Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders

Thomas J Ford, Eric Yii, Novalia Sidik, Richard Good, Paul Rocchiccioli, Margaret McEntegart, Stuart Watkins, Hany Eteiba, Aadil Shaukat, Mitchell Lindsay, Keith Robertson, Stuart Hood, Ross McGeoch, Robert McDade, Peter McCartney, David Corcoran, Damien Collison, Christopher Rush, Bethany Stanley, Alex McConnachie, Naveed Sattar, Rhian M Touyz, Keith G Oldroyd, Colin Berry, Thomas J Ford, Eric Yii, Novalia Sidik, Richard Good, Paul Rocchiccioli, Margaret McEntegart, Stuart Watkins, Hany Eteiba, Aadil Shaukat, Mitchell Lindsay, Keith Robertson, Stuart Hood, Ross McGeoch, Robert McDade, Peter McCartney, David Corcoran, Damien Collison, Christopher Rush, Bethany Stanley, Alex McConnachie, Naveed Sattar, Rhian M Touyz, Keith G Oldroyd, Colin Berry

Abstract

Background: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA).

Methods: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3-3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P<0.001) but with lower cardiovascular risk scores (ASSIGN score median 20% versus 24%; P=0.003). INOCA subjects had similar burden of angina (Seattle Angina Questionnaire) but reduced quality of life compared with coronary artery disease; subjects (EQ5D-5 L index 0.60 versus 0.65 units; P=0.041).

Results: An interventional diagnostic procedure with reference invasive tests including coronary flow reserve, microvascular resistance, and vasomotor responses to intracoronary acetylcholine (vasospasm provocation) was performed in 151 INOCA subjects. Overall, 78 (52%) had isolated microvascular angina, 25 (17%) had isolated vasospastic angina, 31 (20%) had both, and 17 (11%) had noncardiac chest pain. Regression analysis showed inducible ischemia on treadmill testing (OR, 7.5 [95% CI, 1.7-33.0]; P=0.008) and typical angina (OR, 2.7 [1.1-6.6]; P=0.032) were independently associated with microvascular angina. Female sex tended to associate with a diagnosis of microvascular angina although this was not significant (OR, 2.7 [0.9-7.9]; P=0.063). Vasospastic angina was associated with smoking (OR, 9.5 [2.8-32.7]; P<0.001) and age (OR, 1.1 per year, [1.0-1.2]; P=0.032].

Conclusions: Over three quarters of patients with INOCA have identifiable disorders of coronary vasomotion including microvascular and vasospastic angina. These patients have comparable angina burden but reduced quality of life compared to patients with obstructive coronary artery disease. Microvascular angina and vasospastic angina are distinct disorders that may coexist but differ in associated clinical characteristics, symptoms, and angina severity.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193294.

Keywords: angina pectoris; dyspnea; microvascular angina; prevalence; quality of life.

Figures

Figure 1.
Figure 1.
Study overview—prevalence of coronary vasomotion disorders in ischemia and no obstructive coronary artery disease (INOCA). Figure showing screening and enrollment process with a total of 185 INOCA patients and 206 oCAD patients. IDP indicates interventional diagnostic procedure; MVA, microvascular angina; oCAD, obstructive epicardial disease; and VSA, vasospastic angina.
Figure 2.
Figure 2.
Invasive assessment for coronary vasomotion disorders in angina. A, Shows different diagnoses within ischemia and no obstructive coronary artery disease (INOCA) population while (B) shows the heterogenous nature of microvascular angina. ACh indicates acetylcholine; CFR, coronary flow reserve; IDP, interventional diagnostic procedure; IMR, index of microcirculatory resistance (abnormal ≥25); MVA, microvascular angina; and VSA, vasospastic angina.
Figure 3.
Figure 3.
Differences in angina and quality of life between microvascular angina (MVA) and vasospastic angina (VSA). Figure showing the differences in angina and quality of life (QoL) score with VSA group having almost 20% lower overall angina summary score compared with MVA. SAQ indicates Seattle Angina Questionnaire.

References

    1. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, Douglas PS, Foody JM, Gerber TC, Hinderliter AL, et al. American College of Cardiology Foundation/American Heart Association Task Force. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012;126:e354–e471. doi: 10.1161/CIR.0b013e318277d6a0.
    1. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, et al. Task Force Members; ESC Committee for Practice Guidelines; Document Reviewers. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34:2949–3003. doi: 10.1093/eurheartj/eht296.
    1. 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.116.024534.
    1. Ford TJ, Corcoran D, Berry C. Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need. Heart. 2018;104:284–292. doi: 10.1136/heartjnl-2017-311446.
    1. Kaski JC, Crea F, Gersh BJ, Camici PG. Reappraisal of ischemic heart disease. Circulation. 2018;138:1463–1480. doi: 10.1161/CIRCULATIONAHA.118.031373.
    1. Crea F, Camici PG, Bairey Merz CN. Coronary microvascular dysfunction: an update. Eur Heart J. 2014;35:1101–1111. doi: 10.1093/eurheartj/eht513.
    1. 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.2018.09.006.
    1. Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN Coronary Vasomotion Disorders International Study Group (COVADIS) International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16–20. doi: 10.1016/j.ijcard.2017.08.068.
    1. Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, Handberg EM, Johnson BD, Sopko G, Bairey Merz CN. Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the national heart, lung and blood institute WISE (Women’s Ischemia Syndrome Evaluation) study. J Am Coll Cardiol. 2010;55:2825–2832. doi: 10.1016/j.jacc.2010.01.054.
    1. Fearon WF, Balsam LB, Farouque HM, Caffarelli AD, Robbins RC, Fitzgerald PJ, Yock PG, Yeung AC. Novel index for invasively assessing the coronary microcirculation. Circulation. 2003;107:3129–3132. doi: 10.1161/01.CIR.0000080700.98607.D1.
    1. Pijls NH, De Bruyne B, Smith L, Aarnoudse W, Barbato E, Bartunek J, Bech GJ, Van De Vosse F. Coronary thermodilution to assess flow reserve: validation in humans. Circulation. 2002;105:2482–2486. doi: 10.1161/01.cir.0000017199.09457.3d.
    1. Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN Coronary Vasomotion Disorders International Study G. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565–2568. doi: 10.1093/eurheartj/ehv351.
    1. Ford TJ, Corcoran D, Oldroyd KG, McEntegart M, Rocchiccioli P, Watkins S, Brooksbank K, Padmanabhan S, Sattar N, Briggs A, et al. Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Angina (CorMicA) stratified medicine clinical trial. Am Heart J. 2018;201:86–94. doi: 10.1016/j.ahj.2018.03.010.
    1. Rose G, McCartney P, Reid DD. Self-administration of a questionnaire on chest pain and intermittent claudication. Br J Prev Soc Med. 1977;31:42–48. doi: 10.1136/jech.31.1.42.
    1. Woodward M, Brindle P, Tunstall-Pedoe H SIGN Group on Risk Estimation. Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC). Heart. 2007;93:172–176. doi: 10.1136/hrt.2006.108167.
    1. Murthy VL, Naya M, Taqueti VR, Foster CR, Gaber M, Hainer J, Dorbala S, Blankstein R, Rimoldi O, Camici PG, Di Carli MF. Effects of sex on coronary microvascular dysfunction and cardiac outcomes. Circulation. 2014;129:2518–2527. doi: 10.1161/CIRCULATIONAHA.113.008507.
    1. Fearon WF, Kobayashi Y. Invasive assessment of the coronary microvasculature: the index of microcirculatory resistance. Circ Cardiovasc Interv. 2017;10:e005361. doi: 10.1161/CIRCINTERVENTIONS.117.005361.
    1. De Bruyne B, Baudhuin T, Melin JA, Pijls NH, Sys SU, Bol A, Paulus WJ, Heyndrickx GR, Wijns W. Coronary flow reserve calculated from pressure measurements in humans. Validation with positron emission tomography. Circulation. 1994;89:1013–1022. doi: 10.1161/01.cir.89.3.1013.
    1. Ge J, Jeremias A, Rupp A, Abels M, Baumgart D, Liu F, Haude M, Görge G, von Birgelen C, Sack S, et al. New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and doppler. Eur Heart J. 1999;20:1707–1716. doi: 10.1053/euhj.1999.1661.
    1. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR, Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101:948–954. doi: 10.1161/01.cir.101.9.948.
    1. Aziz A, Hansen HS, Sechtem U, Prescott E, Ong P. Sex- related differences in vasomotor function in patients with angina and unobstructed coronary arteries. J Am Coll Cardiol. 2017;70:2349–2358. doi: 10.1016/j.jacc.2017.09.016.
    1. Sara JD, Widmer RJ, Matsuzawa Y, Lennon RJ, Lerman LO, Lerman A. Prevalence of coronary microvascular dysfunction among patients with chest pain and nonobstructive coronary artery disease. JACC Cardiovasc Interv. 2015;8:1445–1453. doi: 10.1016/j.jcin.2015.06.017.
    1. Delgado-Rodríguez M, Llorca J. Bias. J Epidemiol Community Health. 2004;58:635–641. doi: 10.1136/jech.2003.008466.
    1. Steckelberg JM, Melton LJ, 3rd, Ilstrup DM, Rouse MS, Wilson WR. Influence of referral bias on the apparent clinical spectrum of infective endocarditis. Am J Med. 1990;88:582–588. doi: 10.1016/0002-9343(90)90521-e.
    1. Ogawa H, Akasaka T, Hattori R, Inoue T, Kawashima S, Kawasuji M, Kimura K, Miwa K, Mizuno K, Mohri M, et al. Group JCSJW. Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ J. 2014;78:2779–2801. doi: 10.1253/circj.cj-66-0098.
    1. Ong P, Athanasiadis A, Borgulya G, Vokshi I, Bastiaenen R, Kubik S, Hill S, Schäufele T, Mahrholdt H, Kaski JC, Sechtem U. Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation. 2014;129:1723–1730. doi: 10.1161/CIRCULATIONAHA.113.004096.
    1. Taqueti VR, Solomon SD, Shah AM, Desai AS, Groarke JD, Osborne MT, Hainer J, Bibbo CF, Dorbala S, Blankstein R, et al. Coronary microvascular dysfunction and future risk of heart failure with preserved ejection fraction. Eur Heart J. 2018;39:840–849. doi: 10.1093/eurheartj/ehx721.
    1. Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, Brindis RG, Douglas PS. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886–895. doi: 10.1056/NEJMoa0907272.
    1. Patel MR, Dai D, Hernandez AF, Douglas PS, Messenger J, Garratt KN, Maddox TM, Peterson ED, Roe MT. Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J. 2014;167:846–52.e2. doi: 10.1016/j.ahj.2014.03.001.
    1. Hochman JS, Reynolds HR, Bangalore S, O’Brien SM, Alexander KP, Senior R, Boden WE, Stone GW, Goodman SG, Lopes RD, et al. ISCHEMIA Research Group. Baseline characteristics and risk profiles of participants in the ISCHEMIA randomized clinical trial. JAMA Cardiol. 2019;4:273–286. doi: 10.1001/jamacardio.2019.0014.
    1. Reid CJ, Tanner M, Murphy C. Is angiography overused for the investigation of suspected coronary disease? A single-centre study. Br J Cardio. 2014:21.
    1. Suda A, Shimokawa H, Takahashi J, Hao K, Komatsu M, Miyata S, Shindo T, Kikuchi Y, Matsumoto Y, Odaka Y, et al. Important prognostic impact of comorbid coronary microvascular dysfunction in patients with vasospastic angina. Eur Heart J. 2017;38
    1. Mygind ND, Michelsen MM, Pena A, Frestad D, Dose N, Aziz A, Faber R, Høst N, Gustafsson I, Hansen PR, et al. Coronary microvascular function and cardiovascular risk factors in women with angina pectoris and no obstructive coronary artery disease: the iPOWER Study. J Am Heart Assoc. 2016;5:e003064. doi: 10.1161/JAHA.115.003064.
    1. Schroder J, Mygind ND, Frestad D, Michelsen M, Suhrs HE, Bove KB, Gustafsson I, Kastrup J, Prescott E. Pro-inflammatory biomarkers in women with non-obstructive angina pectoris and coronary microvascular dysfunction. Int J Cardiol Heart Vasc. 2019;24:100370. doi: 10.1016/j.ijcha.2019.100370.
    1. Okumura K, Yasue H, Matsuyama K, Goto K, Miyagi H, Ogawa H, Matsuyama K. Sensitivity and specificity of intracoronary injection of acetylcholine for the induction of coronary artery spasm. J Am Coll Cardiol. 1988;12:883–888. doi: 10.1016/0735-1097(88)90449-4.
    1. Ford TJ, Berry C, De Bruyne B, Yong ASC, Barlis P, Fearon WF, Ng MKC. Physiological predictors of acute coronary syndromes: Emerging Insights From the Plaque to the vulnerable patient. JACC Cardiovasc Interv. 2017;10:2539–2547. doi: 10.1016/j.jcin.2017.08.059.
    1. Sueda S, Kohno H, Fukuda H, Inoue K, Suzuki J, Watanabe K, Ochi T, Uraoka T. Clinical and angiographical characteristics of acetylcholine- induced spasm: relationship to dose of intracoronary injection of acetylcholine. Coron Artery Dis. 2002;13:231–236. doi: 10.1097/00019501-200206000-00005.
    1. Sheikh AR, Zeitz CJ, Rajendran S, Di Fiore DP, Tavella R, Beltrame JF. Clinical and coronary haemodynamic determinants of recurrent chest pain in patients without obstructive coronary artery disease - A pilot study. Int J Cardiol. 2018;267:16–21. doi: 10.1016/j.ijcard.2018.04.077.
    1. Williams MC, Hunter A, Shah A, Assi V, Lewis S, Mangion K, Berry C, Boon NA, Clark E, Flather M, et al. Scottish COmputed Tomography of the HEART (SCOT-HEART) Trial Investigators. Symptoms and quality of life in patients with suspected angina undergoing CT coronary angiography: a randomised controlled trial. Heart. 2017;103:995–1001. doi: 10.1136/heartjnl-2016-310129.
    1. Sidik NP, McEntegart M, Roditi G, et al. Rationale and Design of the British Heart Foundation (BHF) coronary microvascular function and CT coronary angiogram (CorCTCA) study. Am Heart J. 2019 [in press]. doi: 10.1016/j.ahj.2019.11.015.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj