A Headache for Cardiologists: Ischemia with Non-Obstructive Disease

Treating patients with functional stress test induced ischemia and non-obstructive coronary artery disease (INOCA) is complex and often frustrating. 

Isquemia con enfermedad NO obstructiva.

The multifactorial nature of this disease in addition to the complex physiopathological relationship between angina and ischemia turn these patients into a real headache for cardiologists.

The CIAO-ISCHEMIA was recently published in Circulation and was designed to describe the natural history of symptoms and ischemia in patients with INOCA.

Patients included in this study are peculiar because they had been excluded from ISCHEMIA randomization for failing to meet the criteria for obstructive coronary artery disease.

They all presented angina and stress-induced wall motion abnormalities. The echocardiographic core laboratory was blinded to symptoms, coronary and the presence of coronary artery disease (CAD). 

The pharmacological treatment was left to physician criteria. Primary end point was the correlation between changes in angina frequency and changes in stress echocardiogram. Predictors were analyzed at one year after changes in symptoms and ischemia. These patients were also compared against those included in the ISCHEMIA trial (the only difference being the presence of obstructive CAD).

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Patients with INOCA included in the CIAO were far more often women (66% vs 26%) vs ISCHEMIA patients with obstructive CAD (p<0.001). Despite the latter, ischemia magnitude resulted similar between cohorts (median 4 ischemic segments).

Ischemia and angina symptoms were not correlated in CIAO or ISCHEMIA.

After one year, stress echocardiogram resulted normal in half the CIAO participants, while a quarter continued with severe to moderate stress induced ischemia (≥3 ischemic segments). Angina improved in nearly half of patients (43%) though not necessarily the same who saw improved ischemia. In fact, there was no correlation. 

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These are the inconsistencies between stress symptoms and signs that make INOCA patients so challenging when it comes to treating them.  


Treatment improved ischemia and angina in INOCA patients, even though there was no correlation between both. Stress induced ischemia amounts resulted similar between the CIAO cohort (with no obstructive lesions) and the ISCHEMIA cohort (with obstructive CAD). 

Original Title: Natural History of Patients with Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

Reference: Harmony R. Reynolds et al. Circulation. 2021 Jun 1. Online ahead of print. doi: 10.1161/CIRCULATIONAHA.120.046791. 

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