冠状动脉微血管疾病的诊断与治疗中国专家共识（2023版）-英文版.pdf

Received:24 August 2023Revised:11 November 2023Accepted:16 November 2023DOI:10.1002/mco2.438REVIEWChinese expert consensus on the diagnosis and treatmentof coronary microvascular diseases(2023 Edition)Wenqiang Chen1Mei Ni1He Huang2Hongliang Cong3Xianghua Fu4Wei Gao5Yuejin Yang6Mengyue Yu6Xiantao Song7Meilin Liu8Zuyi Yuan9Bo Zhang10Zhaohui Wang11Yan Wang12Yundai Chen13,Cheng Zhang1,Yun Zhang1,1The National Key Laboratory for Innovation and Transformation of Luobing Theory,The Key Laboratory of Cardiovascular Remodeling andFunction Research,Chinese Ministry of Education,Chinese National Health Commission and Chinese Academy of Medical Science,Department ofCardiology,Qilu Hospital of Shandong University,Jinan,Shandong,China2Department of Cardiology,Sir Run Run Shaw Hospital affiliated with Zhejiang University School of Medicine,Hangzhou,China3Department of Cardiology,Tianjin Chest Hospital,Tianjin University,Tianjin,China4Department of Cardiology,The Second Hospital of Hebei Medical University,Shijiazhuang,Hebei,China5Department of Cardiology,Peking University Third Hospital,Beijing,China6Department of Cardiology,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences and Peking UnionMedical College,Beijing,China7Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing,China8Department of Geriatrics,Peking University First Hospital,Beijing,China9Department of Cardiology,The First Affiliated Hospital of Xian Jiaotong University,Xian,China10Department of Cardiology,First Affiliated Hospital,Dalian Medical University,Dalian,Liaoning,China11Department of Cardiology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China12Department of Cardiology,Xiamen Cardiovascular Hospital,Xiamen University,Xiamen,China13Senior Department of Cardiology,Sixth Medical Center of Chinese PLA General Hospital,Beijing,China;for the Basic Research Group,Atherosclerosis and Coronary Heart Disease Group,Interventional Cardiology Group,and Womens Heart Health Group of the Chinese Society ofCardiologyCorrespondenceCheng Zhang,Department of Cardiology,Qilu Hospital,Shandong University,No.107,Wen Hua Xi Road,Jinan,Shandong250012,China.Email:Yundai Chen,Senior Department ofCardiology,Sixth Medical Center ofChinese PLA General Hospital,No.6,Fucheng Road,Haidian District,Beijing100048,ChinaEmail:Yun Zhang,Deparment of Cardiology,Qilu Hospital,Shandong University,No.AbstractSince the four working groups of the Chinese Society of Cardiology issued firstexpert consensus on coronary microvascular diseases(CMVD)in 2017,interna-tional consensus documents on CMVD have increased rapidly.Although someof these documents made preliminary recommendations for the diagnosis andtreatment of CMVD,they did not provide classification of recommendationsand levels of evidence.In order to summarize recent progress in the field ofCMVD,standardize the methods and procedures of diagnosis and treatmentand identify the scientific questions for future research,the four working groupsof the Chinese Society of Cardiology updated the 2017 version of the Chineseexpert consensus on CMVD and adopted a series of measures to ensure theThis is an open access article under the terms of the Creative Commons Attribution License,which permits use,distribution and reproduction in any medium,provided theoriginal work is properly cited.2023 The Authors.MedComm published by Sichuan International Medical Exchange&Promotion Association(SCIMEA)and John Wiley&Sons Australia,Ltd.MedComm.2023;4: of 40https:/doi.org/10.1002/mco2.4382 of 40CHEN et al.107,Wen Hua Xi Road,Jinan,Shandong250012,China.Email:Funding informationNational Natural Science Foundation ofChina,Grant/Award Numbers:82241203,81920108003,82030051;State Key R&DProgram,Chinese Ministry of Science andTechnology,Grant/Award Number:2021YFF0501403;Key R&D Program,Shandong Provincial Department ofScience and Technology,Grant/AwardNumbers:2021SFGC0503,2021ZLGX02,2021ZDSYS05,2020ZLYS05;NaturalScience Foundation,Shandong ProvincialDepartment of Science and Technology,Grant/Award Number:ZR202102190727;Taishan Scholars Program,ShandongProvincial Department of Science andTechnology,Grant/Award Number:(ZhangC.)qualityofthisdocument.ThecurrentconsensushasraisedanewclassificationofCMVD,summarized new epidemiological findings for different types of CMVD,analyzed key pathological and molecular mechanisms,evaluated classical andnovel diagnostic technologies,recommended diagnostic pathways and criteria,and therapeutic strategies and medications,for patients with CMVD.In view ofthe current progress and knowledge gaps of CMVD,future directions were pro-posed.It is hoped that this expert consensus will further expedite the researchprogress of CMVD in both basic and clinical scenarios.KEYWORDScoronary microvascular disease,myocardial ischemia,myocardial infarction,atherosclerosis,non-atherosclerotic heart disease,Chinese expert consensus1INTRODUCTIONSinceLikoffetal.1firstreportedtheclinicalmanifestationsof a group of patients with a definite diagnosis of coronaryheart disease(CHD)but a normal coronary angiogram in1967,basic and clinical research on coronary microvascu-lar diseases(CMVD)has continued for half a century.In2013,the European Society of Cardiology(ESC)guidelinesfor the treatment of stable coronary artery disease(CAD)first recognized CMVD as a clinical type of CHD andmade preliminary recommendations for the diagnosis andtreatment of CMVD.2In 2017,the Basic Research Group,Interventional Cardiology Group,Womens Heart HealthGroup,and Atherosclerosis and Coronary Heart DiseaseGroup of the Chinese Society of Cardiology issuedChi-nese expert consensus on the diagnosis and treatment ofcoronary microvascular diseases,”the first expert consen-sus on CMVD in the literature,3which clarified a numberof unclear issues and expedited the progress of basic andclinical research in the field of CMVD in China.Since 2017,international consensus documents onCMVDhaveincreasedrapidly.In2018,theCoronaryVaso-motion Disorders International Study Group(COVADIS)recommended the diagnostic criteria for type 1 coro-nary artery microvascular dysfunction,namely primaryCMVD.4In 2019,the ESC published guidelines for thediagnosis and treatment of chronic coronary syndrome,in which microvascular angina(MVA)pectoris was classi-fied as an important type of chronic coronary syndrome,and corresponding diagnostic and treatment strategieswere recommended.5In 2019,the American Heart Asso-ciation(AHA)issued a scientific statement on the diag-nosis and treatment of myocardial infarction(MI)withnonobstructive coronary arteries(MINOCA),stating thatMVA pectoris,micro-vasospasm,and slow coronary floware important causes of MINOCA.6In 2020,the Euro-pean Association of Percutaneous Cardiovascular Inter-ventions(EAPCI)and ESC jointly issued a consensus doc-ument on ischemia with nonobstructive coronary arteries(INOCA),indicating that CMVD and epicardial coronaryartery spasm are the main causes of INOCA.7In 2020,ESC Working Group on Coronary Pathophysiology andMicrocirculation published position paper on coronarymicrovascular dysfunction,dividing CMVD into six clin-ical types.8These international documents focused onmainly research progress of CMVD,and although some ofthese documents made preliminary recommendations forthediagnosisandtreatmentofCMVD,theydidnotprovideclassification of recommendations and levels of evidence.Thus,the guidance value of these documents in clinicalpractice is limited.In order to summarize recent progress in the field ofCMVD,standardize the methods and procedures of diag-nosis and treatment of CMVD,and identify the scientificquestions for future research,the Basic Research Group,Atherosclerosis and Coronary Heart Disease Group,Inter-ventional Cardiology Group,and Womens Heart HealthGroup of the Chinese Society of Cardiology held a meet-ing in November 2021,discussed current issues in thefield of CMVD and decided to update the 2017 version ofChinese expert consensus on CMVD.The four workinggroupsadoptedthefollowingmeasurestocontrolthequal-ity of this document:first,a consensus revision committeeand a consensus drafting group were formed and their 26882663,2023,6,Downloaded from https:/ by CochraneChina,Wiley Online Library on 20/12/2023.See the Terms and Conditions(https:/ Wiley Online Library for rules of use;OA articles are governed by the applicable Creative Commons LicenseCHEN et al.3 of 40TABLE 1Classes for recommendations.DefinitionClass ITreatments or procedures that have been proven and/or unanimously recognized to be beneficial,useful or effective,and recommendedClass IITreatments or procedures for which there is conflicting evidence and/or a divergence of opinion about theusefulness/efficacyClass IIaThe evidence/opinion tends to be useful and/or effective,and it is reasonable to apply these treatments or proceduresClass IIbThe relevant evidence/opinions have not been fully proven to be useful and/or valid and can be considered forapplicationClass IIITreatments or procedures that have been confirmed and/or unanimously recognized as useless and/or ineffective andmay be harmful in some cases,and not recommendedTABLE 2Levels of evidence.DefinitionLevel AEvidence based on multiple randomized clinical trials or meta-analyses.Level BEvidence based on a single randomized clinical trial or multiple nonrandomized controlled trialsLevel CConsensus of expert opinion and/or evidence based on small-scale studies,retrospective studies,and registration studiesmembers were nominated by the four working groups;second,search keywords on CMVD in the literature weresuggested by the drafting group and approved by the con-sensus revision committee;third,English and Chineseliteratures published from 2016 to 2021 were extensivelysearched using approved key words and major searchengines;fourth,poor quality,repetitive and small samplestudies were deleted using the quality standard predefinedby the consensus revision committee,and the remain-ing literatures were classified according to their researcharea;fifth,a consensus outline was suggested by thedrafting group after a thorough investigation of classi-fied literatures,and approved by the consensus revisioncommittee;sixth,the consensus revision committee anddrafting expert group held several meetings to discussthe manuscript,which were revised for several times andfinally approved by the consensus revision committee andthe Chinese Society of Cardiology.The recommendations of diagnosis and treatment ofCMVD in this consensus were based on ACC/AHA crite-ria as illustrated in Tables 1 and 2.9The following aspectsof CMVD were discussed in this consensus sequentially:(1)definition,clinical classification,and epidemiology ofCMVD;(2)pathogenetic mechanism of CMVD;(3)diag-nostic techniques for CMVD;(4)clinical manifestationsand diagnostic criteria of CMVD;(5)treatment of CMVD;and(6)gaps of knowledge and future perspectives.Theupdated recommendations and opinions in the new con-sensus were given in Table 3 as compared to the ChineseexpertconsensusonthediagnosisandtreatmentofCMVDissued in 2017.2DEFINITION,CLINICALCLASSIFICATION,AND EPIDEMIOLOGYOF CMVD2.1DefinitionCMVDisaclinicalsyndromeofacuteandchronicmyocar-dial ischemia caused by abnormalities in structure andfunction of coronary prearterioles,arterioles,and capil-laries induced by atherosclerotic and non-atheroscleroticpathogenic factors.2.2Clinical classificationsThis consensus divides CMVD into four major types andnine sub-types(Table 4).2.3EpidemiologyMost epidemiological studies of CMVD were performedin European and American populations,some of whichincluded Asian populations as well.No studies have yetreportedethnicdifferencesintheincidenceofCMVD.Theincidence of CMVD varies greatly in different studies,rangingfrom10%to80%duetotheinconsistencyofCMVDdefinition and diagnostic criteria.Likewise,owing to thedifferences in endpoints and follow-up duration,therewere significant differences in mortality and the incidenceof adverse cardiovascular events in CMVD patients in4 of 40CHEN et al.TABLE 3New concepts and recommendations in the consensus 2023 compared with the consensus 2017.New concepts and recommendations in 2023Section 2.2 Clinical classifications1CMVD associated with myocardial ischemiaNew2CMVD associated with myocardial infarction3CMVD associated with coronary revascularization4CMVD associated with non-atherosclerotic heart diseaseSection 3 Pathogenetic mechanism of CMVD1Regulatory mechanism of coronary blood flowNew2Structural abnormalities of the coronary microcirculationUpdated3Microvascular obstructionNew4Functional abnormalities of the coronary microcirculationUpdatedSection 4.1 Vasoactive drugs for evaluating coronary microvascular functionRegadenoson and nicorandilNewSection 4.2 Noninvasive techniques for evaluating coronary microvascular function1TTDEUpdated2MCENew3SPECTUpdated4PETUpdated5CMRUpdated6CTPNewSection 4.3 Invasive techniques for evaluating coronary microvascular function1CAGUpdated2Bolus and continuous thermodilutionUpdated3Intracoronary Doppler flow velocity measurementUpdated4Diagnostic flow chartNewSection 5 Clinical manifestations and diagnostic criteria of CMVDDiagnostic criteria for different types of CMVDNewSection 6 Treatment of CMVD1Treatment for CMVD associated with INOCARisk factor management and lifestyle modificationsCoronary and endothelial function testStratified medical therapyUpdated2Treatment of CMVD associated with IOCALifestyle modificationsAntiatherosclerosis therapyStratified medical therapyCoronary revascularizationUpdated3Treatment of CMVD associated with MINOCAStratified medical therapySecondary preventionUpdated4Treatment of CMVD associated with MIOCAPharmacological treatment before PCIPharmacological treatment during PCINonpharmacological treatmentUpdated5Treatment of CMVD after successful intervention for AMIPharmacological treatmentNonpharmacological treatmentNew(Continues)CHEN et al.5 of 40TABLE 3(Continued)New concepts and recommendations in 20236Treatment of CMVD with non-atherosclerotic heart diseaseTreatment of CMVD with myocardial hypertrophyTreatment of CMVD without myocardial hypertrophyNewAbbreviations:AMI,acute myocardial infarction;CAG,coronary angiography;CTP,computed tomography perfusion;CMR,cardiovascular magnetic resonance;CMVDcoronary microvascular disease;INOCA,ischemia with nonobstructive coronary arteries;IOCA,ischemia with obstructive coronary arteries;MCE,myocardial contrast echocardiography;MINOCA,myocardial infarction with nonobstructive coronary arteries;MIOCA,myocardial infarction with obstructivecoronary arteries;PCI,percutaneous coronary intervention;PET,positron emission tomography;SPECT,single-photon emission computed tomography;TTDE,transthoracic Doppler echocardiography.TABLE 4Clinical classifications of CMVD.Classifications1.CMVD associated with myocardial ischemiaCMVD associated with INOCACMVD ass