![](media/image1.png){width="5.96875in" height="0.41944444444444445in"}

Top of Form

## Complete Summary

#### GUIDELINE TITLE

American College of Cardiology/European Society of Cardiology clinical
expert consensus document on hypertrophic cardiomyopathy. A report of
the American College of Cardiology Foundation Task Force on Clinical
Expert Consensus Documents and the European Society of Cardiology
Committee for Practice Guidelines.

#### BIBLIOGRAPHIC SOURCE(S)

Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman
CE, Shah PM, Spencer WH 3rd, Spirito P, Ten Cate FJ, Wigle ED, Vogel RA,
Abrams J, Bates ER, Brodie BR, Danias PG, Gregoratos G, Hlatky MA,
Hochman JS, et al. American College of Cardiology/European Society of
Cardiology Clinical Expert Consensus Document on Hypertrophic
Cardiomyopathy. A report of the American College of Cardiology
Foundation Task Force on Clinical Expert Consensus Documents. Eur Heart
J 2003 Nov;24(21):1965-91. \[273 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14585256)

#### GUIDELINE STATUS

This is the current release of the guideline.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [August 16, 2007, Coumadin
    (Warfarin)](http://www.fda.gov/medwatch/safety/2007/safety07.htm#Warfarin):
    Updates to the labeling for Coumadin to include pharmacogenomics
    information to explain that people\'s genetic makeup may influence
    how they respond to the drug.

-   [October 6, 2006, Coumadin (warfarin
    sodium)](http://www.fda.gov/medwatch/safety/2006/safety06.htm#Coumadin):
    Revisions to the labeling for Coumadin to include a new patient
    Medication Guide as well as a reorganization and highlighting of the
    current safety information to better inform providers and patients.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Hypertrophic cardiomyopathy

#### GUIDELINE CATEGORY

Management\
Treatment

#### CLINICAL SPECIALTY

Cardiology\
Family Practice\
Internal Medicine\
Medical Genetics\
Pediatrics

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

-   To provide a perspective on the current state of management of
    patients with hypertrophic cardiomyopathy

-   To clarify and place into perspective those clinical issues relevant
    to the rapidly evolving management for hypertrophic cardiomyopathy

-   To create a document that is not only current and pertinent but also
    has the potential to remain relevant for many years

#### TARGET POPULATION

Patients with or at high risk for hypertrophic cardiomyopathy

#### INTERVENTIONS AND PRACTICES CONSIDERED

1.  Beta-adrenergic blocking agents

    -   Propranolol; atenolol; metoprolol; nadolol; sotalol

    -   Dosage

    -   Monotherapy versus combination therapy

2.  Calcium antagonist

    -   Verapamil; diltiazem

    -   Dosage

    -   Monotherapy versus combination therapy

3.  Type I-A antiarrhythmic agent

    -   Disopyramide; procainamide; quinidine

    -   Dosage

    -   Monotherapy versus combination therapy

4.  Diuretics

5.  Phosphodiesterase inhibitors

6.  Surgical options

    -   Heart transplantation

    -   Ventricular septal myectomy

    -   Myectomy with aortotomy

    -   Mitral valve replacement

    -   Mitral valvuloplasty (plication)

7.  Dual-chamber pacing

8.  Percutaneous alcohol septal ablation

#### MAJOR OUTCOMES CONSIDERED

-   Disease progression

-   Morbidity and mortality

-   Survival rate

-   Quality of life

-   Risk of death due to heart failure and stroke

-   Risk for premature sudden and unexpected death

-   Risk for progressive symptoms

-   Risk for progression to advanced congestive heart failure (the
    \"end-stage phase\") with left ventricular remodeling and systolic
    dysfunction

-   Risk of complications attributable to atrial fibrillation, including
    embolic stroke.

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

Not stated

#### NUMBER OF SOURCE DOCUMENTS

428

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

**Levels of Evidence**

A.  The data were derived from multiple randomized clinical trials

B.  The data are based on a limited number of randomized trials,
    nonrandomized studies, or observational registries

C.  The primary basis for the recommendation was expert consensus

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

This clinical scientific statement represents the consensus of a panel
of experts appointed by the American College of Cardiology (ACC) and the
European Society of Cardiology (ESC). The writing group comprises
cardiovascular specialists and molecular biologists, each having
extensive experience with hypertrophic cardiomyopathy (HCM). The panel
focused largely on the management of this complex disease and derived
prudent, practical, and contemporary treatment strategies for the many
subgroups of patients comprising the broad HCM disease spectrum.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Class of Recommendation**

**Class I**: Conditions for which there is evidence for and/or general
agreement that the procedure or treatment is useful and effective.

**Class II**: Conditions for which there is conflicting evidence and/or
a divergence of opinion about the usefulness/efficacy of a procedure or
treatment.

**Class IIa**: Weight of evidence or opinion is in favor of the
procedure or treatment

**Class IIb**: Usefulness/efficacy is less well established by evidence
or opinion.

**Class III**: Conditions for which there is evidence and/or general
agreement that the procedure or treatment is not useful/effective and in
some cases may be harmful.

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The document was reviewed by 2 official reviewers nominated by the
American College of Cardiology Foundation (ACCF), 3 official reviewers
nominated by the European Society of Cardiology (ESC), 12 members of the
ACCF Clinical Electrophysiology Committee, and 4 additional content
reviewers nominated by the Writing Committee. The document was approved
for publication by the ACCF Board of Trustees in August 2003 and the
Board of ESC in July 2003.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The reader should refer to the original guideline document for
discussions of clinical diagnosis, obstruction to left ventricular
outflow, genetics and molecular diagnosis, and general considerations
for natural history and clinical course.

**[Symptoms and pharmacological management strategies]{.underline}**

A fundamental goal of treatment in hypertrophic cardiomyopathy (HCM) is
the alleviation of symptoms related to heart failure. Pharmacological
therapy has traditionally been the initial therapeutic approach for
relieving disabling symptoms of exertional dyspnea (with or without
associated chest pain) and improving exercise capacity for more than 35
years, since the introduction of beta-blockers in the mid-1960s. Also,
drugs are often the sole therapeutic option available to the many
patients *without* obstruction to left ventricular (LV) outflow, under
resting or provocable conditions, which constitute a substantial
proportion of the HCM population. Indeed, it is the convention to
empirically initiate pharmacologic therapy when symptoms of exercise
intolerance intervene, although there have been few randomized trials to
compare the effect of drugs in HCM.

Exertional dyspnea and disability (often associated chest pain),
dizziness, presyncope, and syncope usually occur in the presence of
preserved systolic function and a nondilated LV. Symptoms appear to be
caused in large measure by diastolic dysfunction with impaired filling
due to abnormal relaxation and increased chamber stiffness, leading in
turn to elevated left atrial and LV end-diastolic pressures (with
reduced stroke volume and cardiac output), pulmonary congestion, and
impaired exercise performance with reduced oxygen consumption at peak
exercise.

The pathophysiology of such symptoms, due to this form of diastolic
heart failure, may also be intertwined with other important
pathophysiologic mechanisms such as myocardial ischemia, outflow
obstruction associated with mitral regurgitation, and atrial
fibrillation (AF). Indeed, many patients may experience symptoms largely
from diastolic dysfunction or myocardial ischemia in the absence of
outflow obstruction (or severe hypertrophy). Other patients (i.e., those
with LV outflow obstruction) are more disabled by elevated LV pressures
and concomitant mitral regurgitation than by diastolic dysfunction, as
is evidenced by the often dramatic symptomatic benefit derived from
major therapeutic interventions that reduce or obliterate outflow
gradient (most frequently myectomy or alcohol ablation).

Chest pain in the absence of atherosclerotic coronary artery disease
(CAD) may be typical of angina pectoris or atypical in character. Most
chest discomfort is probably due by bursts of myocardial ischemia,
evidenced by the findings of scars at autopsy, fixed or reversible
myocardial perfusion defects and the suggestion of scarring by magnetic
resonance imaging, net lactate release during atrial pacing, and
impaired coronary vasodilator capacity. Myocardial ischemia is probably
a consequence of abnormal microvasculature, consisting of intramural
coronary arterioles with thickened walls (from medial hypertrophy) and
narrowed lumen, and/or a mismatch between the greatly increased LV mass
and coronary flow. Because typical anginal chest pain may be part of the
HCM symptom-complex, associated atherosclerotic CAD (which may
complicate clinical course) is often overlooked in these patients.
Therefore, coronary arteriography is indicated in patients with HCM and
persistent angina who are over 40 years of age or who have risk factors
for CAD, or when CAD is judged possible prior to any invasive treatment
for HCM such as septal myectomy (or alcohol septal ablation).

**Beta-adrenergic blocking agents**

Beta-blockers are negative inotropic drugs that have traditionally been
administered to HCM patients with or without obstruction, usually
relying on the patient\'s own subjective and historical perception of
benefit. However, judgments regarding treatment strategies in HCM with
beta-blockers are often difficult, taking into account the frequent
day-to-day variability in magnitude of symptoms. Treadmill or bicycle
exercise---with or without measurement of peak oxygen consumption---have
proved helpful in targeting patients for therapy or determining when
changes in dosage or drugs are appropriate. If limiting symptoms
progress, drug dosage may be increased within the accepted therapeutic
range. Patient responses to drugs are highly variable in terms of
magnitude and duration of benefit, and the selection of medications has
not achieved widespread standardization and has been dependent, in part,
on the experiences of individual practitioners, investigators, and
centers.

Propranolol was the first drug used in the medical management of HCM,
and long-acting preparations of propranolol or more cardioselective
agents such as atenolol, metoprolol, or nadolol have been employed more
recently. There are many reports of subjective symptomatic improvement
and enhanced exercise capacity in a dose range of up to 480 mg per day
for propranolol (2 mg/kg in children), both in patients with and without
outflow obstruction. Although some investigators have administered
massive doses of propranolol (up to 1,000 mg per day), claiming
symptomatic benefit and long-term survival without major side effects,
this is not generally accepted practice. However, even moderate doses of
beta-blockers may affect growth in young children or impair school
performance, or trigger depression in children and adolescents, and
should be closely monitored in such patients.

Substantial experience suggests that standard dosages of these drugs can
mitigate disabling symptoms and limit the latent outflow gradient
provoked during exercise when sympathetic tone is high and heart failure
symptoms occur. However, there is little evidence that beta-blocking
agents consistently reduce outflow obstruction under resting conditions.
Consequently, beta-blockers are a preferred drug treatment strategy for
symptomatic patients with outflow gradients present only with exertion.

The beneficial effects of beta-blockers on symptoms of exertional
dyspnea and exercise intolerance appear to be attributable largely to a
decrease in the heart rate with a consequent prolongation of diastole
and relaxation and an increase in passive ventricular filling. These
agents lessen LV contractility and myocardial oxygen demand and possibly
reduce microvascular myocardial ischemia. Potential side effects include
fatigue, impotence, sleep disturbances, and chronotropic incompetence.

**Verapamil**

In 1979, the calcium antagonist verapamil was introduced as another
negative inotropic agent for the treatment of HCM, and it has been
widely used empirically in both the nonobstructive and obstructive
forms, with a reported benefit for many patients, including those with a
component of chest pain. Verapamil in doses up to 480 mg per day
(usually in a sustained-release preparation) has favorable effects on
symptoms, probably by virtue of improving ventricular relaxation and
filling as well as relieving myocardial ischemia and decreasing LV
contractility. However, aside from the mild side effects of constipation
and hair loss, verapamil may also occasionally harbor a potential for
clinically important adverse consequences and has been reported to cause
death in a few HCM patients with severe disabling symptoms (orthopnea
and paroxysmal nocturnal dyspnea) and markedly elevated pulmonary
arterial pressure in combination with marked outflow obstruction.
Adverse hemodynamic effects of verapamil are presumably the result of
the vasodilating properties predominating over negative inotropic
effects, resulting in augmented outflow obstruction, pulmonary edema,
and cardiogenic shock. Because of these concerns, caution should be
exercised in administering verapamil to patients with resting outflow
obstruction and severe limiting symptoms. Some investigators discourage
the use of calcium antagonists in the management of obstructive HCM and
instead favor disopyramide (often with a beta-blocker) for such patients
with severe symptoms. Verapamil is not indicated in infants due to the
risk for sudden death that has been reported with intravenous
administration. Dosages of oral verapamil have not been established for
infants and preadolescent children.

Most clinicians favor using beta-blockers over verapamil for the initial
medical treatment of exertional dyspnea, although it does not appear to
be of crucial importance which drug is administered first. It has been
common practice, however, to administer verapamil to those patients who
do not experience a benefit from beta-blockers or who have a history of
asthma. Improvement with verapamil may be due to the primary actions of
the drug, and in some instances, partially attributable to withdrawal of
beta-blockers and the abolition of side effects that evolved insidiously
over time. At present, there is no evidence that combined medical
therapy with administration of beta-blockers and verapamil is more
advantageous than the use of either drug alone.

**Disopyramide**

The negative inotropic and Type I-A antiarrhythmic agent disopyramide
was introduced into the treatment regimen for patients with obstructive
HCM in 1982. There are reports of disopyramide producing symptomatic
benefit (at 300 mg to 600 mg per day with a dose-response effect) in
severely limited patients with resting obstruction, because of a
decrease in systolic anterior motion (SAM), outflow obstruction, and
mitral regurgitant volume. Anticholinergic side effects such as dry
mouth and eyes, constipation, indigestion, and difficulty in micturition
may be reduced by long-acting preparations through which cardioactive
benefits are more sustained. Because disopyramide may cause accelerated
atrioventricular (A-V) nodal conduction and thus increase ventricular
rate during AF, supplemental therapy with beta-blockers in low doses to
achieve normal resting heart rate has been advised.

Although disopyramide incorporates antiarrhythmic properties, there is
little evidence that proarrhythmic effects have intervened in HCM
patients. Nevertheless, this issue remains of some concern in a disease
associated with an arrhythmogenic LV substrate; prolongation of the QT
interval should be monitored while administering the drug. Furthermore,
disopyramide administration may be deleterious in nonobstructive HCM by
decreasing cardiac output, causing most investigators to limit its use
to patients with outflow obstruction who have not responded to
beta-blockers or verapamil.

At present, the information regarding drugs such as sotalol and other
calcium antagonists (such as diltiazem) is insufficient to recommend
their use in HCM. Diuretic agents may be added to the cardioactive drug
regimen prudently---preferably in the absence of marked outflow
obstruction. Because many patients have diastolic dysfunction and
require relatively high filling pressures to achieve adequate
ventricular filling, it may be advisable to administer diuretics
cautiously. Nifedipine, because of its particularly potent vasodilating
properties, may be deleterious, particularly for patients with outflow
obstruction. Combined therapy with disopyramide and amiodarone (or
disopyramide and sotalol), or quinidine and verapamil (or quinidine and
procainamide), should also be avoided due to concern over proarrhythmia;
also, administration of nitroglycerine, angiotensin-converting enzyme
(ACE) inhibitors or digitalis are generally contraindicated or
discouraged in the presence of resting or provocable outflow
obstruction. In patients with severe heart failure refractory to other
medications, caution is advised in administrating amiodarone in a high
dosage (greater than or equal to 400 mg per day). In patients with
erectile dysfunction, phosphodiesterase (PDE) inhibitors should be used
with the awareness that a mild afterload-reducing effect may be
deleterious in patients with resting or provocable obstruction.

**Drugs in end-stage phase**

A small but important subgroup of patients with nonobstructive HCM
develops systolic ventricular dysfunction and severe heart failure,
usually associated with LV remodeling demonstrable as wall thinning and
chamber enlargement. This particular evolution of HCM occurs in only
about 5% of patients and has been variously known as the \"end-stage,\"
\"burnt-out,\" or \"dilated\" phase. Drug treatment strategies in such
patients with systolic failure differ substantially from strategies in
HCM patients with typical left ventricular hypertrophy (LVH), nondilated
chambers, and preserved systolic function (i.e., involving conversion to
after load-reducing agents such as ACE inhibitors or angiotensin
II-receptor blockers or diuretics, digitalis, beta-blockers or
spironolactone). There is no evidence, however, that beta-blockers
prevent or convey a benefit to congestive heart failure and ventricular
systolic dysfunction of the \"end-of-stage\" (by contrast with the
experience in dilated cardiomyopathy and CAD). Ultimately, patients with
end-stage heart failure may become candidates for heart transplantation,
and they represent the primary subgroup within the broad disease
spectrum of HCM for when this treatment option is considered.

**[Asymptomatic patients]{.underline}**

Data from largely unselected cohorts and genotyping studies in families
suggest that most HCM patients, including many who are not even aware of
their disease, probably have no symptoms or only mild symptoms. While
most of the asymptomatic patients do not require treatment, some
represent therapeutic dilemmas because of their youthful age and the
consideration for prophylactic therapy to prevent sudden cardiac death
(SCD) or disease progression.

Prophylactic drug therapy in asymptomatic (or mildly symptomatic)
patients to prevent or delay development of symptoms and improve
prognosis has been the subject of debate for many years, but it remains
on an entirely empiric basis without controlled data to either support
or contradict its potential efficacy. This issue is unresolved due to
the relatively small patient populations previously available for study,
as well as the infrequency with which adverse end-points occur
prematurely in this disease. Additionally, there is a growing awareness
that an important proportion of HCM patients achieve normal life
expectancy. In general, treatments to delay or prevent progression of
the disease due to heart failure-related symptoms are most appropriately
directed toward relieving LV outflow tract obstruction and controlling
or abolishing AF through pharmacologic or intervention-based strategies.
Indeed, treatments targeted at aborting the disease progression are now
confined to those patients judged to be at high-risk for SCD (as
discussed under Risk Stratification and SCD). The efficacy of empiric,
prophylactic drug treatment with beta-blockers, verapamil, or
disopyramide for delaying the onset of symptoms and favorably altering
the clinical course or outcome in asymptomatic young patients with
particularly marked LV outflow tract gradients (about 75 mm Hg to 100 mm
Hg or more) is unresolved.

**Infective endocarditis prophylaxis**

In HCM there is a small risk for bacterial endocarditis, which appears
largely confined to those patients with LV outflow tract obstruction
under resting conditions or with intrinsic mitral valve disease. The
site of the valvular vegetation is usually the thickened anterior mitral
leaflet, although cases have been reported with lesions on the outflow
tract endocardial contact plaque (at the point of mitral-septal contact)
or on the aortic valve. Therefore, the American Heart Association (AHA)
recommendation should be applied to HCM patients with evidence of
outflow obstruction under resting or exercise conditions at the time of
dental or selected surgical procedures that create a risk for
blood-borne bacteremia.

**Pregnancy**

There is no evidence that patients with HCM are generally at increased
risk during pregnancy and delivery. Absolute maternal mortality is very
low (although possibly higher in patients with HCM than in the general
population) and appears to be confined principally to women with
high-risk clinical profiles. Such patients should be afforded highly
specialized preventive obstetrical care during pregnancy. Otherwise,
most pregnant HCM patients undergo normal vaginal delivery without the
necessity for cesarean section.

**[Treatment options for drug-refractory patients]{.underline}**

In some patients, medical therapy ultimately proves insufficient to
control symptoms, and the quality of life becomes unacceptable to the
patient. At this point in the clinical course, after a trial
administration of maximum drug treatment, the subsequent therapeutic
strategies are dictated largely by whether LV outflow obstruction is
present.

**Surgery**

Patients in a small but important subgroup comprising only about 5% of
all HCM patients in nonreferral settings (but up to 30% in tertiary
referral populations), are generally regarded as candidates for surgery.
These patients have particularly marked outflow gradients (peak
instantaneous usually greater than or equal to 50 mm Hg), as measured
with continuous wave Doppler echocardiography either under resting/basal
conditions and/or with provocation, preferably utilizing physiologic
exercise. In addition, these patients have severe limiting symptoms,
usually of exertional dyspnea and chest pain, that are regarded in
adults as New York Heart Association (NYHA) functional classes III and
IV, refractory to maximum medical therapy. Over the past 40 years, based
on the experience of a number of centers throughout the world, the
ventricular septal myectomy operation (also known as the Morrow
procedure) has become established as a proven approach for amelioration
of outflow obstruction and the standard therapeutic option, and the gold
standard for both adults and children with obstructive HCM and severe
drug-refractory symptoms. The myectomy operation should be confined to
centers experienced in this procedure.

Myectomy is performed through an aortotomy and involves the resection of
a carefully defined relatively small amount of muscle from the proximal
septum (about 5 to 10 g), extending from near the base of the aortic
valve to beyond the distal margins of mitral leaflets (about 3 to 4 cm),
thereby enlarging the LV outflow tract and, as a consequence in the vast
majority of patients, abolishing any significant mechanical impedance to
ejection and mitral valve SAM immediately normalizing LV systolic
pressures, abolishing mitral regurgitation, and ultimately, reducing LV
end-diastolic pressures. Such an abrupt relief of the gradient with
surgery (in contrast to slower reduction with alcohol septal ablation in
many cases) is particularly advantageous in patients with severe
functional limitations.

Some surgeons have utilized a more extensive myectomy procedure for
obstructive HCM, with the septal resection widened and extended far more
distally than in the classic Morrow procedure (i.e., 7 to 8 cm from the
aortic valve to below the level of papillary muscles). In addition, the
anterolateral papillary muscle may be dissected partially free from its
attachment with the lateral LV free wall to enhance papillary muscle
mobility and reduce anterior tethering of the mitral apparatus.
Alternatively, mitral valve replacement or repair has been employed in
selected patients judged to have severe mitral regurgitation due to
intrinsic abnormalities of the valve apparatus (such as myxomatous
mitral valve).

Previously, some surgeons found it advantageous in selected patients to
perform mitral valve replacement when the basal anterior septum in the
area of resection is relatively thin (e.g., less than 18 mm) and
muscular resection was judged to present an unacceptable risk of septal
perforation or inadequate hemodynamic result. However, currently, some
surgical centers experienced with myectomy do not advocate mitral valve
replacement (in the absence of intrinsic mitral valve disease), even in
the presence of a relatively thin ventricular septum; carefully
performed surgical septal reduction is the preferred method.

Mitral valvuloplasty (plication) in combination with myectomy has been
proposed for some patients with particularly deformed or elongated
mitral leaflets. Muscular mid-cavity obstruction due to an anomalous
papillary muscle requires an extended distal myectomy or, alternatively,
mitral valve replacement. Occasionally, patients, usually children, may
demonstrate an obstruction to right ventricular outflow due to excessive
muscular hypertrophy of trabeculae or crista supraventricularis muscle;
resection of the right ventricular outflow tract muscle, with or without
an outflow tract patch, has abolished the gradient.

Published reports of over 2,000 patients from North American and
European centers show remarkably consistent results with the ventricular
septal myectomy operation. Isolated myectomy (without concomitant
cardiac procedures such as valve replacement or coronary artery bypass
grafting) is now performed with low operative mortality in patients of
all ages, including children, at those centers having the most
experience with this procedure (reported as 1 to 3%, and even less in
the most recent cases). Surgical risk may be higher among very elderly
patients (particularly those with severe disabling symptoms associated
with pulmonary hypertension), patients with prior myectomy, or those
undergoing additional cardiac surgical procedures. Complications such as
complete heart block (requiring permanent pacemaker) and iatrogenic
ventricular septal perforation have become uncommon (equal to or less
than 1 to 2%), while partial or complete left bundle branch block is an
inevitable consequence of the muscular resection and is not associated
with adverse sequelae. Intraoperative guidance with echocardiography
(transesophageal or with the transducer applied directly to the right
ventricular surface) is standard at centers performing surgery for HCM
and is useful in assessing the site and extent of the proposed myectomy,
structural features of the mitral valve, and the effect of muscular
resection on SAM and mitral regurgitation.

Septal myectomy is associated with persistent, long-lasting improvement
in disabling symptoms and exercise capacity (i.e., increase by one or
more NYHA classes and demonstrable increase in peak oxygen consumption
with exercise) and decreased frequency of syncope five or more years
after surgery. Symptomatic benefit following myectomy appears to be
largely the consequence of abolishing or substantially reducing the
basal outflow gradient and mitral regurgitation and restoring normal LV
systolic and end-diastolic pressures (in more than 90% of patients),
which may also favorably influence LV diastolic filling and myocardial
ischemia. Because myectomy may result in a decrease in left atrial size,
the likelihood of AF occurring after surgery may be mitigated (and sinus
rhythm restored with greater ease), especially in patients younger than
45 years.

Selected patients in whom severe refractory symptoms are indisputably
linked to marked outflow gradients elicited by exercise (when resting
obstruction is absent or mild) usually also benefit from myectomy.
Reacquisition of SAM and a large resting LV outflow gradient is
exceedingly uncommon after successful myectomy in either adults or
children, and the need for reoperation to reduce recurrent outflow
gradient is extremely uncommon at centers having the most experience
with the septal myectomy operation.

By convention, surgery has not been recommended or performed in
asymptomatic or mildly symptomatic patients with obstructive HCM for a
number of reasons: 1) the effect of surgery per se on longevity is
unresolved, although several surgical series have reported improved late
survival after myectomy compared with the clinical course of nonoperated
medically treated patients with severe symptoms; 2) operative mortality
is now very low, but in some patients the risk of surgery may exceed the
ultimate risks from the disease; 3) outflow obstruction is often
compatible with normal longevity; 4) there is little or no evidence that
surgical relief of outflow obstruction abolishes the risk for
progression to the end-stage phase, which is an independent disease
consequence.

Although definitive evidence is lacking, there is some suggestion in
retrospective nonrandomized studies that surgical relief of outflow
obstruction in severely symptomatic patients may reduce long-term
mortality and possibly SCD. It should be emphasized that surgery is not
regarded as curative but is performed to achieve an improved quality of
life and functional (exercise) capacity. One possible exception to this
tenet may be young asymptomatic or mildly symptomatic patients with
particularly marked outflow obstruction (e.g., 75 mm to 100 mm Hg or
more at rest). There is a paucity of data in this subset, but it is not
unreasonable to at least consider surgical intervention for young
patients, even if they are not severely symptomatic, in the presence of
particularly marked obstruction to LV outflow.

**[Additional approaches to relieve outflow obstruction and
symptoms]{.underline}**

Ventricular septal myectomy has generally been confined to selected
major centers having substantial experience with this procedure.
However, some patients may not have ready access to such specialized
surgical care because of geographical factors; or they may not be
favorable operative candidates, because of concomitant medical
conditions---particularly advanced age, prior cardiac surgery, or
insufficient personal motivation. Two techniques can be considered as
potential alternatives to surgery for selected patients who otherwise
meet the same clinical criteria as candidates for surgery.

**Dual-chamber pacing**

Several groups had investigated the effects of permanent dual-chamber
pacing on severe outflow obstruction and refractory symptoms within
observational and uncontrolled study designs. Data in these studies were
necessarily based on the subjective perception of symptom level by
patients over relatively short periods of time. Such investigations
reported dual-chamber pacing to be associated with a substantial
decrease in outflow gradient, as well as amelioration of symptoms in
most patients. These observations inferred that a reduction of gradient
with pacing in turn consistently relieved symptoms. However, other
catheterization laboratory studies showed that a decrease in the outflow
gradient produced by temporary A-V sequential pacing could be associated
with detrimental effects on ventricular filling and cardiac output.

Subsequently, dual-chamber pacing in HCM was subjected to scrutiny in
three randomized, cross-over studies (double-blind in two) in which
patients received 2 to 3 months each of pacing and also back-up AAI mode
(no pacing) as a control, by activating and deactivating the pacemaker
accordingly. Two randomized, cross-over, double-blind studies (one
multi-center and one from the Mayo Clinic) reported the effects of
pacing in HCM patients to be less favorable than the observational data
had suggested. For example, the average decrease in outflow gradient
with pacing, while statistically significant, was nevertheless much more
modest (about 25 to 40%) than in the uncontrolled studies and varied
substantially among individual patients. In one study, the average
subaortic gradient, even after nine months of pacing, remained in the
preoperative range (e.g., average 48 mm Hg).

In these controlled studies, subjective symptomatic improvement assessed
by quality-of-life score was reported with similar frequency by patients
both after periods of pacing and after the same time period without
pacing (AAI-backup). Objective measures of exercise capacity (e.g.,
treadmill exercise time and maximal oxygen consumption) did not differ
significantly during pacing and without pacing. These observations
demonstrate that subjectively reported symptomatic benefit during pacing
frequently occurs without objective evidence of improved exercise
capacity and can be regarded in part as a placebo effect. Furthermore,
no correlation has been demonstrated for gradient reduction between
short- and long-term pacing, suggesting that testing the gradient
response to short-term pacing in the catheterization laboratory has
limited practical clinical value in judging long-term efficacy. However,
the failure to achieve gradient reduction with temporary pacing suggests
that permanent pacing is probably not indicated.

As part of its design, the randomized, cross-over, single-blind European
multi-center HCM pacing trial, Pacing in Cardiomyopathy (PIC), excluded
from chronic pacing those patients without significant gradient
reduction during temporary pacing. With data very similar to the other
two randomized studies, (but also with a large proportion of patients
who elected to continue pacing based on their own subjective assessment
of treatment), the PIC investigators concluded that pacemaker therapy
was an option for most severely symptomatic patients with obstructive
HCM refractory to drug treatment. Nevertheless, taken together the
available data do not support dual-chamber pacing as a primary treatment
for most severely symptomatic patients with obstructive HCM. In a
nonrandomized study comparing pacing and the myectomy operation,
hemodynamic and symptomatic outcome proved to be superior with surgery.

Although it is not a primary treatment for the disease, there is
nevertheless evidence to support utilizing a trial of dual-chamber
pacing in selected patient subgroups that may benefit in terms of
gradient relief and improvement in symptoms and exercise tolerance. For
example, there may be both subjective and objective symptomatic benefit
with pacing in some patients of advanced age (over 65 years), for whom
alternatives to surgery are often desirable. Otherwise, there are few
predictive data upon which to specifically target those patients who are
most likely to potentially benefit from pacing therapy; for example,
there is little relationship between the magnitude of gradient reduction
with chronic pacing and the symptomatic benefit ultimately achieved.
Pacing-induced LV remodeling with thinning of the wall was claimed in
one uncontrolled study but could not be confirmed in a randomized
investigation. Furthermore, there is no evidence that pacing reduces the
risk of SCD in HCM, alters or aborts underlying progression of the
disease state, or conveys favorable hemodynamic or symptomatic benefit
for patients with the nonobstructive form.

Of potential advantage, pacing therapy permits more aggressive drug
treatment by obviating the concern for drug-induced bradycardia. Some
patients receiving an implantable cardioverter defibrillator (ICD) for
high-risk status, in which obstruction to LV outflow is also present,
may benefit from use of the dual-chamber pacing component of the ICD to
effect a reduction in outflow gradient. The American College of
Cardiology (ACC)/American Heart Association (AHA)/North American Society
of Pacing and Electrophysiology (NASPE) 2002 guidelines have designated
pacing for severely symptomatic and medically refractory HCM patients
with LV outflow obstruction as a class IIB indication.

However, it should be underscored that maintenance of pacing therapy
(directed toward alleviating obstruction and symptoms) may be
substantially more complex in HCM than in other cardiac conditions;
therefore, for optimal results this procedure should be performed in
centers highly experienced in both pacemaker therapy and HCM. Producing
and maintaining a reduction in gradient (and presumably in symptoms)
requires that pre-excitation of the right ventricular apex and distal
septum be established and that complete ventricular capture---both at
rest and during exercise---without compromising ventricular filling and
cardiac output. Hence, ascertaining the optimal A-V interval for
dual-chamber pacing is a crucial element of pacing management in HCM.
Programming of the pacemaker A-V interval to ensure complete ventricular
capture may require slowing of intrinsic A-V nodal conduction with a
beta-blocker or verapamil, or possibly ablation of the A-V node in
selected cases (thereby rendering the patient pacemaker-dependent), has
been suggested. It is also understood that no other treatment modality
in HCM (including surgery and alcohol septal ablation) has undergone
such rigorous randomized testing in order to validate its efficacy. At
present, there are no data concerning the role of biventricular pacing
in HCM patients with severe heart disease.

**Percutaneous alcohol septal ablation**

A second option to surgery is the more recently developed alcohol septal
ablation technique. First reported in 1995, this catheter interventional
treatment involves the introduction of absolute alcohol into a target
septal perforator branch of the left anterior descending coronary artery
for the purpose of producing a myocardial infarction within the proximal
ventricular septum. Septal ablation mimics the hemodynamic consequences
of myectomy by reducing the basal septal thickness and excursion
(producing akinetic or hypokinetic septal motion), enlarging the LV
outflow tract, and thereby lessening the SAM of the mitral valve and
mitral regurgitation.

This technique utilizes conventional methods and technology currently
available for atherosclerotic CAD. After standard coronary arteriograms
are performed, a coronary balloon is placed into a proximal major septal
perforator artery with the aid of flexible coronary guide wires. A
temporary pacing catheter is positioned in the right ventricular apex in
the event that high-grade A-V block occurs. After the balloon is
inflated, an arteriogram is performed through the lumen to verify that
the balloon is located in the desired anatomic position and to ensure
that leakage of alcohol into the left anterior descending coronary
artery or coronary venous system does not occur.

Myocardial contrast echocardiography guidance (with injection of echo
contrast or radio-opaque medium) is important in selecting the
appropriate septal perforator branch. This technique is useful for
determining the precise area of septum targeted for alcohol and
infarction and whether the selected septal perforator also perfuses
other distant and unwanted areas of left or right ventricular myocardium
or papillary muscles. Some groups prefer a pressure-angiographic and
fluoroscopy guided technique. The targeted septal perforator and area
for infarction are identified by an immediate fall in outflow gradient
following balloon occlusion and/or contrast injection.

The amount of ethanol to be injected is estimated by the angiographic
visualization of septal anatomy and whether contrast wash-out is slow or
rapid. Usually, about 1 to 3 cc (average 1.5 to 2 cc) of desiccated
ethanol (of at least 95% concentration) is slowly infused into the
septal perforator and septum via the balloon catheter, inducing a
myocardial infarction demonstrable by 400 to 2,500 units of creatinine
phosphokinase release, equivalent to an area of necrosis estimated to be
3 to 10% of the LV mass (20% of the septum). However, centers performing
a large number of alcohol septal ablation procedures today are using
smaller amounts of ethanol, leading to less creatinine phosphokinase
release and smaller septal infarcts, and also reducing the incidence of
complete heart block.

Successful alcohol septal ablation may trigger a rapid reduction in
resting outflow gradient evident in the catheterization laboratory. More
frequently, a progressive decrease in the gradient occurs after 6 to 12
months, usually achieving levels in a range equivalent to that with
myectomy, and resulting from remodeling of the septum without
significant impairment in global LV ejection. This has been reported for
patients with large resting gradients at baseline as well as those with
outflow obstruction present only under provocable conditions. Often a
biphasic response of the gradient is observed with alcohol septal
ablation in which an acute response with striking reduction (probably
due to stunning of the myocardium) is followed by a rise to about 50% of
its pre-procedure level the next day, but within several months may
reach greatly reduced levels. Results of myectomy and alcohol ablation
compared at two institutions showed similar gradient reductions with the
two techniques. Another comparative analysis from a single institution
showed both surgery and ablation to substantially reduce resting and
provocable gradients, but to a significantly greater degree with
surgery.

A number of other favorable structural and functional effects following
ablation have been reported, representing the expected consequences of
reduced outflow gradient, normalization of LV pressures, and reduced
systolic overload. Echocardiographic analyses from two groups have
reported ablation to be associated with widespread regression of LVH
beyond the alcohol target area, but the extent to which remodeling
occurs with time secondary to this procedure is unpredictable and not
fully understood. Also, there is concern that extensive wall thinning
could lead to arrhythmogenic susceptibility or even the end-stage phase.

A large proportion of ablation patients from several centers have been
reported to demonstrate subjective improvement in limiting symptoms and
in quality of life in observational studies over relatively short-term
follow-up periods of 2 to 5 years. As with surgery, the decrease in
symptoms associated with ablation is often dramatic. In addition,
improved exercise performance has been shown objectively in terms of
total treadmill exercise time and peak oxygen consumption in some
studies. However, alcohol septal ablation has yet to be subjected to the
scrutiny of randomized or controlled studies or long-term follow-up. A
recent study found that both septal myectomy and ablation led to
improved exercise testing parameters, but surgery was superior in this
regard.

The mortality and morbidity associated with alcohol ablation in
experienced centers have proved to be relatively low, although they are
similar in surgical myectomy. Procedure-related mortality has been
reported to be from 1 to 4% but is probably reduced in the more recent
cases. Reports of permanent pacemaker implantation for induced
high-grade A-V block have ranged from 5% to as high as 30%, but this
complication appears to be decreasing substantially with the use of
smaller amounts of alcohol. In contrast to septal myectomy, which
usually produces left bundle branch block, alcohol ablation commonly
results in right bundle branch block. It is also possible for coronary
artery dissection to occur, as well as backward extravasation of
alcohol, producing occlusion or abrupt coronary no-flow and a large
anteroseptal myocardial infarction.

Proper selection of patients for alcohol septal ablation remains a
crucial issue. Similar to patients recommended for septal myectomy, all
candidates for alcohol septal ablation should have severe heart failure
symptoms (NYHA classes III or IV) refractory to all medications utilized
in HCM, as well as a subaortic gradient of 50 mm Hg or more measured
with Doppler echocardiography either under basal conditions and/or with
physiologic provocative maneuvers during exercise. Caution should be
exercised so that in patients selected for alcohol septal ablation,
outflow gradients are documented to be due to SAM and proximal mitral
valve septal contact, exclusive of congenital abnormalities of the
mitral apparatus such as anomalous papillary muscle insertion into
mitral valve, which produces more distal muscular obstruction in the
mid-cavity.

Nevertheless, the number of alcohol ablations performed world-wide now
approaches an estimated 3,000 over only about a six-year period,
exceeding the number of surgical myectomies performed over the 40 years
since this operation was introduced. In some instances, the frequency
with which myectomy surgery has been performed for obstructive HCM has
now been reduced by more than 90% due to the recent accelerated
enthusiasm for ablation.

Disproportionality in the frequency with which alcohol septal ablation
is performed relative to myectomy (ablations are estimated to be at
least 15 to 20 times more common than surgery at present) has raised
concerns that there may have an insidious and unjustifiable lowering of
the symptom and gradient-level threshold in the selection of patients
for ablation, with less symptomatic NYHA class II, less obstructed, and
younger patients now undergoing the procedure. This circumstance has
evolved in part because of the relative ease with which ablation can be
performed (compared to surgery), with substantially less discomfort
during a much shorter postoperative hospitalization and recovery period
in the absence of a sternotomy. However, this fact does not justify less
strict criteria for alcohol septal ablation.

Another factor that has affected patient selection for alcohol septal
ablation is the practice of determining eligibility based solely on a
subaortic gradient provoked by nonphysiologic interventions such as
dobutamine infusion (rather than exercise, for example). Dobutamine is
an inotropic and catecholamine-inducing drug that is a powerful
stimulant of subaortic gradients in normal hearts or in cardiac diseases
other than HCM of questionable physiologic and clinical significance,
and occasionally results in adverse consequences to patients with
obstruction; dependence on dobutamine to induce gradients can expose
some patients to septal ablation in the absence of true impedance to LV
outflow. Therefore, dobutamine is generally not recommended for the
purpose of provoking outflow gradients in severely symptomatic HCM
patients who are regarded as possible candidates for major
interventions.

A predominate concern raised with respect to alcohol septal ablation is
the potential long-term risk for arrhythmia-related cardiac events
(including SCD) directly attributable to the procedure. Unlike myectomy,
alcohol septal ablation potentially creates a permanent arrhythmogenic
substrate in the form of a healed intramyocardial septal scar that could
increase the risk of lethal reentrant arrhythmias. This is particularly
relevant because many patients with HCM already possess an unstable
electrophysiologic substrate as part of their underlying disease.
However, since HCM patients are at increased risk for SCD over
particularly long periods, possibly through much of their lifetimes, it
will require many years (and probably decades) to determine the
likelihood that risk for arrhythmia-related events and SCD is increased
as a consequence of the healed intramyocardial scar produced by alcohol
septal ablation. Indeed, this is particularly relevant for young
patients in whom even a modest annual increase in the risk of SCD would
have the likelihood of shortening life considerably. Reports of the
noninducibility of reentrant ventricular tachyarrhythmia in small
numbers of patients in the short term after septal ablation do not
appear sufficient at this juncture to exclude the possibility of
late-onset ventricular tachyarrhythmias and SCD over the long risk
period characteristic of HCM.

Therefore, at present, the impact of alcohol ablation on the incidence
of SCD is unresolved. Until more is known regarding the natural history
of patients undergoing alcohol septal ablation and there is less
uncertainty regarding the consequences of the intramyocardial scar,
particularly careful selection of patients seems advisable and prudent
(by largely confining the procedure to older adults), particularly when
the option for surgical myectomy is feasible. There would not appear to
be a primary role for alcohol ablation in children, and such procedures
are not advised.

Due to morphologic heterogeneity, not all HCM patients with obstruction
are ideal candidates for septal ablation. This therapy relies on the
fixed anatomic distribution and size of the septal perforator coronary
arteries. Therefore, the ablation technique cannot make adjustments for
variability in the distribution and size of these arterial vessels in
relation to the distribution of septal hypertrophy, or for other
complexities of LV outflow tract morphology such as greatly elongated
mitral leaflets and anomalous papillary muscle. The direct operative
approach provides greater flexibility for relieving obstruction and also
allows surgical treatment for associated cardiac abnormalities such as
primary valvular disease (e.g., myxomatous mitral valve prolapse or
aortic stenosis), atherosclerotic CAD, or segmental myocardial bridging
of the left anterior descending coronary artery, as well as anomalies of
the mitral valve and apparatus. Also, relief of obstruction with surgery
is immediate (but is often delayed with alcohol septal ablation), which
may be crucial in some patients with particularly severe symptoms of
heart failure.

The \"learning curve\" for expertise with the alcohol septal ablation
technique is steep (due, in part, to the relatively small number of
eligible HCM patients), particularly regarding selection of the optimal
septal perforator branch; therefore, ablation should not be regarded as
a routine technique to be employed by any expert interventional
cardiologist. It is advisable that alcohol ablation (as well as
myectomy) be largely confined to centers having substantial and specific
experience with HCM and the procedure in order to assure proper patient
selection, the lowest possible rates of morbidity and mortality, and the
greatest likelihood of achieving benefits.

While alcohol ablation represents an option available to HCM patients
and a selective alternative to surgery, it is not at this time regarded
as the standard and primary therapeutic strategy for all severely
symptomatic patients refractory to maximal medical management with
marked obstruction to LV outflow. Septal myectomy remains the gold
standard for this HCM patient subset.

**[Sudden cardiac death]{.underline}**

**Risk stratification**

Since the modern description of HCM by Teare in 1958, sudden and
unexpected death (unassociated with severe heart failure) has been
recognized as the most devastating and often unpredictable complication
and the most frequent mode of premature demise from this disorder.
Sudden cardiac death may occur as the initial disease presentation, most
frequently in asymptomatic or mildly symptomatic young people. The
high-risk HCM patients constitute only a minority of the overall disease
population, and historically, a major investigative focus has been the
isolation of the small but important subset of patients at high-risk
among the overall HCM spectrum. Since SCD can be the initial
manifestation of HCM, it often occurs without reliable warning signs or
symptoms, and often in the early morning hours after awakening. Although
SCD is most frequent in adolescents and young adults less than 30 to 35
years old, such risk also extends through mid-life and beyond; the basis
for this particular predilection of SCD for the young is unresolved.
Therefore, achieving any particular age does not itself confer an
immunity to sudden HCM-related catastrophe. Sudden cardiac death occurs
most commonly during mild exertion or sedentary activities (or during
sleep), but it is not infrequently triggered by vigorous physical
exertion. Indeed, HCM is the most common cause of cardiovascular-related
SCD in young people, including competitive athletes (most commonly in
basketball and football).

The available data (largely from recorded arrhythmic events that
triggered appropriate defibrillator interventions) suggest that complex
ventricular tachyarrhythmias emanating from an electrically unstable
myocardial substrate are the most common mechanism by which SCD occurs
in HCM. Indeed, ventricular arrhythmias are an important clinical
feature in adults with HCM. On routine ambulatory (Holter) 24-h
electrocardiogram (ECG) monitoring, 90% of adults demonstrate
ventricular arrhythmias, which are often frequent or complex, including
premature ventricular depolarizations (greater than or equal to 200 in
20% of patients), ventricular couplets (in greater than 40%), or
nonsustained bursts of ventricular tachycardia (in 20 to 30%).
Alternatively, it is possible that in some patients supraventricular
tachyarrhythmias could trigger ventricular tachyarrhythmias or that
bradyarrhythmias occur and require back-up pacing.

It has been suggested that life-threatening tachyarrhythmias could be
provoked in HCM by a number of variables either secondary to
environmental factors (e.g., intense physical exertion) or,
alternatively, intrinsic to the disease process. The latter may involve
a vicious cycle of increasing myocardial ischemia and diastolic (or
systolic) dysfunction, possibly impacted by outflow obstruction,
systemic arterial hypotension, or supraventricular tachyarrhythmias that
lead to decreased stroke volume and coronary perfusion.

Although the available data on the stratification of SCD risk are
substantial and a large measure of understanding has been achieved, it
is important to underscore that precise identification of all individual
high-risk patients by clinical risk markers is not completely resolved.
This issue remains a challenge due largely to the heterogeneity of HCM
disease presentation and expression, its relatively low prevalence in
cardiologic practice, and the complexity of potential pathophysiologic
mechanisms. Nevertheless, it is possible to identify most high-risk
patients by noninvasive clinical markers, and only a small minority of
those HCM patients who die suddenly (about 3%) are without any of the
currently acknowledged risk markers. The highest risk for SCD has been
associated with the following: 1) prior cardiac arrest or spontaneously
occurring and sustained ventricular tachycardia (VT); 2) family history
of a premature HCM-related SCD particularly if sudden, in a close
relative, or if multiple in occurrence; 3) identification of a high-risk
mutant gene; 4) unexplained syncope, particularly in young patients or
when exertional or recurrent; 5) nonsustained VT (of 3 beats or more and
of at least 120 beats/min) evident on ambulatory (Holter) ECG
recordings; 6) abnormal blood pressure response during upright exercise
which is attenuated or hypotensive, indicative of hemodynamic
instability, and of greater predictive value in patients less than 50
years old or if hypotensive; and 7) extreme LVH with maximum wall
thickness of 30 mm or more, particularly in adolescents and young
adults.

HCM patients (particularly those less than 60 years old) should undergo
comprehensive clinical assessments on an annual basis for risk
stratification and evolution of symptoms, including careful personal and
family history, noninvasive testing with two-dimensional
echocardiography (primarily for assessment of magnitude of LVH and
outflow obstruction), 24- or 48-h ambulatory (Holter) ECG recording for
VT, and blood pressure response during maximal upright exercise
(treadmill or bicycle). Subsequent risk analysis should be performed
periodically and when there is a perceived change in clinical status.

Recent attention has focused on the magnitude of LVH (as assessed by
conventional two-dimensional echocardiography) as an indicator of risk.
Two independent groups have reported a direct association between
magnitude of LV wall thickness and risk of SCD in large HCM populations.
In one study, extreme LVH (maximum thickness of 30 mm or more), present
in approximately 10% of HCM patients, conveyed substantial long-term
risk. Sudden cardiac death was most common in asymptomatic or mildly
symptomatic adolescents or young adults and was estimated at 20% over 10
years and 40% over 20 years (i.e., annual mortality about 2%). There is
supporting circumstantial evidence from retrospective cross-sectional
analyses that extreme hypertrophy represents a risk factor for premature
SCD because it is observed less commonly in older than in younger
patients; this finding could reflect either preferential SCD at a young
age, structural remodeling with wall thinning, or both. This
relationship of extreme hypertrophy to age is accentuated with wall
thicknesses of 35 mm or more, which appear in less than 1% of patients
older than 50 years. Another group, however, has maintained that extreme
hypertrophy is a predictor of SCD only when associated with other risk
factors such as unexplained syncope, family history of premature SCDs,
nonsustained VT on Holter, or an abnormal blood pressure response during
exercise. At present, although it is not unequivocally resolved as to
whether extreme hypertrophy as a sole risk factor is sufficient to
justify a recommendation for prevention of SCD with an ICD, serious
consideration for such an intervention should be given to young
patients.

The concept that risk of SCD is related to the magnitude of hypertrophy
does not, however, infer that the risk is necessarily low when LV wall
thickness is less than 30 mm, because other risk markers may be present
in a given patient; indeed, the majority of patients who die suddenly
do, in fact, have wall thicknesses of less than 30 mm. Furthermore, a
small number of high-risk pedigrees with troponin T and I mutations have
been reported in whom SCD was associated with particularly mild forms of
LVH, including a few individuals with normal LV wall thickness and mass.
However, such events appear to be uncommon within the overall HCM
patient spectrum. Although prognosis is generally not tightly linked to
the pattern and distribution of LVH, the preponderance of evidence
suggests that segmental wall thickening at the low end of the
morphologic spectrum (i.e., less than 20 mm thickness, regardless of its
precise location), generally confers a favorable prognosis in the
absence of other major risk factors. Such localized hypertrophy includes
the nonobstructive form of HCM confined to the most distal portion of LV
(\"apical HCM\").

Disorganized cardiac muscle cell arrangement, myocardial replacement
scarring as a repair process following cell death (possibly resulting
from ischemia due to abnormal microvasculature consisting of intramural
small vessel disease or muscle mass-to-coronary flow mismatch) and the
expanded interstitial (matrix) collagen compartment probably serve as
the primary arrhythmogenic substrate predisposing some susceptible
patients to reentrant, life-threatening ventricular tachyarrhythmias.
That extreme degrees of LVH can be linked to sudden events is perhaps
not unexpected, considering the potential impact of such wall thickening
on myocardial architecture, oxygen demand, coronary vascular resistance,
and capillary density, all of which thereby create an
electrophysiologically unstable substrate. The degree of hypertrophy
does not appear to be directly associated with the severity of diastolic
dysfunction and limiting symptoms. Paradoxically, most patients with
massive degrees of LVH do not experience marked symptomatic disability,
LV outflow obstruction, or left atrial enlargement.

It is a clinical perception that the premonitory symptom most associated
with the likelihood of SCD in HCM is impaired consciousness (i.e.,
syncope or near syncope). However, the sensitivity and specificity of
syncope as a predictor of SCD is low, possibly because most such events
in this disease are probably not in fact secondary to arrhythmias or
related to outflow obstruction. Indeed, there are many potential causes
of syncope, some of which are unrelated to the basic disease state and
are often neurocardiogenic (i.e., vagal, neurally-mediated syndromes) in
origin. Even when an underlying cause for impaired consciousness cannot
be identified, this symptom-complex can be compelling in some HCM
patients, particularly when it is exertional or recurrent, when it
occurs in the young, or in the context of a single recent syncopal
episode judged to be disease-related. Therefore, syncope may represent
the basis of a defibrillator implant to ensure preservation of life
should a life-threatening arrhythmia intervene.

Available data suggest that LV outflow obstruction (gradient 30 mm Hg or
more) can only be regarded as a minor risk factor for SCD in HCM. The
impact of gradient on SCD risk is not sufficiently strong (positive
predictive value of only 7%) for obstruction to merit a role as the sole
(or predominant) deciding clinical parameter and the primary basis for
decisions to intervene prophylactically with an ICD.

Identification of HCM in young children is exceedingly uncommon and
often creates a specific clinical dilemma because such an initial
diagnosis occurring so early in life (frequently fortuitously) raises
uncertainty regarding future risk over particularly long time periods.
One report suggests that short tunneled (bridged) intramyocardial
segments of left anterior descending coronary artery independently
convey increased risk for cardiac arrest, probably mediated by
myocardial ischemia. However, potential biases in patient selection, the
frequency of coronary arterial bridging in surviving adults and those
who have died of noncardiac causes, and the need for routine invasive
coronary arteriography in order to identify this abnormality
prospectively seem to mitigate the potential power of coronary bridging
as a risk factor for SCD.

It has been proposed, based on genotype-phenotype correlations, that the
genetic defects responsible for HCM could represent the primary
determinant and stratifying marker of prognosis and for SCD and heart
failure risk, with specific mutations conveying either favorable or
adverse prognosis (i.e., high- and low-risk mutations). For example, it
has been suggested that some cardiac beta-myosin heavy chain mutations
(such as Arg403Gln and Arg719Gln) and some troponin-T mutations are
associated with higher incidence of premature death, decreased life
expectancy, and early onset disease manifestations, while other HCM
genes, such as cardiac myosin-binding protein C (particularly InsG791)
or alpha-tropomyosin (Asp175Asn), convey a more favorable prognosis.
However, routine clinical testing for specific mutations believed to be
high (or low) risk has been shown to have low yield. Therefore, it is
premature to draw definitive conclusions regarding gene-specific
clinical outcomes based solely on the presence of a particular mutation,
by virtue of extrapolation from available epidemiologic-genetic data
which are formulated from relatively small numbers of genotyped families
largely skewed toward high-risk status. Consequently, it is becoming
increasingly evident that the presence or absence of a particular
mutation does not by itself represent sufficient data to convey clear
prognostic implications and that HCM mutations may not possess
distinctive clinical signatures.

The particular prognosis attached to adult carriers with a mutant HCM
gene but without LVH and clinical expression of HCM, or those
individuals who develop hypertrophy *de novo* in adulthood, is
uncertain; however, at this early juncture, this subgroup would not
appear to be associated with an adverse prognosis. An exception to this
tenet may be the small number of SCDs in young people with little or no
LVH reported in a very few families with troponin-T mutations.

There is no convincing evidence that invasive markers such as those
defined with laboratory electrophysiologic testing (i.e., programmed
ventricular stimulation) have an important routine role in identifying
those HCM patients who have an unstable electrical substrate and are at
high-risk for SCD due to life threatening arrhythmias. Similar to the
experience in CAD and dilated cardiomyopathy, polymorphic VT and
ventricular fibrillation (VF) (which are the most commonly provoked
arrhythmias) are generally regarded as nonspecific electrophysiologic
testing responses to multiple ventricular extra-stimuli, and these
specialized laboratory studies are highly dependant on the level of
aggression of the protocol. For example, stimulation with three
ventricular premature depolarizations rarely triggers monomorphic VT in
HCM (in contrast to CAD), but frequently induces polymorphic VT or VF,
even in some patients at low risk for SCD.

It is now the predominant view that the risk stratification strategies
involving laboratory induction of such ventricular arrhythmias are
neither desirable in HCM patients on a routine basis nor, *per se*,
justify aggressive intervention. Electrophysiologic studies with or
without programmed ventricular stimulation may, however, have some value
in selected patients such as those with otherwise unexplained syncope.

Most of the clinical markers of SCD risk in HCM are limited by
relatively low positive predictive values due in part to relatively
low-event rates. However, the high negative predictive values (at least
90%) of these markers suggest that the *absence* of risk factors and
certain other clinical features can be used to develop a profile of
patients having a low likelihood of SCD or other adverse events. Adult
patients can probably be considered *low risk* if they demonstrate: 1)
no or only mild symptoms of chest pain or exertional dyspnea (NYHA
functional classes I and II); 2) absence of family history of premature
death from HCM; 3) absence of syncope judged to be HCM-related; 4)
absence of nonsustained ventricular tachycardia during ambulatory
(Holter) ECG; 5) outflow tract gradient at rest of less than 30 mm Hg;
6) normal or relatively mild increase in left atrial size (less than 45
mm); 7) normal blood-pressure response to upright exercise; and 8) mild
LVH (wall thickness less than 20 mm).

Patients with an apparently favorable prognosis in the absence of risk
factors constitute an important proportion of the overall HCM
population. Most such patients probably will not require aggressive
major medical treatment and generally deserve a large measure of
reassurance regarding their prognoses. Little or no restriction is
necessary with regard to recreational activities and employment,
although exclusion from intense competitive sports is advised.

**Prevention**

Efforts at the prevention of SCD have historically targeted only the
minority of patients with HCM in whom SCD risk was unacceptably high.
Historically, treatment strategies to prophylactically reduce the risk
for SCD or delay progression of congestive symptoms have been predicated
on the administration of drugs such as beta adrenergic-blockers,
verapamil, and type I-A antiarrhythmic agents (i.e., quinidine,
procainamide) to those patients perceived to be at high risk. However,
there is no evidence that this practice of prophylactically
administering such drugs empirically to asymptomatic HCM patients to
mitigate the risk for SCD is efficacious, and this strategy now seems
outdated with the current availability of measures that more effectively
prevent SCD, such as the ICD. In addition, low-dose (less than 300 mg)
amiodarone has been associated with improved survival in HCM, but this
agent requires careful monitoring and may not be tolerated due to its
potential toxicity over the long risk periods incurred by young
patients.

When risk level for SCD is judged by contemporary criteria to be
unacceptably high and deserving of intervention, the ICD is the most
effective and reliable treatment option available, harboring the
potential for absolute protection and altering the natural history of
this disease in some patients. In one multicenter retrospective study,
ICDs appropriately sensed and automatically aborted potentially lethal
ventricular tachyarrhythmias by restoring sinus rhythm in almost 25% of
a high-risk cohort, followed for a relatively brief period of 3 years.
Appropriate device interventions occurred at a rate of 11% per year for
secondary prevention (the implant following cardiac arrest or
spontaneous and sustained ventricular tachycardia) and at 5% per year
for primary prevention (implant based solely on noninvasive risk
factors), usually in patients with no or only mild prior symptoms. There
was only a 4 to 1 excess of ICDs implanted to lives saved. Patients
receiving appropriate defibrillation shocks were generally young (mean
age 40 years). ICDs often remained dormant for prolonged periods before
discharging (up to 9 years), emphasizing the unpredictable timing of SCD
events in this disease, the potentially long risk period, and the
requirement for extended follow-up duration to assess survival in HCM
studies. Therefore, while the decision to implant a defibrillator for
primary prevention cannot reasonably be deferred beyond the time when
high-risk status is first judged to be present, it may precede
considerably the time at which the device ultimately discharges. There
is an ongoing multicenter international study of HCM patients with ICDs
for the purpose of obtaining data on interventional devices in a much
larger population over longer periods of time.

The ICD is strongly warranted for secondary prevention of SCD in those
patients with prior cardiac arrest or sustained and spontaneously
occurring VT. The presence of multiple clinical risk factors conveys
increasing risk for SCD of sufficient magnitude to justify aggressive
prophylactic treatment with an ICD for primary prevention of SCD. Strong
consideration should be afforded for a prophylactic ICD in the presence
of one risk factor regarded as major in that patient (e.g., a family
history of SCD in close relatives).

Because the positive predictive value of any single risk factor is low,
such management decisions must often be based on individual judgment for
the particular patient, by taking into account the overall clinical
profile including age, the strength of the risk factor identified, the
level of risk acceptable to the patient and family, and the potential
complications largely related to the lead systems and to inappropriate
device discharges. It is also worth noting that physician and patient
attitudes toward ICDs (and the access to such devices within the
respective health care system) can vary considerably among countries and
cultures and thereby have an important impact on clinical
decision-making and the threshold for implant in HCM. The ACC/AHA/NASPE
2002 guidelines have designated the ICD for primary prevention of SCD as
a class IIb indication and for secondary prevention (after cardiac
arrest) as a class I indication.

There is, at present, an understandable reluctance on the part of
pediatric cardiologists to implant such devices chronically in children
(particularly for primary prevention) considering the necessary, ongoing
commitment required for maintenance and the likelihood that lead or
other (ICD-related) complications will occur over very long time
periods. However, while adolescence may represent a psychologically
difficult age to be encumbered by an ICD, it should also be emphasized
that this is coincidently the period of life consistently showing the
greatest predilection for SCD in HCM. One alternative but empiric
strategy proposed for some very young high-risk children is the
administration of amiodarone as a bridge to later ICD placement after
sufficient growth and maturation has occurred. Some investigators also
regard the end-stage phase of HCM as a risk factor for SCD, justifying
implantation of a cardioverter defibrillator during the waiting period
prior to the availability of a heart for transplant.

**Athlete recommendations**

In accord with the recommendations of the Expert Consensus panel of the
26th Bethesda Conference, young patients with HCM should be restricted
from intense competitive sports to reduce the risk for SCD that may be
associated with such extreme lifestyle. A linkage has been established
between SCD and intense exertion in trained athletes with underlying
cardiovascular disease (including HCM) and SCD.

There is indirect and circumstantial evidence that the removal of young
athletes from the competitive arena reduces risk for SCD. Not all
trained athletes with HCM die suddenly during their competitive phase of
life, only some HCM-related SCDs are associated with intense physical
activity, and precision in the stratification of risk for athletes with
HCM is particularly difficult given the extreme environmental conditions
to which they are often exposed (associated with alterations in blood
volume hydration and with electrolytes). Nevertheless, the consensus of
the general medical community prudently supports avoiding exposure to
most competitive sports for young athletes with HCM to reduce SCD risk,
and therefore withdrawal from the athletic arena can be regarded as a
treatment modality in this disease. However, stringent lifestyle or
employment modifications for other HCM patients (who are not
participants in organized athletics) do not seem justified or practical,
although intense physical activity involving burst exertion (e.g.,
sprinting) or systematic isometric exercise (e.g., heavy lifting) should
be discouraged. Although data are scarce, there is presently no evidence
to suggest that genetically affected but phenotypically normal family
members are generally at increased risk for SCD. Therefore, there is
little basis for subjecting such individuals to the same activity
restrictions as many other HCM patients, or excluding them from
competitive athletics in the absence of cardiac symptoms, family history
of SCD, or a mutant gene regarded as malignant. However, periodic
(probably annual) noninvasive clinical evaluation directed toward risk
assessment is warranted in this subset of patients.

**[Atrial fibrillation]{.underline}**

Atrial fibrillation is the most common sustained arrhythmia in HCM and
usually justifies aggressive therapeutic strategies. Paroxysmal episodes
or chronic AF ultimately occur in 20 to 25% of HCM patients, linked to
left atrial enlargement and an increasing incidence with age.
Furthermore, it is possible that subclinical AF (i.e., identified only
by Holter recording) may be even more common. Clinical cohort studies
show that AF is reasonably well tolerated by about one-third of patients
and is not an independent determinant of sudden unexpected death;
however, it is possible that in certain susceptible patients, AF may
trigger life-threatening ventricular arrhythmias. Nevertheless, AF is
independently associated with heart failure-related death, occurrence of
fatal and nonfatal stroke, as well as long-term disease progression with
heart failure symptoms; transient episodes occur in about 30% of
patients immediately following septal myectomy, often in patients with a
prior history of AF. Risk for complications of AF is enhanced when the
arrhythmia becomes chronic, onset is before 50 years of age, and outflow
obstruction is present.

Paroxysmal episodes of AF may also be responsible for acute clinical
deterioration, with syncope or heart failure resulting from the reduced
diastolic filling and cardiac output---as a consequence of increased
ventricular rate and with the loss of atrial contraction (and its
contribution to ventricular filling) in a hypertrophied LV with
preexisting impaired relaxation and compliance. Atrial fibrillation in
HCM should be managed generally in accordance with the ACC/AHA
guidelines. In particular, electrical or pharmacologic cardioversion are
indicated in those patients presenting within 48 h of onset, assuming
that the presence of atrial thrombi can be excluded with a reasonable
degree of certainty. Although comparative data regarding the efficacy of
antiarrhythmic drugs are not available for HCM patients, amiodarone is
generally regarded as the most effective antiarrhythmic agent for
preventing recurrences of AF, based largely on extrapolation from its
use in other heart diseases.

A generally aggressive strategy for maintaining sinus rhythm is
warranted in HCM because of the association of AF with progressive heart
failure and mortality, as well as stroke. In chronic AF, beta-blockers,
verapamil (and digoxin) have proved effective in controlling heart rate,
although A-V node ablation and permanent ventricular pacing may
occasionally be necessary in selected patients. Anticoagulant therapy
(with warfarin) is indicated in patients with either paroxysmal or
chronic AF. Because even one or two episodes of paroxysmal AF have been
associated with increased risk for systemic thromboembolization in HCM,
the threshold for initiation of anticoagulant therapy should be low and
can include patients after the initial AF paroxysm. Since warfarin has
proved superior to aspirin in other cardiac conditions associated with
AF, it is the recommended anticoagulant agent in HCM patients judged to
be at risk for thromboembolism. While anticoagulation reduces the risk
of thromboembolic events in patients with AF and HCM, it is also
recognized that anticoagulation does not completely abolish the risk of
stroke. Such clinical decisions should be tailored to the individual
patient after considering the risk for hemorrhagic complications,
lifestyle modifications, and expectations for compliance.

The most appropriate management for patients with asymptomatic
nonsustained supraventricular tachycardia (detected only on ambulatory
\[Holter\] ECG or exercise testing), and associated with left atrial
enlargement is presently unresolved. Also, at present, there is little
experience specifically in HCM patients with emerging and novel
alternative treatment strategies for AF such as pulmonary vein
radio-frequency ablation, the surgical MAZE procedure, or implantable
atrial defibrillators to warrant definitive recommendations at this
time.

#### CLINICAL ALGORITHM(S)

An algorithm is provided in the original guideline document for the
clinical presentation and treatment strategies for patient subgroups
within the broad clinical spectrum of hypertrophic cardiomyopathy.

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of supporting evidence is not specifically stated for each
recommendation.

Because of the relatively low prevalence of hypertrophic cardiomyopathy
(HCM) in general cardiologic practice, its diverse presentation, and
mechanisms of death and disability and skewed patterns of patient
referral, the level of evidence governing management decisions for drugs
or devices has often been derived from nonrandomized and retrospective
investigations.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Appropriate management of hypertrophic cardiomyopathy using prudent,
practical, and contemporary treatment strategies

#### POTENTIAL HARMS

-   Even moderate doses of beta-blockers may affect growth in young
    children or impair school performance, or trigger depression in
    children and adolescents, and should be closely monitored in such
    patients.

-   Potential side effects \[of beta-blockers\] include fatigue,
    impotence, sleep disturbances, and chronotropic incompetence.

-   Aside from the mild side-effects of constipation and hair loss,
    verapamil may also occasionally harbor a potential for clinically
    important adverse consequences and has been reported to cause death
    in a few hypertrophic cardiomyopathy (HCM) patients with severe
    disabling symptoms (orthopnea and paroxysmal nocturnal dyspnea) and
    markedly-elevated pulmonary arterial pressure in combination with
    marked outflow obstruction. Adverse hemodynamic effects of verapamil
    are presumably the result of the vasodilating properties
    predominating over negative inotropic effects, resulting in
    augmented outflow obstruction, pulmonary edema, and cardiogenic
    shock.

    -   Because of these concerns, caution should be exercised in
        administering verapamil to patients with resting outflow
        obstruction and severe limiting symptoms.

-   Anticholinergic side effects \[of disopyramide\] such as dry mouth
    and eyes, constipation, indigestion, and difficulty in micturition
    may be reduced by long-acting preparations through which
    cardioactive benefits are more sustained.

-   Disopyramide administration may be deleterious in nonobstructive
    hypertrophic cardiomyopathy by decreasing cardiac output.

-   Nifedipine, because of its particularly potent vasodilating
    properties, may be deleterious, particularly for patients with
    outflow obstruction.

-   Combined therapy with disopyramide and amiodarone (or disopyramide
    and sotalol), or quinidine and verapamil (or quinidine and
    procainamide), should also be avoided due to concern over
    proarrhythmia.

-   Verapamil is not indicated in infants due to the risk for sudden
    death that has been reported with intravenous administration.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

Administration of nitroglycerine, angiotensin-converting enzyme
inhibitors, or digitalis is generally contraindicated or discouraged in
the presence of resting provocable outflow obstruction.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   Because of the relatively low prevalence of hypertrophic
    cardiomyopathy (HCM) in general cardiologic practice, its diverse
    presentation, and mechanisms of death and disability and skewed
    patterns of patient referral, the level of evidence governing
    management decisions for drugs or devices has often been derived
    from nonrandomized and retrospective investigations. Large-scale
    controlled and randomized study designs, such as those that have
    provided important answers regarding the management of coronary
    artery disease (CAD) and congestive heart failure, have generally
    not been available in HCM as a result of these factors. Therefore,
    treatment strategies have necessarily evolved based on available
    data that have frequently been observational in design, sometimes
    obtained in relatively small patient groups, or derived from the
    accumulated clinical experience of individual investigators, and
    reasonable inferences drawn from other cardiac diseases.
    Consequently, the construction of strict clinical algorithms
    designed to assess prognosis and dictate treatment decisions for all
    patients has been challenging and has not yet achieved general
    agreement. In some clinical situations, management decisions and
    strategies unavoidably must be individualized to the particular
    patient.

-   Understanding of the molecular basis, clinical course, and treatment
    of HCM has increased substantially in the last decade. In
    particular, there has been a growing awareness of the clinical and
    molecular heterogeneity characteristic of this disorder and the many
    patient subgroups that inevitably influence considerations for
    treatment. Some of these management strategies are novel and
    evolving, and this guideline cannot, in all instances, convey
    definitive assessments of their role in the treatment armamentarium.
    Also, for some uncommon subsets within the broad disease spectrum,
    there are little data currently available to definitively guide
    therapy. With these considerations in mind, the panel has aspired to
    create a guideline that is not only current and pertinent but also
    has the potential to remain relevant for many years.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Clinical Algorithm\
Personal Digital Assistant (PDA) Downloads\
Pocket Guide/Reference Cards\
Slide Presentation

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness\
Staying Healthy

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman
CE, Shah PM, Spencer WH 3rd, Spirito P, Ten Cate FJ, Wigle ED, Vogel RA,
Abrams J, Bates ER, Brodie BR, Danias PG, Gregoratos G, Hlatky MA,
Hochman JS, et al. American College of Cardiology/European Society of
Cardiology Clinical Expert Consensus Document on Hypertrophic
Cardiomyopathy. A report of the American College of Cardiology
Foundation Task Force on Clinical Expert Consensus Documents. Eur Heart
J 2003 Nov;24(21):1965-91. \[273 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14585256)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2003 Nov

#### GUIDELINE DEVELOPER(S)

American College of Cardiology Foundation - Medical Specialty Society\
European Society of Cardiology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

The American College of Cardiology Foundation Task Force on Clinical
Expert Consensus Documents and the European Society of Cardiology
Committee for Practice Guidelines

#### GUIDELINE COMMITTEE

American College of Cardiology Foundation Task Force on Clinical Expert
Consensus Documents; European Society of Cardiology Committee for
Practice Guidelines

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*Writing Committee Members*: Barry J. Maron, (Co-Chair), American
College of Cardiology (ACC), European Society of Cardiology (ESC);
William J. McKenna\*, (Co-Chair), ACC, ESC; Gordon K. Danielson, ACC;
Lukas J. Kappenberger\*, ACC, ESC; Horst J. Kuhn\*, ESC; Christine E.
Seidman; Pravin M. Shah, ACC; William H. Spencer III, ACC; Paolo
Spirito\*, ACC, ESC; Folkert J. Ten Cate\*, ACC, ESC; E. Douglas Wigle,
ACC

*ACC Foundation Task Force on Clinical Expert Consensus Documents
Members*: Robert A. Vogel, (Chair); Jonathan Abrams; Eric R. Bates;
Bruce R. Brodie\*\*; Peter G. Danias\*\*; Gabriel Gregoratos; Mark A.
Hlatky; Judith S. Hochman; Sanjiv Kaul; Robert C. Lichtenberg; Jonathan
R. Lindner; Robert A. O´Rourke\*\*\*; Gerald M. Pohost; Richard S.
Schofield; Cynthia M. Tracy\*\*; William L. Winters, Jr.\*\*

*ESC Committee for Practice Guidelines Members\**: Werner W. Klein,
(Chair); Silvia G. Priori, (Co-Chair); Angeles Alonso-Garcia; Carina
Blomstrom-Lundqvist; Guy De Backer; Jaap Deckers; Markus Flather;
Jaromir Hradec; Ali Oto; Alexander Parkhomenko; Sigmund Silber; Adam
Torbicki

\*Official representatives of the European Society of Cardiology\
\*\*Former members of Task Force\
\*\*\*Former Chair of Task Force

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

The Task Force on Clinical Expert Consensus Documents makes every effort
to avoid any actual or potential conflicts of interest that might arise
as a result of an outside relationship or personal interest of a member
of the writing panel. Specifically, all members of the writing panel are
asked to provide disclosure statements of all such relationships that
might be perceived as real or potential conflicts of interest to inform
the writing effort. These statements are reviewed by the parent task
force, reported orally to all members of the writing panel at the first
meeting, and updated as changes occur.

#### ENDORSER(S)

Armenian Society of Cardiology - Medical Specialty Society\
Belgian Society of Cardiology - Medical Specialty Society\
British Cardiac Society - Medical Specialty Society\
Bulgarian Society of Cardiology - Medical Specialty Society\
Czech Society of Cardiology - Medical Specialty Society\
Estonian Society of Cardiology - Medical Specialty Society\
Finnish Cardiac Society - Medical Specialty Society\
French Society of Cardiology - Medical Specialty Society\
German Society of Cardiology - Medical Specialty Society\
Hellenic Cardiological Society - Medical Specialty Society\
Israel Heart Society - Medical Specialty Society\
Italian Federation of Cardiology - Medical Specialty Society\
Latvian Society of Cardiology - Medical Specialty Society\
Lithuanian Society of Cardiology - Medical Specialty Society\
Netherlands Society of Cardiology - Medical Specialty Society\
Norwegian Society of Cardiology - Medical Specialty Society\
Portuguese Society of Cardiology - Medical Specialty Society\
Romanian Society of Cardiology - Medical Specialty Society\
San Marino Society of Cardiology - Medical Specialty Society\
Society of Cardiology of the Russian Federation - Medical Specialty
Society\
Spanish Society of Cardiology - Medical Specialty Society\
Swedish Society of Cardiology - Medical Specialty Society\
Turkish Society of Cardiology - Medical Specialty Society

#### GUIDELINE STATUS

This is the current release of the guideline.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the [European Society of Cardiology
(ESC) Web
site](http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/hypertrophic-cardiomyopathy.aspx).

Print copies: Available from Elsevier Publishers Ltd. 32 Jamestown Road,
London, NW1 7BY, United Kingdom. Tel: +44.207.424.4422; Fax: +44 207 424
4515; E-mail: <gr.davies@elsevier.com>.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ,
    Seidman CE, Shah PM, Spencer WH, Spirito P, Ten Cage FJ, Wigle ED.
    Comprehensive bibliography on hypertrophic cardiomyopathy, including
    relevant, supplementary references to the ACC/ESC Clinical Expert
    Consensus Document on Hypertrophic Cardiomyopathy. American College
    of Cardiology Foundation and the European Society of
    Cardiology. 2003. Electronic copies: Available from the [European
    Society of Cardiology (ESC) Web
    site](http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-HCM-biblio-2003.pdf).

-   Hypertrophic cardiomyopathy. Pocket guidelines. Available from the
    [ESC Web
    site](http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/HCM-pocket.aspx).
    Also available for PDA download from the [ESC Web
    site](http://pocketgram.net/escardio/).

-   Slide set for hypertrophic cardiomyopathy. Electronic copies:
    Available from the [ESC Web
    site](http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-HCM-slides.pdf).

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on May 13, 2004. The information
was verified by the guideline developer on July 29, 2004. This summary
was updated by ECRI on March 6, 2007 following the U.S. Food and Drug
Administration (FDA) advisory on Coumadin (warfarin sodium). This
summary was updated by ECRI Institute on September 7, 2007 following the
revised U.S. Food and Drug Administration (FDA) advisory on Coumadin
(warfarin).

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

#### NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce,
approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced
under the auspices of medical specialty societies, relevant professional
associations, public or private organizations, other government
agencies, health care organizations or plans, and similar entities.

Guidelines represented on the NGC Web site are submitted by guideline
developers, and are screened solely to determine that they meet the NGC
Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

NGC, AHRQ, and its contractor ECRI Institute make no warranties
concerning the content or clinical efficacy or effectiveness of the
clinical practice guidelines and related materials represented on this
site. Moreover, the views and opinions of developers or authors of
guidelines represented on this site do not necessarily state or reflect
those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or
hosting of guidelines in NGC may not be used for advertising or
commercial endorsement purposes.

Readers with questions regarding guideline content are directed to
contact the guideline developer.

Bottom of Form

© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008