Left Atrial Distensibility to Predict Left Ventricular Filling Pressure and Prognosis in Patients With Severe Mitral Regurgitation

Introduction LA volume provides the significantly prognostic information in the general population and patients with heart disease, including acute myocardial infarction, left ventricular dysfunction, mitral regurgitation, cardiomyopathy and atrial fibrillation. Large LA volume, which represents chronic diastolic dysfunction, is associated with poor outcome, regardless of systolic function. Thereby, LA volume provides a long-term view of whether or not the patient has the disease of diastolic dysfunction, regardless of whatever loading conditions are present at the time of the examination, as the hemoglobin A1C in diabetes mellitus. Until now, the relation between LA volume and LV filling pressure confirmed directly by simultaneous echocardiography-catheterization is sparse. This study therefore assessed the correlation between LA volume and LV filling pressure in patients with severe mitral regurgitation (MR). As LA pressure rises to maintain adequate LV diastolic filling, increased atrial wall tension tends to dilate the chamber and stretch the atrial myocardium. Therefore, the smaller LA stretchability, the more pressure LA faces. The study is designed to assess 1) the relationship between LV filling pressure and LA distensibility, and 2) the power of left atrial distensibility to predict the prognosis, including operation mortality, the rate of post-operation atrial fibrillation, and late heart failure event in patients with severe mitral regurgitation.

Methods Study population: Between August 2010 and July 2012, this study will enroll 100 severe MR patients who will receive cardiac catheterization for pre-operation evaluation. Exclusion criteria are the following: 1) presence of mitral stenosis, 2) more than mild severity of aortic valvular problem, 3) any abnormality of atrial septum (e.g., atrial septal defect or aneurysm), and 4) rhythm other than sinus rhythm. MR are categorized by mapping jet expansion in the LA in 4- and 2-chamber views at end systole from three separate cardiac cycles. MR is considered severe when regurgitant jet area occupies more than 40% of the LA area. The grade of MR is increased by one degree (moderate to severe) in cases of eccentric MR jet based on evidence of reduced color-flow jet areas due to loss of momentum in jets adjacent to chamber walls. Significant coronary lesion is defined as diameter stenosis > 70% in at least one major coronary artery. The control group consisted of 50 other comorbid disease-, age- and gender-matched patients with negative results of coronary angiography, despite positive result of screen test for coronary artery disease (treadmill, Thallium scan, stress echocardiography, or 64-slides CT angiography), and they are selected after confirming no evidence of valvular heart disease by echocardiography. All patients and controls will give written informed consent to participate in the study, and the study is approved by the institutional review board.

Cardiac catheterization: Coronary angiography will be performed to evaluate hemodynamic condition and to test for coronary artery disease. The LV filling pressure is continuously recorded (50 mm/s) by a 6-F pigtail catheter placed at the apex of the left ventricle and is taken from 3 to 5 end-respiratory cycles if patients can tolerate breath holding. The LV filling pressure value is calculated as the mean of at least 3 consecutive cardiac cycles. An LV filling pressure > 15 mmHg is considered elevated.

Conventional echocardiographic and myocardial tissue Doppler measurement: Echocardiography will be performed immediately after LV filling pressure measurements. LV ejection fraction is calculated using Simpson's method for biplane images. Mitral inflow is assessed by pulsed-wave Doppler echocardiography form the apical 4-chamber view. From the mitral inflow profile, the E-wave velocity, A-wave velocity, and E-deceleration time are measured. Pulsed-wave tissue Doppler imaging (TDI) is performed using spectral pulsed Doppler signal filters, by adjusting the Nyquist limit to 15 - 20 cm/s and using the minimum optimal gain. In the apical 4-chamber view, a 3-mm, a pulsed-wave Doppler sample volume is placed at the level of the mitral annulus over the septal border. Pulsed-wave TDI results are characterized by a myocardial systolic wave (S') and 2 diastolic waves: early (E') and atrial contraction (A'). The pulsed-wave TDI tracing is recorded over 5 cardiac cycles at a sweep speed of 100 mm/s and is used for offline calculations.

Measurements of LA volume: All LA volume measurements will be calculated from apical 4- and 2-chamber views using the biplane area-length method (15). The LA volumes are measured at 3 points: 1) immediately before the mitral valve opening (maximal LV volume or Volmax); 2) at onset of the P-wave on electrocardiography (pre-atrial contraction volume or Volp); and 3) at mitral valve closure (minimal LV volume or Volmin). The LA distensibility was calculated as (Volmax - Volmin) / Volmin. The LA ejection fraction is calculated as (Volp - Volmin) / Volp. In all patients, LA volumes are indexed to body surface area (BSA).