{"paper_id":"ec0b87c5-95f2-46fd-b115-33987fd5e18e","body_text":"Auctores Publishing – Volume 3(13)-113 www.auctoresonline.org \nISSN: 2641-0419 Page 1 of 4  \nJ Clinical Research and Reports Copy rights@ Meera D Kondapaneni et.al. \n \n \nMyocardial infarction in the absence of obstructive coronary artery \ndisease (MINOCA): A Challenge to Diagnose and Manage \nMeera D Kondapaneni*, Ahmad Jabri, Aisha Siraj and Saima Karim \nHeart and Vascular Institute, MetroHealth Medical Center / Case Western Reserve University, 2500 MetroHealth Dr, Cleveland, OH, USA, 44109 \n*Corresponding Author: Meera D Kondapaneni, Heart and Vascular Institute, MetroHealth Medical Center / Case Western Reserve \nUniversity, 2500 MetroHealth Dr, Cleveland, OH, USA. \nReceived Date: November 20, 2020; Accepted Date: December 08, 2020; Published Date: December 16, 2020 \nCitation: Meera D Kondapaneni, Ahmad Jabri, Aisha Siraj and Saima Karim., (2020) Myocardial infarction in the absence of obstructive coronary \nartery disease (MINOCA): A Challenge to Diagnose and Manage.. J. Clinical Cardiology and Cardiovascular Interventions, 3(13); \nDoi:10.31579/2641-0419/112 \nCopyright: © 2020 Meera D Kondapaneni, This is an open-access article distributed under the terms of the Creative Commons Attribution \nLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n \n \nIntroduction: \nMyocardial Infarction in the absence of obstructive coronary artery \ndisease [MINOCA] is seen in 5 -6% of the patients presenting with \nmyocardial infarction and is more prevalent in females compared with \nmales. [1][2] The d isease entity was first identified 75 years ago when \nmyocardial necrosis was reported in autopsies without the evidence of \nsignificant coronary atherosclerosis. [3] Substantial variability exits in the \nmanner patients with suspected MINOCA are evaluated and treated. The \npresent review aims at summarizing the updated definition for the broadly \nlabelled term MINOCA and provide a clinical framework for the \nevaluation and management of these patients. \nDisease epidemiology \nEarly angiographic studies by Likoff et. al. and Eliot et. al. reported the \nparadox of myocardial ischemia and necrosis in patients with normal \ncoronary arteriograms. [4,5] Further angiographic studies by DeWood et. \nal. reported a prevalence of non -obstructive coronary arteries in nearly \n5% of myocardial infarction patients undergoing angiography. [6] These \nnumbers were further sustained by individual studies and pooled analysis \nwhich reported similar prevalence of non-obstructive coronary arteries in \nmyocardial infarction patients undergoing angiography. [2] The disease \nwas initially referred to as myocardial infarction with normal coronary \n \narteries [MINC] but later changed to MINOCA to include patients with \natherosclerotic coronary arteries which were not severe enough to \ncompromise myocardial blood flow. [7,8] While patients with MINOCA \ncan present with either ST segment elevation or non-ST segment elevation \nmyocardial infarction, they are less likely to have ST segment deviation \non electrocardiography and have a smaller degree of cardiac biomarker \nelevation compared to their obstructive coronary artery disease \ncounterparts. [9,10] Furthermo re, patients with MINOCA are usually \nyounger compared with patients presenting with obstructive coronary \nartery disease. [9, 10] MINOCA is more prevalent in blacks, Maori or \nPacific race, and Hispanic ethnicity. [10,11] Traditional risk factors like \ndyslipidemia, hypertension, diabetes mellitus, tobacco abuse and a family \nhistory of myocardial infarction are less prevalent in patients presenting \nwith MINOCA. \nDefinition \nThe European Society of Cardiology drafted the first international \nposition article on MI NOCA and defined MINOCA based on Third \nUniversal Definition of Myocardial Infarction. [12,13] A recent scientific \nstatement from the American Heart Association further refined the \ndefinition of MINOCA based on Fourth Universal Definition of \nMyocardial Infarction as: 1) Acute Myocardial Infarction as defined by \nAbstract: \nMyocardial Infarction in the absence of obstructive coronary artery disease [MINOCA] is seen in 5 -6% of the \npatients presenting with myocardial infarction. While patients with MINOCA can present with either ST \nsegment elevation or non-ST segment elevation myocardial infarction, they are less likely to have ST segment \ndeviation on electrocardiography and have less of cardiac biomarker elevation compared to their obstructive \ncoronary artery disease counterparts. Patients with MINOCA are usually younger and with lower prevalence of \ntraditional cardiovascular risk factors compared with patients presenting with obstructive coronary artery \ndisease. A variety of atherosclerotic and non-atherosclerotic mechanisms can lead to MINOCA. A diagnosis of \nMINOCA can only be made in patients whose clinical presentation is attributed to an ischemic event after \nexcluding obstructive coronary artery disease and alternate causes for troponin elevation. A systematic approach \nto diagnosing the underlying causes is warranted to optimally treat patients presenting with MINOCA. \nKey words: myocardial infarction in the absence of obstructive coronary artery disease; minoca; \nmanagement \n  Open Access  Review Article \nJournal of Clinical Cardiology and Cardiovascular Interventions \nMeera D Kondapaneni* \nAUCTORES \nGlobalize your Research \n\nJ Clinical Research and Reports Copy rights@ Meera D Kondapaneni et.al. \nAuctores Publishing – Volume 3(13)-113 www.auctoresonline.org \nISSN: 2641-0419 Page 2 of 4 \n \n \n \nthe “Fourth Universal Definition of Myocardial Infarction”; (2) \nNonobstructive coronary arteries on angiography, with no lesions ≥50% \nin a major epicardial vessel (normal coronary arteries, mild luminal \nirregularities (<30% stenoses) or moderate coronary a therosclerotic \nlesions (>30% but <50% stenoses) ; and (3) No specific alternate \ndiagnosis for the clinical presentation where in alternate diagnoses \ninclude but are not limited to non -ischemic causes such as sepsis, \npulmonary embolism, and myocarditis. [1, 14] \nEtiology \nThe underlying mechanisms for myocardial necrosis in patients \npresenting with MINOCA can be broadly classified into atherosclerotic \nand nonatherosclerotic causes. [1] \nAtherosclerotic causes of Myocardial Necrosis \n \nAtherosclerotic causes of my ocardial necrosis are due to plaque \ndisruption which includes plaque rupture, plaque erosion and calcific \nnodules. [1] Plaque disruption was observed in one -third of the women \npatients diagnosed with MINOCA. [15] Plaque rupture, typically caused \nby inflamm ation, is discontinuity of fibrous cap leading to a \ncommunication between plaque cavity and the coronary lumen leading to \nthrombus formation. Whereas, plaque erosion is primarily caused by \nendothelial erosion with a thrombus that is contiguous to the luminal \nsurface of a plaque without signs of rupture. [16] Plaque disruption can \ncause thrombus formation with distal emboli zation, and in some cases, \ntransient complete thrombosis with spontaneous thrombolysis. [15] \nAngiographic evidence of occlusion may not be evident due to non- \nocclusive thrombus in patients with MINOCA. \nNonatherosclerotic causes of Myocardial Necrosis \n \nCoronary artery vasospasm is defined as intense (>90%) transient \nvasospasm of the coronary arteries associated with angina and ischemic \nelectrocardiographic changes either spontaneously or in response to a \nprovocative stimulus as defined by Coronary Vasomotio n Disorders \nInternational Study Group (COVADIS). [17] Though Prinzmetal et al. \nfirst described coronary artery spasms in patients with obstructive \ncoronary artery disease, it is now more often considered in patients with \nnonobstructive coronary artery disease. [18] Further studies have reported \ncoronary artery vasospasm as the leading cause of MINOCA with \nevidence for coronary vasospasm reported in nearly 46% of the patients \npresenting with MINOCA undergoing provocative tests. [2,19] \nThe coronary microcircu lation which accounts for nearly 70% of the \ncoronary resistance can potentially contribute to the pathogenesis of \nMINOCA. Further, coronary artery emboli can result in MINOCA if it \ninvolves the coronary microcirculation. Hypercoagulable state secondary \nto inherited disorders, thrombotic thrombopenic purpura, and heparin \ninduced thrombocytopenia can precipitate embolic phenomenon and lead \nto occlusion of coronary microcirculation causing MINOCA. \nSpontaneous coronary artery dissection can be considered a poss ible \ncause of MINOCA. [10] Though most patients with spontaneous coronary \nartery dissection have a visible obstruction on angiography, the arteries \ncan be normal because of the gradual tapering of the vessels. [20] \nFurthermore, few patients may have a supply -demand mismatch which \ncan present as MINOCA. [21,22] \nManagement \nThe management strategies for patients with myocardial infarction \nsecondary to obstructive causes are well established. However, its \ncounterpart with non -obstructive coronary artery disease management \nlacks evidence -based guidelines and hence the variab le standards in \ndiagnosis and management of MINOCA. Some progress was made in the \nrealm of multi -modality imaging as a tool to identify potential \nmechanisms leading to MINOCA. Reynolds et. al in a recent prospective, \nmulticenter, observational study demons trated that Coronary Optical \nCoherence Tomography (OCT) and Cardiac Magnetic Resonance \nImaging (CMR) together can diagnose identifiable etiology in \napproximately 85% of women presenting with MINOCA. [23] \nAlthough the prognosis of patients with MINOCA has b een shown to be \nbetter than their counterparts with obstructive coronary artery disease and \npresenting with AMI, the mortality and morbidity associated with \nMINOCA is not negligible and substantially higher than general \npopulation without cardiovascular disease. [1,10] A more recent study by \nChoo et.al on behalf of KAMIR-NIH investigators has revealed that risk \nof all-cause death and recurrent MI were similar between patients with \nMINOCA and MI due to obstructive coronary artery disease at 2 years. \n[24] Hence it is imperative that a systematic approach is needed towards \ndiagnosing this heterogenous entity and further define and treat the \nunderlying cause. Position statements from European Society of \nCardiology and American Heart Association provide a n excellent \nframework for diagnosis and management of MINOCA. [1,12] \nDiagnosis \nThe diagnostic algorithm for MINOCA include an initial evaluation to \nexclude clinically overt causes for myocardial injury from a non-ischemic \nevent. [1,12] This should be followed by further evaluation to identify \npotentially overlooked obstructive coronary artery disease by re - \nreviewing the angiogram to rule out distal cut -offs suggesting \nthromboembolic occlusion and spontaneous c oronary artery dissection. \nFurther investigation focusing on individual etiologies for the ischemic \nevent leading to MINOCA can be considered including coronary vascular \nimaging with Intravascular Ultrasound (IVUS) and OCT to identify \nplaque disruption, in vasive coronary provocative testing to rule out \nepicardial coronary vasospasm, and coronary functional assessment with \nCoronary Flow Reserve to assess microvascular function. Furthermore, \nCMR should be considered in patients with MINOCA to differentiate it  \nfrom myocarditis, Takotsubo cardiomyopathy and other \ncardiomyopathies as well as to confirm ischemic etiology with evidence \nsuggestive of infarction. [23] \nIndividualized treatment strategies \nAfter excluding all possible alternate diagnoses mimicking AMI and \nidentifying potential underlying mechanism for MINOCA, cause-specific \ntargeted therapy should be considered. [1] MINOCA patients secondary \nto plaque disruption should be treated with cardio protective therapies in \naccordance with the AMI guidelines with aspirin being the main \ncornerstone of management because the pathophysiology is similar to that \nof myocardial infarction due to obstructive coronary artery disease. \nFurther, patients with MINO CA are usually not treated with stents, as \nsupported by a study which treated MINOCA patients with dual \nantiplatelet therapy alone and reported an acceptable 1 -year \nrevascularization rate of 5.7%. [25] Calcium channel blockers are the \n\nJ Clinical Research and Reports Copy rights@ Meera D Kondapaneni et.al. \nAuctores Publishing – Volume 3(13)-113 www.auctoresonline.org \nISSN: 2641-0419 Page 3 of 4 \n \n \n \nmainstay of treatment in patients presenting with MINOCA secondary to \ncoronary spasm. [26, 27] Treating underlying cause remains the mainstay \nfor patients presenting with supply-demand mismatch. \nCardioprotective therapies \nThe role of cardioprotective therapies in secondary prevention is not \nclearly outlined for patients with MINOCA unlike MI with obstructive \ncoronary artery disease with no completed prospective, randomized \ncontrolled trials to date. An observational cohort study of patients with \nMINOCA enrolled in SWEDEHEART registry indicated that \nangiotensin-converting enzyme inhibitors/angiotensin receptor blockers \n(ACEI/ARB) and statin therapy were associated with lower major adverse \ncardiac events defined as all -cause m ortality, hospitalization for \nmyocardial infarction, ischemic stroke and heart failure after 4.1 years of \nmean follow up. [28] Beta-blockers were associated with a trend towards \nlow event rate in the same study whereas dual antiplatelet therapy was not \nassociated with a lower event rate. A multicenter prospective registry by \nChoo et. al. also confirmed the independent association of nonuse of \nrenin-angiotensin system blockers and statins with an increased risk of \nall-cause mortality at 2 year follow up. [24 ] MINOCA -BAT, a multi - \nnational, multi-center, randomized clinical trial is currently underway to \nevaluate the effect of beta-blocker and ACEI/ARB therapy on long -term \nclinical outcomes in patients with MINOCA. [29] \n \nConclusion \nA systematic multi -modality approach to diagnosing underlying \nmechanisms leading to MINOCA and excluding alternate diagnoses of \nmyocardial injury is crucial in establishing this challenging heterogenous \ndiagnosis. Management of MINOCA should focus on individualizing \ntreatment with ca use-specific targeted therapies and institution of \ncardioprotective therapies for secondary prevention. \nReferences \n \n1. Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis \nES, Brown TM, et.al. Contemporary diagnosis and  \nmanagement of patients with myocardial infarction in the  \nabsence of obstructive coronary artery disease: a scientific  \nstatement from the American Heart Association. Circulation.  \n2019; 139: e891–e908. \n2. 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Am  \nHeart J. 2021; 231: 96-104. \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nThis work is licensed under Creative \nCommons Attribution 4.0 License \n \nTo Submit Your Article Click Here: \n \nDOI:10.31579/2641-0419/106 \nSubmit Article \nReady to submit your research? Choose Auctores and benefit from: \n \n fast, convenient online submission \n rigorous peer review by experienced research in your field \n rapid publication on acceptance \n authors retain copyrights \n unique DOI for all articles \n immediate, unrestricted online access \nAt Auctores, research is always in progress. \nLearn more www.auctoresonline.org/journals/clinical-cardiology-and- \ncardiovascular-interventions \n2020. Nov 14.","source_license":"CC0","license_restricted":false}