Adaptation Of Right Ventricle Research Articles

Deep phenotyping the right ventricle to establish translational MRI biomarkers for characterization of adaptive and maladaptive states in pulmonary hypertension

Deep phenotyping the right ventricle (RV) is essential for understanding the mechanisms of adaptive and maladaptive RV responses to pulmonary hypertension (PH). In this study, feature selection coupled with machine learning classification/ranking of specific cardiac magnetic resonance imaging (MRI) features from cine-MRI, flow-sensitized, and extracellular-volume techniques were used to assess RV remodelling in monocrotaline (MCT) and Sugen hypoxia (SuHx) PH rats. Early physiological changes associated with RV adaptation were detected along with prediction of RV maladaptive outcomes. Key adaptation features included haemodynamic alterations of pulmonary blood flow ejection and wave reflection, mild RV dilatation, progressive RV hypertrophy with subtle extracellular volume growth of RV wall. A dominant component of maladaptation was the extracellular matrix increase at RV insertion points and septum, observations compatible with histopathologic and RNA-sequencing results. The upregulation of mammalian target of rapamycin (mTOR) paralleled by AMP-activated protein kinase (AMPK) deactivation was seen at 4-week MCT and 8-week SuHx, along with reduced sarcoplasmic/endoplasmic reticulum Ca2+ATPase (SERCA2) expression, strongly associated with the RV systolic malfunction seen at this stage in vivo. The here established MRI features can serve as potential imaging biomarkers to evaluate PH treatment efficacy in preclinical studies and build up translational markers for the PH clinic.

Abstract 4142768: Association Between Right Ventricular-Pulmonary Arterial Coupling and Outcomes in Patients with Heart Failure with Preserved Ejection Fraction

Introduction: Right ventricle (RV)-pulmonary artery (PA) coupling reflects functional adaptation of RV to afterload. Impaired RV-PA coupling is associated with worse outcomes in patients with pulmonary hypertension. However, the association between RV-PA coupling and outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not well established. Objective: To assess the association between RV-PA coupling and outcomes in patients with HFpEF and determine an optimal cutpoint of the TAPSE/RVSP ratio for prediction of adverse events. Methods: Participants with a diagnosis of HFpEF were enrolled at the University of Toledo Medical Center from March 2012 and were followed until August 2023. The ratio of tricuspid annular plain systolic excursion (TAPSE) to right ventricular systolic pressure (RVSP) on echocardiogram was used as a measure of RV-PA coupling. The primary endpoint was death or heart failure hospitalization. ROC analysis was performed to determine an optimal cutpoint point for TAPSE/RVSP. Cox proportional hazards regression model was used to assess the association between TAPSE/RVSP and outcomes. Results: 83 participants (age 68.69 ± 10.72, 67.5% female) with HFpEF and available echocardiogram data were enrolled in the study. The median TAPSE/RVSP was 0.41. Death or heart failure hospitalization occurred in 51 (56.6%) individuals. Using ROC curve analysis, we identified the optimal cutpoint of TAPSE/RVSP of 0.31 which had a sensitivity of 57% and specificity of 88% for predicting mortality (AUC 0.756, 0.622-0.889). TAPSE/RVSP less than 0.31 was associated with higher risk of death or heart failure (HF) hospitalization (HR=2.61, CI=1.28-5.33, p= 0.008), death (HR=3.40, CI=1.34-8.64, p= 0.01), and HF hospitalization (HR=2.45, CI=1.06-5.68, p= 0.03). Conclusion: Worse RV-PA coupling was associated with worse outcomes in individuals with HFpEF. The TAPSE/RVSP cutpoint of <0.31 had a good specificity for prediction of adverse events including death or HF hospitalization.

Alterations of biaxial viscoelastic properties of the right ventricle in pulmonary hypertension development in rest and acute stress conditions.

Introduction: The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates. Methods: PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively. Results and Discussion: We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups-the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress.

Evaluating the effectiveness of an apelin analog as a potential treatment for pulmonary arterial hypertension using a sugen-hypoxia rat model

Background: Pulmonary arterial hypertension (PAH) is a debilitating syndrome characterized by heightened pulmonary arterial pressures, and adverse pulmonary vascular remodeling. Eventually, the right ventricle (RV) decompensates, and fatal right heart failure ensues. Existing treatments for PAH are ineffective at improving survival. Apelin is an endogenous cardioprotective peptide, and disruption of apelin signaling was associated with the development of PAH. Restoring the activity of the apelin pathway is a promising approach in reversing the arteriopathy underlying PAH to protect the RV. The salutary actions of apelin are limited by its short half-life; recently, apelin analogs designed with extended half-lives offer a novel therapeutic avenue requiring further testing. Objective: Our project aims to evaluate the effectiveness of an apelin analog as a potential treatment for PAH using a Sugen-Hypoxia (SuHx) rat model of PAH which recapitulates disease characteristics seen in humans. We hypothesize that the apelin analog treatment will improve pulmonary hemodynamics and preserve RV adaptation in rats exposed to SuHx and assuage the pulmonary arteriopathy seen in PAH rats. Experimental design: Male Sprague Dawley rats aged 9 weeks were randomly split into a placebo or treated PAH group. For 3 weeks, a control group was kept within normal room air while the placebo and treated PAH rats were kept in a hypoxia chamber (10% O 2 ). Placebo and treated rats were injected with SU5416 (20 mg/kg, SQ) once at the start of the 3 weeks to induce disease. The normoxic period lasted 5 weeks following the 3 weeks of hypoxia. Treated rats received apelin analog (0.5 μmol/kg, IV, b.i.d.) for the final 3 weeks of normoxia; the placebo group received the same dose of saline. Results: At endpoint, glomerular filtration rate (GFR) measurements showed that placebo treated (PAH-P) PAH rats had reduced GFR while apelin treated (PAH-A) PAH rats had recovered GFR. Echocardiography revealed that PAH-A rats had improved cardiac function compared to PAH-P rats. RV Pressure-volume loop surgeries showed that PAH-A rats had ameliorated RV hemodynamic pressures in contrast to PAH-P rats. Histological analysis demonstrated reduced cardiac fibrosis and hypertrophy, and fewer formations of pulmonary vascular lesions within PAH-A rats compared to PAH-P rats. Single nucleus RNA sequencing performed on RV and lung tissue delineated mitigation of disease progression within the PAH-A group compared to PAH-P rats. Electrocardiography recordings showed more severe electrical remodeling in the PAH-P group compared to the PAH-A rats. Conclusions & significance: Rats with PAH treated with apelin had overall improved cardiopulmonary health outcomes compared to placebo treated PAH rats. The results of this study provide insight into the beneficial role of the apelin pathway in the setting of PAH to propose a new treatment for patients with PAH to improve their duration and quality of life. Canadian Institutes of Health Research Grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Right Ventricular Architectural Remodeling and Functional Adaptation in Pulmonary Hypertension.

Global indices of right ventricle (RV) function provide limited insights into mechanisms underlying RV remodeling in pulmonary hypertension (PH). While RV myocardial architectural remodeling has been observed in PH, its effect on RV adaptation is poorly understood. Hemodynamic assessments were performed in 2 rodent models of PH. RV free wall myoarchitecture was quantified using generalized Q-space imaging and tractography analyses. Computational models were developed to predict RV wall strains. Data from animal studies were analyzed to determine the correlations between hemodynamic measurements, RV strains, and structural measures. In contrast to the PH rats with severe RV maladaptation, PH rats with mild RV maladaptation showed a decrease in helical range of fiber orientation in the RV free wall (139º versus 97º; P=0.029), preserved global circumferential strain, and exhibited less reduction in right ventricular-pulmonary arterial coupling (0.029 versus 0.017 mm/mm Hg; P=0.037). Helical range correlated positively with coupling (P=0.036) and stroke volume index (P<0.01). Coupling correlated with global circumferential strain (P<0.01) and global radial strain (P<0.01) but not global longitudinal strain. Data analysis suggests that adaptive RV architectural remodeling could improve RV function in PH. Our findings suggest the need to assess RV architecture within routine screenings of PH patients to improve our understanding of its prognostic and therapeutic significance in PH.

Different right ventricular maladaptation in heart failure patients with reduced or preserved ejection fraction: diagnostic and prognostic implication

Abstract Background The prognostic impact of right ventricle (RV) dysfunction and pulmonary hypertension (PH) in patients affected by chronic heart failure (HF) has been well described by several studies in both patients affected by HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It has been been demonstrated that tricuspidal anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio, may provide additional prognostic information. However, the pathophysiological mechanisms leading to RV dysfunction may differ in HFpEF and HFrEF. Aims In this study we would like to evaluate: 1. Different RV adaptation in hospitalized HF patients with reduced or preserved EF 2. prognostic significance of an early echocardiographic assessment of RV structure comparing TAPSE/PASP vs s'/PASP in HFrEF and HFpEF. Methods We included 381 patients included in the study, 209 had HFrEF and 172 had HFpEF who were studied by echocardiography. S' wave and RV longitudinal function strain (RVLS) were obtained by apical four chamber view and optimal visualization of RV lateral free wall. RV diameter was measured at basal level below tricuspidal anular plane. Patients were followed for 6 months after discharge for the composite outcome of cardiovascular death and re-hospitalization. Results Patients with HFrEF demonstrated a larger RV end diastolic diameter (EDD) compared to HFpEF (43 [37–45] vs 39 [36–44] mm; p=0.009) and more reduced TAPSE (19 [16–21] vs 20 [17–22] mm; p=0.04). Whereas PASP values were similar in both groups. Conversely, s' wave and RVLS were much more reduced in HFpEF (9 [7–11] vs 12 [9–13] cm/sec; p=0.008; 16 [14–21] vs 20 [15–23]% p&amp;gt;0.05) than in HFrEF. TAPSE/PASP was significantly reduced in HFrEF (0.38 [0.29–0.42] vs 0.43 [0.35–0.48]; p=0.02). Conversely s'/PAPS was lower in HFpEF group (0.29 [0.24–0.33] vs 0.25 [0.21–0.31]; p=0.01). At univariate analysis several parameters were related to outcome: TAPSE≤14 mm, (HR 1.70 [1.14–2.52]; p=0.009), PASP≥40 mmHg (HR 1.51 [1.05–2.17]; p=0.02), RVEDD &amp;gt;38 mm (HR; 1.88 [1.36–2.61]; p&amp;lt;0.001), s wave&amp;lt;9 (HR1.88 [1.30–2.41] p&amp;lt;0.001),inferior cave vein diameter&amp;gt;21 mm (HR 1.90 [1.31–2.75]; p=0.001. Multivariable analysis confirmed prognostic role of TAPSE, RVEDD, IVC and s' wave. Therefore TAPSE /PAPS was associated with adverse event in HFrEF but not in HFpEF (HR 1,75 [1.41–2.92] in HFrEF, p=0.003; HR 1.02 [0.67–1.32] in HFpEF, p=0.55). Whereas, s/PAPS was associated with more increased risk in HFpEF (HR 1.88 [1.65–3.46] in HFpEF, p&amp;lt;0.001; HR 1.34 [1,08–4.32] in HFrEF, p=0.03). Conclusions Right ventricular dysfunction and maladaptation are associated with poor outcome in either HFrEF and HFpEF. Tissue excursion and longitudinal strain are much more impaired in HFpEF, whereas RV dilatation and reduced longitudinal function are closely related to HFrEF. Funding Acknowledgement Type of funding sources: None.

Avalanches in cardiology.

Sudden cardiac death (SCD) accounts for 15%–60% of mortality in patients with heart disease. Generally, this has been attributed to ventricular tachyarrhythmia. However, ventricular tachyarrhythmia has been documented or strongly suspected on clinical grounds in a relatively small proportion of SCD patients (8%–50%). Attempted prophylaxis of SCD by implantation of cardioverter-defibrillator is associated with variable success in different subsets of high-risk cardiac patients (30%–70%). A significant number of SCD, therefore, appear to be due to catastrophic circulatory failure. Multiple interdependent compensatory mechanisms help to maintain circulation in advanced cardiac disease. Rapid, unexpected, and massive breakdown of the compensated state can be precipitated by small and often imperceptible triggers. The initial critical but stable state followed by rapid circulatory failure and death has been considered to be analogous to snow avalanches. It is typically described in patients with left ventricular (LV) dysfunction (ischemic or nonischemic). It is now recognized that SCD can also happen in conditions where the right ventricle (RV) takes the brunt of the hemodynamic load. Advanced pulmonary arterial hypertension and operated patients of tetralogy of Fallot with pulmonary regurgitation are of particular interest to pediatric cardiologists. A large amount of data is available on LV changes and mechanics, while relatively little information is available on the mechanisms of RV adaptation to increased load and RV failure. Whether the triggers and the decompensatory processes are similar for the two ventricles is a moot point. This article highlights the currently available knowledge on the pathophysiology of SCD in RV overload states, with special reference to RV adaptive and decompensatory mechanisms, and therapeutic measures that can potentially interrupt the vicious downward course (cardiac avalanches).

Right Ventricular Function and Region-Specific Adaptation in Athletes Engaged in High-Dynamic Sports: A Meta-Analysis.

Structural remodeling of the right ventricle (RV) is widely documented in athletes. However, functional adaptation, including RV pressure generation and systolic free-wall longitudinal mechanics, remains equivocal. This meta-analysis compared RV pressure and function in athletes and controls. A systematic review of online databases was conducted up to June 4, 2020. Meta-analyses were performed on RV systolic pressures, at rest and during exercise, tricuspid annular plane systolic displacement, myocardial velocity (S'), and global and regional longitudinal strain. Bias was assessed using Egger regression for asymmetry. Data were analyzed using random-effects models with weighted mean difference and 95% CI. Fifty-three studies were eligible for inclusion. RV systolic pressure was obtained from 21 studies at rest (n=1043:1651; controls:athletes) and 8 studies during exercise (n=240:495) and was significantly greater in athletes at rest (weighted mean difference, 2.9 mmHg [CI, 1.3-4.5 mmHg]; P=0.0005) and during exercise (11.0 [6.5-15.6 mm Hg]; P<0.0001) versus controls. Resting tricuspid annular plane systolic displacement (P<0.0001) and S' (P=0.001) were greater in athletes. In contrast, athletes had similar RV free-wall longitudinal strain (17 studies; n=450:605), compared with controls but showed greater longitudinal apical strain (16 studies; n=455:669; 0.9%, 0.1%-1.8%; P=0.03) and lower basal strain (-2.5% [-1.4 to -3.5%]; P<0.0001). Functional RV adaptation, characterized by increased tricuspid annular displacement and velocity and a greater base-to-apex strain gradient, is a normal feature of the athlete's heart, together with a slightly elevated RV systolic pressure. These findings contribute to our understanding of RV in athletes and highlight the importance of considering RV function in combination with structure in the clinical interpretation of the athlete's heart.

Mechanical contraction patterns of the systemic right ventricle: a 3D echocardiography study

Abstract Funding Acknowledgements Type of funding sources: None. Background. In patients with transposition of great arteries (TGA) post atrial switch operation or with congenitally corrected TGA (ccTGA), the morphologically right ventricle (RV) has to adapt to the chronically increased systemic pressure. Purpose. To investigate the functional adaptation of the systemic RV in patients with TGA post Mustard repair or ccTGA. Methods. RV volumes and EF were measured by 3D echocardiography in 33 patients with the systemic RV (21 TGA and 12 ccTGA; 45 ± 13y, 61% male), and in 33 healthy volunteers (44 ± 13y, 61% male). The 3D RV model was postprocessed by the ReVISION software and its contraction was decomposed along the longitudinal, radial and anteroposterior directions (Fig.A, Systemic RV in TGA) providing longitudinal, radial and anteroposterior EF (LEF, REF and AEF). Relative contribution of each component was measured as the ratio between LEF, REF and AEF to the global RVEF (LEFi, REFi and AEFi). Results. Systemic RV was significantly larger with reduced function compared to controls (Tab). 3D RVEF demonstrated stronger correlation with BNP (Rho -0.76, p &amp;lt; 0.0001) compared to other parameters of RV function (free wall strain 0.55, p = 0.0083; FAC -0.47, p = 0.024; S’ -0.39 and TAPSE 0.06, p &amp;gt; 0.05). While in healthy volunteers, all 3 components of RV systolic function contributed equally to the global RV EF, in patients with TGA the relative contribution of the anteroposterior component was dominant and differed significantly from longitudinal and radial components (AEFi 0.48 ± 0.06 vs LEFi 0.31 ± 0.07 vs REFi 0.36 ± 0.09, p &amp;lt; 0.0001)(Fig. B,C). In patients with ccTGA the longitudinal component was dominant and provided a relative compensation for the reduced anteroposterior and radial components (LEFi 0.47 ± 0.07 vs AEFi 0.34 ± 0.07, p = 0.0002 and vs REFi 0.36 ± 0.09, p = 0.0023)(Fig. B,C). Relative contribution of the radial contraction was significantly reduced in all systemic RV patients. Conclusions. Systemic RV contraction patterns change significantly with anteroposterior contraction being dominant in patients with TGA post Mustard repair and longitudinal component being dominant in ccTGA. 3DE should be a part of routine assessment of the systemic RV, especially in TGA since no conventional echo parameters take into account anteroposterior RV contraction. Parameters of RV systolic function Parameter Control group (N = 33) All SRV patients (N = 33) TGA (N = 21) ccTGA (N = 12) 3D EF, % 60 ± 3.8 36 ± 8.6* 34 ± 7.3* 38 ± 10* FAC, % 41.4 ± 3.7 25.9 ± 9.3* 25.1 ± 9.2* 27.1 ± 9.9* TAPSE, mm 24.6 ± 4.2 11.9 ± 3.9* 11.1 ± 2.9* 13.2 ± 5.1* RV free wall strain, % -32.5 ± 4.2 -14.5 ± 3.5* -14.5 ± 2.9* -15.5 ± 3.5* * p &amp;lt; 0.0001 Abstract Figure.

Medical Therapy for Heart Failure Associated With Pulmonary Hypertension.

The past 2 decades have witnessed a >40% improvement in mortality for patients with heart failure and left ventricular systolic dysfunction. 1 This success has coincided with the stepwise availability of drugs that target neurohormonal activation: β-adrenergic receptor blockers (β-blockers), ACE (angiotensin-converting enzyme) inhibitors and ANG (angiotensin) II blockers, neprilysin inhibitors, and aldosterone antagonists. Our understanding of right heart failure (RHF) has lagged behind and many proven targeted therapies for left heart failure do not appear to provide similar benefits for RHF. Until recently, the right ventricle (RV) has often been viewed as less important than the left ventricle and in contemporary literature received the moniker "The Forgotten Ventricle". Recent advances in echocardiography and magnetic resonance imaging have enabled detailed assessments of RV anatomy and physiology in both health and disease allowing us to more accurately describe the clinical sequelae and end-organ manifestations of RHF. RV function is now recognized as one of the most important predictors of prognosis in many cardiovascular disease states. 2 Despite the significance of RV function to survival, there are no clinically approved therapies that directly nor selectively improve RV function. As well, relative to our understanding of left heart failure, the basis for RHF remains poorly understood. This article aims to condense the current knowledge on RV adaptation and failure, review current management strategies for RHF, and explore evolving therapeutic approaches.

Abstract 17209: Impaired Ventricular-Vascular Coupling in Young Adults Born Preterm

Background: Preterm birth affects 10% of live births in the United States, often requiring mechanical ventilation and oxygen supplementation. Although a known risk factor for neonatal and childhood pulmonary vascular disease, little is known regarding the long-term impact on the right ventricle (RV). Here, we utilize novel techniques to investigate RV afterload, contractility, and ventricular-vascular coupling (VVC) in young adults born preterm. Methods: Adults born premature (n=7; 4; current age 26.7±0.4 years; gestational age 28.6±1.1 weeks) born with very low birth weight (≤1500g) were recruited from the Newborn Lung Project. Control subjects (n=7; 2) from the same birth years were recruited from the general population. All subjects had no known cardiopulmonary disease. Right heart catheterization (RHC) and magnetic resonance imaging (MRI) were performed to assess right ventricular hemodynamics. Asynchronously acquired pressure and volume data (from RHC and MRI, respectively) were used to compute effective arterial elastance (Ea), end-systolic elastance (Ees), and VVC as: [ESP/SV], [(P max -ESP)/SV], and [Ees/Ea], respectively, where ESP is the end-systolic pressure, SV is the stroke volume, and P max is the maximum isovolumetric pressure estimated from a novel single-beat approach. Results were analyzed via two-sample t-test; p&lt;0.05 was considered significant. Results: Preterm subjects had significantly increased Ea, a measure of RV afterload (Figure 1A). No difference Ees, a measure of RV contractility, was evident (Figure 1B), resulting in significantly impaired VVC in preterm subjects (Figure 1C). Conclusion: Otherwise healthy young adults born preterm have high resistance-low compliance pulmonary vascular beds with no RV adaptation, resulting in impaired right ventricular-pulmonary vascular coupling. These findings add to the growing literature that preterm birth has profound lifelong consequences that warrant further study.

STRAIN-DEPENDENT DEFECT IN RIGHT VENTRICULAR ADAPTATION IN FISCHER RATS WITH SEVERE PULMONARY ARTERIAL HYPERTENSION IS ASSOCIATED WITH DYSREGULATION IN METABOLIC AND ANGIOGENIC PATHWAYS

Fischer rats exhibit a very high mortality in the SU5416 (SU) / chronic hypoxia (CH) model of severe pulmonary arterial hypertension (PAH) compared to Sprague Dawley (SD) rats, despite nearly identical increases in right ventricular systolic pressure (RVSP). This was associated with greater dilatation and reduced function of the right ventricle (RV) suggesting a strain-specific defect in RV adaptation to increased afterload. The aim of this study was to explore the mechanisms responsible for this marked difference in compensatory remodeling of the RV that drives poor prognosis and high mortality.

Inter-individual variability in right ventricle adaptation after an endurance race.

Right ventricle (RV) dysfunction has been described in athletes after endurance races. We aimed to understand and characterize the RV response to endurance exercise, the impact of individual variability and the effects of the amount of exercise. Echocardiography was performed in 55 healthy adults at baseline and after a three-stage trail race: short (14 km; n = 17); medium (35 km; n = 21); and long (56 km; n = 17). Standard and speckle tracking echocardiographic assessment of the RV was performed with global and separate analysis of the RV basal (inflow) and apical regions. Although no change was observed in the short distance runners, the RV systolic deformation decreased significantly (p < 0.05) after both the medium length and long races (Δ% RV global strain -7.6 ± 20.1 and -8.7 ± 21.8, respectively) with significant RV dilatation (Δ% RV volume +10.6 ± 9.9 and +15.3 ± 12.8, respectively). The RV basal segment made a major contribution to stroke volume during exercise, showing larger increases in size and strain compared with the apex. Various patterns of RV adaptation to exercise, ranging from increases in both RV segmental strains and sizes to an insufficient increase in size and a decrease in strain, were identified; this individual variability was not correlated with prior training. An acute RV impairment was demonstrated after a trail-running race and was related to the amount of exercise. A high inter-individual variability was observed. Differences in RV adaptation patterns were independent of prior training, suggesting the influence was due to other individual factors.

Abstract 15922: Fischer Rats Exhibit High Mortality in the Su5416 Model of Severe Pulmonary Arterial Hypertension Related to Failure of Right Ventricular Adaptation

Introduction: Inhibition of VEGFR2 with SU5416 (SU) in combination with chronic hypoxia (CH), produces severe pulmonary arterial hypertension (PAH) in rats with complex arterial remodeling that closely resembles plexiform lesions typical of human PAH. Survival in severe PAH is related to the ability of the right ventricle (RV) to adapt to increased afterload. In this study, we explored the effect of genetic background on right ventricular adaptation and survival in the Methods: PAH was induced by a single subcutaneous injection of SU5416 (20mg/kg) in 6-week old Sprague-Dawley (SD, Harlan, USA) or Fischer rats (CDF, Charles River), followed by a 3-week exposure to CH (10% O2). RV structure and function was assessed by echocardiography (Vevo 2100, Visual Sonics) and cardiac MRI (Agilent 7.0T). Exercise capacity was evaluated at 4 weeks post-SU by treadmill testing. At end study (4 or 7 weeks post-SU), right ventricular systolic pressure (RVSP) was assessed by right heart catheterization. Results: SD and Fischer rats exhibited in similar elevations in RVSP (104± 13 vs 102 ±6 mmHg, respectively), number of occlusive pulmonary vascular lesions and RV hypertrophy (RV/LV+S) in response to SU/CH. However, Fischer rats exhibited markedly higher mortality, with only 27% surviving to 7 weeks compared with 100% survival in SD rats (p&lt;0.01), which was associated with significantly greater RV dilatation (RV/LV end diastolic diameter: 2.16 ± 0.24 vs. 1.19 ± 0.09 mm, p&lt;0.001) at 4 weeks post-SU (Figure 1). Additionally, RV capillary density (516 ± 55 vs 786 ± 38 capillaries/mm2) and exercise capacity (treadmill distance, 59 ± 29 vs 210 ± 52 m, p&lt;0.05) were also significantly reduced in Fischer vs SD SU/CH rats. Conclusions: These data suggest that the high mortality in Fischer compared to SD rats in the SU/CH model of severe PAH is related to a strain-dependent abnormality in RV adaptation at least in part due to lack of adequate microvascular angiogenesis in the hypertrophied RV.

HIGH MORTALITY OF FISCHER VS. SPRAGUE-DAWLEY RATS IN THE SU5416 MODEL OF SEVERE PULMONARY ARTERIAL HYPERTENSION IS ASSOCIATED WITH STRAIN-SPECIFIC FAILURE OF RIGHT VENTRICULAR ADAPTATION: EFFECTS OF CARDIAC-SPECIFIC THERAPY WITH CARDIOTROPHIN-1

HIGH MORTALITY OF FISCHER VS. SPRAGUE-DAWLEY RATS IN THE SU5416 MODEL OF SEVERE PULMONARY ARTERIAL HYPERTENSION IS ASSOCIATED WITH STRAIN-SPECIFIC FAILURE OF RIGHT VENTRICULAR ADAPTATION: EFFECTS OF CARDIAC-SPECIFIC THERAPY WITH CARDIOTROPHIN-1

Circulation : Clinical Summaries

<i>Circulation</i> : Clinical Summaries

Evaluation of myocardial function in pediatric patients with transposition of great arteries after arterial switch operation.

Objective:An arterial switch operation converts the left ventricle (LV) into the systemic ventricle, replacing the right ventricle (RV), which is the systemic ventricle during the prenatal period. The procedure is performed in patients with arterial transposition and those in whom a coronary reimplantation procedure is performed. Therefore, the adaptation of LV and RV to the arterial switch operations is an interesting issue. This study aimed to evaluate systolic and diastolic functions in the LV and RV myocardium using echocardiography in pediatric patients with transposed great arteries after an arterial switch operation.Methods:This observational case control study included 28 patients and 20 gender-and age-matched healthy controls. A group study was performed using patients who were followed for at least 6 months after the operation and who visited the pediatric cardiology outpatient between October 2009 and May 2011. Systolic and diastolic parameters, LV and RV myocardial performance index (MPI) values, and left atrium (LA) volume index were assessed in both groups.Results:The LV MPI and tricuspid valve (TV) E/Ea ratio measured using pulsed-wave Doppler were higher in the patient group than in the control group. The TV E/A ratio and late velocity of lateral mitral annulus (Aa) and systolic velocity (Sa)-early diastolic velocity (Ea)-late velocity (Aa) of the septal mitral annulus and systolic velocity (Sa)-early diastolic velocity (Ea)-late velocity (Aa) of the lateral tricuspid annulus were lower in the patient group than in the control group.Conclusion:Considering the present study’s findings obtained during short-to mid-term follow-up, the RV tissue Doppler flows and the LV MPI were found impaired.

Remodeling process in right and left ventricle after percutaneous atrial septal defect closure in adult patients.

The aim of this study was to evaluate acute cardiac remodeling after transcatheter closure of atrial septal defect (ASD) in adult patients. This study included 19 patients (40.0 ± 13.51 mean age) with secundum ASD who underwent successful transcatheter closure. All patients received routine transthoracic echocardiography, including tissue Doppler left ventricle (LV) and right ventricle (RV) myocardial performance indices (MPI), mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) before ASD closure, on first day, and at first and third months after closure. Left ventricle end-diastolic diameter (LVEDD) increased (37 ± 4 mm to 44 ± 5 mm, p<0.001); RVEDD decreased markedly after closure (40 ± 4 mm to 32 ± 5 mm, p<0.001); and differences existed in LV and RV adaptation. While MAPSE (1.87 ± 0.22 cm to 2.01 ± 0.23 cm, p<0.001) and LVMPI improved soon after procedure (0.44 ± 0.04 to 0.36 ± 0.03, p<0.001), RVMPI worsened until the first month post-procedure (0.25 ± 0.02 to 0.31 ± 0.03, p<0.001), but recovered by the third month follow-up visit (0.31 ± 0.03 to 0.27 ± 0.02, p<0.001). TAPSE remained unchanged (2.49 ± 0.46 cm to 2.51 ± 0.32 cm, p=0.078). Closure of ASD using the Amplatzer Septal Occluder device led to a decrease in RV size and an increase in LV size. In the early period, while LV function improved, RV function deteriorated, probably due to RV functional and anatomical differences.

Right Ventricle Functional Assessment

This review explores the historical development of conductance catheterization of the human right ventricle (RV) and its current diagnostic role in assessing RV function in an era of contemporary noninvasive imaging. Significant advances in echocardiography, cardiothoracic computed tomography, and cardiac magnetic resonance in the last decade have led a paradigm shift away from invasive hemodynamic assessment toward noninvasive measurement of RV function. However, imaging modalities are not without some disadvantages. For example, they do not provide the beat-to-beat pressure-volume assessment that is obtained by conductance catheterization, which is still arguably the gold standard for measuring cardiac performance. Right heart catheterization remains an integral part of the assessment of patients with RV dysfunction, and a burgeoning interest in early RV insufficiency in a range of cardiopulmonary diseases has brought the detailed interrogation of RV function back into focus. Although conductance volume assessment of the RV is more limited than the left ventricle, the scope for improving the understanding of RV adaptation to pulmonary and valvular pathologies and RV myocardial disease by using a conductance catheter still exists. We review the up-to-date functional applications of echocardiography and computed tomography/cardiac magnetic resonance to assess the RV and illustrate the potential of contemporary conductance catheter techniques to complement noninvasive imaging in the assessment of RV function.

Attenuated right ventricular energetics evaluated using 11C-acetate PET in patients with pulmonary hypertension

The right ventricle (RV) has a high capacity to adapt to pressure or volume overload before failing. However, the mechanisms of RV adaptation, in particular RV energetics, in patients with pulmonary hypertension (PH) are still not well understood. We aimed to evaluate RV energetics including RV oxidative metabolism, power and efficiency to adapt to increasing pressure overload in patients with PH using (11)C-acetate PET. In this prospective study, 27 patients with WHO functional class II/III PH (mean pulmonary arterial pressure 39.8 ± 13.5 mmHg) and 9 healthy individuals underwent (11)C-acetate PET. (11)C-acetate PET was used to simultaneously measure oxidative metabolism (k mono) for the left ventricle (LV) and RV. LV and RV efficiency were also calculated. The RV ejection fraction in PH patients was lower than in controls (p = 0.0054). There was no statistically significant difference in LV k mono (p = 0.09). In contrast, PH patients showed higher RV k mono than did controls (0.050 ± 0.009 min(-1) vs. 0.030 ± 0.006 min(-1), p < 0.0001). PH patients exhibited significantly increased RV power (p < 0.001) and hence increased RV efficiency compared to controls (0.40 ± 0.14 vs. 0.017 ± 0.12 mmHg·mL·min/g, p = 0.001). The RV oxidative metabolic rate was increased in patients with PH. Patients with WHO functional class II/III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing pulmonary arterial pressure.