RSS-Feed abonnieren
DOI: 10.1055/s-2005-866802
© Georg Thieme Verlag Stuttgart · New York
Der plötzliche Herztod bei familiärer hypertropher Kardiomyopathie
Identifizierung von HochrisikopatientenSudden cardiac death in familial hypertrophic cardiomyopathy. Identification of high-risk patientsPublikationsverlauf
eingereicht: 20.12.2004
akzeptiert: 17.3.2005
Publikationsdatum:
26. April 2005 (online)

Zusammenfassung
Die hypertrophe Kardiomyopathie (HCM) ist eine relativ häufige, genetisch bedingte, primäre Herzmuskelerkrankung, die durch eine meist asymmetrische Septumhypertrophie mit oder ohne linksventrikuläre Ausflussbahnobstruktion charakterisiert ist. Die Erkrankung ist genetisch heterogen, zwölf krankheitsverursachende Gene wurden bisher beschrieben. Histologisch finden sich hypertrophierte Myofibrillen mit atypischen Verzweigungen (myocardial disarray) sowie eine Vermehrung des interstitiellen Bindegewebes. Zu den typischen Symptomen gehören Palpitationen, Belastungsdyspnoe und/oder Angina pectoris. Ventrikuläre Herzrhythmusstörungen und plötzliche Todesfälle treten gehäuft auf; in erster Linie sind hiervon junge Menschen betroffen.
Die vorliegende Arbeit stellt die Kriterien für die Risikostratifizierung bei HCM und deren Bewertung dar. Um von einem plötzlichen Herztod (PHT) bedrohte Patienten zu identifizieren, ist eine ausführliche klinisch-kardiologische Untersuchung notwendig, in die auch neuere bildgebende Verfahren wie beispielsweise die Magnetresonanz-Tomographie mit einbezogen werden sollten. Als Marker für ein erhöhtes PHT-Risiko gelten ein durchgemachter Herzstillstand bzw. Kammerflimmern, nicht-anhaltende und anhaltende Kammertachykardien, plötzliche Todesfälle in der Familie, ungeklärte Synkopen, eine abnorme Blutdruckreaktion unter Belastung und eine Septumdicke von ≥ 3 cm. Da manche Mutationen mit einem besonders hohen Risiko für einen plötzlichen Herztod assoziiert zu sein scheinen, wäre die Kenntnis des zugrunde liegenden genetischen Defektes wünschenswert. Leider steht die genetische Diagnostik bei HCM als Routineverfahren heute noch nicht zur Verfügung.
Therapie der Wahl bei dokumentierten lebensbedrohlichen Arrhythmien oder überlebtem PHT ist der implantierbare Kardioverter/Defibrillator (ICD), der auch im Rahmen der Primärprophylaxe eingesetzt wird, wenn die Risikostratifizierung positiv ausfällt. Hierfür stehen Algorithmen und Scores zur Verfügung. Der Entschluss zur prophylaktischen Implantation eines Kardioverters/Defibrillators bleibt aber immer eine individuelle Entscheidung.
Hypertrophic cardiomyopathy (HCM) is a relatively frequent, genetically determined primary cardiomyopathy, characterized by most often asymmetric hypertrophy of the ventricular septum with or without systolic obstruction of the left ventricular outflow tract. HCM is a genetically heterogeneous disease, with 12 different disease-causing genes beeing indentified to date. Histologically the disease is characterized by hypertophy and disarray of myofibrils as well as by an increase in myocardial fibrosis. Clinically, these changes may lead to palpitations, dyspnoe on exertion, and/or angina pectoris. However, they also lead to an increased propensity to the development of severe ventricular tachyarrhythmias and sudden cardiac death. The incidence of sudden death is significantly increased in HCM, particularly in affected young subjects. Risk stratification in HCM should include a complete clinical-cardiological evaluation that should also consider new diagnostic features, e. g. MR imaging. Major risk factors for sudden cardiac death include a survived cardiac arrest (ventricular fibrillation), non-sustained and sustained ventricular tachycardia, a history of premature familial sudden death, unexplained syncope, an abnormal blood pressure response on exercise, and left ventricular thickness greater than or equal to 3 cm. Ideally, risk stratification should also include genetic testing, since some gene mutations seem to be associated with a higher risk for sudden cardiac death than others. However, genetic testing in HCM in not yet available on a routine basis. The implantation of a cardioverter/defibrillator is first-line therapy in patients with documented ventricular tachycardia/fibrillation or patients who have survived sudden cardiac death. These devices also play an important role in the primary prevention of sudden cardiac death in HCM. Algorithms and scores are available to estimate the risk of sudden death, however, the decision to implant a cardioverter/defibrillator remains an individual decision in every single patient.
Literatur
- 1
Behr E R, Elliott P, McKenna W J.
Role of invasive EP testing in the evaluation and management of hypertrophic cardiomyopathy.
Card Electrophysiol Rev.
2002;
6
482-486
MissingFormLabel
- 2
Bonne G, Carrier L, Bercovici J. et al .
Cardiac myosin binding protein-C gene splice acceptor site mutation is associated
with familial hypertrophic cardiomyopathy.
Nat Genet.
1995;
11
438-440
MissingFormLabel
- 3
Burkhard-Meier C, Hoppe U C.
Primary prevention of sudden cardiac death.
Dtsch Med Wochenschr.
2003;
128
2547-2552
MissingFormLabel
- 4
Cecchi F, Maron B J, Epstein S E.
Long-term outcome of patients with hypertrophic cardiomyopathy successfully resuscitated
after cardiac arrest.
J Am Coll Cardiol.
1989;
13
1283-1288
MissingFormLabel
- 5
Charron P, Dubourg O, Desnos M. et al .
Diagnostic value of electrocardiography and echocardiography for familial hypertrophic
cardiomyopathy in a genotyped adult population.
Circulation.
1997;
96
214-219
MissingFormLabel
- 6
Dilsizian V, Bonow R O, Epstein S E, Fananapazir L.
Myocardial ischemia detected by thallium scintigraphy is frequently related to cardiac
arrest and syncope in young patients with hypertrophic cardiomyopathy.
J Am Coll Cardiol.
1993;
22
796-804
MissingFormLabel
- 7
Elliott P, McKenna W J.
Hypertrophic cardiomyopathy.
Lancet.
2004;
363
1881-1891
MissingFormLabel
- 8
Elliott P M, Gimeno B, Mahon N G, Poloniecki J D, McKenna W J.
Relation between severity of left-ventricular hypertrophy and prognosis in patients
with hypertrophic cardiomyopathy.
Lancet.
2001;
357
420-424
MissingFormLabel
- 9
Elliott P M, Poloniecki J, Dickie S. et al .
Sudden death in hypertrophic cardiomyopathy: identification of high risk patients.
J Am Coll Cardiol.
2000;
36
2212-2218
MissingFormLabel
- 10
Elliott P M, Sharma S, Varnava A, Poloniecki J, Rowland E, McKenna W J.
Survival after cardiac arrest or sustained ventricular tachycardia in patients with
hypertrophic cardiomyopathy.
J Am Coll Cardiol.
1999;
33
1596-1601
MissingFormLabel
- 11
Fananapazir L, Chang A C, Epstein S E, McAreavey D.
Prognostic determinants in hypertrophic cardiomyopathy. Prospective evaluation of
a therapeutic strategy based on clinical, Holter, hemodynamic, and electrophysiological
findings.
Circulation.
1992;
86
730-740
MissingFormLabel
- 12
Frenneaux M P, Counihan P J, Caforio A L, Chikamori T, McKenna W J.
Abnormal blood pressure response during exercise in hypertrophic cardiomyopathy.
Circulation.
1990;
82
1995-2002
MissingFormLabel
- 13
Geier C, Perrot A, Ozcelik C. et al .
Mutations in the human muscle LIM protein gene in families with hypertrophic cardiomyopathy.
Circulation.
2003;
107
1390-1395
MissingFormLabel
- 14
Geisterfer-Lowrance A A, Kass S, Tanigawa G. et al .
A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin
heavy chain gene missense mutation.
Cell.
1990;
62
999-1006
MissingFormLabel
- 15
Hoffmann B, Schmidt-Traub H, Perrot A, Osterziel K J, Gessner R.
First mutation in cardiac troponin C, L29Q, in a patient with hypertrophic cardiomyopathy.
Hum Mutat.
2001;
17
524
MissingFormLabel
- 16
Kimura A, Harada H, Park J E. et al .
Mutations in the cardiac troponin I gene associated with hypertrophic cardiomyopathy.
Nat Genet.
1997;
16
379-382
MissingFormLabel
- 17
Klues H G, Schiffers A, Maron B J.
Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy:
morphologic observations and significance as assessed by two-dimensional echocardiography
in 600 patients.
J Am Coll Cardiol.
1995;
26
1699-1708
MissingFormLabel
- 18
Maron B J.
The electrocardiogram as a diagnostic tool for hypertrophic cardiomyopathy: revisited.
Ann Noninvasive Electrocardiol.
2001;
6
277-279
MissingFormLabel
- 19
Maron B J.
Hypertrophic cardiomyopathy: a systematic review.
JAMA.
2002;
287
1308-1320
MissingFormLabel
- 20
Maron B J.
Hypertrophic cardiomyopathy: an important global disease.
Am J Med.
2004;
116
63-65
MissingFormLabel
- 21
Maron B J, Gardin J M, Flack J M, Gidding S S, Kurosaki T T, Bild D E.
Prevalence of hypertrophic cardiomyopathy in a general population of young adults.
Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk
Development in (Young) Adults.
Circulation.
1995;
92
785-789
MissingFormLabel
- 22
Maron B J, McKenna W J, Danielson G K. 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 and the European Society
of Cardiology Committee for Practice Guidelines.
Eur Heart J.
2003;
24
1965-1991
MissingFormLabel
- 23
Maron B J, Seidman J G, Seidman C E.
Proposal for contemporary screening strategies in families with hypertrophic cardiomyopathy.
J Am Coll Cardiol.
2004;
44
2125-2132
MissingFormLabel
- 24
Maron B J, Shen W K, Link M S. et al .
Efficacy of implantable cardioverter-defibrillators for the prevention of sudden death
in patients with hypertrophic cardiomyopathy.
N Engl J Med.
2000;
342
365-373
MissingFormLabel
- 25
Maron B J, Shirani J, Poliac L C, Mathenge R, Roberts W C, Mueller F O.
Sudden death in young competitive athletes. Clinical, demographic, and pathological
profiles.
JAMA.
1996;
276
199-204
MissingFormLabel
- 26
McKenna W, Deanfield J, Faruqui A, England D, Oakley C, Goodwin J.
Prognosis in hypertrophic cardiomyopathy: role of age and clinical, electrocardiographic
and hemodynamic features.
Am J Cardiol.
1981;
47
532-538
MissingFormLabel
- 27
McKenna W J, Behr E R.
Hypertrophic cardiomyopathy: management, risk stratification, and prevention of sudden
death.
Heart.
2002;
87
169-176
MissingFormLabel
- 28
McKenna W J, Franklin R C, Nihoyannopoulos P, Robinson K C, Deanfield J E.
Arrhythmia and prognosis in infants, children and adolescents with hypertrophic cardiomyopathy.
J Am Coll Cardiol.
1988;
11
147-153
MissingFormLabel
- 29
Mogensen J, Klausen I C, Pedersen A K. et al .
Alpha-cardiac actin is a novel disease gene in familial hypertrophic cardiomyopathy.
J Clin Invest.
1999;
103
R39-R43
MissingFormLabel
- 30
Moolman J A, Reith S, Uhl K. et al .
A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for
inherited hypertrophic cardiomyopathy with incomplete disease penetrance.
Circulation.
2000;
101
1396-1402
MissingFormLabel
- 31
Moon J C, Fisher N G, McKenna W J, Pennell D J.
Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance
in patients with non-diagnostic echocardiography.
Heart.
2004;
90
645-649
MissingFormLabel
- 32
Moon J C, McKenna W J, McCrohon J A, Elliott P M, Smith G C, Pennell D J.
Toward clinical risk assessment in hypertrophic cardiomyopathy with gadolinium cardiovascular
magnetic resonance.
J Am Coll Cardiol.
2003;
41
1561-1567
MissingFormLabel
- 33
Moon J C, Reed E, Sheppard M N. et al .
The histologic basis of late gadolinium enhancement cardiovascular magnetic resonance
in hypertrophic cardiomyopathy.
J Am Coll Cardiol.
2004;
43
2260-2264
MissingFormLabel
- 34
Niimura H, Patton K K, McKenna W J. et al .
Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly.
Circulation.
2002;
105
446-451
MissingFormLabel
- 35
Olivotto I, Maron B J, Montereggi A, Mazzuoli F, Dolara A, Cecchi F.
Prognostic value of systemic blood pressure response during exercise in a community-based
patient population with hypertrophic cardiomyopathy.
J Am Coll Cardiol.
1999;
33
2044-2051
MissingFormLabel
- 36
Poetter K, Jiang H, Hassanzadeh S. et al .
Mutations in either the essential or regulatory light chains of myosin are associated
with a rare myopathy in human heart and skeletal muscle.
Nat Genet.
1996;
13
63-69
MissingFormLabel
- 37
Polderman F N, Cohen J, Blom N A. et al .
Sudden unexpected death in children with a previously diagnosed cardiovascular disorder.
Int J Cardiol.
2004;
95
171-176
MissingFormLabel
- 38
Richard P, Charron P, Carrier L. et al .
Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations,
and implications for a molecular diagnosis strategy.
Circulation.
2003;
107
2227-2232
MissingFormLabel
- 39
Richardson P, McKenna W, Bristow M. et al .
Report of the 1995 World Health Organization/International Society and Federation
of Cardiology Task Force on the Definition and Classification of cardiomyopathies.
Circulation.
1996;
93
841-842
MissingFormLabel
- 40
Sadoul N, Prasad K, Elliott P M, Bannerjee S, Frenneaux M P, McKenna W J.
Prospective prognostic assessment of blood pressure response during exercise in patients
with hypertrophic cardiomyopathy.
Circulation.
1997;
96
2987-2991
MissingFormLabel
- 41
Satoh M, Takahashi M, Sakamoto T, Hiroe M, Marumo F, Kimura A.
Structural analysis of the titin gene in hypertrophic cardiomyopathy: identification
of a novel disease gene.
Biochem Biophys Res Commun.
1999;
262
411-417
MissingFormLabel
- 42
Shirani J, Pick R, Roberts W C, Maron B J.
Morphology and significance of the left ventricular collagen network in young patients
with hypertrophic cardiomyopathy and sudden cardiac death.
J Am Coll Cardiol.
2000;
35
36-44
MissingFormLabel
- 43
Spirito P, Bellone P, Harris K M, Bernabo P, Bruzzi P, Maron B J.
Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic
cardiomyopathy.
N Engl J Med.
2000;
342
1778-1785
MissingFormLabel
- 44
Spirito P, Seidman C E, McKenna W J, Maron B J.
The management of hypertrophic cardiomyopathy.
N Engl J Med.
1997;
336
775-785
MissingFormLabel
- 45
Thierfelder L, Watkins H, MacRae C. et al .
Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy:
a disease of the sarcomere.
Cell.
1994;
77
701-712
MissingFormLabel
- 46
Torricelli F, Girolami F, Olivotto I. et al .
Prevalence and clinical profile of troponin T mutations among patients with hypertrophic
cardiomyopathy in tuscany.
Am J Cardiol.
2003;
92
1358-1362
MissingFormLabel
- 47
Van Driest S L, Ellsworth E G, Ommen S R, Tajik A J, Gersh B J, Ackerman M J.
Prevalence and spectrum of thin filament mutations in an outpatient referral population
with hypertrophic cardiomyopathy.
Circulation.
2003;
108
445-451
MissingFormLabel
- 48
Van Driest S L, Jaeger M A, Ommen S R. et al .
Comprehensive analysis of the beta-myosin heavy chain gene in 389 unrelated patients
with hypertrophic cardiomyopathy.
J Am Coll Cardiol.
2004;
44
602-610
MissingFormLabel
- 49
Van Driest S L, Vasile V C, Ommen S R. et al .
Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy.
J Am Coll Cardiol.
2004;
44
1903-1910
MissingFormLabel
- 50
Watkins H, McKenna W J, Thierfelder L. et al .
Mutations in the genes for cardiac troponin T and alpha-tropomyosin in hypertrophic
cardiomyopathy.
N Engl J Med.
1995;
332
1058-1064
MissingFormLabel
- 51
Yetman A T, McCrindle B W, MacDonald C, Freedom R M, Gow R.
Myocardial bridging in children with hypertrophic cardiomyopathy-a risk factor for
sudden death.
N Engl J Med.
1998;
339
1201-1209
MissingFormLabel
Christina Pellnitz
Med. Klinik mit Schwerpunkt Kardiologie, Charité - Universitätsmedizin Berlin, Campus
Virchow-Klinikum
Augustenburger Platz 1
13353 Berlin
Telefon: +49/30/450553366
Fax: +49/30/450553961
eMail: Christina.pellnitz@charite.de