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Dtsch Med Wochenschr 2005; 130(18): 1150-1154
DOI: 10.1055/s-2005-866802
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Kardiologie
© 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 patientsC. Pellnitz1 , C. Geier1 , A. Perrot1 , R. Dietz1 , K. J. Osterziel1 , W. Haverkamp
  • 1Medizinische Klinik mit Schwerpunkt Kardiologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
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Publication History

eingereicht: 20.12.2004

akzeptiert: 17.3.2005

Publication Date:
26 April 2005 (online)

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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
    Google Scholar
  • 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
    Google Scholar
  • 3 Burkhard-Meier C, Hoppe U C. Primary prevention of sudden cardiac death.  Dtsch Med Wochenschr. 2003;  128 2547-2552
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 7 Elliott P, McKenna W J. Hypertrophic cardiomyopathy.  Lancet. 2004;  363 1881-1891
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 18 Maron B J. The electrocardiogram as a diagnostic tool for hypertrophic cardiomyopathy: revisited.  Ann Noninvasive Electrocardiol. 2001;  6 277-279
    Google Scholar
  • 19 Maron B J. Hypertrophic cardiomyopathy: a systematic review.  JAMA. 2002;  287 1308-1320
    Google Scholar
  • 20 Maron B J. Hypertrophic cardiomyopathy: an important global disease.  Am J Med. 2004;  116 63-65
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 27 McKenna W J, Behr E R. Hypertrophic cardiomyopathy: management, risk stratification, and prevention of sudden death.  Heart. 2002;  87 169-176
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar
  • 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
    Google Scholar

Christina Pellnitz

Med. Klinik mit Schwerpunkt Kardiologie, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum

Augustenburger Platz 1

13353 Berlin

Phone: +49/30/450553366

Fax: +49/30/450553961

Email: Christina.pellnitz@charite.de

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