Study Population

Twenty-five patients who had dual-chamber (DDD) pacemaker implanted either for sick-sinus or carotid-sinus syndrome were included in this prospective study. All patients presented in sinus rhythm (SR) at their regularly scheduled visits at the pacemaker clinic of our hospital, and only patients with atrial and/or ventricular pacing < 20% on interrogation of the pacemaker were included. All patients had the ventricular lead placed at the right ventricular apex and the atrial electrode at the right atrial appendage. Patients with structural heart disease, more than mild valvular regurgitation and any degree of valve stenosis, known coronary heart disease or symptoms suggestive of coronary heart disease, atrioventricular block, bundle branch block, or atrial fibrillation, symptomatic heart failure or an ejection fraction < 50% were excluded from the study. Informed consent was given by all study participants, and the study protocol was approved by the scientific committee of “Alexandra” University Hospital.

Study Protocol

Interrogation of the pacemaker was performed and the baseline characteristics and functional parameters of the pacemaker were noted. A comprehensive baseline echocardiographic study in SR was also performed. Atrial (AAI) pacing at 10 beats/min above baseline (to ensure continuous atrial pacing) was then performed for 5 min before a second echocardiographic evaluation. After 5 min in SR, DDD pacing was applied at 10 beats/min above the baseline sinus rate, with an atrioventricular delay 20 msec shorter than the intrinsic rate to ensure continuous atrial and ventricular pacing. Further echocardiographic images were acquired after 5 min of DDD pacing, which was again followed by a 5-min period in SR. Finally, VVI pacing was performed for 5 min at 10 beats/min above the baseline SR heart rate, and a last echocardiographic evaluation was performed.

Echocardiography

In each individual, a standard, comprehensive baseline two-dimensional, M-mode, and Doppler study was performed in SR. Study participants were imaged in the left lateral decubitus position with a commercially available system (GE Vivid 7 Dimension; GE Vingmed Ultrasound AS, Horten, Norway) using a 3.5-MHz (M4S) transducer.

Parasternal long-axis views were used to measure LV internal dimensions at end-diastole and end-systole, interventricular septal and posterior wall thickness, and left atrial end-systolic diameter according to the recommendations of the American Society of Echocardiography. LV end-diastolic and end-systolic volumes, as well as ejection fraction, were derived from the apical four- and two-chamber views using the biplane Simpson’s rule. The Doppler examination included interrogation of mitral inflow, and early (E) and late (A) peak diastolic velocities and deceleration time were measured. Tissue Doppler analysis included pulsed-wave interrogation of the medial and lateral mitral annulus, and the mean value was calculated. Peak diastolic early e′ and late a′ annular velocities were obtained, and the E/e′ ratio was calculated.

Speckle-Tracking Echocardiography

Speckle-tracking analysis was applied to estimate LV rotational mechanics and circumferential strain parameters. Parasternal short-axis views at the level of the mitral valve and apex and standard apical views (four-, two-, and three-chamber) were recorded for each study participant during each pacing mode, according to the recommendations of the European Association of Echocardiography and the American Society of Echocardiography. Five consecutive beats in each view were stored digitally for offline analysis. The frame rate was set at 50 to 100 frames/sec, the sector width was set as narrow as possible, and gain settings were optimized. Offline analysis was performed using EchoPAC PC 08 version 7.0.0 (GE Medical Systems, Milwaukee, WI). The endocardial border was traced manually in an end-systolic frame, and the region of interest was adjusted to include the entire myocardium. Optimal visualization of the myocardial walls with minimization of dropout and clear delineation of myocardial tissue was sought in every individual. Image acquisition was performed during an end-expiratory breath-hold. Only subjects with optimal tracking quality, automatically validated by software, were included for further analysis. For each view, three consecutive beats were analyzed, and mean values were calculated for all parameters derived. The following parameters were measured: peak systolic rotation of the base and apex, peak twist, peak systolic twisting rate, peak untwisting rate, and peak systolic circumferential strain of the base and apex. The time from QRS onset to the peak value was measured for each of the above parameters in each pacing mode, and the time to peak as a percentage of systolic duration (perTTP) was calculated ( Figure 1 ).

Assessment of basal (A) and apical (B) rotation and twist (C) by using speckle-tracking imaging. The endocardial border is traced manually in an end-systolic frame, and the region of interest is adjusted to include the entire myocardium. LV twist is depicted with the white line in (C) and is calculated as the net difference between LV apical ( green line ) and basal ( purple line ) rotation.

Coronary Blood Flow in the Left Anterior Descending Coronary Artery (LAD)

In each pacing mode, the blood flow in the mid-distal part of the LAD was assessed with Doppler echocardiography, as previously described. Briefly, a modified foreshortened two- or three-chamber view was obtained by sliding the transducer more superiorly and medially than the standard views, and the distal LAD was sought with color flow mapping guidance over the epicardial part of the anterior wall or the interventricular septum. Color Doppler echocardiography was performed with the velocity range set at 12 to 16 cm/sec.

When adequate visualization of flow in the LAD had been achieved, pulsed-wave Doppler echocardiography was applied by placing the sample volume (3–4 mm in size) on the color signal in the LAD, taking into account the diastolic position of the vessel.

Adequate measurement of coronary blood flow velocity was ensured when the angle between the color flow and Doppler beam was <20° and was kept as low as possible. Every effort was made to obtain the pulsed-wave Doppler signal at the same position in each patient for every pacing mode. A spectral trace of the coronary flow and determination of peak and mean diastolic velocities, as well as the velocity-time integral, was performed offline by an experienced investigator. Diastolic components of the coronary flow during three cardiac cycles were taken into account, because Doppler signals acquired during systole were inadequate for analysis as a result of cardiac motion ( Figure 2 ).

Spectral trace of mid-LAD diastolic flow and assessment of the d-VTI (centimeters) in SR (A) , AAI pacing (B) , DDD pacing (C) , and VVI pacing (D) in the same patient.

Statistical Analysis

Quantitative variables are presented as mean ± SD. Repeated-measurements analysis of variance was used to evaluate differences in echocardiographic parameters between SR and the AAI, DDD, and VVI pacing modes, and Bonferroni correction was applied. Pearson correlation coefficients ( r ) and random-effects regression analysis were used to explore the association between diastolic flow velocity parameters in the LAD and the other echocardiographic parameters.

Regression coefficients (β) with their standard errors were computed from the results of the random-effects regression analysis. For 10 participants, the analysis of peak systolic strain and LV twist data was repeated after 2 weeks by the same observer on the same two-dimensional echocardiographic loop and the same cardiac cycle to define the intraobserver variability in the analysis. In addition, a second independent observer analyzed the same cardiac cycle to define the interobserver variability in the analysis of tissue tracking–derived deformation and rotational parameters. For each segment, the differences in strain and twist data were calculated and given as the relative deviation between these two measurements. All P values reported are two tailed. Statistical significance was set at .05, and analyses were conducted using Stata version 9.0 (StataCorp LP, College Station, TX).