Subendocardial and Transmural Myocardial Ischemia: Clinical Characteristics, Prevalence, and Outcomes
K Lance Gould1, Tung Nguyen1, Richard Kirkeeide1
1Weatherhead PET Center for Preventing and Reversing Atherosclerosis, Division of Cardiology, Department of Medicine, McGovern Medial Medical School, University of Texas, and Memorial Hermann Hospital, Houston, Texas, USA.
Insights
Quantifying subendocardial ischemia with positron emission tomography (PET) reveals reduced coronary flow capacity (CFC) is linked to major adverse cardiac events. Revascularization significantly lowers mortality in patients with severely reduced CFC.
Area of Science:
- Cardiovascular Imaging
- Nuclear Cardiology
- Myocardial Perfusion Imaging
Background:
- Subendocardial ischemia is frequently diagnosed but lacks precise quantification through imaging techniques.
- Current diagnostic methods often fail to assess the extent and severity of myocardial perfusion deficits.
Purpose of the Study:
- To define the size and severity of subendocardial and transmural stress perfusion deficits.
- To investigate clinical associations and patient outcomes related to these perfusion abnormalities.
- To evaluate the prognostic value of coronary flow capacity (CFC) in patients undergoing myocardial perfusion imaging.
Main Methods:
- Utilized positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in 6,331 patients.
- Measured regional rest-stress perfusion, coronary flow reserve, coronary flow capacity (CFC), and various stress-to-rest ratios.
- Conducted a prospective 10-year follow-up to assess major adverse cardiac events (MACE) and mortality, with and without revascularization.
Main Results:
- Severely reduced CFC was identified in 20.7% of PET scans, associated with a higher incidence of angina or ST-segment depression.
- Over 10-year follow-up, severely reduced CFC correlated with significantly higher MACE (44.4% vs. 8.8%) and mortality (15.2% without revascularization).
- Revascularization significantly reduced mortality in patients with severely reduced CFC (6.9% vs. 15.2%), but not in those with normal CFC (3% vs. 3%).
Conclusions:
- Reduced subendocardial perfusion without significant stenosis, often seen with dipyridamole PET, is common and carries a low risk of MACE.
- Severely reduced coronary flow capacity (CFC) is a strong predictor of adverse outcomes and high mortality risk.
- Revascularization is effective in reducing mortality for patients with severely reduced CFC, highlighting its prognostic importance.
Background:
Subendocardial ischemia is commonly diagnosed but not quantified by imaging.
Objectives:
This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes.
Methods:
Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization.
Results:
Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) >1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ >1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ >1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P < 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P < 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90).
Conclusions:
Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization.
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