ACC_ESC 2003 肥厚型心肌病专家共识

ACC/ESC Expert consensus document 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 GuidelinesM Writing Committee Members, Barry J. Maron, (Co-Chair)a,b, William J. McKenna, (Co-Chair)a,b*, Gordon K. Danielsona, Lukas J. Kappenbergera,b*, Horst J. Kuhnb*, Christine E. Seidman, Pravin M. Shaha, William H. Spencer IIIa, Paolo Spiritoa,b*, Folkert J. Ten Catea,b*, E. Douglas Wiglea ACCF 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 Blomstro¨m-Lundqvist, Guy De Backer, Jaap Deckers, Markus Flather, Jaromir Hradec, Ali Oto, Alexander Parkhomenko, Sigmund Silber, Adam Torbicki Table of contents Preamble .................................................. 1966 Introduction ............................................... 1966 Organization of committee and evidence review. 1966 Purpose of this Expert Consensus Document ..... 1966 General considerations and perspectives............. 1966 Nomenclature, definitions, and clinical diagnosis .. 1967 Obstruction to LV Outflow .............................. 1967 Genetics and molecular diagnosis ..................... 1968 General considerations for natural history, and clinical course........................................ 1970 Symptoms and pharmacological management strategies ............................................. 1972 Beta-adrenergic blocking agents ................... 1972 Verapamil .............................................. 1973 Disopyramide .......................................... 1973 Drugs in end-stage phase ........................... 1974 Asymptomatic patients .............................. 1974 Infective endocarditis prophylaxis ................. 1974 Pregnancy .............................................. 1974 Treatment options for drug-refractory patients..... 1974 Additional approaches to relieve outflow obstruction and symptoms ......................... 1976 M When citing this document, the American College of Cardiology Foundation and the European Society of Cardiology would appreciate the following citation format: Maron BJ, McKenna WJ, Danielson GK, Kappenberger LJ, Kuhn HJ, Seidman CE, Shah PM, Spencer WH, Spirito P, Ten Cate FJ, Wigle ED. ACC/ESC clinical expert consensus document on hypertrophic cardiomyopathy: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines (Committee to Develop an Expert Consensus Document on Hypertrophic Cardiomyopathy). Eur Heart J 2003; doi:10.1016/S0195-668X(03)00479-2. Copies: This document is available on the Web sites of the ACC at www.acc.org and ESC at www.escardio.org. Copies of this document are available by calling 800-253-4636 (US only) or writing the American College of Cardiology Foundation, Resource Center, 9111 Old Georgetown Road, Bethesda, MD 20814-1699 as well as by calling or writing ESC Guidelines–Reprints, Elsevier Publishers Ltd., 32 Jamestown Road, London, NW1 7BY, United Kingdom, Tel: +44.207.424.4422; Fax: +44.207.424.4433; Email: gr.davies@elsevier.com a American College of Cardiology b European Society of Cardiology * Official representatives of the European Society of Cardiology † Former members of Task Force ‡ Former Chair of Task Force European Heart Journal (2003) 24, 1965–1991 0195-668X/03/$ - see front matter © 2003 American College of Cardiology Foundation and European Society of Cardiology. Published by Elsevier Ltd. doi:10.1016/S0195-668X(03)00479-2 Dual-chamber pacing ................................ 1976 Percutaneous alcohol septal ablation ............. 1977 Sudden Cardiac Death ................................... 1980 Risk stratification ..................................... 1980 Prevention ............................................. 1982 Athlete recommendations ........................... 1983 Atrial Fibrillation ......................................... 1984 References................................................. 1984 Preamble This document has been developed as a Clinical Expert Consensus Document (CECD), combining the resources of the American College of Cardiology Foundation (ACCF) and the European Society of Cardiology (ESC). It is intended to provide a perspective on the current state of management of patients with hypertrophic cardiomyo- pathy. Clinical Expert Consensus Documents are intended to inform practitioners, payers, and other interested parties of the opinion of the ACCF and the ESC concerning evolving areas of clinical practice and/or technologies that are widely available or new to the practice com- munity. Topics chosen for coverage by expert consensus documents are so designed because the evidence base, the experience with technology, and/or the clinical practice are not considered sufficiently well developed to be evaluated by the formal American College of Cardiology/American Heart Association (ACC/AHA) Practice Guidelines process. Often the topic is the sub- ject of considerable ongoing investigation. Thus, the reader should view the CECD as the best attempt of the ACC and the ESC to inform and guide clinical practice in areas where rigorous evidence may not yet be available or the evidence to date is not widely accepted. When feasible, CECDs include indications or contraindications. Some topics covered by CECDs will be addressed subse- quently by the ACC/AHA Practice Guidelines Committee. The Task Force on Clinical Expert Consensus Docu- ments 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 writ- ing 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. Robert A. Vogel, MD, FACC, Chair, ACCF Task Force on Clinical Expert Consensus Documents Werner W. Klein, MD, FACC, FESC Chair, ESC Committee for Practice Guidelines Introduction Organization of committee and evidence review The Writing Committee consisted of acknowledged experts in hypertrophic cardiomyopathy (HCM) repre- senting the American College of Cardiology Foundation and the European Society of Cardiology. Both the academic and private practice sectors were represented. The document was reviewed by 2 official reviewers nominated by the ACCF, 3 official reviewers were nomi- nated by the 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. This document will be considered current until the Task Force on Clinical Expert Consensus Documents revises or withdraws it from distribution. In addition to the references cited as part of this document, a compre- hensive bibliography including relevant, supplementary references is available on the ACCF and ESC websites. Purpose of this Expert Consensus Document Hypertrophic cardiomyopathy is a complex and relatively common genetic cardiac disorder (about 1:500 in the general adult population)1 that has been the subject of intense scrutiny and investigation for over 40 years.2–15 Hypertrophic cardiomyopathy affects men and women equally and occurs in many races and countries, although it appears to be under-diagnosed in women, minorities, and under-served populations.16–20 Hypertrophic cardiomyopathy is a particularly com- mon cause of sudden cardiac death (SCD) in young people (including trained athletes)21–29 and may cause death and disability in patients of all ages, although it is also frequently compatible with normal longevity.30–35 Because of its heterogeneous clinical course and expression,7,36–42 HCM frequently presents uncertainty and represents a management dilemma to cardiovascular specialists and other practitioners, particularly those infrequently engaged in the evaluation of patients with this disease. Furthermore, with the recent introduction of novel treatment strategies targeting subgroups of patients with HCM,7,43–49 controversy is predictable, and difficult questions periodically arise. Consequently, it is now par- ticularly timely to clarify and place into perspective those clinical issues relevant to the rapidly evolving management for HCM. General considerations and perspectives This clinical scientific statement represents the con- sensus of a panel of experts appointed by the ACC and ESC. The writing group is comprised of cardiovascular specialists and molecular biologists, each having extensive experience with 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. Because of the rela- tively low prevalence of HCM in general cardiologic practice,50 its diverse presentation, and mechanisms of death and disability and skewed patterns of patient referral,7,11,13,36–38,42,51–59 the level of evidence govern- ing management decisions for drugs or devices has often been derived from non-randomized and retrospective 1966 B.J. Maron and W.J. McKenna investigations. Large-scale controlled and randomized study designs, such as those that have provided import- ant answers regarding the management of coronary artery disease (CAD) and congestive heart failure,60–62 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 sub- groups that inevitably influence considerations for treat- ment. Some of these management strategies are novel and evolving, and this document cannot, in all instances, convey definitive assessments of their role in the treat- ment 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 document that is not only current and pertinent but also has the potential to remain relevant for many years. Nomenclature, definitions, and clinical diagnosis The clinical diagnosis of HCM is established most easily and reliably with two-dimensional echocardiography by demonstrating left ventricular hypertrophy (LVH) (typically asymmetric in distribution, and showing virtually any diffuse or segmental pattern of left ven- tricular (LV) wall thickening).36 Left ventricular wall thickening is associated with a nondilated and hyper- dynamic chamber (often with systolic cavity obliteration) in the absence of another cardiac or systemic disease (e.g., hypertension or aortic stenosis) capable of produc- ing the magnitude of hypertrophy evident, and indepen- dent of whether or not LV outflow obstruction is present.1,5,7,36 Although the usual clinical diagnostic cri- teria for HCM is a maximal wall thickness greater than or equal to 15 mm, genotype-phenotype correlations have shown that virtually any wall thickness (including those within normal range) are compatible with the presence of a HCM mutant gene.6,17,19,63–65 Mildly increased LV wall thicknesses of 13 mm to 14 mm potentially due to HCM should be distinguished from certain extreme expressions of the physiologically-based athlete's heart.66–68 The ad- vent of contemporary magnetic resonance imaging that provides high-resolution tomographic images of the entire LV may represent an additional diagnostic modality69 particularly in the presence of technically suboptimal echocardiographic studies or when segmental hypertrophy is confined to unusual locations within the LV wall. Since the modern description by Teare in 1958,12 HCM has been known by a confusing array of names that largely reflect its clinical heterogeneity, relatively uncommon occurrence in cardiologic practice, and the skewed experience of early investigators. This problem in nomenclature has been an obstacle to general recogni- tion of the disease within the medical and non-medical community. Hypertrophic cardiomyopathy (or HCM) is now widely accepted as the preferred term7 because it describes the overall disease spectrum without intro- ducing misleading inferences that LV outflow tract obstruction is an invariable feature of the disease, such as is the case with hypertrophic obstructive cardio- myopathy,70 muscular subaortic stenosis,71 or idiopathic hypertrophic subaortic stenosis.72 Indeed, most patients with HCM do not demonstrate outflow obstruction under resting (basal) conditions, although many may develop dynamic subaortic gradients of varying magnitude with provocative maneuvers or agents.7,13,41,72–77 Of note, even though the absence of obstruction (at rest) is com- mon, both in patients with and without symptoms, most treatment modalities have targeted those symptomatic HCM patients with outflow obstruction.41,43–49,78–108 Obstruction to LV Outflow It is of clinical importance to distinguish between the obstructive or nonobstructive forms of HCM, based on the presence or absence of a LV outflow gradient under resting and/or provocable conditions.5,7,11,13,41,109,110 Indeed, in most patients, management strategies have traditionally been tailored to the hemodynamic state. Outflow gradients are responsible for a loud apical sys- tolic ejection murmur associated with a constellation of unique clinical signs,14,72,111 hypertrophy of the basal portion of ventricular septum and small outflow tract, and an enlarged and elongated mitral valve in many patients.39,112–114 Obstruction may either be sub- aortic13,71,72 or mid-cavity13,115 in location. Subaortic obstruction is caused by systolic anterior motion (SAM) of the mitral valve leaflets and mid-systolic contact with the ventricular septum.13,71,113,116–119 This mechanical impedance to outflow occurs in the presence of high velocity ejection in which a variable proportion of the forward blood flow may be ejected early in systole.120,121 Systolic anterior motion is probably attributable to a drag effect117,122 or possibly a Venturi phenomenon13,118 and is responsible not only for subaortic obstruction, but also the concomitant mitral regurgitation (usually mild-to- moderate in degree) due to incomplete leaflet apposi- tion, which is typically directed posteriorly into the left atrium.111,123 When the mitral regurgitation jet is directed centrally or anteriorly into the left atrium, or if multiple jets are present, independent abnormalities intrinsic to the mitral valve should be suspected (e.g., myxomatous degeneration, mitral leaflet fibrosis, or ACC/ESC Expert consensus document on hypertrophic cardiomyopathy 1967 anomalous papillary muscle insertion).13,91,115,124 Occa- sionally (perhaps in 5% of cases), gradients and impeded outflow are caused predominately by muscular apposi- tion in the mid-cavity region—usually in the absence of mitral-septal contact—involving anomalous direct inser- tion of anterolateral papillary muscle into the anterior mitral leaflet, or excessive mid-ventricular or papillary muscle hypertrophy and malalignment.13,91,115 Although it has previously been subject to periodic controversy,72,120,125,126 there is now widespread recog- nition that the subaortic gradient (30 mm Hg or more) and associated elevations in intra-cavity LV pressure reflect true mechanical impedance to outflow and are of pathophysiologic and prognostic importance to patients with HCM.127,128 Indeed, outflow obstruction is a strong, independent predictor of disease progression to HCM- related death (relative risk vs. nonobstructed patients, 2.0), to severe symptoms of New York Heart Association (NYHA) class III or IV, and to death due specifically to heart failure and stroke (relative risk vs. nonobstructed patients, 4.4).127 However, the likelihood of severe symptoms and death from outflow tract obstruction was not greater when the gradient was increased in magnitude above the threshold of 30 mm Hg.127 Disease consequences related to chronic outflow gradients are likely to be mediated by the resultant increase in LV wall stress, myocardial ischemia and even- tually cell death and replacement fibrosis.7,127,129 There- fore, the presence of LV outflow obstruction justifies intervention to reduce or abolish significant subaortic gradients in severely symptomatic patients who are refractory to maximum medical management.11,14,41,127 Obstruction in HCM is characteristically dynamic (i.e., not fixed): the magnitude (or even presence) of an out- flow gradient may be spontaneously labile and vary con- siderably with a number of physiologic alterations as diverse as a heavy meal or ingestion of a small amount of alcohol.72,73,109 Different gradient cut-offs have been proposed for segregating individual patients into hemo- dynamic subgroups, but rigorous partitioning into such hemodynamic categories according to gradient can be difficult because the unpredictable dynamic changes that may occur in individual patients.72,73 Nevertheless, it is reasonable to divide the overall HCM disease spectrum into hemodynamic subgroups, based on the representative peak instantaneous gradi- ent as assessed with continuous wave Doppler: 1) obstructive gradient under basal (resting) conditions equal to or greater than 30 mm Hg (2.7 m/s by Doppler), 2) latent (provocable) obstructive—gradient less than 30 mm Hg under basal conditions and equal to or greater than 30 mm Hg with provocation 3) nonobstructive—less than 30 mm Hg under both basal and (provocable) con- ditions. By current clinical convention, LV outflow gradi- ents are routinely measured noninvasively with continuous wave Doppler echocardiography, generally obviating the need for serial cardiac catheterizations in this disease (except when atherosclerotic CAD or other associated anomalies such as intrinsic valvular disease are suspected). It is important to underscore that a variety of inter- ventions have been traditionally employed to elicit latent (inducible) gradients in the echocardiography, cardiac catheterization, and exercise laboratories (i.e., amyl nitrite inhalation, Valsalva