Shortcomings in Managing Patients With Ischemia With Nonobstructed Coronary Arteries

HomeCirculation: Cardiovascular Quality and OutcomesVol. 15, No. 7Shortcomings in Managing Patients With Ischemia With Nonobstructed Coronary Arteries Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBShortcomings in Managing Patients With Ischemia With Nonobstructed Coronary Arteries Rosanna Tavella, BSc (Hons), PhD and John F. Beltrame, BSc, BMBS, PhD Rosanna TavellaRosanna Tavella Central Adelaide Local Health Network, Basil Hetzel Institute, University of Adelaide, Adelaide, South Australia, Australia. and John F. BeltrameJohn F. Beltrame Correspondence to: John F Beltrame, BSc, BMBS, PhD, The Queen Elizabeth Hospital, Discipline of Medicine, 28 Woodville Rd, Woodville South, SA. 5011. Australia. Email E-mail Address: [email protected] https://orcid.org/0000-0002-4294-6510 Central Adelaide Local Health Network, Basil Hetzel Institute, University of Adelaide, Adelaide, South Australia, Australia. Originally published19 Jul 2022https://doi.org/10.1161/CIRCOUTCOMES.122.008746Circulation: Cardiovascular Quality and Outcomes. 2022;15In this issue of the Journal, Lucy Flanagan details her dreadful journey with ischemia with nonobstructed coronary arteries (INOCA), and unfortunately, this scenario is far too common among patients with this condition. Many similar experiences can be found on social media and have prompted the development of patient support groups, such as INOCA International (https://inocainternational.com/) and the International Heart Spasm Alliance (https://www.internationalheartspasmsalliance.org/). The frustration and anxiety encountered by these patients largely result from shortcomings in contemporary clinical medicine, resulting in delayed/misdiagnosis and suboptimal treatment. If these shortcomings could be addressed, these patients would have significantly improved outcomes.See Article by FlanaganCurrent ShortcomingsThe patient journey described by Lucy Flanagan provides an insightful forum into the current shortcomings in clinical medicine with respect to INOCA. These shortcomings are further elaborated on below.Pathophysiological understanding shortcoming: The presenting symptoms were exertional chest pain and dyspnea prompting a routine exercise test, which was abnormal and invoked a coronary angiogram to be performed. In the absence of obstructive (INOCA) coronary artery disease (CAD), she was informed "there was nothing wrong with your heart," as so commonly occurs in routine practice. If so, why was the exercise test abnormal? The common explanation offered is that women often have a 'false positive exercise test'. This is on the premise that an exercise test (as a noninvasive screening test for obstructive CAD) has limited value in predicting obstructive CAD on coronary angiography. However, these investigations are evaluating different pathophysiological entities, with the exercise test evaluating the presence of ischemia and coronary angiography the presence of obstructive coronary artery disease. Hence the clinical findings can be readily interpreted as the patient experiencing exertional chest pain due to effort-induced myocardial ischemia (ie angina), which is not explained by epicardial CAD (ie, INOCA). Thus, in the case presented, the clinician should be seeking an explanation for the exercise-induced ischemia (demonstrated on the initial stress ECG, as well as the cardiac magnetic resonance imaging performed 8 years later), other than obstructive CAD.Diagnostic shortcoming: Despite the absence of obstructive CAD on angiography, other coronary causes may be responsible for myocardial ischemia. Indeed, the epicardial coronary arteries evaluated on angiography represent only 5% of the coronary circulation and myocardial ischemia may equally arise from the extensive but unseen coronary microcirculation. Moreover, routine angiography only evaluates the resting state of the epicardial coronary arteries, which are susceptible to transient coronary artery spasms that may also give rise to myocardial ischemia. Accordingly, since the routine structural angiography did not identify obstructive CAD as a cause for the effort-induced ischemia, functional angiography is required, where the presence of epicardial coronary artery spasm or microvascular spasm is assessed by provocative spasm testing with intracoronary acetylcholine and coronary microvascular dysfunction evaluated by coronary blood flow responses to adenosine. Despite being available for >30 years, these functional angiography techniques have been seldom utilized. Their utility in improving patient outcomes has been recently confirmed,1 prompting their inclusion in chronic coronary syndrome guidelines2 and hopefully the increased use of these techniques. If functional angiography was initially undertaken in the case at hand, it would have spared 8 years of misdiagnosis and lack of appropriate therapy, which resulted in the considerable anxiety, frustration, and disability.Therapeutic shortcomings: Following an appropriate diagnosis, therapy can be instituted but needs to be targeted to the underlying pathophysiology since the efficacy of treatments differ between the large epicardial arteries and the microvasculature. As detailed in a recent comprehensive systematic review,3 calcium channel blockers are first-line therapy in the treatment of epicardial coronary artery spasm (vasospastic angina) but first-line therapy for coronary microvascular dysfunction (the coronary microvascular disorders) is unclear. Indeed, the therapeutic evidence-base for INOCA is largely limited to small single-center studies and the first large multicentre trial is still in progress.4 Moreover, there is a need to develop novel therapies to treat these disabled patients, since the last new anti-anginal agent was approved >15 years ago. With the limited evidence-base and available novel therapies, it is not surprising that patients with coronary microvascular disorders (such as the current case) are managed with a trial and error treatment strategy.Educational shortcomings: Central to the problems encountered by Lucy Flanagan is a lack of awareness among clinicians of INOCA. This is despite 59% of patients with suspected CAD undergoing elective angiography have no evidence of obstructive CAD,3 many of whom may have INOCA. Furthermore, the misconception that this condition is not life-threatening needs to be addressed since patients with vasospastic angina may clearly experience life-threatening events such as myocardial infarction, malignant arrhythmias, and sudden death.5 In addition to disseminating what is known about INOCA, research is required to define the INOCA subtypes (since microvascular dysfunction may arise from constriction or inadequate dilation), since these may require different therapeutic strategies.Addressing the ShortcomingsThe patient support groups such as INOCA International and the International Heart Spasms Alliance play a pivotal role in addressing the above shortcomings, by providing affected patients with medical information, a discussion forum, and thus an appreciation that they are not alone. These organizations source their information from medical experts in the field, thereby ensuring that the information is current and appropriate.From a medical perspective, COVADIS (Coronary Vasomotor Disorders International Study group; https://covadis.online/) has been established. This organization has (1) established international diagnostic criteria for vasospastic angina6 and microvascular angina,7 thereby standardizing the nomenclature for future clinical trials, (2) promoted clinical interest and research in INOCA, (3) undertaken an international registry of microvascular angina characteristics and prognosis,8 and (4) increased awareness of INOCA amongst clinicians via educational conferences and scientific publications. These initiatives have increased the clinical interest in INOCA and prompted position statements from professional societies.9,10With these innovations, it is hoped that future poor experiences and outcomes (as described by Lucy Flanagan) are relegated to the annals of medical history and patients with INOCA will be promptly diagnosed and optimally treated.Article InformationSources of FundingSupport for studies in INOCA has been provided by The Hospital Research Foundation Group.Disclosures None.FootnotesThe articles published in Viewpoints reflect the opinions of the authors and do not reflect the policy or position of the American Heart Association, and the American Heart Association provides no warranty as to their accuracy or reliability.For Sources of Funding and Disclosures, see page 531.Correspondence to: John F Beltrame, BSc, BMBS, PhD, The Queen Elizabeth Hospital, Discipline of Medicine, 28 Woodville Rd, Woodville South, SA. 5011. Australia. Email john.[email protected]edu.auReferences1. Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, et al. Stratified medical therapy using invasive coronary function testing in angina: the CorMicA trial.J Am Coll Cardiol. 2018; 72(23 Pt A):2841–2855. doi: 10.1016/j.jacc.2018.09.006CrossrefMedlineGoogle Scholar2. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, et al; Group ESCSD. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes.Eur Heart J. 2019; 41:407–477. doi: 10.1093/eurheartj/ehz425CrossrefGoogle Scholar3. Beltrame JF, Tavella R, Jones D, Zeitz C. Management of ischaemia with non-obstructive coronary arteries (INOCA).BMJ. 2021; 375:e060602. doi: 10.1136/bmj-2021-060602MedlineGoogle Scholar4. Handberg EM, Merz CNB, Cooper-Dehoff RM, Wei J, Conlon M, Lo MC, Boden W, Frayne SM, Villines T, Spertus JA, et al. 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International standardization of diagnostic criteria for microvascular angina.Int J Cardiol. 2018; 250:16–20. doi: 10.1016/j.ijcard.2017.08.068CrossrefMedlineGoogle Scholar8. Shimokawa H, Suda A, Takahashi J, Berry C, Camici PG, Crea F, Escaned J, Ford T, Yii E, Kaski JC, et al. Clinical characteristics and prognosis of patients with microvascular angina: an international and prospective cohort study by the Coronary Vasomotor Disorders International Study (COVADIS) Group.Eur Heart J. 2021; 42:4592–4600. doi: 10.1093/eurheartj/ehab282CrossrefMedlineGoogle Scholar9. Bairey Merz CN, Pepine CJ, Walsh MN, Fleg JL. Ischemia and No Obstructive Coronary Artery Disease (INOCA): developing evidence-based therapies and research agenda for the next decade.Circulation. 2017; 135:1075–1092. doi: 10.1161/CIRCULATIONAHA.116.024534LinkGoogle Scholar10. Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, Prescott E, Karam N, Appelman Y, Fraccaro C, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group.Eur Heart J. 2020; 41:3504–3520. doi: 10.1093/eurheartj/ehaa503CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 2022Vol 15, Issue 7 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCOUTCOMES.122.008746PMID: 35861783 Originally publishedJuly 19, 2022 Keywordscoronary artery diseaseischemiasocial mediavariant microvascular anginaangina pectorisclinical medicinecoronary arteriesPDF download Advertisement