Silent Myocardial Ischemia

Etiology

Silent myocardial ischemia's most common causes include atherosclerotic plaque rupture, coronary vasospasm, coronary vasculitis, trauma, coronary embolism, sympathomimetic drugs like cocaine, and supply-demand mismatch. The associated risk factors play a significant role in causation. The following risk factors increase susceptibility to asymptomatic ischemic episodes and are pertinent to developing silent myocardial ischemia: 

Diabetes Mellitus

DM is a significant risk factor for CAD and correlates with a higher incidence of silent myocardial ischemia. Cardiac autonomic dysfunction is the main culprit in patients with DM, which involves pain receptors, afferent neurons, or higher brain areas.[4][5] Studies have shown that atherogenic dyslipidemia strongly correlates with an increased risk of silent myocardial ischemia and CAD in patients with DM. Atherogenic dyslipidemia management may help reduce the high residual burden of cardiovascular disease.[6]

Perioperative Myocardial Infarction

The geriatric population has a relatively high perioperative myocardial infarction incidence. Studies have shown that patients who underwent coronary artery bypass grafting (CABG) had episodes of silent myocardial ischemia detected by Holter monitoring. Perioperative silent myocardial ischemia is usually asymptomatic. Hence, ECG monitoring is recommended during this period. Risk factors like prior myocardial infarction history and the presence of peripheral artery disease increase the odds of perioperative myocardial infarction.[7]

Older Patients

Older patients are particularly susceptible to silent myocardial ischemia. A study of 678 healthy men and women with no prior atherosclerotic cardiovascular disease revealed that the prevalence of silent myocardial ischemia, detected by Holter monitoring, was 11.4%. Silent ischemia in this population was associated with 3 times the risk of adverse cardiovascular events after adjusting for other risk factors.[8]

Intensive Care

Critically ill patients in the intensive care unit admitted for noncardiac causes are also at risk of acute myocardial ischemia. Transient myocardial ischemia and advanced age are significant predictors of cardiac events. 

Sleep Apnea

Obstructive sleep apnea carries correlations with myocardial ischemia (silent or symptomatic), cardiac arrhythmias, pulmonary hypertension, heart failure, transient ischemic attack, and stroke.

Epidemiology

Patients with Prior Coronary Artery Disease

At least 15% to 30% of patients with acute myocardial infarction have evidence of prior silent myocardial ischemia, and at least 30% to 40% of those with unstable angina had prior myocardial infarction. Around 20% to 50% of patients with stable angina have a previous history of myocardial infarction.[9][10] A greater prevalence of multivessel CAD is apparent in patients with silent ischemia detected on stress testing. At least 20% out of 937 patients with stable CAD had inducible silent ischemia on stress testing.[11]

Patients without Prior Coronary Artery Disease

Silent myocardial ischemia is infrequent in patients without CAD. For example, the adjusted prevalence of silent myocardial ischemia was 0.89% in a cohort of 4842 patients undergoing serial ischemia evaluation.[12] However, this condition's prevalence varies with the presence and number of associated risk factors. For example, a prevalence of 22% was observed in a cohort of 631 asymptomatic patients with DM and 2 additional risk factors.[13] Further, the coronary artery's calcium score predicts individuals with silent myocardial ischemia, and a higher score is associated with an increased chance of ischemia.[14]

Studies show that silent myocardial ischemia's incidence rate is higher in men than women. Both men and women with silent myocardial ischemia experience an elevated risk of coronary heart disease deaths and all-cause mortality. However, women are anticipated to face a more significant increase in risk.[15]

Pathophysiology

Silent myocardial ischemia resembles the pathophysiology of myocardial infarction from any cause. An imbalance between oxygen demand and supply can produce the condition.

Myocardial infarction primarily results from atherosclerotic plaque rupture in the coronary arteries. Atherosclerotic plaque formation involves inflammatory cell migration, cholesterol engulfment leading to macrophage transformation into foam cells, and growth factor release inducing fibrin and smooth muscle incorporation. Plaques may have a thin or thick fibrous cap. Plaque rupture causes devastating ischemic injury in regions where it occurs (see Image. Coronary Artery Disease Pathophysiology).[16] 

Meanwhile, the following explanations are suggested for why certain patients experience silent myocardial ischemia: inability to reach the person's pain threshold, brief ischemic episodes going unnoticed, higher β-endorphin levels, more cytokines blocking pain transmission, and altered or defective pain perception.[17][18] Silent myocardial ischemia follows a circadian rhythm, with greater incidences in the early morning hours. This phenomenon may be attributed to certain hemodynamic or physiological factors with circadian variation, including increased heart rate and blood pressure, higher vasomotor tone, elevated adrenergic levels, and enhanced platelet aggregation.[19]

Histopathology

Histological findings become evident if the ischemic state remains long enough to initiate myocardial damage. The following findings may be appreciated in the setting of acute myocardial infarction. 

• Characteristic histological features within the first 24 hours of insult include cardiomyocyte coagulation necrosis, neutrophilic infiltration, and interstitial edema and erythrocyte accumulation (see Image. Coagulative Necrosis in Myocytes During Silent Myocardial Infarction). Eosinophilic-appearing ischemic cardiomyocytes are evident with loss of the cross-striations and nuclei. Coagulative necrosis is established within the next 24 to 48 hours. After 3 to 5 days, myocyte nuclei and striations typically disappear in the infarct's central portion. After 5 to 7 days, macrophages and fibroblasts appear. At 1 week, neutrophil numbers start to decline, and granulation tissue forms with lymphocytic and plasma cell infiltration. 
• Healing continues and may be complete as early as 4 weeks or require 8 weeks or longer, depending on the extent of necrosis. Occasionally, larger infarcts may heal at the borders, leaving the central area with mummified myocytes for extended periods.
• Reperfusion within 4 to 6 hours may result in a subendocardial infarct without transmural extension. Macrophages appear by day 2 to 3, and fibroblasts appear by day 3 to 5, with early signs of healing. Subendocardial infarcts heal earlier than nonreperfused infarcts. These lesions may undergo complete healing in 2 to 3 weeks. Infarcts that take longer than 6 hours to be reperfused produce extensive hemorrhage areas.[20][21]

Both myocardial infarction and silent myocardial ischemia involve hypoxic damage. However, myocardial infarction's histopathological features typically reflect more severe and irreversible tissue damage compared to silent myocardial ischemia, which may exhibit milder and more localized changes.

History and Physical

Patients with silent myocardial ischemia may have one of the following clinical presentations:

• Type I: Asymptomatic without prior myocardial infarction. Silent myocardial ischemia is detected on ambulatory monitoring or stress testing.
• Type II: Asymptomatic with a prior history of symptomatic myocardial ischemia
• Type III: Patients with known symptomatic or asymptomatic CAD, the largest group

Ischemic chest pain is the hallmark manifestation of acute coronary syndromes. Patients have either no history of prior myocardial infarction or angina, a previous myocardial infarction episode, or both angina and asymptomatic ischemic episodes.

The history of present illness and physical examination provide an immediate source of information for clinicians to stratify the patients for further workup. Pertinent comorbidities include DM, hypertension, dyslipidemia, and CAD or the presence of other CAD risk factors. The physical examination may be benign in these patients or suggest signs of ventricular dysfunction, such as S3, or ischemia, such as S4. 

Evaluation

A 1-mm downsloping or horizontal ST depression is suggestive of myocardial ischemia in patients with previously normal ECG. Cardiac biomarkers like troponin-I and ambulatory ECG monitoring help detect postoperative myocardial infarction. These modalities may also help screen older individuals and patients with DM presenting to the hospital for unrelated complaints but are at risk of CAD. Radionuclide imaging is instrumental in detecting ischemia in asymptomatic individuals. 

The following combination of tests is used to detect silent myocardial ischemia.[22][23]

• Bedside ECG monitoring is used for continuous cardiac electrical activity assessment and detection of ischemic changes.
• Cardiac markers measure the levels of enzymes or proteins released into the bloodstream during myocardial injury.
• Ambulatory ECG monitoring tracks cardiac activity during daily activities, providing valuable information on silent myocardial ischemia episodes.
• Exercise stress testing evaluates cardiovascular response to physical exertion to detect exercise-induced ischemic changes.
• Radionuclide imaging techniques provide functional assessment of myocardial perfusion to identify ischemic regions.
• Continuous intracardiac monitoring offers real-time assessment of cardiac function and ischemic events, which is particularly useful in high-risk patients.
• Computed tomography provides detailed anatomical imaging of the coronary arteries and myocardial structure.

These tests can provide valuable information about the presence and severity of myocardial ischemia to guide treatment decisions and risk stratification. Combining these tests can enhance diagnostic accuracy and improve care and outcomes.

Treatment / Management

Medical Therapy

β-blockers are the most efficacious option for enhancing outcomes in individuals with silent myocardial ischemia, significantly reducing the number and duration of ischemic episodes. Calcium channel blockers (CCBs) are also effective. CCB monotherapy is often primarily used in patients with CCB-responsive conditions, eg, vasospastic angina, or intolerance to β-blockers. Aspirin for antiplatelet therapy and statins for lipid lowering are also used. The combination of β-blockers, nitrates, and CCBs may be prescribed in patients who demonstrate ischemia on ambulatory monitoring or radionuclide scans. 

Revascularization

Decisions on the necessity of coronary artery revascularization are not solely guided by findings consistent with silent myocardial ischemia, as data supporting the effectiveness of this intervention in treating silent ischemia is limited. A study showed no significant mortality difference between the groups who underwent revascularization and those who continued medical therapy (19.1% and 18.3%, respectively).[24][25] However, revascularization should be attempted in patients with high-risk features, such as ischemia to a large myocardial area, detected by ambulatory or noninvasive testing. (B2)

Psychosocial Stress Management

Mental stress can provoke silent ischemia, especially in patients with underlying CAD. Data suggests a possible benefit from behavioral stress reduction in individuals with CAD.

Differential Diagnosis

The differential diagnosis should include the following:

1. Aortic dissection: Tear in the aortic intimal layer, causing layer separation and potentially life-threatening bleeding. Chest pain is prominent.
2. Pleurisy: Inflammation of the pleura, resulting in sharp chest pain exacerbated by breathing or coughing. This condition may be accompanied by breathlessness and chest pain.
3. Pulmonary embolism: Blockage of lung arteries, often by a blood clot, leading to sudden shortness of breath and chest pain.
4. Myocarditis: Heart muscle inflammation that can cause fatigue, chest pain, and shortness of breath.
5. Lung pathologies: Various diseases affecting the lungs, such as pneumonia, pulmonary fibrosis, and lung cancer, presenting with respiratory symptoms.
6. Musculoskeletal etiology or those involving the gastrointestinal tract: Conditions affecting the muscles, bones, or gastrointestinal system, which can cause chest pain or discomfort, such as costochondritis, gastroesophageal reflux disease, or esophageal spasm.[26]

In contrast, silent myocardial ischemia is asymptomatic. However, chest pain and respiratory distress may arise if silent myocardial ischemia develops into an acute myocardial infarction. A thorough clinical history and judicious diagnostic evaluation can help differentiate silent myocardial ischemia from these conditions.

Prognosis

Silent myocardial ischemia's outcomes depend on the patient's risk factor profile and comorbid conditions like ischemic heart disease. Patients with a prior history of stable angina have a worse prognosis. Inducible ischemia in the absence of reported symptoms has twice the risk of a consequent ischemic event.[27] Patients with silent but documented ischemia on ambulatory monitoring also have greater chances of cardiac death.[28] Silent ischemia after an acute coronary syndrome episode is also associated with an increased risk of subsequent adverse events. In patients without CAD, the presence of silent ischemia, whether inducible or detected through ambulatory monitoring, correlates with an increased risk of adverse cardiovascular events and mortality.

Individuals with a history of silent myocardial ischemia have a higher incidence of new coronary events than people without silent ischemia, suggesting that an aggressive diagnostic and therapeutic approach must be employed for these patients. Older people present with atypical symptoms associated with acute myocardial infarction, including confusion, nausea, vomiting, and abdominal pain. Managing modifiable risk factors and adopting lifestyle changes can enhance patients' quality of life.[22]