Left atrial function in health and disease

The Objectives of this thesis are: 1) To study possible atrial interaction in patients with right and left ventricular outflow tract obstruction due to significant pulmonary (PS) and aortic valve stenosis (AS), respectively. 2) To assess left atrial (LA) intrinsic myocardial function and its relationship to indirect measures of left ventricular (LV) filling pressures in patients with paroxysmal atrial fibrillation (PAF). 3) To test the hypothesis that the LA function is affected in patients with pulmonary arterial hypertension (PAH). 4) To test the hypothesis that raised LA pressure as shown by pulmonary capillary wedge pressure (PCWP) correlates with severity of LA intrinsic systolic function. We conducted 4 studies to achieve the objective sabove. Study I Methods: We studied 41 PS patients (age 36±10 year) and 41 AS patients (age 35 ± 12 year) and compared them with 27 controls (age 30 ± 7 year). RV and LV filling were recorded by conventional PW Doppler. Biventricular segmental function was studied using the PW tissue Doppler imaging (TDI) and M mode techniques. Results: The 2 patient groups had similar degree of ventricular outflow tract obstruction. In the pressureoverloaded ventricle, global systolic function was preserved but long axis function was impaired.Patients had higher peak late filling (Awave)and TDI late diastolic (a’) velocities recorded in the disease free ventricles despite having similar peak early filling velocities (E wave), E wave deceleration time and E/e’ ratios were not different from controls (p>0.05 for all). The accentuation of atrial activity (A wave) was moderately correlated with the degree of contra lateral ventricular outflow tract obstruction (p<0.001 for both). Conclusion: In the pressure overloaded ventricle long axis function is more sensitive than global function in revealing myocardial dysfunction. The increased contra lateral atrial systolic activity suggests an evidence for atrial interaction in the form of ‘Cross Talk’. Study II Methods: Twentyfive PAF patients (age 68±7 year, 10 males) with Doppler signs of raised filling pressures were studied using speckle tracking echocardiography and compared with 21 controls. LA segmental longitudinal strain (S), strain rate (SR) and myocardial velocities during atrial systole were measured as were LA longitudinal and transverse diameters. Markers of LV filling pressures were E/A andE/e’. Results: LA longitudinal diameter was larger in patients (5.5±0.6 vs. 4.8±0.6cm,p<0.01) and global LAS and SR were reduced (p<0.05 for both) and correlated with E/A (r=0.52 and r=0.43, p<0.05 for both). LA segmental S and SR were uniformly reduced compared with controls (p<0.05 for all) and also correlated with E/A (p<0.05 for all). LA myocardial velocities (TDI) were highest at the annular level and lowest at the rear in both patients and controls (p<0.01 for all), with the absolute values at each level not different between groups. Myocardial velocities negatively correlated with E/A at the annular level only in patients (septal: r=0.52; lateral: r=0.62, p<0.01 for both). Conclusion: In PAF patients, LA systolic function is suppressed and is directly related to the raised filling pressures. While intrinsic global and segmental function can reproducibly be studied by S and SR, myocardial velocities reflect only regional motion. These findings provide a sound explanation to the known beneficial effect of vasodilators in PAF patients. Study III Methods: We studied LA size and reservoir function in 35 patients (age 63 ± 15 years, 16 male) with idiopathic PAH using speckle tracking echocardiography who also underwent right heart catheterization simultaneously to assess pulmonary artery systolic pressure, and compared them with 27 age and gender normal controls. Results: In PAH patients, LA longitudinal diameter was not different from controls but transverse diameter was reduced (3.0 ± 0.6 vs. 3.7 ± 0.5cm, p<0.001). LA lateral wall strain rate (SR) during LV systole (atrial reservoir function was reduced at annular (p<0.001) and mid cavity (p<0.01) levels as were septal segments (p<0.03, for both) compared to controls. Opposite to controls, the two LA walls responded differently to right heart pressures. Lateral SR inversely correlated with pulmonary artery systolic pressure (PASP) (annular: r=0.45, p<0.005 and midcavity: r=0.43, p<0.01), but not with right atrial pressure (RAP). In contrast, septal SR inversely correlated with RAP (annular: r=0.39, p=0.02 and midcavity: r=0.38, p=0.03) but not with PASP. Conclusion: In patients with PAH, LA reservoir function is significantly impaired showing reduced myocardial strain rate properties. In addition,segmental function differs in their response to raised right heart pressures with the septal wall related to right atrial pressure and lateral wall related to the PASP. These findings suggest an evidence for atrial interaction in PAH, which is likely to have significant impact on LV performance. Study IV Methods: We studied 46 patients, mean age 61 ± 13 years, 17 males, of various etiologies with exertional breathlessness who underwent right heart catheterization and simultaneous transthoracic Doppler echocardiography using spectral, tissue Doppler and speckle tracking echocardiography techniques for assessing LA structure and function. Results: PCWP correlated with direct measurements of LA structure and function: LA volume (r= 0.43, p<0.01), LA global systolic strain rate (r=0.79, p<0.001) and to a lesser extent with LA systolic filling fraction (r=0.52, p<0.001). PCWP also correlated with indirect measures of LA pressure: LV E/A (r=0.66, p<0.001), E wave deceleration time (r=0.54, p<0.001), lateral E/e’ (r=0.49, p<0.001) and LV isovolumic relaxation time (r=0.36, p<0.01). LA strain rate was 78% sensitive and 84% specific in identifying patients with PCWP>15 mmHg, having accurately predicted PCWP in 63% of the cases. Conclusion: PCWP correlates with LA intrinsic systolic function and to a much lesser degree with indirect Doppler measures of raised LV filling pressures. These findings should have significant clinical implications in identifying breathless patients with raised LA pressure