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Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients
International Journal of Cardiology 208 (2016) 115–119
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients Alexander C. Egbe a, Heidi M. Connolly a, Talha Niaz b, Christopher J. McLeod a,⁎ a b
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA Department of Pediatrics, Mayo Clinic, Rochester, MN, USA
a r t i c l e
i n f o
Article history: Received 19 December 2015 Received in revised form 16 January 2016 Accepted 22 January 2016 Available online 23 January 2016 Keywords: Cardioversion Fontan Atrial arrhythmia Arrhythmia recurrence
a b s t r a c t Background: Limited data are available about direct current cardioversion (DCCV) in Fontan patients. Methods: Retrospective review of adult Fontan patients that underwent DCCV for atrial arrhythmias at Mayo Clinic, 1994–2014. Study endpoints were to determine procedural success, safety, and the freedom from arrhythmia recurrence after DCCV. Procedural success was defined as termination of the presenting atrial arrhythmia prior to leaving the cardioversion suite. Results: 86 patients underwent 152 DCCV; age 27 ± 8 years; male 49 (57%); atriopulmonary Fontan, 64 (74%); atrial flutter/interatrial reentry tachycardia 125 (82%). Freedom from recurrence was 84% and 47% at 12 and 36 months; freedom from repeat DCCV was 91% and 64% at 12 and 36 months. Procedural failure occurred in 41 (27%); predictors of procedural failure were older age (HR 1.91, CI 1.16–2.73 per decade) and prior DCCV (HR 2.71, CI 1.22–3.21). Concomitant oral class I or III antiarrhythmic medication was associated with an increased likelihood of success (HR 0.64, CI 0.41–0.87). Predictors of recurrence were older age (HR 3.26, CI 1.19–6.55 per decade); duration of arrhythmia (HR 1.87, CI 1.14–2.56 per decade); and presence of atriopulmonary Fontan (HR 1.54, CI 1.27–1.85). Procedural complications were symptomatic bradycardia in 2 cases (1%). No thromboembolic complications or deaths occurred. Conclusion: DCCV in Fontan patients is safe but is associated with significant procedural failure and recurrence rates. Ideally, antiarrhythmic medication should be instituted prior to DCCV in stable patients and DCCV alone should be considered as a temporizing measure to maintain sinus rhythm. © 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Atrial arrhythmias are common after a Fontan operation and the prevalence of these arrhythmias increases with the duration of Fontan circulation [1–4]. Atrial arrhythmias are associated with impaired quality of life, increased risk of thromboembolism, ventricular dysfunction and death [3,5–7]. The Fontan physiology is a ‘low cardiac output’ state with limited physiological reserve [8,9] and as a result, atrial arrhythmias can be less well tolerated in Fontan patients compared to those with biventricular circulation. Restoration of sinus rhythm is important in certain subsets of patients to avoid acute and chronic hemodynamic deterioration. Direct current cardioversion (DCCV) is typically an effective therapy for the termination of arrhythmias in patients with congenital heart disease but its efficacy varies based on the underlying anatomy [10,11]. Abbreviations: AAD, Anti-arrhythmic drug; DCCV, Direct current cardioversion; TEE, Transesophageal echocardiogram. ⁎ Corresponding author at: Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. E-mail addresses: [email protected] (A.C. Egbe), [email protected] (H.M. Connolly), [email protected] (T. Niaz), [email protected] (C.J. McLeod).
http://dx.doi.org/10.1016/j.ijcard.2016.01.209 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
The Fontan procedure involves multiple atrial scars, fibrosis, and commonly with significant atrial dilation. The combination of these factors can provide an arrhythmogenic milieu for the initiation and maintenance of atrial arrhythmias [12,13]. In addition, the lack of a systolic forward vector in the Fontan circulation frequently leads to sluggish blood flow and associated Fontan thrombus. There is limited data on the efficacy and safety of DCCV in Fontan patients and the purpose of this study is to determine procedural success, safety and the freedom from arrhythmia recurrence after DCCV for atrial arrhythmia. 2. Methods 2.1. Patient selection and data extraction The Mayo Clinic Institutional Review Board approved this study. We identified all adults (N18 years) with history of Fontan operation who underwent DCCV for atrial arrhythmia at Mayo Clinic from January 1994 to June 2014 using free text search software (Advanced Clinical Explorer). Patients with less than 12 months of follow-up after DCCV (n = 17) were excluded. Atrial arrhythmias were defined as intra-atrial reentry tachycardia/ atrial flutter, atrial fibrillation and ectopic atrial tachycardia. We reviewed
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clinical notes, electrocardiograms pre- and post DCCV, Holter monitor records, echocardiograms and cardiac catheterization data. 2.2. Study design The study endpoints were to determine procedural success, procedural safety and the freedom from arrhythmia recurrence after DCCV. Procedural success was defined as termination of the presenting atrial arrhythmia prior to leaving the cardioversion suite. DCCV complications were defined as symptomatic bradycardia requiring pacing, new onset tachyarrhythmia immediately after DCCV, esophageal injury during intubation for transesophageal echocardiogram (TEE), death or thromboembolism (stroke/transient ischemic attack, pulmonary embolism) within 30 days of DCCV. 2.3. Anticoagulation Therapeutic anticoagulation was defined as partial thromboplastin time ≥ 55 s (while on unfractionated Heparin) or international normalized ratio ≥ 2.0 (while in Warfarin) within 48 h prior to DCCV. TEEguided DCCV was performed in the patients with subtherapeutic anticoagulation, and in the patients considered to be at high risk for intracardiac thrombi. 2.4. Sedation and procedural data Fentanyl and midazolam were used for conscious sedation during TEE. After TEE was performed, an anesthesiologist administers anesthesia using thiopental or propofol. DCCV was performed using a standardized protocol. Defibrillator pads were placed to the right of the sternum anteriorly and over the left scapula posteriorly. Synchronized DCCV was performed in all cases starting from 75 J and successively increased to 150, 300, and 360 J if DCCV was unsuccessful. A 12-lead electrocardiogram was obtained after a successful DCCV. If atrial arrhythmia recurred less than 5 min after an initial success, one more shock at the energy level that was previously successful was performed. 2.5. Statistical analysis All statistical calculations were performed with the JMP version 10.0 software (SAS Institute Inc., Cary, NC, USA). Categorical variables were expressed as percentages while continuous variables were expressed as mean ± standard deviation. Comparison of categorical variables was performed using chi-square test or Fisher exact test, while comparison of continuous variables was performed with two-sided unpaired Student t-test or Wilcoxon rank sum test as appropriate. We used total number of patients (n = 86) for censor of recurrence and total number of procedure (n = 152) for censor of procedural failure. Univariable and multivariable Cox proportional-hazard models were used to identify predictors of procedural failure and arrhythmia recurrence. The risk for each variable was expressed in hazard ratio (HR) and 95% confidence interval (CI). The freedom from arrhythmia recurrence and repeat DCCV were calculated with the Kaplan–Meier method and compared using the log-rank test. All p values were two sided, and p values b 0.05 were considered significant. 3. Results 3.1. Baseline patient characteristics We identified 86 adult Fontan patients who underwent DCCV for atrial arrhythmias at Mayo Clinic from 1994 to 2014 and met inclusion criteria. The mean age was 27 ± 8 years; mean age at the time of Fontan operation was 14 ± 9 years; and 49 (57%) were males. The most common type of Fontan connection was atriopulmonary Fontan, 64 (74%); most common ventricular morphology was the left ventricle,
63 (73%); and the most common diagnosis was tricuspid atresia, 34 (40%), Table 1.
3.2. Procedural success There were 152 DCCV performed within the study period; 57 patients (66%) underwent 2 DCCV and 9 patients (10%) underwent ≥ 3 DCCV for arrhythmia recurrence. For 131 (86%) of the DCCV, the patient was on an AAD at the time of the DCCV, of which 112 (74%) were either on class I or III AAD. The most common atrial arrhythmia was atrial flutter/IART, 125 (82%). Out of 152 DCCV, 111 (73%) were successful, Table 2.
3.3. Procedural safety Eighty-eight (58%) of all DCCV in our cohort were TEE-guided (TEE performed on the day of DCCV); additional 47 (31%) had TEE performed within 48 h prior to DCCV; and the 17 (11%) patients who did not have TEE within 48 h had documented therapeutic INR. All TEEs were negative for intracardiac thrombus. A total of 104 patients had INR assays within 48 h prior to DCCV, and 91 (87%) of these assays showed therapeutic INR. All 13 patients (13%) with subtherapeutic INR were on heparin (unfractionated heparin, n = 12; and low molecular weight heparin, n = 1).
Table 1 Baseline characteristics. Number of patients Age, year Age at onset of arrhythmia, year Age at Fontan, year Time from Fontan operation, year Male (%) FU post DCCV, months H/o of prior catheter ablation Fontan type Atrio-pulmonary Fontan LTF/IAC Extracardiac Fontan Ventricular morphology Left ventricle Right ventricle Indeterminate Initial diagnosis Tricuspid atresia Mitral atresia Common inlet ventricle Double inlet left ventricle Pulmonary atresia Others Echocardiography (n = 86) M/S right atrial enlargement M/S ventricular dysfunction M/S AVV regurgitation Cardia catheterization data (n = 61) Fontan pressure, mm Hg VEDP, mm Hg Cardiac index, L/min/m2 Systemic saturation PVRi, WU ∗ m2 DCCV: Direct current cardioversion. FU: Follow up. H/o: History of. IAC: Intraatrial conduit. LTF: Lateral tunnel Fontan. M/S: Moderate–severe. AVV: Atrioventricular valve. VEDP: Ventricular end-diastolic pressure. PVRi: Pulmonary vascular resistance index. WU ∗ m2: Wood units × meters squared.
86 27 ± 8 24 ± 11 14 ± 9 13 ± 8 49 (57%) 48 ± 21 4 (5%) 64 (74%) 16 (19%) 6 (7%) 63 (73%) 19 (22%) 4 (5%) 34 (40%) 3 (4%) 10 (12%) 29 (33%) 5 (5%) 5 (5%) 56 (65%) 33 (38%) 13 (15%) 16 ± 3 11 ± 4 2.0 ± 0.3 89 ± 5 2.5 ± 0.7
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3.5. Predictors of arrhythmia recurrence and procedural failure
Table 2 Direct current cardioversion data. Number of DDCV Number of patients Atrial arrhythmia type Atrial flutter/IART Atrial fibrillation Ectopic atrial tachycardia AAD use at time of DCCV Class I Class II Class III Class IV Digoxin Number of shocks Emergent/urgent DCCV within 48 h TEE-guided (within 24 h*) TEE-guided (within 48 h**) INR (N2.0)*** Successful DCCV
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152 86 125 (82%) 24 (16%) 3 (3%) 131 (86%) 47 (31%) 109 (72%) 65 (43%) 97 (64%) 14 (9%) 1 (1–5) 14 (9%) 40 (26%) 88 (58%) 135 (89%) 91 (87%) 111 (73%)
AAD: Antiarrhythmic drug. IART: Intraatrial reentry tachycardia. INR: International normalized ratio. INR***: only 104 procedures had INR assay within 48 h prior to DCCV. TEE: Transesophageal echocardiogram. TEE-guided (within 24 h*): TEE performed within 24 h of DCCV. TEE-guided (within 48 h**): TEE performed within 48 h of DCCV.
The only complications attributed to DCCV were 2 cases (1%) of symptomatic bradycardia requiring temporary pacing. There were no tachyarrhythmia and no complication related to esophageal intubation during TEE. There were no thromboembolic complications immediately or within 30 days of DCCV. No deaths occurred related to DCCV during the study period.
3.4. Arrhythmia recurrence Seventy-nine patients (92%) experienced recurrence over a mean follow-up period of 48 ± 21 months. The freedom from recurrence was 84%, 47% and 19% at 12, 36 and 60 months respectively. The freedom from recurrence was significantly lower in patients with atriopulmonary Fontan compared to other types of Fontan connections, P = 0.010 (Fig. 1A). Freedom from repeat DCCV was 91%, 64% and 35% at 12, 36 and 60 months respectively, Fig. 1B.
Forty-one (27%) DCCV were unsuccessful in terminating arrhythmia. Multivariable predictors of procedural failure were older age (HR 1.91, CI 1.16–2.73) for every decade increase in age and history of prior DCCV (HR 2.71, CI 1.22–3.21). Being on class I or III antiarrhythmic drugs at the time of DCCV was protective (HR 0.64, CI 0.41–0.87), Table 3. Multivariable predictors of recurrence were older age (HR 3.26, CI 1.19–6.55.73) for every decade increase in age, duration of arrhythmia (HR 1.87, CI 1.14–2.56) for decade increase in duration, and presence of atriopulmonary Fontan (HR 1.54, CI 1.27–1.85), Table 4. 4. Discussion These findings underscore that cardioversion can be performed safely and with reasonable success in patients with a Fontan circulation in a specialized multidisciplinary care group. 4.1. Procedural success This study indicates that DCCV is successful in terminating arrhythmia in the majority (76%) of cases, yet this is significantly lower that the success rate of more than 90% reported for congenital heart disease population with biventricular circulation [10,11]. A prior retrospective analysis [10] of 63 patients with congenital heart disease reported that DCCV was successful in 94% of cases. This series included only 16 Fontan patients. Anatomical and surgical features of the Fontan such as multiple atrial surgical scars, extensive atrial fibrosis and atrial dilation does distinguish this from other repaired congenital heart disease diagnosis, and is distinctly more arrhythmogenic [12,13]. These factors may be responsible for the higher incidence of atrial arrhythmias as well as DCCV procedural failure in Fontan patients compared to other types of congenital heart disease. Independent predictors of procedural failure in our cohort were older age and prior DCCV. Conversely, current therapy with class I or III AAD augmented cardioversion success. This correlates with prior reports confirming the efficacy of the class III agent, sotalol in a small cohort of Fontan patients; where sotalol was effective as sole therapy in terminating atrial arrhythmias in 7 out of 9 patients. Importantly two patients within this group did require permanent pacemaker implant for sinus bradycardia [14]. In contrast to class IA drugs, the class III agents are known to decrease defibrillation thresholds, and thereby
Fig. 1. (A) Freedom from arrhythmia recurrence; atriopulmonary Fontan cohort (red), lateral tunnel/intraatrial conduit/extracardiac Fontan (green), All Fontan types (blue). P value is for the comparison of red and green curves; (B) Freedom from repeat cardioversion. LTF: lateral tunnel Fontan; IAC: intraatrial conduit; ECF: extracardiac Fontan. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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Table 3 Predictors of procedural failure. Variables
Age (per decade increase) Duration of Fontan physiology (per decade increase) Duration of arrhythmia (per decade increase) AAD use at the time of DCCV Class I or III AAD use at the time of DCCV DCCV within 48 h of arrhythmia onset Atriopulmonary Fontan Atrial fibrillation Prior DCCV Spontaneous echocardiographic contrast M/S right atrial enlargement M/S ventricular dysfunction Fontan pressure (per unit increase) VEDP (per unit increase) Cardiac index (per unit increase) PVRi (per unit increase)
Univariate
Multivariate
HR (95% CI)
P value
HR (95% CI)
P value
3.43 (2.24–8.16) 2.13 (1.64–4.16) 4.32 (1.21–6.45) 0.83 (0.23–1.97) 0.76 (0.22–0.91) 1.44 (0.73–3.65) 3.32 (0.18–8.54) 3.43 (0.89–15.32) 4.37 (2.65–6.29) 1.31 (0.72–1.98) 2.66 (1.53–3.34) 1.01 (0.22–4.12) 2.06 (0.31–5.63) 1.75 (0.53–4.74) 1.34 (0.28–4.12) 2.43 (0.30–4.63)
0.002 0.019 0.024 0.27 0.001 0.19 0.18 0.29 0.014 0.15 0.001 0.71 0.29 0.41 0.39 0.31
1.91 (1.16–2.73) 2.14 (0.93–4.42) 2.19 (0.67–4.23)
0.022 0.06 0.14
0.64 (0.41–0.87)
0.031
2.71 (1.22–3.21)
0.025
1.96 (0.84–3.44)
0.42
CI: Confidence interval. HR: Hazard ratio.
augment chances of a successful cardioversion [15,16]. Yet these data suggest that both classes of agents were preferable to no antiarrhythmic therapy, and thereby implying that Fontan patients who are hemodynamically stable should perhaps be preemptively loaded with anti-arrhythmic therapy prior to DCCV in order to improve cardioversion success.
4.2. Procedural safety DCCV was safe in our Fontan patients; the most common complication was bradycardia. There were no thromboembolic complications within 30 days after DCCV in our cohort. This result is consistent with other studies demonstrating no DCCV-related thromboembolic complications in 63 patients with congenital heart disease [10]. The slow flow state in the Fontan commonly results in chronic and acute thrombus, and a major clinical concern for patients with this type of repair is dislodgement of fresh thrombus with cardioversion and potentially fatal pulmonary thromboembolism [17]. Although intracardiac thrombus is identified frequently in patients with Fontan repairs and coexistent atrial arrhythmias, the systemic atrium appears to be rarely involved, and DCCV has not been associated with a higher incidence of stroke or systemic embolism in this group [6].
4.3. Arrhythmia recurrence More than 80% of our cohort experienced recurrence of atrial arrhythmias during follow-up and 66% were treated with repeat DCCV. Arrhythmia recurrence after DCCV in the congenital heart disease population has been reported to be 50–60% [10,11] and this varied by arrhythmia type, structural heart disease type and patient characteristics. Fontan patients are likely prone to recurrence because of more atrial substrate abnormality [12,13]. The presence of spontaneous contrast identified by TEE examination and the presence of atrial fibrillation (versus atrial flutter/atrial tachycardia) have been reported as predictors of recurrence in patients with congenital heart disease [10]. In contrast, this study did not identify the same predictors for atrial arrhythmias. Instead, older patients and those with atriopulmonary Fontan were more prone to recurrence. The presence of atrial fibrillation, however, does also stand out as a predictor of atrial arrhythmia recurrence in several other studies [18,19]. In patients with acquired heart disease or even in the normal heart, this particular form of atrial arrhythmia is typically considered a disease of the left atrium [20]. Commonly, the left atrium in patients with Fontan repairs is normal in size, and it is likely that atrial fibrillation in the Fontan patient is a worse prognostic sign, suggestive of worse Fontan substrate and potentially bi-atrial disease. Due to the high risk of recurrence, DCCV should be considered as a temporizing measure to acutely terminate arrhythmia in
Table 4 Predictors of arrhythmia recurrence. Variables
Age (per decade increase) Duration of Fontan physiology (per decade increase) Duration of arrhythmia (per decade increase) Use of AAD therapy Use of Class I or III AAD therapy Atriopulmonary Fontan H/o atrial fibrillation Spontaneous echocardiographic contrast M/S right atrial enlargement M/S ventricular dysfunction Fontan pressure (per unit increase) VEDP (per unit increase) Cardiac index (per unit increase) PVRi (per unit increase)
Univariate
Multivariate
HR (95% CI)
P value
HR (95% CI)
P value
6.71 (2.61–8.33) 2.21 (1.76–3.11) 3.61 (2.41–5.82) 1.34 (0.47–3.51) 1.85(0.46–3.91) 1.53(1.26–2.21) 2.63 (1.46–3.89) 2.12 (0.53–3.94) 0.41(0.11–0.83) 1.31(0.72–1.98) 1.75 (0.53–4.74) 1.01(0.22–4.12) 2.06(0.3–5.63) 0.81(0.33–1.73)
b0.0001 b0.0001 0.001 0.142 0.16 0.003 0.002 0.31 0.007 0.15 0.41 0.71 0.29 0.37
3.26 (1.19–6.55) 1.52 (0.66–3.89) 1.87 (1.14–2.56)
0.031 0.42 0.001
1.54 (1.27–1.85) 2.49 (0.66–4.21)
0.024 0.17
1.55 (0.82–2.14)
0.09
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the setting of hemodynamic instability, or to restore sinus rhythm and improve cardiovascular efficiency in a stable patient with persistent arrhythmia despite antiarrhythmic therapy. 4.4. Limitations This is a retrospective study. There may be selection bias because we reviewed only the Fontan patients that actually underwent DCCV and not all Fontan patients with atrial arrhythmias. We are unable to account for patients excluded from DCCV because of suspected intracardiac thrombus on TEE, thus our estimate of DCCV-related thromboembolic complications might underestimate the risk in the Fontan population. Additionally, we relied on documentation of thromboembolic complications as reported by the patients and silent thromboembolic complications may have been missed [21,22]. All these limitations affect generalizability of our data. 5. Conclusion Direct current cardioversion appears to be a safe procedure in those patients with a prior Fontan repair when performed by a specialized multidisciplinary team. This intervention is associated with a substantial rate of late recurrence of arrhythmia, and should be considered a temporizing measure, prompting referral to a congenital heart rhythm specialist to plan long-term therapy. The use of a class I or III AAD appears to be the strongest salutary influence, and it therefore should be considered antecedently if hemodynamics permit. Of all the risk factors influencing the outcome of DCCV, the use of AAD is the only modifiable factor, and the clinician should take advantage of this. Conflict of interest None. Funding None. Acknowledgement None. References [1] J. Weipert, C. Noebauer, C. Schreiber, et al., Occurrence and management of atrial arrhythmia after long-term Fontan circulation, J. Thorac. Cardiovasc. Surg. 127 (2004) 457–464.
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Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients Alexander C. Egbe a, Heidi M. Connolly a, Talha Niaz b, Christopher J. McLeod a,⁎ a b
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA Department of Pediatrics, Mayo Clinic, Rochester, MN, USA
a r t i c l e
i n f o
Article history: Received 19 December 2015 Received in revised form 16 January 2016 Accepted 22 January 2016 Available online 23 January 2016 Keywords: Cardioversion Fontan Atrial arrhythmia Arrhythmia recurrence
a b s t r a c t Background: Limited data are available about direct current cardioversion (DCCV) in Fontan patients. Methods: Retrospective review of adult Fontan patients that underwent DCCV for atrial arrhythmias at Mayo Clinic, 1994–2014. Study endpoints were to determine procedural success, safety, and the freedom from arrhythmia recurrence after DCCV. Procedural success was defined as termination of the presenting atrial arrhythmia prior to leaving the cardioversion suite. Results: 86 patients underwent 152 DCCV; age 27 ± 8 years; male 49 (57%); atriopulmonary Fontan, 64 (74%); atrial flutter/interatrial reentry tachycardia 125 (82%). Freedom from recurrence was 84% and 47% at 12 and 36 months; freedom from repeat DCCV was 91% and 64% at 12 and 36 months. Procedural failure occurred in 41 (27%); predictors of procedural failure were older age (HR 1.91, CI 1.16–2.73 per decade) and prior DCCV (HR 2.71, CI 1.22–3.21). Concomitant oral class I or III antiarrhythmic medication was associated with an increased likelihood of success (HR 0.64, CI 0.41–0.87). Predictors of recurrence were older age (HR 3.26, CI 1.19–6.55 per decade); duration of arrhythmia (HR 1.87, CI 1.14–2.56 per decade); and presence of atriopulmonary Fontan (HR 1.54, CI 1.27–1.85). Procedural complications were symptomatic bradycardia in 2 cases (1%). No thromboembolic complications or deaths occurred. Conclusion: DCCV in Fontan patients is safe but is associated with significant procedural failure and recurrence rates. Ideally, antiarrhythmic medication should be instituted prior to DCCV in stable patients and DCCV alone should be considered as a temporizing measure to maintain sinus rhythm. © 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Atrial arrhythmias are common after a Fontan operation and the prevalence of these arrhythmias increases with the duration of Fontan circulation [1–4]. Atrial arrhythmias are associated with impaired quality of life, increased risk of thromboembolism, ventricular dysfunction and death [3,5–7]. The Fontan physiology is a ‘low cardiac output’ state with limited physiological reserve [8,9] and as a result, atrial arrhythmias can be less well tolerated in Fontan patients compared to those with biventricular circulation. Restoration of sinus rhythm is important in certain subsets of patients to avoid acute and chronic hemodynamic deterioration. Direct current cardioversion (DCCV) is typically an effective therapy for the termination of arrhythmias in patients with congenital heart disease but its efficacy varies based on the underlying anatomy [10,11]. Abbreviations: AAD, Anti-arrhythmic drug; DCCV, Direct current cardioversion; TEE, Transesophageal echocardiogram. ⁎ Corresponding author at: Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. E-mail addresses: [email protected] (A.C. Egbe), [email protected] (H.M. Connolly), [email protected] (T. Niaz), [email protected] (C.J. McLeod).
http://dx.doi.org/10.1016/j.ijcard.2016.01.209 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
The Fontan procedure involves multiple atrial scars, fibrosis, and commonly with significant atrial dilation. The combination of these factors can provide an arrhythmogenic milieu for the initiation and maintenance of atrial arrhythmias [12,13]. In addition, the lack of a systolic forward vector in the Fontan circulation frequently leads to sluggish blood flow and associated Fontan thrombus. There is limited data on the efficacy and safety of DCCV in Fontan patients and the purpose of this study is to determine procedural success, safety and the freedom from arrhythmia recurrence after DCCV for atrial arrhythmia. 2. Methods 2.1. Patient selection and data extraction The Mayo Clinic Institutional Review Board approved this study. We identified all adults (N18 years) with history of Fontan operation who underwent DCCV for atrial arrhythmia at Mayo Clinic from January 1994 to June 2014 using free text search software (Advanced Clinical Explorer). Patients with less than 12 months of follow-up after DCCV (n = 17) were excluded. Atrial arrhythmias were defined as intra-atrial reentry tachycardia/ atrial flutter, atrial fibrillation and ectopic atrial tachycardia. We reviewed
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clinical notes, electrocardiograms pre- and post DCCV, Holter monitor records, echocardiograms and cardiac catheterization data. 2.2. Study design The study endpoints were to determine procedural success, procedural safety and the freedom from arrhythmia recurrence after DCCV. Procedural success was defined as termination of the presenting atrial arrhythmia prior to leaving the cardioversion suite. DCCV complications were defined as symptomatic bradycardia requiring pacing, new onset tachyarrhythmia immediately after DCCV, esophageal injury during intubation for transesophageal echocardiogram (TEE), death or thromboembolism (stroke/transient ischemic attack, pulmonary embolism) within 30 days of DCCV. 2.3. Anticoagulation Therapeutic anticoagulation was defined as partial thromboplastin time ≥ 55 s (while on unfractionated Heparin) or international normalized ratio ≥ 2.0 (while in Warfarin) within 48 h prior to DCCV. TEEguided DCCV was performed in the patients with subtherapeutic anticoagulation, and in the patients considered to be at high risk for intracardiac thrombi. 2.4. Sedation and procedural data Fentanyl and midazolam were used for conscious sedation during TEE. After TEE was performed, an anesthesiologist administers anesthesia using thiopental or propofol. DCCV was performed using a standardized protocol. Defibrillator pads were placed to the right of the sternum anteriorly and over the left scapula posteriorly. Synchronized DCCV was performed in all cases starting from 75 J and successively increased to 150, 300, and 360 J if DCCV was unsuccessful. A 12-lead electrocardiogram was obtained after a successful DCCV. If atrial arrhythmia recurred less than 5 min after an initial success, one more shock at the energy level that was previously successful was performed. 2.5. Statistical analysis All statistical calculations were performed with the JMP version 10.0 software (SAS Institute Inc., Cary, NC, USA). Categorical variables were expressed as percentages while continuous variables were expressed as mean ± standard deviation. Comparison of categorical variables was performed using chi-square test or Fisher exact test, while comparison of continuous variables was performed with two-sided unpaired Student t-test or Wilcoxon rank sum test as appropriate. We used total number of patients (n = 86) for censor of recurrence and total number of procedure (n = 152) for censor of procedural failure. Univariable and multivariable Cox proportional-hazard models were used to identify predictors of procedural failure and arrhythmia recurrence. The risk for each variable was expressed in hazard ratio (HR) and 95% confidence interval (CI). The freedom from arrhythmia recurrence and repeat DCCV were calculated with the Kaplan–Meier method and compared using the log-rank test. All p values were two sided, and p values b 0.05 were considered significant. 3. Results 3.1. Baseline patient characteristics We identified 86 adult Fontan patients who underwent DCCV for atrial arrhythmias at Mayo Clinic from 1994 to 2014 and met inclusion criteria. The mean age was 27 ± 8 years; mean age at the time of Fontan operation was 14 ± 9 years; and 49 (57%) were males. The most common type of Fontan connection was atriopulmonary Fontan, 64 (74%); most common ventricular morphology was the left ventricle,
63 (73%); and the most common diagnosis was tricuspid atresia, 34 (40%), Table 1.
3.2. Procedural success There were 152 DCCV performed within the study period; 57 patients (66%) underwent 2 DCCV and 9 patients (10%) underwent ≥ 3 DCCV for arrhythmia recurrence. For 131 (86%) of the DCCV, the patient was on an AAD at the time of the DCCV, of which 112 (74%) were either on class I or III AAD. The most common atrial arrhythmia was atrial flutter/IART, 125 (82%). Out of 152 DCCV, 111 (73%) were successful, Table 2.
3.3. Procedural safety Eighty-eight (58%) of all DCCV in our cohort were TEE-guided (TEE performed on the day of DCCV); additional 47 (31%) had TEE performed within 48 h prior to DCCV; and the 17 (11%) patients who did not have TEE within 48 h had documented therapeutic INR. All TEEs were negative for intracardiac thrombus. A total of 104 patients had INR assays within 48 h prior to DCCV, and 91 (87%) of these assays showed therapeutic INR. All 13 patients (13%) with subtherapeutic INR were on heparin (unfractionated heparin, n = 12; and low molecular weight heparin, n = 1).
Table 1 Baseline characteristics. Number of patients Age, year Age at onset of arrhythmia, year Age at Fontan, year Time from Fontan operation, year Male (%) FU post DCCV, months H/o of prior catheter ablation Fontan type Atrio-pulmonary Fontan LTF/IAC Extracardiac Fontan Ventricular morphology Left ventricle Right ventricle Indeterminate Initial diagnosis Tricuspid atresia Mitral atresia Common inlet ventricle Double inlet left ventricle Pulmonary atresia Others Echocardiography (n = 86) M/S right atrial enlargement M/S ventricular dysfunction M/S AVV regurgitation Cardia catheterization data (n = 61) Fontan pressure, mm Hg VEDP, mm Hg Cardiac index, L/min/m2 Systemic saturation PVRi, WU ∗ m2 DCCV: Direct current cardioversion. FU: Follow up. H/o: History of. IAC: Intraatrial conduit. LTF: Lateral tunnel Fontan. M/S: Moderate–severe. AVV: Atrioventricular valve. VEDP: Ventricular end-diastolic pressure. PVRi: Pulmonary vascular resistance index. WU ∗ m2: Wood units × meters squared.
86 27 ± 8 24 ± 11 14 ± 9 13 ± 8 49 (57%) 48 ± 21 4 (5%) 64 (74%) 16 (19%) 6 (7%) 63 (73%) 19 (22%) 4 (5%) 34 (40%) 3 (4%) 10 (12%) 29 (33%) 5 (5%) 5 (5%) 56 (65%) 33 (38%) 13 (15%) 16 ± 3 11 ± 4 2.0 ± 0.3 89 ± 5 2.5 ± 0.7
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3.5. Predictors of arrhythmia recurrence and procedural failure
Table 2 Direct current cardioversion data. Number of DDCV Number of patients Atrial arrhythmia type Atrial flutter/IART Atrial fibrillation Ectopic atrial tachycardia AAD use at time of DCCV Class I Class II Class III Class IV Digoxin Number of shocks Emergent/urgent DCCV within 48 h TEE-guided (within 24 h*) TEE-guided (within 48 h**) INR (N2.0)*** Successful DCCV
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152 86 125 (82%) 24 (16%) 3 (3%) 131 (86%) 47 (31%) 109 (72%) 65 (43%) 97 (64%) 14 (9%) 1 (1–5) 14 (9%) 40 (26%) 88 (58%) 135 (89%) 91 (87%) 111 (73%)
AAD: Antiarrhythmic drug. IART: Intraatrial reentry tachycardia. INR: International normalized ratio. INR***: only 104 procedures had INR assay within 48 h prior to DCCV. TEE: Transesophageal echocardiogram. TEE-guided (within 24 h*): TEE performed within 24 h of DCCV. TEE-guided (within 48 h**): TEE performed within 48 h of DCCV.
The only complications attributed to DCCV were 2 cases (1%) of symptomatic bradycardia requiring temporary pacing. There were no tachyarrhythmia and no complication related to esophageal intubation during TEE. There were no thromboembolic complications immediately or within 30 days of DCCV. No deaths occurred related to DCCV during the study period.
3.4. Arrhythmia recurrence Seventy-nine patients (92%) experienced recurrence over a mean follow-up period of 48 ± 21 months. The freedom from recurrence was 84%, 47% and 19% at 12, 36 and 60 months respectively. The freedom from recurrence was significantly lower in patients with atriopulmonary Fontan compared to other types of Fontan connections, P = 0.010 (Fig. 1A). Freedom from repeat DCCV was 91%, 64% and 35% at 12, 36 and 60 months respectively, Fig. 1B.
Forty-one (27%) DCCV were unsuccessful in terminating arrhythmia. Multivariable predictors of procedural failure were older age (HR 1.91, CI 1.16–2.73) for every decade increase in age and history of prior DCCV (HR 2.71, CI 1.22–3.21). Being on class I or III antiarrhythmic drugs at the time of DCCV was protective (HR 0.64, CI 0.41–0.87), Table 3. Multivariable predictors of recurrence were older age (HR 3.26, CI 1.19–6.55.73) for every decade increase in age, duration of arrhythmia (HR 1.87, CI 1.14–2.56) for decade increase in duration, and presence of atriopulmonary Fontan (HR 1.54, CI 1.27–1.85), Table 4. 4. Discussion These findings underscore that cardioversion can be performed safely and with reasonable success in patients with a Fontan circulation in a specialized multidisciplinary care group. 4.1. Procedural success This study indicates that DCCV is successful in terminating arrhythmia in the majority (76%) of cases, yet this is significantly lower that the success rate of more than 90% reported for congenital heart disease population with biventricular circulation [10,11]. A prior retrospective analysis [10] of 63 patients with congenital heart disease reported that DCCV was successful in 94% of cases. This series included only 16 Fontan patients. Anatomical and surgical features of the Fontan such as multiple atrial surgical scars, extensive atrial fibrosis and atrial dilation does distinguish this from other repaired congenital heart disease diagnosis, and is distinctly more arrhythmogenic [12,13]. These factors may be responsible for the higher incidence of atrial arrhythmias as well as DCCV procedural failure in Fontan patients compared to other types of congenital heart disease. Independent predictors of procedural failure in our cohort were older age and prior DCCV. Conversely, current therapy with class I or III AAD augmented cardioversion success. This correlates with prior reports confirming the efficacy of the class III agent, sotalol in a small cohort of Fontan patients; where sotalol was effective as sole therapy in terminating atrial arrhythmias in 7 out of 9 patients. Importantly two patients within this group did require permanent pacemaker implant for sinus bradycardia [14]. In contrast to class IA drugs, the class III agents are known to decrease defibrillation thresholds, and thereby
Fig. 1. (A) Freedom from arrhythmia recurrence; atriopulmonary Fontan cohort (red), lateral tunnel/intraatrial conduit/extracardiac Fontan (green), All Fontan types (blue). P value is for the comparison of red and green curves; (B) Freedom from repeat cardioversion. LTF: lateral tunnel Fontan; IAC: intraatrial conduit; ECF: extracardiac Fontan. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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Table 3 Predictors of procedural failure. Variables
Age (per decade increase) Duration of Fontan physiology (per decade increase) Duration of arrhythmia (per decade increase) AAD use at the time of DCCV Class I or III AAD use at the time of DCCV DCCV within 48 h of arrhythmia onset Atriopulmonary Fontan Atrial fibrillation Prior DCCV Spontaneous echocardiographic contrast M/S right atrial enlargement M/S ventricular dysfunction Fontan pressure (per unit increase) VEDP (per unit increase) Cardiac index (per unit increase) PVRi (per unit increase)
Univariate
Multivariate
HR (95% CI)
P value
HR (95% CI)
P value
3.43 (2.24–8.16) 2.13 (1.64–4.16) 4.32 (1.21–6.45) 0.83 (0.23–1.97) 0.76 (0.22–0.91) 1.44 (0.73–3.65) 3.32 (0.18–8.54) 3.43 (0.89–15.32) 4.37 (2.65–6.29) 1.31 (0.72–1.98) 2.66 (1.53–3.34) 1.01 (0.22–4.12) 2.06 (0.31–5.63) 1.75 (0.53–4.74) 1.34 (0.28–4.12) 2.43 (0.30–4.63)
0.002 0.019 0.024 0.27 0.001 0.19 0.18 0.29 0.014 0.15 0.001 0.71 0.29 0.41 0.39 0.31
1.91 (1.16–2.73) 2.14 (0.93–4.42) 2.19 (0.67–4.23)
0.022 0.06 0.14
0.64 (0.41–0.87)
0.031
2.71 (1.22–3.21)
0.025
1.96 (0.84–3.44)
0.42
CI: Confidence interval. HR: Hazard ratio.
augment chances of a successful cardioversion [15,16]. Yet these data suggest that both classes of agents were preferable to no antiarrhythmic therapy, and thereby implying that Fontan patients who are hemodynamically stable should perhaps be preemptively loaded with anti-arrhythmic therapy prior to DCCV in order to improve cardioversion success.
4.2. Procedural safety DCCV was safe in our Fontan patients; the most common complication was bradycardia. There were no thromboembolic complications within 30 days after DCCV in our cohort. This result is consistent with other studies demonstrating no DCCV-related thromboembolic complications in 63 patients with congenital heart disease [10]. The slow flow state in the Fontan commonly results in chronic and acute thrombus, and a major clinical concern for patients with this type of repair is dislodgement of fresh thrombus with cardioversion and potentially fatal pulmonary thromboembolism [17]. Although intracardiac thrombus is identified frequently in patients with Fontan repairs and coexistent atrial arrhythmias, the systemic atrium appears to be rarely involved, and DCCV has not been associated with a higher incidence of stroke or systemic embolism in this group [6].
4.3. Arrhythmia recurrence More than 80% of our cohort experienced recurrence of atrial arrhythmias during follow-up and 66% were treated with repeat DCCV. Arrhythmia recurrence after DCCV in the congenital heart disease population has been reported to be 50–60% [10,11] and this varied by arrhythmia type, structural heart disease type and patient characteristics. Fontan patients are likely prone to recurrence because of more atrial substrate abnormality [12,13]. The presence of spontaneous contrast identified by TEE examination and the presence of atrial fibrillation (versus atrial flutter/atrial tachycardia) have been reported as predictors of recurrence in patients with congenital heart disease [10]. In contrast, this study did not identify the same predictors for atrial arrhythmias. Instead, older patients and those with atriopulmonary Fontan were more prone to recurrence. The presence of atrial fibrillation, however, does also stand out as a predictor of atrial arrhythmia recurrence in several other studies [18,19]. In patients with acquired heart disease or even in the normal heart, this particular form of atrial arrhythmia is typically considered a disease of the left atrium [20]. Commonly, the left atrium in patients with Fontan repairs is normal in size, and it is likely that atrial fibrillation in the Fontan patient is a worse prognostic sign, suggestive of worse Fontan substrate and potentially bi-atrial disease. Due to the high risk of recurrence, DCCV should be considered as a temporizing measure to acutely terminate arrhythmia in
Table 4 Predictors of arrhythmia recurrence. Variables
Age (per decade increase) Duration of Fontan physiology (per decade increase) Duration of arrhythmia (per decade increase) Use of AAD therapy Use of Class I or III AAD therapy Atriopulmonary Fontan H/o atrial fibrillation Spontaneous echocardiographic contrast M/S right atrial enlargement M/S ventricular dysfunction Fontan pressure (per unit increase) VEDP (per unit increase) Cardiac index (per unit increase) PVRi (per unit increase)
Univariate
Multivariate
HR (95% CI)
P value
HR (95% CI)
P value
6.71 (2.61–8.33) 2.21 (1.76–3.11) 3.61 (2.41–5.82) 1.34 (0.47–3.51) 1.85(0.46–3.91) 1.53(1.26–2.21) 2.63 (1.46–3.89) 2.12 (0.53–3.94) 0.41(0.11–0.83) 1.31(0.72–1.98) 1.75 (0.53–4.74) 1.01(0.22–4.12) 2.06(0.3–5.63) 0.81(0.33–1.73)
b0.0001 b0.0001 0.001 0.142 0.16 0.003 0.002 0.31 0.007 0.15 0.41 0.71 0.29 0.37
3.26 (1.19–6.55) 1.52 (0.66–3.89) 1.87 (1.14–2.56)
0.031 0.42 0.001
1.54 (1.27–1.85) 2.49 (0.66–4.21)
0.024 0.17
1.55 (0.82–2.14)
0.09
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the setting of hemodynamic instability, or to restore sinus rhythm and improve cardiovascular efficiency in a stable patient with persistent arrhythmia despite antiarrhythmic therapy. 4.4. Limitations This is a retrospective study. There may be selection bias because we reviewed only the Fontan patients that actually underwent DCCV and not all Fontan patients with atrial arrhythmias. We are unable to account for patients excluded from DCCV because of suspected intracardiac thrombus on TEE, thus our estimate of DCCV-related thromboembolic complications might underestimate the risk in the Fontan population. Additionally, we relied on documentation of thromboembolic complications as reported by the patients and silent thromboembolic complications may have been missed [21,22]. All these limitations affect generalizability of our data. 5. Conclusion Direct current cardioversion appears to be a safe procedure in those patients with a prior Fontan repair when performed by a specialized multidisciplinary team. This intervention is associated with a substantial rate of late recurrence of arrhythmia, and should be considered a temporizing measure, prompting referral to a congenital heart rhythm specialist to plan long-term therapy. The use of a class I or III AAD appears to be the strongest salutary influence, and it therefore should be considered antecedently if hemodynamics permit. Of all the risk factors influencing the outcome of DCCV, the use of AAD is the only modifiable factor, and the clinician should take advantage of this. Conflict of interest None. Funding None. Acknowledgement None. References [1] J. Weipert, C. Noebauer, C. Schreiber, et al., Occurrence and management of atrial arrhythmia after long-term Fontan circulation, J. Thorac. Cardiovasc. Surg. 127 (2004) 457–464.
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