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Should complex ACHD patients have periodic Holter monitoring?
Progress in Pediatric Cardiology 34 (2012) 43–46
Contents lists available at SciVerse ScienceDirect
Progress in Pediatric Cardiology journal homepage: www.elsevier.com/locate/ppedcard
Should complex ACHD patients have periodic Holter monitoring? Douglas S. Moodie a, b, c,⁎, Craig Broberg d a
Pediatric Cardiology, Texas Children's Hospital, Houston, TX, United States Pediatric Cardiology Fellowship Program, Texas Children's Hospital, Houston, TX, United States c Adult Congenital Heart Center, Texas Children's Hospital, United States d Adult Congenital Heart Program, Oregon Health and Science University, Portland, OR, United States b
a r t i c l e Keywords: Holter monitor ECG ACHD Arrhythmia
i n f o
a b s t r a c t This article stems from a debate held at the Adult Congenital Heart Meetings at Cincinnati in the summer of 2011 where Dr. Moodie and Broberg debated whether complex adult congenital heart patients should have regular Holter monitor studies done. Dr. Moodie took the pro position and Dr. Broberg the con and this article is a result of that debate. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Pro Position: Complex Patients Should Have Routine Periodic ECG Monitoring Adult congenital heart disease (ACHD) patients develop a myriad of problems as they age, including heart failure, arrhythmias, stroke and the need for surgical or catheter-based intervention [1]. Arrhythmias are the most common cardiologic reason for hospital admission and atrial fibrillation and flutter are the most frequent arrhythmias encountered in this population [2]. As many as one-third of patients with repaired tetralogy of Fallot develop symptomatic atrial tachycardia by adulthood, and only 40% of those with transposition of the great vessels who have had a Mustard or Senning repair are in sinus rhythm 20 years after their operation [3,4]. Atrial tachycardia has been reported in up to 57% of patients with an aortopulmonary connection [5]. In a study of adults who had undergone a Mustard operation for transposition of the great vessels, 9% had sustained ventricular tachycardia or sudden death after immediate follow-up of 9 years after transition of care from pediatric to the adult clinic [6]. Between 1998 and 2005, the number of admissions because of arrhythmias in ACHD patients more than doubled [7]. In a population based analysis of ACHD by Bouchardy, the 20-year risk of developing atrial arrhythmia was 7% in a 20 year-old subject and 38% in a 50 year-old subject [8]. The lifetime incidence of ACHD developing atrial arrhythmia increased steadily with age, and the development of atrial arrhythmias was associated with the doubling of the risk of adverse events: mortality, morbidity, and intervention. More than 50% of patients with severe congenital heart disease over 18 years of age developed atrial arrhythmias by 65 years of age. ACHD
⁎ Corresponding author at: Pediatric Cardiology, Texas Children's Hospital, Houston, TX, United States. E-mail address: [email protected] (D.S. Moodie). 1058-9813/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ppedcard.2012.05.010
patients with atrial arrhythmias have an approximately 50% increase in mortality, more than double the risk of morbidity (stroke or heart failure), and three times the risk of cardiac intervention. In the ACHD literature, sudden death is the most common cause of death (26%), followed by progressive heart failure (21%), and perioperative death (18%) [9] (Fig. 1). Silka et al. [10] described the actual probability of sudden cardiac death after surgical treatment of coarctation, tetralogy, aortic stenosis and transposition (Fig. 2). In a review of over 4000 ACHD patients in Europe, 18% had supraventricular arrhythmias and 5% had ventricular arrhythmias [11]. Ventricular arrhythmias were especially common in patients with tetralogy of Fallot. The 2008 American College of Cardiology/American Heart Association Guidelines for Adult Congenital Heart Disease recommended Holter monitoring in specific patients such as those with repaired tetralogy of Fallot and AV septal defects [12]. These guidelines also indicate that rhythm abnormalities and transposition of the great vessels, congenitally corrected the transposition of the great vessels, and Ebstein's anomaly may be further elucidated by periodic ambulatory Holter monitoring. Thus, the two major organizations in cardiology today, the American Heart Association and the American College of Cardiology, have recommended routine Holter evaluation in a significant number of complex patients and substantiate the need for Holter monitoring in these patients. There is very little data on Holter monitoring in adult congenital heart disease. We recently looked at the incidence of unsuspected arrhythmias identified on electrocardiogram and Holter monitors in an adult congenital heart population. Our study involved patients seen in our adult congenital heart clinic from July 2004 to December 2007. The inclusion criteria were that the patient had congenital heart disease, was over 18 years of age, and had a recent ECG and a 24-hour Holter monitor. The search identified 332 patients with 500 clinic visits; 140 patients met the inclusion criteria. The mean age of the
44
D.S. Moodie, C. Broberg / Progress in Pediatric Cardiology 34 (2012) 43–46 Table 1 Patient characteristics of the Baylor ACHD study.
Fig. 1. Age at death for adults with CHD.
adult congenital heart disease patients was 26.5 years with an age range of 18 to 66 years and a wide range of cardiac diagnoses (Table 1). Analysis of the ECGs revealed that 15% (N= 21) of ACHD had arrhythmias. Arrhythmias consisted of frequent ectopy (6%), supraventricular tachycardia (SVT) (3%), pacemaker issues (2%), and previously unrecognized high grade AV block (AVB) (1%). The majority of patients with arrhythmias on their presenting ECG (76%, N = 16) were asymptomatic. Analysis of the Holters revealed that 31% (N= 43) had an arrhythmia. Abnormalities included ectopy (17%), sustained and nonsustained SVT (12%), VT (7%), high grade AVB (5%), and pacemaker issues (3%). More than one type of arrhythmia on Holter monitoring was seen in 36% of patients. Of the patients with arrhythmias on the Holter monitor, 80% (N= 35) were asymptomatic. In those without arrhythmias on ECG, 26% (N= 31) had arrhythmias on Holter monitor. Of these patients, only 10% reported symptoms. Of the 47 patients who had multiple Holter monitors, 34% (N= 16) had a new arrhythmia noted. New arrhythmias included the development of SVT (N= 9), frequent ectopy (N= 8), VT (N= 4), pacemaker issues (N= 3), and high grade AVB (N= 2). There was a significant correlation between increasing age and the presence of arrhythmias on both ECGs and Holter monitor (P= 0.001 and b0.001, respectively). ACHD patients with SVT were more likely to be more symptomatic than patients with other types of arrhythmias on ECGs, although no patients in the cohort had VT on ECG monitoring alone (P = 0.001). On Holter monitoring, symptomatic patients were not more likely to have one type of arrhythmia versus another (P= −0.176). Arrhythmias are frequently encountered in patients with repaired congenital heart disease and vary according to their cardiac anatomy and interventions performed. The electric pathophysiology involves a complex interplay among many factors, including cardiac anatomy,
Fig. 2. Actuarial probability of SCD-free survival after surgical treatment.
Characteristic
Overall (n = 140)
Mean age
26.5 (range 18–66)
Cardiac diagnosis
Percentage of total (n = 140)
Tetralogy of Fallot D-TGA Atrial septal defects Single ventricle Ventricular septal defects Other Total
Arrhythmias on ECG
Arrhythmias on Holter monitoring
Symptomatic
21%
13%
43%
10%
6% 7%
22% 10%
33% 30%
0% 30%
5%
57%
29%
29%
4%
20%
40%
0%
57% 100%
11% 15%
27% 31%
10% 11%
ccTGA = congenitally corrected transposition of the great arteries; D-TGA = dextrotransposition of the great arteries; ECG = electrocardiogram.
chamber enlargement, cellular injury, fibrosis of sites of suture lines and direct trauma to the specialized induction tissues [13]. The concern regarding patients with asymptomatic arrhythmias detected on Holter monitoring is that they may have a lethal arrhythmia which can be detected and potentially treated. From the period of 1979 to 2005, the primary contributing cause of death among adults with cyanotic lesions was arrhythmias followed by heart failure [14]. Our data demonstrated that the vast majority of patients with arrhythmias (80%) were asymptomatic. As has been previously noted [1], ventricular arrhythmias were especially common in patients with tetralogy of Fallot. Repaired tetralogy of Fallot may lead to an increase in the number of ventricular arrhythmias after right ventriculotomy. In our study, greater than 20% of participants had a history of tetralogy of Fallot and greater than 40% of these patients had arrhythmias on Holter monitoring. In patients who have had an atriopulmonary Fontan operation, the right atrium is invariably distended and arrhythmias are more prevalent in the group with right atrial distension, compared to those whose atrium is not distended [15]. For this reason, rhythm monitoring is an important aspect of the clinical management of ACHD. Those patients with high risk of developing arrhythmias, such as those with tetralogy of Fallot and those with an atriopulmonary Fontan we feel benefit from routine Holter monitoring. We not only feel this based on our own personal study but also because the recommendation of the Task Force from the American Heart and American College recommends the same thing. Frequent ectopy can evolve into life-threatening arrhythmias. As the ACHD population grows, a corresponding increase in the prevalence of arrhythmias is expected, especially pronounced in patients with more severe types of congenital heart disease [3]. Late survivors of tetralogy of Fallot, the Fontan operation, and corrected transposition showed a close relationship between residual or late acquired structural abnormalities and the onset of ventricular dysfunction and arrhythmias [16]. In our patient population, older age was significantly correlated to an increased risk of arrhythmia on both Holter monitoring and ECG. The presence of arrhythmia may be an indication of worsening cardiac physiology. Conversely, late arrhythmias may lead to an unfavorable hemodynamics and further ventricular deterioration. As noted in our study, patients with significant arrhythmias may not be aware of any symptoms. Warnes [17] describes how ACHD patients may have the misconception of surgical cure and as a result, residual lesions and sequelae are frequently overlooked until patients present with symptoms. These patients may not detect a subtle change in exercise capacity, and when patients notice dyspnea and exercise limitation, valvular regurgitation and ventricular dysfunction
D.S. Moodie, C. Broberg / Progress in Pediatric Cardiology 34 (2012) 43–46
may be severe and irreversible. Arrhythmias are traditionally diagnosed in the presence of symptoms using ECG and Holter monitor. When patients are asymptomatic, the need for further studies may be overlooked. With routine monitoring, the early recognition of arrhythmias may allow earlier intervention, including catheter-based and/or surgical therapy. Arrhythmias are present in a significant percentage of ACHD patients undergoing ECGs and Holter monitoring. Many of these arrhythmias detected on ECG or Holter monitoring are asymptomatic, even those which may be life-threatening. Of ACHD patients with no arrhythmias on ECGs, many have abnormal Holter monitor results. Repeat Holter monitoring can identify new arrhythmias which have not been detected on previous studies. For these reasons, we recommend a formal study of ECG and Holter monitoring in ACHD patients routinely so that significant arrhythmias may be identified and treated. 2. Con Position: Complex Patients Should Not Have Routine Periodic ECG Monitoring There is no argument against the fact that arrhythmias are rampant in this patient population [8,18,19]. Also true is the observation that such events may be clinically silent and therefore unreported by the patient. Given the above, and the accepted fact that ambulatory electrocardiography, or “Holter monitoring,” carries essentially zero risk of harm, why should a Holter monitor not be performed with some frequency even in asymptomatic individuals? Considering the above, regular Holter monitoring was previously part of my clinical management of complex patients. But after recognizing that the majority of those studies were negative, that results rarely if ever altered my care of the patient, and that many patients were faced with considerable out-of-pocket expenses for the test, I have since abandoned the practice. Here, I will explore the rationales for this decision and examine whether it was justified. This discussion should not be interpreted as an argument against the practice altogether in patients with palpitations or syncope; without question Holter monitoring has an important role in ACHD care. But like many controversial screening programs [20], its use as a routine tool in patients without symptoms is not straightforward and begs for stronger justification. Current recommendations do not support routine monitoring in asymptomatic individuals. The joint guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) on adult congenital heart disease state, “testing should be arranged in response to clinical problems, particularly Holter monitor if there is concern about arrhythmia,” [11] (italics added) with similar statements elsewhere in the document regarding specific conditions. The European Society of Cardiology recommendations on congenital heart disease state, “Evaluation of arrhythmias, primarily in symptomatic patients, may require Holter monitoring,” (italics added) and elsewhere recommend, “Assessment of arrhythmias using Holter monitoring if indicated,” (italics added) also reiterating that these tests are intended to address clinical symptoms [21]. Specific ACC/AHA guidelines on Holter monitoring discuss indications for patients without symptoms [22]. Of these, there are no class I nor class IIa indications. Class IIb indications include post-MI patients with LV dysfunction, patients with idiopathic hypertrophic cardiomyopathy, or patients with congestive heart failure. One could argue the point that some complex congenital patients may fall into the latter category of heart failure, but that hardly seems to justify the practice on the whole, and one would expect such patients to be symptomatic. One rationale for these guideline statements is that the chance of finding a significant arrhythmia during a random 24-hour period is low, though there are only sparse data demonstrating how infrequently events occur. Rather, the value of the test can be examined by considering likely responses to either a negative or a positive study. While most studies are negative, it is difficult to imagine a situation where a negative routine screening study would alter the clinical management. Would a negative study argue for alteration of medical therapy, or discontinuation
45
of anticoagulation, or the delay of needed surgery? Most likely these decisions would be made based on other factors, including clinical events and symptoms. Instead, the stronger rationale for Holter monitoring is the intent of acting on a positive finding, such as significant bradycardia, atrial tachyarrhythmia, or ventricular tachyarrhythmia (VT). Bradycardia in an asymptomatic patient is not an indication for an implanted pacemaker in most instances. ACC/AHA guidelines on device implant specifically for individuals with congenital heart disease state that, “indications for pacemaker implantation in these patients need to be based on the correlation of symptoms with relative bradycardia rather than absolute heart rate criteria. … The primary criterion for pacemaker implantation is the concurrent observation of a symptom (e.g., syncope) with bradycardia [23].” Therefore asymptomatic screening for bradycardia is not justifiable. For atrial arrhythmias, since these events do not usually pose a life-threatening risk, management is still usually driven by symptoms, especially if only events of short duration are encountered as would be expected in asymptomatic individuals. Ventricular tachyarrhythmias, or factors associated with risk for such, remain the most ominous potential finding on Holter monitoring that might argue for preemptive action and should be considered in more depth. Most of the available data on Holter monitoring come from studies done in tetralogy of Fallot patients known to be at risk for VT including sudden cardiac death (SCD). This includes 8 studies showing Holter monitor findings to be risk factors for VT, and one that did not, as summarized in ACC/AHA guidelines [11]. Identification as a risk factor however does not mean that screening is effective. As these are all retrospective studies, most certainly the majority of the screenings were done in symptomatic patients, not asymptomatic, though admittedly this is not expressly stated. One of the largest of these studies examined Holter monitor results in some 300 individuals as part of the overall study [24]. Data summarized from the study are shown (Table 2). Findings on Holter monitoring were very common (about half the population), including premature ventricular contractions (PVCs), and ventricular couplets or triplets in addition to non-sustained VT. Clinical outcomes during follow-up included no arrhythmia, VT/SCD, or atrial fibrillation/flutter. Patients with VT/SCD on follow up had the same or less ventricular ectopy as those with no clinical arrhythmia (47% vs. 62%). Patients with atrial fibrillation/flutter also did not have more frequent ectopy than those without follow up events (68% and 62% respectively). Even if this difference had been significant, one would be hard pressed to offer some therapy for possible future atrial arrhythmia based purely on the finding of multiple PVCs. In contrast, the study showed strong differences in baseline ECG findings among the outcome groups including a QRS interval >180 ms or an annual increase in QRS duration that was predictive of outcomes. In another report of 252 patients undergoing electrophysiologic (EP) study after tetralogy of Fallot repair, a review of prior Holter monitor data was included in the analysis of predictors of inducible sustained VT. The modified Lown score ≥2 was marginally predictive (OR 5.6, 95% CI 1.0–30.9, p = 0.0493), but hardly significant compared to other findings carrying more weight clinically [25]. Again, the study was not done expressly in asymptomatic individuals. These same authors include non-sustained VT on Holter monitoring as only one of many Table 2 Findings on Holter monitoring. Data from Gatzoulis, MA et al., Lancet 2000;356:975–981. Outcome event
Frequent PVCs
Couplets
Tripletsa
Any finding
No arrhythmia VT/SCD Atrial arrhythmia
62% 47% 68%
27% 31% 23%
3% 3% 0%
48% 53% 68%
PVC = premature ventricular contraction. VT/SCD = ventricular tachycardia or sudden cardiac death. a Indicates that findings of more than 3 ventricular beats in succession were also included in this category.
46
D.S. Moodie, C. Broberg / Progress in Pediatric Cardiology 34 (2012) 43–46
factors with which to estimate a base risk, from which to therefore determine appropriateness for intervention including EP study, etc. [26]. In other words, as a stand-alone test, Holter monitor data do not seem to carry significant weight for altering practice patterns even in a relatively high-risk population. From these studies, one cannot determine the potential impact of symptoms alone as a predictor of events, aside from the Holter monitor findings. Though data are sparse, there is no evidence that Holter monitoring can accurately predict significant future arrhythmia in other high-risk groups such as systemic right ventricle patients or single ventricle/ Fontan patients. In the Mustard/Senning population, risk factors for sudden death are elusive and essentially none has a strong predictive value, including Holter monitoring in symptomatic individuals [27]. Arrhythmias are very common in single ventricle patients following Fontan palliation. In a series of 72 children after Fontan 82% had no findings on Holter monitoring [28]. Positive findings included 4 with sinus bradycardia, 8 with atrial tachyarrhythmia, and 1 with non-sustained VT. Other series have shown similar trends [29,30]. It is unclear how the findings influenced the patient management; medical, interventional, and device therapies for Fontans are all problematic and not likely pursued without symptoms. Therefore, because of the low likelihood of positive findings in an asymptomatic individual, the unclear impact of potential findings on patient management, and in support of existing guidelines, I no longer perform routine Holter monitoring in complex congenital heart patients who are asymptomatic. I submit that given the limitations of current data, the question may best be addressed in a simple clinical trial. Because symptoms suggestive of arrhythmia are ubiquitous in complex congenital heart disease, Holter monitoring is used frequently whenever warranted by clinical events. In my view, the tool should be reserved for evaluation of such symptoms. References [1] Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005;26:2325–33. [2] Somerville J. Management of adults with congenital heart disease: an increasing problem. Annu Rev Med 1997;48:283–93. [3] Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007;115:534–45. [4] Gelatt M, Hamilton RM, McCrindle BW, et al. Arrhythmia and mortality after the Mustard procedure: a 30-year single-center experience. J Am Coll Cardiol 1997;29: 194–201. [5] Gatzoulis MA, Munk MD, Williams WG, Webb GD. Definitive palliation with cavopulmonary or aortopulmonary shunts for adults with single ventricle physiology. Heart 2000;83:51–7. [6] Schwerzmann M, Salehian O, Harris L, et al. Ventricular arrhythmias and sudden death in adults after a Mustard operation for transposition of the great arteries. Eur Heart J 2009;30:1873–9. [7] Opotowsky AR, Siddiqi OK, Webb GD. Trends in hospitalizations for adults with congenital heart disease in the U.S. J Am Coll Cardiol 2009;54:460–7.
[8] Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation 2009;120:1679–86. [9] Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of death in adults with congenital heart disease. Am J Cardiol 2000;86:1111–6. [10] Silka et al. Probability of sudden cardiac re-survival after surgical treatment. J Am Coll Cardiol 1998;32:245–51. [11] Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Circulation 2008;118:e714–833. [12] Rodriguez FH, Moodie DS, Neeland M, Adams GJ, Snyder CS. Identifying arrhythmias in adults with congenital heart disease by 24-hour ambulatory electrocardiography. Pediatr Cardiol 2012;33:591–5. [13] Walsh EP. Interventional electrophysiology in patients with congenital heart disease. Circulation 2007;115:3224–34. [14] Pillutla P, Shetty KD, Foster E. Mortality associated with adult congenital heart disease: Trends in the US population from 1979 to 2005. Am Heart J 2009;158:874–9. [15] Wong T, Davlouros PA, Li W, Millington-Sanders C, Francis DP, Gatzoulis MA. Mechano-electrical interaction late after Fontan operation: relation between P-wave duration and dispersion, right atrial size, and atrial arrhythmias. Circulation 2004;109:2319–25. [16] Capelli H. Grown-up congenital heart disease: The problem of late arrhythmia and ventricular dysfunction. Prog Pediatr Cardiol 2006;22:165–73. [17] Warnes CA. The adult with congenital heart disease: born to be bad? J Am Coll Cardiol 2005;46:1–8. [18] Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010;122:868–75. [19] Landzberg MJ, Cecchin F. Atrial arrhythmias: a “call to arms” for congenital heart disease caregivers. Circulation 2009;120:1649–50. [20] Sackett DL, Holland WW. Controversy in the detection of disease. Lancet 1975;2:357–9. [21] Baumgartner H, Bonhoeffer P, De Groot NM, et al. ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 2010;31:2915–57. [22] Crawford MH, Bernstein SJ, Deedwania PC, et al. ACC/AHA guidelines for ambulatory electrocardiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the guidelines for ambulatory electrocardiography). Circulation 1999;100:886–93. [23] Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51:e1–62. [24] Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet 2000;356:975–81. [25] Khairy P, Landzberg MJ, Gatzoulis MA, et al. Value of programmed ventricular stimulation after tetralogy of Fallot repair: a multicenter study. Circulation 2004;109:1994–2000. [26] Khairy P, Dore A, Poirier N, et al. Risk stratification in surgically repaired tetralogy of Fallot. Expert Rev Cardiovasc Ther 2009;7:755–62. [27] Yap SC, Harris L. Sudden cardiac death in adults with congenital heart disease. Expert Rev Cardiovasc Ther 2009;7:1605–20. [28] Kalra S, Sharma R, Bhan A, et al. Ambulatory 24-hour electrocardiographic monitoring following total cavopulmonary connection. Indian Heart J 1999;51:425–8. [29] Gelatt M, Hamilton RM, McCrindle BW, et al. Risk factors for atrial tachyarrhythmias after the Fontan operation. J Am Coll Cardiol 1994;24:1735–41. [30] Paul T, Ziemer G, Luhmer L, Bertram H, Hecker H, Kallfelz HC. Early and late atrial dysrhythmias after modified Fontan operation. Pediatr Med Chir 1998;20:9–11.
Contents lists available at SciVerse ScienceDirect
Progress in Pediatric Cardiology journal homepage: www.elsevier.com/locate/ppedcard
Should complex ACHD patients have periodic Holter monitoring? Douglas S. Moodie a, b, c,⁎, Craig Broberg d a
Pediatric Cardiology, Texas Children's Hospital, Houston, TX, United States Pediatric Cardiology Fellowship Program, Texas Children's Hospital, Houston, TX, United States c Adult Congenital Heart Center, Texas Children's Hospital, United States d Adult Congenital Heart Program, Oregon Health and Science University, Portland, OR, United States b
a r t i c l e Keywords: Holter monitor ECG ACHD Arrhythmia
i n f o
a b s t r a c t This article stems from a debate held at the Adult Congenital Heart Meetings at Cincinnati in the summer of 2011 where Dr. Moodie and Broberg debated whether complex adult congenital heart patients should have regular Holter monitor studies done. Dr. Moodie took the pro position and Dr. Broberg the con and this article is a result of that debate. © 2012 Elsevier Ireland Ltd. All rights reserved.
1. Pro Position: Complex Patients Should Have Routine Periodic ECG Monitoring Adult congenital heart disease (ACHD) patients develop a myriad of problems as they age, including heart failure, arrhythmias, stroke and the need for surgical or catheter-based intervention [1]. Arrhythmias are the most common cardiologic reason for hospital admission and atrial fibrillation and flutter are the most frequent arrhythmias encountered in this population [2]. As many as one-third of patients with repaired tetralogy of Fallot develop symptomatic atrial tachycardia by adulthood, and only 40% of those with transposition of the great vessels who have had a Mustard or Senning repair are in sinus rhythm 20 years after their operation [3,4]. Atrial tachycardia has been reported in up to 57% of patients with an aortopulmonary connection [5]. In a study of adults who had undergone a Mustard operation for transposition of the great vessels, 9% had sustained ventricular tachycardia or sudden death after immediate follow-up of 9 years after transition of care from pediatric to the adult clinic [6]. Between 1998 and 2005, the number of admissions because of arrhythmias in ACHD patients more than doubled [7]. In a population based analysis of ACHD by Bouchardy, the 20-year risk of developing atrial arrhythmia was 7% in a 20 year-old subject and 38% in a 50 year-old subject [8]. The lifetime incidence of ACHD developing atrial arrhythmia increased steadily with age, and the development of atrial arrhythmias was associated with the doubling of the risk of adverse events: mortality, morbidity, and intervention. More than 50% of patients with severe congenital heart disease over 18 years of age developed atrial arrhythmias by 65 years of age. ACHD
⁎ Corresponding author at: Pediatric Cardiology, Texas Children's Hospital, Houston, TX, United States. E-mail address: [email protected] (D.S. Moodie). 1058-9813/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ppedcard.2012.05.010
patients with atrial arrhythmias have an approximately 50% increase in mortality, more than double the risk of morbidity (stroke or heart failure), and three times the risk of cardiac intervention. In the ACHD literature, sudden death is the most common cause of death (26%), followed by progressive heart failure (21%), and perioperative death (18%) [9] (Fig. 1). Silka et al. [10] described the actual probability of sudden cardiac death after surgical treatment of coarctation, tetralogy, aortic stenosis and transposition (Fig. 2). In a review of over 4000 ACHD patients in Europe, 18% had supraventricular arrhythmias and 5% had ventricular arrhythmias [11]. Ventricular arrhythmias were especially common in patients with tetralogy of Fallot. The 2008 American College of Cardiology/American Heart Association Guidelines for Adult Congenital Heart Disease recommended Holter monitoring in specific patients such as those with repaired tetralogy of Fallot and AV septal defects [12]. These guidelines also indicate that rhythm abnormalities and transposition of the great vessels, congenitally corrected the transposition of the great vessels, and Ebstein's anomaly may be further elucidated by periodic ambulatory Holter monitoring. Thus, the two major organizations in cardiology today, the American Heart Association and the American College of Cardiology, have recommended routine Holter evaluation in a significant number of complex patients and substantiate the need for Holter monitoring in these patients. There is very little data on Holter monitoring in adult congenital heart disease. We recently looked at the incidence of unsuspected arrhythmias identified on electrocardiogram and Holter monitors in an adult congenital heart population. Our study involved patients seen in our adult congenital heart clinic from July 2004 to December 2007. The inclusion criteria were that the patient had congenital heart disease, was over 18 years of age, and had a recent ECG and a 24-hour Holter monitor. The search identified 332 patients with 500 clinic visits; 140 patients met the inclusion criteria. The mean age of the
44
D.S. Moodie, C. Broberg / Progress in Pediatric Cardiology 34 (2012) 43–46 Table 1 Patient characteristics of the Baylor ACHD study.
Fig. 1. Age at death for adults with CHD.
adult congenital heart disease patients was 26.5 years with an age range of 18 to 66 years and a wide range of cardiac diagnoses (Table 1). Analysis of the ECGs revealed that 15% (N= 21) of ACHD had arrhythmias. Arrhythmias consisted of frequent ectopy (6%), supraventricular tachycardia (SVT) (3%), pacemaker issues (2%), and previously unrecognized high grade AV block (AVB) (1%). The majority of patients with arrhythmias on their presenting ECG (76%, N = 16) were asymptomatic. Analysis of the Holters revealed that 31% (N= 43) had an arrhythmia. Abnormalities included ectopy (17%), sustained and nonsustained SVT (12%), VT (7%), high grade AVB (5%), and pacemaker issues (3%). More than one type of arrhythmia on Holter monitoring was seen in 36% of patients. Of the patients with arrhythmias on the Holter monitor, 80% (N= 35) were asymptomatic. In those without arrhythmias on ECG, 26% (N= 31) had arrhythmias on Holter monitor. Of these patients, only 10% reported symptoms. Of the 47 patients who had multiple Holter monitors, 34% (N= 16) had a new arrhythmia noted. New arrhythmias included the development of SVT (N= 9), frequent ectopy (N= 8), VT (N= 4), pacemaker issues (N= 3), and high grade AVB (N= 2). There was a significant correlation between increasing age and the presence of arrhythmias on both ECGs and Holter monitor (P= 0.001 and b0.001, respectively). ACHD patients with SVT were more likely to be more symptomatic than patients with other types of arrhythmias on ECGs, although no patients in the cohort had VT on ECG monitoring alone (P = 0.001). On Holter monitoring, symptomatic patients were not more likely to have one type of arrhythmia versus another (P= −0.176). Arrhythmias are frequently encountered in patients with repaired congenital heart disease and vary according to their cardiac anatomy and interventions performed. The electric pathophysiology involves a complex interplay among many factors, including cardiac anatomy,
Fig. 2. Actuarial probability of SCD-free survival after surgical treatment.
Characteristic
Overall (n = 140)
Mean age
26.5 (range 18–66)
Cardiac diagnosis
Percentage of total (n = 140)
Tetralogy of Fallot D-TGA Atrial septal defects Single ventricle Ventricular septal defects Other Total
Arrhythmias on ECG
Arrhythmias on Holter monitoring
Symptomatic
21%
13%
43%
10%
6% 7%
22% 10%
33% 30%
0% 30%
5%
57%
29%
29%
4%
20%
40%
0%
57% 100%
11% 15%
27% 31%
10% 11%
ccTGA = congenitally corrected transposition of the great arteries; D-TGA = dextrotransposition of the great arteries; ECG = electrocardiogram.
chamber enlargement, cellular injury, fibrosis of sites of suture lines and direct trauma to the specialized induction tissues [13]. The concern regarding patients with asymptomatic arrhythmias detected on Holter monitoring is that they may have a lethal arrhythmia which can be detected and potentially treated. From the period of 1979 to 2005, the primary contributing cause of death among adults with cyanotic lesions was arrhythmias followed by heart failure [14]. Our data demonstrated that the vast majority of patients with arrhythmias (80%) were asymptomatic. As has been previously noted [1], ventricular arrhythmias were especially common in patients with tetralogy of Fallot. Repaired tetralogy of Fallot may lead to an increase in the number of ventricular arrhythmias after right ventriculotomy. In our study, greater than 20% of participants had a history of tetralogy of Fallot and greater than 40% of these patients had arrhythmias on Holter monitoring. In patients who have had an atriopulmonary Fontan operation, the right atrium is invariably distended and arrhythmias are more prevalent in the group with right atrial distension, compared to those whose atrium is not distended [15]. For this reason, rhythm monitoring is an important aspect of the clinical management of ACHD. Those patients with high risk of developing arrhythmias, such as those with tetralogy of Fallot and those with an atriopulmonary Fontan we feel benefit from routine Holter monitoring. We not only feel this based on our own personal study but also because the recommendation of the Task Force from the American Heart and American College recommends the same thing. Frequent ectopy can evolve into life-threatening arrhythmias. As the ACHD population grows, a corresponding increase in the prevalence of arrhythmias is expected, especially pronounced in patients with more severe types of congenital heart disease [3]. Late survivors of tetralogy of Fallot, the Fontan operation, and corrected transposition showed a close relationship between residual or late acquired structural abnormalities and the onset of ventricular dysfunction and arrhythmias [16]. In our patient population, older age was significantly correlated to an increased risk of arrhythmia on both Holter monitoring and ECG. The presence of arrhythmia may be an indication of worsening cardiac physiology. Conversely, late arrhythmias may lead to an unfavorable hemodynamics and further ventricular deterioration. As noted in our study, patients with significant arrhythmias may not be aware of any symptoms. Warnes [17] describes how ACHD patients may have the misconception of surgical cure and as a result, residual lesions and sequelae are frequently overlooked until patients present with symptoms. These patients may not detect a subtle change in exercise capacity, and when patients notice dyspnea and exercise limitation, valvular regurgitation and ventricular dysfunction
D.S. Moodie, C. Broberg / Progress in Pediatric Cardiology 34 (2012) 43–46
may be severe and irreversible. Arrhythmias are traditionally diagnosed in the presence of symptoms using ECG and Holter monitor. When patients are asymptomatic, the need for further studies may be overlooked. With routine monitoring, the early recognition of arrhythmias may allow earlier intervention, including catheter-based and/or surgical therapy. Arrhythmias are present in a significant percentage of ACHD patients undergoing ECGs and Holter monitoring. Many of these arrhythmias detected on ECG or Holter monitoring are asymptomatic, even those which may be life-threatening. Of ACHD patients with no arrhythmias on ECGs, many have abnormal Holter monitor results. Repeat Holter monitoring can identify new arrhythmias which have not been detected on previous studies. For these reasons, we recommend a formal study of ECG and Holter monitoring in ACHD patients routinely so that significant arrhythmias may be identified and treated. 2. Con Position: Complex Patients Should Not Have Routine Periodic ECG Monitoring There is no argument against the fact that arrhythmias are rampant in this patient population [8,18,19]. Also true is the observation that such events may be clinically silent and therefore unreported by the patient. Given the above, and the accepted fact that ambulatory electrocardiography, or “Holter monitoring,” carries essentially zero risk of harm, why should a Holter monitor not be performed with some frequency even in asymptomatic individuals? Considering the above, regular Holter monitoring was previously part of my clinical management of complex patients. But after recognizing that the majority of those studies were negative, that results rarely if ever altered my care of the patient, and that many patients were faced with considerable out-of-pocket expenses for the test, I have since abandoned the practice. Here, I will explore the rationales for this decision and examine whether it was justified. This discussion should not be interpreted as an argument against the practice altogether in patients with palpitations or syncope; without question Holter monitoring has an important role in ACHD care. But like many controversial screening programs [20], its use as a routine tool in patients without symptoms is not straightforward and begs for stronger justification. Current recommendations do not support routine monitoring in asymptomatic individuals. The joint guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) on adult congenital heart disease state, “testing should be arranged in response to clinical problems, particularly Holter monitor if there is concern about arrhythmia,” [11] (italics added) with similar statements elsewhere in the document regarding specific conditions. The European Society of Cardiology recommendations on congenital heart disease state, “Evaluation of arrhythmias, primarily in symptomatic patients, may require Holter monitoring,” (italics added) and elsewhere recommend, “Assessment of arrhythmias using Holter monitoring if indicated,” (italics added) also reiterating that these tests are intended to address clinical symptoms [21]. Specific ACC/AHA guidelines on Holter monitoring discuss indications for patients without symptoms [22]. Of these, there are no class I nor class IIa indications. Class IIb indications include post-MI patients with LV dysfunction, patients with idiopathic hypertrophic cardiomyopathy, or patients with congestive heart failure. One could argue the point that some complex congenital patients may fall into the latter category of heart failure, but that hardly seems to justify the practice on the whole, and one would expect such patients to be symptomatic. One rationale for these guideline statements is that the chance of finding a significant arrhythmia during a random 24-hour period is low, though there are only sparse data demonstrating how infrequently events occur. Rather, the value of the test can be examined by considering likely responses to either a negative or a positive study. While most studies are negative, it is difficult to imagine a situation where a negative routine screening study would alter the clinical management. Would a negative study argue for alteration of medical therapy, or discontinuation
45
of anticoagulation, or the delay of needed surgery? Most likely these decisions would be made based on other factors, including clinical events and symptoms. Instead, the stronger rationale for Holter monitoring is the intent of acting on a positive finding, such as significant bradycardia, atrial tachyarrhythmia, or ventricular tachyarrhythmia (VT). Bradycardia in an asymptomatic patient is not an indication for an implanted pacemaker in most instances. ACC/AHA guidelines on device implant specifically for individuals with congenital heart disease state that, “indications for pacemaker implantation in these patients need to be based on the correlation of symptoms with relative bradycardia rather than absolute heart rate criteria. … The primary criterion for pacemaker implantation is the concurrent observation of a symptom (e.g., syncope) with bradycardia [23].” Therefore asymptomatic screening for bradycardia is not justifiable. For atrial arrhythmias, since these events do not usually pose a life-threatening risk, management is still usually driven by symptoms, especially if only events of short duration are encountered as would be expected in asymptomatic individuals. Ventricular tachyarrhythmias, or factors associated with risk for such, remain the most ominous potential finding on Holter monitoring that might argue for preemptive action and should be considered in more depth. Most of the available data on Holter monitoring come from studies done in tetralogy of Fallot patients known to be at risk for VT including sudden cardiac death (SCD). This includes 8 studies showing Holter monitor findings to be risk factors for VT, and one that did not, as summarized in ACC/AHA guidelines [11]. Identification as a risk factor however does not mean that screening is effective. As these are all retrospective studies, most certainly the majority of the screenings were done in symptomatic patients, not asymptomatic, though admittedly this is not expressly stated. One of the largest of these studies examined Holter monitor results in some 300 individuals as part of the overall study [24]. Data summarized from the study are shown (Table 2). Findings on Holter monitoring were very common (about half the population), including premature ventricular contractions (PVCs), and ventricular couplets or triplets in addition to non-sustained VT. Clinical outcomes during follow-up included no arrhythmia, VT/SCD, or atrial fibrillation/flutter. Patients with VT/SCD on follow up had the same or less ventricular ectopy as those with no clinical arrhythmia (47% vs. 62%). Patients with atrial fibrillation/flutter also did not have more frequent ectopy than those without follow up events (68% and 62% respectively). Even if this difference had been significant, one would be hard pressed to offer some therapy for possible future atrial arrhythmia based purely on the finding of multiple PVCs. In contrast, the study showed strong differences in baseline ECG findings among the outcome groups including a QRS interval >180 ms or an annual increase in QRS duration that was predictive of outcomes. In another report of 252 patients undergoing electrophysiologic (EP) study after tetralogy of Fallot repair, a review of prior Holter monitor data was included in the analysis of predictors of inducible sustained VT. The modified Lown score ≥2 was marginally predictive (OR 5.6, 95% CI 1.0–30.9, p = 0.0493), but hardly significant compared to other findings carrying more weight clinically [25]. Again, the study was not done expressly in asymptomatic individuals. These same authors include non-sustained VT on Holter monitoring as only one of many Table 2 Findings on Holter monitoring. Data from Gatzoulis, MA et al., Lancet 2000;356:975–981. Outcome event
Frequent PVCs
Couplets
Tripletsa
Any finding
No arrhythmia VT/SCD Atrial arrhythmia
62% 47% 68%
27% 31% 23%
3% 3% 0%
48% 53% 68%
PVC = premature ventricular contraction. VT/SCD = ventricular tachycardia or sudden cardiac death. a Indicates that findings of more than 3 ventricular beats in succession were also included in this category.
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D.S. Moodie, C. Broberg / Progress in Pediatric Cardiology 34 (2012) 43–46
factors with which to estimate a base risk, from which to therefore determine appropriateness for intervention including EP study, etc. [26]. In other words, as a stand-alone test, Holter monitor data do not seem to carry significant weight for altering practice patterns even in a relatively high-risk population. From these studies, one cannot determine the potential impact of symptoms alone as a predictor of events, aside from the Holter monitor findings. Though data are sparse, there is no evidence that Holter monitoring can accurately predict significant future arrhythmia in other high-risk groups such as systemic right ventricle patients or single ventricle/ Fontan patients. In the Mustard/Senning population, risk factors for sudden death are elusive and essentially none has a strong predictive value, including Holter monitoring in symptomatic individuals [27]. Arrhythmias are very common in single ventricle patients following Fontan palliation. In a series of 72 children after Fontan 82% had no findings on Holter monitoring [28]. Positive findings included 4 with sinus bradycardia, 8 with atrial tachyarrhythmia, and 1 with non-sustained VT. Other series have shown similar trends [29,30]. It is unclear how the findings influenced the patient management; medical, interventional, and device therapies for Fontans are all problematic and not likely pursued without symptoms. Therefore, because of the low likelihood of positive findings in an asymptomatic individual, the unclear impact of potential findings on patient management, and in support of existing guidelines, I no longer perform routine Holter monitoring in complex congenital heart patients who are asymptomatic. I submit that given the limitations of current data, the question may best be addressed in a simple clinical trial. Because symptoms suggestive of arrhythmia are ubiquitous in complex congenital heart disease, Holter monitoring is used frequently whenever warranted by clinical events. In my view, the tool should be reserved for evaluation of such symptoms. References [1] Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005;26:2325–33. [2] Somerville J. Management of adults with congenital heart disease: an increasing problem. Annu Rev Med 1997;48:283–93. [3] Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007;115:534–45. [4] Gelatt M, Hamilton RM, McCrindle BW, et al. Arrhythmia and mortality after the Mustard procedure: a 30-year single-center experience. J Am Coll Cardiol 1997;29: 194–201. [5] Gatzoulis MA, Munk MD, Williams WG, Webb GD. Definitive palliation with cavopulmonary or aortopulmonary shunts for adults with single ventricle physiology. Heart 2000;83:51–7. [6] Schwerzmann M, Salehian O, Harris L, et al. Ventricular arrhythmias and sudden death in adults after a Mustard operation for transposition of the great arteries. Eur Heart J 2009;30:1873–9. [7] Opotowsky AR, Siddiqi OK, Webb GD. Trends in hospitalizations for adults with congenital heart disease in the U.S. J Am Coll Cardiol 2009;54:460–7.
[8] Bouchardy J, Therrien J, Pilote L, et al. Atrial arrhythmias in adults with congenital heart disease. Circulation 2009;120:1679–86. [9] Oechslin EN, Harrison DA, Connelly MS, Webb GD, Siu SC. Mode of death in adults with congenital heart disease. Am J Cardiol 2000;86:1111–6. [10] Silka et al. Probability of sudden cardiac re-survival after surgical treatment. J Am Coll Cardiol 1998;32:245–51. [11] Warnes CA, Williams RG, Bashore TM, et al. ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (writing committee to develop guidelines on the management of adults with congenital heart disease). Circulation 2008;118:e714–833. [12] Rodriguez FH, Moodie DS, Neeland M, Adams GJ, Snyder CS. Identifying arrhythmias in adults with congenital heart disease by 24-hour ambulatory electrocardiography. Pediatr Cardiol 2012;33:591–5. [13] Walsh EP. Interventional electrophysiology in patients with congenital heart disease. Circulation 2007;115:3224–34. [14] Pillutla P, Shetty KD, Foster E. Mortality associated with adult congenital heart disease: Trends in the US population from 1979 to 2005. Am Heart J 2009;158:874–9. [15] Wong T, Davlouros PA, Li W, Millington-Sanders C, Francis DP, Gatzoulis MA. Mechano-electrical interaction late after Fontan operation: relation between P-wave duration and dispersion, right atrial size, and atrial arrhythmias. Circulation 2004;109:2319–25. [16] Capelli H. Grown-up congenital heart disease: The problem of late arrhythmia and ventricular dysfunction. Prog Pediatr Cardiol 2006;22:165–73. [17] Warnes CA. The adult with congenital heart disease: born to be bad? J Am Coll Cardiol 2005;46:1–8. [18] Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010;122:868–75. [19] Landzberg MJ, Cecchin F. Atrial arrhythmias: a “call to arms” for congenital heart disease caregivers. Circulation 2009;120:1649–50. [20] Sackett DL, Holland WW. Controversy in the detection of disease. Lancet 1975;2:357–9. [21] Baumgartner H, Bonhoeffer P, De Groot NM, et al. ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 2010;31:2915–57. [22] Crawford MH, Bernstein SJ, Deedwania PC, et al. ACC/AHA guidelines for ambulatory electrocardiography: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee to revise the guidelines for ambulatory electrocardiography). Circulation 1999;100:886–93. [23] Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51:e1–62. [24] Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet 2000;356:975–81. [25] Khairy P, Landzberg MJ, Gatzoulis MA, et al. Value of programmed ventricular stimulation after tetralogy of Fallot repair: a multicenter study. Circulation 2004;109:1994–2000. [26] Khairy P, Dore A, Poirier N, et al. Risk stratification in surgically repaired tetralogy of Fallot. Expert Rev Cardiovasc Ther 2009;7:755–62. [27] Yap SC, Harris L. Sudden cardiac death in adults with congenital heart disease. Expert Rev Cardiovasc Ther 2009;7:1605–20. [28] Kalra S, Sharma R, Bhan A, et al. Ambulatory 24-hour electrocardiographic monitoring following total cavopulmonary connection. Indian Heart J 1999;51:425–8. [29] Gelatt M, Hamilton RM, McCrindle BW, et al. Risk factors for atrial tachyarrhythmias after the Fontan operation. J Am Coll Cardiol 1994;24:1735–41. [30] Paul T, Ziemer G, Luhmer L, Bertram H, Hecker H, Kallfelz HC. Early and late atrial dysrhythmias after modified Fontan operation. Pediatr Med Chir 1998;20:9–11.