scholarly journals Dynamic right ventricular–pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986243 ◽  
Author(s):  
Inderjit Singh ◽  
Farbod N. Rahaghi ◽  
Robert Naeije ◽  
Rudolf K.F. Oliveira ◽  
Rebecca R. Vanderpool ◽  
...  

Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular–pulmonary arterial [RV–PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV–PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO2 %predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV–PA coupling. The dynamic RV–PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO2 as PAH. In conclusion, dynamic rest-to-peak exercise RV–PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV–PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.

2017 ◽  
Vol 49 (6) ◽  
pp. 1601419 ◽  
Author(s):  
Roberto Badagliacca ◽  
Silvia Papa ◽  
Gabriele Valli ◽  
Beatrice Pezzuto ◽  
Roberto Poscia ◽  
...  

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.


2020 ◽  
Vol 10 (1) ◽  
pp. 204589401989751
Author(s):  
Geeshath Jayasekera ◽  
Kathryn S. Wilson ◽  
Hanna Buist ◽  
Rosemary Woodward ◽  
Aysel Uckan ◽  
...  

Cardiac magnetic resonance-derived ventricular variables are predictive of mortality in pulmonary arterial hypertension. Rodent models which emphasize ventricular function, allowing serial monitoring, are needed to identify pathophysiological features and novel therapies for pulmonary arterial hypertension. We investigated longitudinal changes in the Sugen–hypoxia model during disease progression. Sprague Dawley rats ( n = 32) were divided into two groups. (1) Sugen–hypoxia: a dose of subcutaneous Sugen-5416 and placed in hypobaric hypoxia for two weeks followed by normoxia for three weeks. (2) Normoxia: maintained at normal pressure for five weeks. Rats were examined at five or eight weeks with right-heart catheter, cardiac magnetic resonance, and autopsy. Compared to normoxic controls (23.9 ± 4.1 mmHg), right ventricular systolic pressure was elevated in Sugen–hypoxia rats at five and eight weeks (40.9 ± 15.5 mmHg, p = 0.026; 48.9 ± 9.6 mmHg, p = 0.002). Right ventricular end-systolic volume index was increased in eight weeks Sugen–hypoxia (0.28 ± 0.04 µlcm–2, p = 0.003) compared to normoxic controls (0.18 ±0.03 mlcm–2). There was progressive dilatation of the right ventricular at eight weeks Sugen–hypoxia compared to normoxic controls (0.75 ± 0.13 µlcm–2 vs 0.56 ± 0.1 µlcm–2 p = 0.02). Ventricle mass index by cardiac magnetic resonance at five weeks (0.34 ± 0.06, p = 0.003) and eight weeks Sugen–hypoxia (0.34 ± 0.06, p = 0.002) were higher than normoxic controls (0.21 ± 0.04). Stroke volume, right ventricular ejection fraction, and left ventricular variables were preserved in Sugen–hypoxia. Ventricular changes during the course of illness in a pulmonary arterial hypertension rodent model can be examined by cardiac magnetic resonance. These changes including right ventricular hypertrophy and subsequent dilatation are similar to those seen in pulmonary arterial hypertension patients. Despite the persisting pulmonary hypertension, there are features of adaptive cardiac remodeling through the study duration.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Natalia J Braams ◽  
Joost W van Leeuwen ◽  
anton vonk noordegraaf ◽  
Harm Jan Bogaard ◽  
Lilian J Meijboom ◽  
...  

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH)) are both associated with right ventricular (RV) failure and death. Although both conditions develop in the pre-capillary pulmonary vasculature, patient characteristics are different. CTEPH patients are older, predominantly male and more often have a history of venous thromboembolism. Therefore, the RV might be affected differently in CTEPH compared to iPAH. We aimed to compare RV adaptation in CTEPH and iPAH. Methods: Between 2000 and 2019 all treatment naive iPAH and CTEPH patients diagnosed in the Amsterdam UMC were included if a right heart catheterization and cardiac magnetic resonance imaging (CMR) were performed at the time of diagnosis. RV volumes, mass and function were assessed with CMR. RV contractility, afterload, RV-pulmonary artery (RV-PA) coupling and diastolic stiffness (Eed) were obtained using single beat pressure-volume loop analysis. Differences in RV phenotypes between iPAH and CTEPH were analyzed using multiple linear regression with interaction testing after correcting for confounders. Results: A total of 235 patients were included, 116 with CTEPH and 119 with iPAH. CTEPH patients were older, predominantly male, had a higher systemic blood pressure and a lower pulmonary vascular resistance at the time of diagnosis. After correcting for these confounders, RV function and RV-PA coupling were similar in both groups. However, CTEPH patients had a higher RV end-diastolic volume index (87±27 ml/m2 vs. 82±25 ml/m2), and a lower RV wall thickness (0,6±0,1 g/ml vs. 0,7±0,2 g/ml; figure 1A). The increase in afterload in CTEPH was associated with a disproportionally larger increase in diastolic stiffness compared to iPAH, independent of RV wall thickness (figure 1B). Conclusions: Despite a similar RV function, the RV in CTEPH is more dilated and stiffer than the RV in iPAH, independent of age, sex and afterload.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Raluca Jumatate ◽  
Annika Ingvarsson ◽  
Gustav Jan Smith ◽  
Anders Roijer ◽  
Ellen Ostenfeld ◽  
...  

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.


2017 ◽  
Vol 312 (4) ◽  
pp. H691-H700 ◽  
Author(s):  
Georgina Palau-Caballero ◽  
John Walmsley ◽  
Vanessa Van Empel ◽  
Joost Lumens ◽  
Tammo Delhaas

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.


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
H Sato ◽  
Y Someya ◽  
M Nishiyama ◽  
W Satoh ◽  
K Kumasaka ◽  
...  

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 &lt; 0.05) than that between RVEF and dF/dtmax (r = 0.24). In 5 MCT-rats with preserved RVEF (&gt;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 (&gt; -20%)/preserved-RVEF (&gt; 50%), MCT-rats with increased-RVGCS (&lt; -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.


2018 ◽  
Vol 8 (2) ◽  
pp. 204589401876535 ◽  
Author(s):  
Toshitaka Nakaya ◽  
Ichizo Tsujino ◽  
Hiroshi Ohira ◽  
Takahiro Sato ◽  
Taku Watanabe ◽  
...  

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.


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