Upcoming guidelines on inherited arrhythmias contain surprises

DENVER – Major new guidelines on the diagnosis and management of patients with inherited primary arrhythmia syndromes have been jointly issued by the Heart Rhythm Society and its European and Asian counterparts.

The guidelines were sorely needed, according to Dr. Silvia G. Priori, cochair of the expert consensus panel writing group.

The field of inherited arrhythmias is rapidly evolving, with new pathogenic genetic mutations being found all the time. Much has changed in the 7 years since issuance of the last major guidelines: the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines on prevention of sudden cardiac death (Circulation 2006;114:e385-484), noted Dr. Priori of the University of Pavia (Italy).

Her cochair, Dr. Arthur A. Wilde of the University of Amsterdam pointed out that the new 69-page report is the first major document to address some of the newer inherited arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome, early repolarization, and progressive cardiac conduction disease (PCCD). In addition, the new report proposes major changes in the diagnostic criteria for the two most common primary arrhythmia syndromes: long QT syndrome (LQTS) and Brugada syndrome.

"Many of our colleagues in the field will be surprised," Dr. Priori predicted.

Here are the highlights:

• LQTS: With an estimated prevalence of roughly 1 per 2,000 live births worldwide, this is the most common of the inherited arrhythmia syndromes. What is likely to come as a surprise to many physicians is the expert consensus panel’s recommendation that the diagnosis of LQTS requires either the finding of an unequivocally causative mutation in one of the LQTS genes or, in the absence of such a defect, either a QTc interval of 480-499 ms in repeated 12-lead ECGs in a patient with unexplained syncope or a QTc of 500 ms in repeated ECGs in the absence of a secondary cause for QT prolongation in a nonsyncopal patient.

"A single ECG reading 10 ms above the upper limit of normal is not enough to establish the diagnosis. That’s quite different from what’s being done in common practice. Many of the patients who are referred to the centers of expertise on inherited arrhythmias are borderline patients in whom maybe one ECG was abnormal, and yet because of that they’ve been labeled as being affected by a genetic disease even if the genetic studies were negative. A single abnormal QTc measurement in a patient with negative genetic testing is not enough," Dr. Priori declared.

Dr. Wilde said the new guidelines loosen up the guidance on participation in competitive sports. The blanket prohibition of the past has been replaced by a case-by-case approach, with a Class I recommendation for routine referral to a clinical expert for evaluation of the risk posed by athletic activity. For example, although swimming is a very-high-risk activity for patients with the LQTS1 genotype, that’s not true for those who have LQTS2 or -3.

"It’s clear that if a patient with long QT syndrome has exercise-related syncopal events, that patient should not participate in competitive sports. But if the patient is asymptomatic and has minor QT prolongation, there’s probably not much reason for concern," he said.

"This is a sharp departure," Dr. Priori observed. "In several European countries, if you have the diagnosis of long QT syndrome, sports participation is not permitted, even if your physician clears you. So we hope with this document to slowly, carefully, begin to allow patients with this condition to do sports safely. We wanted to lift the ban so that a physician who feels a specific patient would have a low risk in the proper environment could make that recommendation."

• Brugada syndrome: Far more common in Asia than the western world, Brugada syndrome is 8- to 10-fold more frequent in males than females. The big change in the new guidelines is that the diagnosis no longer requires specific ECG changes plus clinical manifestations. Now, Brugada syndrome, like LQTS, is a pure ECG diagnosis. It is made definitively when a type 1 ST-segment elevation is noted either spontaneously or after administration of an intravenous sodium channel-blocking agent; the ST finding has to be observed in at least one right precordial lead placed in a standard or superior position up to the second intercostal space.

An implantable cardioverter-defibrillator is clearly indicated in a Brugada syndrome patient with a prior cardiac arrest or documented ventricular arrhythmias. The controversy lies in how to manage the asymptomatic patient. The guidelines give ICD implantation a weak Class IIb recommendation – meaning it "may be considered" – when such patients exhibit inducible ventricular arrhythmias during programmed electrical stimulation in the electrophysiology lab.

• Catecholaminergic polymorphic ventricular tachycardia: The prevalence of CPVT is unclear, but it has been estimated at 1 per 5,000 live births, according to Dr. Wilde. This highly malignant condition is diagnosed in patients with a known pathogenic mutation, or in the presence of a structurally normal heart, a normal resting ECG, and unexplained exercise- or catecholamine-induced bidirectional VT of polymorphic ventricular premature beats or VT before age 40 years. First-line therapy is a long-acting beta-blocker such as nadolol, coupled with exercise restriction. ICD therapy is problematic because the inevitable inappropriate shocks increase sympathetic tone, triggering true shockable arrhythmias in a vicious cycle.

• Short QT syndrome: This is a rare channelopathy. It is diagnosed on the basis of a QTc of 330 ms or less, or a QTc of less than 360 ms in the presence of a pathogenic mutation, family history of sudden death before age 40 years, cardiac arrest in the absence of structural heart disease, or a family history of short QT syndrome.

• Progressive cardiac conduction disease: Still incompletely understood, PCCD is diagnosed in individuals under age 50 years who have unexplained progressive conduction abnormalities and a structurally normal heart with no skeletal myopathies. Pacemaker implantation is the most useful therapy.

• Early repolarization: The first report linking this extremely common ECG finding to sudden death came less than 5 years ago. Early repolarization, as characterized by J-point and ST-segment elevation in two or more contiguous leads, is present in up to 10% of normal individuals. In preparticipation athletic screening programs, it can be found in up to 15%-20% of subjects.

"There’s no reason for concern if that’s the only thing you find. It’s something you shouldn’t even communicate if there is no other issue. If a patient with early repolarization has no symptoms and no family history of premature sudden death, just leave it," Dr. Wilde advised.

On the other hand, if a patient with the early repolarization ECG pattern in two or more contiguous inferior and/or lateral leads experiences exercise-induced syncopal symptoms, further evaluation is warranted. Given how common and generally benign the early repolarization ECG pattern is, the expert panel recommended a conservative approach to diagnosis, urging that the formal diagnosis of early repolarization syndrome be restricted largely to those with the characteristic ECG findings who in addition have been resuscitated from unexplained ventricular fibrillation or polymorphic VT.

Dr. Priori emphasized that the guidelines have as a Class I recommendation that patients with a diagnosed or suspected inherited arrhythmia syndrome that can result in sudden cardiac death – and their first-degree relatives, as well – should be evaluated in a specialized multidisciplinary inherited arrhythmia clinic. Such clinics are more common in Europe than the United States; however, thought leaders in American electrophysiology now recognize that the increasing complexity of the field requires that more of these dedicated clinics be created in the United States, she said.

The expert consensus statement was a joint project of the Heart Rhythm Society, the European Heart Rhythm Association, and the Asia Pacific Heart Rhythm Society. The document is available at the HRS website and will be published this fall in Heart Rhythm, EP Europace, and the Journal of Arrhythmias.

Dr. Priori reported serving as a consultant to Medtronic, Boston Scientific, Biotronic, and Transgenomic. Dr. Wilde disclosed serving as a consultant to Sorin.

bjancin@frontlinemedcom.com

DENVER – Major new guidelines on the diagnosis and management of patients with inherited primary arrhythmia syndromes have been jointly issued by the Heart Rhythm Society and its European and Asian counterparts.

The guidelines were sorely needed, according to Dr. Silvia G. Priori, cochair of the expert consensus panel writing group.

The field of inherited arrhythmias is rapidly evolving, with new pathogenic genetic mutations being found all the time. Much has changed in the 7 years since issuance of the last major guidelines: the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines on prevention of sudden cardiac death (Circulation 2006;114:e385-484), noted Dr. Priori of the University of Pavia (Italy).

Her cochair, Dr. Arthur A. Wilde of the University of Amsterdam pointed out that the new 69-page report is the first major document to address some of the newer inherited arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome, early repolarization, and progressive cardiac conduction disease (PCCD). In addition, the new report proposes major changes in the diagnostic criteria for the two most common primary arrhythmia syndromes: long QT syndrome (LQTS) and Brugada syndrome.

"Many of our colleagues in the field will be surprised," Dr. Priori predicted.

Here are the highlights:

• LQTS: With an estimated prevalence of roughly 1 per 2,000 live births worldwide, this is the most common of the inherited arrhythmia syndromes. What is likely to come as a surprise to many physicians is the expert consensus panel’s recommendation that the diagnosis of LQTS requires either the finding of an unequivocally causative mutation in one of the LQTS genes or, in the absence of such a defect, either a QTc interval of 480-499 ms in repeated 12-lead ECGs in a patient with unexplained syncope or a QTc of 500 ms in repeated ECGs in the absence of a secondary cause for QT prolongation in a nonsyncopal patient.

"A single ECG reading 10 ms above the upper limit of normal is not enough to establish the diagnosis. That’s quite different from what’s being done in common practice. Many of the patients who are referred to the centers of expertise on inherited arrhythmias are borderline patients in whom maybe one ECG was abnormal, and yet because of that they’ve been labeled as being affected by a genetic disease even if the genetic studies were negative. A single abnormal QTc measurement in a patient with negative genetic testing is not enough," Dr. Priori declared.

Dr. Wilde said the new guidelines loosen up the guidance on participation in competitive sports. The blanket prohibition of the past has been replaced by a case-by-case approach, with a Class I recommendation for routine referral to a clinical expert for evaluation of the risk posed by athletic activity. For example, although swimming is a very-high-risk activity for patients with the LQTS1 genotype, that’s not true for those who have LQTS2 or -3.

"It’s clear that if a patient with long QT syndrome has exercise-related syncopal events, that patient should not participate in competitive sports. But if the patient is asymptomatic and has minor QT prolongation, there’s probably not much reason for concern," he said.

"This is a sharp departure," Dr. Priori observed. "In several European countries, if you have the diagnosis of long QT syndrome, sports participation is not permitted, even if your physician clears you. So we hope with this document to slowly, carefully, begin to allow patients with this condition to do sports safely. We wanted to lift the ban so that a physician who feels a specific patient would have a low risk in the proper environment could make that recommendation."

• Brugada syndrome: Far more common in Asia than the western world, Brugada syndrome is 8- to 10-fold more frequent in males than females. The big change in the new guidelines is that the diagnosis no longer requires specific ECG changes plus clinical manifestations. Now, Brugada syndrome, like LQTS, is a pure ECG diagnosis. It is made definitively when a type 1 ST-segment elevation is noted either spontaneously or after administration of an intravenous sodium channel-blocking agent; the ST finding has to be observed in at least one right precordial lead placed in a standard or superior position up to the second intercostal space.

An implantable cardioverter-defibrillator is clearly indicated in a Brugada syndrome patient with a prior cardiac arrest or documented ventricular arrhythmias. The controversy lies in how to manage the asymptomatic patient. The guidelines give ICD implantation a weak Class IIb recommendation – meaning it "may be considered" – when such patients exhibit inducible ventricular arrhythmias during programmed electrical stimulation in the electrophysiology lab.

• Catecholaminergic polymorphic ventricular tachycardia: The prevalence of CPVT is unclear, but it has been estimated at 1 per 5,000 live births, according to Dr. Wilde. This highly malignant condition is diagnosed in patients with a known pathogenic mutation, or in the presence of a structurally normal heart, a normal resting ECG, and unexplained exercise- or catecholamine-induced bidirectional VT of polymorphic ventricular premature beats or VT before age 40 years. First-line therapy is a long-acting beta-blocker such as nadolol, coupled with exercise restriction. ICD therapy is problematic because the inevitable inappropriate shocks increase sympathetic tone, triggering true shockable arrhythmias in a vicious cycle.

• Short QT syndrome: This is a rare channelopathy. It is diagnosed on the basis of a QTc of 330 ms or less, or a QTc of less than 360 ms in the presence of a pathogenic mutation, family history of sudden death before age 40 years, cardiac arrest in the absence of structural heart disease, or a family history of short QT syndrome.

• Progressive cardiac conduction disease: Still incompletely understood, PCCD is diagnosed in individuals under age 50 years who have unexplained progressive conduction abnormalities and a structurally normal heart with no skeletal myopathies. Pacemaker implantation is the most useful therapy.

• Early repolarization: The first report linking this extremely common ECG finding to sudden death came less than 5 years ago. Early repolarization, as characterized by J-point and ST-segment elevation in two or more contiguous leads, is present in up to 10% of normal individuals. In preparticipation athletic screening programs, it can be found in up to 15%-20% of subjects.

"There’s no reason for concern if that’s the only thing you find. It’s something you shouldn’t even communicate if there is no other issue. If a patient with early repolarization has no symptoms and no family history of premature sudden death, just leave it," Dr. Wilde advised.

On the other hand, if a patient with the early repolarization ECG pattern in two or more contiguous inferior and/or lateral leads experiences exercise-induced syncopal symptoms, further evaluation is warranted. Given how common and generally benign the early repolarization ECG pattern is, the expert panel recommended a conservative approach to diagnosis, urging that the formal diagnosis of early repolarization syndrome be restricted largely to those with the characteristic ECG findings who in addition have been resuscitated from unexplained ventricular fibrillation or polymorphic VT.

Dr. Priori emphasized that the guidelines have as a Class I recommendation that patients with a diagnosed or suspected inherited arrhythmia syndrome that can result in sudden cardiac death – and their first-degree relatives, as well – should be evaluated in a specialized multidisciplinary inherited arrhythmia clinic. Such clinics are more common in Europe than the United States; however, thought leaders in American electrophysiology now recognize that the increasing complexity of the field requires that more of these dedicated clinics be created in the United States, she said.

The expert consensus statement was a joint project of the Heart Rhythm Society, the European Heart Rhythm Association, and the Asia Pacific Heart Rhythm Society. The document is available at the HRS website and will be published this fall in Heart Rhythm, EP Europace, and the Journal of Arrhythmias.

Dr. Priori reported serving as a consultant to Medtronic, Boston Scientific, Biotronic, and Transgenomic. Dr. Wilde disclosed serving as a consultant to Sorin.

bjancin@frontlinemedcom.com

DENVER – Major new guidelines on the diagnosis and management of patients with inherited primary arrhythmia syndromes have been jointly issued by the Heart Rhythm Society and its European and Asian counterparts.

The guidelines were sorely needed, according to Dr. Silvia G. Priori, cochair of the expert consensus panel writing group.

The field of inherited arrhythmias is rapidly evolving, with new pathogenic genetic mutations being found all the time. Much has changed in the 7 years since issuance of the last major guidelines: the American College of Cardiology/American Heart Association/European Society of Cardiology guidelines on prevention of sudden cardiac death (Circulation 2006;114:e385-484), noted Dr. Priori of the University of Pavia (Italy).

Her cochair, Dr. Arthur A. Wilde of the University of Amsterdam pointed out that the new 69-page report is the first major document to address some of the newer inherited arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome, early repolarization, and progressive cardiac conduction disease (PCCD). In addition, the new report proposes major changes in the diagnostic criteria for the two most common primary arrhythmia syndromes: long QT syndrome (LQTS) and Brugada syndrome.

"Many of our colleagues in the field will be surprised," Dr. Priori predicted.

Here are the highlights:

• LQTS: With an estimated prevalence of roughly 1 per 2,000 live births worldwide, this is the most common of the inherited arrhythmia syndromes. What is likely to come as a surprise to many physicians is the expert consensus panel’s recommendation that the diagnosis of LQTS requires either the finding of an unequivocally causative mutation in one of the LQTS genes or, in the absence of such a defect, either a QTc interval of 480-499 ms in repeated 12-lead ECGs in a patient with unexplained syncope or a QTc of 500 ms in repeated ECGs in the absence of a secondary cause for QT prolongation in a nonsyncopal patient.

"A single ECG reading 10 ms above the upper limit of normal is not enough to establish the diagnosis. That’s quite different from what’s being done in common practice. Many of the patients who are referred to the centers of expertise on inherited arrhythmias are borderline patients in whom maybe one ECG was abnormal, and yet because of that they’ve been labeled as being affected by a genetic disease even if the genetic studies were negative. A single abnormal QTc measurement in a patient with negative genetic testing is not enough," Dr. Priori declared.

Dr. Wilde said the new guidelines loosen up the guidance on participation in competitive sports. The blanket prohibition of the past has been replaced by a case-by-case approach, with a Class I recommendation for routine referral to a clinical expert for evaluation of the risk posed by athletic activity. For example, although swimming is a very-high-risk activity for patients with the LQTS1 genotype, that’s not true for those who have LQTS2 or -3.

"It’s clear that if a patient with long QT syndrome has exercise-related syncopal events, that patient should not participate in competitive sports. But if the patient is asymptomatic and has minor QT prolongation, there’s probably not much reason for concern," he said.

"This is a sharp departure," Dr. Priori observed. "In several European countries, if you have the diagnosis of long QT syndrome, sports participation is not permitted, even if your physician clears you. So we hope with this document to slowly, carefully, begin to allow patients with this condition to do sports safely. We wanted to lift the ban so that a physician who feels a specific patient would have a low risk in the proper environment could make that recommendation."

• Brugada syndrome: Far more common in Asia than the western world, Brugada syndrome is 8- to 10-fold more frequent in males than females. The big change in the new guidelines is that the diagnosis no longer requires specific ECG changes plus clinical manifestations. Now, Brugada syndrome, like LQTS, is a pure ECG diagnosis. It is made definitively when a type 1 ST-segment elevation is noted either spontaneously or after administration of an intravenous sodium channel-blocking agent; the ST finding has to be observed in at least one right precordial lead placed in a standard or superior position up to the second intercostal space.

An implantable cardioverter-defibrillator is clearly indicated in a Brugada syndrome patient with a prior cardiac arrest or documented ventricular arrhythmias. The controversy lies in how to manage the asymptomatic patient. The guidelines give ICD implantation a weak Class IIb recommendation – meaning it "may be considered" – when such patients exhibit inducible ventricular arrhythmias during programmed electrical stimulation in the electrophysiology lab.

• Catecholaminergic polymorphic ventricular tachycardia: The prevalence of CPVT is unclear, but it has been estimated at 1 per 5,000 live births, according to Dr. Wilde. This highly malignant condition is diagnosed in patients with a known pathogenic mutation, or in the presence of a structurally normal heart, a normal resting ECG, and unexplained exercise- or catecholamine-induced bidirectional VT of polymorphic ventricular premature beats or VT before age 40 years. First-line therapy is a long-acting beta-blocker such as nadolol, coupled with exercise restriction. ICD therapy is problematic because the inevitable inappropriate shocks increase sympathetic tone, triggering true shockable arrhythmias in a vicious cycle.

• Short QT syndrome: This is a rare channelopathy. It is diagnosed on the basis of a QTc of 330 ms or less, or a QTc of less than 360 ms in the presence of a pathogenic mutation, family history of sudden death before age 40 years, cardiac arrest in the absence of structural heart disease, or a family history of short QT syndrome.

• Progressive cardiac conduction disease: Still incompletely understood, PCCD is diagnosed in individuals under age 50 years who have unexplained progressive conduction abnormalities and a structurally normal heart with no skeletal myopathies. Pacemaker implantation is the most useful therapy.

• Early repolarization: The first report linking this extremely common ECG finding to sudden death came less than 5 years ago. Early repolarization, as characterized by J-point and ST-segment elevation in two or more contiguous leads, is present in up to 10% of normal individuals. In preparticipation athletic screening programs, it can be found in up to 15%-20% of subjects.

"There’s no reason for concern if that’s the only thing you find. It’s something you shouldn’t even communicate if there is no other issue. If a patient with early repolarization has no symptoms and no family history of premature sudden death, just leave it," Dr. Wilde advised.

On the other hand, if a patient with the early repolarization ECG pattern in two or more contiguous inferior and/or lateral leads experiences exercise-induced syncopal symptoms, further evaluation is warranted. Given how common and generally benign the early repolarization ECG pattern is, the expert panel recommended a conservative approach to diagnosis, urging that the formal diagnosis of early repolarization syndrome be restricted largely to those with the characteristic ECG findings who in addition have been resuscitated from unexplained ventricular fibrillation or polymorphic VT.

Dr. Priori emphasized that the guidelines have as a Class I recommendation that patients with a diagnosed or suspected inherited arrhythmia syndrome that can result in sudden cardiac death – and their first-degree relatives, as well – should be evaluated in a specialized multidisciplinary inherited arrhythmia clinic. Such clinics are more common in Europe than the United States; however, thought leaders in American electrophysiology now recognize that the increasing complexity of the field requires that more of these dedicated clinics be created in the United States, she said.

The expert consensus statement was a joint project of the Heart Rhythm Society, the European Heart Rhythm Association, and the Asia Pacific Heart Rhythm Society. The document is available at the HRS website and will be published this fall in Heart Rhythm, EP Europace, and the Journal of Arrhythmias.

Dr. Priori reported serving as a consultant to Medtronic, Boston Scientific, Biotronic, and Transgenomic. Dr. Wilde disclosed serving as a consultant to Sorin.

bjancin@frontlinemedcom.com