Rate-Related Ischemia: Demand Ischemia
Rate-related ischemia is called "demand ischemia" or "Type 2 myocardial infarction" when it results in myocardial injury, characterized by an imbalance between myocardial oxygen supply and demand driven primarily by increased heart rate and metabolic demands. 1, 2
Terminology and Classification
The American College of Cardiology/American Heart Association defines this condition as Type 2 myocardial infarction: demand-supply mismatch, which occurs when conditions other than coronary artery disease contribute to an imbalance between myocardial oxygen supply and/or demand 1. This includes scenarios involving tachyarrhythmias, coronary endothelial dysfunction, coronary artery spasm, anemia, respiratory failure, and hypotension 1.
Pathophysiologic Mechanism
Heart rate is the primary driver of rate-related ischemia through multiple mechanisms 2, 3:
- Tachycardia reduces diastolic filling time, which is critical because coronary perfusion occurs predominantly during diastole 2, 4
- Increased heart rate elevates myocardial oxygen consumption through enhanced contractility and workload 2, 4
- Subendocardial perfusion is inversely related to heart rate when coronary vasodilation is maximal, making the subendocardium particularly vulnerable 4
Research demonstrates that 81% of ambulatory ischemic episodes are preceded by heart rate increases ≥5 beats per minute, with the likelihood of developing ischemia proportional to the magnitude and duration of heart rate elevation 3. The probability ranges from 4% with modest increases (5-9 bpm for <10 minutes) to 60% with substantial increases (≥20 bpm for ≥40 minutes) 3.
Clinical Context and Triggers
Common precipitants of demand ischemia include 2:
- Sepsis (combines tachycardia, hypotension, and increased metabolic demands)
- Gastrointestinal bleeding (causes anemia and compensatory tachycardia)
- Acute COPD exacerbation (hypoxemia with increased work of breathing)
- Severe aortic stenosis (pressure overload with limited coronary flow reserve)
- Fever and hyperthyroidism (elevated metabolic rate and heart rate)
Diagnostic Features
Rate-related ischemia presents with distinct characteristics 1, 2:
- Troponin elevation occurs despite absence of acute coronary plaque rupture, reflecting myocyte injury from supply-demand mismatch 2
- ECG changes typically show ST-segment depression or T-wave inversions rather than ST elevation 2
- A rising and/or falling troponin pattern distinguishes acute from chronic elevations 2
- Ischemic episodes with heart rate increases display a daytime peak, whereas non-rate-related ischemia occurs evenly throughout the day 3
Critical Clinical Pitfall
The key distinction from Type 1 MI is the absence of acute atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection with intraluminal thrombus 1. However, demand ischemia can unmask underlying coronary disease, so evaluation must address both the precipitating cause and any contributing coronary pathology 2.
Management Approach
Treatment prioritizes correcting the underlying supply-demand imbalance 2:
- Address the primary trigger (treat sepsis, correct anemia, manage hypoxemia)
- Optimize hemodynamics by controlling heart rate and maintaining adequate blood pressure 2
- Beta-blockers reduce myocardial oxygen consumption by decreasing heart rate, contractility, and the magnitude/duration of heart rate increases 2, 3
- Propranolol specifically reduces the proportion of heart rate-related ischemic episodes compared to placebo 3
When coronary perfusion is normalized per heartbeat (flow per beat rather than per minute), a single relationship exists between subendocardial blood flow and regional performance across different heart rates, supporting the concept of perfusion-contraction matching 4. This explains why heart rate reduction is therapeutically effective even when fixed coronary stenosis is present 4.