Right Ventricular Afterload Indices in Lung Surgery (RAILS)

September 3, 2026 updated by: Dr Ben Shelley, University of Glasgow

Characterising Pressure-derived Right Ventricular Afterload Indices During Lung Resection Surgery - a Feasibility Study

Lung cancer is a leading cause of cancer death in Scotland and the UK. Surgery, typically using a keyhole approach, provides the best chance of cure. Golden Jubilee National Hospital performs over 600 operations each year, making this the busiest lung surgery department in the country. Unfortunately, some patients suffer disabling breathlessness and a limited ability to perform even very gentle exercise after surgery, even if they had no breathing problems before surgery. Understanding the causes and preventing this breathlessness is the focus of this research.

Despite advances in techniques, lung cancer surgery can result in long-term weakening of the muscular chamber of the right (-hand side of the) heart which pumps blood to the lungs. During surgery, the pressure against which this pump works increases, making it more difficult to push blood into the lungs.

Even after surgery, when the pressure returns to normal, the right heart can remain weak. This weakening can contribute to breathlessness and exercise limitation. Preventing or reducing this right heart weakening may improve quality of life after surgery.

The investigators are interested in understanding why this weakening occurs after lung surgery and then to develop treatments to prevent it. The answer may lie in reversing the high resistance against which the heart pumps during surgery. Ultimately, the aim is to improve patients' recovery from surgery and improve both breathing and the ability to exercise. This problem may be treatable with existing drugs which are proven to be safe, easy to deliver and are already available. These drugs can be given around the time of surgery.

This study will not involve administering new treatments, though future clinical trial(s) are anticipated. Participants' care will be the same as is usually provided. Participants taking part will undergo more tests and monitoring than usual to help understand the changes taking place during and after surgery.

Before a drug trial to test this idea, there are some key things to clarify . This study plans to recruit 15 participants having keyhole lung cancer surgery. The following will be performed:

Blood Tests: blood samples before and after surgery to check for heart injury.
Heart monitoring: temporarily insert a thin tube called a right heart catheter into a large blood vessel in the participants' neck the morning of surgery. This will allow continuous measurement of the pressure in the right heart and lung blood vessels. This will help design and deliver treatments, and how best to measure the effects. This heart catheter will be removed the day after surgery.
Heart scans: perform magnetic resonance imaging (MRI) scans before and after surgery to measure blood flow and examine the impact of surgery on the heart.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The investigators hypothesise that a transient, acute rise in right ventricular (RV) afterload occurring during lung resection surgery triggers a sterile inflammatory RV injury resulting in persistent RV dysfunction - even in the absence of sustained postoperative pulmonary vascular resistance - which contributes to disabling postoperative dyspnoea and exercise limitation.

Therapeutic pulmonary vasodilation is a mainstay of treatment to reduce RV afterload and improve V/Q matching in complex conditions such as pulmonary hypertension, thoracic organ transplant, respiratory distress syndromes and congenital cardiac disease, with well-established safety and feasibility profiles. Anti-inflammatory and cytoprotective properties have also been demonstrated. The inhaled route provides systemic and renovascular stability, ease of administration, selective targeting of the pulmonary vasculature, with high bioavailability and a short half-life. Unlike traditional approaches focussing on PH management, the application of IPVs for postoperative RV dysfunction may simultaneously address both contractility and afterload reduction.

Perioperative inhaled pulmonary vasodilator (IPV) therapy may prove to protect the RV from the relatively homogenous insult occurring in controlled clinical conditions as described above. Prior to clinical trials of IPVs, it is necessary to first demonstrate the feasibility of continuous RV / pulmonary vascular haemodynamic perioperative monitoring in lung resection, understand the time course of the perioperative afterload insult and characterise pulmonary vasoreactivity. This study seeks to characterise intraoperative haemodynamics, demonstrating feasibility and inform power calculation for a future early phase IPV trial in lung resection patients.

Aims

Perform a pragmatic single-centre, prospective study of adults undergoing elective lung resection by VATS and RATS to:

Assess the feasibility and quality of continuous pressure-derived right ventricular afterload measurement using right heart catheterisation in contemporary elective thoracic surgical patient pathway.
Characterise perioperative RV and PA haemodynamics (PVR/time area under curve relationship) throughout the perioperative lung resection pathway.
Quantify perioperative pulmonary vasoreactivity.

Methods

RHC and continuous cardiac output (CCO) monitoring with novel "RVCO" (right ventricular cardiac output) algorithm to permit continuous perioperative RV/pulmonary haemodynamic measures.
Contrast CMR to quantify cardiopulmonary blood flow, as the gold standard measure against which other measures (RHC) are compared.
Interval cardiac biomarker (HsTn & BNP) measurement to provide standard for measurement of perioperative RV injury.
Characterise perioperative pulmonary vasoreactivity using oxygen and iNO.
Conduct validated patient-reported quality of recovery questionnaires.

Primary objective

• Assess the feasibility of collecting perioperative RHC-derived CCO RV/pulmonary haemodynamic data in 15 adult patients undergoing elective lung resection.

Secondary objectives

Obtain perioperative (esp. intraoperative) PVR vs time area under the curve (AUC).
Characterise scale, chronology and predictability of intraoperative pulmonary vasoreactivity.
Quantify the cardiac bio-inflammatory response to lung resection.
Clinical and patient-reported outcome measures.
Assess the precision of RHC-measured, RVP waveform-derived PA flow waveform against CMR (gold standard for flow volumes).

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Ben Shelley, MBChB, MD
Phone Number: 4293 +44(0)1419515000
Email: benjamin.shelley@glasgow.ac.uk

Study Contact Backup

Name: Gareth Lipton, MBChB
Phone Number: 4293 +44(0)1419515000
Email: gareth.lipton@glasgow.ac.uk

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

The study population will be comprised of elective (planned) adult patients listed for minimally invasive (robotic- or video-assisted thoracoscopic surgery: RATS, VATS) lobectomy for lung cancer under general anaesthesia with one-lung ventilation at GJNH, a large national tertiary cardiothoracic centre located in Clydebank, Glasgow, UK.

Description

Inclusion Criteria:

Age ≥18
Presumed or confirmed non-small cell lung cancer
Planned (elective) minimally invasive (VATS/RATS) lobectomy using OLV
Able to provide informed consent

Exclusion Criteria:

Pulmonary / RV physiological: Severe right sided valvular (tricuspid, pulmonary) disease, Preoperative atrial fibrillation / flutter / non-controlled tachydysrhythmia, Severe RA/RV dilatation, Severe PH (mPAP >55mmHg).
Awake RHC contraindicated: Severe coagulopathy (PTr >1.5, PTTr >1.5), Thrombocytopenia (<50x109/L), Abnormal vasculature, Unable to lie supine and head down, Endocarditis or intra-cardiac tumour or thrombus, Right-sided valve prosthesis or other implanted cardiac device (e.g. pacing wire), Skin/soft tissue infection overlying insertion point.
CMR contraindicated: Severe claustrophobia/unable to lie supine, Class III obesity (BMI >40), Presence of non-MRI compatible foreign body or implanted device.
Gadolinium contrast contraindicated: CMR contraindicated (as above) and/or: Intravenous (IV) contrast (Gadolinium) allergy, Acute or chronic renal failure (eGFR <59ml/min).
Surgical / medical: Planned sub-lobar resection / wedge resection / isolated middle lobectomy / segmentectomy / pneumonectomy, Planned secondary procedure (e.g. mediastinal/cardiac), Pregnancy.
Research: Ongoing participation in other investigational research which would undermine the scientific basis of this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients for whom meaningful haemodynamic data is obtained at clinically relevant timepoints Time Frame: 24 hours	Time per patient from initiation of right heart catheter (RHC)-derived continuous cardiac output (CCO) monitoring to planned postoperative RHC removal that high-quality* RV/pulmonary haemodynamic data is obtained: *High quality defined as: ≥80% of patients (≥12/15) in whom ≥80% of planned time point measurements can be obtained for the duration of the planned (24 hour) CCO monitoring window. Proportion of planned time per patient in which RHC provides any CCO monitoring for the duration of the planned (24 hour) CCO monitoring window. Number of patients in whom RHC dislodged and/or premature removal required.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemodynamic 1: PVR vs time Time Frame: 24 hours	Perioperative PVR (Wood units) vs. time (seconds) area under the curve (AUC)	24 hours
Haemodynamic 2: RHC-derived vs. CMR-derived pulmonary artery flow Time Frame: 24 hours	RHC-derived PA flow (RVP waveform analysis: L/min) vs CMR-derived PA flow (L/min)	24 hours
Vasoreactivity Time Frame: 24 hours	% reduction in PVR on vasoreactivity testing (before vs during vs after OLV).	24 hours
Cardiac biomarker 1: BNP Time Frame: 48 hours	Serum B-type natriuretic peptide (BNP) level preoperatively, postoperative days 1 and 2.	48 hours
Cardiac biomarker 2: HsTn Time Frame: 48 hours	Serum high-sensitivity troponin (HsTn) level preoperatively, postoperative days 1 and 2.	48 hours
Clinical indicator 1: Length of stay Time Frame: 30 days	Length of postoperative hospital stay (days)	30 days
Clinical indicator 2: Mortality Time Frame: 30 days	Mortality at 30 days.	30 days
Clinical indicator 3: Unplanned hospital readmission (all cause) Time Frame: 30 days	Unplanned hospital readmission (all cause) at 30 days.	30 days
Validated patient-reported outcome: quality of recovery Time Frame: 48 hours	Fifteen-item Quality of Recovery-15 (QoR-15) scale, a fifteen-item patient-reported questionnaire, each question scored on 11-point scale from 0-10, where 0 is very poor and 10 is excellent. Minimum score 0, maximum score 150.	48 hours
Postoperative complications at 30 days: highest Clavien-Dindo score Time Frame: 30 days	Postoperative in-hospital complications during index surgical admission within 30 days of surgery. The outcome measure is the highest Clavien-Dindo score (only score ≥2 included) [scored 1-5 with 5 representing the greatest degree of severity] informed by the Standardising Endpoints in Perioperative trials consensus definitions. The following complication domains are included: Cardiovascular Renal Pulmonary Infection Neurological	30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Glasgow

Collaborators

Golden Jubilee National Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Murphy E, Glass A, McCall P, Shelley B. Myocardial inflammation after major non-cardiac thoracic surgery. British Journal of Anaesthesia, 126, e80-e81. DOI: 10.1016/j.bja.2020.11.012.
Murphy E, Glass A, McCall P, Shelley B. Peri-operative kinetics of B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in patients undergoing lung resection: An observational cohort study. Eur J Anaesthesiol. 2025 May 1;42(5):480-482. doi: 10.1097/EJA.0000000000002137. Epub 2025 Feb 14. No abstract available.
Shelley B, Glass A, Keast T, McErlane J, Hughes C, Lafferty B, Marczin N, McCall P. Perioperative cardiovascular pathophysiology in patients undergoing lung resection surgery: a narrative review. Br J Anaesth. 2023 Jan;130(1):e66-e79. doi: 10.1016/j.bja.2022.06.035. Epub 2022 Aug 13.
McCall PJ, Arthur A, Glass A, Corcoran DS, Kirk A, Macfie A, Payne J, Johnson M, Kinsella J, Shelley BG. The right ventricular response to lung resection. J Thorac Cardiovasc Surg. 2019 Aug;158(2):556-565.e5. doi: 10.1016/j.jtcvs.2019.01.067. Epub 2019 Jan 26.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 1, 2026

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

October 1, 2027

Study Registration Dates

First Submitted

August 24, 2026

First Submitted That Met QC Criteria

September 3, 2026

First Posted (Actual)

September 10, 2026

Study Record Updates

Last Update Posted (Actual)