Right Ventricular Pressure Research Articles

A Dynamic Sheep Model to Induce Pulmonary Hypertension and Right Ventricular Failure.

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript describes the method to induce an ovine PH-RVF model that utilizes left pulmonary artery (LPA) ligation, progressive main pulmonary artery (MPA) banding, and insertion of an RV pressure line for monitoring. The PA cuff and RV pressure tubing are connected to subcutaneous access ports. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV's phenotypic response. Subjects undergo progressive PA band adjustments twice per week for approximately 9weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO2). Subjects can further be exercised on a livestock treadmill while hemodynamic parameters are captured. At the initiation and endpoint of this model, ventricular function and dimensions are assessed using echocardiography. In this model, RV mean and systolic pressure increased to 28±5 and 57±7mmHg at week 1, and further to 44±7 and 93±18mmHg by week 9, respectively. Echocardiography demonstrates characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The rate of PA banding has a significant impact on SvO2 and thus the model can be titrated to elicit varying RV phenotypes. When the PA cuff is tightened rapidly, it can lead to a precipitous decline in SvO2, leading to RV decompensation, whereas a slower, more paced strategy leads to an adaptive RV stress-load response that maintains physiologic SvO2. A faster rate of PA banding will also lead to more severe liver fibrosis. The addition of controlled exercise provides a useful platform for assessing the effects of physical exertion in a PH-RVF model. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and evaluating mechanical circulatory support systems.

The Sugen/Hypoxia Rat Model for Pulmonary Hypertension and Right Heart Failure.

Pulmonary hypertension (PH) is a devastating disease, characterized by complex remodeling of the pulmonary vasculature. PH is classified into five groups based on different etiology, pathology, as well as therapy and prognosis. Animal models are essential for the study of underlying mechanisms, pathophysiology, and preclinical testing of new therapies for PH. The complexity of the disease with different clinical entities dictates the necessity for more than one animal model to resemble PH, as a single model cannot imitate the broad spectrum of human PH.Here we describe a detailed protocol for creating a rat model of PH with right ventricular (RV) failure. Furthermore, we present how to characterize it hemodynamically by invasive measurements of RV and pulmonary arterial (PA) pressures. Animals subjected to this model display severe pulmonary vascular remodeling and RV dysfunction. In this model, rats undergo a single subcutaneous injection of Sugen (SU5416, a vascular endothelial growth factor inhibitor) and are immediately exposed to chronic hypoxia in a hypoxia chamber for 3-6weeks. This Sugen/Hypoxia rat model resembles Group 1 PH.

Assessment of Right Ventricular-Arterial Coupling by Echocardiography in Patients with Right Ventricular Pressure and Volume Overload.

Right ventricle-pulmonary arterial (RV-PA) coupling is considered the gold standard for assessing right ventricular (RV) function and can be evaluated noninvasively by echocardiography. The ratios of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP), RV global longitudinal strain (G-RVLS)/PASP, and stroke volume/end-systolic volume (SV/ESV) have been proposed as surrogates of RV-PA coupling. The relationship of these parameters remains incompletely understood in patients with volume and pressure loading conditions. We aimed to compare these parameters and evaluate their relationship with 3D RV data in patients with RV pressure and volume overload. This study was performed on 110 individuals who underwent 2D and 3D echocardiography. Fifty-four patients had RV volume overload (atrial septal defect (ASD) group), 34 patients had RV pressure overload (pulmonary hypertension (PH) group), and 22 were controls. TAPSE/PASP, G-RVLS/PASP and SV/ESV ratios were calculated. Correlations between parameters of RV-PA coupling and 3D data were assessed using general linear mixed models. Compared with the ASD group, the PH group had lower TAPSE/PASP and G-RVLS/PASP ratios. The SV/ESV ratio had a strong correlation with right ventricle ejection fraction (RVEF) in both ASD and PH patients (r = 0.8703, p 0.001 and r = 0.9388, p 0.001, respectively). The G-RVLS/PASP ratio showed a strong or moderately negative relationship with end-diastolic volume (EDV), ESV and SV (r = -0.7768, p = 0.001; r = -0.7327, p = 0.0005 and r = -0.6816, p = 0.0018, respectively) in PH patients. The TAPSE/PASP ratio showed moderately negative correlations with EDV and ESV (r = -0.5712, p = 0.0012 and r = -0.5594, p = 0.0016, respectively) in PH patients. Non-invasive RV-PA coupling parameters derived from echocardiography appear similar, but not identical to profiles in pressure-overloaded and volume-overloaded patients. The correlations between non-invasive RV-PA coupling parameters and 3D data displayed various degrees of correlation.

A Noninvasive Circulating Signature of Combined Right Ventricular Pressure and Volume Overload in Tetralogy of Fallot/Pulmonary Atresia/Major Aortopulmonary Collateral Arteries.

Background: Despite surgical advances, children with tetralogy of Fallot/pulmonary atresia/major aortopulmonary collaterals (TOF/PA/MAPCAs) are subject to chronic right ventricular (RV) pressure and volume overload. Current diagnostic tools do not identify adverse myocardial remodeling and cannot predict progression to RV failure. We sought to identify a noninvasive, circulating signature of the systemic response to right heart stress to follow disease progression. Methods: Longitudinal data were collected from patients with TOF/PA/MAPCAs (N = 5) at the time of (1) early RV pressure overload and (2) late RV pressure and volume overload. Plasma protein and microRNA expression were evaluated using high-throughput data-independent mass spectroscopy and Agilent miR Microarray, respectively. Results: At the time of early RV pressure overload, median patient age was 0.34 years (0.02-9.37), with systemic RV pressures, moderate-severe hypertrophy, and preserved systolic function. Late RV pressure and volume overload occurred at a median age of 4.08 years (1.51-10.83), with moderate RV hypertrophy and dilation, and low normal RV function; 277 proteins were significantly dysregulated (log2FC ≥0.6/≤-0.6, FDR≤0.05), predicting downregulation in lipid transport (apolipoproteins), fibrinolytic system, and extracellular matrix structural proteins (talin 1, profilin 1); and upregulation in the respiratory burst. Increasing RV size and decreasing RV function correlated with decreasing structural protein expression. Similarly, miR expression predicted downregulation of extracellular matrix-receptor interactions and upregulation in collagen synthesis. Conclusion: To our knowledge, we show for the first time a noninvasive protein and miR signature reflecting the systemic response to adverse RV myocardial remodeling in TOF/PA/MAPCAs which could be used to follow disease progression.

Current status of ECMO for massive pulmonary embolism.

Massive pulmonary embolism (MPE) carries significant 30-day mortality and is characterized by acute right ventricular failure, hypotension, and hypoxia, leading to cardiovascular collapse and cardiac arrest. Given the continued high mortality associated with MPE, there has been ongoing interest in utilizing extracorporeal membrane oxygenation (ECMO) to provide oxygenation support to improve hypoxia and offload the right ventricular (RV) pressure in the belief that rapid reduction of hypoxia and RV pressure will improve outcomes. Two modalities can be employed: Veno-arterial-ECMO is a reliable process to decrease RV overload and improve RV function, thus allowing for hemodynamic stability and restoration of tissue oxygenation. Veno-venous ECMO can support oxygenation but is not designed to help circulation. Several societal guidelines now suggest using ECMO in MPE with interventional therapy. There are three strategies for ECMO utilization in MPE: bridge to definitive interventional therapy, sole therapy, and recovery after interventional treatment. The use of ECMO in MPE has been associated with lower mortality in registry reviews, but there has been no significant difference in outcomes between patients treated with and without ECMO in meta-analyses. Considerable heterogeneity in studies is a significant weakness of the available literature. Applying ECMO is also associated with substantial multisystem morbidity due to a systemic inflammatory response, hemorrhagic stroke, renal dysfunction, and bleeding, which must be factored into the outcomes. The application of ECMO in MPE should be combined with an aggressive pulmonary interventional program and should strictly adhere to the current selection criteria.

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.

Robotic right ventricle is a biohybrid platform that simulates right ventricular function in (patho)physiological conditions and intervention

The increasing recognition of the right ventricle (RV) necessitates the development of RV-focused interventions, devices and testbeds. In this study, we developed a soft robotic model of the right heart that accurately mimics RV biomechanics and hemodynamics, including free wall, septal and valve motion. This model uses a biohybrid approach, combining a chemically treated endocardial scaffold with a soft robotic synthetic myocardium. When connected to a circulatory flow loop, the robotic right ventricle (RRV) replicates real-time hemodynamic changes in healthy and pathological conditions, including volume overload, RV systolic failure and pressure overload. The RRV also mimics clinical markers of RV dysfunction and is validated using an in vivo porcine model. Additionally, the RRV recreates chordae tension, simulating papillary muscle motion, and shows the potential for tricuspid valve repair and replacement in vitro. This work aims to provide a platform for developing tools for research and treatment for RV pathophysiology.

Right ventricular pressure-strain-volume loop-derived myocardial work for the noninvasive assessment of volume overload-induced dysfunction in patients with secondary tricuspid regurgitation

Abstract Development of secondary tricuspid regurgitation (TR) is associated with poor outcomes in patients with left-sided cardiac diseases. Severe TR imposes substantial volume overload (VO) on the right ventricle (RV), inducing a vicious circle of progressive RV remodelling and dysfunction. Although previous studies have established the value of speckle tracking echocardiography (STE)-derived strain and pressure-strain loop-derived myocardial work indices, these metrics neglect chamber geometry, limiting their utility in conditions accompanied by VO. Accordingly, we aimed to (1) incorporate instantaneous RV volume into myocardial work calculation to define a method capable of detecting VO-induced RV dysfunction using 3D echocardiography (3DE) and (2) to test its prognostic power in patients with secondary TR. We enrolled 195 patients (age: 64±15 years, 69% male) with left-sided cardiac diseases and followed them for a median of 42 months. The primary endpoint was all-cause mortality. TR severity was graded according to current guidelines and we compared patients with significant (moderate+) TR (sTR, n=85) versus non-significant TR (nsTR, n=110). All patients underwent 3DE to measure left (LV), and RV volumes and ejection fractions (EF). A reference RV pressure curve was constructed using previously acquired right heart catheterization data and was individually adjusted by non-invasively estimated RV pressures. To obtain RV pressure-strain loops and global myocardial work index (GMWI), RV pressure and 3DE-derived RV circumferential strain tracings were concatenated. We further adjusted GMWI to instantaneous RV volumes (GMWIV) and constructed pressure-strain-volume loops (Figure 1). Twenty-three patients (11.8%) died during follow-up (16 out of 85 in the sTR group, and 7 out of 110 in the nsTR group). There were no differences in LV and RV volumes and EFs between the sTR and nsTR groups. Interestingly, patients with sTR had significantly higher values of GMWI (sTR vs. nsTR; 667 [438-879] vs. 567 [414-770] mmHg%, p=0.01), whereas GMWIV (292 [169-467] vs. 282 [170-399] mmHg%/mL, p=0.57) did not show difference. We compared patients with versus without adverse outcomes within the sTR group. Patients with sTR who died, presented with significantly lower volume-adjusted GMWIV values (dead vs. alive; 158 [122-332] vs. 312 [207-502] mmHg%/mL, p=0.02), while GMWI did not differ. By Cox regression analysis, GMWIV (hazard ratio [95% CI]: 0.997 [0.994-1.000], p<0.05) was a significant predictor of all-cause mortality in the entire population, whereas GMWI was not. By integrating RV volume into the pressure-strain relationship, our novel metric could detect the detrimental effects of VO on RV function with prognostic implications in patients with secondary TR. Our approach can be able to capture VO-induced subclinical RV dysfunction that conventional echocardiographic metrics could not unveil.Figure 1

Transcatheter mitral valve repair and its impact on reverse right ventricular remodelling

Abstract Introduction Transcatheter edge-to-edge repair (TEER) has been proven to reduce cardiovascular events in a particular subset of patients with severe mitral insufficiency (MR) and left ventricle dysfunction. Nevertheless, its short and long-term impact on the right ventricle (RV) remained to be determined. Our goal was to assess the effect of TEER on the RV and right chamber pressures. Methods Patients were consecutively enrolled from Nov 2018 to Jul 2022. Clinical, laboratory echocardiographic and procedural data were collected. Follow-up information of admissions for heart failure, New York Heart Association (NYHA) functional class and survival was collected. The data was analysed prior to and at 3 and 12 months after the procedure. RV dysfunction was defined as Tricuspid Annular Plane Systolic Excursion (TAPSE) < 17mm or S’ < 9cm/s. Changes between baseline and follow-up parameters were assessed using the paired t-test. Results A total of 46 patients were included. Average age was 77.28 ± 7.92 years and 30 were male (65.2%). Twelve patients were on NYHA class III (26.1%) and most had functional mitral insufficiency (25; 54.3%) and mild to moderate tricuspid insufficiency (36; 78.3%). All patients had severe mitral insufficiency (estimated regurgitant orifice area 41.28 ± 16.77mm; regurgitant volume 62 ± 28.96mL). Seventeen patients had diabetes (37.0%), 10 had coronary artery disease (21.7%), 23 had atrial fibrillation (50.0%) and 6 had chronic kidney disease (13.0%). At 3 months, mean right ventricular/right atrial gradient (RV/RAgrad) was significantly lower (37.26 ± 9.66 mmHg vs 30.81 ± 17.36 mmHg; p 0.017) as well as MR (2.98 ± 0.15 vs 1.67 ± 0.63; p < 0.001). There were no differences regarding severity of tricuspid regurgitation (TR) and RV and left ventricle (LV) function. At 1 year follow-up there was a marked improvement of RV/RAgrad (37.49 ± 10.87 mmHg vs 28.12 ± 10.13 mmHg; p 0.009), TAPSE (18.83 ± 4.22 mm vs 20.88 ± 3.08 mm; p 0.035), S’ (10.81 ± 4.00 cm/s vs 13.5 ± 1.97 cm/s, p 0.015) and MR severity (2.98 ± 0.15 vs 1.83 ± 0.71; p <0.001). Number of heart failure readmissions was also lower at 1 year follow-up post TEER (0.35 ± 0.80 vs 0.81 ± 0.87; p 0.032). Over a mean follow-up time of 1.72 ± 1.16 years, only 8.7% of patients died and 17.4% were readmitted due to heart failure. Conclusion TEER has a positive impact on right ventricle function and pressures. This effect was more prominent at 1 year follow-up and suggests reverse remodelling continues even after 3 months. Overall, patients with TEER had low rates of death and heart failure readmissions.

Acyl ghrelin increases cardiac output and preserves right ventricular-pulmonary arterial coupling in patients with heart failure

Abstract Background Pulmonary hypertension and right ventricular (RV) failure are common in heart failure with reduced ejection fraction (HFrEF). Acyl ghrelin improves cardiac output (CO) in HFrEF but when CO increases there is a risk of increased pulmonary vascular resistance (PVR). This may impair the right ventricular-pulmonary artery coupling (RVPAC) and in the long term further harm the afterload sensitive RV in HFrEF or in patients with pulmonary arterial hypertension (WHO group 1). Animal data suggest that acyl ghrelin has beneficial effects on the pulmonary vasculature. Purpose To investigate if grehlin increases CO without worsening the right-sided hemodynamics in HFrEF assessed by RVPAC measured as the non-invasive surrogate tricuspid annular plane systolic excursion/tricuspid regurgitation velocity (TAPSE/TRV). Methods The Karolinska Acyl Ghrelin Trial (ClinicalTrials.gov NCT05277415) was a double-blind placebo-controlled trial of acyl ghrelin vs. placebo in HFrEF. In this secondary analysis we assessed RVPAC. Patients (n = 15+15) received either acyl ghrelin 30 pmol/kg/min or placebo (normal saline) intravenously during 120 min. Echocardiography exams at baseline and 120 min were assessed for RV parameters and patients were included if both TAPSE and TRV could be assessed at both time-points. Changes within groups (acyl ghrelin and placebo) at baseline vs. 120 min were analysed by Wilcoxon rank sign test. Analysis of variance was used to test for difference in change acyl ghrelin vs. placebo, adjusted for baseline values. Results A total of 22 patients (acyl ghrelin n = 12, placebo = 10) were included. Clinical characteristics were similar [median (IQR) acyl ghrelin vs. placebo): age 71 (65-77) vs. 74 (72-77) years, EF 29 (20-35) vs. 18 (13-36) %. Despite a 15% increase in CO in the acyl ghrelin group [from 4.0 (3.5-4.6) to 4.6 (3.9-6.1) L/min, p = 0.003], RVPAC remained unchanged; 5.9 (5.3-7.6) to 6.3 (4.8-7.5) mm·(m/s)-1, p = 0.372, while it was reduced in the placebo group, 5.2 (4.3-6.4) to 4.8 (4.2-5.8) mm·(m/s)-1, p = 0.035. Similarly, TAPSE remained unchanged in the acyl ghrelin group 18.0 (14.8-20.5) to 17.5 (13.8-19.3), p = 0.188, while it decreased in the placebo group 14.5 (13.0-17.5) to 13.5 (11.3-15.0), p = 0.028. There were no differences in TRV. When comparing the changes between groups adjusted for baseline, CO increased in the acyl ghrelin group vs. placebo (p = 0.036) while there were no significant differences in RVPAC or TRV (Figure 1). Conclusion These preliminary findings indicate that acyl ghrelin may preserve or even improve RVPAC without increasing the RV pressure gradient. This may be due to acyl ghrelin causing improved contractility, reduced PVR and/or reduced left sided filling pressures. These potential effects strengthen the role of acyl ghrelin therapy in HFrEF and suggest potentially beneficial effects also in patients with isolated or combined pre- and post-capillary pulmonary hypertension.

Interleukin-22 deficiency exacerbates right ventricular remodeling during pressure overload

Abstract Background Fibrosis and remodeling of right ventricle (RV) are associated with prognosis in patients with RV failure. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, play roles in tissue protection and wound repair. We have previously shown that IL-22 plays an important role in cardiac remodeling after acute myocardial infarction; however, the role of IL-22 in RV fibrosis and remodeling remains elusive. Purpose We investigated the role of IL-22 in the pathogenesis of RV remodeling during pressure overload. Methods Pulmonary artery banding (PAB) is performed by placing a 6-0 suture around the pulmonary artery over a 24 G needle in wild type mice (C57BL/6J) and IL-22 knockout mice (IL-22 KO). Only mice with moderate pulmonary artery stenosis (peak pressure gradient across the pulmonary band: 25–40 mmHg at 1 week after surgery by echo Doppler) were included in the study protocol. Two weeks after PAB, RV function was measured by echocardiography and real-time PCR analysis was performed to measure IL-22, IL-22 receptor subunit alpha 1 (IL-22RA1), and IL-22 signaling inhibitor IL-22 binding protein (IL-22BP). Results 2 weeks after PAB, IL-22 KO mice showed markedly increased RV weight (IL-22 KO mice vs. wild-type mice; RV/LV+IVS: 0.48±0.05 vs 0.40±0.02, P=0.002). IL-22 KO mice exhibited significant RV enlargement and RV dysfunction 2 weeks after PAB. (IL-22 KO mice vs wild type mice; RVEDV: 10±2.3mm2 vs 12.9±3.1mm2, P=0.005, TAPSE: 10.8±1.8mm vs 9.5±1.7mm, P=0.04, FAC: 35.2±7.8% vs 23±6.0%, P<0.001). The expression of IL-22, IL-22RA1 and IL-22BP in the RV tended to increase 2 weeks after PAB (wild-type mice with PAB (n=3) vs. wild-type mice with sham; IL-22: 0.0023 vs 0.0028, P=0.18 IL-22RA1: 1.489 vs 1.773, P=0.175, IL-22BP: 0.025 vs 0.067, p=0.005). Conclusion These results suggest that IL-22 is involved in RV remodeling during RV pressure overload.

Right ventricular-pulmonary artery coupling and in-hospital mortality of patients with first acute coronary syndrome

Abstract Background Right ventricular-pulmonary artery (RV-PA) coupling is a means of indexing RV performance to the existent RV afterload. Although non-invasive analysis of RV-PA coupling is a well-recognized prognosticator in chronic RV pressure overload conditions such as heart failure and pulmonary hypertension, its impact in patients with myocardial infarction and acute elevations in RV afterload remains undetermined. Aim This study sought to investigate the associations and short term prognostic value of RV-PA coupling in patients with first acute coronary syndrome (ACS), as assessed by two standard echocardiographic measurements: tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). Methods A total of 300 consecutive patients with first ACS (mean age 61.2±11.8 years, 74% males) were prospectively enrolled. A comprehensive transthoracic echocardiographic assessment was undertaken within 24 hours after revascularization. In-hospital mortality was the study endpoint. The study population was dichotomized according to the optimal TAPSE/PASP cut-off, as determined by receiver-operating characteristic curve analysis. Univariable and multivariable logistic regression analysis was performed to determine predictors of impaired TPASE/PASP and the association of TAPSE/PASP with in-hospital mortality. To further assess the incremental prognostic value of TAPSE/PASP over a baseline model the change in x² was assessed using the likelihood ratio test. Results A total of 23 (7.7%) patients died in-hospital despite successful revascularization. The optimal cut-off value of TAPSE/PASP to determine in-hospital mortality was 0.49. Among others, univariable associates of impaired TAPSE/PASP were the Global Registry of Acute Coronary event (GRACE) risk score, Killip Class >2, late presentation after symptoms onset, NT-pro-BNP, and left ventricular ejection fraction (LVEF). In multivariable analysis LVEF was the only independent predictor of impaired TAPSE/PASP (OR 0.889, 95% CI [0.821-0.963], p=0.004). The subgroup of patients with LVEF<40% and TAPSE/PASP<0.49mm/mmHg exhibited the worst in-hospital mortality rate (Abstract Picture 1). TAPSE/PASP was significantly associated with in-hospital mortality (OR 0.037, 95% CI [0.009-0.153], p<0.001), and retained this association after adjusting for GRACE risk score and LVEF (OR 0.137, 95% CI [0.032-0.578], p=0.007). The incremental prognostic value of TAPSE/PASP<0.49mm/mmHg for in-hospital mortality was evaluated by adding it to a model including the GRACE risk-score, LVEF<40% and TAPSE<17mm. The further addition of impaired TAPSE/PASP significantly increased the x² of the model from 21.627 to 86.213, p<0.001 (Abstract Picture 2). Conclusion RV-PA coupling assessed non-invasively by echocardiography 24 hours after revascularization was an independent predictor of in-hospital mortality in patients with first ACS and may improve risk stratification.In hospital mortality ratesIncremental prognostic value

Abstract 17742: Anterior Papillary Muscle Rupture After a Motor Vehicle Collision: A Rare Case of Torrential Tricuspid Regurgitation After Blunt Cardiac Injury

Introduction: Blunt cardiac injury is difficult to diagnose in the setting of polytrauma. Here we present a rare case of a torrential tricuspid regurgitation from a ruptured anterior papillary muscle after a motor vehicle collision (MVC). Case: A 55-year-old male presented to the ED after an MVC. He was hemodynamically unstable and hypoxic en route complaining of severe chest and left leg pain. Imaging demonstrated multiple rib fractures, a left acetabular fracture, and left open distal femur fracture. EKG identified atrial fibrillation with RVR and nonspecific ST changes. Labs were significant for leukocytosis and a troponin elevation to 11.98 concerning for blunt cardiac injury. A TTE demonstrated a mobile density in the RA and RV consistent with papillary muscle rupture and severe tricuspid regurgitation. An underfilled left ventricle compressed by the right heart and dilated RV were noted with septal flattening consistent with RV pressure and volume overload. Cardiothoracic surgery was consulted and recommended delayed tricuspid valve repair after other acute injuries were addressed considering the need for full anticoagulation. While in the ICU, his orthopedic injuries were addressed though his hemodynamics were complicated by frequent orthopedic interventions requiring blood transfusions. He later underwent TV replacement and it was found that the anterior papillary muscle was ruptured at its base without leaflet perforation. One week post-operatively the patient suffered a hypoxic PEA arrest. The shock team was consulted and he underwent bedside ECMO cannulation with impella placement for LV failure. After ten days on ECMO he was decannulated. Ultimately, the patient recovered well and was discharged to acute rehab. Discussion: MVCs are a leading cause of traumatic tricuspid insufficiency. However, this life-threatening condition may go undetected due polytrauma and the presence of coexisting distracting injuries. Guidelines are needed for the specific management of traumatic tricuspid regurgitation and associated right heart dysfunction. Additionally, the need for multiple surgical interventions can preclude anticoagulation which is a unique barrier to urgent valve replacement in these patients.

Abstract 17909: Pulmonary Hypertension is Associated With Morbidity, Mortality and Prolonged Hospitalization in Premature Infants With Bronchopulmonary Dysplasia

Introduction: Pulmonary hypertension (PH) is a common comorbidity in premature infants with bronchopulmonary dysplasia (BPD). We sought to assess factors associated with PH and determine its association with morbidity and mortality in a large contemporary BPD cohort. Hypothesis: PH is independently associated with increased mortality in premature neonates with BPD. Methods: This single center retrospective cohort study identified all infants with BPD born 2010-2021. BPD severity was defined by previously established literature guidelines. PH was defined at ≥ 36 weeks post-menstrual age by echocardiography (RV pressure > 40 mmHg, eccentricity index > 1.1), cardiac catheterization (mean pulmonary artery pressure > 20 mmHg, pulmonary capillary wedge pressure ≤ 15 mmHg and pulmonary vascular resistance ≥ 3 iWU), or treatment with enteral pulmonary vasodilators. Outcomes of death, tracheostomy, hospital duration and comorbidities were compared against a positive PH diagnosis. Univariate and multivariable models were used to assess associations of PH and covariates with clinical outcomes. Results: The sample cohort consisted of 726 neonates (median Gestational Age: 26 weeks [IQR 25.0, 28.0], 48.4% female) with PH diagnoses in 190 (26%). 92 PH patients received enteral PH therapy, with 84 (44%) on mono and 8 (5%) on dual therapy, which was discontinued by a median age 9.5 months (IQR 6.6 - 15.3). Lower gestational age (p=0.016), higher BPD severity (p<0.0001), and non-white race (p=0.002) were associated with PH in multivariable models. PH was associated with higher mortality rate (18% vs 5%, p <0.0001), higher tracheostomy rate (50% vs 16%, p<0.0001), and longer hospital duration (median 116 (IQR 61-182) vs 58 (IQR 11-132) days, p = 0.001) in univariate and multivariable models. PH was associated with pulmonary vein stenosis (9% vs 1%, p=0.001), but not NEC, ROP or IVH after adjusting for covariates. Conclusions: This study demonstrates that BPD-PH carries an independent risk for mortality and morbidity including BPD severity, tracheostomy, pulmonary vein stenosis, and longer hospitalization. Enteral pulmonary vasodilators were used in almost half of all PH patients, with resolution of PH within 1 year of diagnosis in the majority of infants.

Abstract 12001: To Bleed or Not to Bleed: The Challenging Management of Saddle Pulmonary Embolism in a Patient With Widely Metastatic Breast Cancer

Introduction: In patients with high-risk pulmonary embolism (PE), anticoagulation (AC) is the mainstay of treatment before and after systemic thrombolysis and/or catheter-directed therapy. Our case highlights a challenging clinical decision where AC had to be initiated due to hemodynamic instability despite its controversial role in patients with CNS metastases. Case Description: A 52 years old female with ER+/PR+/HER2- breast cancer with widespread brain & vertebral metastases presented after a syncopal event. She had tachycardia and hypotension necessitating IV fluids and vasopressors. Echocardiogram showed RV dilation with reduced systolic function & septal wall motion concerning for RV pressure overload. CTA of chest showed large saddle PE with extension into bilateral segmental arteries and enlarged RV. Significant labs: Troponin-I 1.64 ng/mL, BNP 186 pg/mL, hemoglobin 8 g/dL, and platelets 54,000/μl. She was initiated on IV heparin but given worsening hemodynamic instability, she underwent catheter-based thrombectomy with improvement in hemodynamics. Serial CT head showed no evidence of intracranial hemorrhage but she developed diffuse alveolar hemorrhage necessitating intubation. Her bleeding eventually resolved, and she was extubated and discharged on DOAC. Discussion: This patient had high-risk PE given her hemodynamic instability, elevation in cardiac biomarkers, and RV strain on imaging. Treatment includes AC followed by systemic thrombolysis or catheter-directed therapy followed by AC. This patient’s management was complicated due to widespread metastases, thrombocytopenia and anemia. AC was nonetheless initiated due to her hemodynamic instability and patient eventually required thrombectomy. Conclusion: Brain metastases are an absolute contraindication to systemic thrombolysis, but the role of systemic AC is controversial. Our case highlights the importance of personalized decision-making regarding AC.

Abstract 17220: Mathematical Modeling of Echocardiographic Underestimation of Right Ventricular Systolic Pressure in Severe Tricuspid Regurgitation

Background: Echocardiography approximates right ventricular systolic pressure (RVSP) by the simplified Bernoulli Equation (SBE), adding mean right atrial pressure (mRA) to convective pressure (4v 2 ), where v is maximal tricuspid regurgitant (TR) velocity. As TR worsens, the inertance of TR flow increases which may cause TR peak velocity to lag behind the maximal RVSP time point. As a result, using SBE may underestimate RVSP in patients with significant TR. Currently, inertance is not measurable by echo, but theory suggests it is linearly related to regurgitant orifice diameter (3 X ROD). We sought to confirm the principle of RVSP underestimation in ≥severe TR by comparing a lumped parameter model (LPM) of the heart to cath/echo data. Methods: In MATLAB, the LPM uses time-varying elastance of atria/ventricles and the complete Bernoulli equation to model pressure and flow in all chambers/vascular beds. LPM parameters for trace and torrential TR cases yielded convective, inertial, RA and RV pressure curves and critical TR variables: TR volume, mRA, and TR velocity, which were compared to simultaneous cath/echo data in clinical patients. Results: Trace TR pressure curves aligned with RVSP and convective pressure peaks, and near perfect echo prediction. Torrential TR pressure curves show earlier peak RVSP with up to 20mmHg of inertial pressure, resulting in predicted 3.1mmHg underestimation, closely matching the observed underestimation of 3.6mmHg. For modeling demonstration, we show (from 90 subjects) 1 patient with trace TR (ROD 1.1mm), A, and 1 patient with torrential TR (ROD=11.3mm), B, in Figure 1. Conclusions: Our analysis shows the importance of inertial pressure in ≥severe TR: earlier peak RVSP congruent with accelerating increased regurgitant mass and improved approximation of RVSP by inertial pressure quantification modeling. Further clinical study of RVSP underestimation in cases of ≥severe TR and its correction by including inertial forces is recommended.

Percutaneous Transseptal Extracorporeal Membrane Oxygenation to Rescue a Failing Right Ventricle in an Animal Model

Objective: We tested the feasibility and effectiveness of a percutaneous atrial transseptal extracorporeal membrane oxygenation (ECMO) cannulation strategy in a right ventricular failure (RVF) model. Methods: We performed 4 nonsurvival porcine experiments. Percutaneous transseptal access was achieved using a steerable introducer. For guidance, we used fluoroscopy, transesophageal echocardiogram (TEE), and intracardiac echocardiography (ICE). A ProtekDuo rapid deployment cannula (LivaNova, London, UK) was advanced across the septum into the left atrium by 2 to 3 cm. Pulmonary hypertension (PH) was induced by partially clamping the pulmonary artery. ECMO flow was cycled from high (2 to 3 L/min) to low (0.2 to 0.3 L/min) over 2 to 3 hours. Results: Transseptal access using TEE and fluoroscopy was successful in 1 animal and unsuccessful in 1 animal. ICE provided optimal visualization for the remaining 2 animals. Mean arterial pressure (MAP) was associated immediately and consistently with high versus low ECMO flow rate (mean difference: 29 ± 3.1 mm Hg, P = 0.004) but was not restored to baseline values. RV pressure values were dynamic. Given time to equilibrate, mean RV pressure was restored to a baseline level. Conclusions: Percutaneous right atrium to left atrium transseptal cannulation relieved PH-RVF. MAP was restored to a viable level, and mean RV pressure was restored to a baseline level. Transseptal ECMO shows promise as a cannulation strategy to bridge patients with PH-RVF to lung transplant.

Serial RV wall stress measurements: association with right ventricular function in repaired Tetralogy of Fallot patients

BackgroundOptimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Ventricular wall stress is considered to be an early marker of right ventricular (RV) dysfunction.ObjectivesTo investigate the association of RV wall stresses and their change over time with functional parameters in TOF patients.MethodsTen TOF patients after surgical repair with moderate/severe pulmonary regurgitation were included. At two timepoints (median follow-up time 7.2 years), patient-specific computational biventricular models for wall stress assessment were created using CMR short-axis cine images and echocardiography-based RV pressures. RV ejection fraction (RVEF), NT-proBNP and cardiopulmonary exercise tests were used as outcome measures reflecting RV function. Associations between regional RV diastolic wall stress and RV function were investigated using linear mixed models.ResultsIncreased wall stress correlated with lower RV mass (rrm = −0.70, p = 0.017) and lower RV mass-to-volume (rrm = −0.80, p = 0.003) using repeated measures. Wall stress decreased significantly over time, especially in patients with a stable RVEF (p < 0.001). Higher wall stress was independently associated with lower RVEF, adjusted for left ventricular ejection fraction, RV end-diastolic volume and time since initial surgery (decrease of 1.27% RVEF per kPa increase in wall stress, p = 0.029) using repeated measurements. No association was found between wall stress, NT-proBNP, and exercise capacity.ConclusionsUsing a computational method to calculate wall stress locally in geometrically complex ventricles, we demonstrated that lower wall stress might be important to maintain ventricular function. RV wall stress assessment can be used in serial follow-up, and is potentially an early marker of impending RV dysfunction.

A surgical mouse model of neonatal right ventricular outflow tract obstruction by pulmonary artery banding

Diseased animal models play an extremely important role in preclinical research. Lacking the corresponding animal models, many basic research studies cannot be carried out, and the conclusions obtained are incomplete or even incorrect. Right ventricular (RV) outflow tract (RVOT) obstruction leads to RV pressure overload (PO) and reduced pulmonary blood flow (RPF), which are two of the most important pathophysiological characteristics in pediatric cardiovascular diseases and seriously affect the survival rate and long-term quality of life of many children. Due to the lack of a neonatal mouse model for RVOT obstruction, it is largely unknown how RV PO and RPF regulate postnatal RV and pulmonary development. The aim of this study was to construct a neonatal RVOT obstruction mouse model. Here, we first introduced a neonatal mouse model of RVOT obstruction by pulmonary artery banding (PAB) on postnatal day 1. PAB induced neonatal RVOT obstruction, RV PO, and RPF. Neonatal RV PO induced cardiomyocyte proliferation, and neonatal RPF induced pulmonary dysplasia, the two features that are not observed in adult RVOT obstruction. As a result, PAB neonates exhibited overall developmental dysplasia, a sign similar to that of children with RVOT obstruction. Because many pediatric cardiovascular diseases are associated with RV PO and RPF, the introduction of a neonatal mouse model of RVOT obstruction may greatly enhance our understanding of these diseases and eventually improve or save the lives of many children.

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.