scholarly journals Hemodynamics and right-ventricle functional characteristics of a swine carotid artery-jugular vein shunt model of pulmonary arterial hypertension: An 18-month experimental study

2015 ◽  
Vol 240 (10) ◽  
pp. 1362-1372 ◽  
Author(s):  
Ji Wu ◽  
Xiaoju Luo ◽  
Yuanyuan Huang ◽  
Yun He ◽  
Zhixian Li
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Carotid Artery ◽  
Pulmonary Artery ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Jugular Vein ◽  
Surgical Anastomosis ◽  
Non Invasive ◽  
Pulmonary Arterial ◽  
Rv Function

The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery–jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH.

scholarly journals Multimodal assessment of right ventricle overload-metabolic and clinical consequences in pulmonary arterial hypertension

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Remigiusz Kazimierczyk ◽  
Lukasz A. Malek ◽  
Piotr Szumowski ◽  
Stephan G. Nekolla ◽  
Piotr Blaszczak ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Global Longitudinal Strain ◽  
Systolic Pressure ◽  
End Point ◽  
Coupling Parameters ◽  
Pulmonary Arterial ◽  
Rv Function

Abstract Background In pulmonary arterial hypertension (PAH) increased afterload leads to adaptive processes of the right ventricle (RV) that help to maintain arterio-ventricular coupling of RV and preserve cardiac output, but with time the adaptive mechanisms fail. In this study, we propose a multimodal approach which allows to estimate prognostic value of RV coupling parameters in PAH patients. Methods Twenty-seven stable PAH patients (49.5 ± 15.5 years) and 12 controls underwent cardiovascular magnetic resonance (CMR). CMR feature tracking analysis was performed for RV global longitudinal strain assessment (RV GLS). RV-arterial coupling was evaluated by combination of RV GLS and three proposed surrogates of RV afterload—pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC). 18-FDG positron emission tomography (PET) analysis was used to assess RV glucose uptake presented as SUVRV/LV. Follow-up time of this study was 25 months and the clinical end-point was defined as death or clinical deterioration. Results Coupling parameters (RV GLS/PASP, RV GLS/PVR and RV GLS*PAC) significantly correlated with RV function and standardized uptake value (SUVRV/LV). Patients who experienced a clinical end-point (n = 18) had a significantly worse coupling parameters at the baseline visit. RV GLS/PASP had the highest area under curve in predicting a clinical end-point and patients with a value higher than (−)0.29%/mmHg had significantly worse prognosis. It was also a statistically significant predictor of clinical end-point in multivariate analysis (adjusted R2 = 0.68; p < 0.001). Conclusions Coupling parameters are linked with RV hemodynamics and glucose metabolism in PAH. Combining CMR and hemodynamic measurements offers more comprehensive assessment of RV function required for prognostication of PAH patients. Trial Registration: NCT03688698, 09/26/2018, retrospectively registered; Protocol ID: 2017/25/N/NZ5/02689

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.

scholarly journals Identification of Long Noncoding RNA H19 as a New Biomarker and Therapeutic Target in Right Ventricular Failure in Pulmonary Arterial Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (15) ◽  
pp. 1464-1484 ◽  
Author(s):  
Junichi Omura ◽  
Karima Habbout ◽  
Tsukasa Shimauchi ◽  
Wen-Hui Wu ◽  
Sandra Breuils-Bonnet ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Therapeutic Target ◽  
Noncoding Rna ◽  
Pulmonary Artery Banding ◽  
Pulmonary Arterial ◽  
Rv Function

Background: Right ventricular (RV) function is the major determinant for both functional capacity and survival in patients with pulmonary arterial hypertension (PAH). Despite the recognized clinical importance of preserving RV function, the subcellular mechanisms that govern the transition from a compensated to a decompensated state remain poorly understood and as a consequence there are no clinically established treatments for RV failure and a paucity of clinically useful biomarkers. Accumulating evidence indicates that long noncoding RNAs are powerful regulators of cardiac development and disease. Nonetheless, their implication in adverse RV remodeling in PAH is unknown. Methods: Expression of the long noncoding RNA H19 was assessed by quantitative PCR in plasma and RV from patients categorized as control RV, compensated RV or decompensated RV based on clinical history and cardiac index. The impact of H19 suppression using GapmeR was explored in 2 rat models mimicking RV failure, namely the monocrotaline and pulmonary artery banding. Echocardiographic, hemodynamic, histological, and biochemical analyses were conducted. In vitro gain- and loss-of-function experiments were performed in rat cardiomyocytes. Results: We demonstrated that H19 is upregulated in decompensated RV from PAH patients and correlates with RV hypertrophy and fibrosis. Similar findings were observed in monocrotaline and pulmonary artery banding rats. We found that silencing H19 limits pathological RV hypertrophy, fibrosis and capillary rarefaction, thus preserving RV function in monocrotaline and pulmonary artery banding rats without affecting pulmonary vascular remodeling. This cardioprotective effect was accompanied by E2F transcription factor 1-mediated upregulation of enhancer of zeste homolog 2. In vitro, knockdown of H19 suppressed cardiomyocyte hypertrophy induced by phenylephrine, while its overexpression has the opposite effect. Finally, we demonstrated that circulating H19 levels in plasma discriminate PAH patients from controls, correlate with RV function and predict long-term survival in 2 independent idiopathic PAH cohorts. Moreover, H19 levels delineate subgroups of patients with differentiated prognosis when combined with the NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels or the risk score proposed by both REVEAL (Registry to Evaluate Early and Long-Term PAH Disease Management) and the 2015 European Pulmonary Hypertension Guidelines. Conclusions: Our findings identify H19 as a new therapeutic target to impede the development of maladaptive RV remodeling and a promising biomarker of PAH severity and prognosis.

scholarly journals P371 Right ventricle end-systolic remodeling index in patients with atrial septal defect and severe pulmonary arterial hypertension

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Selegny ◽  
E Fournier ◽  
M Amsallem ◽  
M Tortigue ◽  
M Kara ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pericardial Effusion ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Atrial Septal Defect ◽  
Septal Defect ◽  
Remodeling Index ◽  
Pulmonary Arterial ◽  
Rv Function ◽  
Severe Pulmonary Arterial Hypertension

Abstract Background Outcome of patients with atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH) relates to right ventricular (RV) function. Magnetic resonance imaging (MRI) remains the gold standard for evaluating the RV function but it is not used routinely. We investigated the relationship between MRI and multiple echocardiography parameters, including the Right Ventricle End-Systolic Remodeling Index (RVESRI), a new prognostic marker in patients with PAH. Methods 23 patients with ASD and severe PAH (median age 49y.o.[39-59], Sp0 2 92% [90-95], WHO functional class II or III, mean pulmonary artery pressure 51mmHg [40-59]) were included between 2014 and 2018. All patients underwent MRI and echocardiography assessment. Echocardiographic measurements of RV remodeling and function included TAPSE, RV fractional area change (RVFAC), peak systolic velocity of the tricuspid valve (S’TV), right atrial (RA) area, RV strain, Systolic to diastolic ratio, eccentricity index and RVESRI, defined by septum length divided by lateral wall length (Figure 1). Pericardial effusion was noted. Results Median RV ejection fraction (EF) evaluated with MRI was 46 % [34-59]. RV dysfunction (RVEF &lt; 45%) was observed in 43% of patients. Median RVFAC and RVESRI were 29.6%[23-34] and 1.6[1.4-1.7] respectively. By spearman correlation, RVFAC and RVESRI were significantly correlated to RVEF (Rho 0.62, p &lt; 0.007 and Rho -0.51,p &lt; 0.02 respectively). By linear regression, RVFAC and RVESRI were also correlated to RVEF (R 2 =0.36, p &lt; 0.003 and R 2 =0.34, p &lt; 0.08). Pericardial effusion was associated with RV dysfunction (p&lt; 0.008) and a lower RVFAC (p &lt; 0.01). TAPSE, S’TV and RV strain were not correlated with RVEF. Conclusion RVFAC, RVESRI and pericardial effusion were markers of RV dysfunction in patients with ASD and severe PAH. RVESRI appears as a simple and reliable parameter for follow-up. Its prognostic value in patients with CHD remains to be demonstrated.

scholarly journals Transthoracic Pulmonary Artery Denervation for Pulmonary Arterial Hypertension

2019 ◽  
Vol 39 (4) ◽  
pp. 704-718 ◽  
Author(s):  
Yuan Huang ◽  
Yi-Wei Liu ◽  
Hai-Zhou Pan ◽  
Xiao-Ling Zhang ◽  
Jun Li ◽  
...  
Keyword(s):  
Nervous System ◽  
Pulmonary Arterial Hypertension ◽  
Sympathetic Nervous System ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Sham Group ◽  
Renin Angiotensin Aldosterone System ◽  
Pulmonary Arterial ◽  
Sympathetic Nervous ◽  
Rv Function

Objective— Pulmonary arterial hypertension is characterized by progressive pulmonary vascular remodeling and persistently elevated mean pulmonary artery pressures and pulmonary vascular resistance. We aimed to investigate whether transthoracic pulmonary artery denervation (TPADN) attenuated pulmonary artery (PA) remodeling, improved right ventricular (RV) function, and affected underlying mechanisms. We also explored the distributions of sympathetic nerves (SNs) around human PAs for clinical translation. Approach and Results— We identified numerous SNs in adipose and connective tissues around the main PA trunks and bifurcations in male Sprague Dawley rats, which were verified in samples from human heart transplant patients. Pulmonary arterial hypertensive rats were randomized into TPADN and sham groups. In the TPADN group, SNs around the PA trunk and bifurcation were completely and accurately removed under direct visualization. The sham group underwent thoracotomy. Hemodynamics, RV function, and pathological changes in PA and RV tissues were measured via right heart catheterization, cardiac magnetic resonance imaging, and pathological staining, respectively. Compared with the sham group, the TPADN group had lower mean pulmonary arterial pressures, less PA and RV remodeling, and improved RV function. Furthermore, TPADN inhibited neurohormonal overactivation of the sympathetic nervous system and renin-angiotensin-aldosterone system and regulated abnormal expressions and signaling of neurohormone receptors in local tissues. Conclusions— There are numerous SNs around the rat and human main PA trunks and bifurcations. TPADN completely and accurately removed the main SNs around PAs and attenuated pulmonary arterial hypertensive progression by inhibiting excessive activation of the sympathetic nervous system and renin-angiotensin-aldosterone system neurohormone-receptor axes.

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