P2774Galectin-3, GDF-15, and ST2 in noninvasive assessment of myocardial remodelling in chronic thromboembolic pulmonary hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S D Kriechbaum ◽  
K Peters ◽  
R Ajnwojner ◽  
J S Wolter ◽  
M Haas ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Disease Severity ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Control Group ◽  
Right Heart ◽  
Non Invasive ◽  
Galectin 3 ◽  
Myocardial Remodelling ◽  
Thromboembolic Pulmonary Hypertension

Abstract Background In chronic thromboembolic pulmonary hypertension (CTEPH), pulmonary artery obstruction leads to impaired pulmonary hemodynamics and secondary right heart failure, which is highly predictive of outcome. Thus, the extent of myocardial -especially right heart- remodelling is an indicator of disease severity. Purpose The aim of the present study was to assess growth differentiation factor-15 (GDF-15), galectin-3, and suppression of tumorigenicity 2 (ST2) as non-invasive biomarkers of myocardial remodelling in patients suffering from CTEPH. Methods We analysed the serum levels of GDF-15, galectin-3 and ST2 in a cohort of 64 CTEPH patients and in a control group of 25 patients without cardiovascular disease. The biomarker levels were further correlated with clinical, laboratory, and hemodynamic data, including 6-minute walking distance (6-MWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), mean pulmonary artery pressure (meanPAP), pulmonary vascular resistance (PVR), and right atrial pressure (RAP). Results The biomarker levels in the control group were: galectin-3: 3.5 ng/l (IQR 2.7–4.0), GDF-15: 92.6 pg/ml (IQR 78.5–129.1), and ST2: 48.65 ng/l (IQR 35.5–57.0). CTEPH patients had higher levels of GDF-15 (196.7 pg/ml; IQR 128.4–302.8; p<0.001) and ST2 (52.6 ng/l; IQR 44.5–71.9; p=0.05) but not galectin-3 (3.4 ng/l; IQR 2.7–4.3; p=0.84). In the CTEPH cohort, patients with a meanPAP >35 mmHg (GDF-15: p=0.01; ST2: p=0.04) and patients with a PVR >500 dyn sec cm–5 (GDF-15: p=0.004; ST2: p=0.002) had significantly increased biomarker levels. For the detection of a meanPAP >35mmHg, ROC analysis revealed an AUC of 0.71 for GDF-15 and 0.67 for ST2. The level of GDF-15 correlated with the level of NT-proBNP (rrs=0.69; p≤0.001) and the RAP (rrs=0.54; p≤0.001) and inversely with the 6-MWD (rrs=−0.47; p≤0.001). The level of ST2 correlated with the level of NT-proBNP (rrs=0.67; p≤0.001) and the RAP (rrs=0.54; p≤0.001) and inversely with the 6-MWD (rrs=-0.31; p=0.02). Conclusion Our results demonstrate that GDF-15 and ST2, non-invasive biomarkers of myocardial remodelling, are significantly elevated in patients suffering from CTEPH. The correlation of biomarker levels with established outcome predictors suggests a use as indicators of disease severity.

scholarly journals Model of chronic thromboembolic pulmonary hypertension in rats, caused by repeated intravenous administration of biodegradable microspheres from sodium alginate

2019 ◽  
Vol 18 (1) ◽  
pp. 86-95
Author(s):  
A. A. Karpov ◽  
N. A. Anikin ◽  
D. E. Cherepanov ◽  
A. M. Mikhailova ◽  
M. V. Krasnova ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Sodium Alginate ◽  
Autologous Blood ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Control Group ◽  
Biodegradable Microspheres ◽  
Treadmill Test ◽  
Thromboembolic Pulmonary Hypertension

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the most severe complications of pulmonary embolism (PE), characterized by poor prognosis and insuffcient effectiveness of standard treatment approaches. A small number of representative models of CTEPH make it diffcult to conduct preclinical studies of promising pharmacological substances.Objective – development and validation of the experimental model of CTEPH in rats by embolization of the distal branches of the pulmonary artery with biodegradable microspheres.Material and methods. Male Wistar rats were used for the experiments. Biodegradable microspheres (MS) based on sodium alginate and autologous blood clots (AT) were used as embolizing particles. The animals were divided into groups: control: saline solution was injected 4 times with an interval of 8 days into the tail vein; AT: according to the above protocol, 50 μL of AT was injected; MS was administered intravenously in a volume of 50 μl of MS according to two protocols: MS4: 4 times with an interval of 8 days; MS8: 8 times with an interval of 4 days. After 2 and 6 weeks after the last injection, a histological examination of the lungs was performed; after 6 weeks: echocardiographic study (TTE), right ventricular catheterization (RV) with measurement of right ventricular systolic pressure (RVSP), treadmill test, assessment of serum endothelin­1 levels by the immunoassay method.Results. During the experiments, the survival rate in the MS8 group was 50 %. In the other groups, there were no animal losses. According to the treadmill test 6 weeks after the modeling of PE, exercise tolerance was signifcantly reduced in the MC4 and MC8 groups compared with the control group. TTE data indicate a signifcant increase in the diameter of the pulmonary trunk and the right ventricular outflow tract in the MC8 compared with the control and AT. There were signifcant increase in RVSP and the level of endothelin­1 compared with the control only in the MS8. After 6 weeks, the index of hypertrophy of vessel wall of the pulmonary artery in the MC4 and MC8 was signifcantly higher compared with the control and AT groups.Conclusion. Based on the use of MS, administered under the MS 8 protocol, a new representative model of CTEPH has been created, which can be used to test promising pharmacological substances.

scholarly journals Balloon pulmonary angioplasty for patients with inoperable chronic thromboembolic pulmonary hypertension

2019 ◽  
Vol 91 (4) ◽  
pp. 43-47
Author(s):  
N M Danilov ◽  
Yu G Matchin ◽  
A M Chernyavsky ◽  
A G Edemsky ◽  
D S Grankin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Functional Class ◽  
Reverse Remodeling ◽  
Systolic Pulmonary Artery Pressure ◽  
Right Heart ◽  
Balloon Pulmonary Angioplasty ◽  
Thromboembolic Pulmonary Hypertension ◽  
The Right

Aim. To evaluate the effectiveness of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Materials and methods. Forty patients with inoperable CTEPH were enrolled in this study. The indications were determined by multidisciplinary team. The average age of patients was 53.5 [43; 63] years. In 65% of cases patients had functional class III (according to WHO); the distance in the 6-minute walk test (6MWD) was 327 [280; 400] m; catheterization of the right heart revealed systolic pulmonary artery pressure (SPAP) 82 [64; 100] mm Hg, mean pulmonary artery (mPAP) 48.5 [38; 56] mm Hg, pulmonary vascular resistance (PVR) 784 [525; 1257] dyn·s/cm-5. Each patient underwent 6 BPA. Results and discussion. The effectiveness of BPA was assessed 2 months after the last session. According to the data of right heart catheterization SPAP decreased by 27.3%, mPAP by 26%, PVR by 34.5% from baseline. After all series of BPA echocardiography and magnetic resonance imaging demonstrated reverse remodeling of the right heart. Also significant decrease in the level of BNP by 62%, increasing in 6MWD distance by 39% and improvement of the functional class up to I in 60% cases and up to II in 40% cases were noted. Conclusion. The results of the present study demonstrated a high efficacy of BPA allowing to normalize hemodynamic and clinical parameters, increasing the physical activity. Balloon pulmonary angioplasty is a new highly effective, safe method for treating patients with inoperable CTEPH.

scholarly journals Chronic Thromboembolic Pulmonary Hypertension

2018 ◽  
Vol 35 (02) ◽  
pp. 136-142 ◽  
Author(s):  
G. Pretorius ◽  
Stuart Jamieson
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Right Heart Failure ◽  
Scar Tissue ◽  
Right Heart ◽  
Fibrotic Scar ◽  
Thromboembolic Pulmonary Hypertension

AbstractChronic thromboembolic pulmonary hypertension occurs when acute thromboemboli fail to dissolve completely. The resulting fibrotic scar tissue within the pulmonary arteries is obstructive and eventually leads to right heart failure. Medical therapy for this condition is supportive, but surgery with pulmonary artery endarterectomy is curative, and carries a low mortality at experienced centers.

The protective effects of radiofrequency pulmonary artery denervation on the progression of chronic thromboembolic pulmonary hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Rudenko ◽  
D Feshchenko
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Control Group ◽  
Artery Pressure ◽  
Mean Pulmonary Artery Pressure ◽  
Thromboembolic Pulmonary Hypertension ◽  
The Mean

Abstract   This study aimed to assess the safety and efficacy of radiofrequency pulmonary artery denervation with the Simplicity system in patients with distal chronic thromboembolic pulmonary hypertension. Methods and results 60 chronic thromboembolic pulmonary hypertension patients with mean pulmonary artery pressure &gt;25 mm Hg and absence of proximal artery lesion defined by pulmonary angiography were randomized into 2 groups. Group 1 included 30 patients who underwent pulmonary artery denervation procedure. The other 30 patients were assigned to the control group (only angio plus right heart catheterization). The procedure of pulmonary artery denervation was performed at the lateral wall of main pulmonary artery and ostium of the left and right pulmonary arteries using the electrode from Simplicity denervation system. The programmed ablation parameters were temperature &gt;50°C and time = 120 s. Using the coronary guiding technique, the tip of electrode was applied at each spot rotating the tip with pace of 2 mm. The success was defined by decrease of mean pulmonary artery pressure &gt;10%, absence of complications. The primary end point was comparison of mean pulmonary artery pressure change from baseline to 12 months in pulmonary artery denervation group compared with change from baseline to 12 months in control group. The secondary point was change in 6-min walk distance and pulmonary vascular resistance at the 12-month follow-up. There were no complications after pulmonary artery denervation. The hemodynamic success was achieved in 93% of all cases. The mean number of radiofrequency applications to achieve success was 10.3 per patient. During follow-up period 3 patients died in pulmonary artery denervation group: (1 died of gastro-intestinal bleeding, 2 – of right ventricular failure) and 3 patients in control group. The mean decreases in the mean pulmonary artery pressure were 8.7 mm Hg in the pulmonary artery denervation group and 3.1 mm Hg in control group (p&lt;0.05). After pulmonary artery denervation in comparison with the control group was observed significant decrease in pulmonary vascular resistance (8.3±2.8 WU vs. 11.2±3.7). 6-min walk distance significantly increased by 81 m after pulmonary artery denervation and 29 m in control group (p&lt;0.05). This improvement was associated with significant improvements in the WHO functional class. Conclusions The usage of the Simplicity denervation system in pulmonary artery denervation procedure is safe and effective. Further studies are required to determine the role of pulmonary artery denervation in the treatment of chronic thromboembolic pulmonary hypertension. The next step of pulmonary artery denervation development will be the use of this method combined with recommended treatment (medical therapy, pulmonary endarterectomy and balloon pulmonary angioplasty) as additional option, that may sufficiently improve outcomes in some patients Funding Acknowledgement Type of funding source: None

scholarly journals Model of Chronic Thromboembolic Pulmonary Hypertension in Rats Caused by Repeated Intravenous Administration of Partially Biodegradable Sodium Alginate Microspheres

2021 ◽  
Vol 22 (3) ◽  
pp. 1149
Author(s):  
Andrei A. Karpov ◽  
Nikita A. Anikin ◽  
Aleksandra M. Mihailova ◽  
Sergey S. Smirnov ◽  
Dariya D. Vaulina ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Exercise Tolerance ◽  
Complex Disease ◽  
Histopathological Examination ◽  
Main Pulmonary Artery ◽  
Systolic Pressure ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Control Group ◽  
Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and life-threatening complication of pulmonary embolism. As existing animal models of CTEPH do not fully recapitulate complex disease pathophysiology, we report a new rat model for CTEPH evoked by repetitive embolization of the distal pulmonary artery branches with partially biodegradable alginate microspheres (MSs). MSs (180 ± 28 μm) were intravenously administered eight times at 4-day intervals; control animals received saline. The validity of the model was confirmed using transthoracic echocardiography, exercise testing, catheterization of the right ventricle, and histological examination of the lung and heart. The animals in the CTEPH group demonstrated a stable increase in right ventricular systolic pressure (RVSP) and decreased exercise tolerance. Histopathological examination revealed advanced medial hypertrophy in the small pulmonary arteries associated with fibrosis. The diameter of the main pulmonary artery was significantly larger in the CTEPH group than in the control group. Marinobufagenin and endothelin-1 serum levels were significantly elevated in rats with CTEPH. In conclusion, repetitive administration of alginate MSs in rats resulted in CTEPH development characterized by specific lung vasculature remodeling, reduced exercise tolerance, and a persistent rise in RVSP. The developed model can be used for pre-clinical testing of promising drug candidates.

scholarly journals Thrombotic Lesion of the Pulmonary Vessels in Patients with Pulmonary Embolism

2020 ◽  
Vol 16 (6) ◽  
pp. 1002-1008
Author(s):  
A. A. Klimenko ◽  
N. A. Demidova ◽  
N. A. Shostak ◽  
M. O. Anischenko
Keyword(s):  
Pulmonary Embolism ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Disease ◽  
Combined Therapy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Right Heart ◽  
Pulmonary Thrombosis ◽  
Thromboembolic Pulmonary Hypertension ◽  
The Right

After suffering pulmonary embolism (PE), doctors are confronted with various consequences of the disease, from asymptomatic residual pulmonary thrombosis to the formation of chronic thromboembolic pulmonary hypertension (CTEPH). There is also a subgroup of patients who have undergone pulmonary embolism, who experience shortness of breath during physical exertion, absent before pulmonary embolism, or shortened dyspnea preceding PE, combined with residual thrombosis of pulmonary artery (PA) and normal average pressure in PA at rest during catheterization of the right heart (CRH). This condition is defined as chronic thromboembolic pulmonary disease or post thromboembolic syndrome. Pathogenetic aspects of this condition are not fully investigated. It is important to predict the development of postembolic syndrome and to develop algorithms for the diagnosis, treatment and rehabilitation of patients with symptoms and residual pulmonary thrombosis. In case of the development of pulmonary vasculopathy in some patients who have undergone pulmonary embolism, a severe life-threatening condition forms - CTEPH, characterized by an increase in pressure in the pulmonary artery, right heart failure due to the presence of organized blood clots that have entered the pulmonary vascular bed during PE. The volume of thrombotic masses does not always correlate with clinical symptoms, which indicates the importance of microvascular remodeling. If CTEPH is suspected, a diagnostic algorithm is required, including ventilation-perfusion scintigraphy, CT angiopulmonography and catheterization of the right heart. Treating a patient with CTEPH is a difficult task fora doctor. The timely referral of the patient to the center where they are involved in treatment, including surgery and CTEPH is extremely important. Timely performed thrombendarterectomy in some cases allows to completely cure the patient. In the case of inoperable CTEPH or residual pulmonary hypertension after thrombendarterectomy, balloon angioplasty of the PA is used as well as drug treatment with specific drugs that reduce the pressure in the PA (riociguat), endothelin receptor antagonists (bosentan, macitentan), prostanoids (inhalant illoprost) phosphodiesterase-5 inhibitor and combined therapy. In this article we considered some consequences directly related to PE: asymptomatic residual pulmonary thrombosis, chronic thromboembolic pulmonary disease, chronic thromboembolic pulmonary hypertension.

Pulmonary Endarterectomy: Assessment of Operability, Surgical Description, and Post-op Care

2014 ◽  
Vol 12 (4) ◽  
pp. 186-192 ◽  
Author(s):  
David Poch ◽  
Victor Pretorius
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Arteries ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Artery Wedge Pressure ◽  
Pulmonary Endarterectomy ◽  
Pulmonary Thromboendarterectomy ◽  
Thromboembolic Pulmonary Hypertension ◽  
Wedge Pressure

Chronic thromboembolic pulmonary hypertension (CTEPH) is defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≤15 mm Hg in the presence of occlusive thrombi within the pulmonary arteries. Surgical pulmonary thromboendarterectomy (PTE) is considered the best treatment option for CTEPH.

scholarly journals EXPRESS: Chronic thromboembolic pulmonary hypertension following pulmonary embolism with a right ventricular thrombus: A report of two cases

2021 ◽  
pp. 204589402110136
Author(s):  
Tailong Zhang ◽  
Weitao Liang ◽  
Longrong Bian ◽  
Zhong Wu
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Imaging Features ◽  
Pulmonary Endarterectomy ◽  
Right Heart ◽  
Thromboembolic Pulmonary Hypertension ◽  
The Right ◽  
Cardiac Masses

Right heart thrombus (RHT) accompanied by chronic thromboembolic pulmonary hypertension (CTEPH) is a rare entity. RHT may develop in the peripheral veins or in situ within the right heart chambers. The diagnosis of RHT is challenging, since its symptoms are typically non-specific and its imaging features resemble those of cardiac masses. Here, we report two cases of RHT with CTEPH that presented as right ventricular masses initially. Both patients underwent simultaneous pulmonary endarterectomy (PEA) and resection of the ventricular thrombi. Thus, when mass-like features are confirmed by imaging, RHT should be suspected in patients with CTEPH, and simultaneous RHT resection is required along with PEA.

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