Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure

Study Overview
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Brief Summary
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A number of 100 patients with pulmonary hypertension associated with the left Heart failure scheduled for elective pulmonary arterial denervation (PADN) are randomized 1:1 to either PADN or control group.

Detailed Description
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Heart failure patients must have completed the right heart catheterization. All the patients accepted the optimal medical therapies,including diuretics, Nitrate esters, β-blockers, ACE inhibitors or receptor blocker aldosterone antagonists and/or digoxin).The patients of pulmonary hypertension are defined into two groups: passive pulmonary hypertension(mPAP≥25 mmHg, PCWP>15 mmHg and pulmonary vascular resistance<3 woods unit) increase due to backward transmission of increased left ventricular filling pressure, reactive pulmonary hypertension (mPAP≥25 mmHg, PCWP>15 mmHg and pulmonary vascular resistance >3 woods unit) increase in resistance due to either pulmonary vasoconstriction or structural changes in the pulmonary vasculature. All the reactive pulmonary hypertension patients are eligible for the randomized study in PADN group or control group according to the computer generated random table.

Official Title
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Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure: a Randomised Controlled Trial

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Procedure: Pulmonary arterial denervation
* Drug: Standard treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>18yr ReactivePulmonary Hypertension in Left Heart Failure: mPAP≥25 mmHg, PCWP>15 mmHg and pulmonary vascular resistance (PVR) [The PVR =(mPAP-PCWP)/ carbon monoxide]>3.0 woods unit Voluntary acceptance of all follow-up assessment of program requirements. Exclusion Criteria: WHO group I, III, IV, V pulmonary artery hypertension Severe Renal dysfunction (Ccr<30 ml/min) Blood platelet count<100,000/L Expected life span<12-month In pregnancy Systematical inflammation Malignant cancer(s) Tricuspid valve stenosis, Supra-pulmonary valve stenosis Allergic to studied drugs or metal materials

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pulmonary Arterial Denervation (PADN)<br>Contrast pulmonary artery （PA) angiography was performed to localize the pulmonary artery bifurcation level and calculate the PA diameter.Once the anatomy was deemed acceptable, the radiofrequency ablation catheter was introduced into ostium of the left PA, ostium of the right PA , and the distal bifurcation area of the main PA.This was then maneuvered within the PA to allow energy delivery in a circumferential manner to ensure that the electrodes were tightly in contact with the endovascular surface. About four to eight ablations at 10 W for 60 seconds each were performed in ostium of the left PA, ostium of the right PA , and the distal bifurcation area of the main PA. | Procedure: Pulmonary arterial denervation<br>* Contrast pulmonary artery （PA) angiography was performed to localize the pulmonary artery bifurcation level and calculate the PA diameter.Once the anatomy was deemed acceptable, the radiofrequency ablation catheter was introduced into the distal bifurcation area of the main PA.This was then maneuvered within the PA to allow energy delivery to ensure that the electrodes were tightly in contact with the endovascular surface. About two to three ablations at 1-15 W for 240 seconds each point were performed in the distal bifurcation area of the main PA.<br>* Other names: PADN;Drug: Standard treatment<br>* Patients in the standard treatment group will take their baseline anti-heart failure medications at the original doses, without any changes except when medically required.The anti-heart failure drugs treatment is consistent in both arms.Patients in the standard treatment group will take one or combination of the following target drugs: endothelin receptor antagonist, 5'-PDE and prostacyclin. On the other hand, patients in the PADN group do not take any of the target drugs mentioned above.<br>* Other names: Digoxin;|
| Active Comparator: Standard treatment<br>Patients in the standard treatment group will take their baseline anti-heart failure medications at the original doses, without any changes except when medically required.The anti-heart failure drugs treatment is consistent in both arms. | Drug: Standard treatment<br>* Patients in the standard treatment group will take their baseline anti-heart failure medications at the original doses, without any changes except when medically required.The anti-heart failure drugs treatment is consistent in both arms.Patients in the standard treatment group will take one or combination of the following target drugs: endothelin receptor antagonist, 5'-PDE and prostacyclin. On the other hand, patients in the PADN group do not take any of the target drugs mentioned above.<br>* Other names: Digoxin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-min-walk distance increase | The primary effectiveness endpoint is change in 6-min-walk distance (6-MWD) from baseline to 6 months post-randomization. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary vascular resistance | Measure pulmonary vascular resistance using 2D doppler echocardiogram w/definity. Correlation coefficients between the technique above the the gold standard right heart catheterization measures of pulmonary vascular resistance. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension, pulmonary arterial denervation, left heart failure, 6-min walk distance