Right Ventricular Pressure-volume Research Articles

Abstract 4137364: Sex differences in the right ventricle in the Sugen-Hypoxia rat model of pulmonary arterial hypertension

Background: An unexplained estrogen puzzle exists in pulmonary arterial hypertension (PAH): PAH occurs ~4 fold more frequently in women than men; however, women with PAH have better right ventricular (RV) function and survival than the men. Sex differences and the associated mechanism in RV in PAH are not well understood. Aim: To characterize sex differences in RV function and structure in PAH. Methods: Sprague-Dawley rats were injected with Sugen (SU5416, 25mg/kg), and subjected to 3 weeks of hypoxia, followed by 5 weeks of normoxia. Control rats received vehicle and stayed in normoxia for up to 8 weeks. RV pressure-volume, mitochondrial properties, weight, myocyte size, cell proliferation, and interstitial and perivascular (right coronary arteries, RCA) fibrosis were obtained. Results: Sugen-Hypoxia (SuHx) caused significant increases in RV systolic pressure (RVSP) and effective arterial elastance (Ea) in both sexes (P<0.05), but caused slightly greater increase in RV end-systolic elastance (Ees) in females vs males, leading to a preserved RV-pulmonary artery coupling (Ees/Ea) in females and a significant decrease in Ees/Ea in males (P<0.05). SuHx caused a significant increase in RV diastolic pressure only in males (P<0.05), which is associated with significantly higher amount of RV interstitial fibrosis in males vs females. In addition, SuHx caused significant increase in cell proliferation in both sexes (P<0.05) though with slightly greater in crease in males, which is well correlated with RV interstitial fibrosis. Whilst there was no sex difference in RV hypertrophy in SuHx rats as indicated by both fulton index and myocyte size, female RV had smaller myocytes than males at baseline, indicating a greater increase in myocyte size in response to SuHx. Finally, there was a significant increase in RCA fibrosis in male SuHx rats (P<0.05) but not in females, potentially leading to a greater degree of ischemia in male SuHx RV, and this is consistent with impaired mitochondrial properties (decreased mitochondrial fusion, membrane potential an superoxide) in male SuHx rat RV (P<0.05) but preserved mitochoindrial properties in females. Conclusions: SuHx resulted in similar level of RV afterload in both sexes, but compared to males, RV in females responded differently in both function (Ees and mitochondrial properties) and structure (myocyte size and fibrosis). Future studies on the associated mechanism are needed to gain therapeutic insight for RV in PAH.

Intraoperative right ventricular end-systolic pressure–volume loop analysis in patients undergoing cardiac surgery: A proof-of-concept methodology

BackgroundPerioperative right ventricular (RV) dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to demonstrate proof of concept in generating intraoperative RV pressure–volume (PV) loops and conducting an end-systolic PV relationship (ESPVR) analysis using data obtained from routinely used intraoperative monitors. MethodsAdult patients undergoing cardiac surgery with the placement of a pulmonary artery catheter (PAC) between May 2023 and March 2024 were included prospectively. The PV loops were generated using 3-dimensional echocardiographic RV volume data and continuous RV pressure data obtained from a PAC. The volume–time and pressure–time curves were digitized using the semiautomatic WebPlotDigitizer program and synchronized to reconstruct an RV PV loop and analyze ESPVR using the previously validated single-beat method. ResultsIntraoperative RV PV loops were generated for 25 patients, including 17 patients with preserved RV systolic function (group 1) and 8 patients with reduced systolic function (group 2). Mean Ees, Ea, and Ees/Ea ratio were 0.63 ± 0.25 mm Hg/mL, 0.60 ± 0.23 mm Hg/mL, and 1.0 8 ± 0.31 mm Hg/mL, respectively, by the Pmax method and 0.56 ± 0.32 mm Hg/mL, 0.60 ± 0.23 mm Hg/mL, and 0.91 ± 0.21 mm Hg/mL, respectively, by the V0 method. Group 1 had a significantly higher Ees compared to group 2 regardless of the calculation method and a larger Ees/Ea ratio calculated by the V0 method. ConclusionsIt is clinically feasible to derive RV PV loops from routine hemodynamic and echocardiographic data. With further validation and technological support, this can be a potential real-time intraoperative RV function monitoring tool.

Tailoring the Best Positive End-Expiratory Pressure Through Invasive Right Ventricular Pressure-Volume Loops in a Patient Supported by Veno-Arterial Extracorporeal Membrane Oxygenation.

Patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) typically suffer from cardiogenic pulmonary edema and lung atelectasis, which can exacerbate right ventricular (RV) dysfunction through an increase in lung elastance and RV afterload. Invasive mechanical ventilation settings, and positive end-expiratory pressure (PEEP) in particular, can help to improve RV performance by optimizing lung recruitment and minimizing alveolar overdistention. In this report, we present a VA-ECMO supported patient in whom in vivo RV pressure-volume (PV) loops were measured during a decremental PEEP trial, leading to the identification of an optimum PEEP level from a cardio-respiratory viewpoint. This innovative approach of tailoring mechanical ventilation settings according to cardio-respiratory physiology through in vivo RV PV loops may provide a novel way to optimize hemodynamics and patient outcomes.

Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis

BackgroundInterventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. ObjectivesThis study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). MethodsThe investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. ResultsWith faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). ConclusionsInterventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.

Abstract 15773: The Forgotten Ventricle: Insight Into Dynamic Effects of Left Ventricular Assist Device Ramp on Right Ventricle Function

Introduction: Left ventricular assist devices (LVAD) with magnetically levitated impellers have become standard due to hemocompatibility and survival profile. To optimize LVAD speeds, we previously introduced simultaneous right and left heart (RH/LH) catheterization during ramp studies. Here, we report pairing of this approach with pressure-volume (PV) assessment in a patient with a HeartMate 3 LVAD with mitral regurgitation (MR). The combined approach evaluated left ventricular (LV) hemodynamics and right ventricular (RV) PV-relationships during ramp testing. Methods: A 68-year-old male with ischemic cardiomyopathy, two years following HeartMate3 implantation, presented with NYHA class III symptoms. To evaluate for dyspnea, he underwent a RH/LH catheterization ramp study. RV PV-loops were created by use of a conductance catheter system, allowing creation of PV loops. Results: At the baseline LVAD speed of 5300 rotations per minute (RPM), right atrial pressure was elevated at 16 mmHg and pulmonary artery (PA) pressure of 26 mmHg. Left-end diastolic pressure (LVEDP) was elevated (16mmHg). Baseline cardiac index (CI) was 2.01 L/min/m 2 . Ramp testing was performed, increasing speeds from 5300 to 5800 RPM. Progressive LV unloading was observed with a 5 mmHg drop in LVEDP and a 3 mmHg drop in PA pressure. However, RV PV loop monitoring revealed a negative impact on RV contractility with the maximal elastance (Emax) slope demonstrating a 22% reduction. Furthermore, a 17% reduction in RV stroke volume was documented, while diastolic function remained unchanged. Thus, despite excellent LV offloading and diminishment of RV afterload, the significant negative impact on Emax resulted in no net increase in CI (+0.04 L/min/m 2 ) during the ramp evaluation. Inotrope therapy was initiated for RV function with increased LVAD RPM to outcompete MR. Conclusions: While RH/LH catheterization provides a real-time perspective of the interventricular relationship during ramp, the impact of increasing LVAD speeds on RV function has yet to be directly measured. Here, the RV PV loop relationship during LVAD ramp showed that although LVAD speed increases in the setting of MR may facilitate LV unloading, a drop in RV afterload did not compensate for reduction in RV contractility.

Adaptive versus maladaptive right ventricular remodelling.

Right ventricular (RV) function and its adaptation to increased afterload [RV-pulmonary arterial (PA) coupling] are crucial in various types of pulmonary hypertension, determining symptomatology and outcome. In the course of disease progression and increasing afterload, the right ventricle undergoes adaptive remodelling to maintain right-sided cardiac output by increasing contractility. Exhaustion of compensatory RV remodelling (RV-PA uncoupling) finally leads to maladaptation and increase of cardiac volumes, resulting in heart failure. The gold-standard measurement of RV-PA coupling is the ratio of contractility [end-systolic elastance (Ees)] to afterload [arterial elastance (Ea)] derived from RV pressure-volume loops obtained by conductance catheterization. The optimal Ees/Ea ratio is between 1.5 and 2.0. RV-PA coupling in pulmonary hypertension has considerable reserve; the Ees/Ea threshold at which uncoupling occurs is estimated to be ~0.7. As RV conductance catheterization is invasive, complex, and not widely available, multiple non-invasive echocardiographic surrogates for Ees/Ea have been investigated. One of the first described and best validated surrogates is the ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP), which has shown prognostic relevance in left-sided heart failure and precapillary pulmonary hypertension. Other RV-PA coupling surrogates have been formed by replacing TAPSE with different echocardiographic measures of RV contractility, such as peak systolic tissue velocity of the lateral tricuspid annulus (S'), RV fractional area change, speckle tracking-based RV free wall longitudinal strain and global longitudinal strain, and three-dimensional RV ejection fraction. PASP-independent surrogates have also been studied, including the ratios S'/RV end-systolic area index, RV area change/RV end-systolic area, and stroke volume/end-systolic volume. Limitations of these non-invasive surrogates include the influence of severe tricuspid regurgitation (which can cause distortion of longitudinal measurements and underestimation of PASP) and the angle dependence of TAPSE and PASP. Detection of early RV remodelling may require isolated analysis of single components of RV shortening along the radial and anteroposterior axes as well as the longitudinal axis. Multiple non-invasive methods may need to be applied depending on the level of RV dysfunction. This review explains the mechanisms of RV (mal)adaptation to its load, describes the invasive assessment of RV-PA coupling, and provides an overview of studies of non-invasive surrogate parameters, highlighting recently published works in this field. Further large-scale prospective studies including gold-standard validation are needed, as most studies to date had a retrospective, single-centre design with a small number of participants, and validation against gold-standard Ees/Ea was rarely performed.

Abstract 10899: Excessive Right Ventricular Afterload in Pulmonary Arterial Hypertension: Effects on Diastolic Function and the Left Ventricle

Introduction: Right ventricular (RV) diastolic dysfunction in pulmonary arterial hypertension (PAH) remains poorly understood. In this study, we used RV pressure-volume (PV) loops to assess RV diastology as a function of afterload in PAH. Methods: RV PV loops were prospectively measured in control (n=9) and PAH (n=39) patients at rest and during supine bike exercise. PAH patients were stratified by effective arterial elastance (Ea), a lumped measure of total afterload, into two groups: high afterload (HA, n=20) and severe afterload (SA, n=19). Results: PAH groups were matched with respect to age, sex, and PAH medication usage. Ea at rest and exercise was higher in SA PAH (1.8 vs. 0.6 mmHg/ml, P <0.0001 at rest; 2.3 vs 0.8 mmHg/ml, P < 0.0001 with exercise). In the SA group, RV end-diastolic pressure (RVEDP) was higher at rest (13.3 vs 7.6 mmHg, P = 0.0017) and rose markedly with exertion (23.4 vs 13.1 mmHg, P=0.0001). Because RV volumes changed similarly in both groups, SA patients exhibited stiffer RVs (dP/dV 0.30 vs 0.11 mmHg/mL, P=.024). To understand pericardial-interventricular interactions, we calculated the RVEDP-to-pulmonary capillary wedge pressure (PCWP) ratio and the left ventricular (LV) transmural filling pressure (LVTMFP). RVEDP/PCWP was substantially higher in SA (2.1 vs 1.0, P=.005). Therefore, even though PCWP rose considerably in SA (mean 16 mmHg), exercise LVTMFP was significantly reduced in SA vs HA PAH (-7.5 vs 2.55 mmHg, P=0.002). Along with reduced LV size seen by concomitant echo, we thus revealed blunted LV filling specifically in SA PAH. Accordingly, exercise cardiac index, stroke volume index, and LV stroke work index were all markedly reduced in SA PAH. Conclusions: Severe afterload in PAH results in high RV diastolic pressures and RV stiffening, which in turn blunt LV filling and LV output with exertion. Due to ventricular interactions, exercise PCWP may rise considerably in PAH, thus reducing its ability to differentiate from left heart disease.

Vagal nerve stimulation preserves right ventricular function in a rat model of right ventricular pressure overload.

Vagal nerve stimulation (VNS) ameliorates pulmonary vascular remodeling and improves survival in a rat model of pulmonary hypertension (PH). However, the direct impact of VNS on right ventricular (RV) function, which is the key predictor of PH patients, remains unknown. We evaluated the effect of VNS among the three groups: pulmonary artery banding (PAB) with sham stimulation (SS), PAB with VNS, and control (no PAB). We stimulated the right cervical vagal nerve with an implantable pulse generator, initiated VNS 2 weeks after PAB, and stimulated for 2 weeks. Compared to SS, VNS increased cardiac index (VNS: 130 ± 10 vs. SS: 93 ± 7 ml/min/kg; p < 0.05) and end-systolic elastance assessed by RV pressure-volume analysis (VNS: 1.1 ± 0.1 vs. SS: 0.7 ± 0.1 mmHg/μl; p < 0.01), but decreased RV end-diastolic pressure (VNS: 4.5 ± 0.7 vs. SS: 7.7 ± 1.0 mmHg; p < 0.05). Furthermore, VNS significantly attenuated RV fibrosis and CD68-positive cell migration. In PAB rats, VNS improved RV function, and attenuated fibrosis, and migration of inflammatory cells. These results provide a rationale for VNS therapy as a novel approach for RV dysfunction in PH patients.

Utility of Real-Time Three-Dimensional Echocardiography for the Assessment of Right Ventricular Morphology and Function in Large Animal Models.

Real-time three-dimensional echocardiography (RT3DE) enables a noninvasive assessment of right ventricular (RV) morphology. However, no study has evaluated the relationship between RV function obtained by RT3DE and RV pressure-volume loops. This hypothesis-driven, experimental study aimed to assess the utility of RT3DE in the evaluation of RV morphology and function. Ten anesthetized beagle dogs sequentially underwent dobutamine infusion, acute infusion of lactated Ringer’s solution, and furosemide administration to alter RV contractility and loading conditions. RV pressure-volume loop-derived hemodynamic measurements and echocardiography, including two-dimensional speckle-tracking echocardiography and RT3DE, were performed in each study protocol. Bland–Altman analysis showed strong agreement in RV volume, ejection fraction, and stroke volume obtained by right heart catheterization and RT3DE. Multiple regression analyses revealed that the peak myocardial velocity of the lateral tricuspid annulus (RV s’) and global RV longitudinal strain rate were significantly associated with end-systolic elastance (adjusted r2 = 0.66, p < 0.001). RV s’, RV free wall longitudinal strain, and RT3DE-derived stroke volume/end-systolic RV volume ratio were associated with RV pressure-volume loops-derived end-systolic/arterial elastance ratio (adjusted r2 = 0.34, p < 0.001). RT3DE could detect the changes in catheterization-derived RV volume with a strong agreement and might be useful in estimating RV-pulmonary arterial coupling.

Interventricular Interactions and Right Ventricular Function in LVAD Recipients: Insights from Pressure Volume Analyses

<h3>Purpose</h3> Data supporting the hypothesis that interventricular interaction contribute to right ventricular (RV) failure after left ventricular assist device (LVAD) implantation are lacking. <h3>Methods</h3> Patients underwent a protocolized hemodynamic ramp test where RV pressure-volume (PV) loops were recorded with a conductance catheter. The end-systolic PV relationship was characterized by the ratio of end-systolic pressure and volume (R_es). The end-diastolic PV relationship (EDPVR) was characterized by the V₁₀ index (i.e., the volume at which the EDPVR reaches a pressure of 10 mmHg). ΔR_es and ΔV₁₀ (i.e., the maximal change across the range of tested LVAD speeds) were used to compare systolic and diastolic function between patients. <h3>Results</h3> Six adult males with HeartMate3 LVADs completed the study protocol (Fig. 1). ΔR_es and ΔV₁₀ both exhibited minimal changes in 3 subjects (mean ΔR_es=7.24%, mean ΔV₁₀=8.14 mL), suggesting neither RV systolic nor diastolic function was impacted by LV unloading. In contrast, 2 subjects showed predominantly diastolic responses to changing LVAD speed (mean ΔV₁₀=17.4), but no significant systolic response (mean ΔR_es=5.47%). The final subject's ramp study was stopped prematurely because of suction events: ΔR_es and ΔV₁₀ were 23.2% and 1.4 mL, respectively, indicating a significant decrement in systolic function with greater LVAD speed. The mean PA systolic pressures were significantly greater in the 3 participants without systolic or diastolic changes relative to their counterparts (42.3 vs. 25.3 mmHg, p=0.038). <h3>Conclusion</h3> Interventricular interaction exerts a heterogenous influence on RV performance: Systolic interactions diminish RV contractile function, while diastolic interactions improve RV compliance. Further work is required to establish whether interventricular interaction is, indeed, a rare cause of post-LVAD RV dysfunction, and if chronic exposure to afterload blunts the RV's sensitivity to interventricular interaction.

Right Ventricular Performance During Exercise In Patients With Heart Failure

<h3>Purpose</h3> : To characterize resting and exertional right ventricular (RV) function during exercise among patients with heart failure with reduced ejection fraction (HFrEF). <h3>Methods</h3> : Six patients (five males, 60±9yrs) completed invasive cardiopulmonary exercise testing (CPET) on upright cycle ergometry with conductance catheters for real-time RV pressure-volume (PV) analysis, as well as radial arterial catheterization for blood pressure monitoring. Data were collected at rest, two submaximal levels of exercise (Steady-States 1, 2) below ventilatory threshold, and peak effort. Breath-by-breath gas-exchange parameters were determined by indirect calorimetry. Cardiac output (Qc) was determined by direct Fick. <h3>Results</h3> : Cohort characteristics are displayed in <b>Table 1</b>. VO2Max was severely reduced (11.8±5.0) and ventilatory efficiency was severely abnormal (46±15). Exercise Qc increased from rest to Steady-State 1, but there were no increases thereafter at higher workloads or at peak effort. Exercise myocardial energetics (stroke work) were also blunted with a modest increase from rest to Steady-State 2. Diastolic reserve (dpdt_min) increased modestly from rest to Steady-State 1 only. <b>Table 2</b> displays exercise hemodynamics and gas-exchange parameters. An example figure of hemodynamics and RV PV loops during exercise is displayed in <b>Figure 1</b>. <h3>Conclusion</h3> : HFrEF patients experience impairments in RV contractile and lusitropic reserve, and energy utilization during exercise. These findings demonstrate how exertional RV dysfunction contributes to impairments in functional capacity.

Abstract 13419: Novel Methods to Quantify Limitation of Right Ventricular Exercise Reserve in Pulmonary Hypertension: Afterload vs Ventricular Interdependency

Introduction: In this study, we report novel methods to investigate impact of pulmonary arterial (PA) afterload with impedance and ventricular interdependency with myocardial strain on right ventricular (RV) reserve with exercise and RV:PA coupling. Hypothesis: In pre-capillary pulmonary hypertension (PH), RV is conditioned to a higher contractility (end-systolic elastance: Ees) due to increased impedance and RV reserve is independent of left ventricle. However, in isolated post-capillary PH (Ipc-PH), RV is not conditioned due to lower impedance, yet contractility reserve is poor due to lower interventricular septal strain. Methods: In 4 subjects (Table 1), we performed invasive cardiopulmonary exercise tests with simultaneous echocardiogram for impedance quantification with spectral analysis, followed by real-time RV pressure volume loops (Figure 1A: data recorded at rest and every 25 watts till peak-exercise). Cardiac MRI was performed within 24-hours to assess myocardial function, strain, and 4D flow at rest and exercise in the bore. Results: The augmentation of RV contractility (Ees) with exercise is poor in Ipc-PH, despite an afterload (Ea) similar to the normal subject. The left ventricular septal strain is reduced in Ipc-PH which may indicate enhanced interventricular dependency. Due to increased afterload in pre-capillary PH, RV is conditioned to higher contractility (Ees), and RV reserve is possibly independent of the left ventricle. Conclusion: Our novel methods provide an opportunity to investigate mechanisms of poor RV reserve with exercise in different phenotypes of PH. We will further validate these preliminary findings in our ongoing studies.

Investigation of the influence of manual ventilation-controlled respiration on right ventricular pressure-volume loops and echocardiographic variables in healthy anesthetized dogs.

To evaluate the influence of manual ventilation-controlled respiration on right ventricular (RV) pressure-volume loop-derived and echocardiographic variables in dogs. 8 healthy, anesthetized Beagles. In a prospective experimental study, pressure-volume catheters were percutaneously inserted into the right ventricle of each dog, and manual ventilation was performed; RV pressure-volume loop (hemodynamic) data and conventional echocardiographic variables were assessed. Two-dimensional speckle tracking echocardiography-derived RV strain (RVS) and RV systolic strain rate (RVSR) were obtained with RV free wall-only analysis (free wall) and RV global analysis (RVGA; interventricular septum). Variables were compared between end-inspiratory and end-expiratory phases of respiration by statistical methods. Multiple regression analysis was used to assess associations between selected hemodynamic and echocardiographic variables. The RV pressure significantly increased, and RV volume, stroke volume, tricuspid annular plane systolic excursion, RV fractional area change, peak myocardial systolic velocity of the lateral tricuspid annulus, and RV free wall only-assessed RVS and RVSR significantly decreased in the inspiratory phase, compared with the expiratory phase. There were no significant differences in end-systolic elastance or RVGA-assessed RVS or RVSR between respiratory phases. The RVGA-assessed RVSR was significantly associated with stroke volume and end-systolic elastance. Specific RV echocardiographic variables were significantly affected by respiration. In contrast, RVS and RVSR determined with RVGA were not affected by respiration and were associated with hemodynamic indicators of RV contractility.

Right Ventricular Pressure–Volume Analysis During Left Ventricular Assist Device Speed Optimization Studies: Insights Into Interventricular Interactions and Right Ventricular Failure

BackgroundInterventricular interaction, which refers to the impact of left ventricular (LV) function on right ventricular (RV) function and vice versa, has been implicated in the pathogenesis of RV failure in LV assist device (LVAD) recipients. We sought to understand more about interventricular interaction by quantifying changes in the RV systolic and diastolic function with varying LVAD speeds. Methods and ResultsFour patients (ages 22–69 years, 75% male, and 25% with ischemic cardiomyopathy) underwent a protocolized hemodynamic ramp test within 12 months of LVAD implantation where RV pressure–volume loops were recorded with a conductance catheter. The end-systolic PV relationship and end-diastolic PV relationship were compared using the V20 and V10 indices (volumes at which end-systolic PV relationship and end-diastolic PV relationship reach a pressure of 20 and 10 mm Hg, respectively). The ∆V20 and ∆V10 refer to the change in V20 and V10 from the minimum to maximum LVAD speeds. RV PV loops demonstrated variable changes in systolic and diastolic function with increasing LVAD speed. The end-systolic PV relationship changed in 1 patient (patient 2, ∆V20 = 23.5 mL), reflecting a decrease in systolic function with increased speed, and was unchanged in 3 patients (average ∆V20 = 7.4 mL). The end-diastolic PV relationship changed with increasing speed in 3 of 4 patients (average ∆V10 = 12.5 mL), indicating an increase in ventricular compliance, and remained unchanged in one participant (patient 1; ∆V10 = 4.0 mL). ConclusionsInterventricular interaction can improve RV compliance and impair systolic function, but the overall effect on RV performance in this pilot investigation is heterogeneous. Further research is required to understand which patient characteristics and hemodynamic parameters influence the net impact of interventricular interaction.

Right ventricular pressure-volume loop produced with simultaneous application of three-dimensional echocardiography and high-fidelity micromanometry in a patient with pulmonary arterial hypertension.

Accurate assessment of right ventricular (RV) function has received a growing attention. Pressure-volume (PV) loop analysis is the gold standard method for evaluating RV function; however, it is not widely employed because of its invasive nature and complexity. The present report is the first to have drawn a RV PV loop in a patient with pulmonary hypertension, with a simultaneous recording of RV pressure and volume using high-fidelity micromanometry and three-dimensional echocardiography. This allows for less invasive and simple assessment of RV function, potentially promoting better understanding and management of pulmonary hypertension and other cardiovascular diseases.

Right ventricular pressure-volume loop shape and systolic pressure change in pulmonary hypertension.

Right ventricular (RV) function determines outcome in pulmonary arterial hypertension (PAH). RV pressure-volume loops, the gold standard for measuring RV function, are difficult to analyze. Our aim was to investigate whether simple assessments of RV pressure-volume loop morphology and RV systolic pressure differential reflect PAH severity and RV function. We analyzed multibeat RV pressure-volume loops (obtained by conductance catheterization with preload reduction) in 77 patients with PAH and 15 patients without pulmonary hypertension in two centers. Patients were categorized according to their pressure-volume loop shape (triangular, quadratic, trapezoid, or notched). RV systolic pressure differential was defined as end-systolic minus beginning-systolic pressure (ESP - BSP), augmentation index as ESP - BSP/pulse pressure, pulmonary arterial capacitance (PAC) as stroke volume/pulse pressure, and RV-arterial coupling as end-systolic/arterial elastance (Ees/Ea). Trapezoid and notched pressure-volume loops were associated with the highest afterload (Ea), augmentation index, pulmonary vascular resistance (PVR), mean pulmonary arterial pressure, stroke work, B-type natriuretic peptide, and the lowest Ees/Ea and PAC. Multivariate linear regression identified Ea, PVR, and stroke work as the main determinants of ESP - BSP. ESP - BSP also significantly correlated with multibeat Ees/Ea (Spearman's ρ: -0.518, P < 0.001). A separate retrospective analysis of 113 patients with PAH showed that ESP - BSP obtained by routine right heart catheterization significantly correlated with a noninvasive surrogate of RV-arterial coupling (tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio; ρ: -0.376, P < 0.001). In conclusion, pressure-volume loop shape and RV systolic pressure differential predominately depend on afterload and PAH severity and reflect RV-arterial coupling in PAH.

Exercise right ventricular ejection fraction predicts right ventricular contractile reserve

Right ventricular (RV) contractile reserve shows promise as an indicator of occult RV dysfunction in pulmonary vascular disease. We investigated which measure of RV contractile reserve during exercise best predicts occult RV dysfunction and clinical outcomes. We prospectively studied RV contractile reserve in 35 human subjects referred for right heart catheterization for known or suspected pulmonary hypertension. All underwent cardiac magnetic resonance imaging, echocardiography, and supine invasive cardiopulmonary exercise testing with concomitant RV pressure-volume catheterization. Event-free survival was prospectively adjudicated from time of right heart catheterization for a 4-year follow-up period. RV contractile reserve during exercise, as measured by a positive change in end-systolic elastance (Ees) during exertion, was associated with elevation in pulmonary pressures but preservation of RV volumes. Lack of RV reserve, on the other hand, was tightly coupled with acute RV dilation during exertion (R2 = 0.76, p< 0.001). RV Ees and dilation changes each predicted resting RV-PA dysfunction. RV ejection fraction during exercise, which captured exertional changes in both RV Ees and RV dilation, proved to be a robust surrogate for RV contractile reserve. Reduced exercise RV ejection fraction best predicted occult RV dysfunction among a variety of resting and exercise RV measures, and was also associated with clinical worsening. RV ejection fraction during exercise, as an index of RV contractile reserve, allows for excellent identification of occult RV dysfunction, more so than resting measures of RV function, and may predict clinical outcomes as well.

Right ventricular function and cardiopulmonary performance among patients with heart failure supported by durable mechanical circulatory support devices

Patients with continuous-flow left ventricular assist devices (CF-LVADs) experience limitations in functional capacity and frequently, right ventricular (RV) dysfunction. We sought to characterize RV function in the context of global cardiopulmonary performance during exercise in this population. A total of 26 patients with CF-LVAD (aged 58 ± 11 years, 23 males) completed a hemodynamic assessment with either conductance catheters (Group 1, n = 13) inserted into the right ventricle to generate RV pressure‒volume loops or traditional Swan‒Ganz catheters (Group 2, n = 13) during invasive cardiopulmonary exercise testing. Hemodynamics were collected at rest, 2 sub-maximal levels of exercise, and peak effort. Breath-by-breath gas exchange parameters were collected by indirect calorimetry. Group 1 participants also completed an invasive ramp test during supine rest to determine the impact of varying levels of CF-LVAD support on RV function. In Group 1, pump speed modulations minimally influenced RV function. During upright exercise, there were modest increases in RV contractility during sub-maximal exercise, but there were no appreciable increases at peak effort. Ventricular‒arterial coupling was preserved throughout the exercise. In Group 2, there were large increases in pulmonary arterial, left-sided filling, and right-sided filling pressures during sub-maximal and peak exercises. Among all participants, the cardiac output‒oxygen uptake relationship was preserved at 5.8:1. Ventilatory efficiency was severely abnormal at 42.3 ± 11.6. Patients with CF-LVAD suffer from limited RV contractile reserve; marked elevations in pulmonary, left-sided filling, and right-sided filling pressures during exercise; and severe ventilatory inefficiency. These findings explain mechanisms for persistent reductions in functional capacity in this patient population.

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

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

Effect of left ventricular assist device implantation on right ventricular function: Assessment based on right ventricular pressure-volume curves.

Right ventricular (RV) failure is significantly associated with morbidity and mortality after left ventricular assist device (LVAD) implantation. However, it remains unclear whether LVAD implantation could worsen RV function. Therefore, we aimed to investigate the effect of LVAD implantation on RV function by comparing RV energetics derived from the RV pressure-volume curve between before and after LVAD implantation. This exploratory observational study was performed between September 2016 and January 2018 at a national center in Japan. Twenty-two patients who underwent LVAD implantation were included in the analysis. We measured RV energetics parameters: RV stroke work index (RVSWI), which was calculated by integrating the area within the RV pressure-volume curve; RV minute work index (RVMWI), which was calculated as RVSWI × heart rate; and right ventriculo-arterial coupling, which was estimated as RV stroke volume/RV end-systolic volume. We compared RV energetics between before and after LVAD implantation. Although RVSWI was similar [424.4 mmHg · mL/m2 (269.5-510.3) vs. 379.9 mmHg · mL/m2 (313.1-608.8), P = 0.485], RVMWI was significantly higher after LVAD implantation [29834.1 mmHg · mL/m2 /min (18272.2-36357.1) vs. 38544.8 mmHg · mL/m2 /min (29016.0-57282.8), P = 0.001], corresponding to a significantly higher cardiac index [2.0 L/min/m2 (1.4-2.2) vs. 3.7 L/min/m2 (3.3-4.1), P < 0.001] to match LVAD flow. Right ventriculo-arterial coupling was significantly higher after LVAD implantation [0.360 (0.224-0.506) vs. 0.480 (0.343-0.669), P = 0.025], suggesting that the efficiency of RV performance improved. In conclusion, higher RVMWI with higher cardiac index to match LVAD flow and improved efficiency of RV performance indicate that LVAD implantation might not worsen RV function.