scholarly journals Sex Differences in Right Ventricular Dysfunction: Insights From the Bench to Bedside

2021 ◽  
Vol 11 ◽  
Author(s):  
Jennifer Keen ◽  
Sasha Z. Prisco ◽  
Kurt W. Prins
Keyword(s):  
Sex Differences ◽  
Right Ventricular ◽  
Sex Hormones ◽  
Arrhythmogenic Right Ventricular Cardiomyopathy ◽  
Unmet Need ◽  
Right Ventricular Dysfunction ◽  
Sex Hormone ◽  
Life Threatening ◽  
Pulmonary Arterial ◽  
Rv Function

There are inherent distinctions in right ventricular (RV) performance based on sex as females have better RV function than males. These differences are magnified and have very important prognostic implications in two RV-centric diseases, pulmonary hypertension (PH), and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). In both PH and ARVC/D, RV dysfunction results in poor patient outcomes. However, there are no currently approved therapies specifically targeting the failing RV, an important unmet need for these two life-threatening disorders. In this review, we highlight human data demonstrating divergent RV phenotypes in healthy, PH, and ARVC/D patients based on sex. Furthermore, we discuss the links between estrogen (the female predominant sex hormone), testosterone (the male predominant sex hormone), and dehydroepiandrosterone (a precursor hormone for multiple sex hormones in males and females) and RV function in both disorders. To provide potential mechanistic insights into sex differences in RV function, we review data that investigate how sex hormones combat or contribute to pathophysiological changes in the RV. Finally, we highlight the ongoing clinical trials in pulmonary arterial hypertension targeting estrogen and dehydroepiandrosterone signaling. Hopefully, a greater understanding of the factors that promote superior RV function in females will lead to novel therapeutic approaches to combat RV dysfunction in PH and ARVC/D.

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 Exaggerated Right Ventricular Dysfunction in Females with Group 3 Pulmonary Hypertension

2021 ◽  
Author(s):  
Sasha Z Prisco ◽  
Felipe Kazmirczak ◽  
Kurt W Prins ◽  
Thenappan Thenappan
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Dysfunction ◽  
Right Ventricular Dysfunction ◽  
Female Group ◽  
Biological Sex ◽  
Effects Of Ph ◽  
Pulmonary Arterial ◽  
Group 3 ◽  
Rv Function

Group 3 pulmonary hypertension (PH) patients have disproportionate right ventricular dysfunction (RVD) as compared to pulmonary arterial hypertension (PAH) patients, but the cause of the divergent RV phenotypes is unknown. One potential mechanism may be biological sex as females have better RV function than males. However, the combined effects of PH type and sex on RV function are unexplored. Therefore, we evaluated how sex and PH etiology modulated RVD in a single-center cohort study. Male sex was not associated with significant differences in RV function when comparing PH etiologies. However, female Group 3 patients had more pronounced RVD than female PAH patients. In particular, Group 3 females had marked reduction in RV function when pulmonary vascular resistance was matched. Group 3 females were older than PAH females, but the exaggerated RVD was still observed in postmenopausal (age≥55) Group 3 females. This suggests lung disease exacerbates RVD in Group 3 females.

scholarly journals Regulatory Role of Sex Hormones in Cardiovascular Calcification

2021 ◽  
Vol 22 (9) ◽  
pp. 4620
Author(s):  
Holly J. Woodward ◽  
Dongxing Zhu ◽  
Patrick W. F. Hadoke ◽  
Victoria E. MacRae
Keyword(s):  
Cardiovascular Disease ◽  
Sex Differences ◽  
Sexual Dimorphism ◽  
Aortic Stenosis ◽  
Sex Hormones ◽  
Sex Hormone ◽  
Increased Risk ◽  
Male Sex ◽  
Primary Male

Sex differences in cardiovascular disease (CVD), including aortic stenosis, atherosclerosis and cardiovascular calcification, are well documented. High levels of testosterone, the primary male sex hormone, are associated with increased risk of cardiovascular calcification, whilst estrogen, the primary female sex hormone, is considered cardioprotective. Current understanding of sexual dimorphism in cardiovascular calcification is still very limited. This review assesses the evidence that the actions of sex hormones influence the development of cardiovascular calcification. We address the current question of whether sex hormones could play a role in the sexual dimorphism seen in cardiovascular calcification, by discussing potential mechanisms of actions of sex hormones and evidence in pre-clinical research. More advanced investigations and understanding of sex hormones in calcification could provide a better translational outcome for those suffering with cardiovascular calcification.

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.

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 Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes

2019 ◽  
Vol 316 (2) ◽  
pp. H326-H334 ◽  
Author(s):  
Tayler A. Buchan ◽  
Stephen P. Wright ◽  
Sam Esfandiari ◽  
Felipe C. Fuchs ◽  
Taylor Gray ◽  
...  
Keyword(s):  
Steady State ◽  
Right Ventricular ◽  
Exercise Intensity ◽  
Prolonged Exercise ◽  
Middle Aged ◽  
Functional Responses ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Wedge Pressure ◽  
Rv Function

Right ventricular (RV) function is closely coupled to pulmonary arterial (PA) hemodynamics and is believed to decline with prolonged exercise. A linear pressure-flow relationship is thought to exist between PA pressures and increasing exercise intensity in athletes, yet a paucity of directly measured pulmonary hemodynamic data exists supporting this contention. We sought to describe the PA pressure, PA wedge pressure (PAWP), and RV functional responses to brief and prolonged exercise in endurance-trained athletes. Twenty-one healthy athletes (54 ± 5 yr) underwent right heart catheterization to assess pulmonary hemodynamics during graded, submaximal exercise. Measurements were made at rest and during three stages of steady-state, semiupright cycle ergometry at heart rates of 100 beats/min (EX1), 130 beats/min (EX2), and 150 beats/min (EX3). Five athletes completed an additional 34 min at 130 beats/min for a total exercise time of 60 min [prolonged exercise (PLG)]. PA pressures and PAWP increased significantly at EX1 without a further rise at EX2, EX3, or PLG. PAWP adjusted for absolute work rate demonstrated a significant decline as exercise intensity increased from EX1 to EX2. The resistance compliance time constant decreased at EX1 without further changes at EX2, EX3, and prolonged exercise. RV function did not decline during PLG. After an initial rise in PA pressure and PAWP during early, nonsteady-state exercise, values remained constant despite increases in exercise intensity and duration. These data indicate that in healthy, middle-aged endurance-trained athletes, the PA and pulmonary venous/left atrial compartments rapidly accommodate high conduit flows produced during intensive and prolonged exercise while maintaining RV function. NEW & NOTEWORTHY The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout of endurance training integrating a transition from rest to exercise with successive increases in intensity, progressing to steady-state, sustained exercise. We demonstrated a remarkably constant response of the PA and PA wedge pressure during incremental, steady-state exercise and that no changes occur in pulmonary pressures throughout prolonged exercise, concomitant to a preservation of RV performance.

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 &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.

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