A Breakthrough in the Pathogenesis of Ischemic Heart Disease: the MINOCA and INOCA Challenge

Ricardo Esper, Juan Carlos Kaski


Classical coronary syndromes as angina pectoris, ischemiaand myocardial infarction, which were describedmany years ago, are generally attributed tothe presence of different degrees of coronary arteryobstruction caused by atherosclerotic plaques.Atherosclerosis is a chronic inflammatory diseaseaffecting both sexes that starts in childhood, and evenin intrauterine life, and progresses throughoutthe years, especially in subjects with cardiovascularrisk factors. In this inflammatory process, and in thepresence of a specific or inadequate metabolic environments,such as diabetes mellitus or those resultingfrom traditional risk factors, β-lipoproteins and glycatedproteins oxidize becoming antigenic and causingendothelial dysfunction. This favors the penetrationof these molecules into vascular subendotheliallayers where they generate an immunogenic reaction,activating monocytes that are transformed into macrophages,which, together with other cells involved inthis process, create a lipid inflammatory core. Vascularsmooth muscle cells, recruited by inflammation,change from a contractile phenotype to a secretoryphenotype and generate collagen, which surroundsthe lipid inflammatory core and promotes calciumdeposition, completing the formation of the atheromatousplaque. This complex process (briefly describedhere) involves a multitude of molecules thatare produced as a result of oxidation, inflammation,apoptosis, angiogenesis, degradation of the fibrouscap, influx of red cells, tissue factor expression andother components that determine the progression ofthe atherosclerotic plaque over time.


Napoli C, D’Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997;100:2680-90. http://doi.org/fst5jq

Esper RJ, Nordaby RA, Vilariño JO, Paragano A, Cacharrón JL, Machado RA. Endothelial dysfunction: A comprehensive appraisal. Cardiovasc Diabetol 2006;5:4. http://www.cardiab.com/content/5/1/4 http://doi.org/c4nw7n

Libby P, Folco E, Esper RJ. Inmunidad, Inflamación y Ateroesclerosis. En: Esper RJ, Vilariño JO (Eds): Progresos en Aterotrombosis. Buenos Aires, Ediciones Médicas del Sur, 2011, p: 21-48

Esper RJ, García Guiñazú CA, Bereziuk E, Ingino CA: Electrocardiografia.Buenos Aires, Editorial La Agenda, 1977

Kaski JC, Crea F, Gersch BJ, Camici PJ. Reappraisal of ischemic heart disease. Fundamental role of coronary microvascular dysfunction in the pathogenesis of angina pectoris. Circulation 2018;138:1463-80. http://doi.org/gfdg24

Beltrame JF. Assessing patients with myocardial infarction

and non-obstructed coronary arteries (MINOCA). J Intern Med

;273:182-5. http://doi.org/c9g6

Tamis-Holland JE, Jneid H. Myocardial infarction with nonobstructive coronary arteries (MINOCA): It’s time to face reality. J Am Med Assoc 2018;7:e009635. http://doi.org/c9g7

Ciliberti G, Coiro S, Tritto I, Benedetti M, Ambrosio G. Predictors of poor clinical outcomes in patients with acute myocardial infarction and non-obstructed coronary arteries (MINOCA). Int J Cardiol 2018;267:41-5. http://doi.org/c9g8

Esper RJ, Nordaby RA, Vilariño JO. Endothelium and acute cardiovascular events. En: Milei J, Ambrosio G (Eds): Recent Advances in Cardiology. New York, Nova Sciences Publishers Inc., 2014, p: 1-22 10. Niccoli G, Montone RA, Lanza GA, Crea F. Angina after percutaneous coronary intervention: The need for precision medicine. Int J Cardiol 2017;248:14-9. http://doi.org/c9g9

Arbab-Zadeh A, Nakano M, Virmani RF, Fuster V. Acute coronary events. Circulation 2012; 125:447-56. http://doi.org/c9hc

Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the

vulnerable plaque. J Am Coll Cardiol 2006;47:C13-C18. http://doi.org/d692gf

Falk E, Shah P, Fuster V. Coronary plaque disruption. Circulation 1995;92:657-71. http://doi.org/c9hd

Riufol G, Finet G, Andre-Fouet X, Rossi R, Vialle E, Desjoyaux E, et al. Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 2002;106:804-8. http://doi.org/dftnth

Khot UN, Khor MB, Bajzer ZE, Sapp SK, Ohman EM, Brener SJ, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003;290:898-904. http://doi.org/d9h69r

Kalkman DN, Aquino M, Claessen BE, Baber U, Guedeney P, Sorrentino S, et al. Residual inflammatory risk and the impact f clinical outcomes in patients after percutaneous coronary interventions. Eur

Heart J 2018;39:4101-8. http://doi.org/gfhb9h

Lindahl B, Baron T, Erlinge D, Hadziosmanovic N, Nordenskjold A, Gard A, Jernberg T. Medical therapy for secondary prevention and long-term outcome in patients with myocardial infarction with nonobstructive corfonary artery disease. Circulation 2017;135:1481-9. http://doi.org/f9r8pg

Niccoli G, Scalone G, Crea F. Acute myocardial infarction with no obstructive coronary atherosclerosis: Mechanism and management. Eur Heart J 2015;36:475-81. http://doi.org/f66pnt

Pasupathy S, Tavella R, McRae S, Beltrame JF. Myocardial infarction with non-obstructive coronay arteries. Eur Cardiol Review 2015;10:79-82. http://doi.org/c9hf

Ford TJ, Rocchiccioly P, Good R, McEntegart M, Eiteba H, Watkins S, et al. Systemic microvascular dysfunction in microvascular and vasospastic angina. Eur Heart J 2018;39:4086-97. http://doi.org/c9hf

Allen EV. Thromboangiitis obliterans: methods of diagnosis of chronic occlusive arterial lesions distal to the wrist with illustrative cases. Am J Med Sci 1929;2:1-8. http://doi.org/b2p42m

Esper RJ, Esper Antivero P, Ingino CA, Vilariño JO. Disparadores emocionales de Ataques Cardiovasculares. En: Ingino CA, Vilariño JO, Lylyk P, Esper RJ (Eds), Toma de Decisiones en Urgencias Cardio-Neuro-Vasculares. Buenos Aires, Ediciones Médicas del Sur, 2017,Tomo I, p: 59-78.

Full Text


  • There are currently no refbacks.

Licencia Creative Commons
The documents published in this journal are under the licencia Creative Commons Atribución-NoComercial-Compartir-Igual 2.5 Argentina.

Revista argentina de cardiología. ISSN en línea 1850-3748. Argentine journal of cardiology (English ed. Online ISSN 2314-2286) Sociedad Argentina de Cardiología. Azcuénaga 980 (C1115AAD),Ciudad Autónoma de Buenos Aires, República Argentina. Tel. (54 11) 4961-6027/8/9 Fax: 4961-6020 www.sac.org.ar revista@sac.org.ar