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Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations
LETTERS TO THE EDITOR To the Editor—Early Repolarization ECG Pattern in Patients with ARVC: Normal Variant? We read with interest the study entitled “Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations” by Bauce et al1 in the November 2011 issue of HeartRhythm. The ECG displayed in their Figure 1 shows early repolarization (ER) and “J waves” in the inferior leads, but whether this ECG should be considered normal, as the authors remark, is arguable. Moreover, “J waves” are not specifically pointed out as one of the “ECG [electrocardiogram] features” in their Table 2, although an “RV conduction delay” is mentioned. At present, there is considerable controversy whether “J waves” represent a marker for an increased risk of sudden death. Recently, a large study evaluating resting ambulatory ECG found no significant association between any component of ER and cardiac mortality.2 Nevertheless, it is worth mentioning that not all patterns of ER are necessarily the same.3 Accordingly, it has been questioned whether J-point elevation with slurring or notching seen independently from ST elevation is, in fact, delayed activation in the inferolateral left ventricular wall.4 Additionally, different ECG patterns of ER have been categorized: a benign form, with a rapidly ascending ST segment; and a malignant form, with a horizontal/descending ST-segment morphology.2 The latter pattern has been postulated to reflect an abnormal depolarization, possibly due to structural heart disease, which could be a plausible explanation for the abnormal changes seen in the mentioned ECG. On the other hand, arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) as well as the Brugada syndrome (BS) are characterized by arrhythmias originating in the right ventricle.5 In BS, an inferior–lateral ER pattern has also been reported and, importantly, was associated with a more severe phenotype.6 Whether this is the case in ARVC is still unknown, and further studies are needed in order to clarify the significance of ER in patients with structural heart disease, including ARVC. Hence, we believe there is a need to better characterize the ECG patterns, and, although it does not represent a criterion for diagnosis of ARVC by itself, this ECG alteration should not be considered a normal variant in this entity at this time. We again would like to congratulate the authors for this interesting study. We hope the point we raised helps in further understanding the whole spectrum of this important condition. Moisés Rodríguez-Mañero, MD [email protected] Andrea Sarkozy, MD, PhD
Mehdi Namdar, MD Jayakeerthi Y. Rao, MD Pedro Brugada, MD, PhD Heart Rhythm Management Centre UZB Brussels, Belgium
References 1.
2.
3. 4. 5.
6.
Bauce B, Rampazzo A, Basso C, et al. Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations. Heart Rhythm 2011;8:1686 –1695. Tikkanen JT, Junttila MJ, Anttonen O, et al. Early repolarization: electrocardiographic phenotypes associated with favorable long-term outcome. Circulation 2011;123:2666 –2673. Bastiaenen R, Behr ER. Benign or malignant, early or delayed: the changing face of early repolarization. Europace 2012;14:5–7. Wellens HJ. Early repolarization revisited. N Engl J Med 2008;358:2063–2065. Yodogawa K, Morita N, Kobayashi Y, et al. A new approach for the comparison of conduction abnormality between arrhythmogenic right ventricular cardiomyopathy/dysplasia and Brugada syndrome. Ann Noninvasive Electrocardiol 2011; 16:263–269. Sarkozy A, Chierchia GB, Paparella G, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009:2:154 –161.
Reply to the Editor— Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations We thank Dr. Rodríguez-Mañero et al for their interest in our article.1 They argue that the ECG of our Figure 1 should not be considered normal because of the presence of signs of early repolarization (ER) in the inferior leads. ER has traditionally been regarded as an idiopathic and benign ECG phenomenon, with an estimated prevalence in healthy young individuals of 1% to 2%, and a clear male preponderance.2 The ER pattern is the rule rather than the exception among highly trained athletes, in whom the pattern is observed in 50% to 80% of resting ECGs. The ER repolarization ECG shows elevation of the QRS–ST junction (J point) of at least 0.1 mV from baseline, associated with notching or slurring of the terminal QRS complex that may vary in degree, morphology, and location.3 ER recently has gained renewed interest because of its possible association with idiopathic ventricular fibrillation and thus is considered a potential marker of arrhythmic risk.4 It has been advanced that a malignant variant of ER may share electrogenetic and arrhythmogenic mechanisms with Brugada syndrome, both conditions being included among the so-called “J-wave syndromes.”5 Of note, in patients with Brugada syndrome, the presence of inferior–lateral slurring of terminal QRS (inferolateral “J waves”) has been demonstrated to be associated with a more severe phenotype.6 The ECG in Figure 1 of our article was recorded from a 10-year-old asymptomatic family member (desmoplakin gene mutation carrier) and shows a mild slurring of the
1547-5271/$ -see front matter © 2012 Heart Rhythm Society. All rights reserved.
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Heart Rhythm, Vol 9, No 5, May 2012
terminal portion of QRS in D3 and a notched aspect in aVF. The available data do not support the view that in the general population of asymptomatic young individuals or healthy gene carriers, such an ECG pattern is predictive of an increased risk of malignant ventricular arrhythmias. Until further prospective studies on the clinical significance and prognostic value of ER in a large population of asymptomatic young individuals are available, this ECG pattern still should be considered a physiological and benign ECG change that per se does not require alarm or further clinical evaluation. Barbara Bauce, MD, PhD [email protected] Domenico Corrado, MD, PhD Gaetano Thiene, MD Department of Cardiac, Thoracic and Vascular Sciences University of Padova Padova, Italy
a table with the characteristics of the perioperative matched cohort after multivariate analyses of the whole population. It also is of concern that the costs and the length of stay were not different between the two groups, although it is well known, as the authors says in the Introduction, that AF is associated with higher morbidity and health care costs. This could represent a residual unmeasured bias not identified in the study that could have been considered in the analyses. To overcome this scenario, it is recommended that the authors evaluate a tracer outcome that is certainly not influenced by statin use, which was already done in previous databank studies.4 If there are no differences in the group results, the possibility of unrecognized confounding is much lower. We do believe that statins have a crucial role in perioperative patients, especially in preventing cardiovascular complications after vascular surgeries.5 However, we need much more evidence to conclude that statins can influence postoperative AF. Gabriel A.L. Carmo, MD [email protected] Daniela Calderaro, PhD André C. Marques, PhD Pai C. Yu, PhD Danielle M. Gualandro, PhD Bruno Caramelli, PhD
References 1.
2.
3. 4. 5. 6.
Bauce B, Rampazzo A, Basso C, et al. Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations. Heart Rhythm 2011;8:1686 –1695. Brady WJ. Benign early repolarization: electrocardiographic manifestations and differentiation from other ST segment elevation syndromes. Am J Emerg Med 1998;16:592–597. Gussak I, Antzelevitch C. Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms. J Electrocardiol 2000;33:299 –309. Haïssaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016 –2023. Antzelevitch C, Yan GX J. J-wave syndromes: from cell to bedside. J Electrocardiol 2011;44:656 – 661. Sarkozy A, Chierchia GB, Paparella G, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009:2:154 –161.
To the Editor—Statins and Postoperative Atrial Fibrillation: A Long Way Ahead Bhave et al1 examined the effect of statin use and the incidence of postoperative atrial fibrillation (AF) in patients undergoing major noncardiac surgery. They concluded that these medications are associated with markedly reduced odds of developing clinically significant AF. However, several limitations preclude this conclusion. First, the authors used length of stay as a classification of high-risk surgery, which is not recognized by the current guidelines as a criterion for procedure stratification2 and was not validated in this or previous studies. Second, the time window considered for “statin use” was too narrow, excluding those patients who had used statins until the day before the procedure. Furthermore, drug discontinuation should have been included in the analysis because, as the authors state, it is a well-known risk factor for cardiovascular complications.3 To reduce the possibility of false-positive cases, the authors excluded intravenous beta-blocker from the outcome variable as well as digoxin, amiodarone, calcium channel blockers, and cardioversion in separate analyses. However, this was done in a bivariate fashion and not as multivariate. It would have been useful if the authors could have provided
Heart Institute (InCor)–University of Sao Paulo Medical School Sao Paulo, Brazil
References 1.
2.
3.
4.
5.
Bhave PD, Goldman LE, Vittinghoff E, Maselli JH, Auerbach A. Statin use and postoperative atrial fibrillation after major noncardiac surgery. Heart Rhythm 2012;9:163–169. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation 2007;116:e418 – e499. Schouten O, Hoeks SE, Welten GM, et al. Effect of statin withdrawal on frequency of cardiac events after vascular surgery. Am J Cardiol 2007;100:316 – 320. Wijeysundera DN, Beattie WS, Karkouti K, et al. Association of echocardiography before major elective non-cardiac surgery with postoperative survival and length of hospital stay: population based cohort study. Bmj 2011;342:d3695. Durazzo AES, Machado FS, Ikeoka DT, et al. Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vasc Surg 2004;39:967–975.
Reply to the Editor— Statin use and postoperative atrial fibrillation after major noncardiac surgery We thank Carmo et al for their interest in our work.1 Although we agree that we lacked data on prehospital use of statins, it seems unlikely that these drugs were started only in the hospital or afterward. We did define perioperative statin administration strictly because we believed that st-
Mehdi Namdar, MD Jayakeerthi Y. Rao, MD Pedro Brugada, MD, PhD Heart Rhythm Management Centre UZB Brussels, Belgium
References 1.
2.
3. 4. 5.
6.
Bauce B, Rampazzo A, Basso C, et al. Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations. Heart Rhythm 2011;8:1686 –1695. Tikkanen JT, Junttila MJ, Anttonen O, et al. Early repolarization: electrocardiographic phenotypes associated with favorable long-term outcome. Circulation 2011;123:2666 –2673. Bastiaenen R, Behr ER. Benign or malignant, early or delayed: the changing face of early repolarization. Europace 2012;14:5–7. Wellens HJ. Early repolarization revisited. N Engl J Med 2008;358:2063–2065. Yodogawa K, Morita N, Kobayashi Y, et al. A new approach for the comparison of conduction abnormality between arrhythmogenic right ventricular cardiomyopathy/dysplasia and Brugada syndrome. Ann Noninvasive Electrocardiol 2011; 16:263–269. Sarkozy A, Chierchia GB, Paparella G, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009:2:154 –161.
Reply to the Editor— Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations We thank Dr. Rodríguez-Mañero et al for their interest in our article.1 They argue that the ECG of our Figure 1 should not be considered normal because of the presence of signs of early repolarization (ER) in the inferior leads. ER has traditionally been regarded as an idiopathic and benign ECG phenomenon, with an estimated prevalence in healthy young individuals of 1% to 2%, and a clear male preponderance.2 The ER pattern is the rule rather than the exception among highly trained athletes, in whom the pattern is observed in 50% to 80% of resting ECGs. The ER repolarization ECG shows elevation of the QRS–ST junction (J point) of at least 0.1 mV from baseline, associated with notching or slurring of the terminal QRS complex that may vary in degree, morphology, and location.3 ER recently has gained renewed interest because of its possible association with idiopathic ventricular fibrillation and thus is considered a potential marker of arrhythmic risk.4 It has been advanced that a malignant variant of ER may share electrogenetic and arrhythmogenic mechanisms with Brugada syndrome, both conditions being included among the so-called “J-wave syndromes.”5 Of note, in patients with Brugada syndrome, the presence of inferior–lateral slurring of terminal QRS (inferolateral “J waves”) has been demonstrated to be associated with a more severe phenotype.6 The ECG in Figure 1 of our article was recorded from a 10-year-old asymptomatic family member (desmoplakin gene mutation carrier) and shows a mild slurring of the
1547-5271/$ -see front matter © 2012 Heart Rhythm Society. All rights reserved.
e12
Heart Rhythm, Vol 9, No 5, May 2012
terminal portion of QRS in D3 and a notched aspect in aVF. The available data do not support the view that in the general population of asymptomatic young individuals or healthy gene carriers, such an ECG pattern is predictive of an increased risk of malignant ventricular arrhythmias. Until further prospective studies on the clinical significance and prognostic value of ER in a large population of asymptomatic young individuals are available, this ECG pattern still should be considered a physiological and benign ECG change that per se does not require alarm or further clinical evaluation. Barbara Bauce, MD, PhD [email protected] Domenico Corrado, MD, PhD Gaetano Thiene, MD Department of Cardiac, Thoracic and Vascular Sciences University of Padova Padova, Italy
a table with the characteristics of the perioperative matched cohort after multivariate analyses of the whole population. It also is of concern that the costs and the length of stay were not different between the two groups, although it is well known, as the authors says in the Introduction, that AF is associated with higher morbidity and health care costs. This could represent a residual unmeasured bias not identified in the study that could have been considered in the analyses. To overcome this scenario, it is recommended that the authors evaluate a tracer outcome that is certainly not influenced by statin use, which was already done in previous databank studies.4 If there are no differences in the group results, the possibility of unrecognized confounding is much lower. We do believe that statins have a crucial role in perioperative patients, especially in preventing cardiovascular complications after vascular surgeries.5 However, we need much more evidence to conclude that statins can influence postoperative AF. Gabriel A.L. Carmo, MD [email protected] Daniela Calderaro, PhD André C. Marques, PhD Pai C. Yu, PhD Danielle M. Gualandro, PhD Bruno Caramelli, PhD
References 1.
2.
3. 4. 5. 6.
Bauce B, Rampazzo A, Basso C, et al. Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations. Heart Rhythm 2011;8:1686 –1695. Brady WJ. Benign early repolarization: electrocardiographic manifestations and differentiation from other ST segment elevation syndromes. Am J Emerg Med 1998;16:592–597. Gussak I, Antzelevitch C. Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms. J Electrocardiol 2000;33:299 –309. Haïssaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016 –2023. Antzelevitch C, Yan GX J. J-wave syndromes: from cell to bedside. J Electrocardiol 2011;44:656 – 661. Sarkozy A, Chierchia GB, Paparella G, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009:2:154 –161.
To the Editor—Statins and Postoperative Atrial Fibrillation: A Long Way Ahead Bhave et al1 examined the effect of statin use and the incidence of postoperative atrial fibrillation (AF) in patients undergoing major noncardiac surgery. They concluded that these medications are associated with markedly reduced odds of developing clinically significant AF. However, several limitations preclude this conclusion. First, the authors used length of stay as a classification of high-risk surgery, which is not recognized by the current guidelines as a criterion for procedure stratification2 and was not validated in this or previous studies. Second, the time window considered for “statin use” was too narrow, excluding those patients who had used statins until the day before the procedure. Furthermore, drug discontinuation should have been included in the analysis because, as the authors state, it is a well-known risk factor for cardiovascular complications.3 To reduce the possibility of false-positive cases, the authors excluded intravenous beta-blocker from the outcome variable as well as digoxin, amiodarone, calcium channel blockers, and cardioversion in separate analyses. However, this was done in a bivariate fashion and not as multivariate. It would have been useful if the authors could have provided
Heart Institute (InCor)–University of Sao Paulo Medical School Sao Paulo, Brazil
References 1.
2.
3.
4.
5.
Bhave PD, Goldman LE, Vittinghoff E, Maselli JH, Auerbach A. Statin use and postoperative atrial fibrillation after major noncardiac surgery. Heart Rhythm 2012;9:163–169. Fleisher LA, Beckman JA, Brown KA, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation 2007;116:e418 – e499. Schouten O, Hoeks SE, Welten GM, et al. Effect of statin withdrawal on frequency of cardiac events after vascular surgery. Am J Cardiol 2007;100:316 – 320. Wijeysundera DN, Beattie WS, Karkouti K, et al. Association of echocardiography before major elective non-cardiac surgery with postoperative survival and length of hospital stay: population based cohort study. Bmj 2011;342:d3695. Durazzo AES, Machado FS, Ikeoka DT, et al. Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. J Vasc Surg 2004;39:967–975.
Reply to the Editor— Statin use and postoperative atrial fibrillation after major noncardiac surgery We thank Carmo et al for their interest in our work.1 Although we agree that we lacked data on prehospital use of statins, it seems unlikely that these drugs were started only in the hospital or afterward. We did define perioperative statin administration strictly because we believed that st-