Abstract
Background
This study investigates the association between prolonged total atrial conduction time and the development of new-onset atrial fibrillation (AF) following transcatheter aortic valve implantation (TAVI).
Methods
We enrolled 307 patients who underwent TAVI. Total atrial conduction time was calculated as the time between the onset of the P wave on the electrocardiography and the peak of the a′ wave velocity (PA-TDI duration) on tissue Doppler imaging echocardiography.
Results
A total of 263 patients were analyzed after excluding 44 with pre-existing AF. Of these 263 patients, 47 (17.8%) experienced new-onset AF after the TAVI procedure. The new-onset AF group had an older median age (80.6 vs. 77.5 years) and a higher incidence of paravalvular aortic regurgitation than those without AF (none 29.8%, mild 46.8%, moderate 23.4%). The new-onset AF group had increased end-systolic diameter (35.0 vs. 31.7 mm, p = 0.03), left atrial diameter (44.7 vs. 41.9 mm, p = 0.049), and PA-TDI duration (137.0 vs. 125.4 ms, p = 0.009). Older age, the presence of paravalvular aortic regurgitation, and prolonged PA-TDI duration were independently associated with new-onset AF in multivariate analysis. The optimal cut-off value for PA-TDI duration was 123.5 ms.
Conclusions
AF in patients treated with TAVI may pose significant risks for morbidity and mortality. PA-TDI duration, a readily available echocardiographic parameter, can detect patients with a high risk of new-onset AF.
Keywords: Atrial fibrillation, Tissue Doppler imaging, Total atrial conduction time, Transcatheter aortic valve implantation
Abbreviations
AF, Atrial fibrillation
ECG, Electrocardiography
PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria
SAVR, Surgical aortic valve replacement
TAVI, Transcatheter aortic valve implantation
TDI, Tissue Doppler imaging
INTRODUCTION
Transcatheter aortic valve implantation (TAVI) is the mainstay of treatment in patients with symptomatic aortic stenosis who are not eligible for surgery.1 While atrial fibrillation (AF) is the most common arrhythmia in adults, with an estimated prevalence of 2-4%, it is more common in the elderly population, who represent the target population for aortic valve intervention due to their advanced age.2 AF is one of the most common and devastating complications of both surgical aortic valve replacement (SAVR) and TAVI. Although the reported incidence rates of AF are higher in SAVR than in TAVI, new-onset AF may pose a higher risk of morbidity and mortality in TAVI compared to SAVR.3-5 In a large, global registry, new-onset AF was found to be associated with an increased risk of stroke in patients undergoing TAVI, while pre-existing AF did not have such an association.6 Therefore, the early identification of patients at risk of developing new-onset AF before the procedure and implementing appropriate treatment strategies is essential.
AF in aortic stenosis is a consequence of atrial remodeling in response to left ventricular hypertrophy and concomitant diastolic dysfunction.7,8 The P wave to peak a′ on tissue Doppler imaging of the atria (PA-TDI) duration is a noninvasive estimate of the total atrial conduction time from the beginning of the P-wave to the peak of the a′ wave velocity, and it can provide information on the electrical stability of the atrial wall and the risk of AF.9 Previous research has demonstrated a correlation between PA-TDI duration and the risk of AF development in different populations, such as those receiving SAVR and those with hypertrophic cardiomyopathy.10,11 The aim of the present study was to investigate whether prolonged PA-TDI duration is associated with the development of AF in patients undergoing TAVI.
METHODS
Patient population and procedure
In this single-center retrospective cohort study, 307 patients who underwent TAVI between February 2013 and March 2020 were enrolled. Baseline characteristics of all patients were retrospectively collected. The presence of AF was evaluated in the patients before the procedure. AF was defined as the presence of an irregular rhythm with fibrillatory waves and the absence of P waves in the electrocardiography (ECG). ECGs and medical records were used to confirm the presence of AF. Patients with pre-existing AF were excluded from this study. Patients with valvular diseases requiring interventions other than aortic valve implantation were also excluded from this study.
A dedicated "valve team" consisting of cardiac surgeons, interventional cardiologists, general cardiologists, and echo specialists determined patient eligibility for TAVI.12 All patients underwent the procedure through a transfemoral approach using self-expanding prostheses. Following valve implantation, the patients were monitored at the cardiac intensive care unit until the day of discharge. The detection of new-onset AF was based on continuous electrocardiographic records during post-procedural intensive care unit hospitalization. The patients were monitored with three-channel ECG, and all events were recorded. Any arrhythmias were detected by our computerized monitoring system, and interpreted by the physicians. New-onset AF was defined as any episode lasting at least 30 seconds on a rhythm strip during hospitalization.13 All patients were hospitalized up to a maximum of 48 hours, depending on their clinical situation, unless there was cardiac tamponade, pacemaker requirement, or major access site-related complications. None of the individuals included in the study developed major complications that would prolong hospitalization. The patients were categorized into two groups based on the presence of new-onset AF. Clinical follow-up after TAVI was performed through clinic visits at 1, 6, and 12 months. This study was approved by the institutional review board, complied with the Declaration of Helsinki, and all patients provided written informed consent.
Echocardiography
All patients underwent a thorough transthoracic echocardiographic evaluation using a Vivid E9 ultrasound system (GE Vingmed Ultrasound). The same cardiologist analyzed all echocardiographic measurements without knowing the patient’s clinical status. Echocardiographic data were collected one day before the TAVI procedure. Standard 2D-based images and Doppler measurements, including parasternal and apical views, were taken as per the current expert consensus document.14 Measurement of the echocardiographic aortic annulus was performed in parasternal long axis view and in the zoom mode using standard electronic calipers in mid-systole, between the hinge points of the aortic valve leaflets from inner edge to inner edge. The diagnosis of severe aortic stenosis was made based on clinical, echocardiographic, and hemodynamic criteria according to current guidelines.15 The PA-TDI duration was measured on tissue Doppler imaging data from the onset of the P wave on the surface ECG to the peak a′ wave velocity recorded at the left atrial wall (Figure 1).9 For each patient, PA-TDI duration was measured once by a single clinician (UNK).
Figure 1.
The PA-TDI duration (124 ms) (red colored segment) measured from the onset of the P wave on the electrocardiogram (blue colored solid dot) to the peak a′ wave (black colored solid dot) of the left atrial wall. ECG, electrocardiography; LA, left atrium; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria; TDI, tissue Doppler imaging.
Statistical analysis
Statistical analysis was performed using SPSS software (version 20.0; SPSS Inc., Chicago, IL, USA). Variables with normal distribution were presented as mean ± standard deviation, while those without normal distribution were presented as median and minimum-maximum. For determining whether a variable showed normal distribution, Kolmogorov-Smirnov and Shapiro-Wilk tests were used. In addition, skewness and kurtosis values of given variables were controlled. Categorical variables were presented as numbers and percentages. Between the two groups, a comparison of continuous variables was performed with the t-test for independent variables with normal distribution, Mann-Whitney U and Kolmogorov-Smirnov tests for those without normal distribution, and the chi-square test for categorical variables. While the correlations among the variables with normal distribution were analyzed with Pearson correlation, Spearman correlation analysis was used for variables without normal distribution. Univariate regression analysis was performed for each potential risk variable. Baseline clinical and echocardiographic characteristics were included as independent variables in the multivariate regression analysis with the "enter" model to predict the occurrence of new-onset AF. During the multivariate regression analysis, the tolerance and variance inflation factor values of collinearity statistics were considered to avoid potentially strong correlations among the independent variables. A p value less than 0.05 was considered statistically significant.
RESULTS
A total of 263 patients were analyzed after excluding 44 patients who had pre-existing AF. Of these 263 patients, 47 (17.8%) developed new-onset AF following the TAVI procedure. Table 1 shows the baseline characteristics. The patients with AF were older than those without AF (80.6 ± 8.4 vs. 77.5 ± 11.2 years). All AF recordings were obtained within the first 24 hours of post-procedural hospitalization. The cardiovascular risk factors, STS and Logistic EuroSCORE, valve size, and valve-in-valve requirements were comparable between the groups. The patients with AF had a higher incidence of paravalvular aortic regurgitation (none 29.8%; mild 46.8%; moderate 23.4%) compared to those without AF (none 43.1%; mild 45.4%; moderate 11.6%, p = 0.030) (Figure 2).
Table 1. Clinical characteristics of study population.
| Total population (n = 263) | No AF (n = 216) | AF (n = 47) | p value | |
| Age (years) | 78.0 ± 10.8 | 77.5 ± 11.2 | 80.6 ± 8.4 | 0.032 |
| Gender (female/male) | 144/119 | 118/98 | 26/21 | 0.932 |
| Body mass index (kg/m2) | 27.3 ± 4.8 | 27.2 ± 5.0 | 27.8 ± 4.2 | 0.358 |
| Heart rate (/bpm) | 76.6 ± 5.8 | 76.3 ± 5.7 | 77.4 ± 6.0 | 0.236 |
| Hypertension (%) | 74.7% | 71.4% | 92.9% | 0.091 |
| Diabetes mellitus (%) | 30.2% | 29% | 37.5% | 0.493 |
| Dyslipidemia (%) | 24.8% | 25.4% | 20.6% | 0.649 |
| Coronary artery bypass (%) | 26.1% | 28.6% | 13.3% | 0.219 |
| Beta-blocking agents (%) | 88.2% | 87.9% | 89.3% | 0.979 |
| Calcium channel blockers (%) | 6.0% | 6.0% | 6.3% | 0.790 |
| Chronic kidney disease (%) | 9.5% | 9.7% | 8.5% | 0.798 |
| COPD (%) | 14.8% | 16.7% | 6.4% | 0.073 |
| STS score | 8 [4-16.6] | 8 [4-16.6] | 7.3 [6-11] | 0.777 |
| Logistic EuroSCORE | 27 [16.3-60] | 27 [16.3-60] | 33 [20-55] | 0.173 |
| Valve size (mm) | 28.5 ± 2.5 | 28.6 ± 2.6 | 28.3 ± 2.4 | 0.588 |
| Valve-in-valve | 7 (2.7%) | 7 (3.2%) | - | 0.212 |
| Paravalvular AR | 0.030 | |||
| None | 107 (40.7%) | 93 (43.1%) | 14 (29.8%) | |
| Mild | 120 (45.6%) | 98 (45.4%) | 22 (46.8%) | |
| Moderate | 36 (13.7%) | 25 (11.6%) | 11 (23.4%) |
AF, atrial fibrillation; AR, aortic regurgitation; COPD, chronic obstructive pulmonary disease; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria.
Figure 2.
Distribution of paravalvular aortic regurgitation according to the presence of new-onset atrial fibrillation. AF, atrial fibrillation.
Table 2 shows the baseline echocardiographic features. Left ventricular end-diastolic diameter, left ventricular ejection fraction, left atrial volume index, peak and mean aortic gradient and aortic valve area were similar in both groups. However, the AF group had significant increases in end-systolic diameter (35.0 vs. 31.7 mm, p = 0.03), left atrial diameter (44.7 vs. 41.9 mm, p = 0.049), and PA-TDI duration (137.0 vs. 125.4 ms, p = 0.009).
Table 2. Echocardiographic characteristics of the study population.
| Total population (n = 263) | No AF (n = 216) | AF (n = 47) | p value | |
| LV end-diastolic diameter (mm) | 48.2 ± 3.5 | 47.9 ± 5.3 | 49.3 ± 5.4 | 0.202 |
| LV end-systolic diameter (mm) | 32.2 ± 5.5 | 31.7 ± 5.0 | 35.0 ± 6.8 | 0.030 |
| LV ejection fraction (%) | 55.2 ± 10.9 | 55.4 ± 10.9 | 54.2 ± 11.1 | 0.515 |
| Left atrial diameter (mm) | 42.9 ± 6.5 | 41.9 ± 6.6 | 44.7 ± 6.1 | 0.049 |
| LAVI (mL/m2) | 27.3 ± 9.9 | 26.3 ± 9.5 | 29.2 ± 10.5 | 0.200 |
| Aortic annulus (mm) | 22.3 ± 3.0 | 22.3 ± 3.1 | 22.3 ± 2.9 | 0.958 |
| Ascending aorta (mm) | 36.1 ± 4.2 | 35.9 ± 4.2 | 36.9 ± 4.1 | 0.274 |
| Peak aortic gradient (mmHg) | 78.6 ± 20.5 | 79.2 ± 20.5 | 77.2 ± 20.7 | 0.660 |
| Mean aortic gradient (mmHg) | 46.8 ± 13.5 | 46.6 ± 13.2 | 47.2 ± 14.3 | 0.838 |
| Aortic valve area (cm2) | 0.73 ± 0.15 | 0.73 ± 0.15 | 0.74 ± 0.14 | 0.734 |
| PA-TDI duration (ms) | 127.0 ± 26.7 | 125.4 ± 26.2 | 137.0 ± 27.2 | 0.009 |
AF, atrial fibrillation; LAVI, left atrial volume index; LV, left ventricle; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria.
Univariate regression analysis showed that the occurrence of new-onset AF was significantly influenced by paravalvular aortic regurgitation, left ventricular end-systolic diameter, and PA-TDI duration (Table 3). Multivariate analysis, which included parameters with a p value < 0.1 in the univariate analysis, showed an independent association of new-onset AF with increased age, the presence of paravalvular aortic regurgitation, and prolonged PA-TDI duration (Table 4). In the receiver operating characteristic curve analysis (Figure 3), the area under the curve for PA-TDI duration was 0.630 (95% CI, 0.540-0.721; p = 0.005), and the optimal cut-off value of PA-TDI duration was 123.5 ms (sensitivity of 68.1% and specificity of 50.5%). The area under the curve for age, however, was 0.587 (95% CI, 0.501-0.673; p = 0.062).
Table 3. Univariate regression analysis for each potential risk factors for the development of new onset atrial fibrillation.
| Univariate | |||
| Hazard ratio | 95% confidence interval | p value | |
| Age (years) | 1.032 | 0.997-1.068 | 0.072 |
| Gender (male) | 1.028 | 0.545-1.939 | 0.931 |
| Body mass index (kg/m2) | 1.029 | 0.962-1.101 | 0.407 |
| Hypertension | 0.192 | 0.024-1.560 | 0.123 |
| Diabetes mellitus | 0.681 | 0.227-2.046 | 0.493 |
| Dyslipidemia | 1.362 | 0.361-5.134 | 0.648 |
| Coronary artery bypass graft | 2.600 | 0.542-12.481 | 0.233 |
| COPD | 2.933 | 0.863-9.966 | 0.085 |
| Chronic kidney disease | 1.158 | 0.378-3.545 | 0.798 |
| Valve size (mm) | 0.964 | 0.842-1.104 | 0.964 |
| Paravalvular aortic regurgitation | 1.683 | 1.068-2.652 | 0.025 |
| LV end-diastolic diameter (mm) | 1.047 | 0.977-1.122 | 0.191 |
| LV end-systolic diameter (mm) | 1.095 | 1.021-1.175 | 0.012 |
| LV ejection fraction (%) | 0.991 | 0.963-1.018 | 0.505 |
| Left atrial diameter (mm) | 1.067 | 0.997-1.143 | 0.061 |
| Left atrial volume index (mL/m2) | 1.029 | 0.986-1.074 | 0.192 |
| Aortic annulus (mm) | 0.996 | 0.861-1.153 | 0.958 |
| Peak aortic gradient (mmHg) | 0.995 | 0.975-1.016 | 0.655 |
| Mean aortic gradient (mmHg) | 1.003 | 0.973-1.034 | 0.836 |
| Aortic valve area (cm2) | 1.603 | 0.104-24.797 | 0.736 |
| PA-TDI duration (ms) | 1.016 | 1.004-1.029 | 0.008 |
COPD, chronic obstructive pulmonary disease; LV, left ventricle; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria.
Table 4. Multivariate regression analysis, which includes parameters with a p value less than 0.100 from the univariate analysis, and those showing an independent association of new-onset atrial fibrillation occurrence.
| Multivariate | |||
| Hazard ratio | 95% confidence interval | p value | |
| Age (years) | 1.142 | 1.049-1.243 | 0.002 |
| COPD | 5.958 | 0.717-49.532 | 0.099 |
| Paravalvular aortic regurgitation | 3.780 | 1.379-10.363 | 0.010 |
| LV end-systolic diameter (mm) | 1.049 | 0.933-1.178 | 0.424 |
| Left atrial diameter (mm) | 1.041 | 0.949-1.143 | 0.393 |
| PA-TDI duration (ms) | 1.040 | 1.013-1.068 | 0.004 |
COPD, chronic obstructive pulmonary disease; LV, left ventricle; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria.
Figure 3.
Area under the receiver-operating-characteristic curve for PA-TDI duration. AUC, area under the curve; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria.
DISCUSSION
In the present study, we found a significant independent association between new-onset AF in patients undergoing TAVI and prolonged PA-TDI duration, increased age, and paravalvular aortic regurgitation. AF is a common complication associated with TAVI, with occurrence rates of new-onset AF in different studies ranging between 7.2% and 50.4%.16,17 In our study, 17.8% of patients undergoing TAVI developed new-onset AF, which is consistent with earlier research.
New-onset AF following TAVI originates from numerous potential underlying mechanisms. One of the primary contributing factors is advanced age. Because TAVI is the preferred treatment for patients experiencing symptomatic aortic stenosis, this population tends to be of advanced age. Kalra et al.17 observed a statistically significant relationship between the occurrence of new-onset AF during TAVI and advancing age. Similarly, the patients in our study who had new-onset AF were older than those who did not. Furthermore, age has been identified as an independent predictor for the development of new-onset AF. In addition, an increase in intracardiac pressure due to paravalvular leakage, even for a short time, has been associated with new-onset AF.18 Accordingly, in the present study, paravalvular aortic regurgitation was found to be an independent factor for new-onset AF. While none of our patients had severe aortic regurgitation following TAVI, mild and moderate regurgitations were significantly more common among the patients with new-onset AF compared to those without new-onset AF. These findings may suggest that there could be a hemodynamic connection between paravalvular aortic regurgitation and the occurrence of new-onset AF. Lastly, the access route is considered to be a potential risk factor for new-onset AF following TAVI. Previous studies have reported that patients treated with the transapical or transaortic approaches had a significantly higher incidence of new-onset AF compared to those treated with the transfemoral approach.16,19 This association has been previously attributed to epicardial and pericardial injury, as well as the local inflammatory response associated with transapical access.20 However, all procedures in our study were performed through the transfemoral approach.
Several left atrial parameters have been reported to be able to predict the development of new-onset AF after TAVI, including dimensions, volume index, and strain imaging.21-23 In contrast, these parameters were not linked to new-onset AF in the current study. Instead, the PA-TDI duration, which is a readily available, cost-effective, and easy-to-use echocardiographic parameter, was linked to the development of new-onset AF in patients undergoing TAVI. The duration of PA-TDI has been studied in different populations to predict AF risk, such as patients undergoing surgical aortic and mitral valve interventions and those with hypertrophic cardiomyopathy.10,11,24 In this study, we present a new finding that PA-TDI duration is independently linked to the development of new-onset AF in patients undergoing TAVI (Central Illustration).
Central Illustration.
The PA-TDI duration derived using echocardiography and ECG predicts the risk of developing atrial fibrillation after TAVI. ECG, electrocardiography; PA-TDI, P wave to peak a′ on tissue Doppler imaging of the atria; TAVI, transcatheter aortic valve implantation.
Stroke remains one of the most severe complications of the TAVI procedure, causing increased mortality and decreased quality of life for the patients.25 As TAVI procedures continue to increase, identifying stroke risk has become crucial to manage this population. Previous studies have shown that new-onset AF is associated with an increased risk of cerebrovascular events, with most cases occurring within the first week after TAVI. In contrast to new-onset AF, pre-existing AF has not been shown to predict stroke after TAVI.6,25,26 According to the present study, the PA-TDI duration, which was found to be an independent predictor for new-onset AF after TAVI, may be able to identify patients at risk for new-onset AF, and, therefore, stroke after TAVI. It has been shown that early anticoagulation treatment can result in a significant reduction in cerebrovascular events in patients who develop new-onset AF following TAVI.27 Thus, an increase in PA-TDI duration may serve as a useful indicator for the early detection of new-onset AF prior to the procedure and inform appropriate anticoagulation strategies. In the present study, 44 of 47 patients were discharged in sinus rhythm in the new-onset AF group. Additionally, these patients were given non-vitamin K antagonist oral anticoagulation for at least one month, based on their risk profile, renal function, and age, and long-term anticoagulation was evaluated at the first-month visit.
The limitations to this are the lack of clinical endpoints and relatively limited patient sample size. The primary objectives of this study were to determine whether new-onset AF had occurred and examine the effectiveness of the PA-TDI duration in predicting AF. Additionally, this study did not assess cerebrovascular events, the primary complication of AF. Thus, any implications and relationships among the PA-TDI duration, new-onset AF, and stroke would be theoretical and require further investigation. The current outcomes should be confirmed in a more comprehensive, prospective study with clinical follow-up. Second, new-onset AF was defined as any AF episodes occurring during the index hospitalization. Thus, any arrhythmic events beyond this period or silent arrhythmic episodes undetectable before TAVI treatment were not accounted for. Therefore, we only managed to record events that occurred within the hospital. Third, AF is a complex arrhythmia with multiple factors. Although left atrial parameters were also assessed in this study, predicting the development of AF with a single parameter may not be a reliable approach for clinical use. Advanced imaging methods, including magnetic resonance imaging and biomarkers demonstrating atrial remodeling and fibrosis, can provide more detailed and mechanistic explanations. Nonetheless, accessibility and cost-effectiveness may remain challenges for these tools.
New knowledge gained
Determining which patients scheduled for TAVI will experience AF can be determined by using a simple echocardiographic parameter. The most important predictive value to remember is simple for the PA-TDI value: 1-2-3!
CONCLUSIONS
The present study showed that increases in PA-TDI duration, age, and paravalvular aortic regurgitation independently predicted new-onset AF following TAVI. The PA-TDI duration, a noninvasive echocardiographic parameter, could detect patients at risk of new-onset AF who require further evaluation to reduce AF-related complications.
DECLARATIONS OF CONFLICT OF INTEREST
All the authors declare no conflict of interest.
Acknowledgments
None.
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