.44 – 6.44). Mean left ventricular ejection fraction (LVEF) was 56.86 ± 10.51%, mean TAPSE 18.29 ± 5.36 mm and mean RVFWLS was -23.60 ± 7.96 %. In separate multivariable Cox regression models after adjustment for age , sex and mitral stenosis severity, TAPSE/PASP ratio < 0.36mm/mmHg (HR 2.025 , 95% CI 1.395-2.939, p < 0.001 ) and RVFWLS/PASP ratio ≥ - 0.5%/mm Hg (HR 2.031 95% CI 1.404 – 2.938 , p< 0.001) remained independently associated with mortality , heart failure hospitalization and valve intervention. Conclusion TAPSE/PASP and RVFWLS/PASP were independently associated with all-cause mortality, heart failure hospitalization and valve intervention in patients with moderate to severe mitral stenosis.

Prognostic value of exercise right ventricular-pulmonary arterial coupling in primary mitral regurgitation

Abstract Background Exercise-induced pulmonary hypertension (mPAP/CO slope >3mmHg/L/min) was recently associated with worse outcome in >moderate PMR. However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods Cohort study including consecutive pts submitted to CPET-echo with >moderate PMR, no/discordant symptoms, preserved LV function and without >moderate concomitant valvular disease or atrial fibrillation (AF). Thorough assessment of RV systolic function and RVPAc (TAPSE/sPAP ratio) was obtained by echocardiography using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of all-cause mortality, cardiovascular hospitalization (CVH), new-onset AF and valvular intervention; secondary outcome was the composite of CVH and new-onset AF. Results A total of 128 consecutive pts (64±11 years, 61% men) underwent CPET-echo. Event-free survival rate was 55% and 46% at 1 and 2 years. Pts that reached the primary combined endpoint were significantly older, had larger left atrium indexed volumes (LAVi), higher proportion of grade 4 MR, lower absolute and normalized peak VO2, and a significantly higher mPAP/CO slope (2,1±0,8 vs.3,7±2,6). They had a significantly lower rest and exercise TAPSE/sPAP, RV global and free wall longitudinal strain, rest and exercise TAPSE and exercise RV free wall S’. Rest and low exercise TAPSE/sPAP scored the highest accuracy in predicting the primary combined endpoint among variables statistically significant in the univariate analysis and therefore were used in the multivariate model. Sequentially adding rest and low exercise TAPSE/sPAP significantly improved the baseline predictive model (age, LAVi and MR grade). Low exercise TAPSE/sPAP and LAVi remained as significant independent variables in the multivariate model. They also correlated with new-onset AF and CVH; with rest and low exercise TAPSE/sPAP constituting significant steps (Fig 2). Replacing low exercise TAPSE/sPAP for mPAP/CO slope in the proposed model only slightly improved its accuracy in predicting the primary and secondary composite outcomes. Adding predicted peak VO2 (≥80% vs <80%) did not significantly improve the accuracy of any of the multivariate models. Low exercise TAPSE/sPAP and mPAP/CO slope both correlated well with peak VO2 and VE/VCO2 slope. Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in pts with >moderate PMR and no/discordant symptoms. Low exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Low exercise TAPSE/sPAP is a potential alternative to mPAP/CO slope in this population and it may be simpler to adopt in clinical practice.Central Illustration

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 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-pulmonary artery coupling assessed by two-dimensional strain predicts in- hospital complications in takotsubo syndrome

Abstract Background and purpose Takotsubo syndrome (TTS) may lead to serious in-hospital complications. Our study aims to investigate the prognostic impact of right ventricular-to-pulmonary artery (RV-PA) coupling in patients with TTS. Methods Consecutive TTS patients were prospectively enrolled. RV function was evaluated by RV global longitudinal strain (RVGLS) and RV free wall strain (RVFWS) and RV-PA coupling was measured as the ratio of either tricuspid annular plane systolic excursion (TAPSE), RVGLS or RVFWS to pulmonary artery systolic pressure (PASP). Data about in-hospital complications (defined as acute heart failure, life-threatening arrhythmias and death from any cause) were collected. Results A total of 80 patients were analysed (71±11 years, female 77.5%) and in-hospital complications occurred in 33 (41%). Patients who experienced in-hospital complications had lower LV ejection fraction (LVEF), lower TAPSE/PASP, RVFWS/PASP and RVGLS/PASP and higher left atrial volume indexed (LAVi) values. LVEF (OR 0.913, 95% CI [0.858–0.971], p=0.004) and RVGLS/PASP (OR 0.098, 95% CI [0.012–0.788], p= 0.029) were independent predictors of in-hospital complications. Receiver operating characteristics (ROC) curve analysis showed an area under the curve (AUC) of 0.696 (95% CI [0.57–0.82], p= 0.002) of RVGLS/PASP for the prediction of in-hospital complications. A cut-off value of RVGLS/PASP of ≤ 0.48 %/mmHg showed a sensitivity and specificity of 75% and 60%, and allowed to identify 24% of patients who experienced in-hospital complications despite a preserved LVEF (≥50%). Conclusion RV-PA coupling assessed by RVGLS/PASP may help identifying TTS patients at higher risk of cardiovascular complications with an additional prognostic value to LVEF alone.

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.

Unravel novel therapeutic targets in heart failure and associated pulmonary hypertension

Abstract Background Heart Failure (HF) is a complex clinical syndrome with poor prognosis. Pulmonary hypertension (PH) often complicates HF but can hardly be addressed therapeutically. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with HF. Whether SGLT2i positively impact on HF-associated PH is poorly understood. Omics offer great promise in the discovery of novel biomarkers and therapeutic targets for HF and PH. Aims We investigated novel markers associated with HF and PH, as well as how these biomarkers vary in response to HF-modyfing therapies, including SGLT2i. We also explored the impact of SGLT2i, compared with conventional anti-HF therapy, on HF-associated PH and right ventricular function. Methods Seventy-four patients with HF and reduced ejection fraction (HFrEF) with/without diabetes were divided into a gliflozin (G)-group receiving 10 mg/day empagliflozin or dapagliflozin, and a control (C)-group receiving conventional anti-HF therapy. Resting echocardiography, analyses on senescence markers [leucocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)], as well as measurement of two microRNAs (miRNA-21 and miRNA-92, recently implicated in response to treatment in HFpEF patients), were performed. Shotgun proteomic analyses were conducted on peripheral blood mononuclear cells. Results Compared to group C, group G had a significantly higher ejection fraction (EF, 42±13 vs 33±8, p=0.001), reduced left ventricular filling pressures (11±3 vs 15±5, p=0.001), reduced pulmonary artery systolic pressure (PAPs, 31±11 vs 46±15, p=0.001), better right ventricular-pulmonary artery coupling index (0.64±0.31 vs 0.44±0.22, p=0.002), increased LTL (Figure 1 A), higher mtDNAcn (Figure 1 B), reduced miRNA-21 levels (Figure 1 C) and no significant changes of miRNA-92 (Figure 1 D). Functional proteomic analysis showed that, compared with the C-group, the protein cargo from the G-group was able to trigger several biological pathways, showing a significant activation of T lymphocytes immune response (p-value=9.67x10-06, z-score=2.21) chemotaxis of monocytes (p-value=9.39x10-07, z-score=2.0), leukocytes (p-value=9.67x10-10, z-score=2.0)and phagocytes (p-value)=3.10x10-10, z-score=2.03) (Figure 2). Compared with the C-group, the G-group showed a downregulation of activin signaling pathway (z-score=-2.12), which is a novel therapeutic target in pulmonary arterial hypertension (PAH). Conclusions In HF patients, SGLT2i therapy is associated with improved left ventricular function and improved pulmonary hemodynamics. Activin is overactive in HF patients and its serum levels may be reduced by SGLT2i. SGLT2i may preserve LTL and mtDNA-cn as well as modulate the expression of specific miRNA implied in the regulation of endothelial function. SGLT2i may represent an additional therapeutic tool in patients with HF-associated PH, an area with no approved treatment options beyond traditional HF therapy.Figure 1:genomic analysesFigure 2:proteomic analyses

Right ventricular-pulmonary artery coupling for prognostication in acute pulmonary embolism.

Acute pulmonary embolism (PE) increases pulmonary pressure and impair right ventricular (RV) function. Echocardiographic investigation can quantify this mismatch as the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) ratio. The aim of the study was to investigate the prognostic capabilities of TAPSE/PASP ratio in patients with acute PE. We utilized the RIETE registry to analyze consecutive hemodynamically stable PE patients. We used multivariable logistic regression analyses to assess the association between the TAPSE/PASP ratio and 30-day all-cause mortality across the strata of European Society of Cardiology (ESC) risk categories. We included 4,478 patients, of whom 1,326 (30%) had low-risk, 2,425 (54%) intermediate-low risk, and 727 (16%) intermediate-high risk PE. Thirty-day mortality rates were 0.7%, 2.3% and 3.4%, respectively. Mean TAPSE/PASP ratio was 0.65±0.29 in low-risk patients, 0.46±0.30 in intermediate-low risk, and 0.33±0.19 in intermediate-high risk patients. In multivariable analyses, there was an inverse association between TAPSE/PASP ratio and 30-day mortality (adjusted OR 1.32 [95%CI 1.14-1.52] per 0.1 decrease in TAPSE/PASP). TAPSE/PASP ratio below optimal cut-points was associated with increased mortality in low- (<0.40, aOR: 5.88; 95%CI:1.63-21.2), intermediate-low (<0.43, aOR: 2.96; 95%CI:1.54-5.71) and intermediate-high risk patients (<0.34, aOR: 4.37; 95%CI:1.27-15.0). TAPSE/PASP <0.44 showed net reclassification improvement of 18.2% (95%CI:0.61-35.8) vs. RV/LV ratio >1, and 27.7% (95%CI:10.2-45.1) vs. ESC risk strata. Decreased TAPSE/PASP ratio was associated with increased mortality. The ratio may aid in clinical decision-making, particularly for intermediate-risk patients for whom the discriminatory capability of the current risk stratification tools is limited.

Clinical and echocardiographic parameters associated with outcomes in patients with moderate secondary mitral regurgitation

BackgroundSignificant secondary mitral regurgitation (SMR) is known to be associated with worse prognosis. However, data focusing specifically on moderate SMR and associated risk factors are lacking. In the present study,...

Non-invasive surrogates for right Ventricular-Pulmonary arterial coupling: a systematic review and Meta-Analysis.

Right ventricle-pulmonary artery (RV-PA) coupling describes the energetic relationship between RV contractility and its afterload. The gold standard for assessment of this relationship requires invasive pressure-volume (PV) loop measurements. Non-invasive surrogates of RV-PA coupling have been developed, such as the echocardiographic tricuspid annular plane systolic excursion to pulmonary artery systolic pressure ratio (TAPSE/PASP), but their performance has not been systematically assessed. We sought to assess performance of TAPSE/PASP ratio compared to PV loop-defined RV-PA coupling. A systematic search was conducted. Studies were included if PV loop derived RV-PA coupling metrics were compared to echocardiographic or magnetic resonance imaging surrogates. We conducted a meta-analysis of TAPSE/PASP correlation to PV loop-defined RV-PA coupling. 1452 studies were identified in the initial search, of which ten met inclusion criteria. Five studies allowed for pooled analysis of TAPSE/PASP to Ees/Ea correlation (r = 0.52, 95% confidence interval 0.36-0.65). There was moderate heterogeneity across the pooled studies. Despite the common use of Non-invasive surrogates of RV-PA coupling, there is only moderate correlation with gold standard measurements. These metrics do not inform on the individual components of RV-PA coupling, limiting their use in the management of patients with RV dysfunction.

Role of right ventricular–pulmonary arterial coupling assessed by echocardiography to predict adverse outcomes in patients with acute pulmonary embolism

BackgroundPulmonary embolism (PE) is a lethal type of venous thromboembolic disease. Right ventricular (RV) failure is not an uncommon complication of PE leading to higher adverse outcomes. The tricuspid annular peak systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio as a surrogate for RV–pulmonary artery coupling has proven to be among the predictor of clinical outcomes in multiple patient groups. We evaluated in this study the role of TAPSE/PASP ratio in predicting adverse clinical outcomes in patients with acute PE.ResultsAmong patients with established diagnosis of acute PE admitted to the coronary care unit, echocardiography was done within 12 h of admission and TAPSE/PASP ratio was calculated. The patients were followed during hospitalization and after discharge for 3 months for development of adverse outcomes including rehospitalization due to heart failure, recurrent PE and mortality. A total of fifty-five consecutive patients were recruited with mean age 58.3 ± 6.9 years and nearly equal male-to-female ratio. The mean ratio of TAPSE/PASP was 0.479 ± 0.206. In-hospital and 3-month follow-up showed that 10.9% needed rehospitalization with heart failure, 14.5% developed recurrent pulmonary embolism, and mortality was 9.1%. TAPSE/PASP ratio was significantly lower among the patients who developed adverse outcomes. TAPSE/PASP ratio was among the independent predictors of rehospitalization with heart failure, recurrent pulmonary embolism but not mortality at 3-month follow-up. TAPSE/PASP ratio predicted rehospitalization with heart failure at a cutoff point ≤ 0.325, with 100% sensitivity and 79.6% specificity, and predicted recurrent pulmonary embolism at a cutoff point ≤ 0.325, with 75% sensitivity and 78.7% specificity.ConclusionTAPSE/PASP ratio is a noninvasive tool that can predict the development of early adverse outcomes in patients with acute PE including rehospitalization with heart failure and recurrent pulmonary embolism.

Pulmonary artery saturation as a primary endpoint for mechanical thrombectomy

As catheter-directed mechanical thrombectomies become more prevalent to treat intermediate-risk pulmonary embolisms (PE), an objective measure of efficacy and risk stratification is needed. Studies currently use indirect measures of afterload reduction, such as the right ventricle (RV)/left ventricle ratio and mean pulmonary pressure. They lack nuance in identifying patients who have reestablished RV compensation or right ventricular-pulmonary artery (PA) coupling. In this review, we discuss the potential benefits of monitoring the pulmonary artery saturation (SvO2) for predicting the success of mechanical thrombectomy for intermediate-risk PE patients. As an index of cellular oxygen delivery, PA saturation has been established as a critical component of understanding complex shock states and hemodynamic instability. In addition, it can be readily measured in these patients during PA instrumentation, requiring minimal additional procedure time.

Prognostic Relevance of Tricuspid Annular Plane Systolic Excursion to Systolic Pulmonary Arterial Pressure Ratio and Its Association With Exercise Hemodynamics in Patients With Normal or Mildly Elevated Resting Pulmonary Arterial Pressure

BackgroundEchocardiographic TAPSE/sPAP ratio is a non-invasive surrogate for right ventricular-pulmonary arterial (RV-PA) coupling. It has been related to outcome in patients with moderate to severe pulmonary hypertension (PH). Research QuestionIs RV-PA coupling of prognostic relevance in patients with suspected PH but only normal or mildly elevated mean pulmonary arterial pressure (mPAP) and is it associated with impaired exercise capacity and exercise hemodynamics? Study Design and MethodsPatients with mPAP<25mmHg who underwent echocardiography and exercise right heart catheterization in our PH-clinic, were retrospectively analyzed. Mild PH was defined by mPAP 21-24mmHg and exercise PH (EPH) by a mPAP/cardiac-output (CO) slope >3mmHg/L/min. Multivariate analysis was performed to identify independent predictors for clinical worsening, defined by disease-related hospitalization, transplantation, or death. Results237 patients (female: N=155; median age: 64 (IQR 54-73) years, no PH N=147; mild PH N=90; EPH N=202) were included. During the observation time of 63 (IQR:29-104) months, 36 patients died and 126 events of clinical worsening occurred. TAPSE/sPAP ratio turned out as age- and sex independent predictor of mortality (HR 0.09 95% CI: (0.01 – 0.62) p=0.014) and clinical worsening (HR 0.05 95% CI: (0.35-0.78); p=0.002). TAPSE/sPAP was also significantly correlated to 6-minute walk distance (r= 0.33; p<0.001) and exercise hemodynamics (mPAP/CO slope: rρ=-0.56, p<0.001). The best multivariate predictive model for clinical worsening in this patient collective consisted of TAPSE/sPAP ratio (HR: 0.71 (0.53-0.95), p=0.021), NT-proBNP (HR 1.15 (0.99-1.34), p=0.065) and 6MWD (HR: 0.998 (0.995-1.00), p=0.042). InterpretationIn patients with suspected PH but normal or only mildly elevated resting mPAP, TAPSE/sPAP ratio is an independent predictor of outcome. In addition, it is significantly associated with exercise capacity and exercise hemodynamics and may be a helpful tool in the prediction of future clinical worsening of this patient population.

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.

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.

The value of right ventricular pulmonary artery coupling in determining the prognosis of patients with sepsis

The outcomes of patients with sepsis are influenced by the contractile function of the right ventricle (RV), but the impact of cardiopulmonary interaction in ICU-mortality of sepsis patients remains unclear. This study aims to investigate the ICU-mortality impact of right ventricular-pulmonary artery (RV-PA) coupling in patients with sepsis. We employed echocardiography to assess patients with sepsis within the initial 24 h of their admission to the ICU. RV-PA coupling was evaluated using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio. A total of 92 subjects were enrolled, with 55 survivors and 37 non-survivors. TAPSE/PASP ratio assessed mortality with an area under the curve (AUC) of 0.766 (95% CI 0.670–0.862) and the optimal cutoff value was 0.495 mm/mmHg. We constructed a nomogram depicting the TAPSE/PASP in conjunction with IL-6 and Lac for the joint prediction of sepsis prognosis, and demonstrated the highest predictive capability (AUC = 0.878, 95% CI 0.809–0.948). In conclusion, the TAPSE/PASP ratio demonstrated prognostic value for ICU mortality in sepsis patients. The nomogram, which combines the TAPSE/PASP, IL-6, and LAC, demonstrated enhanced predictive efficacy for the prognosis of sepsis patients.