Clinical Review & Education

JAMA Cardiology Clinical Guidelines Synopsis

Management of Ventricular Arrhythmias and Sudden Cardiac

Death Risk Associated With Cardiac Channelopathies
Sana M. Al-Khatib, MD, MHS; William G. Stevenson, MD

GUIDELINE TITLE 2017 American Heart Association
(AHA)/American College of Cardiology (ACC)/Heart Rhythm
Society (HRS) Guideline for Management of Patients With
Ventricular Arrhythmias and the Prevention of Sudden Cardiac
Death
DEVELOPERS AHA/ACC/HRS
RELEASE DATE October 30, 2017 (online)
PRIOR VERSION September 5, 2006
FUNDING SOURCE AHA/ACC/HRS
TARGET POPULATION Adults with ventricular arrhythmias (VA)
and/or at risk for sudden cardiac death (SCD)
MAJOR RECOMMENDATIONS This synopsis focuses on
recommendations on managing VA and SCD risk that is
associated with cardiac channelopathies. These
recommendations are supported by moderate-quality
evidence. All implantable cardioverter-defibrillator (ICD)
recommendations require that patients have meaningful
survival of greater than 1 year.
• In first-degree relatives of patients who have a causative
mutation for long QT syndrome, catecholaminergic polymor-
phic ventricular tachycardia, short QT syndrome, or Brugada
syndrome, genetic counseling and mutation-specific genetic
testing are recommended.
• In patients with a cardiac channelopathy and sudden cardiac
arrest, an ICD is recommended.
• In patients with long QT syndrome with a resting corrected
QT interval greater than 470 milliseconds, a β-blocker is rec-
ommended.
• In high-risk patients with symptomatic long QT syndrome in
whom a β-blocker is ineffective or not tolerated, an intensifi-
cation of therapy with additional medications (guided by
considering the particular long QT syndrome type), left car-
diac sympathetic denervation, and/or an ICD is recom-
mended.
• In patients with long QT syndrome and recurrent appropri-
ate ICD shocks despite receiving the maximum tolerated
doses of a β-blocker, an intensification of medical therapy
with additional medications (guided by considering the par-
ticular long QT syndrome type) or left cardiac sympathetic
denervation is recommended.
• In patients with clinically diagnosed long QT syndrome, ge-
netic counseling and genetic testing are recommended.
• In patients with suspected long QT syndrome, ambulatory
electrocardiographic monitoring, recording the electrocar-
diogram (ECG) lying down and immediately on standing,
and/or treadmill exercise testing can be useful for establish-
ing a diagnosis and monitoring the response to therapy.
• In asymptomatic patients with long QT syndrome and a rest-
ing corrected QT interval of less than 470 milliseconds, long-
term therapy with a β- blocker is reasonable.
• In patients with catecholaminergic polymorphic ventricular
tachycardia, a β-blocker is recommended.
• In patients with catecholaminergic polymorphic ventricular
tachycardia and recurrent sustained VT or syncope, while
the patient is receiving adequate or maximally tolerated
β-blocker, treatment intensification with either combination
medication therapy (eg, beta blocker, flecainide), left cardiac
sympathetic denervation, and/or an ICD is recommended.
• In patients with catecholaminergic polymorphic ventricular
tachycardia and clinical ventricular tachycardia (VT) or exer-
tional syncope, genetic counseling and genetic testing are
reasonable.
• In asymptomatic patients with only an inducible type 1 Bru-
gada electrocardiographic pattern, observation without
therapy is recommended.
• In patients with Brugada syndrome with a spontaneous type
1 Brugada electrocardiographic pattern and cardiac arrest,
sustained VA, or a recent history of syncope presumed to be
caused by VA, an ICD is recommended.
• In patients with Brugada syndrome who are experiencing
recurrent ICD shocks for polymorphic VT, an intensification
of therapy with quinidine or catheter ablation is recom-
mended.
• In patients with spontaneous type 1 Brugada electrocardio-
graphic pattern and symptomatic VA who either are not can-
didates for or decline to have an ICD implanted, quinidine or
catheter ablation is recommended.
• In patients with suspected Brugada syndrome in the absence
of a spontaneous type 1 Brugada electrocardiographic pat-
tern, a pharmacological challenge using a sodium channel
blocker can be useful for diagnosis.
• In asymptomatic patients with an early repolarization pat-
tern on ECG, observation without treatment is recom-
mended.
• In patients with early repolarization pattern on ECG results
and cardiac arrest or sustained VA, an ICD is recommended.

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 Clinical Review & Education JAMA Cardiology Clinical Guidelines Synopsis

Summary of the Clinical Problem
Although cardiac channelopathies account for only 3% of sudden
cardiac deaths (SCDs) that occur in young people, they have been
the focus of much research because of their traumatic effect on
families and society.1 Many ad-
vances have been made in the
Supplemental content diagnosis, risk stratification, and
treatment of these conditions
that have informed practices and formed the foundation of profes-
sional guidelines and statements.2,3 One such guideline is the Ameri-
can Heart Association (AHA)/American College of Cardiology (ACC)/
Heart Rhythm Society (HRS) Guideline for Management of Patients
With Ventricular Arrhythmias and the Prevention of Sudden Cardiac
Death, the focus of this synopsis.3 This guideline covered the follow-
ing cardiac channelopathies: long QT syndrome (LQTS), catechol-
aminergic polymorphic ventricular tachycardia (CPVT), Brugada
syndrome, early repolarization, and short QT syndrome.3
Characteristics of the Guideline Source
The guideline writing committee included 19 members: 12 adult elec-
trophysiologists, 1 pediatric electrophysiologist, 3 general cardiologists
(1 with expertise in heart failure), 1 pediatric cardiologist, 1 geriatrician
with expertise in shared decision making, and 1 patient/consumer rep-
resentative. Each recommendation in this guideline was assigned a
class of recommendation (COR) and a level of evidence (LOE).3 The
COR reflects the strength of the recommendation based on an assess-
ment of the estimated benefit vs the risk; a class I COR means the ben-
efit of an intervention far exceeds its risk, a class IIa means the ben-
efit of the intervention moderately exceeds the risk, a class IIb means
the benefit may not exceed the risk, and a class III means the benefit
is equivalent to or is exceeded by the risk. The LOE conveys the qual-
ity of the scientific evidence that supports the intervention. An LOE
A indicates that the evidence was derived from high-quality random-
ized clinical trials, B-R indicates that the evidence was derived from
moderate-quality randomized clinical trials, B-NR indicates that the
evidence was derived from well-designed nonrandomized studies,
C-LD indicates that the evidence was derived from randomized or non-
randomized studies with limitations of design or execution, and C-EO
indicates that the recommendation was based on expert opinion.3 The
chair and most of the guideline writing committee members had no
relevant relations with the industry.
Evidence Base
For treating patients with cardiac channelopathies, the recommen-
dations covered the roles of genetic counseling and genetic test-
ing, the importance of β-blocker therapy in patients with LQTS and
CPVT, the benefits of the ICD (especially for secondary prevention
of SCD), and the possible roles of catheter ablation and left cardiac
sympathetic denervation. The medical literature was reviewed
through March 2017. Studies had to involve human participants, be
published in English, and be indexed in MEDLINE (through PubMed),
EMBASE, the Cochrane Library, or the Agency for Healthcare Re-
search and Quality. Studies resulting from the literature search were
systematically reviewed.3
Of 28 recommendations involving treating patients with car-
diac channelopathies, 16 (57.1%) were class I, 6 (21.4%) were class
IIa, 4 (14.3%) were class IIb, and 3 (10.75%) were class III recom-
mendations. None of the recommendations had an LOE A or B-R.
All class I recommendations had an LOE B-NR and were based on
moderate-quality evidence. Four of the class IIa recommendations
had an LOE B-NR and 2 had an LOE C-LD.3
Benefits and Harms
The writing group carefully reviewed the benefits and risks of ge-
netic testing, genetic counseling, and every intervention. Recom-
mendations for treating patients with LQTS are shown in eFigure in
the Supplement.3
Discussion
Most recommendations on treating patients with cardiac channelo-
pathies were based on moderate-quality evidence.3 Higher-quality
evidence is needed on the role of genetic counseling and genetic test-
ing in facilitating the cascade screening of relatives of patients with
suspected or established Brugada syndrome.3
Areas in Need of Future Study or Ongoing Research
Many gaps in knowledge exist in relation to SCD prevention in pa-
tients with cardiac channelopathies that could benefit from future
research. Such research should focus on understanding the role of
the ICD in patients with inherited cardiac channelopathies. In that
regard, comparisons between transvenous and subcutaneous ICDs
are needed. Likewise, it is important to prospectively study the out-
comes of VT catheter ablation and left cardiac sympathetic dener-
vation in different patient populations. Risk stratification for SCD
should be enhanced in all cardiac channelopathies, especially Bru-
gada syndrome. Finally, the causes of different types of LQTS, CPVT,
and Brugada syndrome should be identified and the genotype-
phenotype associations and genotype-dependent risk should be
better understood to enable genotype-based tailoring of therapies
for patients with cardiac channelopathies.

ARTICLE INFORMATION
Author Affiliations: Division of Cardiology and
Duke Clinical Research Institute, Duke University
Hospital, Durham, North Carolina (Al-Khatib);
Cardiovascular Division, Vanderbilt University
Medical Center, Nashville, Tennessee (Stevenson).
Corresponding Author: Sana M. Al-Khatib, MD,
MHS, Department of Medicine, Duke Clinical
Research Institute, Duke Health, 2400 Pratt St,
Durham, NC 27705 (sana.alkhatib@duke.edu).
Published Online: June 27, 2018.
doi:10.1001/jamacardio.2018.1116
Conflict of Interest Disclosures: Both authors
have completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest. Dr
Stevenson reports having received consulting fees
from St Jude Medical and speaking fees from
Boston Scientific. He is a coholder of a patent for
needle ablation that is consigned to Brigham
Hospital. No other disclosures were reported.
REFERENCES
1. Ackerman M, Atkins DL, Triedman JK. Sudden
cardiac death in the young. Circulation. 2016;133
(10):1006-1026.
2. Priori SG, Wilde AA, Horie M, et al.
HRS/EHRA/APHRS expert consensus statement on
the diagnosis and management of patients with
inherited primary arrhythmia syndromes:
document endorsed by HRS, EHRA, and APHRS in
May 2013 and by ACCF, AHA, PACES, and AEPC in
June 2013. Heart Rhythm. 2013;10(12):1932-1963.
3. Al-Khatib SM, Stevenson WG, Ackerman MJ,
et al. AHA/ACC/HRS guideline for management of
patients with ventricular arrhythmias and the
prevention of sudden cardiac death [published
online October 30, 2017]. Circulation. doi:10.1161
/CIR.0000000000000549

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