scholarly journals CMR feature tracking cloud assess right ventricular functional reserve with pulmonary arterial hypertension

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
H Sato ◽  
Y Someya ◽  
M Nishiyama ◽  
W Satoh ◽  
K Kumasaka ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Feature Tracking ◽  
Global Longitudinal Strain ◽  
Early Career ◽  
Functional Reserve ◽  
Cine Mr ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI, Grant-in-Aid for Early-Career Scientists. Background   Pulmonary arterial hypertension (PAH) remains a fatal disorder characterized by elevated pulmonary arterial pressure. Survival of the patients with PAH is determined from right ventricular (RV) function. CMR has become an attractive modality for following up and providing prognosis in such patients, and CMR feature tracking has been used as a newer useful parameter to assess RV function. However, it has not yet been determined whether CMR feature tracking can assess RV functional reserve in patients with PAH. Purpose We investigated whether CMR feature tracking can estimate RV functional reserve using a rat model with PAH. Methods  Rats were received injections with monocrotaline (MCT-rats, n = 19) or solvent (Ctr-rats, n = 5). Four weeks after the injections, we performed CMR on 7-T MRI scanner and imaged retrospective ECG-gated cine MR (16 phases/beat). RV ejection fraction (RVEF) and RV strain were analyzed before and after addition of 0.5∼3 nmol endothelin-1 (ET-1). After the measurements, we dissected trabeculae (length = 1.45 ± 0.07 mm, width = 334 ± 27 µm, thickness = 114 ± 6 µm) from the RVs of rat hearts. Trabeculae were electrically stimulated with 2-s intervals at extracellular Ca2+ of 0.7 and 2.0 mmol/L (24°C). Force and maximum dF/dt (dF/dtmax) were then measured using a silicon strain gauge in the absence and presence of 0.1 µM ET-1. Results  MCT-rats showed higher systolic RV pressure (RVP), lower RVEF, and lower RV global longitudinal strain (RVGLS) in CMR imaging and showed lower developed force and lower dF/dtmax in their trabeculae. Correlation between RVGLS and dF/dtmax was higher (r = 0.53, p < 0.05) than that between RVEF and dF/dtmax (r = 0.24). In 5 MCT-rats with preserved RVEF (>50%), RVGLS had already been reduced, suggesting that RVGLS is reduced earlier than RVEF. ET-1 increased developed force and dF/dtmax in trabeculae from MCT-rats (12.2 ± 5.7 to 17.4 ± 3.1 mN/mm2 and 0.08 ± 0.03 to 0.14 ± 0.06 mN/mm2/sec, respectively, n = 6), and ET-1 also increased RVP in MCT-rats and Ctr-rats (49.0 ± 19.3 to 59.7 ± 16.8 mmHg in MCT-rats, n = 6, 17.3 ± 7.5 to 20.4 ± 7.8 mmHg in Ctr-rats, n = 2). According to RV global circumferential strain (RVGCS) and RVEF, we could divide MCT-rats into three groups as follows: MCT-rats with reduced-RVGCS (> -20%)/preserved-RVEF (> 50%), MCT-rats with increased-RVGCS (< -30%)/preserved-RVEF and MCT-rats with reduced-RVGCS/reduced-RVEF. ET-1 reduced RVGCS in MCT-rats with reduced-RVGCS/preserved-RVEF, while ET-1 did not change RVGCS in MCT-rats with increased-RVGCS/preserved-RVEF. MCT-rats with reduced-RVGCS/reduced-RVEF died after injection of ET-1.  In Ctr-rats, ET-1 did not change RVGCS and RVEF.  These results suggest that RVGCS can be useful to assess RV functional reserve. Conclusion  CMR feature tracking can estimate RV functional reserve earlier and more accurately than RVEF in rats with PAH.  RV strain may become an important parameter to assess RV functional reserve in patients with PAH.

scholarly journals Right ventricular stroke work index by echocardiography in adult patients with pulmonary arterial hypertension

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Raluca Jumatate ◽  
Annika Ingvarsson ◽  
Gustav Jan Smith ◽  
Anders Roijer ◽  
Ellen Ostenfeld ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Adult Patients ◽  
Stroke Work ◽  
Non Invasive ◽  
Work Index ◽  
Stroke Work Index ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Background In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, resulting in a poor prognosis. In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) measured by right heart catheterization (RHC) represents a promising index for RV function. The aim of the present study was to comprehensively evaluate non-invasive measures to calculate RVSWI derived by echocardiography (RVSWIECHO) using RHC (RVSWIRHC) as a reference in adult PAH patients. Methods Retrospectively, 54 consecutive treatment naïve patients with PAH (65 ± 13 years, 36 women) were analyzed. Echocardiography and RHC were performed within a median of 1 day [IQR 0–1 days]. RVSWIRHC was calculated as: (mean pulmonary arterial pressure (mPAP)—mean right atrial pressure (mRAP)) x stroke volume index (SVI)RHC. Four methods for RVSWIECHO were evaluated: RVSWIECHO-1 = Tricuspid regurgitant maximum pressure gradient (TRmaxPG) x SVIECHO, RVSWIECHO-2 = (TRmaxPG-mRAPECHO) x SVIECHO, RVSWIECHO-3 = TR mean gradient (TRmeanPG) x SVIECHO and RVSWIECHO-4 = (TRmeanPG–mRAPECHO) x SVIECHO. Estimation of mRAPECHO was derived from inferior vena cava diameter. Results RVSWIRHC was 1132 ± 352 mmHg*mL*m−2. In comparison with RVSWIRHC in absolute values, RVSWIECHO-1 and RVSWIECHO-2 was significantly higher (p < 0.001), whereas RVSWIECHO-4 was lower (p < 0.001). No difference was shown for RVSWIECHO-3 (p = 0.304). The strongest correlation, with RVSWIRHC, was demonstrated for RVSWIECHO-2 (r = 0.78, p < 0.001) and RVSWIECHO-1 ( r = 0.75, p < 0.001). RVSWIECHO-3 and RVSWIECHO-4 had moderate correlation (r = 0.66 and r = 0.69, p < 0.001 for all). A good agreement (ICC) was demonstrated for RVSWIECHO-3 (ICC = 0.80, 95% CI 0.64–0.88, p < 0.001), a moderate for RVSWIECHO-4 (ICC = 0.73, 95% CI 0.27–0.87, p < 0.001) and RVSWIECHO-2 (ICC = 0.55, 95% CI − 0.21–0.83, p < 0.001). A poor ICC was demonstrated for RVSWIECHO-1 (ICC = 0.45, 95% CI − 0.18–0.77, p < 0.001). Agreement of absolute values for RVSWIECHO-1 was − 772 ± 385 (− 50 ± 20%) mmHg*mL*m−2, RVSWIECHO-2 − 600 ± 339 (-41 ± 20%) mmHg*mL*m−2, RVSWIECHO-3 42 ± 286 (5 ± 25%) mmHg*mL*m−2 and for RVSWIECHO-4 214 ± 273 (23 ± 27%) mmHg*mL*m−2. Conclusion The correlation with RVSWIRHC was moderate to strong for all echocardiographic measures, whereas only RVSWIECHO-3 displayed high concordance of absolute values. The results, however, suggest that RVSWIECHO-1 or RVSWIECHO-3 could be the preferable echocardiographic methods. Prospective studies are warranted to evaluate the clinical utility of such measures in relation to treatment response, risk stratification and prognosis in patients with PAH.

Right ventricular longitudinal strain with CMR can more accurately estimate right ventricular functional reserve in rats with pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Sato ◽  
Y Someya ◽  
Y Takahashi ◽  
K Kumasaka ◽  
W Sato ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Longitudinal Strain ◽  
Weight Ratio ◽  
Contractile Properties ◽  
Funding Source ◽  
Functional Reserve ◽  
Pulmonary Arterial ◽  
Cmr Imaging

Abstract Background Right ventricular (RV) function is an important prognostic factor in patients with pulmonary arterial hypertension (PAH). Recently, CMR has become an attractive modality for follow up and providing prognosis in the patients, and strain has been used as a newer parameter to assess contractile properties of ventricle. It has not yet been established, however, whether RV strain with CMR can estimate RV functional reserve in the patients with PAH. Purpose We focused on CMR imaging of RV, investigating whether RV longitudinal strain can estimate RV functional reserve using a rat model with PAH. Method Rats were given a subcutaneous injection of 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). Four weeks after the injection, 25% of MCT-rats died due to RV failure. In the survivors of MCT- (n=19) and Ctr-rats (n=5), retrospective ECG-gated cine MR (16 phases/beat) was imaged with a 7T scanner. Subsequently, we measured RV pressure (RVP) via right internal jugular vein and dissected trabeculae (length = 1.45±0.07 mm, width = 334±27 μm, thickness = 114±6 μm) from RVs. We calculated weight ratio of RV free wall to left ventricle (LV) by RV/(LV+septum). Trabeculae were electrically stimulated with 2-s stimulus intervals, and force was measured using a silicon strain gauge (0.7 mM extracellular Ca2+, 24°C). To determine contractile properties of RV muscle, dF/dt was calculated. Using CMR imaging, we measured RV ejection fraction (RVEF) and RV longitudinal strain (RVLS). To modulate RVP, we intravenously injected 5 nmol endothelin-1 (ET-1) and again measured RVEF and RVLS. Results MCT-rats showed higher systolic RVP (62.5±16.6 vs. 25.9±1.86 mmHg, p&lt;0.01) and higher weight ratio of RV (0.60±0.03 vs. 0.28±0.02, p&lt;0.05). In CMR imaging, MCT-rats showed lower RVEF (36.1±11.2 vs. 64.8±8.4%, p&lt;0.001) and lower RVLS (−18±9 vs. −30±1%, p&lt;0.05). In trabeculae from RVs, MCT-rats showed lower developed force and lower dF/dt (p&lt;0.01). Correlation between RVLS and dF/dt was higher (n=20, r=0.53, p&lt;0.05) than that between RVEF and dF/dt (r=0.24). In addition, RVLS and dF/dt had already been decreased in 5 MCT-rats with relatively preserved RVEF (&gt;50%), suggesting that RVLS decreases earlier than RVEF in MCT-rats. Ten minutes after the injection of ET-1, RVP was increased from 49.4±7.9 to 57.9±6.4 mmHg in MCT-rats (n=6). In MCT-rats with preserved RVEF and decreased RVLS, the increase in RVP chiefly decreased RVEF while it did not change RVLS and RVEF in Ctr-rats, meaning that RV functional reserve had been decreased in MCT-rats. In trabeculae, developed force and dF/dt were increased after the addition of 0.1 μM ET-1 in MCT- (n=11, p&lt;0.01) and Ctr-rats (n=4, p&lt;0.01). Conclusion These results suggest that in rats with PAH, RVLS obtained from CMR can estimate RV functional reserve earlier and more accurately than RVEF. Therefore, RV strain with CMR may become an important parameter to assess RV functional reserve in patients with PAH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Young Scientists

Why septal motion is a marker of right ventricular failure in pulmonary arterial hypertension: mechanistic analysis using a computer model

2017 ◽  
Vol 312 (4) ◽  
pp. H691-H700 ◽  
Author(s):  
Georgina Palau-Caballero ◽  
John Walmsley ◽  
Vanessa Van Empel ◽  
Joost Lumens ◽  
Tammo Delhaas
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pressure Gradient ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Ventricular Relaxation ◽  
Pulmonary Arterial ◽  
Rv Function ◽  
Septal Motion

Rapid leftward septal motion (RLSM) during early left ventricular (LV) diastole is observed in patients with pulmonary arterial hypertension (PAH). RLSM exacerbates right ventricular (RV) systolic dysfunction and impairs LV filling. Increased RV wall tension caused by increased RV afterload has been suggested to cause interventricular relaxation dyssynchrony and RLSM in PAH. Simulations using the CircAdapt computational model were used to unravel the mechanism underlying RLSM by mechanistically linking myocardial tissue and pump function. Simulations of healthy circulation and mild, moderate, and severe PAH were performed. We also assessed the effects on RLSM when PAH coexists with RV or LV contractile dysfunction. Our results showed prolonged RV shortening in PAH causing interventricular relaxation dyssynchrony and RLSM. RLSM was observed in both moderate and severe PAH. A negative transseptal pressure gradient only occurred in severe PAH, demonstrating that negative pressure gradient does not entirely explain septal motion abnormalities. PAH coexisting with RV contractile dysfunction exacerbated both interventricular relaxation dyssynchrony and RLSM. LV contractile dysfunction reduced both interventricular relaxation dyssynchrony and RLSM. In conclusion, dyssynchrony in ventricular relaxation causes RLSM in PAH. Onset of RLSM in patients with PAH appears to indicate a worsening in RV function and hence can be used as a sign of RV failure. However, altered RLSM does not necessarily imply an altered RV afterload, but it can also indicate altered interplay of RV and LV contractile function. Reduction of RLSM can result from either improved RV function or a deterioration of LV function. NEW & NOTEWORTHY A novel approach describes the mechanism underlying abnormal septal dynamics in pulmonary arterial hypertension. Change in motion is not uniquely induced by altered right ventricular afterload, but also by altered ventricular relaxation dyssynchrony. Extension or change in motion is a marker reflecting interplay between right and left ventricular contractility.

scholarly journals Amelioration of right ventricular systolic function and stiffness in a patient with idiopathic pulmonary arterial hypertension treated with oral triple combination therapy

2018 ◽  
Vol 8 (2) ◽  
pp. 204589401876535 ◽  
Author(s):  
Toshitaka Nakaya ◽  
Ichizo Tsujino ◽  
Hiroshi Ohira ◽  
Takahiro Sato ◽  
Taku Watanabe ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Systolic Function ◽  
Right Atrial ◽  
Arterial Elastance ◽  
Triple Combination Therapy ◽  
Pulmonary Vasodilators ◽  
Pulmonary Arterial ◽  
Rv Function

Right ventricular (RV) function is an important determinant of the prognosis in patients with pulmonary arterial hypertension (PAH). In the context of recent therapeutic progress, there is an increasing need for better monitoring of RV function for management of PAH. We present the case of a 42-year-old woman with idiopathic PAH who was treated with three oral pulmonary vasodilators, i.e. tadalafil, ambrisentan, and beraprost. At the baseline assessment, the mean pulmonary arterial pressure (mPAP) was 45 mmHg, cardiac index (CI) was 1.36 L/min/m2, and pulmonary vascular resistance (PVR) was elevated to 21.3 Wood units (WU). However, three months after the start of combination treatment, mPAP and PVR decreased to 42 mmHg and 7.5 WU, respectively, and conventional indices of RV function, such as CI, right atrial area, and right atrial pressure also improved. Beyond three months, however, there were no further improvements in mPAP, PVR, or indices of RV function. In addition, we calculated three recently introduced indices of intrinsic RV function: end-systolic elastance (Ees; an index of RV contractility), Ees/arterial elastance ratio (Ees/Ea; an index of RV/pulmonary arterial coupling), and β (an index of RV stiffness) using cardiac magnetic resonance imaging and Swan-Ganz catheterization measurements. Notably, in contrast to conventional parameters, Ees, Ees/Ea, and β showed persistent improvement during the entire two-year follow-up. The application of Ees, Ees/Ea, and β may play an additional role in a comprehensive assessment of RV function in PAH.

scholarly journals Impaired right ventricular lusitropy is associated with ventilatory inefficiency in pulmonary arterial hypertension

2019 ◽  
Vol 54 (5) ◽  
pp. 1900342 ◽  
Author(s):  
Khodr Tello ◽  
Antonia Dalmer ◽  
Rebecca Vanderpool ◽  
Hossein A. Ghofrani ◽  
Robert Naeije ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Stiffness ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Minute Ventilation ◽  
Cardiopulmonary Exercise Testing ◽  
Arterial Elastance ◽  
Pulmonary Arterial ◽  
Rv Function

Cardiopulmonary exercise testing (CPET) is an important tool for assessing functional capacity and prognosis in pulmonary arterial hypertension (PAH). However, the associations of CPET parameters with the adaptation of right ventricular (RV) function to afterload remain incompletely understood.In this study, 37 patients with PAH (idiopathic in 31 cases) underwent single-beat pressure–volume loop measurements of RV end-systolic elastance (Ees), arterial elastance (Ea) and diastolic elastance (Eed). Pulmonary arterial stiffness was assessed by magnetic resonance imaging. The results were correlated to CPET variables. The predictive relevance of RV function parameters for clinically relevant ventilatory inefficiency, defined as minute ventilation/carbon dioxide production (V′E/V′CO2) slope >48, was evaluated using logistic regression analysis.The median (interquartile range) of the V′E/V′CO2 slope was 42 (32–52) and the V′E/V′CO2 nadir was 40 (31–44). The mean±sd of peak end-tidal carbon dioxide tension (PETCO2) was 23±8 mmHg. Ea, Eed and parameters reflecting pulmonary arterial stiffness (capacitance and distensibility) correlated with the V′E/V′CO2 slope, V′E/V′CO2 nadir, PETCO2 and peak oxygen pulse. RV Ees and RV–arterial coupling as assessed by the Ees/Ea ratio showed no correlations with CPET parameters. Ea (univariate OR 7.28, 95% CI 1.20–44.04) and Eed (univariate OR 2.21, 95% CI 0.93–5.26) were significantly associated with ventilatory inefficiency (p<0.10).Our data suggest that impaired RV lusitropy and increased afterload are associated with ventilatory inefficiency in PAH.

Right Ventricular Dysfunction in Pulmonary Arterial Hypertension: Cellular and Hemodynamic Changes in a Mouse Model

2013 ◽  
Author(s):  
Zhijie Wang ◽  
Jitandrakumar R. Patel ◽  
David A. Schreier ◽  
Richard Moss ◽  
Timothy A. Hacker ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Mouse Model ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Right Ventricular Dysfunction ◽  
Severe Form ◽  
Rapid Progression ◽  
Vegf Receptor ◽  
Pulmonary Arterial ◽  
Rv Function

Pulmonary arterial hypertension (PAH) is the most severe form of pulmonary hypertension due to its rapid progression to right ventricular (RV) failure. Until the recent combination of chronic hypoxia with VEGF receptor blockage by SU5416 [1], there was no mouse model for severe PAH. This new model (HySu) recapitulates hallmarks of human PAH, especially distal arteriolar neointima formation and obliteration [1]. However, the changes in RV function in this model have not been examined. Here we investigate the hypothesis that the HySu mouse model mimics the progression of RV dysfunction found in PAH clinically from compensatory to maladaptive RV remodeling.

scholarly journals Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension

2017 ◽  
Vol 49 (6) ◽  
pp. 1601419 ◽  
Author(s):  
Roberto Badagliacca ◽  
Silvia Papa ◽  
Gabriele Valli ◽  
Beatrice Pezzuto ◽  
Roberto Poscia ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Exercise Capacity ◽  
Speckle Tracking ◽  
Multivariate Analyses ◽  
Right Atrial ◽  
Pulmonary Arterial ◽  
Rv Function

Survival in patients with pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to afterload. How altered RV function impacts on exercise capacity in PAH is not exactly known.104 idiopathic PAH (IPAH) patients aged 52±14 years underwent a diagnostic right heart catheterisation, a comprehensive echocardiography including two-dimensional speckle tracking for RV dyssynchrony evaluation and a cardiopulmonary exercise test. Multivariate analyses were performed to identify independent predictors of peak oxygen uptake (peakV′O2).A first multivariate analysis of only resting haemodynamic variables identified cardiac index, right atrial (RA) pressure and pulmonary arterial compliance as independent predictors, with low predictive capacity (r2=0.31; p<0.001). A second multivariate analysis model which considered only echocardiographic parameters but without RV dyssynchrony, identified RV fractional area change (FAC) and RA area as independent predictors with still low predictivity (r2=0.35; p<0.001). Adding RV dyssynchrony to the second model increased its predictivity (r2=0.48; p<0.001). Repetition of the three multivariate analyses in patients with preserved RVFAC confirmed that inclusion of RV dyssynchrony results in the highest predictive capability of peakV′O2(r2=0.53; p=0.001).A comprehensive echocardiography with speckle tracking-derived assessment of the heterogeneity of RV contraction improves the prediction of aerobic exercise capacity in IPAH.

scholarly journals Acetazolamide Improves Right Ventricular Function and Metabolic Gene Dysregulation in Experimental Pulmonary Arterial Hypertension

2021 ◽  
Vol 8 ◽  
Author(s):  
Fotios Spyropoulos ◽  
Zoe Michael ◽  
Benjamin Finander ◽  
Sally Vitali ◽  
Kosmas Kosmas ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Rat Model ◽  
Metabolic Profile ◽  
Left Ventricular ◽  
Beta Oxidation ◽  
Pulmonary Arterial ◽  
Rv Function

Background: Right ventricular (RV) performance is a key determinant of mortality in pulmonary arterial hypertension (PAH). RV failure is characterized by metabolic dysregulation with unbalanced anaerobic glycolysis, oxidative phosphorylation, and fatty acid oxidation (FAO). We previously found that acetazolamide (ACTZ) treatment modulates the pulmonary inflammatory response and ameliorates experimental PAH.Objective: To evaluate the effect of ACTZ treatment on RV function and metabolic profile in experimental PAH.Design/Methods: In the Sugen 5416/hypoxia (SuHx) rat model of severe PAH, RV transcriptomic analysis was performed by RNA-seq, and top metabolic targets were validated by RT-PCR. We assessed the effect of therapeutic administration of ACTZ in the drinking water on hemodynamics by catheterization [right and left ventricular systolic pressure (RVSP and LVSP, respectively)] and echocardiography [pulmonary artery acceleration time (PAAT), RV wall thickness in diastole (RVWT), RV end-diastolic diameter (RVEDD), tricuspid annular plane systolic excursion (TAPSE)] and on RV hypertrophy (RVH) by Fulton's index (FI) and RV-to-body weight (BW) ratio (RV/BW). We also examined myocardial histopathology and expression of metabolic markers in RV tissues.Results: There was a distinct transcriptomic signature of RVH in the SuHx model of PAH, with significant downregulation of metabolic enzymes involved in fatty acid transport, beta oxidation, and glucose oxidation compared to controls. Treatment with ACTZ led to a pattern of gene expression suggestive of restored metabolic balance in the RV with significantly increased beta oxidation transcripts. In addition, the FAO transcription factor peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) was significantly downregulated in untreated SuHx rats compared to controls, and ACTZ treatment restored its expression levels. These metabolic changes were associated with amelioration of the hemodynamic and echocardiographic markers of RVH in the ACTZ-treated SuHx animals and attenuation of cardiomyocyte hypertrophy and RV fibrosis.Conclusion: Acetazolamide treatment prevents the development of PAH, RVH, and fibrosis in the SuHx rat model of severe PAH, improves RV function, and restores the RV metabolic profile.

Abstract 17254: Right Ventricular Myoarchitecture is Associated With RV Function in Pulmonary Arterial Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Denielli da Silva Goncalves Bos ◽  
Dana Leichter ◽  
Alexander Vang ◽  
Ana Fernandez Nicolas ◽  
Mohsen Nowruzpour ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Global Longitudinal Strain ◽  
Male Rats ◽  
High Angular Resolution ◽  
Fiber Direction ◽  
Angle Distribution ◽  
Functional Parameters ◽  
Pulmonary Arterial

Introduction: Right Ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) is the major cause of mortality. Myocardial architecture determines the basis of heart function and can be assessed by generalized Q-space imaging by MRI (GQI), yet remains understudied in the RV. Therefore, we assessed myocardial fiber architecture patterns and correlated them with disease severity in two models of PAH. Methods: PAH was induced in Sprague-Dawley (SD) and Fischer (CDF) male rats by SU5416 (20 mg/kg; s.c.) followed by 3 wks of hypoxia (10% FiO2). Controls received vehicle and were kept at normoxia. After 4 wks, echocardiography and hemodynamics were performed. Whole hearts were resected in some animals (SD n=9, CDF n=8) and imaged via high-angular resolution GQI using a 7T magnet (512 directions, b=750 s/mm2). Patterns of inter-voxel coherence (tractography) were reconstructed, and transmural helix angle distribution (HAD) were assessed at 3 points across the LV and RV (Panel A) and normalized to a common vector. Finite-element models were developed via registering myofiber direction to anatomical mesh. Results: Both animal strains developed PAH, however CDF rats had lower pulmonary artery acceleration time (14±0.6 vs. 19±1.3 ms, p<0.05) and TAPSE (1.5±0.06 vs. 1.9±0.09 mm, p<0.05) and higher RV afterload (1023±167 vs. 285±17, mmHg/mL p<0.05) compared to SD. PAH was associated with steeper slope of the RV transmural HAD in both SD and CDF vs. controls and slightly higher in CDF-PAH compared to SD-PAH (Panel B). No significant changes were noted in the LV (Panel C). Moreover, the RV HAD slope significantly correlated to RV functional parameters (TAPSE r= 0.58, RV global longitudinal strain r= -0.49) and RA area (r= -0.58). Transmural and regional variation in fiber direction was also observed (Panel D). Conclusion: Myoarchitectural analysis of the RV in the setting of PAH reveals that myocardial HAD relates to functional parameters and may be a marker of maladaptation.

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