The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease Study
Condition: Mitral Regurgitation; Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Mitral Valve Insufficiency
Study type: Observational

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.
    

Detailed description: 
      The current indications for surgery for MR include symptomatic status; asymptomatic status
      with echocardiographic features such as impaired left ventricular function or increased left
      ventricular dimensions; new onset atrial fibrillation or pulmonary hypertension; asymptomatic
      status with a high likelihood of durable repair and low co-morbidity. The limitation in
      strength of the current evidence base is reflected by the class of evidence being expert
      opinion (level C) for all of the above indications with the sole exception of symptomatic
      patients, which is level B.

      The fulcrum point between asymptomatic status and symptomatic status at which patients would
      derive prognostic benefit and thus should be referred for surgery on prognostic grounds still
      remains unclear and controversial. Although elective mitral valve repair carries a low risk
      of mortality, it has been demonstrated that asymptomatic patients with severe degenerative MR
      can be safely followed up before becoming symptomatic or reaching cutoff values for left
      ventricular dimensions, size or pulmonary hypertension; with no significant difference with
      expected survival. As a result, it is debatable whether prophylactic surgery for all patients
      with asymptomatic severe degenerative MR derives prognostic benefit.

      At the other end of the clinical spectrum, the increased operative mortality and worse long
      term prognosis of symptomatic patients is well proven. Patients with New York Heart
      Association Class III or IV status have excessive operative mortality and significantly
      increased mortality at 10 years. Both this study and another have demonstrated that
      preoperative ejection fraction is an independent predictor of long term survival. Although
      this evidence base does not support prophylactic surgery on asymptomatic patients, it does
      highlight the importance of avoiding the long term sequelae of MR in causing symptomatic
      status or left ventricular impairment. Hence attention has turned to objective markers or
      investigations independent of symptomatic status that may be subjectively assessed in the
      early phases; to help identify patients who would prognostically benefit from earlier
      surgical intervention.

      In summary, severe mitral regurgitation is a common valvular pathology that causes a
      significant burden of disease. Current guidelines for timing of operative intervention are
      mostly based on expert opinion rather than randomised trials or studies. The ideal tipping
      point investigation will be an objective marker of functional capacity which correlates with
      known surrogates of survival such as left ventricular function; and detects early decline,
      but returns to normal after successful surgery. The improved evidence base will create an
      epidemiological shift in patterns of referring for mitral valve surgery and reduce the burden
      of disease of heart failure.

      Patients will undergo the following investigations:

      Right heart catheterisation- It is the usual gold standard practice at our institution for
      patients to have a right heart catheterisation before being referred for surgery. Those who
      have not had one may be referred to the Department of Cardiology at Hammersmith Hospital for
      this test.

      Cardiac MRI- patients will have a T1 weighted cardiac MRI. One strength of cardiac MRI over
      transthoracic echocardiogram is objective measurements of right heart function. Parameters
      measured will be ventricular ejection fraction and dimensions, patterns of myocardial
      fibrosis.

      Cardiopulmonary exercise testing (CPEX)- CPEX is a quantitative and validated method of
      assessing cardiorespiratory function and exercise capacity with commonly measured variables
      including maximal oxygen consumption (VO2 max) and the clearance of carbon dioxide during
      exercise (Ve/VCO2). The patient's gaseous exchange is monitored during a 3 minute rest
      period, a three minute "rolling basal" period when they perform exercise on a bicycle with no
      load; and subsequently during the exercise phase when the work load increases at a rate of 30
      Watts per minute. Exercise continues until the patient has to stop or achieves predicted
      maximum heart rate.

      Pulmonary function tests- Patients will have routine spirometry tests and also assessment of
      transfer factor.

      Transthoracic echocardiogram- It is normal practice for patients to have an echocardiogram at
      preassessment clinic to assess biventricular function, dimensions and cardiac structural
      disease.

      Quality of life questionnaire- Patients will be asked to fill out a validated questionnaire
      (SF-36 health survey).
    

Intervention name(s): Cardiac catheterisation; Cardiopulmonary exercise testing; Pulmonary function tests; Cardiac MRI; Quality of life survey; Mitral valve operation; Myocardial biopsies
Intervention type(s): Diagnostic Test; Diagnostic Test; Diagnostic Test; Diagnostic Test; Other; Procedure; Procedure
Intervention description(s): Pre-operative left heart catheterisation +/- right heart catheterisation; Pre and post-operative cardiopulmonary exercise testing; Pre and post-operative pulmonary function tests; Pre and post-operative cardiac MRI; Pre and post-operative quality of life survey (SF36); Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery; Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients undergoing cardiac surgery for severe primary/degenerative mitral regurgitation
        under the current guidelines.
      
Biospecimen description: 
      Left and right ventricular biopsies taken at time of clinically indicated surgery
    
Keywords: Cardiopulmonary exercise testing