CMR Right Ventricular Contractile Reserve Following Lung Resection

Assessment of Right Ventricular Contractile Reserve Following Lung Resection by Dobutamine Stress Cardiac Magnetic Resonance: a Feasibility Study

Feasibility study investigating CMR dobutamine stress testing before and after lung resection

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer; Surgery; Anesthesia
• Intervention / Treatment: Diagnostic test: Dobutamine stress CMR; Diagnostic test: Cardiac biomarker sample

Detailed Description

We hypothesise that following lung resection,

1. the subtle decrease in RV function and increase in afterload we have demonstrated at rest is associated with a marked impairment of RV function on exercise, termed impaired RV contractile reserve (RVCreserve),
2. impaired RVCreserve is associated with impaired functional capacity .

In this study we aim to assess the feasibility of dobutamine stress cardiovascular magnetic resonance (CMR) scanning to assess RVCreserve pre- and post-operatively in patients undergoing lung resection.

Additionally, we hypothesise that one lung ventilation (with and without lung resection) is associated with biomarker evidence of RV injury.We will perform peri-operative cardiac biomarkers to differentiate between the contribution of major surgery (gastrectomy, lung resection and oesophagectomy), one lung ventilation (lung resection and oesophagectomy) and lung resection on RV injury.

• Study Type: Observational
• Enrollment (Estimated): 42

Contacts and Locations

• Study Contact: Name: Adam Glass; Phone Number: +442890976378; Email: a.glass@qub.ac.uk
• Study Contact Backup: Name: Jon Silversides; Email: j.silversides@qub.ac.uk

Study Locations

• United Kingdom
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT12 6BA
      • Recruiting
      • Belfast Health and Social Care Trust
      • Contact: Jon Silversides; Phone Number: 02895041096; Email: jon.silversides@belfasttrust.hscni.net
      • Contact: Adam Glass
      • Contact: Danny McAuley
      • Contact: Jon Silversides

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients presenting for surgical resection of lung, oesophagus or stomach.

Description

Inclusion Criteria:

• 1) Provision of informed consent 2) Age >16 years 3) Planned elective

  1. lobectomy lung resection or
  2. oesophagectomy surgery with one lung ventilation or
  3. gastrectomy

Exclusion Criteria:

1. Pregnancy
2. On-going participation in any investigational research which could undermine the scientific basis of the study
3. Atrial fibrillation at baseline

4. Any contraindication to

   a. CMR, i. Cardiac pacemaker, artificial heart valve, neurostimulator, cochlear implant ii. Aneurysm clips iii. Metal injuries to the eye iv. Loose metal in a part of the body b. Dobutamine stress testing as per the Society for Cardiovascular Magnetic Resonance64 i. Severe systemic arterial hypertension (≥220/120 mmHg) ii. Unstable angina pectoris iii. Severe aortic valve stenosis (peak aortic valve gradient >60mmHg or aortic valve area < 1cm2) iv. Complex cardiac arrhythmias including uncontrolled atrial fibrillation v. Hypertrophic obstructive cardiomyopathy vi. Myocarditis, endocarditis, or pericarditis vii. Uncontrolled heart failure

5. Lung resection specific

   1. Wedge, segmental or sub-lobar lung resection
   2. Pneumonectomy

   3. Isolated right middle lobectomy

      -

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Lung resection; 12 patients undergoing lobectomy. Pre and post-operative dobutamine stress CMR testing and cardiac biomarker testing.	Diagnostic test: Dobutamine stress CMR; Dobutamine stress testing will be undertaken in keeping with local departmental clinical guidelines with a graded increase in dobutamine infusion up to a maximum of 10microgram/kg/min. The patients' medications will be managed in keeping with the usual clinical practice and departmental guidelines. At rest and on each graded level of dobutamine infusion we will collect cine loops of the cardiac cycle including a short-axis stack of the ventricles, a four-chamber view and flow imaging perpendicular to the main, left and right pulmonary arteries. Post-processing will be dual reported by blinded observers using the Argus analysis software (Siemens) according to a standardised protocol. A safety report of each CMR scan will be generated by a consultant cardiologist, any abnormalities identified will be referred to the appropriate medical speciality and highlighted to the patient's clinical team.; Diagnostic test: Cardiac biomarker sample; blood samples will be collected pre-operatively, in recovery, on post-operative days 1 and 2, and at 4-8 weeks post-operatively
Oesophagectomy; 15 patients Peri-operative cardiac biomarker testing.	Diagnostic test: Cardiac biomarker sample; blood samples will be collected pre-operatively, in recovery, on post-operative days 1 and 2, and at 4-8 weeks post-operatively
Gastrectomy; 15 patients Peri-operative cardiac biomarker testing.	Diagnostic test: Cardiac biomarker sample; blood samples will be collected pre-operatively, in recovery, on post-operative days 1 and 2, and at 4-8 weeks post-operatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) Feasibility of dobutamine stress CMR to measure RVCreserve following lung resection.	Reliability and variability will be assessed through dual reporting of the CMR images, testing intra-/inter-observer intraclass correlation coefficient (ICC) and coefficient of variation (CV). Study design will allow comparison to our previous resting studies published exercise literature and between pre- and post-operative imaging.	Pre-operative and 2 months post-operative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1) Acceptability of the dobutamine stress CMR protocol to patients, by questionnaire	Assessed by patient satisfaction questionnaires rate compared to our previous CMR studies that were performed without dobutamine stress testing.	Pre-operative and 2 months post-operative
1) Acceptability of the dobutamine stress CMR protocol to patients, by completion	Assessed by patient recruitment/withdrawal rate compared to our previous CMR studies that were performed without dobutamine stress testing.	Pre-operative and 2 months post-operative
2) Incidence of complications related to dobutamine stress CMR	We will assess for the onset of any of the following during the scan; New onset atrial fibrillation; Ventricular tachycardia; Angina, chest pain, shortness of breath and/or ischaemic ECG changes	Pre-operative and 2 months post-operative
3) Change in RVCreserve change following lung resection	Comparison of the change in RVEF on stress pre- and post-operatively	Pre-operative and 2 months post-operative
4) Change in PVreserve change following lung resection	Comparison of change in wave reflection on stress pre- and post-operatively	Pre-operative and 2 months post-operative
5) Association between the changes in RVCreserve and markers of cardiac inflammation, BNP	Comparison of change in RVCreserve and the change in BNP	Pre-operative and 2 months post-operative
5) Association between the changes in RVCreserve and markers of cardiac inflammation, hsTnT	Comparison of change in RVCreserve and the change in hsTnT.	Pre-operative and 2 months post-operative
1) Post-operative change in BNP	Post-operative change in BNP in oesophagectomy compared to lung resection and gastrectomy.	Peri-operative blood samples, pre-op, immediately post-op, post-op days 1 and 2, 4-8 weeks post-op

Collaborators and Investigators

• Sponsor: Belfast Health and Social Care Trust

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: September 6, 2023
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Dobutamine
• Other Study ID Numbers: 22066JS-AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No