Background: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. Methods: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was an international cohort study conducted from 2014-2019 involving angina assessments (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. This was an ancillary study that included patients with history of angina who were not randomized in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease (CAD) status and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between changes in SAQ Angina Frequency score and change in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and compared CIAO participants with ISCHEMIA participants with obstructive CAD who had stress echocardiography before enrollment, as CIAO participants did. Results: INOCA participants in CIAO were more often female (66% of 208 vs. 26% of 865 ISCHEMIA participants with obstructive CAD, p<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [IQR 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (p=0.46) or ISCHEMIA stress echocardiography participants (p=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over one year was not significantly correlated with change in angina (rho=0.029). Conclusions: Improvement in ischemia and improvement in angina were common in INOCA, but not correlated. Our INOCA cohort had a similar degree of inducible wall motion abnormalities to concurrently enrolled ISCHEMIA participants with obstructive CAD. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02347215

Background: Patients with significant (≥50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. However, the impact of intermediate LMD (stenosis, 25%–49%) on outcomes is unclear. Methods: Randomized ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%–49%) and without (<25%) intermediate LMD. The primary outcome was a composite of cardiovascular mortality, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The primary quality of life outcome was the Seattle Angina Questionnaire summary score. Results: Among the 3699 participants who satisfied the inclusion criteria, 962 (26%) had intermediate LMD. Among invasive strategy participants with intermediate LMD on coronary computed tomography angiography, 49 (7.0%) had significant (≥50% stenosis) left main stenosis on invasive angiography. Patients with intermediate LMD had a higher risk of cardiovascular events in the unadjusted but not in the fully adjusted model compared with those without intermediate LMD. An invasive strategy increased procedural MI and decreased nonprocedural MI with no significant difference for other outcomes including the primary end point. There was no meaningful heterogeneity of treatment effect based on intermediate LMD status except for nonprocedural MI for which there was a greater absolute reduction with invasive management in the intermediate LMD group (−6.4% versus −2.0%; P interaction =0.049). The invasive strategy improved angina-related quality of life and the benefit was durable throughout follow-up without significant heterogeneity based on intermediate LMD status. Conclusions: In the ISCHEMIA trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate LMD status except for a greater absolute risk reduction in nonprocedural MI with invasive management in those with intermediate LMD. An invasive strategy increased procedural MI, reduced nonprocedural MI, and improved angina-related quality of life. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.

Although myocardial revascularization is one of the most studied types of medical interventions, there is a heated discussion in cardiology about the feasibility and indications for it in patients with stable coronary artery disease (chronic coronary syndrome). The recently completed ISCHEMIA trial is the largest current study comparing conservative versus invasive strategies in this category of patients. The article discusses the rationale for revascularization to improve prognosis according to the ISCHEMIA trial.

Цель. Сравнить точность прогнозирования риска фатальных и нефатальных сердечно-сосудистых событий (ССС) на основании расчета по шкале SCORE и ультразвуковой визуализации атеросклеротической бляшки (АСБ) сонных артерий у пациентов без манифестированных атеросклеротических сердечнососудистых заболеваний (АССЗ), находящихся на обследовании в многопрофильном стационаре. Материал и методы. Обследован 841 пациент (353 мужчин; средний возраст 54,9±8 лет), имеющих хотя бы 1 традиционный фактор сердечно-сосудистого риска, без манифестированных АССЗ. Всем пациентам за время госпитализации выполнено УЗИ сонных артерий. Пациенты с нестенозирующей АСБ составили группу АСБ+, без АСБ-группу АСБ-(356 и 485 человек, соответственно). Медиана времени наблюдения составила 4 г (2-6 лет). В качестве ССС в периоде наблюдения регистрировались: острый коронарный синдром, установленный диагноз хронической ишемической болезни сердца, плановая коронарная реваскуляризация, ишемический инсульт/транзиторная ишемическая атака, сердечная смерть. Результаты. Нестенозирующая АСБ сонных артерий была обнаружена у 356 человек (42% обследованных); среди лиц с низким риском SCORE она была выявлена у 64 (23%), с умеренным риском-у 182 (46%). За период наблюдения зарегистрировано 127 ССС (частота-17,8%), из них 84 (66% от общего числа)-в группе АСБ+. Фактическая частота событий значительно превышала расчетную (соотношение фактические/предсказанные события составило 1,6, 5,1 и 7,9 для высокого, умеренного и низкого риска по SCORE, соответственно). По данным многофакторного регрессионного анализа, ОШ для АСБ как предиктора ССС составило 2,54 (95% ДИ 1,6-4,04), и было значительно выше показателя шкалы SCORE (1,04 95% ДИ 0,01-1,07). В качестве предиктора ССС, АСБ имела наибольшую ценность в группе низкого риска SCORE (число ССС в группе низкого риска по SCORE 14 среди пациентов с АСБ vs 10 среди пациентов без АСБ, р=0,001). Заключение. Применение шкалы SCORE недооценивает фактический риск ССС, особенно, у пациентов с низким и умеренным расчетным риском по SCORE. Визуализация АСБ при ультразвуковом исследовании сонных артерий у таких пациентов существенно точнее прогнозирует риск ССС.

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