RV-pulmonary Arterial Coupling Research Articles

Deep phenotyping of unaffected carriers of pathogenic BMPR2 variants screened for pulmonary arterial hypertension.

Pathogenic variants in the gene encoding for BMPR2 are a major genetic risk factor for heritable pulmonary arterial hypertension (PAH). Due to incomplete penetrance, deep-phenotyping of unaffected carriers (UCs) of a pathogenic BMPR2 variant through multi-modality screening may aid in early diagnosis and identify susceptibility traits for future development of PAH. 28 UCs (44±16 years, 57% female) and 21 healthy controls (43±18 years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging (cMRI), transthoracic echocardiography (TTE), cardiopulmonary exercise testing (CPET) and right heart catheterization (RHC). Right ventricular (RV) pressure-volume (PV) loops were constructed to assess load independent contractility and compared with a healthy control group. A transgenic Bmpr2Δ71Ex1/+ rat model was employed to validate findings in humans. UCs had lower indexed right ventricular end-diastolic (80±18 mL·m-2 versus 64±14 mL·m-2;p= 0.003), end-systolic (34±11 mL·m-2 versus 27±8 mL·m-2;p=0.024) and left end-diastolic volumes (69±14 mL·m-2 versus 60±11 mL·m-2;p=0.019) than control subjects. Bmpr2Δ71Ex1/+ rats were also observed to have smaller cardiac volumes than WT rats. PV loop analysis showed significantly higher afterload (Ea) (0.15±0.06 versus 0.27±0.08; p<0.001), and end-systolic elastance (Ees) 0.28±0.07 versus 0.35±0.10; p=0.047) in addition to lower RV-pulmonary artery coupling (Ees/Ea)(2.24±1.03 versus 1.36±0.37; p=0.006) in UCs. During the 4-year follow-up period, two UCs developed PAH with normal NT-proBNP and TTE indices at diagnosis. Unaffected BMPR2 mutation carriers have an altered cardiac phenotype mimicked in Bmpr2Δ71Ex1/+ transgenic rats. Future efforts in establishing an effective screening protocol for individuals at risk for developing PAH warrants longer follow-up periods.

Current trends and latest developments in echocardiographic assessment of right ventricular function: load dependency perspective.

Right ventricle (RV) failure is a common complication of many cardiopulmonary diseases. Since it has a significant adverse impact on prognosis, precise determination of RV function is crucial to guide clinical management. However, accurate assessment of RV function remains challenging owing to the difficulties in acquiring its intricate pathophysiology and imaging its complex anatomical structure. In addition, there is historical attention focused exclusively on the left ventricle assessment, which has led to overshadowing and delayed development of RV evaluation. Echocardiography is the first-line and non-invasive bedside clinical tool for assessing RV function. Tricuspid annular plane systolic excursion (TAPSE), RV systolic tissue Doppler velocity of the tricuspid annulus (RV S'), and RV fractional area change (RV FAC) are conventional standard indices routinely used for RV function assessment, but accuracy has been subject to several limitations, such as load-dependency, angle-dependency, and localized regional assessment. Particularly, load dependency is a vexing issue, as the failing RV is always in a complex loading condition, which alters the values of echocardiographic parameters and confuses clinicians. Recently, novel echocardiographic methods for improved RV assessment have been developed. Specifically, "strain", "RV-pulmonary arterial (PA) coupling", and "RV myocardial work" are newly applied methods for RV function assessment, a few of which are designed to surmount the load dependency by taking into account the afterload on RV. In this narrative review, we summarize the latest data on these novel RV echocardiographic parameters and highlight their strengths and limitations. Since load independency is one of the primary advantages of these, we particularly emphasize this aspect.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension

BackgroundRight ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. MethodsConsecutive incident PAH patients aged ≥ 18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n=152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n=143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n=201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n=519 patients). Risk stratification was based on on the ESC/ERS 3-strata model and REVEAL 2.0 score. ResultsThese phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% C.I. 1.6-2.8, p<0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% C.I. 0.18-0.47, p<0.001). ConclusionsEchocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients.

Right ventricular dysfunction and impaired right ventricular-pulmonary arterial coupling in paradoxical low-flow, low-gradient aortic stenosis.

Paradoxical low-flow, low-gradient aortic stenosis (pLFLG AS) may represent a diagnostic challenge, and its pathophysiology is complex. While left ventricular (LV) systolic function is preserved, right ventricular dysfunction (RVD) and consecutive LV underfilling may contribute to low-flow and reduced stroke volume index, and to adverse outcomes following transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the potential role of RVD in pLFLG AS, and to assess the impact of pre-procedural RVD on clinical outcomes after TAVI in patients with pLFLG AS. Out of 2739 native AS patients, who received TAVI at the University of Cologne Heart Center between March 2013 and June 2021, 114 patients displayed pLFLG AS and were included in this study. Right ventricular (RV) function was assessed by transthoracic echocardiography, and a fractional area change (FAC) ≤35% and/or a tricuspid annular plane systolic excursion (TAPSE) <18 mm determined RVD. In addition, the TAPSE/systolic pulmonary artery pressure ratio (TAPSE/sPAP) was monitored as a measure of RV-pulmonary arterial (PA) coupling. An impaired FAC and TAPSE was present in 21.9% and 45.6% of patients, respectively, identifying RVD in 50.0%. RVD (p = 0.016), reduced FAC (p = 0.049), reduced TAPSE (p = 0.035) and impaired RV-PA coupling (TAPSE/sPAP ratio <0.31 mm/mmHg; p = 0.009) were associated with significantly higher all-cause mortality compared to patients with normal RV function. After adjustment for sex, age, body mass index, EuroSCORE II, previous myocardial infarction and mitral regurgitation, independent predictors for all-cause mortality were FAC, sPAP, TAPSE/sPAP ratio, right atrial area, RV diameter and tricuspid regurgitation. Adverse RV remodelling, RVD and impaired RV-PA coupling provide an explanation for low-flow and reduced stroke volume index in a subset of patients with pLFLG AS, and are associated with excess mortality after TAVI.

Collagen 18A1/Endostatin Expression in the Progression of Right Ventricular Remodeling and Dysfunction in Pulmonary Arterial Hypertension.

Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure-volume loops in patients with PAH to assess RV-pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV-pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH.

Multifaced risk factors and clinical impact of a deep Y descent in patients with heart failure irrespective of RV-PA coupling

BackgroundA deep Y descent in the jugular venous pulse (JVP) is associated with diseases such as a decrease in right ventricular (RV) preload reserve. The present study investigated the relationship between RV-pulmonary arterial (PA) coupling and a deep Y descent, examined risk factors for a deep Y descent and clarified whether a deep Y descent was an independent risk factor for cardiac events irrespective of RV-PA coupling in patients with heart failure (HF). MethodsWe enrolled 350 patients with HF who underwent echocardiography and JVP examination. A deep Y descent was identified by a deeper ‘Y’ descent than ‘X’ descent in the JVP waveform. We defined cardiac events of HF as follows: sudden death, death from HF, the emergent infusion of loop diuretics, or hospitalization for decompensated HF. Results and ConclusionsA deep Y descent and cardiac events were observed in 129 and 83 patients, respectively. The prevalence of a deep Y descent increased with decreases in the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary arterial pressure (SPAP) ratio. Not only the TAPSE/SPAP ratio (odds ratio,0.756 per0.1 mm/mmHg, 95 %confidence interval [CI], 0.660–0.866, p < 0.001), but also age, atrial fibrillation, and the use of beta-blockers were independent factors for a deep Y descent in multivariate logistic model. Multivariate Cox hazard model demonstrated that a deep Y descent was for cardiac events in patients with HF (Hazard ratio,2.682, 95 %CI, 1.599–4.497, p < 0.001) irrespective of the TAPSE/SPAP ratio. The development of therapeutic strategies based on central venous waveform may be needed for patients with HF.

Physiological mechanisms behind respiratory variations in right atrial pressure in pulmonary hypertension

Impaired respiratory variation of right atrial pressure (RAP) in severe pulmonary hypertension (PH) suggests difficulty tolerating increased preload during inspiration. Our study explores whether this impairment links to specific factors: right ventricular (RV) diastolic function, elevated RV afterload, systolic RV function, or RV-pulmonary arterial (PA) coupling. We retrospectively evaluated respiratory RAP variation in all participants enrolled in the EXERTION study. Impaired respiratory variation was defined as end-expiratory RAP − end-inspiratory RAP ≤ 2 mm Hg. RV function and afterload were evaluated using conductance catheterization. Impaired diastolic RV function was defined as end-diastolic elastance (Eed) ≥ median (0.19 mm Hg/mL). Seventy-five patients were included; PH was diagnosed in 57 patients and invasively excluded in 18 patients. Of the 75 patients, 31 (41%) had impaired RAP variation, which was linked with impaired RV systolic function and RV-PA coupling and increased tricuspid regurgitation and Eed as compared to patients with preserved RAP variation. In backward regression, RAP variation associated only with Eed. RAP variation but not simple RAP identified impaired diastolic RV function (area under the receiver operating characteristic curve [95% confidence interval]: 0.712 [0.592, 0.832] and 0.496 [0.358, 0.634], respectively). During exercise, patients with impaired RAP variation experienced greater RV dilatation and reduced diastolic reserve and cardiac output/index compared with patients with preserved RAP variation. Preserved RAP variation was associated with a better prognosis than impaired RAP variation based on the 2022 European Society of Cardiology/European Respiratory Society risk score (chi-square P = 0.025) and survival free from clinical worsening (91% vs 71% at 1 year and 79% vs 50% at 2 years [log-rank P = 0.020]; hazard ratio: 0.397 [95% confidence interval: 0.178, 0.884]). Subgroup analyses in patients with group 1 and group 4 PH demonstrated consistent findings with those observed in the overall study cohort. Respiratory RAP variations reflect RV diastolic function, are independent of RV-PA coupling or tricuspid regurgitation, are associated with exercise-induced haemodynamic changes, and are prognostic in PH.Trial registration. NCT04663217.

Left and right ventricular longitudinal systolic function following aortic valve replacement in the PARTNER 2 trial and registry.

Evaluation of left and right ventricular (RV) longitudinal systolic function may enhance risk stratification following aortic valve replacement (AVR). The study objective was to evaluate the changes in left and RV longitudinal systolic function and RV-pulmonary artery (RV-PA) coupling from baseline to 30 days and 1 year after AVR. Left ventricular (LV) longitudinal strain (LS), tricuspid annulus plane systolic excursion (TAPSE), and RV-PA coupling were evaluated in patients from the PARTNER 2A surgical AVR (SAVR) arm (n = 985) and from the PARTNER 2 SAPIEN 3 registry (n = 719). TAPSE and RV-PA coupling decreased significantly following SAVR, but remained stable following TAVR. Lower LV LS, TAPSE, or RV-PA coupling at baseline was associated with increased risk of the composite of death, hospitalization, and stroke at 5 years [adjusted hazard ratios (HRs) for LV LS < 15%: 1.24, 95% confidence interval (CI) 1.05-1.45, P = 0.001; TAPSE < 14 mm: 1.44, 95% CI 1.21-1.73, P < 0.001; RV-PA coupling < 0.55 mm/mmHg: 1.32, 95% CI 1.07-1.63, P = 0.011]. Reduced TAPSE at baseline was the most powerful predictor of the composite endpoint at 5 years. Patients with LV ejection fraction <50% at baseline had increased risk of the primary endpoint with SAVR (HR: 1.34, 95% CI 1.08-1.68, P = 0.009) but not with TAVR (HR: 1.12, 95% CI 0.88-1.42). Lower RV-PA coupling at 30 days showed the strongest association with cardiac mortality. SAVR but not TAVR was associated with a marked deterioration in RV longitudinal systolic function and RV-PA coupling. Lower TAPSE and RV-PA coupling at 30 days were associated with inferior clinical outcomes at 5 years. In patients with LVEF < 50%, TAVR was associated with superior 5-year outcomes.

Optimal combination of right ventricular functional parameters using echocardiography in pulmonary arterial hypertension.

Novel echocardiographic parameters of right ventricular (RV) function, including speckle-tracking-derived, three-dimensional, and RV-pulmonary artery coupling parameters, have emerged for the evaluation of pulmonary arterial hypertension (PAH). The relative role of these parameters in the risk stratification of PAH patients is unclear. We compared the performance of multiple RV parameters and sought to establish an optimal model for identifying the risk profile of patients with PAH. Comprehensive risk assessments were performed for 70 patients with PAH. The risk profile of every patient was determined based on the guideline recommendations. Conventional parameters, including fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE), novel speckle-tracking-derived RV longitudinal strain (RVLS), and three-dimensional RV ejection fraction (3D-RVEF), were used to evaluate RV function. Pressure-strain loops were measured for the assessment of RV myocardial work, including RV global wasted work (RVGWW). RV-pulmonary artery coupling was assessed by indexing RV parameters to the estimated pulmonary artery systolic pressure (PASP). The median age was 34 (30-43) years, and 62 (88.6%) patients were female. Forty-five patients were classified into the low-risk group, while 25 patients were classified into the intermediate-high-risk group. Most RV parameters could be used to determine the risk profile and exhibited significantly improved diagnostic performance after indexing to PASP (including FAC/PASP, TAPSE/PASP, and 3D-RVEF/PASP). RVLS/PASP showed the best performance, with an area under the curve of 0.895. In multivariate analysis (Model 1), only RVGWW (>90.5mmHg%), RVLS (>-16.7%), and TAPSE (<17.5mm) remained significant (all P<0.05). Model 1 outperformed every single RV parameter, with a significantly larger area under the curve (all P<0.05). With PASP indexing in Model 2, RVLS/PASP>-0.275 [odds ratio (OR) 20.63, 95% confidence interval (CI) 4.62-92.11, P<0.001] and RVGWW>90.5mmHg% (OR 6.17, 95% CI 1.37-27.76, P=0.018) independently identified a higher risk profile. The addition of RVGWW to two models determined incremental value in identification (continuous net reclassification improvement 1.058, 95% CI 0.639-1.477, P<0.001). The combination models for RV function outperformed any single parameter in identifying the risk profile of patients with PAH. Comprehensive assessment of RV-pulmonary artery coupling using multiparametric methods is clinically meaningful in patients with PAH.

Right ventricular-pulmonary arterial uncoupling and ventricular-secondary mitral regurgitation: Relationship with outcomes in advanced heart failure

BackgroundSecondary mitral regurgitation (MR) is common in heart failure with reduced ejection fraction (HFrEF) and associated with poor outcomes. However, there is little evidence regarding secondary MR in advanced HFrEF. Poor outcomes for MR intervention suggest a need for further risk stratification. ObjectivesWe hypothesized adverse prognosis in right ventricles (RV) less able to compensate for increased pulmonary pressures of post-capillary cause in the context of secondary MR. MethodsPatients were assessed with echocardiography, right heart catheterisation (RHC) and cardiopulmonary exercise testing. Ventricular-secondary MR was identified by echocardiography and categorised mild, moderate, or severe according to guidelines. RV ability to compensate for pulmonary pressure rise was assessed by RV-pulmonary artery (PA) coupling, calculated as ratio of tricuspid annular plane systolic excursion (TAPSE) and systolic pulmonary artery pressure (SPAP) (echocardiography for TAPSE and RHC for SPAP). Primary endpoint was a composite of all-cause mortality, urgent heart transplantation or mechanical circulatory support. Results456 patients with ventricular-secondary MR were followed up for a median of 2.39 years, with 237 reaching a primary endpoint. Severe MR conferred a worse prognosis than mild or moderate (HR 2.6, p<0.001). Right atrial pressure was predictive of survival. RV-PA uncoupling, defined as TAPSE/SPAP below median value of 0.37, was associated with reduced survival across all severities of mitral regurgitation (p<0.001). ConclusionsVentricular-secondary MR is common and severity correlates with adverse prognosis in advanced heart failure. RV-PA uncoupling can improve risk stratification in all grades of MR severity, particularly with PA pressure determined invasively.

Application of an echocardiographic index to characterize right ventricular-pulmonary arterial coupling in heart failure.

Heart failure (HF), with its high morbidity and mortality, remains a global public health issue. Right ventricular (RV) dysfunction is a sign of deterioration in the natural history of HF, and a thorough evaluation of the relationship between RV contractility and its afterload through RV-pulmonary arterial (RV-PA) coupling can aid in accurately assessing overall RV function. The ratio of RV end-systolic elastance (Ees) to pulmonary arterial elastance (Ea) invasively measured by right heart catheterization served as the gold standard for evaluating RV-PA coupling. An echocardiographic index termed tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) has been shown to correlate well with Ees/Ea. TAPSE/PASP is recognized as a non-invasive surrogate of RV-PA coupling and has been extensively studied in patients with HF. This review briefly describes the methods of assessing RV-PA coupling, mainly discussing echocardiography, summarizes the clinical utility of TAPSE/PASP in patients with different HF types, and provides an overview of the available literature.

Advanced hemodynamic and cluster analysis for identifying novel RV function subphenotypes in patients with pulmonary hypertension

BackgroundQuantifying right ventricular (RV) function is important to describe the pathophysiology of in pulmonary hypertension (PH). Current phenotyping strategies in PH rely on few invasive hemodynamic parameters to quantify RV dysfunction severity. The aim of this study was to identify novel RV phenotypes using unsupervised clustering methods on advanced hemodynamic features of RV function. MethodsParticipants were identified from the University of Arizona Pulmonary Hypertension Registry (n=190). RV-pulmonary artery coupling (Ees/Ea), RV systolic (Ees) and diastolic function (Eed) was quantified from stored RV pressure waveforms. Consensus clustering analysis with bootstrapping was used to identify the optimal clustering method. Pearson correlation analysis was used to reduce collinearity between variables. RV cluster subphenotypes were characterized using clinical data and compared to pulmonary vascular resistance (PVR) quintiles. ResultsFive distinct RV clusters (C1-C5) with distinct RV subphenotypes were identified using k-medoids with a Pearson distance matrix. Clusters 1 and 2 both have low diastolic stiffness (Eed) and afterload (Ea) but RV-PA coupling (Ees/Ea) is decreased in C2. Intermediate cluster (C3) has a similar Ees/Ea as C2 but with higher PA pressure and afterload. Clusters C4 and C5 have increased Eed and Ea but C5 has a significant decrease in Ees/Ea. Cardiac output was high in C3 distinct from the other clusters. In the PVR quintiles, contractility increased and stroke volume decreased as a function of increased afterload. World Symposium PH classifications were distributed across clusters and PVR quintiles. ConclusionsRV-centric phenotyping offers an opportunity for a more precise-medicine based management approach.

Occult right ventricular dysfunction and right ventricular-vascular uncoupling in left ventricular assist device recipients

BackgroundCurrent assessments remain insensitive for detecting right heart failure post left ventricular assist device (LVAD). Sensitive pressure-volume loop assessments of right ventricle (RV) contractility may improve our appreciation of post-LVAD RV dysfunction. MethodsThirteen LVAD patients and 20 reference (non-LVAD) subjects underwent comparison of echocardiographic, right heart cath hemodynamic, and pressure-volume loop-derived assessments of RV contractility using end-systolic elastance (Ees), RV afterload by effective arterial elastance (Ea), and RV-pulmonary arterial (RV-PA) coupling (ratio of Ees/Ea). ResultsLVAD patients had lower RV Ees (0.20±0.08 vs. 0.30±0.15 mmHg/ml, p=0.01) and lower RV Ees/Ea (0.37±0.14 vs 1.20±0.54, p<0.001) versus reference subjects. Low RV Ees correlated with reduced RV septal strain, an indicator of septal contractility, in both the entire cohort (r=0.68, p=0.004) as well as the LVAD cohort itself (r=0.78, p=0.02). LVAD recipients with low RV Ees/Ea (below the median value) demonstrated more clinical heart failure (71% vs 17%, p=0.048), driven by an inability to augment RV Ees (0.22±0.11 vs 0.19±0.02 mmHg/ml, p=0.95) to accommodate higher RV Ea (0.82±0.38 vs 0.39±0.08 mmHg/ml, p=0.002). Pulmonary artery pulsatility index (PAPi) best identified low baseline RV Ees/Ea (≤0.35) in LVAD patients (AUC=0.80); during ramp study, change in PAPi also correlated with change in RV Ees/Ea (r=0.58, p=0.04). ConclusionsLVAD patients demonstrate occult intrinsic RV dysfunction. In the setting of excess RV afterload, LVAD patients lack the RV contractile reserve to maintain ventriculo-vascular coupling. Depression in RV contractility may be related to LVAD LV unloading which reduces septal contractility.

Left and right ventricular hemodynamic response after transcatheter mitral valve replacement

Abstract Background Transcatheter mitral valve replacement (TMVR) represents a novel treatment option for patients with relevant mitral regurgitation (MR), who are ineligible for surgical treatment. Although complete and predictable elimination of MR is achieved in most patients undergoing TMVR, little is known about left and right ventricular hemodynamic changes after TMVR. Purpose With this study, we sought to investigate left ventricular (LV) remodeling and right ventricular (RV) function in patients undergoing TMVR using data derived from non-invasive, echocardiography-based pressure volume loops. Methods A total of 49 consecutive patients with MR 3+ or 4+ undergoing TMVR with one of four dedicated devices were included in a prospective single-center TMVR registry between 05/2016 until 08/2022. For this study, only patients with technical success and available echocardiographic data at baseline and discharge were included. The end-diastolic and end-systolic pressure-volume relationships (EDPVR and ESPVR) were estimated non-invasively using single-beat echocardiographic measurements. VPed20 was calculated as a parameter describing the end-diastolic volume (EDV) at an end-diastolic pressure (EDP) of 20 mmHg. Ees, the slope describing the ESPVR, was calculated as surrogate parameter for LV contractility. Pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE) and RV-pulmonary artery (PA) coupling were assessed as parameters reflecting RV function. Results A total of 26 patients (77.0 years [IQR 73.9-80.1], N=17 [65.4%] male) with successful TMVR were included (secondary MR [N=21, 80.8%]; median LV ejection fraction 37.0% [IQR 30.7-50.7]). Overall, a significant decrease in VPed20 was observed following TMVR indicating a leftward shift of the EDPVR (165.3±75.8mL vs. 134.0±65.9mL, p&amp;lt;0.001, Figure 1). In addition, Ees increased from 1.4±0.9 at baseline to 2.5±2.4 at discharge (p=0.0071) indicating an increaseed intrinsic LV contractility, while LV ejection fraction remained unchanged, but forward ejection fraction improved significantly (38.9±21.9% vs. 53.4±29.8%, p&amp;lt;0.001) (Figure 1). After the procedure we observed an increased left-ventricular end-diastolic pressure (LVEDP) (22.6±4.0mmHg vs. 26.1±5.1mmHg, p=0.012). However, PASP significantly decreased (50.5±16.5mmHg vs. 35.7±10.8mmHg, p&amp;lt;0.001). While TAPSE (18.1±5.5mm vs. 15.5±5.8mm, p=0.015) was also decreased at discharge, RV-PA coupling remained stable (0.4±0.2mm/mmHg vs. 0.5±0.2mmHg, p=0.19). Conclusions Non-invasive assessment of pressure volume loops before and after TMVR demonstrate an early LV reverse remodelling effect and improved systolic LV contractility, while RV performance was preserved. These results indicate the potential impact of complete MR elimination after TMVR on LV and RV function. Long-term data are needed to assess the prognostic impact of MR elimination and LV reverse remodelling following TMVR.Figure 1

Abstract 12370: Atrial Fibrillation and Atrial Remodeling Deteriorates Right Heart Function With Preserved LV Function in LKB1 f/f /ANF Cre+ Mice

Introduction: Atrial fibrillation (AF) and right ventricular dysfunction(RVD) are each highly prevalent in heart failure (HF) patients; their co-existence represents a severe HF phenotype. AF and RVD in HF are respectively attributed to left atrial remodeling and pulmonary hypertension due to left heart disease. Yet clinical studies have found that AF, not pulmonary pressure, is independently associated with RVD in HF. These findings suggest the possibility that AF can cause RV dysfunction. Hypothesis: Atrial fibrillation can cause progressive RV dysfunction even in the absence of pulmonary hypertension. Methods: We created an atrial-specific LKB1 knockdown (atrial-LKB1 KD) by injecting AAV9-ANF-Cre retro-orbitally into adult male LKB1 fl/fl mice (age 8 wks). Echocardiography and telemetry were performed at 4- and 12- weeks post AAV9-ANF-Cre. At 12-weeks post-AAV injection, both right ventricular and left ventricular pressure- volume loop recordings were performed. Histological and molecular analyses were also performed at study endpoint. LKB1 fl/fl mice (Cre-) were used as controls (CTL). Results: At 12 wks post-injection, the incidence of AF with atrial remodeling was 100% in atrial-LKB1 KD. Echocardiography revealed RV systolic dysfunction by RV FAC (50.72% vs. 60.45%, p&lt;0.05) and TAPSE (0.89mm vs. 1.15mm, p&lt;0.05) in atrial-LKB1 KD vs. CTL. In contrast, LV FS were comparable between atrial-LKB1 KD and CTL. (40.4% vs. 42%, p=0.38). Atrial-LKB1 KD demonstrated abnormal RV-pulmonary arterial coupling, increased RV systolic pressure, and preserved LV function following atrial remodeling. Expression of genes related to remodeling and inflammation were upregulated in the RV of atrial-LKB1 KD. Compared to that of CTL, RV expression level of Nppb was 3.4-fold higher (p&lt;0.05) and IL1β was 7.1 fold higher (p&lt;0.05) in atrial-LKB1 KD. Conclusions: Our findings strongly suggest that atrial fibrillation alone can cause RV dysfunction with concomitant preserved LV function. Remodeling and inflammation of the RV but not LV in the atrial-LKB1 KD also suggests that the right heart is more vulnerable than the left heart to AF-induced dysfunction.

Right Ventricular Contractility and Pulmonary Arterial Coupling After Less Invasive Left Ventricular Assist Device Implantation.

Right ventricular failure contributes significantly to morbidity and mortality after left ventricular assist device implantation. Recent data suggest a less invasive strategy (LIS) via thoracotomy may be associated with less right ventricular failure than conventional median sternotomy (CMS). However, the impact of these approaches on load-independent right ventricular (RV) contractility and RV-pulmonary arterial (RV-PA) coupling remains uncertain. We hypothesized that the LIS approach would be associated with preserved RV contractility and improved RV-PA coupling compared with CMS. We performed a retrospective study of patients who underwent durable, centrifugal left ventricular assist device implantation and had paired hemodynamic assessments before and after implantation. RV contractility (end-systolic elastance [Ees]), RV afterload (pulmonary effective arterial elastance [Ea]), and RV-PA coupling (Ees/Ea) were determined using digitized RV pressure waveforms. Forty-two CMS and 21 LIS patients were identified. Preimplant measures of Ees, Ea, and Ees/Ea were similar between groups. After implantation, Ees declined significantly in the CMS group (0.60-0.40, p = 0.008) but not in the LIS group (0.67-0.58, p = 0.28). Coupling (Ees/Ea) was unchanged in CMS group (0.54-0.59, p = 0.80) but improved significantly in the LIS group (0.58-0.71, p = 0.008). LIS implantation techniques may better preserve RV contractility and improve RV-PA coupling compared with CMS.

Different right ventricular dysfunction and pulmonary coupling in acute heart failure according to the left ventricular ejection fraction

BackgroundRight ventricular (RV) dysfunction and pulmonary uncoupling are two acknowledged features associated with poor outcome, however few data defined RV adaptation across the different left ventricular ejection fraction (EF) cut-off. Additionally, less data are reported in patients with acute heart failure (AHF). AimsThe aim of present study was to analyse RV function in AHF patients presenting with either reduced or preserved EF. MethodsThis is a multi-center observational study including 380 patients affected by AHF: 235 had AHF with reduced EF (AHFrEF) and 145 had AHF with preserved EF (AHFpEF). Pulmonary artery systolic pressure (PASP), tricuspid annular plane systolic excursion (TAPSE), S′ wave velocity, and the RV end-diastolic diameter (RVEDD) were measured by echocardiography. TAPSE/PASP and S′/PASP ratios were calculated as non-invasive surrogates of RV-pulmonary arterial coupling. ResultsFactors associated with poor outcome were higher values of PASP (45 [40–55] mmHg vs 40 [35–46] mmHg; p < 0.001), RVEDD (44 [38–47] mm vs 37 [35–42] mm; p < 0.001), lower TAPSE values (17 [15–20] mm vs 20 [18–22] mm; p < 0.001) and S′ wave (10 [8–12] cm/s vs 11 [10–13] cm/s; p < 0.001), reduced TAPSE/PASP (0.37 [0.29–0.47] vs 0.50 [0.40–0.60]; p < 0.001) and S′/PASP ratios (0.22 [0.18–0.28] vs 0.28 [0.22–0.34]; p < 0.001). However, the prognostic parameters differed according to the LVEF value: in AHFpEF S′/PASP between 0.22 and 0.29 and > 0.29 demonstrated a protective prognostic value (Respectively HR 0.29 (0.16–0.53), p < 0.001 and HR 0.22 [0.12–0.42], p < 0.001). Conversely, in AHFrEF, TAPSE <16 mm (HR 2.59 [1.67–4.03], p < 0.001), ICV > 21 mm (HR 1.17 [1.17–1.28], p = 0.001) and TAPSE/PASP <0.49 HR 1.92 [1.10–3.37], p = 0.023) were related to adverse outcome. ConclusionsRV adaptation and RV pulmonary coupling differ in AHF according to the level of LVEF. S′ wave, and S′/PASP are associated with adverse outcome in patients with preserved EF; reduced TAPSE and TAPSE/PASP are better prognostic predictors in patients with reduced EF.

Clinical and functional relevance of right ventricular contraction patterns in pulmonary hypertension

The right ventricle has a complex contraction pattern of uncertain clinical relevance. We aimed to assess the relationship between right ventricular (RV) contraction pattern and RV-pulmonary arterial (PA) coupling defined by the gold-standard pressure-volume loop-derived ratio of end-systolic/arterial elastance (Ees/Ea). Prospectively enrolled patients with suspected or confirmed pulmonary hypertension underwent three-dimensional echocardiography, standard right heart catheterization, and RV conductance catheterization. RV-PA uncoupling was categorized as severe (Ees/Ea < 0.8), moderate (Ees/Ea 0.8-1.29), and none/mild (Ees/Ea ≥ 1.3). Clinical severity was determined from hemodynamics using a truncated version of the 2022 European Society of Cardiology/European Respiratory Society risk stratification scheme. Fifty-three patients were included, 23 with no/mild, 24 with moderate, and 6 with severe uncoupling. Longitudinal shortening was decreased in patients with moderate vs no/mild uncoupling (p<0.001) and intermediate vs low hemodynamic risk (p<0.001), discriminating low risk from intermediate/high risk with an optimal threshold of 18% (sensitivity 80%, specificity 87%). Anteroposterior shortening was impaired in patients with severe vs moderate uncoupling (p=0.033), low vs intermediate risk (p=0.018), and high vs intermediate risk (p=0.010), discriminating high risk from intermediate/low risk with an optimal threshold of 15% (sensitivity 100%, specificity 83%). Left ventricular (LV) end-diastolic volume was decreased in patients with severe uncoupling (p=0.035 vs no/mild uncoupling). Early RV-PA uncoupling is associated with reduced longitudinal function, whereas advanced RV-PA uncoupling is associated with reduced anteroposterior movement and LV preload, all in a risk-related fashion. GOV: NCT04663217.

Left atrial remodeling and right ventricular-pulmonary arterial coupling after MitraClip implantation

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transcatheter edge-to-edge mitral valve repair (TEER) with the MitraClip system has emerged as a therapeutic alternative to surgical solutions in high risk patients with severe mitral regurgitation (MR). MR is characterized by left ventricular volume overload, which leads to left ventricular dilatation. Furthermore, MR is a common cause of pulmonary hypertension. Right ventricular (RV) intrinsic contractility and its response to afterload is referred to as RV-pulmonary arterial (PA) coupling. Effect of TEER in patients with MR on left atrial (LA) function and RV-PA coupling is less investigated. Purpose The aim of our study was to assess clinical characteristics of patients undergoing MitraClip implantation including LA function and RV-PA coupling. Methods Eighty-eight consecutive patients with chronic severe MR were enrolled in the single-center observational study (mean age 71.5±7.9 years, male 54.5%, ischemic cardiomyopathy 54.5%). Primary MR (PMR) was present in 22.7%, secondary MR (SMR) in 73.9 % and mixed (MxMR) etiology in 3.4%. Conventional and advanced echocardiography examination was performed using speckle tracking echocardiography before TEER and at 6 month post-TEER follow-up. Left atrial maximal (LAV max) and minimal (LAV min) volumes were measured indexed for body surface area. Furthermore, we analysed left atrial functional parameters, such as reservoir strain, conduit strain and contraction strain. Results The technical success of MitraClip implantation was 95,5%. Mortality rate at 6 month follow-up time was 10.8% (1/88 PMR, 7/88 SMR, 1/88 MxMR). Severe residual MR developed during follow-up in 4.2% and New York Heart Association class III-IV functional status was concluded in 6.8% at 6 month post-TEER. Significant decrease in left ventricular end-diastolic median diameter (mm) was observed at follow-up compared to pre-TEER: 57.5 (IQR: 51.25 – 63.75) vs 60.5 (IQR: 52.5 – 66.75), respectively, p = 0.01. Similarly, the median value of pulmonary artery systolic pressure (PASP) substantially decreased (mmHg) after TEER: 42 (IQR: 32 – 52) vs 49.5 (IQR: 41 – 57), respectively, p = 0.003. Tricuspid annulus systolic excursion/PASP median value, representing RV-PA coupling, improved remarkably: 0.45 (IQR: 0.31 – 0.69) vs 0.38 (IQR: 0.29 – 0.52), respectively, p = 0.02. Compared to pre-TEER, median LA volumes and strain parameters did not change significantly at 6 month post-TEER: reservoir strain (%) 12.88 (IQR: 8.18–18.78) vs 11.74 (IQR: 7.48–20.36), p = 0.41; LAV max (ml) 48.70 (IQR: 39.81–62.29) vs 48.17 (IQR: 42.08–58.7), p = 0.31; LAV min (ml) 34.33 (IQR: 24.5–46.32) vs 33.89 (IQR: 26.02–44.53), p = 0.69. Conclusions The function of the enlarged LA was severely reduced, which did not change after MitraClip implantation in our population. However, positive left ventricular remodeling and improvement in RV-PA coupling was observed 6 month after MitraClip procedure.

Assessment and diagnosis of right ventricular failure-retrospection and future directions.

The right ventricle (RV) has a critical role in hemodynamics and right ventricular failure (RVF) often leads to poor clinical outcome. Despite the clinical importance of RVF, its definition and recognition currently rely on patients' symptoms and signs, rather than on objective parameters from quantifying RV dimensions and function. A key challenge is the geometrical complexity of the RV, which often makes it difficult to assess RV function accurately. There are several assessment modalities currently utilized in the clinical settings. Each diagnostic investigation has both advantages and limitations according to its characteristics. The purpose of this review is to reflect on the current diagnostic tools, consider the potential technological advancements and propose how to improve the assessment of right ventricular failure. Advanced technique such as automatic evaluation with artificial intelligence and 3-dimensional assessment for the complex RV structure has a potential to improve RV assessment by increasing accuracy and reproducibility of the measurements. Further, noninvasive assessments for RV-pulmonary artery coupling and right and left ventricular interaction are also warranted to overcome the load-related limitations for the accurate evaluation of RV contractile function. Future studies to cross-validate the advanced technologies in various populations are required.