Pulmonary Arteyr Denervation for Heart Failure

Pulmonary Artery Denervation for Treatment of Patients With Heart Failure: a Safety and Proof-of-principle Cohort Study

Prolonged pulmonary venous congestion culminates in pulmonary hypertension, defined as a mean pulmonary arterial pressure > 20 mmHg and pulmonary artery wedge pressure >15 mmHg at rest, as determined by right heart catheterization. Pulmonary hypertension secondary to heart failure (PH-HF) is further stratified into isolated post-capillary pulmonary hypertension (Ipc-PH, pulmonary vascular resistance (PVR) is ≤2 Woods Unit) and combined pre- and post-capillary pulmonary hypertension (Cpc-PH, PVR > 2 Woods Unit), the later reflecting additional pulmonary vascular constriction or remodeling in addition to passive PH. While medications tailored for World Health Organization defined Group I pulmonary arterial hypertension are not endorsed for PH-HF according to current guidelines, the coexistence of pulmonary hypertension exacerbates the severity of heart failure. Given the presence of pulmonary arterial vasoconstrictor and heightened sympathetic nervous activity in patients with heart failure, the PADN-5 study has demonstrated the safety and efficacy of pulmonary artery denervation (PADN) for patients with CpcPH, characterized by the improvements in left ventricular ejection fraction, cardiac output, clinical outcome, and reductions in left atrial pressure, pulmonary arterial pressure, and PVR. Our objective is to assess the feasibility, safety, and efficacy of PADN for patients with heart failure independent of left ventricular ejection fraction (HFrEF or HFpEF) without pulmonary hypertension (N=30, 15 with HFrEF and another 15 with HFpEF).

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: Pulmonary artery denervation (PADN)

Detailed Description

We conducted a safety and proof-of-principle cohort study at a single centre in China. Eligible patients, aged 18 years or greater, had a documented history of chronic (≥6 months) ischaemic or non-ischaemic cardiomyopathy. They also met the American College of Cardiology/American Heart Association (ACC/AHA) stage C heart failure criteria, with New York Heart Association (NYHA) class III or ambulatory class IV symptoms. Additionally, participants were required to have been receiving guideline-directed medical therapy for at least three months, as tolerated per ACC/AHA guidelines.

Further inclusion criteria encompassed a pulmonary artery wedge pressure exceeding 15 mm Hg, a mean pulmonary arterial pressure less than or equal to 20 mm Hg, and a pulmonary vascular resistance (PVR) less than or equal to 2 Woods Unit. Patients were ineligible if they lacked patent femoral venous or inferior vena cava/right jugular vein access, or exhibited a plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) level below 300 pg/ml, had experienced a stroke or thromboembolic event within the preceding 12 months, had patent foramen ovale or atrial septal defect, or presented with severe (grade 4) mitral regurgitation. Patients with coagulation disorders or contraindications for oral anticoagulation, as well as those harboring pulmonary artery, right atrial, or right ventricular thrombus, were also excluded.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Shao-Liang Chen; Phone Number: 13605157029; Email: chmengx@126.com
• Study Contact Backup: Name: Wen Gu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with heart failure

Description

Inclusion Criteria:

• aged 18 years or greater, had a documented history of chronic (≥6 months) ischaemic or non-ischaemic cardiomyopathy; ACC/AHA stage C heart failure criteria, NYHA class III or ambulatory class IV symptoms; on GDMT for heart failure at least three months; PAWP exceeding 15 mm Hg, mean PAP less than 20 mm Hg, and PVR less 2 Woods Unit

Exclusion Criteria:

Patients lacked patent femoral venous or inferior vena cava/right jugular vein access; had experienced a stroke or thromboembolic event within the preceding 12 months, had patent foramen ovale or atrial septal defect, or presented with severe (grade 4) mitral regurgitation; had coagulation disorders or contraindications for oral anticoagulation; had harboring pulmonary artery, right atrial or right ventricular thrombus; had undergone pacemaker implantation within 1 month.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular ejection fraction	Measured by echocardiography	within 3 months since PADN procedure
6 minute walk distance changes	Walk test	Within 3 months
Tricuspid annuls peak systolic excursion (TAPSE)	Measured by echocardiography	within 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	Any death	Within 3 months
Rehospitalization	Due to heart failure	Within 3 months
NT-proBNP	N-terminal-pro brain natriuretic peptide	Within 3 months
Superoxide dismutase (SOD) 3	To measure SOD concentration in PA and LV	Within 3 months
Plasma noradrenaline	From both PA and LV	within 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
All outcomes will be stratified by HFrEF and HFpEF	HFpEF denotes heart failure with preserved ejection fraction	Within 3 months

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Investigators: Study Director: Hongjuan C Peng, MBBS, Nanjing First Hospital, Nanjing Medical University, China

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: March 14, 2024
• First Submitted That Met QC Criteria: March 14, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Nanjing

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No