The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease Study

NCT03155373 | Completed Results

• 3 other identifiers: 16HH363916/LO/2127199676
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Mitral regurgitation (MR) is a prevalent valvular heart pathology. Indications for surgery include symptoms, impaired left ventricular function or enlarging dimensions, new onset atrial fibrillation, pulmonary hypertension, asymptomatic status with a high likelihood of success. Asymptomatic severe primary MR can be initially monitored without impairing long term survival. However, significant symptoms or impairment of left ventricular function is associated with worse prognosis due to long term heart failure. Some physicians wait for early symptoms before referring for surgery and this is reflected by a great variation in referral patterns, but symptomatic status is subjective and difficult to assess. Nearly all of the surgical indications are based on expert opinion rather than significant evidence base. The primary aim of this project is to improve the current guidelines for surgery for primary MR by finding an objective marker of functional capacity which correlates with surrogates of prognosis and detects early decline, but returns to normal after surgery.

Conditions

Mitral Regurgitation; Pulmonary Hypertension

Keywords

Cardiopulmonary exercise testing

Outcome Measures

Primary Outcomes (2)

• Impaired Post-operative Functional Capacity

  Dichotomic variable of post-operative left ventricular ejection \< 50% and/or post-operative percentage predicted peak VO2 \<= 84%

  1 year

• Imaging Data

  Correlation between transthoracic echocardiogram and cardiac MRI parameters

  1 year

Secondary Outcomes (3)

• Right Heart Catheterisation

  Pre-op

• Quality of Life as Assessed by SF36 Survey

  Baseline (preoperatively), early follow up (6 weeks after surgery), late follow up (6 months after surgery)

• Myocardial Histology

  At surgery

Study Arms (3)

A

Asymptomatic/mild symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction \>60%)

Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies

B

Symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction greater than or equal to 60%)

Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies

C

Patients with impaired pre-operative left ventricular function (defined as left ventricular ejection fraction \<60%)

Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies

Interventions

Cardiac catheterisation DIAGNOSTIC_TEST

Pre-operative left heart catheterisation +/- right heart catheterisation

A; B; C

Cardiopulmonary exercise testing DIAGNOSTIC_TEST

Pre and post-operative cardiopulmonary exercise testing

A; B; C

Pulmonary function tests DIAGNOSTIC_TEST

Pre and post-operative pulmonary function tests

A; B; C

Cardiac MRI DIAGNOSTIC_TEST

Pre and post-operative cardiac MRI

A; B; C

Quality of life survey OTHER

Pre and post-operative quality of life survey (SF36)

A; B; C

Mitral valve operation PROCEDURE

Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery

A; B; C

Myocardial biopsies PROCEDURE

Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery

A; B; C

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients undergoing cardiac surgery for severe primary/degenerative mitral regurgitation under the current guidelines.

You may qualify if:

• Patients listed for surgery for severe primary mitral regurgitation +/- concomitant coronary artery bypass grafting for bystander disease +/- tricuspid valve surgery +/- atrial fibrillation surgery.

You may not qualify if:

• Secondary mitral regurgitation. Significant history of ischaemic heart disease eg. angina. Age \<18 years or \>85 years. Critical preoperative status with multi-organ dysfunction. Emergency cardiac surgical intervention. Pregnancy. Unable to give informed consent or unwilling to participate in research. Patients with definite contraindication for MRI would be excluded from the cardiac MRI element of the study.
• Patients we are unable to take adequate biopsies due to technical difficulties would be excluded from the myocardial biopsy element of the study.

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Left and right ventricular biopsies taken at time of clinically indicated surgery

MeSH Terms

Conditions

Mitral Valve Insufficiency; Hypertension, Pulmonary

Interventions

Cardiac Catheterization; Exercise Test; Respiratory Function Tests

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Catheterization; Therapeutics; Investigative Techniques; Diagnostic Techniques, Respiratory System; Ergometry

Limitations and Caveats

In the initial planning of this project, there were 3 defined arms. However, due to the small n number of patients recruited; there were insufficient numbers for meaningful analysis. Professional statistical advice was to analyse the entire cohort with the pre-defined dichotomous outcome of impaired functional status based on current evidence base/international guidelines (post-op LVEF \<50% and percentage predicted peak VO2 \<=84%) and a multivariate analysis of four pre-defined variables.

Results Point of Contact

• Title: Jonathan Afoke
• Organization: Imperial College Healthcare NHS Trust

j.afoke@nhs.net

02033132026

Study Officials

• Prakash Punjabi, FRCS

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Simon Gibbs, FRCP

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 16, 2017
• Study Start: February 15, 2017
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: February 28, 2023
• Results First Posted: February 28, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)