Pressure-volume Analysis Research Articles

Pressure-volume analysis by three-dimensional echocardiography: an accurate non-invasive alternative for assessing left ventricular contractility

Abstract Introduction Accurately assessing left ventricular (LV) contractility is vital for diagnosing and managing cardiac conditions like heart failure, cardiomyopathies, and ischemic heart disease. LV contractility assessment by traditional invasive pressure-volume (PV) analysis necessitates invasive measurements, introducing significant risks and limitations. However, three-dimensional (3D) echocardiography and non-invasive LV pressure curve estimation enables accurate PV-loop estimation, presenting a harmless and widely available alternative for LV contractility assessment. Aim Validate indices of LV contractility by PV analysis using 3D echocardiography by comparing them to gold-standard invasive measurements. Methods In 10 open-chest canines, invasive LV pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Echocardiography provided non-invasive 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting a reference curve to the valve events and measured peak LV pressure. Invasive LV end-systolic elastance (Ees) was obtained from multiple PV -loops during preload reduction through least square regression of the points on the PV-loops in the upper left corner with longest normalized distance from loop center. Non-invasive Ees was estimated using a simplified one-beat approach as the slope of a line drawn from this PV-loop point to the origin (Figure 1A). Invasive and non-invasive Ees, along with contractility indices peak LV pressure (Pmax)/end-diastolic volume (EDV) and LV pressure at end-systole (Pes)/EDV, were compared during baseline and during dobutamine infusion. Results As shown in the representative experiment illustrated in Figure 1A, non-invasive Ees captured changes in LV contractility in a similar manner as compared to invasive Ees. Indeed, this was consistent across all experiments, resulting in significant increase in non-invasive Ees in parallel with invasive Ees during dobutamine infusion (p < 0.001 for both) (Figure 1B). Consequently, there was a strong correlation and good agreement between the two methods (r = 0.63, p = 0.003; mean difference – 1.5, SD 2.4) (Figure 1C). For LV contractility indices Pmax/EDV and Pes/EDV, results were comparable: both increased significantly during dobutamine infusion, similar to invasive Ees. This was consistent across all experiments, without exceptions (Figure 2A). Consequently, there were strong correlations between Pmax/EDV and Pes/EDV and invasive Ees (r = 0.77, p = 0.0001 and r = 0.79, p < 0.0001, respectively) (Figure 2B). Conclusions 3D echocardiography provides a reliable and non-invasive method for assessing LV contractility, with good agreement with traditional invasive gold standard Ees. These findings support the use of 3D echocardiography as an accurate and easily accessible alternative for evaluating LV contractility in clinical settings. Invasive vs non-invasive LV Ees Pmax/EDV and Pes/EDV

Pressure-volume analysis by three-dimensional echocardiography: a novel and superior method to predict response following cardiac resynchronization therapy

Abstract Introduction Long-term response to cardiac resynchronization therapy (CRT) is primarily assessed by 2D echocardiography. The combination of 3D echocardiography and left ventricular (LV) pressure curve estimation allows for pressure-volume (PV) analysis and LV work efficiency (LVWE) estimation which may be superior to today’s methods. Aim To investigate if PV-analysis by 3D echocardiography is superior to 2D volumes at predicting long-term survival in CRT. Methods In a recent prospective multicenter study, non-invasive PV-analysis (n=106) and 2D volume analysis by biplane Simpson’s method (n=195) were performed, before and 6 months after CRT. The LV pressure curve was estimated by aligning a reference pressure curve with mitral and aortic valve events obtained from echocardiography. The amplitude of the curve was adjusted to brachial systolic cuff pressure and combined with 3D volumes for PV-analysis. As shown in figure 1, LVWE was calculated as the ratio of estimated stroke work (red area) to total mechanical energy (red + blue areas). The cutoff value for change in LV end-systolic volume (ESV) was set at 15% and at >35% for LVWE using Receiver Operator Curve analysis. Volumetric non-responders were subdivided into response based on LVWE. Results After 6±2 years follow-up, 47 (23%) patients had died. Relative change in 3D and 2D LV ESV showed similar ability to predict long-term all-cause mortality (log rank p<0.001 for both) (Figure 2). However, LVWE identified patients with a positive effect of CRT who were volumetric non-responders. These patients had similar outcomes as volumetric responders (HR 1.91, 95% CI: 0.54-6.81) (Figure 3). LVWE also identified non-responders with particularly adverse outcomes (HR 3.46, 95% CI: 1.32-9.10 vs volumetric non-response and LVWE >35%). Conclusions PV-analysis by 3D-echoardiography identifies a new group of patients who respond to CRT without a 15% reduction in ESV who have similar outcomes to volumetric responders. In our data, 3D echocardiography was superior to 2D volumes at predicting long-term all-cause mortality after CRT. LV work efficiency before and after CRT LV work efficiency and survival

Non-invasive assessment of arterial elastance using three-dimensional echocardiography: an accurate alternative to invasive methods

Abstract Introduction Assessing arterial elastance (Ea) is crucial for understanding vascular properties and managing conditions such as hypertension, heart failure, and valvular heart disease. While invasive pressure-volume (PV) analysis provides precise measurements, the procedures involved pose significant risks and limitations. Three-dimensional (3D) echocardiography, combined with non-invasive LV pressure curve estimation, however, offers a highly accurate method for generating non-invasive PV-loops. Thus, this approach has the potential to provide a safe and widely accessible means of assessing Ea. Aim Validate non-invasive Ea by PV analysis using 3D echocardiography, comparing it to gold-standard Ea derived from invasive measurements. Methods In 10 open-chest canines, invasive pressure was measured using a micromanometer, and volume determined from subendocardial piezoelectric crystals, using a three-axis ellipsoid model (Figure 1). Echocardiography provided non-invasive 3D LV volumes and valve event timings. The LV pressure curve was estimated by adjusting a reference curve to the valve events and measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Arterial elastance (Ea) was defined as the absolute slope of the line from volume axis interception at end-diastolic volume to the point on the PV-loop in the upper left quadrant with the longest normalized distance from the loop center. Recordings were performed at baseline and during aortic constriction. Results Panel A in Figure 2 illustrates how tightly non-invasive (dotted lines) followed invasive (solid lines) pressure-volume curves both during baseline (left) and aortic constriction (right) in a representative experiment. As can be seen, this resulted in very similar Ea. Panel B shows pooled data from all experiments, demonstrating that indeed, the non-invasive method captured similar changes in Ea during aortic constriction compared to the invasive method. Furthermore, as shown in panel C, there was an excellent correlation (r = 0.91, p < 0.0001) and good agreement (mean difference 0.3, SD 0.3) between the non-invasive and invasive Ea. Conclusions Three-dimensional echocardiography provides an accurate and non-invasive method for assessing arterial elastance, with excellent agreement with gold standard invasive method. Ultrasound crystals placement Invasive vs non-invasive Ea

Pressure-strain-volume analysis-derived wasted work predicts clinical outcomes after transcatheter tricuspid valve intervention

Abstract Background The pressure-strain loop is a non-invasive alternative to the traditional pressure-volume analysis for calculating myocardial work. Incorporating volume into work calculations may be particularly beneficial in evaluating patients with tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI), who often present with highly varied load conditions. Purpose The study aimed to test the hypothesis that pressure-strain-volume analysis-derived right ventricular (RV) work will predict the composite clinical outcome of heart failure hospitalization (HFH) and death within 12 months after the TTVI. Methods Patients undergoing TTVI at two tertiary centers were included between June 2021 and November 2023. The pre-procedural three-dimensional echocardiographic acquisitions of the RV (to obtain RV volumes and global longitudinal strain) and RV pressures obtained from same day, pre-procedural right heart catheterization or calculated from TR maximal velocity and right atrial pressure were integrated into pressure-strain-volume loops using dedicated software (ReVISION, Argus Cognitive, USA). The pressure-strain-volume derived myocardial work was quantified as the volume under the three-dimensional curve and characterized by the following metrics: global work index (GWIV), global constructive work (GCWV), global wasted work (GWWV), and global work efficiency (GWEV). Conventional pressure-strain analysis-derived metrics were also calculated as previously described (1). The composite outcome was HFH or death within 12 months after TTVI. Cox regression analysis was performed to investigate the possible associations with the composite outcome and included all baseline clinical, echocardiographic, hemodynamic and RV work parameters. Variables were considered for multivariate analysis when they were related to composite endpoint on univariate analysis with a p value <0.05. Results Of 76 patients included, 52.6% were female. The mean age was 79.3 ± 7.5 years and median TRI-Score 5 [4-7] points. Transcatheter interventions included transcatheter tricuspid valve repair (61.8%) and tricuspid valve replacement (38.2%). TR at discharge was trace/mild, moderate, severe or massive in 60.6%, 26.3%, 13.2% and 0% cases respectively. At 12-month follow-up, 26 (34.2%) patients met the composite endpoint. After adjustment for number of HFH 12 months prior to TTVI, atrial fibrillation, glomerular filtration rate and NT-proBNP, GWWV remained the only baseline parameter significantly associated with increased risk of HFH and death at 12-month follow-up in the multivariate analysis with an adjusted OR of 1.079 (95% confidence interval 1.020 - 1.143; p = 0.009). Conclusion Results of this analysis show that baseline pressure-strain-volume analysis-derived wasted work identifies patients at higher risk for HFH or death following TTVI. Thus, the GWWV calculation may help identify individuals who are more likely to benefit from TTVI.

Pressure-volume analysis of thermodynamic workload of voiding - an application in pelvic organ prolapse patients subjected to robotic-assisted sacrocolpopexy

Abstract Purpose Given objective benefits of robotic-assisted sacrocolpopexy (RSCP) to the voiding function/deficit of patients with pelvic organ prolapse (POP) waits to be clarified, this study investigated if RSCP modifies voiding functions of POP patients by focusing on its impact on the outlet resistance-dependent voiding workload using pressure-volume analysis (PVA), a protocol thermodynamically assaying work expenditure by the bladder in voiding cycles. Methods Pre- and post-operative cystometry and PVA of 22 female patients, who underwent RSCP for POP (stage ≥ II), were reviewed. Mean voiding resistance (Rvod), mean voiding pressure (Pvod), mean voiding flow (Fvod), voided volume (Vvod), voiding time (Tvod), and the trajectory-enclosed area (Apv) were analyzed. Results The PVA, in which trajectory shaped an enclosed loop representing a voiding cycle, was established by adapting from the time-domain cystometry. Compared to the pre-operative control, RSCP decreased Rvod, Pvod, and Tvod (p = 0.003, 0.042, and 0.040, respectively. All N = 22) but increased Fvod (p = 0.036, N = 22) without markedly affecting Vvod (p = 0.580, N = 22). Apv was decreased after RSCP (p = 0.017, N = 22). The RSCP-decreased Rvod (ΔRvod) displayed a moderate correlation with both the decreased Pvod (ΔPvod, r = 0.551, p = 0.007, N = 22) and the increased Fvod (ΔFvod, r=-0.625, p = 0.001, N = 22). The ΔFvod moderately correlated with the decreased Tvod (ΔTvod, r=-0.620, p = 0.002, N = 22). Moreover, the RSCP-decreased Apv (ΔApv) displayed correlation with the ΔPvod (r = 0.385, p = 0.047, N = 22). Conclusions Through diminishing outlet resistance of POP patients, RSCP not only prompted urine emission thereby increased voiding efficacy but also decreased the pressure developed for driving urine flow that lessened voiding workload. Clinical Trial Registration ClinicalTrials.gov (NCT05682989).

Abstract 4143219: Pressure-Volume Analysis by Three-Dimensional Echocardiography: A Novel Method to Estimate Left Ventricular Efficiency

Background: Left ventricular (LV) efficiency is a key pathophysiological marker in heart failure (HF). LV pressure curve estimation and three-dimensional (3D) volumes via echocardiography allows for non-invasive pressure-volume (PV) analysis and calculation of an index of efficiency (Figure 1). Aim: Validate efficiency index by 3D echocardiography by comparing it to invasive measurements and efficiency derived from Positron Emission Tomography (PET) metabolism. Methods: Two experimental models were utilized - one with canines (n=21) and another with sheep (n=12). In canines, echocardiography provided 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting the time axis of a reference pressure curve to the valve events and its amplitude to measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Invasive pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Non-invasive and invasive efficiency indices, calculated as the ratio of stroke work to total mechanical energy (Figure 1), were compared during baseline, right ventricular pacing, aortic constriction and dobutamine infusion. Twelve sheep implanted with a pacemaker underwent 8 weeks of rapid dyssynchronous DDD pacing to induce dilated HF. LV efficiency index was calculated as in Figure 1, using measurements from a PV-catheter calibrated to end-diastolic volume by cardiac MRI, and compared to efficiency calculated as stroke work divided by total LV glucose metabolism via PET/CT. Recordings were performed during AAI and DDD pacing, at baseline (n=3) and following 8 weeks pacing-induced HF (n=12). Results: In canines, non-invasive and invasive efficiency indices showed excellent agreement (r=0.95, p<0.0001; mean difference 0.4%, SD 3.4%) (Figure 2). In sheep, the efficiency index showed similar decline compared to efficiency by PET/CT after induction of HF and after switching from AAI to DDD pacing (p<0.05 for all interventions). Overall correlation between the methods was moderate (r=0.67, p=0.0001) but excellent in animals with longitudinal data (r=0.89, p=0.0001) (Figure 3). Conclusions: Efficiency index by 3D echocardiography is accurate and reflects changes in efficiency measured by PET/CT. It may thus be of interest for clinical use.

The effect of afterload on right ventricular pacing-induced left ventricular dysfunction: a translational study

Abstract Introduction Right ventricular (RV) pacing (RVP) impairs left ventricular (LV) function. Nevertheless, the interaction between arterial afterload and RVP-associated LV dysfunction has not been investigated yet. Purpose We sought to examine the effect of afterload on RVP-evoked LV hemodynamic changes in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) as well as in a small animal model of sustained LV pressure overload (PO). Methods Thirty-five patients with AS and a previously implanted pacemaker underwent detailed echocardiographic examination immediately before TAVI and also on the second postoperative day. The ultrasound measurements were carried out during intrinsic, narrow QRS rhythm and during frequency-matched RVP as well. Global myocardial work index (GMWI) was calculated to assess LV contractility. In parallel, LV pressure-volume analysis was performed in Wistar rats with transverse aortic constriction (TAC) or sham operation (Sham) during intrinsic narrow QRS rhythm (termed as TAC-Vsense and Sham-Vsense) as well as during RVP (termed as TAC-Vpace and Sham-Vpace). RVP was achieved in rats by an octopolar electrophysiology catheter placed in the RV. Results RVP decreased LV contractility in AS patients before and after TAVI as well. Nevertheless, the extent of RVP-evoked LV dysfunction was alleviated following pressure unloading (ΔGMWI: -37±7 vs. -25±8%, before TAVI vs. after TAVI, P<0.05). Similarly, although RVP was associated with reduced LV contractility in both the TAC (the slope of the maximum rate of LV pressure rise-end-diastolic volume relation [dPdtmax-EDV]: 92±8 vs. 53±6mmHg/s/µl, TAC-Vsense vs. TAC-Vpace; P<0.05) and Sham groups (dPdtmax-EDV: 74±5 vs. 60±9 mmHg/s/µl, Sham-Vsense vs. Sham-Vpace; P<0.05), the negative inotropic effect of RVP was found to be stronger in the TAC compared to the Sham group (ΔdPdtmax-EDV: -42±4 vs. -19±6%; TAC vs. Sham, P<0.01). Furthermore, reduction of the maximal rate of LV pressure decrease (ΔdPdtmin: -20±3 vs. -5±5%, TAC vs. Sham, P<0.01) and prolongation of the active relaxation time constant (Δτ: 22±3 vs. 6±3%, TAC vs. Sham, P<0.01) also occurred to a greater extent in case of sustained LV PO, indicating augmented diastolic dysfunction. Conclusion Our translational results indicate that RVP-induced LV dysfunction might be afterload dependent.

The role of TandemHeartTM combined with ProtekDuoTM as right ventricular support device: A simulation approach

Background and ObjectiveRight ventricular failure increases short-term mortality in the setting of acute myocardial infarction, cardiogenic shock, advanced left-sided heart failure and pulmonary arterial hypertension. Percutaneous and surgically implanted right ventricular assist devices (RVAD) have been investigated in different clinical settings. The use of the ProtekDuo™ is currently a promising approach due to its features such as groin-free approach leading to early mobilisation, easy percutaneous deployment, compatibility with different pumps and oxygenators, and adaptability to different configurations. The aim of this work was to simulate the behaviour of the TandemHeart™ pump applied “in series” and “in parallel“ mode and the combination of TandemHeart™ and ProtekDuo™ cannula as RVAD using CARDIOSIM© software simulator platform. MethodsTo achieve our aim, two new modules have been implemented in the software. The first module simulated the TandemHeart™ pump in RVAD configuration, both as a right atrial-pulmonary arterial and a right ventricular-pulmonary arterial connection, driven by four different rotational speeds. The second module reproduced the behaviour of the ProtekDuo™ cannula plus TandemHeart™. ResultsThe effects induced on the main haemodynamic and energetic variables were analysed for both the right atrial-pulmonary arterial and right ventricular-pulmonary arterial configuration with different pump rotational speed and following Milrinone administration. The TandemHeart™ increased right ventricular end systolic volume by 10 %, larger increases were evident for higher speeds (6000 and 7500 rpm) and connections with 21-Fr inflow and 17-Fr outflow cannula, respectively. Both TandemHeart™ and ProtekDuo™ support increased left ventricular preload. When different RVAD settings were used, Milrinone therapy increased the left ventricular pressure-volume area and decreased the right pressure-volume area slightly. A reduction in oxygen consumption (demand) was observed with reduced right stroke work and pressure volume area and increased oxygen supply (coronary blood flow). ConclusionsThe outcome of our simulations confirms the effective haemodynamic assistance provided by the ProtekDuo™ as observed in the acute clinical setting. A simulation approach based on pressure-volume analysis combined with modified time-varying elastance and lumped-parameter modelling remains a suitable tool for clinical applications.

Angiotensin receptor-neprilysin inhibition and improved ventricular-arterial coupling in heart failure with reduced ejection fraction.

Sacubitril/valsartan improves outcome in chronic heart failure (HF) with reduced ejection fraction (EF). The underlying mechanisms on left ventricular (LV) myocardial function are incompletely understood. In this study, 117 patients with symptomatic HF and LV-EF ≤ 40% were enrolled prospectively. Non-invasive pressure-volume analysis was calculated from transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements. Primary outcome parameters were LV end-systolic elastance (Ees; a measure of LV contractility), effective arterial elastance (Ea; a measure of afterload), and the ventricular-arterial coupling ratio (Ea/Ees). Mean age was 65±13 years, 30% were female, and 54.7% had ischemic heart disease. During six months of follow-up, eight patients died, three withdrew their consent, and four were lost to follow-up. 102 patients were included in pressure-volume analyses. After six months of sacubitril/valsartan treatment, Ees increased (0.66mmHg/ml [IQR 0.45-0.94] vs. 0.78mmHg/ml [IQR 0.57-1.10], p=0.001), Ea decreased (1.76mmHg/ml [IQR 1.48-2.13] vs. 1.62mmHg/ml [IQR 1.36-1.96], p=0.014), and the Ea/Ees ratio improved (2.52 [IQR 1.88-4.05] vs. 1.93 [IQR 1.50-2.63], p<0.001). LV end-diastolic pressure and LV volumes were reduced, and LVEF increased from 33% to 43% (both p<0.001). Clinical improvement occurred in NYHA functional class, NT-proBNP level, and 6-minute walking distance. Change in LVEF correlated with change in Ees (r=0.33, p=0.0008), while change in NT-proBNP was associated with change in LVEDP (r=0.42, p<0.0001). In conclusion, sacubitril/valsartan is associated with improved ventricular-arterial coupling by enhancing LV contractility and reducing afterload. Beyond LV reverse remodeling, optimized ventricular-arterial interaction may contribute to the favorable outcome of sacubitril/valsartan treatment in HF with reduced EF.

Bladder Compliance Dynamics of Pelvic Organ Prolapse in Women Undergoing Robotic-Assisted Sacrocolpopexy

Although mean/static compliance of bladder filling can be readily assayed via cystometry, a protocol measuring compliance dynamics at a specific stage of bladder filling has not been established in human patients. For patients with pelvic organ prolapse (POP), the objective benefits of robotic-assisted sacrocolpopexy (RSCP) surgical intervention for restoring bladder functions, primarily urine storage, have yet to be established. Also, bladder compliance is a viscoelastic parameter crucially defines the storage function. Therefore, we aimed to investigate the impact of RSCP on bladder compliance of POP patients using a pressure-volume analysis (PVA), which graphically illustrate bladder compliance. A retrospective pre- and post-operative study. Multiple hospitals in Taiwan. 27 female POP patients (stage ≥ II). RSCP for POP repair. We retrospectively reviewed the pre- and post-operative PVAs for women with POP, who underwent RSCP. The mean compliance of the entire (Cm), the early half (C1/2), and the late half (C2/2) of bladder filling were analyzed as primary outcomes. Changes in intra-vesical volume (ΔVive) and detrusor pressure (ΔPdet) of bladder filling, ΔPdet in the early (ΔPdet1/2) and late (ΔPdet2/2) filling, and post-voiding residual volume (Vres) were analyzed as secondary outcomes. Compared with the pre-operative control, RSCP increased Cm (p=0.010, N=27) and C2/2 (p<0.001, N=27) but negligibly affected C1/2 (p=0.457, N=27). Mechanistically, RSCP decreased ΔPdet (p=0.001, N=27) without significantly affecting ΔVive (p=0.863, N=27). Furthermore, RSCP decreased the ΔPdet2/2 (p<0.001, N=27) but not ΔPdet1/2 (p=0.295, N=27). This is the first report of applying PVA in assaying dynamics of bladder compliance in patients with POP. Our results suggest that RSCP improved bladder storage in women with POP since it increased bladder compliance, particularly in the late filling possibly by restoring the anatomical location and geometric conformation for bladder expansion. This study was registered in ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT05682989); registration number: NCT05682989 submitted on 12/28, 2022.

O07 RENAL DENERVATION IMPROVES RIGHT VENTRICULAR FUNCTION, RESTORES MYOCARDIAL NOREPINEPHRINE LEVELS AND REVERSES VENTRICULAR SPECIFICITY OF SELECTED MARKERS IN HYPERTENSIVE RATS WITH HEART FAILURE INDUCED BY VOLUME OVERLOAD

Background and objective: Despite the known anti-hypertensive effect of renal denervation (RDN), its influence on the cardiac function, particularly of the right ventricle (RV) and the cardiac sympathetic nervous system in heart failure (HF) is poorly understood. This study aimed to investigate the effect of RDN on RV function, myocardial norepinephrine (NE), and left versus right ventricular (LV/RV) dominance of HF markers in HF induced by aorto-caval fistula (ACF). Methods: ACF was created in hypertensive Ren-2 transgenic rats. RDN was performed by phenol application. Cardiac function was measured by echocardiography and pressure-volume analysis. NE levels were measured using an ELISA kit, protein expression was assessed by western blotting, gene expression by TaqMan PCR assay, and ROS by Amplex Red assay. Results: RDN in ACF rats decreased RV hypertrophy and dilatation, decreased RV end-systolic pressure and end-diastolic pressure, improved RV function (Ees +45%, FAC +20%), decreased HF gene markers Nppa, Tgm2, Myh7/6 ratio, and increased SOD2 protein expression. RDN decreased plasmatic NE levels, increased NE in RV, and decreased monoamine oxidase (MAO-A) in RV. NE levels and SOD2 were more dominant in RV than LV in control (sham/intact) rats and ACF changed their specificity towards RV dominance, while RDN had no effect in these parameters in ACF on ventricular specificity. In sham/intact rats dominant for LV were hemodynamic parameters Ees, EDPVR, and molecular markers Mao-a, ROS production by MAO-A, Nppa, Myh7, Myh7/6 ratio, Tgm2, Uchl1, and Beta1/Chrm2 ratio. ACF changed the dominance of these selected markers from LV to RV. Interestingly, RDN reversed dominance back towards LV in gene markers Mao-a, Nppa, Myh7, Tgm2, Uchl1, and Beta1/Chrm2 ratio. Conclusions: RDN decreased RV ESP and EDP, improved RV systolic function, restored NE levels, decreased RV gene expression of selected HF markers, and reversed their RV/LV dominance, probably by reduction of central sympathetic nerve drive and alternations of the cardiac sympathetic nervous system.

Abstract Tu057: Renal denervation enhances right ventricular function, reduces myocardial damage, and restores myocardial sympathetic signaling in rats with heart failure induced by volume overload

Introduction: Heart failure (HF) is associated with chronically increased sympathetic nervous activity with depleted norepinephrine (NE) in the myocardium. Despite the known anti-hypertensive effect of renal denervation (RDN), its influence on the function of the right ventricle (RV) and the cardiac sympathetic nervous system in HF is not well comprehended. Hypothesis: RDN improves RV function by reducing central sympathetic drive and changes of a sympathetic nervous branch in the heart. Aims: To investigate the effect of RDN on RV function, HF markers, myocardial NE, and its metabolism in RV in HF induced by aorto-caval fistula (ACF). Methods: HF was induced by ACF in Ren-2 transgenic rats (TGR). One week later, the RDN was performed by phenol application. Two weeks after RDN, RV function was measured by pressure-volume analysis and RV tissue was collected. Echocardiography was done once a week, during the entire experiment. NE levels were measured using an ELISA kit, protein expression was assessed by western blotting, gene expression by TaqMan PCR gene expression assay, and ROS by oxidation of Amplex Red assay. Results: The ACF increased RV weight, RV dimensions (RVD1, RVD2, RVD3), end-systolic (ESP) and end-diastolic pressure (EDP), reduced RV systolic function (end-systolic elastance - Ees, fractional area change - FAC) and ventricular-arterial coupling (Ees/Ea ratio), increased gene expression of HF markers collagen I/III ratio, natriuretic peptide A (Nppa), myosine heavy chain 7/6 (Myh7/6) ratio, transglutaminase 2 (Tgm2), and decreased superoxide dismutase 2 (SOD2) protein expression. ACF increased plasmatic NE levels, depleted NE in RV, decreased tyrosine hydroxylase protein expression in RV, and increased gene, protein expression, and activity of monoamine oxidase A (MAO-A). RDN decreased RV hypertrophy and dilatation (RVD1, RVD2, RVD3), decreased RV ESP (-7 mmHg, p=0.004) and EDP (-2.2 mmHg, p=0.003), improved RV function (Ees +45%, p=0.03, FAC +20%, p=0.005, Ees/Ea ratio +46%, p=0.02), decreased HF markers collagen I/III ratio, Nppa, Tgm2, Myh7/6 ratio, and increased SOD2 protein expression. RDN decreased plasmatic NE levels, increased NE in RV (+32%, p=0.03), and decreased MAO-A in RV. Conclusions: RDN decreased RV ESP and EDP, improved RV systolic function, restored NE levels, and decreased RV gene expression of selected HF markers, probably by reduction of central sympathetic nerve drive and alterations of the cardiac sympathetic nervous system.

Abstract Mo113: An Ovary-Intact Postmenopausal HFpEF Animal Model.

Background: The incidence of HFpEF in women significantly escalates following the age of menopause. This trend cannot solely be attributed to chronological aging, as evidenced by the more gradual increase in prevalence among men with HFpEF. This pattern suggests that menopause is a provocative event for HFpEF. However, the underlying mechanisms remain elusive and challenging to investigate in human subjects; moreover, the attempt to create HFpEF in ovariectomized (OVX) mice was unsuccessful. We aim to create an animal model of postmenopausal HFpEF that resembles the characteristics of HFpEF in women with natural menopause. Methods: We use the 4-vinyl cyclohexene dioxide (VCD) to induce “ovary-intact” menopause, combined with the 2hit regimen (HFpEF inducing regimen elicited by high-fat diet and nitric oxide synthase inhibitor) to model postmenopausal HFpEF. VCD gradually causes ovarian failure, providing the perimenopausal transition and preserving residual ovarian stroma, mimicking natural menopause. The HFpEF phenotypes were studied at the in vivo LV by pressure-volume (PV) analysis and at the single cell level by intact cell force measurement. Results: The Female-VCD-2hit model demonstrates diastolic dysfunction at both the LV and the cellular levels. At the LV level, the increase in the end-diastolic pressure-volume relation (EDPVR) stiffness coefficient and LV end-diastolic pressure (LVEDP) indicates a heightened stiffness of the LV chamber and an elevation in LV filling pressure, an HFpEF-like condition. At the cardiomyocyte level, the female-VCD-2hit model exhibits an increase in cellular diastolic stiffness, suggesting that the observed LV diastolic stiffness is derived from the stiffness of the cardiomyocytes. We compared the female-VCD-2hit mice with the OVX mice subjected to the 2hit regimen. The 2hit-OVX model showed a milder form of diastolic dysfunction, observed as a smaller increase in LV diastolic stiffness (EDPVR) and normal LV filling pressure (LVEDP). Conclusions: Female mice, either premenopausal or ovariectomized, are more resistant to the development of HFpEF, unlike their ovary-intact menopausal (VCD-treated) counterparts, which exhibit a vulnerability to HFpEF, making the VCD-2hit model a suitable model to study postmenopausal HFpEF. The LV diastolic dysfunction observed in the 2hit model is attributed to mechanical dysfunction at the cardiomyocyte level.

Right ventricular pacing-evoked left ventricular dysfunction is exaggerated by sustained left ventricular pressure overload in a rat model

Abstract Introduction A growing body of evidence suggests that in the presence of left bundle branch block-induced electromechanical dyssynchrony, the function of the left ventricle (LV) becomes extremely sensitive to arterial afterload. However, data is scarce whether right ventricular pacing (RVP) also sensitizes the LV to alterations in afterload. Purpose Hence, in the present translational study we aimed to characterize the acute effect of RVP on LV hemodynamics under standard laboratory conditions using a rat model of chronic LV pressure overload (PO). Methods Transverse aortic constriction (TAC group) was carried out in male Wistar rats to evoke sustained LV PO for six weeks. Age- and sex-matched sham-operated animals served as controls (Sham group). LV hemodynamics was assessed in anesthetized rats by pressure-volume analysis using a pressure-conductance micro-catheter (SPR-838) introduced to the LV via the right carotid artery. To evoke RVP, the right jugular vein was cannulated and an ultra-miniature octopolar electrophysiology catheter (EPR-800) was placed into the right ventricle. Pressure-volume loops were registered in the TAC and the Sham groups during intrinsic narrow QRS rhythm (termed as TAC-Vsense and Sham-Vsense) as well as during RVP (termed as TAC-Vpace and Sham-Vpace). Results RVP was associated with impaired diastolic function (active relaxation time constant [τ]: 8.6±0.3 vs. 9.6±0.3ms, Sham-Vsense vs. Sham-Vpace and 8.0±0.3 vs. 9.6±0.4ms, TAC-Vsense vs. TAC-Vpace; P&amp;lt;0.001 for both comparisons) and decreased LV contractility (preload recruitable stroke work [PRSW]: 139±9 vs. 114±9mmHg, Sham-Vsense vs. Sham-Vpace and 255±23 vs. 169±17mmHg, TAC-Vsense vs. TAC-Vpace; P&amp;lt;0.001 for both comparisons) in both the TAC and the Sham groups. Nevertheless, the extent of RVP-evoked active relaxation prolongation (Δτ: 12±2 vs. 20±2%, Sham vs. TAC, P=0.005) and LV contractility reduction (ΔPRSW: -18±4 vs. -34±3%, Sham vs. TAC, P=0.007) was found to be more robust in rats with sustained LV PO compared to controls. Conclusion Our experimental results indicate that RVP-induced LV dysfunction is exaggerated in case of sustained LV PO.

Comparative analysis of ventricular stiffness across species.

Investigating ventricular diastolic properties is crucial for understanding the physiological cardiac functions in organisms and unraveling the pathological mechanisms of cardiovascular disorders. Ventricular stiffness, a fundamental parameter that defines ventricular diastolic functions in chordates, is typically analyzed using the end-diastolic pressure-volume relationship (EDPVR). However, comparing ventricular stiffness accurately across chambers of varying maximum volume capacities has been a long-standing challenge. As one of the solutions to this problem, we propose calculating a relative ventricular stiffness index by applying an exponential approximation formula to the EDPVR plot data of the relationship between ventricular pressure and values of normalized ventricular volume by the ventricular weight. This article reviews the potential, utility, and limitations of using normalized EDPVR analysis in recent studies. Herein, we measured and ranked ventricular stiffness in differently sized and shaped chambers using exvivo ventricular pressure-volume analysis data from four animals: Wistar rats, red-eared slider turtles, masu salmon, and cherry salmon. Furthermore, we have discussed the mechanical effects of intracellular and extracellular viscoelastic components, Titin (Connectin) filaments, collagens, physiological sarcomere length, and other factors that govern ventricular stiffness. Our review provides insights into the comparison of ventricular stiffness in different-sized ventricles between heterologous and homologous species, including non-model organisms.

Echocardiographic estimation of right ventricular diastolic stiffness based on pulmonary regurgitant velocity waveform analysis in precapillary pulmonary hypertension.

Right ventricular (RV) diastolic stiffness is an independent predictor of survival and is strongly associated with disease severity in patients with precapillary pulmonary hypertension (PH). Therefore, a fully validated echocardiographic method for assessing RV diastolic stiffness needs to be established. This study aimed to compare echocardiography-derived RV diastolic stiffness and invasively measured pressure-volume loop-derived RV diastolic stiffness in patients with precapillary PH. We studied 50 consecutive patients with suspected or confirmed precapillary PH who underwent cardiac catheterization, magnetic resonance imaging, and echocardiography within a 1-week interval. Single-beat RV pressure-volume analysis was performed to determine the gold standard for RV diastolic stiffness. Elevated RV end-diastolic pressure (RVEDP) was defined as RVEDP ≥ 8 mmHg. Using continuous-wave Doppler and M-mode echocardiography, an echocardiographic index of RV diastolic stiffness was calculated as the ratio of the atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) to the tricuspid annular plane movement during atrial contraction (TAPMAC). PRPGDAC/TAPMAC showed significant correlation with β (r = 0.54, p < 0.001) and RVEDP (r = 0.61, p < 0.001). A cut-off value of 0.74 mmHg/mm for PRPGDAC/TAPMAC showed 83% sensitivity and 93% specificity for identifying elevated RVEDP. Multivariate analyses indicated that PRPGDAC/TAPMAC was independently associated with disease severity in patients with precapillary PH, including substantial PH symptoms, stroke volume index, right atrial size, and pressure. PRPGDAC/TAPMAC, based on pulmonary regurgitation velocity waveform analysis, is useful for the noninvasive assessment of RV diastolic stiffness and is associated with prognostic risk factors in precapillary PH.

Right ventricular pressure-strain relationship-derived myocardial work reflects contractility: Validation with invasive pressure-volume analysis

Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) is a novel parameter calculated by the area of the RV pressure-strain loop. By adjusting myocardial deformation to instantaneous pressure, it may reflect contractility.To test this hypothesis, we enrolled 60 patients who underwent RV pressure-conductance catheterization to determine load-independent markers of RV contractility and ventriculo-arterial coupling. Detailed 3D echocardiography was also performed, and we calculated RV EF, RV GLS, and using the RV pressure trace curve, RV GWMI.While neither RV EF nor GLS correlated with Ees, GMWI strongly correlated with Ees. In contrast, RV EF and GLS showed a relationship with Ees/Ea. By dividing the population based on their Reveal Lite 2 risk classification, different characteristics were seen among the subgroups.RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with RV dysfunction.

Comprehensive RV Hemodynamic Assessment With Pressure-Volume Analysis During Impella Support: Findings From the CHAMP-IMPELLA Study

Comprehensive RV Hemodynamic Assessment With Pressure-Volume Analysis During Impella Support: Findings From the CHAMP-IMPELLA Study

Right ventricular performance during acute hypoxic exercise.

Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia. Ten healthy participants (34±10 years, 7males) completed three visits: visits 1 and 2 included non-invasive normoxic (fraction of inspired oxygen ( )=0.21) and isobaric hypoxic ( =0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake ( ). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan-Ganz or conductance catheterization to quantify RV performance via pressure-volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic and again at 50% hypoxic ( =0.12). Median (interquartile range) values for non-invasive values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P<0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P=0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dtmax, and end-systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular-arterial coupling was maintained during normoxic exercise at 50% . During submaximal exercise at 50% of hypoxic , ventricular-arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an =0.12 and the associated increase in PA pressures. KEY POINTS: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions. During submaximal exercise, ventricular-arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained. These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure.

The impact of phosphodiesterase-5 inhibition or angiotensin-converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload.

While phosphodiesterase-5 inhibition (PED5i) may prevent hypertrophy and failure in pressure-overloaded heart in an experimental model, the impact of PDE5i on volume-overload (VO)-induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long-term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto-caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin-converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure-volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6-fold, RV: 6.7-fold), and reduced load-independent systolic function (PRSW, LV: -54%, RV: -51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO-induced HF is not responsive to PDE5i therapy.