View largeDownload slide View largeDownload slide This editorial refers to ‘Sudden death in patients with Ebstein anomaly’†, by C.H. Attenhofer Jost et al., on page 1970. Since the original description of this entity by Wilhelm Ebstein in 1866 published in Archiv für Anatomie, Physiologie und wissenschaftliche Medizin (Take home figure),1 there has no doubt been improvement in the care and outcomes of those afflicted by this malformation. Nonetheless, the risk of sudden death (SD) in those with Ebstein’s anomaly remains higher than that in the general congenital heart disease population. This is evident in the account by Attenhofer Jost and colleagues in this issue of the journal2 regarding the Mayo Clinic’s vast experience of caring for these patients over the past four decades, reporting the incidence of SD in a cohort of 968 patients with Ebstein’s anomaly, the majority of whom have had tricuspid valve (TV) surgery. They identify a history of ventricular tachycardia, heart failure, TV surgery, syncope, pulmonary stenosis (PS), and haemoglobin >15 g/dL as predictors of SD in this retrospective analysis. The 70-year risk of SD is reported to be ∼15%, equating to an incidence of ∼0.2% per year, with a striking acceleration in risk demonstrated on their Kaplan–Meier curve after just ∼40 years of age. This risk increases significantly following TV surgery, reaching an estimated rate of just over 2% per year in the first post-operative year, with a fairly linear course thereafter. Take home figure View largeDownload slide The original drawings by Dr. Wyss, included in Wilhelm Ebstein’s detailed description of this tricuspid valve anomaly in his autopsied patient, Joseph Prescher, as published in 1866. The treatment of this young 19 year old male admitted to All-Saint’s Hospital in Breslau in 1864 for worsening cough, weight loss and lower extremity oedema, with evidence of severe cardiomegaly and significant tricuspid regurgitation on examination, was morphine for his persistent cough. The patient was described to have collapsed on the eighth day of hospital admission and ‘die in pulmonary oedema’. We have surely come a long way in the management of these patients over the past century and a half, however, the risk of sudden death remains much higher than many other forms of congenital heart disease. Take home figure View largeDownload slide The original drawings by Dr. Wyss, included in Wilhelm Ebstein’s detailed description of this tricuspid valve anomaly in his autopsied patient, Joseph Prescher, as published in 1866. The treatment of this young 19 year old male admitted to All-Saint’s Hospital in Breslau in 1864 for worsening cough, weight loss and lower extremity oedema, with evidence of severe cardiomegaly and significant tricuspid regurgitation on examination, was morphine for his persistent cough. The patient was described to have collapsed on the eighth day of hospital admission and ‘die in pulmonary oedema’. We have surely come a long way in the management of these patients over the past century and a half, however, the risk of sudden death remains much higher than many other forms of congenital heart disease. At first glance, the study by Attenhofer Jost and colleagues2 suggests that TV surgery itself portends a SD event, questioning experiential guidelines for determining both the need for and appropriate timing of such a procedure. Given the common indications for surgery, such as symptoms of right heart failure, progressive exercise intolerance, and severe cyanosis, has the Mayo Clinic ignored their own data suggesting that the most beneficial effect of improving functional capacity is obtained by closure of an interatrial communication when present?3 In the current study,2 78% of patients had an interatrial communication, with only 17% having this closed prior to their TV surgery at the Mayo Clinic. The majority subsequently had concomitant closure at the time of TV surgery. In light of the increased SD risk with an elevation in haemoglobin (>15 g/dL), could closure of an interatrial communication alone, which can be done transcutaneously, not only improve functional capacity but also decrease the risk of SD? Even more, is this the only structural intervention needed in a large proportion of patients? The current report by the Mayo Clinic certainly raises these questions. In contrast to other outcome studies,4 the degree of tricuspid regurgitation was not itself predictive of SD, warning against chasing this alone as an indication to intervene in the TV in a symptomatic patient. However, similar to their previous report on surgical outcomes,5 right ventricular (RV) systolic dysfunction was related to and potentially can improve following surgery on a poorly functioning TV, with anticipated improvement in functional capacity.3 Intervention on significant residual PS should additionally be considered, as this obstruction clearly increases the risk of poor outcomes, especially when associated with RV systolic dysfunction, potentially related to their combined arrhythmogenic effect.2,5,6 Although the current study reports a normal mean left ventricular (LV) ejection fraction (58 ± 8%) in this large cohort, it is unclear how many of these patients had significant LV systolic dysfunction,2 a clear predictor of poor outcomes and predecessor of the occurrence of arrhythmia.5,7 Previous accounts reported moderate or worse LV systolic function in 10% of operated Ebstein’s patients, improving in the majority following TV surgery, suggesting that surgery on a poorly functioning TV in the presence of LV dysfunction may also be beneficial.7 Conclusions made from the current analysis,2 however, are confounded by the fact that the overwhelming majority of patients in this study underwent TV surgery at a large referral centre which unsurprisingly reports a relatively sicker cohort of patients with more anatomically severe Ebstein’s anomaly operated on at their institution (n = 804) than the smaller sample not having undergone TV surgery at their institution (n = 164). The complete cohort seems far less representative of the gamut of patients encountered than reported by other groups investigating outcomes,6 with poor representation of mild and moderate forms of the disease. Therefore, it is difficult to conclude that the predictive value of TV surgery for SD is a consequence of the surgery itself, but instead is probably related to other factors in this sicker cohort, such as arrhythmia burden, LV and/or RV systolic dysfunction, and increasing cyanosis, plus or minus associated symptoms of heart failure.2,5,7 On the other hand, patients who may have died prior to referral would not be included, potentially excluding a group of patients with more severe disease. It is also worth noting that this study spans four decades during which much has changed, including surgical techniques and technology, as well as peri-operative and long-term management. Atrial and ventricular arrhythmias, both prevalent in patients with Ebstein’s anomaly, and risk factors for, and often preceding SD, can be the consequence of significant tricuspid regurgitation, and ventricular dilation and dysfunction, not to mention surgical intervention and myocardial scarring. These arrhythmias should be actively monitored for and managed aggressively. Interestingly, regarding the aggressive treatment of the condition, Attenhofer Jost and colleagues2 report a concomitant biatrial Maze procedure adding significant risk for SD. Similar to the preceding discussion, it is unclear whether the procedure itself imposes additional risk, or if the higher arrhythmia burden in most patients considered for biatrial Maze, often with atrial fibrillation, augments this risk. In addition to ventricular arrhythmias, on univariate analysis, atrial arrhythmias added increased risk for SD in their study, highlighting the fact that addressing arrhythmia burden prior to or at the time of surgery is prudent.2 The Mayo Clinic group recently provided more insight regarding this in their analysis of outcomes of radiofrequency catheter ablation in Ebstein’s patients, identifying cavotricuspid isthmus atrial flutter as the most common mechanism of induced arrhythmia, being present in almost 60% of those who had history of previous right-sided atrial Maze. This was surprising, as a linear cavotricuspid lesion is standard in the right-sided atrial Maze. Furthermore, few left-sided atrial arrhythmias were identified, highlighting that the inclusion of a biatrial Maze can not only be harmful, potentially leading to sinus and/or atrioventricular node damage, but even unnecessary in many Ebstein’s patients.8 The previous finding that a non-sinus rhythm at the time of discharge following TV surgery is a predictor of late mortality in Ebstein’s anomaly further supports addressing any arrhythmia burden prior to or at the time of surgery, as well as the need for a permanent pacemaker in any patient with evidence of sinus or atrioventricular node failure.7 Rydman and colleagues9 reported that major adverse cardiovascular events in Ebstein’s patients were preceded by clinically documented atrial tachycardia in the overwhelming majority, which itself was often preceded by RV dilation and systolic dysfunction, and more anatomically severe Ebstein’s anomaly. Similarly to other studies, they also identified LV or RV systolic dysfunction as a predictor of these adverse events. Although this arrhythmia burden can be addressed at the time of surgery, many would also advocate for a pre-operative electrophysiology study in any Ebstein’s patient undergoing TV surgery, as a substrate for either atrial or ventricular arrhythmia may be uncovered during diagnostic testing in a large percentage of patients with no previous clinical evidence of arrhythmia,10 supported by the prevalence of inducible and recurrent atrial arrhythmias despite surgical Maze.8 These data also suggest, as we have already discussed, that ventricular dilation and dysfunction may be an inciting factor of arrhythmia burden in many of these patients, and should help guide the timing of any intervention. It is difficult to draw generalized conclusions regarding the appropriateness of indications and timing for TV surgery from this more severe, and historic, cohort of patients with Ebstein’s anomaly. The risk factors of SD all point to late intervention and residual lesions as major causes, with a concerning rise of SD risk in the fourth decade of life. However, early closure of the interatrial communication may be all that is necessary for many symptomatic patients and, given the uncertain impact of previous iterations of surgery, which themselves were quite abusive to the right ventricle, the slavish mantra that early surgery is always better surgery is difficult to sustain with data. The avoidance of significant RV or LV systolic dysfunction and TV incompetence, especially with associated PS, by surgical intervention has long been considered a reasonable goal of surgery in the myopathic ventricles of these patients. Again, the road to hell may be paved with good intentions. At the very least, these patients will require careful arrhythmia surveillance after their operation, as it appears that their ‘unnatural history’ remains relatively poor. Of course, as with every new operation, it is hoped that things may be different with the introduction of the ‘cone’ operation and its variants. In this regard, the data from the Mayo clinic are sobering, and hopefully we will not see another phase of ‘bandwagon jumping’. Indeed, it may be decades before we know whether it truly makes a difference and, while any call for a randomized trial is futile, we must surely remain somewhat circumspect in surgical decision-making, and ever vigilant whether operated or unoperated, in this complex group of patients. Conflicts of interest: none declared. References 1 Schiebler GL , Gravenstein JS , Van Mierop LH. Ebstein’s anomaly of the tricuspid valve. Translation of original description with comments . Am J Cardiol 1968 ; 22 : 867 – 73 . Google Scholar CrossRef Search ADS PubMed 2 Attenhofer Jost CH , Tan NY , Hassan A , Vargas ER , Hodge DO , Dearani JA , Connolly H , Asirvatham SJ , McLeod CJ. Sudden death in patients with Ebstein anomaly . Eur Heart J 2018 ; 39 : 1970 – 1977 . 3 MacLellan-Tobert SG , Driscoll DJ , Mottram CD , Mahoney DW , Wollan PC , Danielson GK. Exercise tolerance in patients with Ebstein’s anomaly . J Am Coll Cardiol 1997 ; 29 : 1615 – 1622 . Google Scholar CrossRef Search ADS PubMed 4 Attie F , Rosas M , Rijlaarsdam M , Buendia A , Zabal C , Kuri J , Granados N. The adult patient with Ebstein anomaly. Outcome in 72 unoperated patients . Medicine (Baltimore) 2000 ; 79 : 27 – 36 . Google Scholar CrossRef Search ADS PubMed 5 Brown ML , Dearani JA , Danielson GK , Cetta F , Connolly HM , Warnes CA , Li Z , Hodge DO , Driscoll DJ ; Mayo Clinic Congenital Heart Center . The outcomes of operations for 539 patients with Ebstein anomaly . J Thorac Cardiovasc Surg 2008 ; 135 : 1120 – 1136 . Google Scholar CrossRef Search ADS PubMed 6 Celermajer DS , Bull C , Till JA , Cullen S , Vassillikos VP , Sullivan ID , Allan L , Nihoyannopoulos P , Somerville J , Deanfield JE. Ebstein’s anomaly: presentation and outcome from fetus to adult . J Am Coll Cardiol 1994 ; 23 : 170 – 176 . Google Scholar CrossRef Search ADS PubMed 7 Brown ML , Dearani JA , Danielson GK , Cetta F , Connolly HM , Warnes CA , Li Z , Hodge DO , Driscoll DJ. Effect of operation for Ebstein anomaly on left ventricular function . Am J Cardiol 2008 ; 102 : 1724 – 1727 . Google Scholar CrossRef Search ADS PubMed 8 Hassan A , Tan NY , Aung H , Connolly HM , Hodge DO , Vargas ER , Cannon BC , Packer DL , Asirvatham SJ , McLeod CJ. Outcomes of atrial arrhythmia radiofrequency catheter ablation in patients with Ebstein’s anomaly . Europace 2018 ; 20 : 535 – 540 . Google Scholar CrossRef Search ADS PubMed 9 Rydman R , Shiina Y , Diller GP , Niwa K , Li W , Uemura H , Uebing A , Barbero U , Bouzas B , Ernst S , Wong T , Pennell DJ , Gatzoulis MA , Babu-Narayan SV. Major adverse events and atrial tachycardia in Ebstein’s anomaly predicted by cardiovascular magnetic resonance . Heart 2018 ; 104 : 37 – 44 . Google Scholar CrossRef Search ADS PubMed 10 Shivapour JK , Sherwin ED , Alexander ME , Cecchin F , Mah DY , Triedman JK , Marx GR , del Nido PJ , Walsh EP. Utility of preoperative electrophysiologic studies in patients with Ebstein’s anomaly undergoing the Cone procedure . Heart Rhythm 2014 ; 11 : 182 – 186 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: firstname.lastname@example.org. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)
European Heart Journal – Oxford University Press
Published: Feb 6, 2018
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