CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension

2020 ◽  
pp. 1901192
Author(s):  
Stanislav Keranov ◽  
Oliver Dörr ◽  
Leili Jafari ◽  
Christian Troidl ◽  
Christoph Liebetrau ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Protein Expression ◽  
Right Ventricular ◽  
Predictive Power ◽  
Pressure Overload ◽  
Serum Levels ◽  
Left Ventricular ◽  
Dilative Cardiomyopathy ◽  
Significant Difference ◽  
Rv Function

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein 1 (CILP1) in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another 9 mice underwent sham surgery. CILP1 protein expression was analysed in all hearts by western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001), and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in ROC analysis (AUC 0.79). There was no significant difference between the AUCs of CILP1 and NT-pro-BNP (AUC 0.82). High CILP1 (≥cut-off value for maladaptive RV of 4373 pg·mL−1) was associated with lower TAPSE/PASP ratios (p<0.001) and higher NT-pro-BNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

scholarly journals Delineating the molecular and histological events that govern right ventricular recovery using a novel mouse model of pulmonary artery de-banding

2019 ◽  
Vol 116 (10) ◽  
pp. 1700-1709 ◽  
Author(s):  
Mario Boehm ◽  
Xuefei Tian ◽  
Yuqiang Mao ◽  
Kenzo Ichimura ◽  
Melanie J Dufva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Model ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Exercise Capacity ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Sequence Of Events ◽  
Reverse Remodelling ◽  
Rv Function

Abstract Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

A novel echocardiographic parameter for assessment of right ventricular function in acute pulmonary embolism: an experimental study

2019 ◽  
Author(s):  
Decai Zeng ◽  
Ji Wu ◽  
Hui Chen ◽  
Ying Tan ◽  
Xueyu Che ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Right Ventricular ◽  
Acute Pulmonary Embolism ◽  
Autologous Blood ◽  
Left Ventricular ◽  
Control Group ◽  
Tei Index ◽  
Significant Difference ◽  
Acute Pe ◽  
Rv Function

Abstract Background Right ventricular (RV) dysfunction played a decisive role in clinical management and associated with poor prognosis in acute pulmonary embolism (PE). It still remains challenging to estimate RV function accurately for the reason of complex structure and geometry. The present study aimed to determine the value of right ventricular outflow tract systolic excursion (RVOT-SE) in evaluating RV function in an animal model with acute PE. Methods Thirty-three healthy New Zealand rabbits were randomly assigned to massive thrombus group, sub-massive thrombus group and control group, 11 rabbits per group. The acute PE model was established by intravenous infusion of autologous blood clots. After 1h of thrombus injection, transthoracic echocardiography was performed to assess RV function in all rabbits. Results The acute PE model was successfully made in 18 rabbits (massive thrombus group, n = 8; sub-massive thrombus group n = 10). Right/left ventricular end-diastolic diameter (RV/LV) ratio and RV myocardial performance (Tei) index were significantly increased, while RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) and RVOT_SE were reduced in massive thrombus group. The value of RVOT-SE and RVFAC in sub-massive thrombus group decreased significantly compared with control group (P < 0.05). But there was no significant difference in RV/LV, TAPSE and Tei index (P > 0.05). ROC analysis showed that RVOT-SE had high sensitivity (94.4%) and specificity (72.7%) in identifying RV dysfunction in acute PE. The area under the ROC curve (AUC) for combined TAPSE and RVOT-SE was greater than that of TAPSE or RVOT-SE alone (AUC= 0.962, P < 0.01). Conclusion RV function in acute PE is significantly decreased, which is closely related to the size of embolus. RVOT_SE is a simple and highly distinctive parameter in identifying RV dysfunction and tends to be superior to conventional parameters in acute PE. The combination of RVOT-SE and TAPSE can further improve the diagnostic accuracy of acute PE.

scholarly journals The SGLT2i Dapagliflozin Reduces RV Hypertrophy Independent of Changes in RV Pressure Induced by Pulmonary Artery Banding

2021 ◽  
Author(s):  
Kim Connelly ◽  
Ellen Wu ◽  
Aylin Visram ◽  
Mark K. Friedberg ◽  
Sri Nagarjun Batchu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Artery ◽  
Protein Expression ◽  
Right Ventricular ◽  
Sglt2 Inhibitor ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Pulmonary Artery Banding ◽  
Calcium Handling ◽  
Sglt2 Inhibition

Abstract Background— Sodium glucose linked transporter 2 (SGLT2) inhibition not only reduces morbidity and mortality in patients with diagnosed heart failure but also prevents the development of heart failure hospitalization in those at risk. While studies to date have focused on the role of SGLT2 inhibition in left ventricular failure, whether this drug class might be similarly efficacious in the treatment and prevention of right heart failure has not been unexplored. Hypothesis: We hypothesized that SGLT2 inhibition would reduce the structural, functional and molecular responses to pressure overload of the right ventricle. Methods: Thirteen-week-old Fischer F344 rats underwent pulmonary artery banding (PAB) or sham surgery prior to being randomized to receive either the SGLT2 inhibitor: dapagliflozin (0.5mg/kg/day) or vehicle by oral gavage. After six weeks of treatment, animals underwent transthoracic echocardiography and invasive hemodynamic studies. Animals were then terminated, and their hearts harvested for structural and molecular analyses. Results: PAB induced features consistent with a compensatory response to increased right ventricular (RV) afterload with elevated mass, end systolic pressure, collagen content and alteration in calcium handling protein expression (all p<0.05 when compared to sham + vehicle). Dapagliflozin reduced RV mass, including both wet and dry weight as well as normalizing the protein expression of SERCA 2A, AMPkinase and LC3I/II ratio expression (all p<0.05). Significance: Dapagliflozin reduces the structural, functional, and molecular manifestations of right ventricular pressure overload. Whether amelioration of these early changes in the RV may ultimately lead to a reduction in RV failure remains to be determined.

P5370Pulmonary pressure overload stimulates cardiac stem or progenitor cell-derived cardiac regeneration in the right ventricular area

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kanda ◽  
T Nagai ◽  
N Kondou ◽  
K Tateno ◽  
M Hirose ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Progenitor Cell ◽  
Pressure Overload ◽  
Right Heart Failure ◽  
Left Ventricular ◽  
Free Wall ◽  
Right Heart ◽  
The Right

Abstract Introduction and purpose The number of patients with right heart failure due to pulmonary hypertension has been increasing. Although several drugs have reportedly improved pulmonary hypertension, no treatments have been established for decompensated right heart failure. The heart has an innate ability to regenerate, and cardiac stem or progenitor cells (e.g., side population [SP] cells) have been reported to contribute to the regeneration process. However, their contribution to right ventricular pressure overload has not been clarified. Here, this regeneration process was evaluated using a genetic fate-mapping model. Methods and results We used Cre-LacZ mice, in which more than 99.9% of the cardiomyocytes in the left ventricular field were positive for 5-bromo-4-chloro-3-indolyl-β-D-galactoside (X-gal) staining immediately after tamoxifen injection. Then, we performed either a pulmonary binding (PAB) or sham operation on the main pulmonary tract. In the PAB-treated mice, the right ventricular cavity was significantly enlarged (right-to-left ventricular [RV/LV] ratio, 0.24±0.04 in the sham group and 0.68±0.04 in the PAB group). Increased peak flow velocity in the PAB group (1021±80 vs 1351±62 mm/sec) was confirmed by echocardiography. One month after the PAB, the PAB-treated mice had more X-gal-negative (newly generated) cells than the sham mice (94.8±34.2 cells/mm2 vs 23.1±10.5 cells/mm2; p<0.01). The regeneration was biased in the RV free wall (RV free wall, 225.5±198.7 cells/mm2; septal area, 88.9±56.5/mm2; LV lateral area, 46.8±22.0/mm2; p<0.05). To examine the direct effects of PAB on the cardiac progenitor cells, bromodeoxyuridine was administered to the mice daily until 1 week after the PAB operation. Then, the hearts were isolated and SP cells were harvested. The SP cell population increased from 0.65±0.23% in the sham mice to 1.87% ± 1.18% in the PAB-treated mice. Immunostaining analysis revealed a significant increase in the number of BrdU-positive SP cells, from 11.6±2.0% to 44.0±18%, therefore showing SP cell proliferation. Conclusions Pulmonary pressure overload stimulated cardiac stem or progenitor cell-derived regeneration with a RV bias, and SP cell proliferation may partially contribute to this process. Acknowledgement/Funding JSPS KAKENHI Grant Number JP 17K17636, GSK Japan Research Grant 2016

scholarly journals Pulmonary Hypertension Related to Left-Sided Cardiac Pathology

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Todd L. Kiefer ◽  
Thomas M. Bashore
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Pressure Overload ◽  
Therapeutic Strategies ◽  
Left Ventricular ◽  
Right Ventricular Failure ◽  
Valve Disease ◽  
Ventricular Failure ◽  
Cardiac Pathology ◽  
Pathologic Processes

Pulmonary hypertension (PH) is the end result of a variety of diverse pathologic processes. The chronic elevation in pulmonary artery pressure often leads to right ventricular pressure overload and subsequent right ventricular failure. In patients with left-sided cardiac disease, PH is quite common and associated with increased morbidity and mortality. This article will review the literature as it pertains to the epidemiology, pathogenesis, and diagnosis of PH related to aortic valve disease, mitral valve disease, left ventricular systolic and diastolic dysfunction, and pulmonary veno-occlusive disease. Moreover, therapeutic strategies, which focus on treating the underlying cardiac pathology will be discussed.

Impaired Left Ventricular Filling Due to Right Ventricular Pressure Overload in Primary Pulmonary Hypertension

CHEST Journal ◽  
2001 ◽  
Vol 119 (6) ◽  
pp. 1761-1765 ◽  
Author(s):  
J. Tim Marcus ◽  
Anton Vonk Noordegraaf ◽  
Roald J. Roeleveld ◽  
Pieter E. Postmus ◽  
Rob M. Heethaar ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Primary Pulmonary Hypertension ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Left Ventricular Filling ◽  
Ventricular Pressure ◽  
Ventricular Filling

Abstract 14130: Effect of Angiovac on Right Ventricular Function Following Removal of Right Atrial Masses in Patients With and Without Malignancy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniel P OBrien ◽  
Tyler E Callese ◽  
John Moriarty ◽  
Eric Yang
Keyword(s):  
Right Ventricular ◽  
Left Ventricular ◽  
Mean Difference ◽  
Right Atrial ◽  
Left Ventricular Ejection ◽  
P Value ◽  
Significant Difference ◽  
Before And After ◽  
The Mean ◽  
Rv Function

Introduction: The AngioVac thrombectomy system (AngioDynamics Inc, Queensbury, NY) is an FDA approved device for removal of thrombi and emboli. Prior studies have shown procedural success for removal of right atrial (RA) and caval masses. This study aims to assess the effect of AngioVac on right ventricular (RV) function in patients undergoing removal of RA masses. Methods: Retrospective institutional study of patients undergoing removal of RA masses with AngioVac at a single tertiary medical center were included. Right ventricular fractional change (RVFC) and tricuspid annular plane systolic excursion (TAPSE) values were collected from echocardiograms before and after AngioVac or obtained manually if not present in the report. Paired 2-sample t test was done to assess for a significant difference between the two values. Results: The mean difference in RVFC before and after AngioVac was 1.6%, with a p-value of 0.327. Ten of the 28 patients had active malignancy, with a mean difference in RVFC of 0.8% and a p value of 0.683. The mean difference in the TAPSE group was 0.07mm and a p value of 0.48. Eight of the 19 patients had active malignancy, with a mean difference in TAPSE of 0.2mm corresponding to a p-value of 0.24. There was no significant difference in left ventricular ejection fraction before and after AngioVac (mean difference of 2.5%, p-value of 0.11). Conclusions: These findings suggest that use of the AngioVac device for removal of RA masses does not cause significant derangements in RV function by echocardiographic assessment. It is a well-tolerated procedure in patients with preprocedural normal RV function. These findings also further assess the use of AngioVac in patients with both right sided cardiac masses and active malignancy.

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