Efficacy of Hemodynamic-Based Management of Tachyarrhythmia After Repair of Tetralogy of Fallot

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1 Circulation Journal Official Journal of the Japanese Circulation Society ORIGINAL ARTICLE Pediatric Cardiology and Adult Congenital Heart Disease Efficacy of Hemodynamic-Based Management of Tachyarrhythmia After Repair of Tetralogy of Fallot Aya Miyazaki, MD; Heima Sakaguchi, MD; Hideo Ohuchi, MD; Michio Matsuoka, MD; Akiko Komori, MD; Tetsuya Yamamoto, MD; Kenji Yasuda, MD; Kazuhiro Satomi, MD; Takaya Hoashi, MD; Shiro Kamakura, MD; Osamu Yamada, MD Background: Supraventricular and ventricular tachyarrhythmias (SVT, VT) are major concerns after repair of tetralogy of Fallot (TOF). This study evaluated the impact of comprehensive treatment, including hemodynamic interventions such as surgery, catheter-based intervention and pacemaker implantation (PMI), on tachyarrhythmia in repaired TOF patients. Methods and Results: Of 66 repaired TOF patients with tachyarrhythmia (age at onset, 23±11 years), 29 patients had sustained SVT, 21 had sustained or non-sustained VT, and 16 had both (SVT + VT). Successful treatment with catheter-directed ablation and/or anti-arrhythmic drugs (AADs) alone was achieved in 31 (69%) and partially achieved in 6 (13%) of 45 patients. Surgery, catheter-based intervention, and/or PMI were performed in 21 (32%) of 66 patients and resulted in complete control of the arrhythmia in 8 (38%) and partial control in 7 (33%) of these 21 patients, 20 (95%) of whom were receiving AADs. Patients with successfully controlled tachyarrhythmia in response to catheter ablation and/or AADs without hemodynamic intervention had a significantly higher probability of absence of sinus node dysfunction (odds ratio [OR], 23.2; 95% confidence interval [CI], ; P=0.02) and lone intra-atrial reentrant tachycardia (OR, 12.4; 95% CI: ; P=0.03). Conclusions: Hemodynamic interventions resulted in an improvement in outcomes in repaired TOF patients with tachyarrhythmia. To effectively manage intractable tachyarrhythmia with hemodynamic abnormalities, it is essential to understand hemodynamics and consider hemodynamic intervention. (Circ J 2012; 76: ) Key Words: Tachyarrhythmia; Tetralogy of Fallot; Treatment Late complications following repair of tetralogy of Fallot (TOF) include arrhythmia, exercise intolerance, heart failure and death. 1 5 In particular, tachyarrhythmia is a major concern after TOF repair and is associated with an increased risk of sudden death. 2 4,6,7 Risk factors for sudden death and sustained ventricular tachycardia (VT) include older age at the time of repair, QRS duration 180 ms, additional right ventricular (RV) structural abnormalities (outflow tract aneurysms and pulmonary or tricuspid regurgitation), positive programmed ventricular stimulation, and severe RV dilatation with either left ventricular (LV) or RV dysfunction. 3,6,8 11 There is a relatively low incidence, however, of serious late problems after TOF repair in the Japanese population. The actuarial survival rate after repair of TOF at 30 years was 98% in a Japanese multicenter study, 12 compared with 80% and 89% in large studies from Western countries. 1,4 Further, the incidence of sustained VT and atrial tachycardia/atrial fibrillation (AT/AF) was 0.4% and 3%, respectively, in Japan, 12 compared with 4% and 4 20%, respectively, in Western countries. 2,3,7,13 In addition, many repaired TOF patients in Japan have fairly good postoperative RV function, while the proportion of patients with QRS duration <120 ms and cardiothoracic ratio (CTR) <59% has been reported to be 60% and 61%, respectively. 12 Therefore, in Japan, hemodynamic assessments tend to be underestimated for patients late after repair of TOF. Given that patient characteristics late after repair of TOF in Japan differ from those in other countries, it is important to consider a different treatment strategy from those used in other coun- Received February 16, 2012; revised manuscript received July 20, 2012; accepted July 23, 2012; released online August 11, 2012 Time for primary review: 27 days Department of Pediatric Cardiology (A.M., H.S., H.O., M.M., A.K., T.Y., K.Y., O.Y.), Division of Arrhythmias and Electrophysiology, Department of Cardiovascular Medicine (K.S., S.K.), and Department of Pediatric Cardiovascular Surgery (T.H.), National Cerebral and Cardiovascular Center, Suita, Japan No grants. Mailing address: Aya Miyazaki, MD, Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Fujishirodai, Suita , Japan. ayamiya@hsp.ncvc.go.jp ISSN doi: /circj.CJ All rights are reserved to the Japanese Circulation Society. For permissions, please cj@j-circ.or.jp

2 2856 MIYAZAKI A et al. Figure 1. Types of tachyarrhythmia after repair of tetralogy of Fallot (TOF) in (A) patients with supraventricular tachyarrhythmias (SVT); (B) patients with ventricular tachyarrhythmias (VT); and (C) patients with both SVT and VT. AF, atrial fibrillation; AT, atrial tachycardia; IART, intra-atrial reentrant tachycardia; JT, junctional tachycardia; NSVT, non-sustained VT; VF, ventricular fibrillation. tries for patients with tachyarrhythmia late after repair of TOF. Moreover, catheter ablation and anti-arrhythmic drugs (AADs) have limited efficacy for the management of tachyarrhythmia in patients with congenital heart disease (CHD). 14 Further, few studies have investigated the efficacy of comprehensive treatment, including hemodynamic intervention such as surgery, catheter intervention and pacemaker implantation (PMI), for tachyarrhythmia in repaired TOF patients. In our experience, previously intractable tachyarrhythmia can be controlled following correction of hemodynamic abnormalities, such as pressure or volume overload of the RV, and following correction of bradyarrhythmia-associated low cardiac output or electrical instability through the use of surgery, catheter-based intervention, or PMI. Thus, to determine the optimal treatment strategy for repaired TOF patients, the present study retrospectively evaluated the clinical course and the efficacy of comprehensive treatment, including catheter ablation, AADs and hemodynamic intervention for the management of tachyarrhythmia. Methods Patients The subjects consisted of 66 patients with tachyarrhythmia following TOF repair who visited the Department of Pediatric Cardiology at the National Cerebral and Cardiovascular Center in Japan from April 1977 to December A total of 695 patients underwent surgical repair of TOF during the same period, and the study subjects also included 16 patients who underwent TOF repair in other institutions. Patients with transient tachyarrhythmia within 1 year after surgery were excluded from this study. The medical records of the 66 study patients were retrospectively reviewed to assess the efficacy of different tachyarrhythmia management strategies. Tachyarrhythmia Tachyarrhythmia was diagnosed based on surface electrocardiography, 24-h ambulatory Holter monitoring, or treadmill exercise tolerance test. Those assessments were performed randomly or when patients complained of symptoms. Sustained supraventricular tachycardia (SVT) of >30 s and sustained/non-sustained VT of >3 beats were included as the targets of treatment in this study. SVT was defined as any kind of sustained narrow-qrs tachycardia including AT, junctional tachycardia, AF, and tachycardia of unknown etiology. Intraatrial reentrant tachycardia (IART) was defined as an AT with reentrant properties. Treatment Efficacy Patients were categorized into 2 groups according to treatment strategy used; these included hemodynamic interventions, such as surgery (pulmonary valve replacement [PVR], RV outflow tract reconstruction, aortic valve replacement and/or tricuspid valve replacement), catheter-based interventions (percutaneous transluminal angioplasty, stenting for pulmonary stenosis, and/or coil embolization for major aortopulmonary collateral artery) and/or PMIs. Indications for hemodynamic intervention varied according to hemodynamic disturbance and the degree of progress in response to the medical treatment over the 30-year study period. For treatment outcomes, complete control of tachyarrhythmia was defined as no recurrence; partial control of tachyarrhythmias was defined as a decrease in frequency and/or symptoms; and treatment failure was defined as the presence of persistent tachyarrhythmia with chronic, frequent recurrent and severe symptoms. Patient Characteristics and Treatment Outcome The following parameters were assessed to evaluate patient characteristics, possible predictors for complete or partial controlled tachyarrhythmias in response to catheter ablation and/ or AADs without hemodynamic intervention, and possible predictors for failed control of tachyarrhythmias with hemodynamic intervention: age at onset of tachyarrhythmia, age at the end of follow-up, gender, follow-up period after onset, chromosomal abnormalities, anatomy, clinical status at onset, history of syncope, sudden death or cerebral infarction, complication of sinus node dysfunction, atrioventricular block II, medications at onset, age at repair of TOF, number of previous open heart surgeries until onset, prior palliative shunts, and surgical procedure at repair (pulmonary transannular patch, external conduit repair, infundibulectomy, and RV outflow tract patch). Further, the following examination parameters at the onset of tachyarrhythmia were recorded: CTR as determined on chest radiography (n=44), QRS duration, P duration, P amplitude on electrocardiogram (n=62), B-type natriuretic peptide (BNP) level (n=36), human atrial natriuretic peptide (hanp)

3 Management of Tachyarrhythmia in Repaired TOF 2857 Table 1. Clinical Subject Characteristics vs. Presence of Hemodynamic Intervention Total Treatment without hemodynamic intervention Treatment with hemodynamic intervention n Age at onset (years) 23±11 24±11 22±10 NS Age at end of follow-up 32±10 32±11 33±10 NS Female 27 (41) 15 (33) 12 (41) NS Follow-up period after onset (years) 9±7 7±7 11± Chromosomal abnormality 5 (8) 4 (9) 1 (5) NS Pulmonary atresia 19 (29) 11 (24) 8 (38) NS PLSVC 8 (12) 4 (9) 4 (19) NS P-value NYHA class II at onset 19 (29) 6 (13) 13 (62) Syncope/sudden death 7 (11) 6 (13) 1 (5) NS History of cerebral infarction 4 (6) 3 (7) 1 (5) NS Complication of SND 11 (17) 2 (4) 9 (17) Complication of AVB II 7 (11) 5 (11) 2 (10) NS Age at repair (years) 6.3± ± ±8.1 NS No. previous open heart surgeries 1.3± ± ±0.7 NS No. previous open chest surgeries 2.0± ± ±1.0 NS Prior palliative shunts 24 (26) 13 (29) 11 (52) Surgical procedure (n=62) Pulmonary transannular patch 32/62 (52) 24/43 (56) 8/19 (42) NS External conduit repair 14/62 (23) 9/43 (21) 5/19 (26) NS Infundibulectomy 11/62 (18) 7/43 (16) 4/19 (21) NS RVOT patch 6/62 (10) 4/43 (9) 2/19 (11) NS Type of tachyarrhythmia SVT 29 (44) 21 (47) 8 (38) VT 21 (32) 16 (36) 5 (24) NS SVT + VT 16 (24) 8 (18) 8 (38) Lone IART 15 (23) 12 (27) 3 (14) NS Complication of AF 6 (9) 3 (7) 3 (14) NS Data given as mean ± SD or n (%). AF, atrial fibrillation; AVB, atrioventricular block; IART, intra-atrial reentrant tachycardia; NYHA, New York Heart Association functional classification; PLSVC, persistent left superior vena cava; RVOT, right ventricular outflow tract; SND, sinus node dysfunction; SVT, supraventricular tachycardia; VT, ventricular tachycardia. level (n=32), tricuspid, mitral and aortic regurgitation severity moderate (n=62), severe pulmonary regurgitation (n=61), LV diastolic diameter (% of normal, n=63) and LV ejection fraction (LVEF; n=62) measured on echocardiography, and RV systolic pressure measured on catheterization or estimated on echocardiography (4[velocity of tricuspid regurgitation] mmhg; n=61). The catheterization data within 1 year before or after onset were also assessed to evaluate patient characteristics. The number of patients who underwent catheterization was limited, because catheterization was performed only for the patients who were suspected to have some hemodynamic abnormalities on non-invasive evaluation. The following parameters were assessed: right atrium (RA) mean pressure (n=32), RV systolic pressure (n=32), pulmonary artery (PA) mean pressure (n=31), LV systolic pressure (n=32), LV end-diastolic pressure (n=32), PA resistance (n=29), and cardiac index using the Fick principle (n=31). The RV and LV volumes were measured on cineangiography using Simpson s rule at the time of catheterization. The end-diastolic volume and end-systolic volume was divided by the body surface area to obtain the end-diastolic and end-systolic volume index (EDVI, ESVI), and the RVEF and LVEF were calculated (RVEDVI, RVEF and LVEF, n=31; LVEDVI, n=32). Statistical Analysis Data are given as the mean ± SD unless otherwise specified. Comparisons between groups were made using 2-tailed unpaired Student t-test, chi-square test or Fisher s exact test, as appropriate. Univariate analysis of potential predictors for group A was performed with a logistic regression model. Univariate predictors with P<0.05 were then tested in a multivariate logistic regression model. Data were analyzed with JMP 9 (SAS Institute, Cary, NC, USA). P<0.05 was considered statistically significant. Results Types of Tachyarrhythmia After TOF Repair Types of tachyarrhythmia in repaired TOF patients are shown in Figure 1. Among 66 patients, 29 patients had SVT, 21 had VT and 16 had both (SVT + VT). IART was the most common type of SVT in patients with SVT or with SVT + VT. In patients with VT, 16 had non-sustained VT (NSVT) and 4 had sustained VT. Another patient who experienced recurrent syncope and was not documented as having any type of VT had induced ventricular fibrillation (VF) by programmed ventricular pacing. In patients with SVT + VT, all VT were NSVT rather than sustained VT.

4 2858 MIYAZAKI A et al. Table 2. Findings at Onset of Tachyarrhythmia n Total subject group n Treatment without hemodynamic interventions n Treatment with hemodynamic interventions P-value CTR (%) 55 60± ± ± Electrocardiogram QRS duration (ms) ± ± ±34 NS P duration (ms) ± ± ±23 NS P amplitude (mv) ± ± ±0.07 NS BNP (pg/ml) 36 86± ± ± hanp (pg/ml) 32 66± ± ±128 NS Catheterization RA mean pressure (mmhg) 32 7±4 19 6±4 13 8±5 NS RV systolic pressure (mmhg) 32 50± ± ±21 NS PA mean pressure (mmhg) 31 16± ± ± LV systolic pressure (mmhg) ± ± ±14 NS LV end diastolic pressure (mmhg) 32 10±4 19 9± ±5 NS PA resistance (Um 2 ) ± ± ± RVEDVI (ml/m 2 ) ± ± ± RVEF (%) 31 46± ± ±12 NS LVEDVI (ml/m 2 ) ± ± ±34 NS LVEF (%) 32 58± ± ±14 NS Fick cardiac index (L/m 2 ) ± ± ±0.8 NS Echocardiography TR moderate (23) 43 7 (16) 19 7 (37) NS Severe PR (34) (38) 19 5 (26) NS MR moderate 62 3 (5) 44 1 (2) 18 2 (11) NS AR moderate 62 3 (5) (17) NS LVDd (% of normal) 63 94± ± ±17 NS LVEF (%) 62 64± ± ± RVp by catheterization or by echocardiography (mmhg) 61 44± ± ±21 < Data given as mean ± SD or n (%). Measured on cine-angiocardiography. BNP, brain natriuretic peptide; CTR, cardiothoracic ratio; hanp, human atrial natriuretic peptide; LV, left ventricle; LVDd, left ventricular diastolic diameter; LVEDVI, left ventricular end-diastolic volume index; LVEF, left ventricular ejection fraction; PA pulmonary artery; PR, pulmonary valve regurgitation; RA, right atrium; RV, right ventricle; RVEDVI, right ventricular end-diastolic volume index; RVEF, right ventricular ejection fraction; RVp, right ventricular pressure. Characteristics of Tachyarrhythmia Patients After TOF Repair Patient characteristics and findings are listed in Tables 1,2. Mean patient age at onset was 23±11 years. Among 66 patients, 45 patients with tachyarrhythmia were treated without hemodynamic intervention, and 21 patients were treated with hemodynamic intervention. The proportion of patients with heart failure of severity greater than New York Heart Association functional classification (NYHA) class II and the incidence of sinus node dysfunction were higher in patients who had hemodynamic intervention than in those without hemodynamic intervention. Syncope or sudden death occurred in 7 patients during the follow-up period. CTR, BNP, PA resistance, RVEDVI, LVEF measured on echocardiography, and RV pressure measured on catheterization or echocardiography were higher in patients who underwent hemodynamic intervention than in those who did not undergo hemodynamic intervention. Treatment for Tachyarrhythmia Forty-five patients were treated without hemodynamic intervention, which resulted in complete control in 31 (69%), partial control in 6 patients (13%), and failed control in 8 patients (18%; Figure 2). Among 20 patients who underwent catheter ablation, complete or partial control of tachyarrhythmia was obtained in 10 of 12 who were receiving AADs and in 8 who were not receiving AADs. Among 18 patients who were treated only with AADs, 15 achieved complete or partial control of tachyarrhythmia. Among the 4 patients who did not undergo catheter ablation or receive AADs, 3 patients with asymptomatic NSVT did not experience further episodes of tachycardia. The other patient with AT or IART achieved complete control of tachyarrhythmia through lifestyle change. In patients with failed control of tachyarrhythmia, 2 patients died suddenly, and 1 died due to heart failure. Among the 5 patients with complete control of tachyarrhythmia who underwent implantation of implantable cardioverter-defibrillator (ICD), 2 had sustained VT, 2 had NSVT, and 1 had syncope but VT was not detected. All 5 patients underwent electrophysiological assessment in which VT or VF was induced, but no patients had sustained VT or VF after implantation of an ICD. These 5 patients did not experience bradycardia, and all of their pacing modes were VVI with cumulative % ventricular pace <1%. Surgery, catheter-based intervention, and/or PMI were performed in 21 patients, which resulted in complete control of tachyarrhythmias in 8 (38%) and partial control of tachyar-

5 Management of Tachyarrhythmia in Repaired TOF 2859 Figure 2. Treatment of tachyarrhythmia without hemodynamic interventions after repair of tetralogy of Fallot (TOF). Among 45 patients treated with catheter ablation and/or anti-arrhythmic drugs (AADs), 31 patients (69%) achieved complete control of tachycardia, and 6 (13%) achieved partial control of tachycardia. Tachycardia was not controlled in the other 8 patients (18%). rhythmias in 7 (33%; Figure 3). PVR was performed in 5 patients, which resulted in complete control of tachyarrhythmia in 2 patients and partial control of tachyarrhythmia in 3 patients with severe RV dilatation. 15 At the end of follow-up, 20 of 21 patients (95%) required AADs even after other effective treatments. Among 3 patients with failed control of tachyarrhythmia, 1 died suddenly, 1 died from heart failure, and 1 died from sepsis. Predictors of Treatment Outcome On multivariate analysis, predictors for complete or partial control of tachyarrhythmia without hemodynamic intervention were absence of sinus node dysfunction (odds ratio [OR], 23.2; 95% confidence interval [CI]: ; P=0.02) and lone IART (OR, 12.4; 95% CI: ; P=0.03; Table 3). AF was a predictor for failed control of tachyarrhythmia with hemodynamic intervention (OR, 29.0; 95% CI: 1.2 2,688.0; P=0.04) in multivariate analysis (Table 3). Sudden Death Data regarding 3 cases of sudden death are given in Table 4. Patient 2 had SVT and severe volume overload. Patient 3 had NSVT, and severe RV pressure overload was detected on routine echocardiography. This patient was referred for hospitalization, but died before additional testing could be performed. Patient 1 had SVT and died at the age of 12 years. This patient had no marked hemodynamic problems and had all the predictors for well-controlled tachyarrhythmia without hemodynamics intervention. Discussion This study had 2 important findings. First, among patients who did not undergo hemodynamic intervention, use of catheter ablation and/or AADs was effective in controlling tachyarrhythmia in 82% of the patients, while 32% of all patients with tachyarrhythmia required hemodynamic intervention, such as surgery, catheter-based intervention and/or PMI. Second, even in the patients who were clinically and hemodynamically ill, tachyarrhythmia was controllable in 71% with hemodynamic interventions. The efficacy of treatment for tachyarrhythmia was further improved by hemodynamic intervention. Characteristics of Japanese Repaired TOF Tachyarrhythmia Patients Clinical findings in the patients from a Japanese single center were relatively mild when compared with those in previous reports. Severe pulmonary regurgitation was present in 34% of patients with tachyarrhythmia in the present study (Table 2), as compared to % in a multicenter study performed in Western countries. 3 Further, moderate to severe tricuspid regurgitation was present in 23% of the current patients as compared to 42 70% and 26 33% of patients in reports from other countries, 3,13 and the average QRS duration was 152 ms in the present study as compared to ms and ms in previous studies. 3,13 The difference between parameters in the present study vs. previous studies may be related to the fact that, since the early 1970 s, Japanese surgeons have performed only a small or no right ventriculostomy using a small transannular patch in an effort to prevent the occurrence of complete right bundle branch block. 16,17

6 2860 MIYAZAKI A et al. Figure 3. Treatment of tachyarrhythmias with hemodynamic interventions in patients after repair of tetralogy of Fallot (TOF). Among 21 patients, 14 (67%) underwent surgery, 10 (48%) underwent catheter-based intervention, and 10 (48%) underwent pacemaker implantation (PMI). In addition, 8 patients (38%) underwent catheter ablation, and 20 (95%) received anti-arrhythmic drugs (AADs). AVR, aortic valve replacement; MAPCA, major aortopulmonary collateral artery; PS, pulmonary artery or pulmonary valve stenosis; PTA, percutaneous transluminal angioplasty; PVR, pulmonary valve replacement; RVOTR, right ventricular outflow tract reconstruction; TVR, tricuspid valve replacement. Table 3. Predictors for Outcome of Tachyarrhythmia Treatment n Univariate Multivariate OR (95% CI) P-value OR (95% CI) P-value Predictors for complete or partial control of tachyarrhythmia without hemodynamic intervention NYHA class I ( ) Absence of SND ( ) ( ) 0.02 No history of prior palliative shunts ( ) 0.02 Surgical procedure other than external conduit repair ( ) Lone IART ( ) ( ) 0.03 No diuretics at onset ( ) 0.02 Low CTR (%) ( ) LVEF (%) by echocardiography ( ) 0.02 Low RV systolic pressure (mmhg) ( ) Predictors for failed control of tachyarrhythmia with hemodynamic intervention NYHA class II ( ) Complication of AF ( ) ( ) 0.04 CTR ( ) Low LVEF (%) on echocardiography ( ) 0.02 RV systolic pressure was measured by catheterization or estimated on echocardiography. CI, confidence interval; OR, odds ratio. Other abbreviations as in Tables 1,2.

7 Management of Tachyarrhythmia in Repaired TOF 2861 Table 4. Sudden Death Case Summary Age at Arrhythmia Patient death (years) Tachyarrhythmia Bradyarrhythmia NYHA Hemodynamic problems CTR (%) RV volume overload 1 12 AT, PVC I 55 Moderate TR 2 21 AT, PVC SND (PMI) II 75 Severe PR, severe TR RVp overload 3 29 NSVT I 59 RVp 70 mmhg Surgical procedures Infundibulectomy RVOT patch, TVR External conduit repair AAD Medications at death ACEI/ARB Diuretics β-blocker, + digoxin β-blocker + + AAD, anti-arrhythmic drug; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; AT, atrial tachycardia; NSVT, non-sustained ventricular tachycardia; PMI, pacemaker implantation; PVC, premature ventricular contraction; TVR, tricuspid valve replacement. Other abbreviations as in Tables 1,2. Figure 4. Management strategy for tachyarrhythmia after repair of tetralogy of Fallot (TOF). Hemodynamic assessment with various modalities was used to guide management of tachyarrhythmia. In addition, the rhythm disturbance was also evaluated at the same time as the hemodynamics, and the treatment strategy (eg, surgery or catheterbased interventions) for the hemodynamic abnormalities was then decided upon. When bradyarrhythmia was detected, pacemaker implantation (PMI) was recommended. The order of treatment is not fixed and is dependent on the individual patient. AADs, anti-arrhythmic drugs; ICD, implantable cardioverter-defibrillator. Efficacy of Catheter Ablation and AADs for Tachyarrhythmia in CHD Patients The efficacy of catheter ablation and AADs for the management of tachyarrhythmia in patients with CHD has historically been limited, although technological refinements have resulted in an increasing success rate. 14,18 In a recent report from Toronto, the acute success rate of catheter ablation for IART in TOF patients was 72%, and the 4-year freedom from IART recurrence after successful catheter ablation was 48%. 19 In addition, use of a variety of AADs, including types IA, IC and III drugs, did not alter the arrhythmia-free survival curves when compared with the use of single-agent digoxin therapy. 20 In the present study, use of catheter ablation and/or AADs resulted in complete control of tachyarrhythmias in 69% of patients who did not undergo hemodynamic interventions and in 38% who did undergo hemodynamic interventions. This relatively good efficacy was presumably related to the appropriate selection of patients based on hemodynamic evaluation. Further, patients with good hemodynamics who had lone IART and absence of sinus node dysfunction had successful control of tachyarrhythmia in response to catheter ablation and/or AADs without hemodynamic interventions. Efficacy of Treatment for Tachyarrhythmia After Improvement of Hemodynamics Hemodynamic abnormalities, such as pressure or volume overload of the RV, low output, or electrical instability caused by bradyarrhythmia, may respond favorably to surgery, catheterbased interventions, or PMI. Two previous reports described the effect of PVR on tachyarrhythmias. 21,22 One showed that PVR for pulmonary regurgitation and/or RV outflow tract obstruction decreased the incidence of VT, 21 but the other study showed that late PVR for symptomatic pulmonary regurgitation and RV dilatation did not reduce the incidence of VT or death. 22 In contrast, in adult patients with heart failure, several studies have reported that reverse remodeling of LV by cardiac resynchronization therapy reduced the incidence of both AT and VT Although patients with TOF have mainly right-sided heart failure, reverse remodeling of the RA and RV could also reduce, albeit not completely eliminate, the arrhythmogenic substrate. In this study, complete success occurred in 38% of the patients who were treated with hemodynamic interventions, but 95% of these patients received AADs even after effective therapy. Ongoing close follow-up of these patients is necessary. Sudden Death Over the 30-year study period, only 3 cases of sudden death

8 2862 MIYAZAKI A et al. related to tachyarrhythmia occurred in repaired TOF patients. Two of these patients had profiles consistent with a high risk of sudden death, but the remaining patient did not. Therefore, it remains important to determine how to prevent sudden death in patients with a good clinical course. Study Limitations The diagnosis of tachyarrhythmias was based mainly on surface electrocardiography and rhythm strips and included SVTs of unknown etiology. Further, ventricular volumes were measured on cine-angiography, and there was some doubt regarding the accuracy of these measurements. Along with general progress in medication treatment, the indications for hemodynamic interventions varied over the 30-year study period. Thus, it was relatively difficult to compare the efficacy of each hemodynamic intervention for tachyarrhythmia. Further, half of the patients required more than 2 types of hemodynamic intervention. Nonetheless, these retrospective results are valuable for the assessment of the efficacy of the treatment for tachyarrhythmia after repair of TOF. Management of Tachyarrhythmias in Repaired TOF Patients Figure 4 details the current management strategy for tachyarrhythmia in repaired TOF patients. We perform echocardiography routinely in these patients. Once tachyarrhythmia is detected, we perform echocardiography, chest roentgenography, plasma BNP/hANP measurement, 24-h ambulatory Holter monitoring, and treadmill exercise tolerance testing. If hemodynamic abnormalities are detected, magnetic resonance imaging and catheterization are performed. Data from these hemodynamic assessments are used to decide whether surgery or catheter-based interventions should be carried out for patients with RV volume or pressure overload. When patients have bradyarrhythmia, PMI is recommended. For patients with a high risk of sudden death, history of syncope, or VT/VF induction on programmed ventricular stimulation, ICD implantation should be considered. Indications for catheter ablation and/or AADs alone in patients without RV volume or pressure overload or bradyarrhythmia include lone IART, NYHA class I, absence of sinus node dysfunction, surgical procedure other than external conduit repair, low CTR and low RV systolic pressure. Conclusions Evaluation of hemodynamics is necessary when formulating a plan for management of tachyarrhythmia after repair of TOF. Conventional therapy, such as catheter ablation or AADs, should be effective in patients without hemodynamic abnormalities. Further, surgery, catheter-based interventions and/or PMI could improve the efficacy of treatment for tachyarrhythmia, and these therapies should be considered in the context of intractable tachyarrhythmia in patients with hemodynamic abnormalities. References 1. 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