The prognostic impact of preexisting atrial fibrillation or flutter (AF) in low-risk patients with severe aortic stenosis treated with transcatheter (TAVR) or surgical aortic valve replacement (SAVR) remains unknown. In this sub-analysis of the PARTNER 3 trial of patients with severe aortic stenosis at low surgical risk randomized 1:1 to TAVR versus SAVR, clinical outcomes were analyzed at 2 years according to AF status. Among 948 patients included in the analysis (452 [47.7%] in the SAVR vs 496 [52.3%] in the TAVR arm), 168 (17.6%) patients had AF [88/452 (19.5%) and 80/496 (16.1%) treated with SAVR and TAVR, respectively]. At 2 years, patients with AF had higher unadjusted rates of the composite outcome of death, stroke or rehospitalization (21.2% vs 12.9%, p = 0.007) and rehospitalization alone (15.3% vs 9.4%, p = 0.03) but not all cause death (3.8% vs 2.6%, p = 0.45) or stroke (4.8% vs 2.6%, p = 0.12). In adjusted analyses, patients with AF had a higher risk for the composite outcome of death, stroke or rehospitalization (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.20–2.71, p = 0.0046) and rehospitalization alone (HR 1.8, 95% CI 0.12–2.9, p = 0.015), but not death or stroke. There was no interaction between treatment modality and AF on the composite outcome (P inter = 0.83).
In conclusion, preexisting AF in patients with severe AS at low surgical risk was associated with increased risk of the composite outcome of death, stroke or rehospitalization at 2 years, irrespective of treatment modality.
Atrial fibrillation or flutter (AF) is the most common comorbid arrhythmia among patients with severe aortic stenosis, observed in up to 40% of patients. In patients with AS at high surgical risk or deemed inoperable undergoing transcatheter aortic valve replacement (TAVR) as well as those undergoing surgical aortic valve replacement (SAVR) preexisting AF has been associated with an increased risk of mortality and rehospitalization. , , Nevertheless, whether AF is a prognostic factor in low-risk patients undergoing TAVR or SAVR for severe AS remains unknown. In the present analysis of the Placement of Aortic Transcatheter Valves (PARTNER) 3 trial, we sought to determine the prognostic implications of preexisting AF in patients with severe AS at low surgical risk who underwent TAVR or SAVR.
Methods
The design of the PARTNER 3 trial has been reported previously. In brief, the PARTNER 3 trial was a multicenter, randomized trial in which TAVR with transfemoral placement of a third-generation balloon-expandable valve was compared with standard surgical aortic-valve replacement in patients with severe AS and a low risk of death with surgery. Patients were eligible for inclusion if they had severe calcific AS and were considered to be at low surgical risk according to the results of clinical and anatomical assessment, including a Society of Thoracic Surgeons Predicted Risk of Mortality score of <4% and agreement by the site heart team and the trial case review committee. Details regarding inclusion and exclusion criteria have previously been reported. Eligible patients were randomly assigned, in a 1:1 ratio, to undergo either TAVR with the SAPIEN 3 system or surgical aortic-valve replacement with a commercially available bioprosthetic valve. The investigation was approved by the institutional review board or ethics committee at each participating center, and all patients signed written informed consent. Major endpoints were adjudicated by an independent clinical events committee (Cardiovascular Research Foundation, New York, New York). The primary end point was a composite of death from any cause, stroke, or rehospitalization at one year after the procedure. History of AF was assessed and determined by the enrolling sites. Patients were excluded from the current analysis if they had missing information on history of AF. For the purpose of the present study, the primary endpoint was defined a priori as the composite outcome of death from any cause, stroke or rehospitalization at 2 years. Secondary endpoints included the individual endpoints of rehospitalization due to procedure/device related adverse events or heart failure, as well as all-cause death, cardiovascular death, stroke and major bleeding including major bleeding and life-threatening bleeding per the VARC-2 definition. Median follow-up for clinical outcomes was 757 days and 95% of patients had complete two year data available for analysis.
All analyses were performed in the as-treated population. Continuous variables are reported as mean ± standard deviation and were compared using the Student t test. Categorical variables are expressed as counts and percentages and were compared with the Fisher’s exact test, as appropriate. Rates of clinical outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. The adjusted associations between AF and adverse clinical outcomes were determined in Cox proportional hazards models including the following predefined clinically pertinent variables: Age, male sex, diabetes, smoking, anemia, left ventricular ejection fraction, chronic obstructive pulmonary disease, body mass index, previous percutaneous coronary intervention and treatment modality. Alternate Cox proportional hazards models including, in addition to the above noted covariates, anticoagulant therapy and concomitant MAZE procedure or left atrial appendage closure were also constructed. A 2-sided p <0.05 was considered statistically significant for all tests. All statistical analyses were performed with the use of SAS version 9.4 (SAS Institute, Cary, North Carolina).
Results
Among 948 patients included in the present analysis, 452 (47.7%) underwent SAVR and 496 (52.3%) underwent TAVR. History of AF was present in 168 patients (17.6%) (88 [19.5%] treated with SAVR and 80 [16.1%] treated with TAVR). Compared to patients without AF, patients with AF were more frequently male and Caucasian, and were more likely to have a history of pacemaker implant and higher body-mass index ( Table 1 ). At discharge, 81.0% of patients with AF were on anticoagulant medication compared to 22.9% of patients without AF (Supplemental Table 1). Baseline characteristics of patients with versus without AF in the TAVR and SAVR arms were overall well balanced (Supplemental Table 2). Compared to patients without AF, patients with history of AF had lower baseline left ventricular ejection fraction , a higher prevalence of mitral and tricuspid regurgitation and larger systolic annular perimeter and systolic annular area ( Table 2 ). Procedural characteristics are shown in Table 3 and Supplemental Table 3. Patients with AF had longer procedure and anesthesia times and more often underwent concomitant procedures compared with patients without AF. Among patients treated with SAVR, patients with AF had longer total aortic cross clamp time and more often underwent concomitant procedures, including MAZE (22/88 [25%]) and left atrial appendage ligation (31/88 (35.2%) compared with patients without AF (Supplemental Table 4).
| Variable | AF (n = 168) | No AF (n = 780) | p Value |
|---|---|---|---|
| Age (years) | 74.0 ± 5.8 | 73.3 ± 6.0 | 0.14 |
| Men | 134/168 (79.8%) | 522/780 (66.9%) | 0.0009 |
| Nonwhite race or ethnic group | 7/168 (4.2%) | 76/780 (9.7%) | 0.02 |
| Body mass index (kg/m 2 ) | 31.4 ± 5.7 | 30.3 ± 5.3 | 0.02 |
| STS score | 2.0 ± 0.6 | 1.9 ± 0.7 | 0.11 |
| EuroSCORE II | 1.4 ± 0.7 | 1.5 ± 1.1 | 0.14 |
| NYHA class III or IV | 53/168 (31.5%) | 210/780 (26.9%) | 0.25 |
| CHA 2 DS 2 -VASc score | 3.7 ± 1.3 | 3.5 ± 1.3 | 0.13 |
| Coronary artery disease | 49/167 (29.3%) | 214/779 (27.5%) | 0.63 |
| Previous myocardial infarction | 14/168 (8.3%) | 40/778 (5.1%) | 0.14 |
| Previous stroke or cerebrovascular accident | 9/168 (5.4%) | 31/779 (4.0%) | 0.40 |
| Carotid disease | 19/160 (11.9%) | 91/761 (12.0%) | 1.00 |
| Peripheral vascular disease | 11/167 (6.6%) | 56/778 (7.2%) | 0.87 |
| Chronic obstructive pulmonary disease | 9/168 (5.4%) | 44/779 (5.6%) | 1.00 |
| Creatinine >2 mg/dL | 0/168 (0.0%) | 2/780 (0.3%) | 1.00 |
| Diabetes mellitus | 56/168 (33.3%) | 235/779 (30.2%) | 0.46 |
| Permanent pacemaker | 9/168 (5.4%) | 16/780 (2.1%) | 0.03 |
| Left bundle-branch block | 7/168 (4.2%) | 23/779 (3.0%) | 0.46 |
| Right bundle-branch block | 18/168 (10.7%) | 95/779 (12.2%) | 0.69 |
| Pulmonary hypertension | 12/168 (7.1%) | 35/779 (4.5%) | 0.17 |
| Hyperlipidemia | 134/167 (80.2%) | 631/780 (80.9%) | 0.83 |
| Hypertension | 146/166 (88.0%) | 662/779 (85.0%) | 0.40 |
| Congestive heart failure | 71/168 (42.3%) | 269/779 (34.5%) | 0.06 |
| Pulmonary disease | 12/168 (7.1%) | 42/779 (5.4%) | 0.36 |
| PCI or CABG | 32/166 (19.3%) | 143/778 (18.4%) | 0.83 |
| Anemia | 12/168 (7.1%) | 61/780 (7.8%) | 0.87 |
| Renal disease | 17/168 (10.1%) | 80/780 (10.3%) | 1.00 |
| History of alcohol abuse | 15/168 (8.9%) | 61/780 (7.8%) | 0.64 |
| History of cancer | 29/167 (17.4%) | 179/777 (23.0%) | 0.12 |
| Cirrhosis | 0/168 (0.0%) | 0/779 (0.0%) | — |
| Thrombocytopenia | 2/168 (1.2%) | 9/779 (1.2%) | 1.00 |
| Coagulopathy | 2/168 (1.2%) | 2/780 (0.3%) | 0.15 |
| Variable | AF (n = 168) | No AF (n = 780) | p Value |
|---|---|---|---|
| Echocardiographic | |||
| Aortic valve area (cm 2 ) | 0.8 ± 0.2 | 0.8 ± 0.2 | 0.61 |
| Aortic valve mean gradient (mm Hg) | 47.7 ± 11.4 | 49.2 ± 12.5 | 0.13 |
| Left ventricular ejection fraction (%) | 64.1 ± 8.5 | 66.3 ± 8.8 | 0.004 |
| Left atrial volume (mL) | 90.2 ± 31.3 | 68.9 ± 20.8 | <0.0001 |
| Peak pulmonary artery systolic pressure (mm Hg) | 39.4 ± 11.6 | 35.1 ± 9.2 | 0.0002 |
| Moderate or severe regurgitation | |||
| Aortic | 6/165 (3.6%) | 24/763 (3.1%) | 0.81 |
| Mitral | 8/163 (4.9%) | 12/749 (1.6%) | 0.02 |
| Tricuspid | 9/162 (5.6%) | 9/739 (1.2%) | 0.002 |
| Computed tomography | |||
| Systolic annular perimeter (mm) | 80.5 ± 7.3 | 77.8 ± 6.9 | <0.0001 |
| Systolic annular area, (mm 2 ) | 503.0 ± 88.9 | 470.4 ± 83.5 | <0.0001 |
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