Left Atrial Distensibility Guiding Management in Advanced Chronic Heart Failure

Background: The use of E/Em (mitral early-diastolic velocity divided by mitral early-diastolic annular velocity) assessing left ventricular filling pressure has some innate defect since it was born to assess the regional function of myocardium. It is rational to infer that ischemic heart disease with regional wall motion defect will affect the measurement of tissue Doppler and, thereupon, influence the accuracy of using regional parameters to estimate global function. Conduction disturbance with bundle branch block is another significant confounder, since it truly influences the data of regional peak Em. Therefore, it is necessary to develop or design a new global parameter to overcome the handicap of tissue Doppler. In our recent studies (1, 2), there are significant logarithmic relationships between LV filling pressure and LA distensibility in patients with acute myocardial infarction received primary percutaneous coronary intervention and in patients with severe mitral regurgitation. In patient received coronary intervention for chronic angina pectoris, the relationship is also similar (submitted to J Am Soc Echocardiogr. under major revision). In our recent ongoing study, LA distensibility is applied to low-risk general population for assessing the risk of stroke, cardiovascular event, mortality and the presence of atrial fibrillation. This time, the investigators try to use this parameter to monitor patients with advanced chronic heart failure (high-risk group) and to adjust patient's management and treatment.

Introduction LA volume provides the significantly prognostic information in the general population and patients with heart disease, including acute myocardial infarction (3), left ventricular dysfunction (4, 5), mitral regurgitation (6), cardiomyopathy (7, 8) and atrial fibrillation (9). Large LA volume, which represents chronic diastolic dysfunction, is associated with poor outcome, regardless of systolic function (10). 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 (10). Until recently, the relation between LA volume and LV filling pressure has been confirmed directly by simultaneous echocardiography-catheterization, which those studies were conduced by our team (1, 2). LA distensibility is associated logarithmically with left ventricular filling pressure in patients with chronic stable angina, acute myocardial infarction, or severe mitral regurgitation. It can be treated as non-invasive Swan-Ganz catheter, which isn't likely to affect by the tissue Doppler confounders of regional wall motion defect and bundle branch block. Since the relationship between LA distensibility and left ventricular filling pressure is logarithmic, LA distensibility would be relatively insensitive in the low-pressure end. Therefore, the investigators conduct an investigation that assesses the risk stratification of cardiovascular risk by LA distensibility in low-risk general population (potential low left ventricular filling pressure) from 2009. This time, LA distensibility will be used to guide the treatment of advanced chronic heart failure.

Methods Study population: Advanced chronic heart failure (HF) will be defined as left ventricular ejection fraction less than 35%, creatinine less than 2 mg/dL, and CHF NY functional class III-IV for more than 3 months. Enrolled patients should be admitted to hospital due to heart failure requiring adjustment of inotropic agents or diuretics within recent 6 months. Three hundred HF cases will be recruited - 100 with sinus rhythm, and 100 with atrial fibrillation served as LA distensibility guided treatment group (guide group) and another 100 patients, either sinus rhythm or atrial fibrillation, served as control group. The management of guide group will be adjusted by LA distensibility, including the adjustments of inotropic agents, diuretics, beta-blocker, ACEI, and AIIB. The control group will be treated by conventional management and traditional echocardiography can be performed as in-charge doctor request. Renal function will be checked 1 time per 3 months. All patients will give written informed consent to participate in the study, and the study will send to the institutional review board for approval.

Conventional echocardiographic and myocardial tissue Doppler measurement: Echocardiography will be performed in each patient initially. 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 (Sm) and 2 diastolic waves: early (Em) and atrial contraction (Am). 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 (11). The LA volumes are measured at 3 points: 1) immediately before the mitral valve opening (maximal LA 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 LA 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) (12). For patients with atrial fibrillation, the average of 5 LA distensibilities will be used for clinical assessment.