Effectiveness of integrating delayed computed tomography angiography imaging for left atrial appendage thrombus exclusion into the care of patients undergoing ablation of atrial fibrillation

1 2 3Q3 4 5 6 7 8 9 10 11 12 13 14 15Q4 Q1 16 17 18 19 20 21 22 23 24 25 26 27 28 Q6 29 30 Q7 31 32 33Q8 34 35 36Q9 37 38Q10 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54

Effectiveness of integrating delayed computed tomography angiography imaging for left atrial appendage thrombus exclusion into the care of patients undergoing ablation of atrial fibrillation Kenneth C. Bilchick, MD, MS, FACC, FHRS,* Augustus Mealor, MD,* Jorge Gonzalez, MD,* Patrick Norton, MD,*† David Zhuo, MD,* Pamela Mason, MD, FHRS,* John D. Ferguson, MD, FHRS,* Rohit Malhotra, MD,* J. Michael Mangrum, MD,* Andrew E. Darby, MD,* John DiMarco, MD, PhD, FHRS,* Klaus Hagspiel, MD,*† John Dent, MD,* Christopher M. Kramer, MD,*† George J. Stukenborg, PhD,‡ Michael Salerno, MD, PhD*†§ From the *Division of Medicine, Cardiovascular Division, University of Virginia Health System, Charlottesville, Virginia, †Department of Radiology and Medical Imaging, University of Virginia Health System, Charlottesville, Virginia, ‡Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, and §Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia. BACKGROUND Computed tomography angiography (CTA) can identify and rule out left atrial appendage (LAA) thrombus when delayed imaging is also performed. OBJECTIVE In patients referred for CTA to evaluate pulmonary vein anatomy before the ablation of atrial fibrillation (AF) or left atrial flutter (LAFL), we sought to determine the effectiveness of a novel clinical protocol for integrating results of CTA delayed LAA imaging into preprocedure care. METHODS After making delayed imaging of the LAA part of our routine preablation CTA protocol, we integrated early reporting of preablation CTA LAA imaging results into clinical practice as part of a formal protocol in June 2013. We then analyzed the effectiveness of this protocol by evaluating 320 AF/LAFL ablation patients with CTA imaging during the time period 2012–2014. RESULTS In CTA patients with delayed LAA imaging, the sensitivity and negative predictive values for LAA thrombus using intracardiac echocardiography or transesophageal echocardiography (TEE) as the reference standard were both 100%. Intracardiac echocardiography during ablation confirmed the absence of thrombus in patients with negative CTA or negative TEE results. No patients with either

The first 2 authors contributed equally to this work. This research was supported by the National Institutes of Health (grant K23 HL094761 to Dr Bilchick and K23 HL112910 to Dr Salerno). Dr Mason has received research grants from Johnson & Johnson, Boston Scientific, and Medtronic. Dr Malhotra has received consulting fees and research grants from Medtronic. Dr Darby has received consulting fees from Biosense Webster and Medtronic and research grants from Boston. Dr DiMarco has received consulting fees from Novartis, Medtronic, and Boston Scientific. Dr Mangrum has received research grants from Hansen Medical, St. Jude Medical, CardioFocus, and Medtronic. Dr Ferguson has received consulting

1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.

negative CTA results or equivocal CTA results combined with negative TEE results had strokes or transient ischemic attacks. Overall, the need for TEE procedures decreased from 57.5% to 24.0% during the 3-year period because of the CTA protocol. CONCLUSION Clinical integration of CTA with delayed LAA imaging Q11 into the care of patients having catheter ablation of AF or LAFL is feasible, safe, and effective. Such a protocol could be used broadly to improve patient care. KEYWORDS Atrial fibrillation; Catheter ablation; Computed tomography angiography; Transesophageal echocardiography; Stroke ABBREVIATIONS AF ¼ atrial fibrillation or left atrial flutter; CTA ¼ computed tomography angiography/angiogram; ICE ¼ intracardiac echocardiography/echocardiogram; LAA ¼ left atrial appendage; LAFL ¼ left atrial flutter; TEE ¼ transesophageal echocardiography/echocardiogram; TIA ¼ transient ischemic attack (Heart Rhythm 2015;0:-2–8) rights reserved.

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2015 Heart Rhythm Society. All

fees from St. Jude Medical and Biosense Webster and research grants from Boston Scientific and Medtronic. Dr Kramer has received consulting fees from St. Jude Medical and research support from Siemens Healthcare. Dr Salerno has received grant support from AstraZeneca and research support from Siemens Healthcare. Dr Bilchick has received consulting fees from Biosense Webster. Address reprint requests and correspondence: Dr Kenneth C. Bilchick, Department of Medicine, Cardiology/Electrophysiology, University of Virginia Health System, P.O. Box 800158, Charlottesville, VA 22908. E-mail address: [email protected].

http://dx.doi.org/10.1016/j.hrthm.2015.09.002

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Introduction

Methods

The prevalence of paroxysmal or persistent atrial fibrillation (AF) has recently been estimated to be 2.2 million in the United States,1 and the prevalence of stroke in patients with nonvalvular AF has been estimated to be 5%–8%.2 Although catheter ablation for AF3–5 is indicated for most patients with symptomatic paroxysmal and persistent arrhythmia,6 the optimal strategy for ruling out thrombus in the left atrial appendage (LAA) before catheter ablation is unclear. Although transesophageal echocardiography (TEE) is currently considered the criterion standard,7 it is a semi-invasive procedure associated with patient discomfort and a small risk of complications. Computed tomography angiography (CTA) is commonly used to evaluate pulmonary vein anatomy before left atrial ablation for AF. There is growing evidence suggesting that CTA could be a noninvasive alternative to TEE for the evaluation of LAA thrombus in patients who are already having a CTA to evaluate pulmonary vein anatomy before ablation, particularly if delayed LAA imaging is performed as part of the CTA imaging protocol.8–18 With these considerations in mind, we hypothesized that in patients undergoing a clinically ordered CTA study for preprocedure evaluation of pulmonary vein anatomy before AF ablation, a clinical protocol with early reporting of the CTA delayed LAA imaging results before the procedure and confirmatory intracardiac echocardiography (ICE) evaluation of the LAA during the procedure could improve clinical efficiency, maintain patient safety, and reduce the need for TEE procedures and their corresponding costs before the catheter ablation of AF or LAFL.

Cohort selection The study was approved by the Institutional Review Board for Human Subjects Research at the University of Virginia. Patients with ablation of AF or left atrial flutter (LAFL) and CTA imaging before ablation during the years 2012–2014 at the University of Virginia Health System were identified using a query of the electronic medical record. Patients with TEE procedures during this period were identified in a similar fashion. The data on these procedures were then merged on the basis of the medical record number using statistical software (SAS 9.4, SAS Institute Inc., Carey, NC).

CTA clinical protocol Before the study period, preprocedural imaging with CTA or cardiac magnetic resonance had become the standard clinical practice for most of our patients undergoing catheter ablation of AF or LAFL in order to evaluate pulmonary vein anatomy. In October 2012, we began to perform delayed LAA imaging as part of our routine preablation CTA protocol. In June 2013, we integrated prompt reporting of these results into clinical practice according to the clinical protocol described in Figure 1. The choice to use the clinical protocol was left to the discretion of the attending electrophysiologist who would be performing the ablation procedure, and patient characteristics including CHA2DS2-VASc scores19 were also integrated as shown in the figure. According to the clinical protocol, an outpatient preprocedure visit was scheduled before 9:00 AM on the preprocedure day and CTA was performed at 9:00 AM to

Figure 1 CTA protocol for patients undergoing catheter ablation of AF or LAFL. A flowchart demonstrating the clinical protocol for preprocedural imaging is shown. AF ¼ atrial fibrillation; CTA ¼ computed tomography angiography; ICE ¼ intracardiac echocardiography; LAA ¼ left atrial appendage; NPO ¼ non per os; TEE ¼ transesophageal echocardiography; TIA ¼ transient ischemic attack.

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Bilchick et al 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 Q13 207 208 209 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235Q14

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follow the office visit while the patient was still in the fasting state. The imager interpreting the study then provided an early read of the CTA delayed LAA imaging with respect to LAA thrombus and reported these results to our clinical nursing staff before 12:00 noon. Patients were instructed to remain in the hospital in a fasting state until noon and informed that they may need a TEE procedure later that day, depending on the results of CTA. If the early read of the CTA was negative for LAA thrombus, the nursing staff communicated this to the patients and let them know that they no longer needed to remain fasting, that they could return home, and that the ablation procedure would proceed as scheduled the following day. If the early read of the CTA was positive or equivocal for LAA thrombus, the nursing staff activated the add-on TEE appointment slot at 3:00 PM that day and told the patients that they should continue fasting. If the TEE was positive for LAA thrombus or another concerning finding, the ablation procedure would be canceled.

Intraprocedural ICE In all ablation procedures, ICE examinations of the LAA were performed to confirm the results of CTA. ICE is a standard part of our ablation procedures, and we routinely visualize the LAA in all patients as standard of care. Phasedarray ICE (Acunav or Soundstar, Biosense Webster, Diamond Bar, CA) was used in most patients, while rotational ICE (Boston Scientific, Washington, DC) was used in other patients. All electrophysiology operators are highly experienced with ICE, and the protocol for LAA imaging with each type of ICE is standardized. When phased-array ICE is used, the catheter is usually positioned near the tricuspid valve to image the LAA and the ridge between the appendage and the left superior pulmonary vein. With rotational ICE, the catheter is positioned in the left atrium at the base of the LAA and carefully rotated and advanced to visualize the appendage completely. We believed that this was preferable to performing TEE procedures routinely in all patients in the electrophysiology laboratory after induction of general anesthesia for several reasons, including (1) TEE procedures performed as part of the procedure add additional time to the procedure and require coordination with echocardiography staff; (2) performance of routine TEE procedures is associated with some additional risk of complications, particularly in AF ablation patients, in whom protection of the esophagus is of high importance; and (3) aborting an ablation procedure after the patient has been taken to the electrophysiology laboratory and has had induction of general anesthesia subjects the patients to additional risk and is more inefficient than canceling the procedure before the procedure day.

CTA imaging protocol CTA was performed using a nongated Siemens FLASH sequence with high-pitched acquisition mode, reference mA 200 mA, reference kVp 120 kVp, and care kV mode, which selects actual mAs and kVp on the basis of the CT topogram.

3 Using a bolus tracking technique and a 60 cubic centimeter3 bolus of intravenous contrast, imaging of the left atrial volume commenced 4 seconds after contrast enhancement reached 150 Hounsfield units in a region of interest in the left atrium. A delayed image volume tailored to the region of the LAA was acquired 40 seconds after the initial CTA images. Noncontrast images were not acquired because they do not contribute significantly to diagnostic utility.

Interpretation of CTA results Four dedicated attending cardiac imagers (M.S., C.M.K., P.N., and K.H.) each with 6–8 years of experience in interpreting cardiac CTA results, including level III training in CTA, read the CTA images in this study. The CTA images were read daily by our cardiac imaging service, which includes one of these attending cardiac imager and several other physicians. All positive or equivocal CTA imaging studies in the present series were also read by at least 1 other attending cardiac imager (M.S., C.M.K., P.N., or K.H.), and agreement was reached in all cases. With respect to image viewing, we use both axial planar viewing and 3-dimensional multiplanar reconstruction (MPR). With regard to the latter, the method used was iterative reconstruction (SAFIRE), with SAFIRE level set to 3, and images were reconstructed with a resolution of 0.5 mm, with a 0.4-mm increment. A CTA was read as negative if there were no filling defects in the LAA on delayed imaging and positive if there was a definite filling defect in the LAA on delayed imaging that had the typical appearance of thrombus. A CTA was read as equivocal if there was a hypointensity in the LAA on delayed imaging that could not be definitively differentiated from a trabeculation or appeared to be possibly caused by an artifact.

Assessment of procedure-related stroke and transient ischemic attack events Procedure-related strokes and transient ischemic attacks (TIAs) were defined as events occurring within 1 month of the procedure. This clinical end point was assessed at routine clinical follow-up 1 month after the procedure according to our usual follow-up protocol after ablation.

Statistical analysis Statistical analyses were performed using SAS 9.4. Distributional characteristics of continuous variables were described using medians and interquartile ranges, and differences between groups for these variables were compared using the Wilcoxon rank sum test. Categorical variable distributions were described on the basis of the number and percentage of each value of the variable in each group, and differences between groups were compared using the Fisher exact test. Correlations were described using the Pearson correlation coefficient, and the associated P values were reported. Characteristics of patients stratified by CHA2DS2-VASc scores and whether TEE procedures were performed were determined by reviewing the patients’ electronic medical records.

236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 Q15 257 258 259 260 Q16 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 Q17 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292

4 293Q27 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 T1 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 P 337 R 338 I 339 N 340 T 341 & W 342 E 343 B 344 4 345 C 346 / 347 F 348 P O 349

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Table 1

Patient Characteristics

Characteristic

No TEE (n ¼ 207)

TEE (n ¼ 113)

P

Age (y) 63.7 (57.1–70.8) 66.8 (57.9–72.8) .13 Sex: female 61 (29.4) 31 (27.4) .80 Persistent AF 32 (15.4) 42 (37.2) o.001 Heart failure 34 (16.4) 24 (21.2) .29 Hypertension 116 (56.0) 80 (70.8) .01 Diabetes 28 (13.5) 17 (15.0) .74 Stroke 9 (4.3) 9 (8.0) .21 Vascular disease 33 (16.0) 19 (16.8) .87 .22 CHA2DS2-VASc score 0–2 141 (68.1) 67 (59.3) 3–4 54 (26.1) 40 (35.4) 45 12 (5.8) 6 (5.3) Values are presented as median (interquartile range) or as n (%). AF ¼ atrial fibrillation; TEE ¼ transesophageal echocardiography.

Results Characteristics of ablation patients with CTA imaging We evaluated 320 consecutive patients with delayed LAA imaging performed within 1 week of catheter ablation during the time period 2012–2014. As shown in Table 1, the median age of patients in the entire cohort with and without TEE procedures during the entire evaluation period was not different (66.8 years vs 63.7 years; P ¼ .13). The proportion of female patients was also similar between the 2 groups (P ¼ .80). Patients with preablation CTAs were more likely

to have TEE procedures if they had persistent AF (37.2% vs 15.4%; P o .001) or hypertension (70.8% vs 56.0%; P ¼ .01).

Performance of CTA delayed LAA imaging In this cohort, CTA delayed LAA imaging showed an excellent performance for the identification of LAA abnormalities, and all positive or equivocal CTA results were confirmed by 2 experienced attending cardiac imaging physicians, as described in the Methods section. Two patients with positive CTA results and confirmed LAA thrombus had their ablation procedures postponed. Both these patients had persistent AF and CHA2DS2-VASc scores of 2. Figure 2 depicts an example of the filling defects seen clearly in one of these patients and thrombus seen on a TEE. Six patients had There were six equivocal CTAs with respect to the findings on delayed LAA imaging, and all subsequently had TEE results that were negative for LAA thrombus. Of these patients, 3 had prominent trabeculations and 2 had significant spontaneous echo contrast in the left atrium. These patients went on to have the ablation procedures performed. During the ablation procedures, absence of LAA thrombus was confirmed by ICE, as per our usual protocol. No periprocedural strokes or TIAs occurred in these patients, and there were also no esophageal complications in any patient. No patients with negative CTA results had thrombus on the TEE (if performed) or intraprocedural ICE, and none of these patients with negative CTA results had procedural-related strokes or TIAs, either. Overall, the

Figure 2 Examples of normal and abnormal CTA delayed left atrial appendage imaging. Filling defects in the left atrial appendage are seen on CTA (yellow arrows). For the case in which the filling defect was seen on both early and delayed imaging (panel C), the findings were confirmed by TEE (true positive). For the case in which the filling defect was seen on early but not delayed imaging (panel B), the finding was not confirmed by TEE (false positive). CTA ¼ computed tomography angiography; TEE ¼ transesophageal echocardiography.

350 351 352 353 354 355 356 357 358 359 360 F2361 362 363 364 Q18 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406

Bilchick et al 407 408 409 P 410 R I 411 N 412 T 413 & 414 W 415 E 416 B 417 4 C 418 / 419 F 420 P 421 O 422 423 424 425 426 F3 427 428 429 430 431 432Q19 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 P 452 R 453 I 454 N T 455 & 456 W 457 E 458 B 459 4 460 C 461 / F 462 P 463 O

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5

Figure 3 Performance of CTA with delayed LAA imaging relative to TEE as the reference standard. The sensitivity, specificity, positive predictive value, and negative predictive value for CTA with delayed LAA imaging relative to TEE as the reference standard are shown. In determining the specificity, the equivocal CTA results may be grouped with the positive CTA results or the negative CTA results. Specificity results obtained using both methods are shown in the example. CTA ¼ computed tomography angiography; TEE ¼ transesophageal echocardiography.

sensitivity and negative predictive value of a negative CTA delayed LAA imaging result for thrombus using ICE as the reference standard were both 100% (Figure 3). The specificity of the test when combining the positive and equivocal CTA results and comparing them with a negative CTA result was 98%.

Radiation dose The radiation dose was low, with a mean (median) dose length product of 257.5 (264) mGy  cm (which corresponds to an effective dose of 3.6 mSv using a coefficient of 0.014 mSv/ (mGy  cm)).

CTA results, TEE results, and protocol participation by patient subgroup As shown in Figure 4, 232 of 320 patients had CTA examinations performed during the protocol period. Of these 232 patients, 216 were in the low-intermediate risk category, and of these 216 patients, 213 had negative CTA results. Most of these patients (163 of 216 [75.4%]) went through the protocol process for the determination of the need for TEE procedures. Of the remaining 24.6% of patients, 53 low-intermediate risk patients with negative CTA results had TEE procedures performed anyway at the ordering

Figure 4 CTA and TEE results by patient subgroup and time period. The number of patients with different CTA and TEE results is shown by patient subgroup and time period. CTA ¼ computed tomography angiography; LAA ¼ left atrial appendage; LAAT ¼ left atrial appendage thrombus; Neg ¼ negative; Pos ¼ positive; SEC ¼ spontaneous echo contrast; TEE ¼ transesophageal echocardiography.

464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 F4483 Q20 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520

6 521 522 523 524 P 525 R 526 I 527 N T 528 & 529 W 530 E 531 B 532 4 533 C 534 / F 535 P 536 O 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555F5 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577

Heart Rhythm, Vol 0, No 0, Month 2015 findings on the CTA. Considering that there were no perioperative strokes or TIAs in any of these patients, these findings suggest that the proportion of patients who need TEE procedures before ablation is even lower. Of note, there were no significant differences before and after CT protocol initiation in patients with previous ablation in the preceding year (8.1% vs 10.3%; P ¼ .48).

Temporal trends in stroke risk score

Figure 5 Temporal trends in preprocedural TEE imaging before the catheter ablation of atrial fibrillation. The proportion of patients with TEE procedures after preprocedural CTA imaging has markedly decreased since the institution of the CTA protocol in June 2013. CTA ¼ computed tomography angiography; TEE ¼ transesophageal echocardiography.

physician's discretion (allowed because the protocol was optional) and 11 high-risk patients with negative CTA results (in whom the protocol recommended TEE procedures regardless of the CTA results) did not have TEE procedures ordered. The latter observation reflects increasing physician confidence in the protocol even for high-risk patients, which was validated by the fact that none of these 11 high-risk patients had evidence of LAA thrombus on ICE or strokes or TIAs during the postoperative period. Of note, all patients with positive or equivocal CTA results had TEE procedures performed as recommended by the protocol.

Temporal trends in preablation CTA results and TEE imaging Figure 5 shows that the proportion of patients with preablation CTAs with delayed LAA imaging who had TEE procedures also significantly decreased from 57.5% in the first half of 2012 to 24.0% in the second half of 2014. As shown in the figure, most of the TEE procedures that were performed after this optional protocol was made available after June 2013 were in patients for whom the protocol was not used, most commonly for one of the reasons listed in Figure 1. With respect to temporal trends in patients meeting protocol criteria for TEE before and after protocol initiation in mid-2013, 3 of 81 low-intermediate risk patients before protocol initiation would have met protocol criteria for TEE procedures based on the CTA results whereas 3 of 216 low-intermediate risk patients after protocol initiation met protocol criteria for TEE procedures based on the CTA results. If the protocol were extended to highrisk patients, 0 of 7 high-risk patients would have met protocol criteria for TEE procedures before protocol initiation, and 2 of 16 high-risk patients would have met protocol criteria for TEE procedures after protocol initiation. Overall, only 1%–3% of the TEE procedures performed during each 6-month time period after June 2013 in patients with preoperative CTA with delayed LAA imaging were associated with positive or equivocal LAA

With respect to temporal trends in of stroke risk, the mean CHA2DS2-VASc score for patients in 2013 was lower than that for patients in 2014 (1.75 vs 2.28; P ¼ .002). The decrease in TEE procedures in CTA patients in 2014 with the CTA protocol is interesting, considering that, if anything, patients in 2014 had a higher stroke risk. TEE procedures were more commonly performed in patients with higher CHA2DS2-VASc scores in 2013 (r ¼ 0.88 for the correlation between the CHA2DS2-VASc score and the percentage of TEE procedures ordered by CHA2DS2-VASc group in 2013; P ¼ .047), while the corresponding correlation was not significant in 2014 (r ¼ 0.78; P ¼ .11) (Figure 6). In the later time period, the weaker relationship between the CHA2DS2-VASc score and the decision to perform a TEE procedure may reflect increasing physician confidence in negative results of CTA imaging of the LAA after institution of the clinical protocol even in patients with higher CHA2DS2-VASc scores.

Discussion The key findings of this analysis are as follows: (1) a novel clinical protocol with early reporting of the results of CTA delayed LAA imaging of the LAA to inform the need for TEE procedures before AF ablation is feasible; (2) there is excellent agreement among CTA results, TEE findings (if performed), and intraprocedural ICE findings; (3) CTA was associated with low radiation doses; (4) the clinical protocol markedly reduced the number of TEE procedures in patients with preablation CTAs from 57.5% to 24%; and (5)

Figure 6 TEE procedures performed before catheter ablation by CHA2DS2VASc score and year. The proportion of patients with preprocedural CTA imaging who also received TEE procedures is shown according to CHA2DS2VASc score and time period (2014 vs 2013). CTA ¼ computed tomography angiography; TEE ¼ transesophageal echocardiography.

578 579 580 581 582 583 584 585 586 Q21 587 588 589 590 591 592 593 594 595 596 597 598 F6599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 P R 621 I 622 N 623 T 624 & 625 W 626 E 627 B 4 628 C 629 / 630 F 631 P 632 O 633 634

Bilchick et al 635 636 637 638 639 640 641 642 643 644Q22 645 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667Q23 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684Q24 685 686 687 688 689 690 691

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the protocol had an excellent safety profile, with no periprocedural strokes or TIAs or esophageal complications. While previous studies have shown that CTA has a high negative predictive value for LAA thrombus,8–18 we provide the first report of how the preprocedural CTA results can be integrated with other ultrasound imaging modalities for the patient undergoing AF ablation to improve clinical efficiency, promote patient safety, reduce the need for TEE procedures, and reduce costs. Before initiating this program, patients would typically be NPO (non per os) for much of the preprocedure day until after they completed their pulmonary vein imaging study and TEE in the early afternoon, and then they would fast again for a significant proportion of the procedure day until they had recovered enough from sedation. The TEE probe represented a potential irritant to the oropharynx in addition to the endotracheal tube placed during the procedure, as well as a potential source of esophageal injury for patients in whom esophageal protection is of major concern because of the left posterior wall ablation performed in proximity to the esophagus during the ablation procedure. Considering that CTA with delayed LAA imaging has a high negative predictive value for LAA thrombus, TEE provided redundant information in many cases, such that the risk-to benefit ratio associated with TEE was no longer favorable in many patients. In other words, although TEE imaging is powerful and useful for a number of clinical applications, the protocol helped to reduce the use of TEE imaging when a negative evaluation for LAA thrombus had already been achieved using another imaging modality (CTA). CTA provides an excellent definition of pulmonary vein anatomy before AF ablation, which can be helpful in defining the presence of a left common ostium, a right middle vein, an accessory vein, or other variant anatomical findings, as well as pulmonary vein and left atrial dimensions. In addition, the relationship between the left atrium and the esophagus is defined well with CTA, and other relevant extracardiac structures are visualized well. With the addition of delayed imaging, CTA can also provide high-quality imaging of filling defects in the LAA. Although cardiac magnetic resonance is an alternative to CTA for defining pulmonary vein anatomy, and late gadolinium enhancement and cine findings may be desired in some patients for whom evaluation of myocardial scar and/ or valvular function is needed, CTA is generally recognized as being superior to cardiac magnetic resonance for the exclusion of LAA thrombus, as current cardiac magnetic resonance protocols for the exclusion of LAA thrombus are not adequate in most cases. Furthermore, although it is true that there is no association of radiation with CMR, the radiation dose is quite low with the current CTA protocol, so this should not be a deterrent to its use. The radiation dose with CTA imaging could also be reduced further by using 100 kVp in most patients. An alternative to our approach would be to perform risk stratification based on the likelihood of LAA thrombus using baseline patient characteristics or risk scores such as the CHA2DS2-VASc score20,21 and not integrate CTA into the preablation protocol. This approach is limited by the lower

7 accuracy of risk stratification based on patient characteristics alone as compared with the present protocol based on both patient characteristics and CTA delayed LAA imaging of the LAA, which is integrated into a CTA examination that would be performed, anyway, for pulmonary vein anatomy. Notably, in our study, none of the patients with negative CTA results had a thrombus identified by TEE regardless of whether they were considered high risk or not using baseline characteristics, offering the possibility of extending the protocol to patients with a higher risk of thrombus. One exception may be patients with previous interventional closure of the LAA, who would likely benefit from TEE in addition to CTA because of the possibility of incomplete closure and the complexity of evaluating the LAA in this setting. TEE may also provide important information with respect to flow and spontaneous echo contrast in selected high-risk patients and those with equivocal LAA findings on the CTA.18

Study limitations The present report is designed to show the impact of a novel clinical protocol on clinical efficiency, patient outcomes, and patient safety. It is not a randomized study of one intervention vs another for a couple of reasons. First, clinical practice varies from physician to physician, there is significant experience with TEE procedures, and we did not want to prevent our electrophysiology physicians from ordering a TEE procedure if they thought it was indicated. Second, we wished to evaluate the effect of this optional clinical protocol on clinical practice without mandating its use, and we believe that the popularity of this clinical protocol among our physicians is a testament to its utility. As our electrophysiologists became more comfortable with the protocol, we saw increased utilization of this protocol. Another limitation of this study is that although patient satisfaction with the new clinical protocol appeared to be qualitatively improved, we did not formally conduct patient satisfaction surveys. Finally, characteristics of patients referred for AF ablation vary from institution to institution.

Conclusion A novel clinical protocol employing CTA with delayed LAA imaging improves clinical efficiency. In our cohort, we have also demonstrated excellent agreement between CTA and ultrasound-based imaging of the LAA, low radiation doses with CTA imaging, a reduced need for additional preablation procedures such as TEE procedures when filling defects in the LAA had been ruled out with CTA, and an excellent safety profile with no procedure-related cerebrovascular or esophageal complications. Such a protocol could be widely adopted by electrophysiology practices and have a positive impact on patient care and patient satisfaction.

Acknowledgments We acknowledge Cherie Parks, RN, Karen Coleman, RN, Felicia Murphy, RN, Susan Gionakos, RN, and our other nurses in the Cardiac Transition Unit for their great help in

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Heart Rhythm, Vol 0, No 0, Month 2015

implementing this protocol. We also acknowledge Anita Barber, BS, and Gregory Megginson, BS, for their help with the database queries.

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CLINICAL PERSPECTIVES This article presents new medical knowledge on how delayed imaging of the left atrial appendage with computed tomography angiography (CTA) can improve the clinical care of patients undergoing catheter ablation of atrial fibrillation and left atrial flutter as part of a novel clinical protocol, particularly when CTA has already been ordered for pulmonary vein anatomy. Although delayed LAA imaging with CTA requires only 1 extra sequence during the study and current CTA protocols involve low radiation doses, CTA delayed LAA imaging of the left atrial appendage is not routinely performed and/or not integrated into preprocedure care in many practices. Furthermore, there have been no published reports outlining a blueprint for this integration and demonstrating associated clinical outcomes. The present article describes the application of a novel clinical protocol in 320 patients at a major academic medical center and demonstrates the following key findings: (1) excellent agreement among CTA results, transesophageal echocardiography (TEE) findings (if performed), and intraprocedural intracardiac echocardiography findings; (2) low radiation doses; (3) marked reduction in the need for semiinvasive (TEE) procedures with such a protocol; and (4) an excellent safety profile, with no periprocedural strokes or transistent ischemic attacks. These findings show that this novel protocol can greatly improve and streamline preablation care, reduce the need for TEE procedures when the information would be superfluous on the basis of negative CTA results, and maintain an excellent safety profile with no cerebrovascular or esophageal complications. Dissemination of our findings will hopefully encourage other electrophysiology practices to implement similar protocols to promote optimal clinical care for preablation patients.

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