2012WHF应用超声心动图诊断风湿性心脏病指南

NATURE REVIEWS | CARDIOLOGY ADVANCE ONLINE PUBLICATION | 1 Green Lane Pediatric and Congenital Cardiac Service, Starship Children’s Hospital, Auckland, New Zealand (B. Reményi, N. Wilson, J. Stirling). Royal Children’s Hospital, Australia (A. Steer). Maputo Heart Institute, Mozambique (B. Ferreira). Fiji Ministry of Health, Fiji Islands (J. Kado). Amrita Institute of Medical Sciences, India (K. Kumar). Stellenbosch University, South Africa (J. Lawrenson). James Cook University, Australia (G. Maguire). Hôpital Européen Georges Pompidou, France (E. Marijon, M. Mirabel). University Eduardo Mondlane, Mozambique (A. O. Mocumbi). Federal University of Minas Gerais, Brazil (C. Mota). WakeMed Hospital, USA (J. Paar). All India Institute of Medical Sciences, India (A. Saxena). Johns Hopkins Hospital, USA (J. Scheel). Medical Specialist Clinic, Samoa (S. Viali). Sri Jayadeva Institute of Cardiovascular Sciences and Research, India (V. I. Balekundri). Women’s and Children’s Hospital, Australia (G. Wheaton). University of Cape Town, South Africa (L. Zühlke). Menzies School of Health Research, Australia (J. Carapetis). Correspondence to: B. Reményi bo.remenyi@ menzies.edu.au World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline Bo Reményi, Nigel Wilson, Andrew Steer, Beatriz Ferreira, Joseph Kado, Krishna Kumar, John Lawrenson, Graeme Maguire, Eloi Marijon, Mariana Mirabel, Ana Olga Mocumbi, Cleonice Mota, John Paar, Anita Saxena, Janet Scheel, John Stirling, Satupaitea Viali, Vijayalakshmi I. Balekundri, Gavin Wheaton, Liesl Zühlke and Jonathan Carapetis Abstract | Over the past 5 years, the advent of echocardiographic screening for rheumatic heart disease (RHD) has revealed a higher RHD burden than previously thought. In light of this global experience, the development of new international echocardiographic guidelines that address the full spectrum of the rheumatic disease process is opportune. Systematic differences in the reporting of and diagnostic approach to RHD exist, reflecting differences in local experience and disease patterns. The World Heart Federation echocardiographic criteria for RHD have, therefore, been developed and are formulated on the basis of the best available evidence. Three categories are defined on the basis of assessment by 2D, continuous-wave, and color-Doppler echocardiography: ‘definite RHD’, ‘borderline RHD’, and ‘normal’. Four subcategories of ‘definite RHD’ and three subcategories of ‘borderline RHD’ exist, to reflect the various disease patterns. The morphological features of RHD and the criteria for pathological mitral and aortic regurgitation are also defined. The criteria are modified for those aged over 20 years on the basis of the available evidence. The standardized criteria aim to permit rapid and consistent identification of individuals with RHD without a clear history of acute rheumatic fever and hence allow enrollment into secondary prophylaxis programs. However, important unanswered questions remain about the importance of subclinical disease (borderline or definite RHD on echocardiography without a clinical pathological murmur), and about the practicalities of implementing screening programs. These standardized criteria will help enable new studies to be designed to evaluate the role of echocardiographic screening in RHD control. Reményi, B. et al. Nat. Rev. Cardiol. advance online publication 28 February 2012; doi:10.1038/nrcardio.2012.7 Introduction Rheumatic heart disease (RHD), the only long-term consequence of acute rheumatic fever (ARF), continues unabated among middle-income and low-income coun- tries and in some indigenous communities of the indus- trialized world. At least 15 million people are estimated to be affected by RHD worldwide.1 The American Heart Association (AHA) has well-established clinical diag- nostic criteria for ARF—the Jones criteria2—and, with some modifications and revisions, these guidelines have been accepted and utilized worldwide.3–5 No such widely accepted criteria exist for RHD. The only cost-effective approach to controlling RHD is secondary prophylaxis in the form of penicillin injections every 3–4 weeks to prevent recurrent attacks of group A streptococcal infection that cause ARF and, thus, the wors- ening of RHD.6 However, the majority of patients who enroll into register-based programs are symptomatic with advanced disease, indicating that they have had a number of silent or undetected attacks of ARF. Patients with mild, asymptomatic RHD have the most to gain from second- ary prophylaxis because, in the absence of ARF recur- rence, the majority will have no detectable disease within 5–10 years.7–9 Screening to detect asymptomatic cases is, therefore, an attractive strategy. Traditionally, RHD was diagnosed by auscultating for a heart murmur in those with a history of ARF. Until the past decade, the stethoscope was the only noninvasive diagnostic tool available to physicians in low-income countries and in remote settings where ARF and RHD are most prevalent. However, detection rates were usually low.10–15 Echocardiography has proven to be more sensitive and specific than auscultation.16–22 RHD detected on echo- cardiography without an associated clinically patho logical cardiac murmur is referred to as ‘subclinical RHD’.16 With the advent of portable technology, echocardiography can now be performed at a relatively low cost, eve n in remote settings.20 This development raises the possibility that people with previously undiagnosed RHD, including those without a known history of ARF, can be diagnosed Competing interests The authors declare no competing interests. REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved 2 | ADVANCE ONLINE PUBLICATION www.nature.com/nrcardio and secondary prophylaxis started at an earlier stage of the illness than previously possible, thus potentially reducing morbidity and mortality. Since 2004, the World Health Organization (WHO) has recommended echocardiographic screening for RHD in high-prevalence regions.23 In 2005, a joint WHO and National Institutes of Health (NIH) working party established consensus case definitions for RHD, which were published 5 years later, in 2010.24 The definitions were based on expert consensus, but have their limi- tations because they were not evidence-based, the full spectrum of morphological features of RHD were not considered, and in 2005 there was insufficient experience with normal echocardiographic findings in children.16 Since 2005, a number of countries—including Australia, Cambodia, Fiji, India, Laos, Mali, Mozambique, New Caledonia, New Zealand, Nicaragua, Pakistan, Samoa, South Africa, Tonga, and Yemen—have embarked on large-scale echocardiography-based RHD screening programs.16–19,21,22 Some of these screening programs used the 2005 WHO and NIH consensus definitions, but others used different criteria to define abnormal- ity of both cardiac valve structure (morphology) and function (regurgitation or stenosis), often on the basis of local experience with RHD. This global experience, and the concern that echocardiography might be overly sensitive in some children with normal variation in valvular structure and function, has given impetus to develop an internationally endorsed evidence-based echocardiographic diagnostic guideline for RHD. In this article, we present the 2012 World Heart Federation (WHF) criteria for echocardiographic diagnosis of RHD. For ease of use in the clinical environment, a concise summary of these guidelines—containing the four key Boxes in this article—is available online as Supplementary Information. Intent of these guidelines Our primary aim in developing these guidelines was to define the minimum echocardiographic criteria for the diagnosis of RHD and to highlight the evidence on which these criteria are based. Use of these guidelines should enable rapid identification of RHD in patients who do not have a history of ARF. Importantly, the guidelines should allow for consistent and reproducible echocardiographic reporting of RHD worldwide and, therefore, facilitate epidemio logic studies and evaluation of interventions, such as group A streptococcal vaccine trials, aimed at reducing the worldwide burden of RHD. The guidelines are also intended to aid the long-term evaluation of minor echocardiographic lesions that do not meet the current echocardiographic criteria for definite RHD. These guidelines are not intended for the diagnosis of carditis in the setting of ARF or for the diagnosis of RHD in patients with a history of ARF. In addition, this document does not contain recommendations on the management of ARF or RHD; for information on treatment, the reader is directed to local guidelines, or to the websites of the AHA,2 WHO,3 Heart Foundation of Australia,4 and Heart Foundation of New Zealand.5 Development of these guidelines An international advisory group of experts in RHD screening and echocardiographic manifestations of RHD was formed in 2009 (see the author list for this article). Under the auspices of the WHF, this group of 21 investi- gators from six continents developed evidence-based echocardiographic diagnostic guidelines for RHD. Expert panel members reported on echo cardiograms online and systematic differences in reporting and diagnostic styles were identified. Via a series of web-based seminars, these differences were resolved and provisional echocardio- graphic criteria for RHD were agreed. A systematic lit- erature review was performed using the Medline, Embase, and Cochrane databases to identify diagnostic features of established RHD by echocardio graphy, at cardiac surgery, and on post mortem examinations. The search terms “echo- cardiography”, “surgery”, “pathology”, “mitral”, “aortic”, “tricuspid”, “valve”, “normal”, “regurgitation”, “sten osis”, “prolapse”, “RHD” and “rheumatic” were optimally com- bined. The search was limited to papers published in the English language and was supplemented by careful review of the reference list of the relevant articles. A total of 3,218 abstracts and 170 full-text articles were reviewed; 108 were found to be directly relevant and are included in the refer- ence list. All relevant articles were reviewed by at least two members of the panel. Evidence-based guidelines were finalized at a workshop in Thailand in 2011, where the expert panel members reviewed the 108 papers identi- fied as directly relating to RHD and echocardiography. Results of completed, but not yet published, studies (by investigators who were part of the expert panel) were also critically reviewed. Whenever evidence for or against the provisional criteria was insufficient, a formal consensus method24 was used to reach agreement. Grading evidence The level of evidence was established and each recom- mendation was graded using the guidelines of the Scottish Intercollegiate Guidelines Network25 (Tables 1 and 2), as they seemed to be the most applicable to this diagnostic setting. Diagnostic criteria Echocardiographic findings should always be inter- preted in conjunction with the patient’s clinical findings and with consideration of the individual’s pretest prob- ability of RHD, which varies with geographical location (level 1+ evidence),1 ethnicity (level 2+ evidence),26,27 and living conditions (level 2+ evidence) (grade B recom- mendation).28,29 An individual’s clinical history, including possible or probable ARF, should also be considered. In those with a history of definite ARF, any structural and functional abnormality of the valves must be considered to represent RHD until proven otherwise. The concise echocardiographic criteria for ‘definite RHD’ and ‘borderline RHD’ are detailed in Boxes 1–3. The optimal settings for the echocardiography machine, which allow objective measurement, are summarized in Box 4. The echocardiographic features listed in Boxes 1–3 are not unique to RHD. Congenital, acquired, REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved NATURE REVIEWS | CARDIOLOGY ADVANCE ONLINE PUBLICATION | 3 and degenerative heart disease should always be excluded as the etiology of mitral valve (MV) and aortic valve (AV) abnormalities before presuming rheumatic origin (grade D recommendation). Congenital cardiac defects are easily differentiated from RHD, as they have unique identifying features (for example, bicuspid AV or MV cleft). Degenerative conditions are rare in the young, and other acquired conditions (for example, infective endo- carditis) can be differentiated from RHD on the basis of clinical findings (level 4 evidence). RHD predominantly affects the left-sided cardiac valves, causing regurgitation, stenosis, or mixed hemodynamic effects. The tricuspid valve and (seldomly) the pulmonary valve can also be affected, but rarely (if ever) without MV involvement (99.3% on echocardiography and 100% on postmortem examination have coexisting disease of the MV;30 level 1+ evidence). Similarly, AV stenosis is rare in isolation (0–0.5%;31–33 level 2+ evidence). Hence, neither right-sided valve lesions nor aortic stenosis are included in the diagnostic criteria (grade B recommendation). Rationale and evidence for criteria Definite RHD Echocardiographic changes that meet the criteria for ‘definite RHD’ are considered to be rheumatic in origin, provided that other etiologies have been excluded by echo- cardiography and clinical context. In interpreting echo- cardiograms, the individual’s pretest probability of RHD must be considered. The subcategories of ‘definite RHD’ (A–D) are listed below. Subcategory A—RHD of the MV with regurgitation Subcategory A of ‘definite RHD’ is defined as pathologi- cal mitral regurgitation and at least two morpho logical features of RHD of the MV. This subcategory has a grade B recommendation for its inclusion in the ‘definite RHD’ category. MV disease in the form of regurgitation is the most- common manifestation of RHD in the young (level 2++ evidence).31–36 Echocardiographic,35–40 surgical,41–43 and postmortem anatomical44–46 studies have demon- strated that a combination of the morphological features (Box 3) is present in advanced disease (level 2+ evidence). Colloquial descriptions of the MVs—such as ‘dog-leg’, ‘elbow’, or ‘hockey stick’ deformities47—also portray a combination of morphological changes (thickening and restricted motion of the anterior MV leaflet; Figures 1 and 2). Subcategory B—RHD of the MV with stenosis Subcategory B of ‘definite RHD’ is defined as mitral steno sis with a mean gradient ≥4 mmHg and at least two morpho logical changes of RHD of the MV. This sub- category has a grade B recommendation for its inclusion in the ‘definite RHD’ category. Worldwide, the most-common cause of MV stenosis is RHD,48–51 and the condition is associated with at least two morphological changes of RHD (level 2+ evidence).51,52 Typically, leaflets are thickened and the posterior leaflet is relatively immobile and moves parallel during diastole with the anterior MV leaflet. The second-most-common etiology of mitral stenosis is congenital MV steno- sis,48,50 which is readily differentiated from RHD as it is frequently associated with abnormal papillary muscle arrangements and (in 84–97% cases) with other congeni- tal cardiac defects (level 2++ evidence).53–56 Worldwide, RHD is still responsible for 95–99.3% of all MV stenoses in indivi duals aged <50 years (level 2++ evidence).48,49 In those aged >50 years, nonrheumatic mitral annular cal- cification is a differential diagnosis of mitral stenosis that should be considered (level 2+ evidence).49,57 Subcategory C—RHD of the AV Subcategory C of ‘definite RHD’ is defined as patho logical aortic regurgitation and at least two morphological features of RHD of the AV. This subcategory only applies to indivi- duals aged <35 years and has a grade B recommendation for its inclusion in the ‘definite RHD’ category. Although less common than isolated MV involvement, isolated disease of the AV is a recognized manifestation of RHD. A large study of 10,000 consecutive patients Table 1 | Levels of evidence, as defined in the guidelines of the SIGN25 Level of evidence Study description 1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias 1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias 1– Meta-analyses, systematic reviews, or RCTs with a high risk of bias 2++ High-quality systematic reviews of case–control or cohort studies, or high-quality case–control or cohort studies with a very low risk of confounding or bias, and a high probability that the relationship is causal 2+ Well-conducted case–control or cohort studies with a low risk of confounding or bias, and a moderate probability that the relationship is causal 2– Case–control or cohort studies with a high risk of confounding or bias, and a significant risk that the relationship is not causal 3 Nonanalytic studies (for example, case reports or case series) 4 Expert opinion Abbreviations: RCT, randomized, controlled trial; SIGN, Scottish Intercollegiate Guidelines Network. Permission obtained from SIGN © 2001–2011. Table 2 | Grade of recommendation, as defined in the guidelines of the SIGN25 Grade* Strength of evidence A At least one meta-analysis, systematic review, or RCT rated as 1++ (see Table 1 for information about various levels of evidence) and directly applicable to the target population; or a body of evidence consisting primarily of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 1++ or 1+ C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 2++ D Evidence level 3 or 4; or extrapolated evidence from studies rated as 2+ *The grade of recommendation relates to the strength of the evidence on which the recommendation is based; it does not reflect the clinical importance of the recommendation. Abbreviations: RCT, randomized, controlled trial; SIGN, Scottish Intercollegiate Guidelines Network. Permission obtained from SIGN © 2001–2011. REVIEWS © 2012 Macmillan Publishers Limited. All rights reserved 4 | ADVANCE ONLINE PUBLICATION www.nature.com/nrcardio with RHD showed that isolated rheumatic AV disease occurs in 4.5% of individuals aged ≤18 years and in 2.8% of indivi duals aged >18 years (level 2+ evidence).58 In smaller series, the prevalence has been reported to be 0–21.4%.31–33,36,59–68 In AV disease, the presence of mul- tiple morphological features (Box 3) enables confirmation of rheumatic etiology on gross inspection (level 2+ evi- dence).69 For consistency with the criteria for MV disease, and to increase specificity, the definite criteria for RHD of the AV require the presence of two rheumatic morpho- logical features of the AV in addition to pathological aortic regurgitation. The two most-common differential diagnoses are bicuspid AV and aortic root dilatation,69 and both are easily differentiated on echocardiography. Other causes, such as endocarditis and other inflamma- tory carditis (systemic lupus erythematosus and ankylos- ing spondylitis), can be excluded by clinical context. Hypertension should also be excluded as an underlying etiology (level 4 evidenc