Familial Hypertrophic Cardiomyopathy

Actionability Adult Summary Report

Genes: ACTC1 (HGNC:143) CSRP3 (HGNC:2472) MYBPC3 (HGNC:7551) MYH7 (HGNC:7577) MYL2 (HGNC:7583) MYL3 (HGNC:7584) PRKAG2 (HGNC:9386) TNNI3 (HGNC:11947) TNNT2 (HGNC:11949) TPM1 (HGNC:12010)
Mode(s) of Inheritance:Autosomal Dominant
Literature Search: 08/14/2017
Curation Status: Released - Under Revision (2.1.1)
Release History
Related Reports
Pediatric Summary Report

Secondary Findings in Adult Subjects. Non-diagnostic, excludes newborn screening & prenatal testing/screening.

Actionability Assertions

Gene Condition (MONDO ID) OMIM ID Final Assertion
ACTC1 N/A (0024573) 612098 Assertion Pending
CSRP3 N/A (0024573) 612124 Assertion Pending
MYBPC3 N/A (0024573) 115197 Assertion Pending
MYH7 N/A (0024573) 192600 Assertion Pending
MYL2 N/A (0024573) 608758 Assertion Pending
MYL3 N/A (0024573) 608751 Assertion Pending
PRKAG2 N/A (0024573) 600858 Assertion Pending
TNNI3 N/A (0024573) 613690 Assertion Pending
TNNT2 N/A (0024573) 115195 Assertion Pending
TPM1 N/A (0024573) 115196 Assertion Pending

Actionability Assertion Rationale

  • This topic was initially scored prior to development of the process for making actionability assertions. The Actionability Working Group decided to defer making an assertion until after the topic could be reviewed through the update process.

Actionability Scores

Outcome / Intervention Pair Severity Likelihood Effectiveness Nature of Intervention Total Score
Sudden Cardiac Death / ICD Implantation 3 2N 3N 2 10NN
View scoring key
Domain of Actionability Scoring Metric State of the Knowledgebase
Severity: What is the nature of the threat to health to an individual? 3 = Sudden death as a reasonably possible outcome
2 = Reasonable possibility of death or major morbidity
1 = Modest morbidity
0 = Minimal or no morbidity 		N/A
Likelihood: What is the chance that the outcome will occur? 3 = >40% chance
2 = 5%-39% chance
1 = 1%-4% chance
0 = <1% chance 		A = Substantial evidence or evidence from a high tier (tier 1)
B = Moderate evidence or evidence from a moderate tier (tier 2)
C = Minimal evidence or evidence from a lower tier (tier 3 or 4)
D = Poor evidence or evidence not provided in the report
N = Evidence based on expert contributions (tier 5)
Effectiveness: What is the effectiveness of a specific intervention in preventing or diminishing the risk of harm? 3 = Highly effective
2 = Moderately effective
1 = Minimally effective
0 = Controversial or unknown effectiveness
IN = Ineffective/No interventiona 		A = Substantial evidence or evidence from a high tier (tier 1)
B = Moderate evidence or evidence from a moderate tier (tier 2)
C = Minimal evidence or evidence from a lower tier (tier 3 or 4)
D = Poor evidence or evidence not provided in the report
N = Evidence based on expert contributions (tier 5)
Nature of intervention: How risky, medically burdensome, or intensive is the intervention? 3 = Low risk, or medically acceptable and low intensity
2 = Moderate risk, moderately acceptable or intensive
1 = Greater risk, less acceptable and substantial intensity
0 = High risk, poorly acceptable or intensive 		N/A
a Do not score the remaining categories

Prevalence of the Genetic Condition

Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease. The prevalence in the general population is estimated at 1:500, which is equivalent to at least 600,000 people affected in the United States.
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768, Gersh BJ, et al. (2011) PMID: 22068435, (2013) URL: www.csanz.edu.au., Epstein AE, et al. (2013) PMID: 23255456

Clinical Features (Signs / symptoms)

HCM is a primary cardiac disorder characterized by hypertrophy, usually left ventricle hypertrophy (LVH), in the absence of other loading conditions. Clinical manifestations of HCM range from asymptomatic LVH to progressive heart failure to sudden cardiac death (SCD). Progressive ventricular outflow obstruction may cause palpitation associated with arrhythmia, congestive heart failure, and sudden death. Other symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. Symptoms can be readily provoked by exercise.
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768, Gersh BJ, et al. (2011) PMID: 22068435, (2013) URL: www.csanz.edu.au., Epstein AE, et al. (2013) PMID: 23255456, Online Medelian Inheritance in Man. (2016) OMIM: 192600

Natural History (Important subgroups & survival / recovery)

HCM is a heterogeneous cardiac disease with a diverse clinical presentation and course, presenting in all age groups from infancy to the very elderly; however, LVH often becomes apparent during adolescence or young adulthood. Although HCM was initially thought to be associated with high mortality, it is now recognized that most affected individuals will have a relatively mild course of disease and can achieve normal life expectancy without disability or the necessity for major therapeutic interventions. In some patients, HCM is associated with disease complications that may be profound with the potential to result in disease progression or premature death. An important minority of persons with HCM are at increased risk for SCD (most often occurring in adolescents or young adults) most likely related to ventricular tachycardia/ventricular fibrillation. Approximately 5-10% of individuals with HCM progress to end-stage disease. The annual mortality rate in individuals with end-stage disease is estimated at 11%. Community-based studies suggest an annual mortality rate in the range of 1%. HCM is the commonest structural cause of SCD in individuals less than 35 years, including competitive athletes. There are very few data on the natural histories of individuals who carry a pathogenic variant and have no phenotype, but recent studies suggest a benign clinical course for most clinically unaffected carriers.
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768, Gersh BJ, et al. (2011) PMID: 22068435, (2013) URL: www.csanz.edu.au., Epstein AE, et al. (2013) PMID: 23255456, Elliott PM, et al. (2014) PMID: 25173338

Description of sources of evidence:

Tier 1: Evidence from a systematic review or a meta-analysis or clinical practice guideline clearly based on a systematic review.
Tier 2: Evidence from clinical practice guidelines or broad-based expert consensus with non-systematic evidence review.
Tier 3: Evidence from another source with non-systematic review of evidence with primary literature cited.
Tier 4: Evidence from another source with non-systematic review of evidence with no citations to primary data sources.
Tier 5: Evidence from a non-systematically identified source.

Mode of Inheritance

Autosomal Dominant

Prevalence of Genetic Variants

Unknown
In up to 60% of adolescents and adults with HCM, the disease is an autosomal dominant trait caused by pathogenic variants in cardiac sarcomere protein genes (MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL3). Five to ten percent of adult cases are caused by other genetic disorders including 1% associated with PRKAG2. (Tier 3) It is unknown how many cases of HCM are due to pathogenic variants in ACTC1 or CSRP3. (Tier 4)
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768, Elliott PM, et al. (2014) PMID: 25173338

Penetrance (Includes any high-risk racial or ethnic subgroups)

Unknown
The association with specific genes and HCM prognosis remains controversial.
Tier 5 View Citations

Sabater-Molina M, et al. (2017) PMID: 28369730

>= 40 %
Penetrance of HCM is variable based on the underlying genotype and the age of patient at assessment. Multiple small studies of relatives of HCM probands have found that the penetrance of HCM (based on cardiac evaluation) is over 40% in at least one gene (MYBPC3).
Tier 5 View Citations

Calore C, et al. (2015) PMID: 25740977, Terauchi Y, et al. (2015) PMID: 25123604, Page SP, et al. (2012) PMID: 22267749, Oliva-Sandoval MJ, et al. (2010) PMID: 21088121, Christiaans I, et al. (2010) PMID: 20019025, Michels M, et al. (2009) PMID: 19666645

5-39 %
One study of 653 HCM patients with an absence of SCD risk factors and no or mild symptoms (aged 10-75) found that over 10 years of follow up the cumulative sudden death risk was 5.9%. During the follow up ICDs were implanted in an additional 6% of patients based on the development of SCD risk factors. The underlying HCM genes were not reported.
Tier 5 View Citations

Spirito P, et al. (2014) PMID: 24630786

5-39 %
A pooled evaluation of found 22.8% (95% CI: 17.3 to 28.2%) of HCM patients with pathogenic variants in sarcomere-encoding genes developed hypertension.
Tier 1 View Citations

Lopes LR, et al. (2013) PMID: 23674365

Relative Risk (Includes any high-risk racial or ethnic subgroups)

Unknown

Expressivity

HCM has variable expressivity; clinical manifestations vary from individual to individual even within the same family.
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768

Description of sources of evidence:

Tier 1: Evidence from a systematic review or a meta-analysis or clinical practice guideline clearly based on a systematic review.
Tier 2: Evidence from clinical practice guidelines or broad-based expert consensus with non-systematic evidence review.
Tier 3: Evidence from another source with non-systematic review of evidence with primary literature cited.
Tier 4: Evidence from another source with non-systematic review of evidence with no citations to primary data sources.
Tier 5: Evidence from a non-systematically identified source.

Patient Management

No treatments currently exist to prevent or decrease disease development or to reverse established manifestations
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768

In all cases of HCM, clinicians should consider evaluation of patients in centers with multidisciplinary teams, with expertise in diagnosis, genetics, risk stratification, and management of heart muscle disease.
Tier 2 View Citations

Elliott PM, et al. (2014) PMID: 25173338

All patients should undergo comprehensive SCD risk stratification at initial evaluation. Patients with multiple risk factors have a substantially increased risk of sudden death sufficient to ward consideration for prophylactic therapy. In a study of 268 patients with HCM, those with two or more risk factors had a lower six-year survival rate from sudden death than those with one or no risk factors (72% versus 94%). 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.
Tier 1 View Citations

Gersh BJ, et al. (2011) PMID: 22068435

SCD risk stratification is reasonable on a periodic basis (12 to 24 months) for patients with HCM who have not undergone ICD therapy. There are no randomized trials or statistically validated prospective prediction models that can be used to guide ICD implantation in patients with HCM. Recommendations are instead based on observational, retrospective cohort studies that have determined the relationship between clinical characteristics and prognosis.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435, Elliott PM, et al. (2014) PMID: 25173338

It is reasonable to recommend an implantable cardioverter-defibrillator (ICD) for patients with one or more major risk factors for SCD (e.g., history of sudden death presumably due to HCM in a first-degree relative, abnormal blood pressure response during exercise, decreased left-ventricular wall thickness). In an international multicenter registry of HCM patients with ICDs, patients with primary prevention ICDs placed on the basis of 1 or more of the conventional risk markers experienced appropriate ICD therapy at a rate of 4% per year. ICD therapy was effective in terminating VT/VF despite the complex HCM phenotype.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435, (2013) URL: www.csanz.edu.au., Epstein AE, et al. (2013) PMID: 23255456, (2014) URL: www.nice.org.uk., Garratt CJ, et al. (2010) PMID: 20663787, Elliott PM, et al. (2014) PMID: 25173338

Within the Swedish ICD Registry, all-cause mortality in 342 HCM patients with an ICD was found to be larger than that of the age and sex-matched Swedish general population (standardized mortality ratio: 3.4 (95% CI: 2.4-4.5; p<0.0001) over a mean follow up of 5.4 years. However, ICDs almost eliminated premature arrhythmic death in the population with only two patients dying suddenly (after having ICD turned off or removed). The main cause of death in individuals was still attributed to HCM primary due to heart failure. The genetic cause of HCM in the population was not reported.
Tier 5 View Citations

Magnusson P, et al. (2016) PMID: 26808417

Healthcare professionals should offer people with HCM clear and consistent information about the prevention of infective endocarditis, including the benefits and risks of antibiotic prophylaxis (including why prophylaxis is no longer routinely recommended), the importance of maintaining good oral health, education regarding the symptoms of infective endocarditis, and the risks of invasive procedures including non-medical procedures such as body piercing or tattooing. Any episodes of infection in people at risk for infective endocarditis should be investigated and treated promptly to reduce the risk of endocarditis developing.
Tier 2 View Citations

(2016) URL: nice.org.uk.

Pregnant women with HCM seeking pregnancy termination should be referred to a hospital-based provider (with patient permission), with the procedure performed in-hospital after consultation with a cardiologist.
Tier 2 View Citations

Guiahi M, et al. (2012) PMID: 23039921, Elliott PM, et al. (2014) PMID: 25173338

Patients with HCM may benefit from beta-blockers and calcium-channel blockers; however, the usefulness of these agents to alter clinical outcomes is not well established for the management of asymptomatic patients with HCM with or without obstruction.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435, (2013) URL: www.csanz.edu.au., Elliott PM, et al. (2014) PMID: 25173338

A pilot randomized controlled trial examined the use of diltiazem (a calcium channel blocker) in 38 individuals with a pathogenic or likely pathogenic variant in a sarcomere gene with no cardiovascular symptoms or concomitant illnesses. Participants had a mean age of 15.8 years (range: 5 to 39 years) and received a median of 756 days of treatment. This initial study found that while heart rate and blood pressure did not significantly differ between groups, improved early LV remodeling was improved in the diltiazem treatment group (p<0.001). Over the course of the study four participants developed overt HCM (two in each treatment group).
Tier 5 View Citations

Ho CY, et al. (2015) PMID: 25543971

A diagnosis of HCM is not a contraindication for pregnancy, but female patients should be carefully evaluated in regard to the risk of pregnancy. Expert maternal/fetal medical care and pre-pregnancy risk counseling is advised. Scheduled (induced) vaginal delivery is recommended as the first choice in most patients.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435, Elliott PM, et al. (2014) PMID: 25173338

Counseling on safe and effective contraception is indicated in all women of fertile age.
Tier 2 View Citations

Elliott PM, et al. (2014) PMID: 25173338

Surveillance

In individuals with pathogenic variants who do not express the HCM phenotype, it is recommended to perform serial electrocardiogram, transthoracic echocardiogram (TTE), and clinical assessment at periodic intervals (every 1 to 5 years in adults), based on the patient’s age and change in clinical status. One study of 235 found that at first cardiac evaluation almost one-quarter of asymptomatic carriers of MYBPC3 variants were clinically diagnosed with HCM. Risk factors for SCD were frequently present and 11% of carriers were at risk for SCD. A second study more broadly addressing 76 individuals with HCM associated pathologic variants identified through DNA testing found clinical HCM in 41% of those examined.
Tier 1 View Citations

Gersh BJ, et al. (2011) PMID: 22068435, Elliott PM, et al. (2014) PMID: 25173338

24-to-48-hour ambulatory (Holter) electrocardiographic monitoring is recommended for initial evaluation of patients with HCM to detect ventricular tachycardia (VT) and identify patients who may be candidates for ICD and upon development of palpations or lightheadedness. On routine ambulatory (Holter) 24-h ECG monitoring, non-sustained burst of ventricular tachycardia (often asymptomatic) are present in 20-30% of adult HCM patients.
Tier 1 View Citations

Gersh BJ, et al. (2011) PMID: 22068435, Elliott PM, et al. (2014) PMID: 25173338

A comprehensive evaluation of diastolic function is recommended to detect diastolic dysfunction and the assessment of LV filling pressures.
Tier 2 View Citations

Elliott PM, et al. (2014) PMID: 25173338

Routine laboratory testing aids the detection of extra-cardiac conditions that cause or exacerbate ventricular dysfunction (for example, thyroid disease, renal dysfunction and diabetes mellitus) and secondary organ dysfunction in patients with severe heart failure. First-line laboratory screening should include hematology, glucose, cardiac enzymes (creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), renal and liver function tests, pH, electrolytes and uric acid.
Tier 2 View Citations

Elliott PM, et al. (2014) PMID: 25173338

Irrespective of symptoms, cardiopulmonary exercise testing with simultaneous measurement of respiratory gases (or standard treadmill or bicycle ergometry when unavailable) should be considered to assess the severity and mechanism of exercise intolerance and change in systolic blood pressure.
Tier 2 View Citations

Elliott PM, et al. (2014) PMID: 25173338

In pregnant women with HCM, increased surveillance for fetal bradycardia is warranted.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435

Circumstances to Avoid

Care should be taken to avoid high dose diuretics, venodilators, and arterial vasodilators to avoid vasodilation because these may exacerbate the degree of ventricular obstruction.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435

Participation in competitive athletics for asymptomatic, genotype-positive HCM patients without evidence of left ventricular hypertrophy is reasonable, particularly in the absence of a family history of HCM-related sudden death. Those who wish to participate should be advised on an individual basis, taking into account the local legal framework, the underlying variant, and the type of sporting activity. Athletes with a probable or unequivocal clinical expression and diagnosis of HCM (i.e., with the disease phenotype of left ventricular hypertrophy) should not participate in most competitive sports, with the exception of those of low intensity.
Tier 2 View Citations

Elliott PM, et al. (2014) PMID: 25173338, Maron BJ, et al. (2015) PMID: 26527714

Avoid burst activities, like sprinting, as well as intense isometric exercise, such as heavy weight lifting; avoid exercise in extreme environmental conditions and maintain adequate hydration.
Tier 2 View Citations

Gersh BJ, et al. (2011) PMID: 22068435

Description of sources of evidence:

Tier 1: Evidence from a systematic review or a meta-analysis or clinical practice guideline clearly based on a systematic review.
Tier 2: Evidence from clinical practice guidelines or broad-based expert consensus with non-systematic evidence review.
Tier 3: Evidence from another source with non-systematic review of evidence with primary literature cited.
Tier 4: Evidence from another source with non-systematic review of evidence with no citations to primary data sources.
Tier 5: Evidence from a non-systematically identified source.

Nature of Intervention

Management of HCM includes regular invasive and non-invasive screening tests and the possible recommendation of ICD therapy, which confers appreciable risk.\n\nReported rates of complications include approximately 25% of patients with HCM who experienced inappropriate ICD discharge; 6% to 13% who experienced lead complications (fracture, dislodgment, oversensing); 4% to 5% who developed a device-related infection; and approximately 2% to 3% who experienced bleeding or thrombosis complications.
Context: Adult
View Citations

Gersh BJ, et al. (2011) PMID: 22068435

Chance to Escape Clinical Detection

General population screening recommendations are inadequate for individuals with HCM. SCD may be the first manifestation of disease.
Context: Adult
View Citations

AL Cirino, et al. (2008) NCBI: NBK1768

Description of sources of evidence:

Tier 1: Evidence from a systematic review or a meta-analysis or clinical practice guideline clearly based on a systematic review.
Tier 2: Evidence from clinical practice guidelines or broad-based expert consensus with non-systematic evidence review.
Tier 3: Evidence from another source with non-systematic review of evidence with primary literature cited.
Tier 4: Evidence from another source with non-systematic review of evidence with no citations to primary data sources.
Tier 5: Evidence from a non-systematically identified source.

References List

AL Cirino, C Ho. Hypertrophic Cardiomyopathy Overview. (2008) [Updated Jan 16 2014]. In: RA Pagon, MP Adam, HH Ardinger, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1768/

Calore C, De Bortoli M, Romualdi C, Lorenzon A, Angelini A, Basso C, Thiene G, Iliceto S, Rampazzo A, Melacini P. (2015) A founder MYBPC3 mutation results in HCM with a high risk of sudden death after the fourth decade of life. Journal of medical genetics. 52(5):338-47.

CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 1; CMH1. Online Medelian Inheritance in Man, OMIM®. Johns Hopkins University, Baltimore, MD. MIM: 192600, (2016) World Wide Web URL: http://omim.org/

Christiaans I, Birnie E, van Langen IM, van Spaendonck-Zwarts KY, van Tintelen JP, van den Berg MP, Atsma DE, Helderman-van den Enden AT, Pinto YM, Hermans-van Ast JF, Bonsel GJ, Wilde AA. (2010) The yield of risk stratification for sudden cardiac death in hypertrophic cardiomyopathy myosin-binding protein C gene mutation carriers: focus on predictive screening. European heart journal. 31(7):842-8.

Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H. (2014) 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). European heart journal. 35(39):2733-79.

Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO. (2013) 2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 127(3):e283-352.

Garratt CJ, Elliott P, Behr E, Camm AJ, Cowan C, Cruickshank S, Grace A, Griffith MJ, Jolly A, Lambiase P, McKeown P, O'Callagan P, Stuart G, Watkins H. (2010) Heart Rhythm UK position statement on clinical indications for implantable cardioverter defibrillators in adult patients with familial sudden cardiac death syndromes. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 12(8):1156-75.

Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H, Seidman CE, Towbin JA, Udelson JE, Yancy CW. (2011) 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 124(24):2761-96.

Guiahi M, Davis A. (2012) First-trimester abortion in women with medical conditions: release date October 2012 SFP guideline #20122. Contraception. 86(6):622-30.

Guidelines for the diagnosis and management of hypertrophic cardiomyopathy. Other (2013) URL: http://www.csanz.edu.au/documents/guidelines/clinical_practice/Hyertrophic_Cardiomyopathy.pdf

Ho CY, Lakdawala NK, Cirino AL, Lipshultz SE, Sparks E, Abbasi SA, Kwong RY, Antman EM, Semsarian C, Gonzalez A, Lopez B, Diez J, Orav EJ, Colan SD, Seidman CE. (2015) Diltiazem treatment for pre-clinical hypertrophic cardiomyopathy sarcomere mutation carriers: a pilot randomized trial to modify disease expression. JACC. Heart failure. 3(2):180-8.

Implantable cardioverter defibrillators and cardiac resynchronisation therapy for arrhythmias and heart failure. NICE (2014) URL: https://www.nice.org.uk/guidance/ta314

Lopes LR, Rahman MS, Elliott PM. (2013) A systematic review and meta-analysis of genotype-phenotype associations in patients with hypertrophic cardiomyopathy caused by sarcomeric protein mutations. Heart (British Cardiac Society). 99(24):1800-11.

Magnusson P, Gadler F, Liv P, Morner S. (2016) Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden. Journal of cardiovascular medicine (Hagerstown, Md.). 17(7):478-84.

Maron BJ, Levine BD, Washington RL, Baggish AL, Kovacs RJ, Maron MS. (2015) Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 2: Preparticipation Screening for Cardiovascular Disease in Competitive Athletes: A Scientific Statement From the American Heart Association and American College of Cardiology. Circulation. 132(22):e267-72.

Michels M, Soliman OI, Phefferkorn J, Hoedemaekers YM, Kofflard MJ, Dooijes D, Majoor-Krakauer D, Ten Cate FJ. (2009) Disease penetrance and risk stratification for sudden cardiac death in asymptomatic hypertrophic cardiomyopathy mutation carriers. European heart journal. 30(21):2593-8.

Oliva-Sandoval MJ, Ruiz-Espejo F, Monserrat L, Hermida-Prieto M, Sabater M, Garcia-Molina E, Ortiz M, Rodriguez-Garcia MI, Nunez L, Gimeno JR, Castro-Beiras A, Valdes M. (2010) Insights into genotype-phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3. Heart (British Cardiac Society). 96(24):1980-4.

Page SP, Kounas S, Syrris P, Christiansen M, Frank-Hansen R, Andersen PS, Elliott PM, McKenna WJ. (2012) Cardiac myosin binding protein-C mutations in families with hypertrophic cardiomyopathy: disease expression in relation to age, gender, and long term outcome. Circulation. Cardiovascular genetics. 5(2):156-66.

Prophylaxis against infective endocarditis: Antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. (2016) Accessed: 2017-06-19. URL: https://nice.org.uk/guidance/cg64

Sabater-Molina M, Perez-Sanchez I, Hernandez Del Rincon JP, Gimeno JR. (2017) Genetics of hypertrophic cardiomyopathy: A review of current state. Clinical genetics.

Spirito P, Autore C, Formisano F, Assenza GE, Biagini E, Haas TS, Bongioanni S, Semsarian C, Devoto E, Musumeci B, Lai F, Yeates L, Conte MR, Rapezzi C, Boni L, Maron BJ. (2014) Risk of sudden death and outcome in patients with hypertrophic cardiomyopathy with benign presentation and without risk factors. The American journal of cardiology. 113(9):1550-5.

Terauchi Y, Kubo T, Baba Y, Hirota T, Tanioka K, Yamasaki N, Furuno T, Kitaoka H. (2015) Gender differences in the clinical features of hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations. Journal of cardiology. 65(5):423-8.

Early Rule-Out Summary

This topic passed the early rule out stage

Findings of Early Rule-Out Assessment

  1. Is there a qualifying resource, such as a practice guideline or systematic review, for the genetic condition?
  2. Does the practice guideline or systematic review indicate that the result is actionable in one or more of the following ways?

    3. a. Patient Management

    b. Surveillance or Screening

    c. Circumstances to Avoid

  3. Is it actionable in an undiagnosed adult with the condition?
  4. Is this condition an important health problem?
  5. Is there at least on known pathogenic variant with at least moderate penetrance (≥40%) or moderate relative risk (≥2) in any population?