Mechanism of Hydralazine-Induced Myocardial Ischemia
Hydralazine can provoke myocardial ischemia primarily through its hemodynamic effects that create an unfavorable myocardial oxygen supply-demand mismatch, particularly in patients with coronary artery disease. 1
Primary Mechanisms
1. Direct Cardiovascular Effects
- Reflex Sympathetic Activation
- Hydralazine causes peripheral vasodilation, leading to decreased arterial blood pressure
- This triggers compensatory reflex tachycardia and increased cardiac output
- The increased heart rate and contractility raise myocardial oxygen demand 1
2. Coronary Steal Phenomenon
- Hydralazine dilates both normal and diseased coronary vessels
- In patients with coronary artery disease, this can lead to:
- Blood flow diversion away from ischemic areas supplied by stenotic vessels
- Preferential flow to areas with normal vessels that dilate more readily
- Resulting in relative hypoperfusion of already compromised myocardial regions 2
3. Preservation of Elevated Left Ventricular Preload
- Unlike other vasodilators (e.g., nitroprusside), hydralazine:
- Causes minimal reduction in left ventricular filling pressure
- Maintains elevated preload while reducing afterload
- This combination increases wall tension and myocardial oxygen demand 2
Clinical Evidence
Research has demonstrated that hydralazine-induced ischemic events often occur:
- In the absence of significant tachycardia or hypotension
- More frequently than with other vasodilators like nitroprusside
- Even when nitroprusside causes greater decreases in systemic arterial pressure 2
In a study of patients with severe heart failure due to coronary artery disease:
- 23% of patients experienced ischemic events during initial hydralazine administration
- These included angina at rest (12 patients) and myocardial infarction (4 patients) 2
High-Risk Populations
Patients at particular risk for hydralazine-induced myocardial ischemia include:
- Those with known or suspected coronary artery disease 1
- Patients with ischemic cardiomyopathy 2
- Individuals with hypertension and concurrent coronary disease 3
Clinical Implications
The FDA drug label explicitly warns: "Myocardial stimulation produced by hydralazine can cause anginal attacks and ECG changes of myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must, therefore, be used with caution in patients with suspected coronary artery disease." 1
Due to these concerns, the American Heart Association recommends against monotherapy with hydralazine in patients with ischemic heart disease, stating: "Given the lack of randomized trial evidence to support the prevention of cardiovascular events by the use of hydralazine in the treatment of primary hypertension and concerns that hydralazine may provoke angina, monotherapy with hydralazine in IHD is not recommended." 3
Monitoring and Management
When hydralazine must be used in patients with risk factors for coronary disease:
- Start with low doses and titrate slowly
- Monitor for symptoms of angina or ECG changes
- Consider combination with nitrates to counterbalance the preload-preserving effects
- Be particularly vigilant in patients with ischemic cardiomyopathy
Summary
Hydralazine provokes myocardial ischemia through multiple mechanisms including reflex sympathetic activation, coronary steal phenomenon, and preservation of elevated left ventricular preload. These effects create an unfavorable myocardial oxygen supply-demand balance, particularly in patients with underlying coronary artery disease.