The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease Study

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.

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).

Eligibility Criteria:
Inclusion Criteria:

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

Exclusion Criteria:

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.