Transmural remodeling of right ventricular myocardium in response to pulmonary arterial hypertension

Abstract Funding Acknowledgements Type of funding sources: None. Background The haemodynamic effect of atrial septal defect (ASD) is a chronic volume overload of the right heart and pulmonary vasculature. Pulmonary overcirculation is generally compensated for by the right ventricular (RV) and pulmonary arterial (PA) reserve. However, in a subset of patients, prolonged pulmonary overcirculation insidiously induces obstructive pulmonary vasculopathy, which results in postoperative residual pulmonary arterial hypertension (PAH) after ASD closure. Postoperative PAH is a major concern because it is closely associated with poor outcomes and impaired quality of life. However, to date, no clinically robust predictors of postoperative residual PAH have been clearly identified. Purpose This study sought to assess the haemodynamic characteristics of ASD patients in terms of mechano-energetic parameters and to identify the predictors of postoperative residual PAH in these patients. Methods A total of 120 ASD patients (age: 58 ± 17 years) and 46 normal controls were recruited. As previously reported, the simplified RV contraction pressure index (sRVCPI) was calculated as an index of RV external work by multiplying the tricuspid annular plane systolic excursion (TAPSE) by the pressure gradient between the RV and right atrium. RV- PA coupling was evaluated using TAPSE divided by PA systolic pressure as an index of the RV length-force relationship. These parameters were measured both at baseline and 6 months after ASD closure. Results As expected, baseline sRVCPI was significantly greater in patients with ASD than in controls (775 ± 298 vs. 335 ± 180 mm Hg • mm, P < 0.01), which indicated significant "RV overwork". As a result, RV-PA coupling in ASD patients was significantly impaired compared to that in controls (0.9 ± 0.8 vs. 3.5 ± 1.7 mm/mm Hg, P < 0.01). All 120 ASD patients underwent transcatheter or surgical shunt closure; 15 of them had residual PAH after closure. After 6 months, RV-PA coupling index significantly improved in patients without residual PAH, from 0.96 ± 0.81 to 1.27 ± 1.24 mm/mm Hg (P = 0.02). Furthermore, RV load was markedly reduced, with sRVCPI falling from 691 ± 258 to 434 ± 217 mm Hg • mm, P < 0.01). However, in patients with residual PAH, RV-PA coupling index deteriorated from 0.64 ± 0.23 to 0.53 ± 0.12 mm/mm Hg (P < 0.01). As a result, RV overload was not significantly relieved (sRVCPI; from 971 ± 382 to 783 ± 166 mm Hg • mm, P = 0.22). In a multivariate analysis, baseline pulmonary vascular resistance (hazard ratio 1.009; P < 0.01) and preoperative sRVPCI (hazard ratio 1.003; P < 0.01) revealed to be independent predictors of residual PAH. Conclusion In terms of mechano-energetic function, preoperative "RV overwork" can be used as a robust predictor of an impaired RV-PA relationship in ASD patients. Moreover, periodic assessment of sRVPCI may contribute to the better management for patients with unrepaired ASD. Abstract Figure.

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Comparative analysis on the anti-inflammatory/immune effect of mesenchymal stem cell therapy for the treatment of pulmonary arterial hypertension

Scientific Reports ◽

10.1038/s41598-021-81244-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Seyeon Oh ◽

Albert Y. Jang ◽

Sehyun Chae ◽

Seungbum Choi ◽

Jeongsik Moon ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Right Ventricular ◽

Ventricular Function ◽

Right Ventricular Function ◽

Treated Group ◽

Therapeutic Effects ◽

Mesenchymal Stem Cell Therapy ◽

Adaptive Immune Cells ◽

Pulmonary Arterial

AbstractDespite the advancement of targeted therapy for pulmonary arterial hypertension (PAH), poor prognosis remains a reality. Mesenchymal stem cells (MSCs) are one of the most clinically feasible alternative treatment options. We compared the treatment effects of adipose tissue (AD)-, bone marrow (BD)-, and umbilical cord blood (UCB)-derived MSCs in the rat monocrotaline-induced pulmonary hypertension (PH) model. The greatest improvement in the right ventricular function was observed in the UCB-MSCs treated group. The UCB-MSCs treated group also exhibited the greatest improvement in terms of the largest decrease in the medial wall thickness, perivascular fibrosis, and vascular cell proliferation, as well as the lowest levels of recruitment of innate and adaptive immune cells and associated inflammatory cytokines. Gene expression profiling of lung tissue confirmed that the UCB-MSCs treated group had the most notably attenuated immune and inflammatory profiles. Network analysis further revealed that the UCB-MSCs group had the greatest therapeutic effect in terms of the normalization of all three classical PAH pathways. The intravenous injection of the UCB-MSCs, compared with those of other MSCs, showed superior therapeutic effects in the PH model for the (1) right ventricular function, (2) vascular remodeling, (3) immune/inflammatory profiles, and (4) classical PAH pathways.

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

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02037-y ◽

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.

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Change of right ventricular systolic pressure can indicate dasatinib‐induced pulmonary arterial hypertension in chronic myeloid leukemia

Cancer Medicine ◽

10.1002/cam4.3588 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1515-1524

Author(s):

Sung‐Eun Lee ◽

Jee Hyun Kong ◽

Soo‐Hyun Kim ◽

Eun‐Jung Jang ◽

Nack‐Gyun Chung ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Chronic Myeloid Leukemia ◽

Arterial Hypertension ◽

Right Ventricular ◽

Myeloid Leukemia ◽

Systolic Pressure ◽

Right Ventricular Systolic Pressure ◽

Ventricular Systolic Pressure ◽

Pulmonary Arterial

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

European Heart Journal ◽

10.1093/ehjci/ehaa946.0225 ◽

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<0.01) and higher weight ratio of RV (0.60±0.03 vs. 0.28±0.02, p<0.05). In CMR imaging, MCT-rats showed lower RVEF (36.1±11.2 vs. 64.8±8.4%, p<0.001) and lower RVLS (−18±9 vs. −30±1%, p<0.05). In trabeculae from RVs, MCT-rats showed lower developed force and lower dF/dt (p<0.01). Correlation between RVLS and dF/dt was higher (n=20, r=0.53, p<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 (>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<0.01) and Ctr-rats (n=4, p<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

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