Background
The purpose of this study was to determine whether atrial electromechanical conduction time (EMT) measured by echocardiography can predict 6-month maintenance of sinus rhythm (SR) after electrical cardioversion in patients with atrial fibrillation (AF).
Methods
Fifty-three patients with persistent AF (>1 month) who had successful cardioversion and 30 controls with SR were prospectively enrolled. SR maintenance was assessed during 6-month follow-up. EMT was measured as the time interval from the onset of the P wave on electrocardiography to the peak of the late diastolic wave from the septal and lateral mitral annulus (EMT-S and EMT-L, respectively) and the lateral tricuspid annulus (EMT-T) on tissue Doppler echocardiography.
Results
Compared with controls, left atrial (LA) volume index, P-wave duration, and EMT were significantly larger in patients with AF (all P values < .001). In patients with AF, the duration of AF ( P = .71) and P-wave duration ( P = .24) were not different between the SR maintenance group (n = 23) and the AF recurrence group (n = 30), and there was a trend toward increased LA volume index in the AF recurrence group (47.0 ± 12.4 vs 45.3 ± 12.6 mL/m 2 , P = .07). EMT-S and EMT-L were significantly larger in the AF recurrence group (131.4 ± 20.9 vs 116.3 ± 15.5 ms, P = .005, and 152.2 ± 15.7 vs 128.9 ± 13.8 ms, P < .001, respectively), but not EMT-T. EMT-S and EMT-L were related to LA volume index ( r = .36, P = .008, and r = .33, P = .02, respectively). On multivariate logistic regression analysis, only EMT-L was an independent predictor of identifying patients who remained in SR ( P < .001), and the sensitivity and specificity for the prediction of 6-month maintenance of restored SR were 82.6% and 83.3% using a cutoff value of EMT-L ≤ 138.0 ms (odds ratio, 0.862; 95% confidence interval, 0.788-0.942; P = .001).
Conclusion
LA EMT was significantly prolonged in patients with recurring AF, indicating significantly depressed atrial conduction in enlarged LA, and can predict 6-month maintenance of SR after electrical cardioversion.
Atrial fibrillation (AF) is the most frequent sustained arrhythmia encountered in clinical practice. Although the mortality benefit of the maintenance of sinus rhythm (SR) in patients with AF is controversial, the restoration of SR is favorable to improve the quality of life, to ameliorate the effects of cardiac dysfunction and congestive heart failure, and to reduce the risk for systemic thromboembolism and long-term anticoagulation treatment complications. Transthoracic direct-current (DC) cardioversion (CV) of AF is one of the most widely used and effective treatments to restore SR in patients with persistent AF. However, the recurrence rate of AF is high, especially during the first 6 months. Potential predictors for the maintenance of SR after CV, including age, duration of AF, left atrial (LA) size, P-wave duration, and LA appendage flow, and pretreatment with antiarrhythmic drugs, have been investigated, but the power of these indicators as independent predictors of SR maintenance is limited. Long-lasting persistent AF causes electrical and mechanical changes in involved atria, leading to a phenomenon known as atrial remodeling that is characterized by atrial dilatation and depressed atrial conduction.
We hypothesized that atrial electromechanical conduction time (EMT), defined as mechanical conduction time in conjunction with electrical conduction time, might better reflect atrial conduction time than either mechanical or electrical conduction time. Recently, atrial EMT was measured using tissue Doppler echocardiography. However, there has been no report on atrial EMT after electrical CV to predict the maintenance of SR in persistent AF.
The purpose of this study was to determine whether atrial EMT can predict 6-month maintenance of restored SR after electrical CV in patients with persistent AF using transthoracic two-dimensional tissue Doppler echocardiography.
Methods
Seventy-two consecutive subjects with sustained AF (>1 month estimated from the initial onset of symptoms until the time of in-hospital conversion) who had undergone first elective DC CV were prospectively enrolled. Exclusion criteria were atrial flutter, significant valvular heart disease, congenital heart disease, history of ischemic heart disease or decreased left ventricular (LV) function (ejection fraction < 50%), and AF with identified reversible causes. As a control group, we included 30 healthy age-matched and sex-matched adult patients who had no histories of cardiovascular disease and normal resting electrocardiographic and echocardiographic results. All patients gave informed consent, and study approval was obtained from the institutional review board of Korea University College of Medicine.
Study Protocol
Echocardiography and electrocardiography were performed within 6 hours of CV when SR persisted. The maximal P-wave duration was measured on standard 12-lead electrocardiography and averaged over ≥5 consecutive beats. After CV, all patients were seen once weekly at an outpatient clinic for the first 2 weeks, then monthly thereafter and at any time they complained of palpitations or other symptoms. At each examination, standard 12-lead electrocardiography was performed, and an inquiry was made about any recurrence of AF. A 24-hour Holter recording was performed monthly for the first 3 months, at 6 months after CV, and at any time the patient had symptoms suggesting a recurrence of AF. All echocardiographic studies were evaluated by two independent observers who had no knowledge of the follow-up results.
Transesophageal Echocardiography and Electrical CV
Transesophageal echocardiography was performed with Acuson Sequoia ultrasonograph (Siemens Medical Solutions USA, Inc, Mountain View, CA) with a 5-MHz phased-array multiplane probe before CV. The presence of a thrombus in the LA appendage was assessed, and LA appendage peak emptying velocity was obtained by pulsed-wave Doppler interrogation at the orifice of the appendage.
Electrical DC CV was performed if LA thrombi were not seen on transesophageal echocardiography. Warfarin was given for anticoagulation to keep international normalized ratio levels between 2.0 and 3.0 for ≥3 weeks before CV. DC shock was delivered after sedation using midazolam (0.04 mg/kg) and sodium pentothal (1.5 mg/kg) intravenously. One defibrillator pad with a 10-cm diameter was placed in the second intercostal space on the right side parasternally; the other was placed in a left-sided lateral position along the midaxillary line. DC shock was delivered with an initial biphasic waveform of 70 or 100 J followed by 150 and 200 J until the restoration of SR or until AF neither converted to SR nor maintained SR.
Echocardiography
A commercially available echocardiography system (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway) with a 3.5-MHz phased-array transducer was used for conventional transthoracic 2-dimensional Doppler echocardiography. Standard comprehensive M-mode, two-dimensional echocardiographic and Doppler echocardiographic studies were performed before and after CV. LV volume and ejection fraction were calculated using the biplane Simpson’s method from apical 4-chamber and 2-chamber views. LA volume was measured using the biplane area-length method from apical 2-chamber and 4-chamber views when the LA area was maximal during end-systole. Right atrial (RA) area was measured in the apical 4-chamber view at end-systole. All volumetric and area parameters were indexed by body surface area. Mitral inflow was obtained by pulsed-wave Doppler echocardiography with the sample volume between mitral leaflet tips during diastole, and early diastolic velocity (E velocity) and its deceleration time and late diastolic velocity (A velocity) were measured. Early diastolic mitral annular velocity of the septal mitral annulus (e′ velocity) was obtained by Doppler tissue imaging, and the E/e′ ratio was calculated.
Measurement of Atrial EMT
Tissue Doppler echocardiography was performed by adjusting the spectral pulsed Doppler signal filters until a Nyquist limit of 15 to 20 cm/s was reached using the minimal optimal gain. The monitor sweep speed was set at 50 to 100 mm/s to optimize the spectral display of myocardial velocities. In the apical 4-chamber view, the pulsed Doppler sample volume (5 mm) was subsequently placed at the levels of the septal mitral annulus, lateral mitral annulus, and tricuspid annulus. The late diastolic annular velocities (a′ velocities) of the septal mitral annulus, lateral mitral annulus, and tricuspid annulus were measured. The time intervals from the onset of the P wave on electrocardiography to the peak of the late diastolic wave (a′ wave), defined as EMT, were obtained from the septal mitral annulus, lateral mitral annulus, and tricuspid annulus (EMT-S, EMT-L, and EMT-T, respectively; Figure 1 ). The difference between EMT-S and EMT-L was defined as diff-EMT. All echocardiographic parameters were measured 3 times and then averaged.
Statistical Analysis
Data are expressed as mean ± SD or as percentages. Student’s t test and the χ 2 test were used for comparison analysis. Relationships between different parameters were assessed by correlation analysis (Pearson’s method). All parameters, including P-wave duration ( F = 0.844, P = .363), LA volume index ( F = 0.074, P = .786), EMT-L ( F = 1.635, P = .207), and the duration of AF ( F = 1.072, P = .305), were normally distributed. To analyze independent predictors of SR maintenance after CV, univariate factors with P values < .10 were analyzed using forward stepwise logistic regression (multivariate analysis). On the basis of receiver operating characteristic curves, the best cutoff value was obtained to be the optimal point with the highest sum of sensitivity and specificity for predicting SR maintenance. All analyses were performed with commercially available statistical software (SPSS version 13.0; SPSS, Inc, Chicago, IL). A P value < .05 was considered statistically significant. Twenty patients were randomly selected for the assessment of intraobserver and interobserver variability, expressed as coefficients of variation by 2 independent investigators.
Results
Sixty-four of 72 consecutive patients (89.9%) restored to SR immediately after CV, and 53 patients (82.8%) maintained SR for 6 hours after all procedures. Of the 53 patients, 30 (56.6%) showed recurring AF (the AF recurrence group) and 23 (43.4%) showed maintenance of SR (the SR maintenance group) over a 6-month follow-up period.
Clinical and Echocardiographic Characteristics
In patients with AF, there were no significant differences in echocardiographic parameters from before to after CV in 6 hours (LV end-diastolic volume index, P = .76; LV ejection fraction, P = .20; LA volume index, P = .31; RA area index, P = .20).
Compared with normal controls, P-wave duration ( P < .001), LA volume index ( P < .001), and RA area index ( P < .001) were significantly greater in patients with AF, and mitral and tricuspid a′ velocities were significantly lower in patients with AF after CV ( Table 1 ).
| Normal controls | All patients with AF | ||
|---|---|---|---|
| Variable | (n = 30) | (n = 53) | P value |
| Age (y) | 57 ± 8 | 59 ± 9 | .27 |
| Men/women | 20/10 | 39/14 | .62 |
| P-wave duration (ms) | 88.2 ± 12.2 | 105.6 ± 18.7 | <.001 |
| Heart rate (beats/min) | 64 ± 11 | 62 ± 7 | .30 |
| LV end-diastolic volume index (mL/m 2 ) | 46.2 ± 8.1 | 46.3 ± 12.4 | .98 |
| LV ejection fraction (%) | 61.9 ± 3.1 | 61.5 ± 6.8 | .76 |
| LA volume index (mL/m 2 ) | 22.2 ± 6.7 | 42.9 ± 11.4 | <.001 |
| RA area index (cm 2 /m 2 ) | 8.3 ± 2.5 | 11.3 ± 3.0 | <.001 |
| Transmitral flow | |||
| E velocity (m/s) | 0.66 ± 0.12 | 0.74 ± 0.18 | .04 |
| A velocity (m/s) | 0.66 ± 0.18 | 0.28 ± 0.16 | <.001 |
| Deceleration time of E velocity (ms) | 204 ± 44 | 180 ± 41 | .02 |
| E/e′ | 9.3 ± 2.3 | 10.9 ± 5.5 | .14 |
| a′ velocity (cm/s) | |||
| Septal mitral annulus | 9.1 ± 2.0 | 3.8 ± 1.3 | <.001 |
| Lateral mitral annulus | 9.3 ± 2.5 | 3.7 ± 1.6 | <.001 |
| Tricuspid annulus | 12.8 ± 2.7 | 7.7 ± 2.9 | <.001 |
| EMT-S (ms) | 91.2 ± 14.6 | 124.8 ± 20.1 | <.001 |
| EMT-L (ms) | 99.2 ± 13.9 | 142.1 ± 18.8 | <.001 |
| diff-EMT (ms) | 9.9 ± 5.7 | 19.3 ± 12.8 | <.001 |
| EMT-T (ms) | 105.9 ± 16.0 | 124.6 ± 23.8 | <.001 |
Between the AF recurrence group and the SR maintenance group, there were no significant differences in clinical or echocardiographic parameters, including the duration of AF ( P = .71), P-wave duration after CV ( P = .24), and the prevalence of hypertension (8 of 30 vs 7 of 23, P = .77), diabetes mellitus (6 of 30 vs 3 of 23, P = .72), and dyslipidemia (4 of 30 vs 4 of 23, P = .71), although there was a trend toward increased LA volume index in AF recurrence group ( P = .07) ( Table 2 ). There was no difference in PR intervals between patients with SR maintenance and with AF recurrence ( P = .17).
| AF recurrence | SR maintenance | ||
|---|---|---|---|
| Variable | (n = 30) | (n = 23) | P value |
| Age (y) | 60 ± 8 | 58 ± 9 | .34 |
| Men/women | 9/21 | 5/18 | .54 |
| AF duration (mo) | 30 ± 30 | 27 ± 26 | .71 |
| P-wave duration (ms) | 108.2 ± 20.0 | 102.2 ± 16.6 | .24 |
| PR interval (ms) | 200.8 ± 26.3 | 188.6 ± 35.1 | .17 |
| Heart rate (beats/min) | 61 ± 7 | 61 ± 7 | .95 |
| Medications | |||
| β-blockers | 9 (30.0%) | 4 (17.4%) | .35 |
| Calcium channel blockers | 4 (13.3%) | 4 (17.4%) | .72 |
| Antiarrhythmic drugs | 18 (60.0%) | 16 (69.6%) | .57 |
| ACE inhibitors or ARBs | 12 (40.0%) | 7 (30.4%) | .57 |
| Maximal DC shock energy (J) | 109 ±34 | 93 ± 43 | .14 |
| Number of DC shocks | 2.2 ± 1.4 | 2.0 ± 1.7 | .59 |
| LV end-diastolic volume index (mL/m 2 ) | 47.0 ± 12.4 | 45.3 ± 12.6 | .63 |
| LV ejection fraction (%) | 62.2 ± 7.2 | 60.7 ± 5.5 | .41 |
| LA volume index (mL/m 2 ) | 45.6 ± 9.8 | 39.5 ± 12.8 | .07 |
| RA area index (cm 2 /m 2 ) | 11.6 ± 2.4 | 11.0 ± 3.7 | .56 |
| Transmitral flow | |||
| E velocity (m/s) | 0.76 ± 0.18 | 0.71 ± 0.18 | .36 |
| A velocity (m/s) | 0.28 ± 0.15 | 0.28 ± 0.17 | .98 |
| Deceleration time of E velocity (ms) | 181.6 ± 39.9 | 177.8 ± 42.1 | .74 |
| E/e′ | 11.1 ± 4.4 | 10.6 ± 6.7 | .77 |
| LA appendage emptying velocity (cm/s) | 39.7 ± 21.2 | 45.4 ± 20.7 | .34 |
| a′ velocity (cm/s) | |||
| Septal mitral annulus | 3.5 ± 1.2 | 4.1 ± 1.5 | .15 |
| Lateral mitral annulus | 3.3 ± 1.3 | 4.2 ± 1.8 | .08 |
| Tricuspid annulus | 7.2 ± 2.0 | 8.2 ± 3.7 | .24 |
| EMT-S (ms) | 131.4 ± 20.9 | 116.3 ± 15.5 | .005 |
| EMT-L (ms) | 152.2 ± 15.7 | 128.9 ± 13.8 | <.001 |
| diff-EMT (ms) | 23.7 ± 13.8 | 13.6 ± 8.7 | .004 |
| EMT-T (ms) | 129.0 ± 24.0 | 117.9 ± 19.5 | .08 |
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