Sex Differences in Right Ventricular-Pulmonary Arterial Coupling in Pulmonary Arterial Hypertension.
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ABSTRACT:
SUBMITTER: Tello K
PROVIDER: S-EPMC7528786 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
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Sex Differences in Right Ventricular-Pulmonary Arterial Coupling in Pulmonary Arterial Hypertension.
Tello Khodr K Richter Manuel J MJ Yogeswaran Athithan A Ghofrani Hossein A HA Naeije Robert R Vanderpool Rebecca R Gall Henning H Tedford Ryan J RJ Seeger Werner W Lahm Tim T
American journal of respiratory and critical care medicine 20201001 7
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Project description:Background Although right ventricular (RV) to pulmonary arterial (RV-PA) coupling is considered the gold standard in assessing RV dysfunction, its ability to predict clinically significant outcomes is poorly understood. We assessed the ability of RV-PA coupling, determined by the ratio of multi-beat (MB) end-systolic elastance (Ees) to effective arterial elastance (Ea), to predict clinical outcomes. Methods and Results Twenty-six subjects with pulmonary arterial hypertension (PAH) underwent same-day cardiac magnetic resonance imaging, right heart catheterization, and RV pressure-volume assessment with MB determination of Ees/Ea. RV ejection fraction (RVEF), stroke volume/end-systolic volume, and single beat-estimated Ees/Ea were also determined. Patients were treated with standard therapies and followed prospectively until they met criteria of clinical worsening (CW), as defined by ≥10% decline in 6-minute walk distance, worsening World Health Organization (WHO) functional class, PAH therapy escalation, RV failure hospitalization, or transplant/death. Subjects were 57±14 years, largely WHO class III (50%) at enrollment, with preserved average RV ejection fraction (RVEF) (47±11%). Mean follow-up was 3.2±1.3 years. Sixteen (62%) subjects met CW criteria. MB Ees/Ea was significantly lower in CW subjects (0.7±0.5 versus 1.3±0.8, P=0.02). The optimal MB Ees/Ea cut-point predictive of CW was 0.65, defined by ROC (AUC 0.78, P=0.01). MB Ees/Ea below this cut-point was significantly associated with time to CW (hazard ratio 5.1, P=0.001). MB Ees/Ea remained predictive of outcomes following multivariate adjustment for timing of PAH diagnosis and PAH diagnosis subtype. Conclusions RV-PA coupling as measured by MB Ees/Ea has prognostic significance in human PAH, even in a cohort with preserved RVEF.
| S-EPMC7660856 | biostudies-literature
Project description:BackgroundMultiparametric risk assessment is used in pulmonary arterial hypertension (PAH) to target therapy. However, this strategy is imperfect because most patients remain at intermediate or high risk after initial treatment, with low risk being the goal. Metrics of right ventricular (RV) adaptation are promising tools that may help refine our therapeutic strategy.Research questionDoes RV adaptation predict therapeutic response over time?Study design and methodsWe evaluated 52 incident treatment-naive patients with advanced PAH by catheterization and cardiac imaging longitudinally at baseline, follow-up 1 (∼3 months), and follow-up 2 (∼18 months). All patients received goal-directed therapy with parenteral treprostinil and/or combination therapy with treatment escalation if functional class I or II was not achieved. On the basis of their therapeutic response, patients were evaluated at follow-up 1 as nonresponders (died) or as responders, and again at follow-up 2 as super-responders (low risk) or partial responders (high/intermediate risk). Multiparametric risk was based on a simplified European Respiratory Society/European Society of Cardiology guideline score. RV adaptation was evaluated with the single-beat coupling ratio (Ees/Ea) and diastolic function with diastolic elastance (Eed). Data are expressed as mean ± SD or as OR (95% CI).ResultsNine patients (17%) were nonresponders. PAH-directed therapy improved the European Respiratory Society low-risk score from 1 (2%) at baseline to 23 (55%) at follow-up 2. Ees/Ea at presentation was nonsignificantly higher in responders (0.9 ± 0.4) vs nonresponders (0.6 ± 0.4; P = .09) but could not be used to predict super-responder status at follow-up 2 (OR, 1.40 [95% CI, 0.28-7.0]; P = .84). Baseline RV ejection fraction and change in Eed were successfully used to predict super-responder status at follow-up 2 (OR, 1.15 [95% CI, 1.0-1.27]; P = .009 and OR, 0.29 [95% CI, 0.86-0.96]; P = .04, respectively).InterpretationIn patients with advanced PAH, RV-pulmonary arterial coupling could not discriminate irreversible RV failure (nonresponders) at presentation but showed a late trend to improvement by follow-up 2. Early change in Eed and baseline RV ejection fraction were the best predictors of therapeutic response.
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Project description:RationalePatients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) continue to have an unacceptably high mortality rate despite the progress achieved with pulmonary arterial vasodilator therapies.ObjectivesWe sought to determine whether SSc-PAH is a clinically distinct pulmonary vascular disease phenotype when compared with idiopathic pulmonary arterial hypertension (IPAH) on the basis of progression of echocardiographic right ventricular (RV) dysfunction.MethodsRetrospective analysis of echocardiographic data in 13 patients with SSc-PAH and 11 patients with IPAH was used to delineate the progression of RV dysfunction during single or combination pulmonary arterial vasodilator therapy. All patients had right heart catheterization-confirmed pulmonary arterial hypertension as well as complete baseline (at the time of diagnosis) and follow-up (most recent) echocardiograms. We excluded patients with significant scleroderma-associated interstitial lung disease. Adjusting for time of follow-up and disease duration, we performed mixed model regression analyses comparing the changes between the two groups for different echocardiographic variables: tricuspid annular plane systolic excursion, tricuspid regurgitation jet velocity, right atrial area, and RV diameter.ResultsThe mean ages for the SSc-PAH and IPAH groups were 60.8 and 48.2 years, respectively. The mean follow-up periods for the two groups were 3.8 and 1.95 years, respectively. Tricuspid annular plane systolic excursion did not improve in patients with SSc-PAH, whereas it increased in the patients with IPAH (-0.38 mm, P = 0.87; vs. +5.6 mm, P = 0.02). The other echocardiographic variables showed a trend toward worsening in the SSc-PAH group and improvement in the IPAH group.ConclusionsOur results indicate that, in patients with SSc-PAH, echocardiographic RV function does not improve over time compared with that of patients with IPAH, despite institution of pulmonary artery vasodilator therapies.
| S-EPMC5802595 | biostudies-literature
Project description:BackgroundRight ventricular (RV) functional reserve affects functional capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis than idiopathic PAH (IPAH), even though many measures of resting RV function and pulmonary vascular load are similar. We therefore tested the hypothesis that RV functional reserve is depressed in SSc-PAH patients.Methods and resultsRV pressure-volume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental atrial pacing or supine bicycle ergometry. Systolic and lusitropic function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH. The recirculation fraction, which indexes intracellular calcium recycling, was also depressed in SSc-PAH (0.32±0.05 versus 0.50±0.05; P=0.039). At matched exercise (25 W), SSc-PAH patients did not augment contractility (end-systolic elastance) whereas IPAH did (P<0.001). RV afterload assessed by effective arterial elastance rose similarly in both groups; thus, ventricular-vascular coupling declined in SSc-PAH. Both end-systolic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas chamber dilation was absent in IPAH (+37±10% versus +1±8%, P=0.004, and +19±4% versus -1±6%, P<0.001, respectively). Exercise-associated RV dilation also strongly correlated with resting ventricular-vascular coupling in a larger cohort.ConclusionsRV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling. During exercise, this results in ventricular-pulmonary vascular uncoupling and acute RV dilation. RV dilation during exercise can predict adverse ventricular-vascular coupling in PAH patients.
| S-EPMC4907868 | biostudies-literature
Project description:BackgroundMale sex is an independent predictor of worse survival in pulmonary arterial hypertension (PAH). This finding might be explained by more severe pulmonary vascular disease, worse right ventricular (RV) function, or different response to therapy. The aim of this study was to investigate the underlying cause of sex differences in survival in patients treated for PAH.MethodsThis was a retrospective cohort study of 101 patients with PAH (82 idiopathic, 15 heritable, four anorexigen associated) who were diagnosed at VU University Medical Centre between February 1999 and January 2011 and underwent right-sided heart catheterization and cardiac MRI to assess RV function. Change in pulmonary vascular resistance (PVR) was taken as a measure of treatment response in the pulmonary vasculature, whereas change in RV ejection fraction (RVEF) was used to assess RV response to therapy.ResultsPVR and RVEF were comparable between men and women at baseline; however, male patients had a worse transplant-free survival compared with female patients (P = .002). Although male and female patients showed a similar reduction in PVR after 1 year, RVEF improved in female patients, whereas it deteriorated in male patients. In a mediator analysis, after correcting for confounders, 39.0% of the difference in transplant-free survival between men and women was mediated through changes in RVEF after initiating PAH medical therapies.ConclusionsThis study suggests that differences in RVEF response with initiation of medical therapy in idiopathic PAH explain a significant portion of the worse survival seen in men.
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Project description:Group 3 pulmonary hypertension (PH) patients have disproportionate right ventricular dysfunction (RVD) compared to pulmonary arterial hypertension. We evaluated how sex and PH etiology modulated RVD. Strain echocardiography showed no intrasex differences between PH types. Heightened RVD in Group 3 PH may be due to a greater male proportion.
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Project description:Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy, characterized by excess proliferation, apoptosis resistance, inflammation, fibrosis, and vasoconstriction. Although PAH therapies target some of these vascular abnormalities (primarily vasoconstriction), most do not directly benefit the right ventricle (RV). This is suboptimal because a patient's functional state and prognosis are largely determined by the success of the adaptation of the RV to the increased afterload. The RV initially hypertrophies but might ultimately decompensate, becoming dilated, hypokinetic, and fibrotic. A number of pathophysiologic abnormalities have been identified in the PAH RV, including: ischemia and hibernation (partially reflecting RV capillary rarefaction), autonomic activation (due to G protein receptor kinase 2-mediated downregulation and desensitization of β-adrenergic receptors), mitochondrial-metabolic abnormalities (notably increased uncoupled glycolysis and glutaminolysis), and fibrosis. Many RV abnormalities are detectable using molecular imaging and might serve as biomarkers. Some molecular pathways, such as those regulating angiogenesis, metabolism, and mitochondrial dynamics, are similarly deranged in the RV and pulmonary vasculature, offering the possibility of therapies that treat the RV and pulmonary circulation. An important paradigm in PAH is that the RV and pulmonary circulation constitute a unified cardiopulmonary unit. Clinical trials of PAH pharmacotherapies should assess both components of the cardiopulmonary unit.
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Project description:Pulmonary arterial hypertension (PAH) is no longer an orphan disease. There are three different classes of drugs for the treatment of PAH that are currently being used and an increasing number of patients are being treated with a single drug or combination therapy. During the last 25 yrs, new insights into the pathobiology of PAH have been gained. The classical mechanical concepts of pressure, flow, shear stress, right ventricle wall stress and impedance have been complemented with the new concepts of cell injury and repair and interactions of complex multicellular systems. Integrating these concepts will become critical as we design new medical therapies in order to change the prognosis of patients with these fatal diseases. This review intends to summarise recent pathobiological concepts of PAH and right ventricle failure mainly derived from human studies, which reflect the progress made in the understanding of this complex group of pulmonary vascular diseases.
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Project description:Increased arterial stiffness elevates aortic load, which can have adverse impacts on left ventricular (LV) function and contribute to the onset of heart failure. This impact is known to be more pronounced in women. Optimal coordination between ventricular contraction and the arterial system is required to maintain efficient cardiac function. This study aimed to investigate sex differences in the impact of ventricular-arterial coupling (VAC) on LV function in patients with hypertension at rest and after handgrip exercise. Echocardiographic indexes of LV volumes, systolic function, and diastolic function were obtained in the usual way. Effective arterial elastance (EA) and index (EAI) were calculated from stroke volume measured using LV outflow waveform. Effective LV end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. Central aortic pressure waveform was recorded using the applanation tonometry. Characteristic impedance (Zc) of aortic root and reflection magnitude (RM) was calculated after Fourier transformation of both aortic pressure and flow waveforms. Sixty-four patients (31 women and 33 men) with hypertension were enrolled. Women showed higher ELVI (1.33±0.34 vs. 1.10±0.29 mmHg/ml∙m2, P = 0.004) and EAI (1.14±0.25 vs. 0.93±0.26 mmHg/ml∙m2, P = 0.001), but VAC was not different (women: 0.88±0.17 vs. men: 0.85±0.11, P = 0.431). Zc and RM were not different between women and men. After handgrip exercise, an increase in ELVI (P = 0.021) and a decrease in VAC (P = 0.035) were observed specifically in men, with no corresponding changes noted in women. In women, VAC was significantly associated with E' velocity (beta -0.344, P = 0.029) and left ventricular global longitudinal strain (beta 0.470, P = 0.012) after adjustment, but in men, no association was found. Hypertensive women demonstrated greater stiffness in both the left ventricle and arterial systems, along with impaired LV contractile reserve in response to handgrip exercise, as compared to men. The ventricular-arterial mismatch had a notable impact on LV diastolic and systolic dysfunction only in women, but not in men.
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Project description:ObjectivesThis cross-sectional analysis from the CZecking Heart Failure in patients with advanced Chronic Kidney Disease trial (ISRCTN18275480) examined pulmonary hypertension and right ventricular-pulmonary arterial coupling in patients on chronic hemodialysis. The aims of this analysis were: 1. To analyze relations between pulmonary hypertension and right ventricular-pulmonary arterial coupling with dialysis access flow and current hydration; 2. To analyze structural heart changes associated with right ventricular-pulmonary arterial uncoupling; 3. To reveal the prevalence, etiology and severity of pulmonary hypertension in the Czech hemodialysis population.MethodsWe performed expert echocardiography, vascular access flow measurements, bioimpedance analysis, and laboratory testing in 336 hemodialysis patients.ResultsPulmonary hypertension was present in 34% (114/336) patients and right ventricular-pulmonary arterial uncoupling was present in 25% of patients with pulmonary hypertension. Only weak associations between the flow of the dialysis arteriovenous access and estimated pulmonary arterial systolic pressure and right ventricular-pulmonary arterial coupling was proved. There was a strong association between hydration status assessed by estimated central venous pressure with pulmonary arterial systolic pressure (Rho 0.6, p < 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.52, p < 0.0001) and association between overhydration to extracellular water ratio with pulmonary arterial systolic pressure (Rho 0.31, p = 0.0001) and right ventricular-pulmonary arterial coupling (Rho -0.29, p = 0.002). The prevalence of heart failure was significantly higher in patients with right ventricular-pulmonary arterial uncoupling (88% vs. 52%, p = 0.0003).ConclusionThese findings suggest that optimizing volume status and treating heart failure should be prioritized in hemodialysis patients to prevent pulmonary hypertension progression and right ventricular-pulmonary arterial uncoupling.
| S-EPMC11852216 | biostudies-literature