CARDIOVASCULAR
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Angiography Doesn't Tell You the Whole Story

Approximately 112 million people globally are affected by angina and undergo coronary angiography, the primary diagnostic test for angina.1 Unfortunately, angiography is limited to assessing the epicardial arteries and cannot assess the microcirculation, which is largely responsible for the regulation and distribution of blood flow to the myocardium.2 Additionally, too often patients with ischemia with non-obstructive coronary arteries (INOCA) on angiography remain undiagnosed.3 About 40-60% of chronic coronary syndrome (CCS) patients undergoing angiography have INOCA, and a large proportion of these patients may have coronary microvascular dysfunction (CMD).4,5 Proper diagnosis of CMD and treatment is the only way to improve outcomes in these patients at high risk for major adverse cardiac events (MACE).4

Prevalence and Purpose of Diagnosing Coronary Microvascular Dysfunction (CMD)

Prof. Divaka Perera, Consultant Cardiologist, London, UK

Diagnosing The Underlying Cause Of Chest Pain Can Be Challenging

 

Ischemic heart disease continues to be the leading cause of death globally.6  Yet chest pain—while often ischemic in nature—could have many etiologies, as illustrated.7 When chest pain is caused by ischemia (angina), proper management depends on accurately identifying and treating the underlying cause of angina.

Chest pain can have many underlying causes

Marinescu MA, Löffler Al, Ouellette M, et al. Coronary microvascular dysfunction and microvascular angina: a systematic review of therapies. JACC Cardiovasc Imaging. 2015; 8:210-220.
Kunadian V, Chieffo A, Cmici PG, et al. EAPCI Expert Consensus Document. EHJ. 2020; 0:1-21.

Structural and functional causes of recurrent or persistent angina despite non-obstructive coronary artery disease.8

RECURRENT OR PERSISTENT ANGINA

Structural Causes8

  • In-stent restenosis
  • Stent thrombosis
  • Progression of atherosclerotic disease in other segments
  • Incomplete revascularization
  • Diffuse atherosclerotic disease without focal stenosis
  • Presence of myocardial bridges

Functional Causes8

  • Coronary microvascular dysfunction
  • Epicardial vasospasm
  • Stent-related mechanical stretch of the arterial wall

The Majority Of Patients In The Cath Lab Are Found To Have No Obstructive Coronary Artery Disease

Only 41% of patients assessed for angina are found to have obstructive chronic coronary artery disease.4 The majority (59%) have no angiographic abnormalities,4 but still have symptoms of a coronary disorder.9

Most angiograms yield no coronary artery disease

Patel et al. Low diagnostic yield of elective coronary angiography. NEJM 2010.

20-30% of patients experience recurrent angina in 1 year after percutaneous coronary intervention (PCI).10

 

20-30% of patients experience recurrent angina in 1 year after percutaneous coronary intervention (PCI)

INOCA patients with persistent angina frequently remain underdiagnosed. Without a clear diagnosis and treatment, this may result in recurrent hospitalizations, poor functional health, and adverse cardiovascular outcomes.11

Up to 50-65% of patients who have angina but non-obstructive CAD are believed to have coronary microvascular dysfunction (CMD).7

Left Undiagnosed And Untreated, Cmd Can Have A Major Impact On Both Patients And Healthcare Systems

The microcirculation carries far more myocardial blood volume compared to the epicardial arteries. CMD can be defined as impaired CFR in the absence of epicardial obstructive CAD—i.e., downstream vasomotor dysfunction.12

INOCA Is Not Benign: The Impact on Clinical Outcomes

Patients with INOCA, including those diagnosed with CMD, have an increase in major adverse cardiac events (MACE) including:

  • Myocardial infarction13
  • Stroke13
  • Diastolic dysfunction12 and heart failure12,13
  • Cardiovascular death13
  • Cardiac death12
  • All-cause mortality13

Coronary Flow Reserve Associated with MACE Risks12

Reduced coronary flow reserve is associated with adverse events

Image adapted from Taqueti et al, J Am Coll Cardiol 201812

Clinical Spectrum of CMD

MACE risk increases with CMD severity

Image adapted from Taqueti et al, J Am Coll Cardiol 201812

The clinical spectrum of CMD may be characterized by three factors:12

  • The severity of CMD
  • The degree of atherosclerosis
  • Any associated clinical risks

The Impact on Healthcare Costs, Cath Labs, and Patients

$2,100 - $7,300

INOCA frequently impacts patient quality of life (QOL) and consumes significant health care expenditures.14,15 With multiple evaluations and frequent hospitalization14,15, each additional hospitalization can add $2,100 (the Netherlands) to $7,300 (the U.S.) in healthcare costs.16

Nevertheless, it is possible to accurately diagnose patients on their first visit to the cath lab and to provide effective treatment.

References

  1. Kunadian V, Chieffo A, Camici PG, et al. An EAPCI Expert Consensus Document on Ischaemic 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. European Heart Journal. 2020; 0:1-21.
  2. Taqueti VR, Di Carli MF. Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review. J Am Coll Cardiol. 2018;72:2625–2641. doi:10.1016/j.jacc.2018.09.042.
  3. Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-744. doi:10.1093/eurheartj/ehr331.
  4. Patel MR , Peterson ED , Dai D , et al. Low diagnostic yield of elective coronary angiography. N Engl J Med. 2010;362:886-895. doi:10.1056/NEJMoa0907272.
  5. Maas A, et al. Microvascular angina: diagnosis, assessment, and treatment. EMJ Int Cardiol. 2019; 7[Suppl 1]2-17.
  6. Wang H, Naghavi M, Allen C, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1459-544.
  7. Marinescu MA, Löffler AI, Ouellette M, et al. Coronary microvascular dysfunction and microvascular angina: a systematic review of therapies. JACC Cardiovasc Imaging. 2015;8:210-220. doi:10.1016/j.jcmg.2014.12.008.
  8. Niccoli G, Montone RA, Lanza GA, et al. Angina after percutaneous coronary intervention: the need for precision medicine. Int J Cardiol. 2017;248:14-19. doi: 10.1016/j.ijcard.2017.07.105.
  9. Ford TJ, Berry C. How to diagnose and manage angina without obstructive coronary artery disease: lessons from the British Heart Foundation CorMicA Trial. Interv Cardiol Rev. 2019;14(2):76-82.
  10. Jeremias A. Blinded Physiological Assessment of Residual Ischemia after Successful Angiographic PCI. ACC 2019.
  11. Lee B, Lim H, Fearon WF, et al. Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation. 2015;131:1054–1060.
  12. Taqueti VR, Di Carli MF. Coronary microvascular disease pathogenic mechanisms and therapeutic options: JACC state-of-the-art review. J Am Coll Cardiol. 2018;72:2625–2641. doi:10.1016/j.jacc.2018.09.042.
  13. Jespersen L, Hvelplund A, Abildstrøm SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J. 2012;33:734-744. doi:10.1093/eurheartj/ehr331.
  14. Lee B, Lim H, Fearon WF, et al. Invasive evaluation of patients with angina in the absence of obstructive coronary artery disease. Circulation. 2015;131:1054–1060.
  15. Reriani M, Flammer AJ, Duhé J, et al. Coronary endothelial function testing may improve long-term quality of life in subjects with microvascular coronary endothelial dysfunction. Open Heart. 2019;6:e000870. doi: 10.1136/openhrt-2018-000870.
  16. Omerovic E. FFR-Guided Complete Revascularization During Primary Angioplasty: Effects on Societal Costs. EuroPCR 2017.
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