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Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A single center experience
IJCA-28121; No of Pages 3 International Journal of Cardiology xxx (xxxx) xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Short communication
Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A single center experience Ghassan Daher a,⁎,1, Ihab Hassanieh a,1, Nikhil Malhotra a,1, Kahee Mohammed a,1, Maryna Popp Switzer b,1, Ali Mehdirad b,1 a b
Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, United States of America Division of Cardiovascular Medicine, Saint Louis University School of Medicine, Saint Louis, MO, United States of America
a r t i c l e
i n f o
Article history: Received 19 September 2019 Received in revised form 31 October 2019 Accepted 6 November 2019 Available online xxxx Keywords: Patent foramen ovale Pulmonary vein isolation Transesophageal echocardiogram Transthoracic echocardiogram Prevalence Cerebrovascular events
a b s t r a c t Background: Patent foramen ovale (PFO) has been reported in 25–30% of the general population. The most commonly used test for detecting PFO is a contrast enhanced transesophageal echocardiography (TEE). PFO presence can be confirmed during pulmonary vein isolation (PVI) procedure by passing the transseptal catheter assembly through the foramen ovale, crossing the septum from the right to the left atrium without using a trans-septal needle for puncture. Methods: We retrospectively reviewed data from a cohort of 178 patients with AF who underwent PVI at Saint Louis University. Pre-PVI procedure, scheduled TEE reports were reviewed to assess for the presence of PFO and the PVI procedure reports were reviewed for confirmation. Results: Records of 178 patients (55.6% male, mean population age 60.4 ± 11.8) were reviewed. 102 of 178 patients had a PFO detected during the PVI procedure. This translates into a 57.3% prevalence of PFO in AF patients. Out of the 178 patients, 75 patients had a pre-PVI procedure TEE for whom PFO presence was reported in 18.7%. The sensitivity and specificity of TEE in detection of PFO were 36.8% and 100%, respectively. There was no statistically significant association between stroke and PFO diagnosed during PVI (RR 1.07; 95% CI, 0.53–2.19; P = 0.805). Conclusions: Our study reports a PFO prevalence of 18.7% using a pre-procedure TEE and 56.6% during the PVI procedure in AF patients. Given that TEE is the gold standard for detection of PFO, our study suggests that the prevalence of PFO may be underestimated in our AF population. © 2019 Elsevier B.V. All rights reserved.
1. Introduction Patent foramen ovale (PFO) has been reported in 25–30% of the general population. This is based on a large experimental autopsy study done at Mayo clinic in 1984 [1]. It is also reported to be present in 50–60% of patients presenting with cryptogenic strokes and is the most common intracardiac defect associated with paradoxical emboli [2]. The most commonly used test for detecting PFO is a contrastenhanced transesophageal echocardiography (TEE) [3]. A less invasive imaging modality, transthoracic contrast echocardiography (TTE), also referred to as a bubble study, is often used as an alternative diagnostic tool [4,5]. Transcranial Doppler, another diagnostic test, has shown to be more sensitive that TEE in detecting PFO, with shunt grade acting
⁎ Corresponding author at: 907 N McKnight Rd, Apt A, Saint Louis, MO 63132, United States of America. E-mail address: [email protected] (G. Daher). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed preparation.
as a strong predictor for recurrent cerebral infarctions [6]. This difference in sensitivity may be attributed PFO presence can be confirmed during left-sided arrhythmia ablation, namely pulmonary vein isolation (PVI) procedure, by passing the transseptal catheter assembly (guidewire, dilator and sheath) through the foramen ovale (FO), and crossing the septum from the right to the left atrium without using a trans-septal needle for puncture. After a thorough literature review, we realized the need to evaluate the prevalence and clinical significance of PFO in patients with atrial fibrillation (AF) due to the scarcity of information relating to that condition. In this study we report the prevalence of PFO in 178 patients with AF who underwent PVI procedure at Saint Louis University hospital (SLUH) as compared to the prevalence detected during the pre-procedure TEE. 2. Methods This is a single center, single operator retrospective study reporting the prevalence of PFO in AF patients at SLUH. The study included all patients who underwent their first PVI for AF at SLUH. Patients who have
https://doi.org/10.1016/j.ijcard.2019.11.088 0167-5273/© 2019 Elsevier B.V. All rights reserved.
Please cite this article as: G. Daher, I. Hassanieh, N. Malhotra, et al., Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A sin..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.11.088
2
G. Daher et al. / International Journal of Cardiology xxx (xxxx) xxx
had a previous PVI procedure were excluded from the study to account for iatrogenic PFO related to previous trans-septal puncture. Patient's records were accessed and reviewed via Epic MAR system and previous clinic files. Data was then collected into a secure database, de-identified and analyzed. Pre-PVI scheduled TEE procedure was reviewed to assess for the presence of PFO and the PVI procedure reports were reviewed for confirmation. FO patency and accessibility were assessed in all patients prior to attempting to use a trans-septal needle for puncture. This was endeavored by the following maneuvers: a 5-French (Fr) sheath in the right femoral vein was exchanged over a wire for an Agilis steerable introducer with an outer diameter and an inner diameter of 11 and 8.5 Fr respectively (Abbott/St Jude Medical). Under fluoroscopic imaging and intracardiac echocardiography (ICE) guidance, and after guidewire pullback to within the dilator, the dilator tip was gradually pulled down on the septum till the FO's tenting was noted. With careful and cautious manipulation of the Agilis dilator and introducer, attempts were given to probe for PFO presence and passage into the left atrium through the FO. In case of inability to obtain access using the above maneuver, and after removal of the guidewire and dilator, a 7 French deflectable/steerable unidirectional quadripolar temperature-controlled mapping/ablation catheter (Biosense Webster or Abbott/St Jude Medical) was inserted into the Agilis introducer. Under fluoroscopic imaging and ICE guidance, attempts were then given to probe for PFO presence and obtaining access into the left atrium. If attempts failed, the transseptal access was obtained using a Brockenbrough (BRK/BRK1) transseptal needle/stylette assembly (Abbott/St Jude Medical). We were fully aware that access using a trans-septal puncture needle would be advantageous as it would provide more inferior and posterior transseptal access compared to a more superior and anterior PFO location on the septum. This in turn would facilitate access to the right-sided pulmonary veins. Trans-septal access was obtained successfully in all patients using one of the aforementioned techniques. Patients were stratified into two groups; those with PFO and those with no PFO detected during PVI procedure. Other clinical variables and co-morbidities were collected and analyzed (Table 1). 2.1. Statistical analysis Descriptive analysis was done for each patient. Continuous variables were presented by means ± standard deviation and dichotomous variables were presented by percentages. In regard to univariate analysis, Independent t-test was used for continuous variables and chi-squared/ Fisher's exact testing for categorical variables as appropriate. Bivariate analysis was performed to compare the cohort of patients with PFO versus patients with no PFO detected on either TEE or during PVI. Both groups had similar clinical characteristics. 3. Results A total of 229 patients with AF who underwent PVI from January 2012 to February 2018 at SLUH were reviewed. We were able to obtain complete records of 178 patients. Table 1 illustrates the baseline clinical characteristics of the cohort population included in this study. Mean population age was 60.4 ± 11.8 with 55.6% being males. 102 of 178 patients had a PFO detected during the PVI procedure, translating into a 57.3% prevalence of PFO in our cohort of AF patients. Out of the 178 patients, 75 patients had a pre-PVI procedure TEE for whom PFO presence was reported in 18.7%. Given that the presence of PFO can be confirmed by our methods during PVI, the sensitivity and specificity of TEE in the detection of PFO were 36.8% and 100%, respectively. Having said that, there was a statistically significant association between PFO diagnosed by TEE and history of stroke (RR 2.3; 95% CI, 1.02–6.79; P = 0.0447) but there was no statistically significant association between stroke and PFO diagnosed during PVI (RR 1.07; 95% CI, 0.53–2.19; P = 0.805). 58.8% of patients with hypertension were found to have a PFO
Table 1 Characteristics of study participants stratified by PFO. Patient characteristics
Overall Mean ± SD or N (%)
PFO Mean ± SD or N (%)
P value
Overall Age Sex Male Female BMI CHADVASC EF N 40% Yes No Missing Valvular heart disease Yes No Missing Hypertension Yes No Missing Diabetes mellitus Yes No PVD/CAD Yes No COPD Yes No Left atrial enlargement Yes No Missing
178 (100) 60.4 ± 11.8
102 (57.3) 59.1 ± 11.7
– 0.127
99 (55.6) 79 (44.4) 31.6 ± 7.3 2.5 ± 1.5
57 (55.9) 45 (44.1) 31.8 ± 7.9 2.4 ± 1.5
0.934
148 (83.2) 12 (6.7) 18 (10.1)
84 (82.3) 6 (5.9) 12 (11.8)
0.630
85 (47.7) 67 (37.6) 26 (14.6)
42 (41.2) 44 (43.1) 16 (15.7)
0.118
113 (63.5) 42 (23.6) 23 (12.9)
60 (58.8) 23 (22.5) 19 (18.6)
0.031
79 (44.4) 99 (55.6)
49 (48.0) 53 (52.0)
0.255
57 (32.0) 121 (68.0)
27 (24.5) 75 (73.5)
0.066
34 (19.1) 144 (80.9)
21 (20.6) 81 (79.4)
0.559
59 (33.1) 12 (6.7) 107 (60.1)
29 (28.4) 5 (4.9) 68 (66.7)
0.105
0.671 0.491
(P = 0.031), but no other association was found between PFO and other clinical comorbidities (Table 1). 4. Discussion In our single-center cohort of AF patients, there was more than a two-fold increase in the detection rate of PFO during the PVI procedure when compared to the general population. Our study reports a PFO prevalence of 18.7% detected on a pre-procedure TEE and 57.3% detected during PVI procedures. Given that TEE is the gold standard for detection of PFO, our study suggests that the prevalence of PFO may be underestimated in our AF population. In light of these findings and the well-established association between PFO and cryptogenic strokes [7,8], it was thought that the increased prevalence of PFO detected during PVI in this subset of patients might act as an additional and independent risk factor to AF for cerebral infarctions. Bearing this hypothesis in mind and the newly published data recommending PFO closure devices over medical therapy for secondary prevention of cryptogenic strokes [9–11], it was thought that patients with AF who have already had a previous episode of stroke should be assessed and evaluated for possible implantation of PFO closure devices. However, there was no statistically significant association between stroke and PFO detected during PVI. One would think that a PFO diagnosed during PVI and not visualized on TEE is clinically silent and most likely would not warrant further evaluation or monitoring likely due to their small size and difficulty for an embolic event to occur through it. This has been noted in a study conducted by Zoppo et al., which showed that PFOs detected during PVI did not seem to be an independent risk factor for cerebral infarction in AF patients [12]. Interestingly, the prevalence of PFO detected in their study was substantially lower than in our study. This might be attributed to the fact that a diagnostic steerable catheter was used, which has significantly less stiffness compared to the Agilis introducer assembly used in our study
Please cite this article as: G. Daher, I. Hassanieh, N. Malhotra, et al., Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A sin..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.11.088
G. Daher et al. / International Journal of Cardiology xxx (xxxx) xxx
to probe for the presence of a PFO. In addition, the single operator dexterity might have played a role. However, Ozdemir et al. suggested that the presence of dyspnea at onset of the stroke, migraine headaches, Valsalva maneuver just prior to the stoke, history of venous thromboembolism or sleep apnea may hint that PFO is causally related to the cryptogenic stroke [13]. Furthermore, the use of TCD with its ability to quantify shunt grade, as an adjunct to echocardiography, may help elucidate more clinically relevant PVI-positive TEE-negative foramina [6].
3
Declaration of competing interest There is no financial support, any relationship or conflict of interest with any industry. Acknowledgement None. References
4.1. Study limitations Since this is a single center retrospective descriptive study, it is subject to selection bias. All PVI procedures were performed by a single operator at SLUH which might have led to increased dexterity in achieving access to the left atrium without the need for a trans-septal needle puncture. The reduced number of patients who had a pre-procedure TEE compared to the number of PVI procedures is another limitation that might have underestimated the sensitivity of contrast-enhanced TEE in detecting PFO. Exposure to radiation should also be considered in our study, however, since we only had scarce information about the procedure and fluoroscopic time, we were unable to comment on this matter. However, most current electrophysiologists perform their ablation procedures via 3D mapping and avoid fluoroscopy use and thus minimize radiation exposure. Finally, this study included a small subset of patients and thus larger studies with greater power are needed in order to establish a reliable correlation between the two variables.
5. Conclusion In Conclusion, our cohort of AF patients undergoing PVI at SLUH was found to have a significantly higher prevalence of PFO compared to the general population. However, PFOs detected during PVI seem to be clinically trivial, with no associated increased risk for cerebral infarction noted. Therefore, no primary or secondary preventive measures, in regard to PFO, are warranted in this subset of patients.
[1] P.T. Hagen, D.G. Scholz, W.D. Edwards, Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts, Mayo Clin. Proc. 59 (1) (1984) 17–20. [2] S. Windecker, S. Stortecky, B. Meier, Paradoxical embolism, J. Am. Coll. Cardiol. 64 (4) (2014) 403–415. [3] B.S. Rana, M.R. Thomas, P.A. Calvert, M.J. Monaghan, D. Hildick-Smith, Echocardiographic evaluation of patent foramen ovale prior to device closure, J. Am. Coll. Cardiol. Img. 3 (7) (2010) 749–760. [4] A. Turley, J. Thambyrajah, P. Finn, A. Griffiths, M. de Belder, M. Stewart, Transthoracic contrast echocardiography in the detection of patent foramen ovale, Crit. Care 10 (2006) P344. [5] F.J. Pinto, When and how to diagnose patent foramen ovale, Heart 91 (2005) 438–440. [6] J. Tobe, C. Bogiatzi, C. Munoz, A. Tamayo, J.D. Spence, Transcranial Doppler is complementary to echocardiography for detection and risk stratification of patent foramen ovale, Can J Cardiol. 32 (8) (2016)(986.e9-.e16). [7] O.Y. Bang, M.J. Lee, S. Ryoo, S.J. Kim, J.W. Kim, Patent foramen ovale and stroke– current status, J Stroke. 17 (2015) 229–237. [8] J.A. Travis, S.B. Fuller, J. Ligush Jr., G.W. Plonk Jr., R.L. Geary, K.J. Hansen, Diagnosis and treatment of paradoxical embolus, J. Vasc. Surg. 34 (5) (2001) 860–865. [9] L. Sondergaard, S.E. Kasner, J.F. Rhodes, G. Andersen, H.K. Iversen, J.E. Nielsen-Kudsk, et al., Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke, N. Engl. J. Med. 377 (11) (2017) 1033–1042. [10] J.L. Saver, J.D. Carroll, D.E. Thaler, R.W. Smalling, L.A. MacDonald, D.S. Marks, et al., Long-term outcomes of patent foramen ovale closure or medical therapy after stroke, N. Engl. J. Med. 377 (11) (2017) 1022–1032. [11] J.L. Mas, G. Derumeaux, B. Guillon, E. Massardier, H. Hosseini, L. Mechtouff, et al., Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke, N Engl J Med. 377 (11) (2017) 1011–1021. [12] F. Zoppo, G. Stabile, A. Pappone, A. Avella, D. Pecora, L. Coro, et al., Prevalence of patent foramen ovale in atrial fibrillation patients with history of cerebral ischemia: a stand-alone additional risk? Int. J. Cardiol. 172 (2) (2014) e290–e291. [13] A.O. Ozdemir, A. Tamayo, C. Munoz, B. Dias, J.D. Spence, Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism, J. Neurol. Sci. 275 (1–2) (2008) 121–127.
Please cite this article as: G. Daher, I. Hassanieh, N. Malhotra, et al., Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A sin..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.11.088
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Short communication
Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A single center experience Ghassan Daher a,⁎,1, Ihab Hassanieh a,1, Nikhil Malhotra a,1, Kahee Mohammed a,1, Maryna Popp Switzer b,1, Ali Mehdirad b,1 a b
Department of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, MO, United States of America Division of Cardiovascular Medicine, Saint Louis University School of Medicine, Saint Louis, MO, United States of America
a r t i c l e
i n f o
Article history: Received 19 September 2019 Received in revised form 31 October 2019 Accepted 6 November 2019 Available online xxxx Keywords: Patent foramen ovale Pulmonary vein isolation Transesophageal echocardiogram Transthoracic echocardiogram Prevalence Cerebrovascular events
a b s t r a c t Background: Patent foramen ovale (PFO) has been reported in 25–30% of the general population. The most commonly used test for detecting PFO is a contrast enhanced transesophageal echocardiography (TEE). PFO presence can be confirmed during pulmonary vein isolation (PVI) procedure by passing the transseptal catheter assembly through the foramen ovale, crossing the septum from the right to the left atrium without using a trans-septal needle for puncture. Methods: We retrospectively reviewed data from a cohort of 178 patients with AF who underwent PVI at Saint Louis University. Pre-PVI procedure, scheduled TEE reports were reviewed to assess for the presence of PFO and the PVI procedure reports were reviewed for confirmation. Results: Records of 178 patients (55.6% male, mean population age 60.4 ± 11.8) were reviewed. 102 of 178 patients had a PFO detected during the PVI procedure. This translates into a 57.3% prevalence of PFO in AF patients. Out of the 178 patients, 75 patients had a pre-PVI procedure TEE for whom PFO presence was reported in 18.7%. The sensitivity and specificity of TEE in detection of PFO were 36.8% and 100%, respectively. There was no statistically significant association between stroke and PFO diagnosed during PVI (RR 1.07; 95% CI, 0.53–2.19; P = 0.805). Conclusions: Our study reports a PFO prevalence of 18.7% using a pre-procedure TEE and 56.6% during the PVI procedure in AF patients. Given that TEE is the gold standard for detection of PFO, our study suggests that the prevalence of PFO may be underestimated in our AF population. © 2019 Elsevier B.V. All rights reserved.
1. Introduction Patent foramen ovale (PFO) has been reported in 25–30% of the general population. This is based on a large experimental autopsy study done at Mayo clinic in 1984 [1]. It is also reported to be present in 50–60% of patients presenting with cryptogenic strokes and is the most common intracardiac defect associated with paradoxical emboli [2]. The most commonly used test for detecting PFO is a contrastenhanced transesophageal echocardiography (TEE) [3]. A less invasive imaging modality, transthoracic contrast echocardiography (TTE), also referred to as a bubble study, is often used as an alternative diagnostic tool [4,5]. Transcranial Doppler, another diagnostic test, has shown to be more sensitive that TEE in detecting PFO, with shunt grade acting
⁎ Corresponding author at: 907 N McKnight Rd, Apt A, Saint Louis, MO 63132, United States of America. E-mail address: [email protected] (G. Daher). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed preparation.
as a strong predictor for recurrent cerebral infarctions [6]. This difference in sensitivity may be attributed PFO presence can be confirmed during left-sided arrhythmia ablation, namely pulmonary vein isolation (PVI) procedure, by passing the transseptal catheter assembly (guidewire, dilator and sheath) through the foramen ovale (FO), and crossing the septum from the right to the left atrium without using a trans-septal needle for puncture. After a thorough literature review, we realized the need to evaluate the prevalence and clinical significance of PFO in patients with atrial fibrillation (AF) due to the scarcity of information relating to that condition. In this study we report the prevalence of PFO in 178 patients with AF who underwent PVI procedure at Saint Louis University hospital (SLUH) as compared to the prevalence detected during the pre-procedure TEE. 2. Methods This is a single center, single operator retrospective study reporting the prevalence of PFO in AF patients at SLUH. The study included all patients who underwent their first PVI for AF at SLUH. Patients who have
https://doi.org/10.1016/j.ijcard.2019.11.088 0167-5273/© 2019 Elsevier B.V. All rights reserved.
Please cite this article as: G. Daher, I. Hassanieh, N. Malhotra, et al., Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A sin..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.11.088
2
G. Daher et al. / International Journal of Cardiology xxx (xxxx) xxx
had a previous PVI procedure were excluded from the study to account for iatrogenic PFO related to previous trans-septal puncture. Patient's records were accessed and reviewed via Epic MAR system and previous clinic files. Data was then collected into a secure database, de-identified and analyzed. Pre-PVI scheduled TEE procedure was reviewed to assess for the presence of PFO and the PVI procedure reports were reviewed for confirmation. FO patency and accessibility were assessed in all patients prior to attempting to use a trans-septal needle for puncture. This was endeavored by the following maneuvers: a 5-French (Fr) sheath in the right femoral vein was exchanged over a wire for an Agilis steerable introducer with an outer diameter and an inner diameter of 11 and 8.5 Fr respectively (Abbott/St Jude Medical). Under fluoroscopic imaging and intracardiac echocardiography (ICE) guidance, and after guidewire pullback to within the dilator, the dilator tip was gradually pulled down on the septum till the FO's tenting was noted. With careful and cautious manipulation of the Agilis dilator and introducer, attempts were given to probe for PFO presence and passage into the left atrium through the FO. In case of inability to obtain access using the above maneuver, and after removal of the guidewire and dilator, a 7 French deflectable/steerable unidirectional quadripolar temperature-controlled mapping/ablation catheter (Biosense Webster or Abbott/St Jude Medical) was inserted into the Agilis introducer. Under fluoroscopic imaging and ICE guidance, attempts were then given to probe for PFO presence and obtaining access into the left atrium. If attempts failed, the transseptal access was obtained using a Brockenbrough (BRK/BRK1) transseptal needle/stylette assembly (Abbott/St Jude Medical). We were fully aware that access using a trans-septal puncture needle would be advantageous as it would provide more inferior and posterior transseptal access compared to a more superior and anterior PFO location on the septum. This in turn would facilitate access to the right-sided pulmonary veins. Trans-septal access was obtained successfully in all patients using one of the aforementioned techniques. Patients were stratified into two groups; those with PFO and those with no PFO detected during PVI procedure. Other clinical variables and co-morbidities were collected and analyzed (Table 1). 2.1. Statistical analysis Descriptive analysis was done for each patient. Continuous variables were presented by means ± standard deviation and dichotomous variables were presented by percentages. In regard to univariate analysis, Independent t-test was used for continuous variables and chi-squared/ Fisher's exact testing for categorical variables as appropriate. Bivariate analysis was performed to compare the cohort of patients with PFO versus patients with no PFO detected on either TEE or during PVI. Both groups had similar clinical characteristics. 3. Results A total of 229 patients with AF who underwent PVI from January 2012 to February 2018 at SLUH were reviewed. We were able to obtain complete records of 178 patients. Table 1 illustrates the baseline clinical characteristics of the cohort population included in this study. Mean population age was 60.4 ± 11.8 with 55.6% being males. 102 of 178 patients had a PFO detected during the PVI procedure, translating into a 57.3% prevalence of PFO in our cohort of AF patients. Out of the 178 patients, 75 patients had a pre-PVI procedure TEE for whom PFO presence was reported in 18.7%. Given that the presence of PFO can be confirmed by our methods during PVI, the sensitivity and specificity of TEE in the detection of PFO were 36.8% and 100%, respectively. Having said that, there was a statistically significant association between PFO diagnosed by TEE and history of stroke (RR 2.3; 95% CI, 1.02–6.79; P = 0.0447) but there was no statistically significant association between stroke and PFO diagnosed during PVI (RR 1.07; 95% CI, 0.53–2.19; P = 0.805). 58.8% of patients with hypertension were found to have a PFO
Table 1 Characteristics of study participants stratified by PFO. Patient characteristics
Overall Mean ± SD or N (%)
PFO Mean ± SD or N (%)
P value
Overall Age Sex Male Female BMI CHADVASC EF N 40% Yes No Missing Valvular heart disease Yes No Missing Hypertension Yes No Missing Diabetes mellitus Yes No PVD/CAD Yes No COPD Yes No Left atrial enlargement Yes No Missing
178 (100) 60.4 ± 11.8
102 (57.3) 59.1 ± 11.7
– 0.127
99 (55.6) 79 (44.4) 31.6 ± 7.3 2.5 ± 1.5
57 (55.9) 45 (44.1) 31.8 ± 7.9 2.4 ± 1.5
0.934
148 (83.2) 12 (6.7) 18 (10.1)
84 (82.3) 6 (5.9) 12 (11.8)
0.630
85 (47.7) 67 (37.6) 26 (14.6)
42 (41.2) 44 (43.1) 16 (15.7)
0.118
113 (63.5) 42 (23.6) 23 (12.9)
60 (58.8) 23 (22.5) 19 (18.6)
0.031
79 (44.4) 99 (55.6)
49 (48.0) 53 (52.0)
0.255
57 (32.0) 121 (68.0)
27 (24.5) 75 (73.5)
0.066
34 (19.1) 144 (80.9)
21 (20.6) 81 (79.4)
0.559
59 (33.1) 12 (6.7) 107 (60.1)
29 (28.4) 5 (4.9) 68 (66.7)
0.105
0.671 0.491
(P = 0.031), but no other association was found between PFO and other clinical comorbidities (Table 1). 4. Discussion In our single-center cohort of AF patients, there was more than a two-fold increase in the detection rate of PFO during the PVI procedure when compared to the general population. Our study reports a PFO prevalence of 18.7% detected on a pre-procedure TEE and 57.3% detected during PVI procedures. Given that TEE is the gold standard for detection of PFO, our study suggests that the prevalence of PFO may be underestimated in our AF population. In light of these findings and the well-established association between PFO and cryptogenic strokes [7,8], it was thought that the increased prevalence of PFO detected during PVI in this subset of patients might act as an additional and independent risk factor to AF for cerebral infarctions. Bearing this hypothesis in mind and the newly published data recommending PFO closure devices over medical therapy for secondary prevention of cryptogenic strokes [9–11], it was thought that patients with AF who have already had a previous episode of stroke should be assessed and evaluated for possible implantation of PFO closure devices. However, there was no statistically significant association between stroke and PFO detected during PVI. One would think that a PFO diagnosed during PVI and not visualized on TEE is clinically silent and most likely would not warrant further evaluation or monitoring likely due to their small size and difficulty for an embolic event to occur through it. This has been noted in a study conducted by Zoppo et al., which showed that PFOs detected during PVI did not seem to be an independent risk factor for cerebral infarction in AF patients [12]. Interestingly, the prevalence of PFO detected in their study was substantially lower than in our study. This might be attributed to the fact that a diagnostic steerable catheter was used, which has significantly less stiffness compared to the Agilis introducer assembly used in our study
Please cite this article as: G. Daher, I. Hassanieh, N. Malhotra, et al., Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A sin..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.11.088
G. Daher et al. / International Journal of Cardiology xxx (xxxx) xxx
to probe for the presence of a PFO. In addition, the single operator dexterity might have played a role. However, Ozdemir et al. suggested that the presence of dyspnea at onset of the stroke, migraine headaches, Valsalva maneuver just prior to the stoke, history of venous thromboembolism or sleep apnea may hint that PFO is causally related to the cryptogenic stroke [13]. Furthermore, the use of TCD with its ability to quantify shunt grade, as an adjunct to echocardiography, may help elucidate more clinically relevant PVI-positive TEE-negative foramina [6].
3
Declaration of competing interest There is no financial support, any relationship or conflict of interest with any industry. Acknowledgement None. References
4.1. Study limitations Since this is a single center retrospective descriptive study, it is subject to selection bias. All PVI procedures were performed by a single operator at SLUH which might have led to increased dexterity in achieving access to the left atrium without the need for a trans-septal needle puncture. The reduced number of patients who had a pre-procedure TEE compared to the number of PVI procedures is another limitation that might have underestimated the sensitivity of contrast-enhanced TEE in detecting PFO. Exposure to radiation should also be considered in our study, however, since we only had scarce information about the procedure and fluoroscopic time, we were unable to comment on this matter. However, most current electrophysiologists perform their ablation procedures via 3D mapping and avoid fluoroscopy use and thus minimize radiation exposure. Finally, this study included a small subset of patients and thus larger studies with greater power are needed in order to establish a reliable correlation between the two variables.
5. Conclusion In Conclusion, our cohort of AF patients undergoing PVI at SLUH was found to have a significantly higher prevalence of PFO compared to the general population. However, PFOs detected during PVI seem to be clinically trivial, with no associated increased risk for cerebral infarction noted. Therefore, no primary or secondary preventive measures, in regard to PFO, are warranted in this subset of patients.
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Please cite this article as: G. Daher, I. Hassanieh, N. Malhotra, et al., Patent foramen ovale prevalence in atrial fibrillation patients and its clinical significance; A sin..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2019.11.088