Tetralogy of fallot is the most common cyanotic heart defect at birth. Surgical repair cannot cure these patients and life expectancy continues to be promised. Numerous researchers have been struggling to identify reliable risk predictors in ToF patients over the last decades.
Tetralogy of fallot is the most common cyanotic heart defect at birth. Surgical repair cannot cure these patients and life expectancy continues to be promised. Numerous researchers have been struggling to identify reliable risk predictors in ToF patients over the last decades.
Tetralogy of fallot is the most common cyanotic heart defect at birth. Surgical repair cannot cure these patients and life expectancy continues to be promised. Numerous researchers have been struggling to identify reliable risk predictors in ToF patients over the last decades.
journey from clinical parameters and surface ECG to in-depth assessment of myocardial mechanics, volume and pressure loading Stefan Orwat, Gerhard-Paul Diller This editorial refers to Contemporary Predictors of Death and Sustained Ventricular Tachycardia in Patients With Repaired Tetralogy of Fallot Enrolled in the INDICATOR Cohort by Valente et al. 1 CHALLENGE OF RISK STRATIFICATION Tetralogy of Fallot (ToF) is the most common cyanotic heart defect at birth. Major advances in cardiac surgery and paediatric cardiology now enable the vast majority of patients born with this condi- tion to survive to adulthood. However, surgical repair cannot cure these patients and life expectancy continues to be com- promised. Haemodynamically relevant pulmonary regurgitation (PR) is common and appears to have a major impact on long-term morbidity and mortality. It causes RV volume overload eventually associated with RV dysfunction and isin itselfassociated with life-threatening arrhythmias and sudden cardiac death. While timely pulmonary valve replace- ment may help to avoid some of the long- term complications associated with PR, 2 it appears that merely replacing the pulmon- ary valve is not sufcient to avoid sudden death in this young population. 3 As a con- sequence, numerous researchers have been struggling to identify reliable risk predic- tors in ToF patients over the last decades. This is not an easy undertaking: the het- erogeneity of the condition combined with the relatively low annual mortality rate requires large patient cohorts and considerable follow-up periods to ensure sufcient statistical power. In addition, not all patients die suddenly and information on the cause of death is not always available. Not surprisingly, the number of risk predictors remains there- fore limited (for an overview of studies, see table 1): the most prominent and widely used one is QRS prolongation on surface ECG. This risk factor is based on the seminal publication by Gatzoulis et al 4 1.5 decades ago, suggesting a strong asso- ciation between a QRS duration 180 ms and poor prognosis. While this association has been conrmed by other studies, it appears that improving surgical techni- ques and trends towards earlier repair may compromise the prognostic value of QRS duration or, at least, will shift the 180 ms cut-off to lower values in future. In addition, a broad QRS complexin isolationis insufcient to identify indi- vidual patients with annual event rates high enough to justify the primary prophylactic implantation of an implanta- ble cardioverter-debrillator (ICD). Subsequently, Khairy et al 5 have proposed a risk score based on clinical history, QRS duration, results of ventricular stimulation and invasive assessment of LV end- diastolic pressures. Uptake of this risk score has been mainly hampered by the fact that invasive pressure measurements and electrophysiological studies are not performed routinely for risk assessment in ToF patients. More recently, the prognos- tic value of LV dysfunction has been high- lighted. This is prima facie surprising as ToF mainly represents a right-sided heart condition. Nevertheless, ToF patients are affected by myocardial ischaemia before corrective surgery that may in part account for late LV dysfunction. 6 Furthermore, myocardial bres are shared between the ventricles and ventricular ventricular interaction 7 may also be responsible for LV dysfunction in patients with advanced RV volume overload and dysfunction. However, systolic LV dys- function assessed by measuring EF 8 lacks sensitivity in detecting early LV dysfunction and is not well suited to iden- tify ToF patients at risk of death or those likely to benet from ICD implantation. Recently, modern myocardial deformation parameters (such as strain on speckle tracking analysis) have been increasingly employed and preliminary studies investi- gating the utility of these methods for risk stratication in ToF patients are promis- ing. 9 Although further conrmation is required, these parameters seem to be more sensitive compared with EF in detecting myocardial damage and their prognostic values appear to be superior to that of conventional measures of ventricu- lar size and function. ROLE OF CMR Regarding risk stratication in ToF, until now, only small, single-centre cardiac MRI (CMR) studies, employing compos- ite end points (including symptomatic deterioration) have been available, not providing convincing results. Despite its prominent role in the evaluation of patients before pulmonary valve replace- ment, 10 CMR has therefore not gained a major role for risk stratication in ambu- latory ToF patients. This may change in the future. Valente et al present the results of a large multicentre effort combining the CMR expertise of four large adult congenital heart disease centres in North America and Europe. Using a well-dened study protocol, 11 the authors assembled CMR data on 873 ToF patients and inves- tigated the association between CMR parameters and outcome. This is an unusually large number of ToF patients using a clinically relevant, end point of death or sustained ventricular tachycardia (VT). The authors identied LVEF and RVEF, RV mass-to-volume ratio 0.3 g/mL and history of atrial tachyarrhythmia as outcome predictors on multivariate ana- lysis. Interestingly, VT was rare and con- rmed sudden cardiac death accounted for only approx. 14% of deaths. In contrast, over 50% of patients died due to unknown or non-cardiac reasons. This limitation should be considered when applying the results of the current study directly for risk stratication of sudden cardiac death in ToF patients. The study by Valente et al also highlights the limitations of using EF as a marker of ventricular dysfunction. Unlike in patients with acquired heart failure, even mildly reduced EF was associated with poor outcome in this study. Therefore, it appears that EF may be suboptimal in this setting and more sensitive markers of sub- clinical ventricular dysfunction are desired and should be increasingly investigated. Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany Correspondence to Dr Stefan Orwat, Division of Adult Congenital and Valvular Heart Disease, Department of Cardiovascular Medicine, University Hospital of Muenster, Albert-Schweitzer-Campus 1; A1, Muenster 48149, Germany; orwat@uni-muenster.de Orwat S, et al. Heart February 2014 Vol 100 No 3 185 Editorial group.bmj.com on September 2, 2014 - Published by heart.bmj.com Downloaded from RV PRESSURE OVERLOAD-NOT A BENIGN CONDITION? One interesting and novel aspect of the study is the reported association between elevated RV pressure or RV hypertrophy and worse outcome. The authors report that patients who died or experienced an episode of sustained VT had on average a RV outow tract (RVOT) gradient of 64 mm Hg and this gradient was signi- cantly higher compared with the remain- ing patients investigated with echocardiography. While the detrimental impact of PR on RV mechanics and risk of sudden death 12 has been highlighted, RV pressure load has received much less attention. As discussed by the authors, RV pressure and RV hypertrophy were related to each other, but provided independent prognostic information. Therefore, one could speculate that beyond the obvious effect of RV pressure overload on RV hypertrophy, alternative factors such as inadequate RVadaptation in the setting of PR may account for this nding. This interpretation is also supported by the fact that the correlation between RV pressures and mass was only modest overall. Although current guidelines suggest that interventions for RVOT obstruction should be considered even in asymptom- atic patients, the level of evidence is low (C) and the proposed RVOT pressure gra- dient necessitating intervention is rela- tively high. 13 Given the results presented by Valente et al, this recommendation may need to be reconsidered. This is espe- cially true in patients with a RVOT conduit who may be good candidates for a percutaneous valve implantation. In addition, the results of the current study raise the question whether accepting a certain degree of RVOT obstruction to avoid PR is indeed a desirable option, both at initial surgical repair and during catheter inventions later in life. Overall, the current paper by Valente et al will not solve the problem of accurate risk stratication in ToF patients but brings us one step closer to develop a compre- hensive risk score, now incorporating CMR data. In addition, the authors have to be commended, as this study also serves as a model for how multicentre efforts can help to overcome the natural limitations of efforts aiming to risk strat- ify adult congenital heart disease patients. Contributors SO and G-PD prepared the draft of the manuscript; both authors have revised the manuscript critically for important intellectual content and have provided nal approval of the manuscript. Competing interests None. Provenance and peer review Commissioned; internally peer reviewed. To cite Orwat S, Diller G-P. Heart 2014;100:185 187. Published Online First 29 November 2013 http://dx.doi.org/10.1136/heartjnl-2013-304958 Heart 2014;100:185187. doi:10.1136/heartjnl-2013-305011 REFERENCES 1 Valente AM, Gauvreau K, Assenza GE, et al. Contemporary predictors of death and sustained ventricular tachycardia in patients with repaired tetralogy of Fallot enrolled in the INDICATOR cohort. Heart 2014;100:24753. 2 Therrien J, Siu SC, Harris L, et al. Impact of pulmonary valve replacement on arrhythmia propensity late after repair of tetralogy of Fallot. Circulation 2001;103:248994. 3 Harrild DM, BERUL CI, Cecchin F, et al. Pulmonary valve replacement in tetralogy of Fallot impact on survival and ventricular tachycardia. Circulation 2009;119:44551. 4 Gatzoulis MA, Till JA, Somerville J, et al. Mechanoelectrical interaction in tetralogy of Fallot: QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death. Circulation 1995;92:2317. 5 Khairy P, Landzberg MJ, Gatzoulis MA, et al. Value of programmed ventricular stimulation after tetralogy of fallot repair. Circulation 2004:109:19942000s. 6 Hausdorf G, Hinrichs C, Nienaber CA, et al. Left ventricular contractile state after surgical correction of tetralogy of Fallot: risk factors for late left ventricular dysfunction. Pediatr Cardiol 1990;11:618. 7 Tzemos N, Harris L, Carasso S, et al. Adverse left ventricular mechanics in adults with repaired tetralogy of Fallot. Am J Cardiol 2009;103:4205. 8 Ghai A, Silversides C, Harris L, et al. Left ventricular dysfunction is a risk factor for sudden cardiac death in adults late after repair of tetralogy of Fallot. JAC 2002;40:167580. 9 Diller G-P, Kempny A, Liodakis E, et al. Left ventricular longitudinal function predicts life-threatening ventricular arrhythmia and death in adults with repaired tetralogy of fallot. Circulation 2012;125:24406. 10 Orwat S, Diller G-P, Baumgartner H. Imaging of congenital heart disease in adults: choice of modalities. Eur Heart J Cardiovasc Imaging 2013; (Epub ahead of print). doi:10.1093/ehjci/jet124 11 Valente AM, Gauvreau K, Assenza GE, et al. Rationale and design of an international multicenter registry of patients with repaired tetralogy of fallot to dene risk factors for late adverse outcomes: the INDICATOR cohort. Pediatr Cardiol 2012;34: 95104. 12 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;356:97581. 13 Baumgartner H, Bonhoeffer P, De Groot NMS, et al. ESC guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 2010;31:291557. Table 1 Overview of studies investigating predictors of death or clinically relevant ventricular arrhythmias in patients with repaired ToF Author Patients (n) Date of repair Parameters Katz et al 14 414 19671977 Older age at repair Presence of a Potts anastomosis Gatzoulis et al 4 178 19581979 QRS duration Nollert et al 15 490 19581977 Date of operation (<1970) Preoperative polycythaemia Use of RV outflow tract patch Berul et al 16 101 19801990 QRS duration Gatzoulis et al 12 793 NA QRS duration, QRS rate of change Older age at repair Pulmonary regurgitation (PR) Ghai et al 8 125 NA Moderate or severe PR QRS duration 180 ms Moderate or severe LV syst. dysfunction Khairy et al 5 252 19852001 Inducible sustained polymorphic VT Khairy et al 17 121 (selected patient population with ICD) NA Prior palliative shunt Inducible sustained polymorphic VT QRS duration 180 ms Ventriculotomy incision Non-sustained VT LVEDP 12 mm Hg Diller et al 9 413 NA QRS duration Right atrial area RV fractional area change LV longitudinal dysfunction Valente et al 1 873 NA RV hypertrophy RV and LV dysfunction Atrial tachyarrhythmias ICD, implantable cardioverter-defibrillator; LVEDP, LV end-diastolic pressure; ToF, Tetralogy of Fallot; VT, ventricular tachycardia. 186 Orwat S, et al. Heart February 2014 Vol 100 No 3 Editorial group.bmj.com on September 2, 2014 - Published by heart.bmj.com Downloaded from 14 Katz NM, Blackstone EH, Kirklin JW, et al. Late survival and symptoms after repair of tetralogy of Fallot. Circulation 1982;65:40310. 15 Nollert G, Fischlein T, Bouterwek S, et al. Long-term survival in patients with repair of tetralogy of Fallot: 36-year follow-up of 490 survivors of the rst year after surgical repair. JACC 1997;30: 137483. 16 Berul CI, Hill SL, Geggel RL, et al. Electrocardiographic markers of late sudden death risk in postoperative tetralogy of Fallot children. J Cardiovasc Electrophysiol 1997;8:134956. 17 Khairy P, Harris L, Landzberg MJ, et al. Implantable cardioverter-debrillators in tetralogy of Fallot. Circulation 2008;117:36370. Orwat S, et al. Heart February 2014 Vol 100 No 3 187 Editorial group.bmj.com on September 2, 2014 - Published by heart.bmj.com Downloaded from doi: 10.1136/heartjnl-2013-305011 2013 2014 100: 185-187 originally published online November 29, Heart
Stefan Orwat and Gerhard-Paul Diller
mechanics, volume and pressure loading
in-depth assessment of myocardial clinical parameters and surface ECG to Tetralogy of Fallot: the long journey from Risk stratification in adults with repaired http://heart.bmj.com/content/100/3/185.full.html Updated information and services can be found at: These include: References http://heart.bmj.com/content/100/3/185.full.html#ref-list-1 This article cites 16 articles, 9 of which can be accessed free at: service Email alerting the box at the top right corner of the online article. Receive free email alerts when new articles cite this article. Sign up in Collections Topic (100 articles) Right sided valvular heart disease (2666 articles) Interventional cardiology (649 articles) Congenital heart disease (3238 articles) Epidemiology (7884 articles) Drugs: cardiovascular system
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