Ms Jones is a 55-year-old woman admitted to your critical care unit from the cardiology clinic after she underwent an exercise stress test, which was strongly positive. She has several months' history of slowly progressive exertional chest discomfort. During the exercise stress test, she developed a prolonged episode of chest discomfort, along with electrocardiographic evidence of ischemia, and was, therefore, admitted for cardiac catheterization to take place the following day. She has few risk factors for coronary artery disease, including borderline hypertension, a family history of premature coronary disease, and smoking as an adolescent. She remained symptom-free overnight, and serial troponin I and creatine kinase-MB measurements were negative.
You care for her again when she returns from the cardiac catheterization procedure. According to the cardiologist, her coronary arteries are free of any coronary disease, and her diagnosis is possibly cardiac syndrome X. She is scheduled to go home later that evening once she is off bed rest and if there are no complications. Although she is relieved at the good news, she asks you why she has chest pressure whenever she walks briskly, what her prognosis is, and what she should do if her chest pain recurs. This article will provide a brief overview of cardiac syndrome X for the critical care nurse.
PREVALENCE
Approximately 10% to 30% of patients undergoing coronary arteriography with typical angina symptoms have normal or minimal coronary artery disease.1 There are approximately 1.7 million cardiac catheterizations performed annually in the United States,2 resulting in 170,000 to 500,000 patients with no clear diagnosis for their chest pain after angiography. Normal or near-normal coronary arteries, along with typical anginal symptoms, are particularly common in postmenopausal women. More than 50% of angiograms done on women show no significant coronary disease.3 A large portion of these may find a noncardiac cause such as gastrointestinal source, but a significant number could eventually be given the diagnosis of cardiac syndrome X.
DEFINITION
Cardiac syndrome X is defined as an absence of significant coronary disease in patients with typical symptoms of angina pectoris and positive electrocardiographic findings on exercise stress testing for coronary ischemia. Cardiac syndrome X is seen more often in women,3 especially in postmenopausal women.4 It has traditionally not been linked to either progression to coronary artery disease or increased risk of myocardial infarction in the few long-term studies concerning this topic.5 For patients to be given this diagnosis, noncardiac causes of symptoms must be excluded. Patients must also be free of cardiomyopathies or vascular spasm during cardiac catheterization to be given this diagnosis.1 It is, by definition, a diagnosis of exclusion.
PATHOPHYSIOLOGY
There are several theories in the pathophysiology of cardiac syndrome X. Although there is no definitive answer, the most common theories revolve around ischemia from microvascular dysfunction1,6-8 or endothelial dysfunction.9 Other studies have explored the role of abnormal pain perception, estrogen deficiency, systemic inflammation, and insulin resistance.9-15
Myocardial ischemia from microvascular dysfunction has been studied as the primary cause of cardiac syndrome X.8 This is indicated by ST segment changes during exercise treadmill testing, reversible perfusion defects on nuclear medicine scans, and, more recently, subendocardial perfusion abnormalities on cardiovascular magnetic resonance imaging.4,8 Studies seem to show that many, but not all patients, have ischemia as the cause of their chest pain.4
Endothelial dysfunction of the coronary microcirculation has also been implicated in several research studies, with chest discomfort due to a lack of proper vasodilation with the increased demand of exercise. A 1993 study found that endothelial-dependent vasodilation was impaired in patients with cardiac syndrome X.9 Recent literature has suggested that chronic inflammation may play a role in endothelial dysfuction.16 Insulin resistance may also be implicated in the endothelial dysfunction of the coronary microcirculation.4
Abnormal or exaggerated cardiac pain perception has also been suggested and studied as a contributor to cardiac syndrome X. A study by Cannon6 showed that patients with cardiac syndrome X report more chest discomfort during catheter manipulation than do other patients with coronary artery disease, valvular disease, or hypertrophic cardiomyopathy. Other studies have also suggested that patients with cardiac syndrome X have an abnormal pain response.
Estrogen deficiency may be a contributing factor in cardiac syndrome X because most patients are postmenopausal women. This is also thought to be due to the role of estrogen in endothelial function.10,13-15,17
TREATMENT
Treatment should be patient-specific, depending on the patient's resting blood pressure, degree of symptomatology, gender, degree of lifestyle limitation, and the patient's desire to take pharmacologic agents. It is important to remember that cardiac syndrome X is generally not believed to be related to increased mortality or progression to large-vessel coronary disease. Therefore, treatment should be guided to decreasing symptoms and improving quality of life.
Pharmacologic treatment is a mainstay of therapy for patients with cardiac syndrome X (see Table 1). [beta]-Blockers are generally thought of as a first-line treatment.15,18 They are thought to improve exercise tolerance and decrease symptoms.1 These agents may be especially useful in those patients with resting tachycardia or those with rapid increase of blood pressure and heart rate during exercise.1 If [beta]-blockade is contraindicated or not tolerated, calcium channel antagonists and nitrates have been used with some success and should be considered as second-line agents.1,11
Although the above anti-ischemic agents treat primarily the symptoms of cardiac syndrome X, agents that deal with the underlying endothelial dysfunction may also be helpful. A small 2003 study showed improvement in exercise duration, time to electrocardiographic ischemia on exercise stress testing, and brachial artery flow-mediated dilation with treatment using "statin" drugs,12 which was believed to be due to improvement in endothelial function. Angiotensin- converting enzyme inhibitors' role with nitric oxide should improve endothelial functions in patients with cardiac syndrome X; however, few studies have been conducted on these agents.1
Estrogen replacement therapy may also alleviate symptoms in postmenopausal women who carry this diagnosis.13,14 Several trials have been conducted, showing differing degrees of decrease in symptoms.13,14 Estrogen is also primarily thought to decrease symptoms by improving endothelial function.
Increased vasoconstriction has been theorized as a potential cause of chest pain in cardiac syndrome X. This has led some clinicians to try [alpha]-antagonist agents such as clonidine as treatment of cardiac syndrome X.15 The results have been mixed, the studies were not randomized, and they will likely not be used routinely.15 Aminophylline has improved time to exercise-induced ischemia and could also be considered as an adjuvant treatment.15 Imipramine has been shown to decrease the amount of chest pain that a patient experiences, but quality-of-life measures were adversely affected, and therefore, this agent should be closely monitored.19-21
Estrogen deficiency in postmenopausal woman has long been considered as a contributor or cause of cardiac syndrome X, given that it is found most frequently in this group.14 Estrogen supplementation may decrease chest pain symptoms by 50%14 but had no effect on either exercise time to symptoms or to electrocardiographic changes.15 It can also be used as an adjuvant therapy.
There have been some studies suggesting that nonpharmocologic interventions may also be beneficial for these patients. Transcendental meditation has been shown to improve both exertional chest pain and even ST segment changes seen during exercise.22 Professional counseling, particularly cognitive-behavioral therapy, has also been shown to improve symptoms.23 Exercise programs are generally thought to improve quality of life for this patient population by improving exercise tolerance and endothelial function.23 Smoking cessation should be recommended as a primary prevention of both vascular disease and vasoconstrictive effects of nicotine. Patients with cardiac syndrome X are a heterogeneous group with differing responses to various treatments. Therefore, clinicians caring for these patients must individualize care.
NURSING INTERVENTIONS
Nursing care should focus greatly on education for this patient population (see Table 2). Patients should be well informed that there is no definitive treatment for this condition. They should report to their clinician that symptoms do not improve with any given treatment. It is important for these patients to understand that there are many different options for treatment. If one modality is not working, a different approach can be explored. Lifestyle modification must be discussed to include an aerobic exercise program, smoking cessation, and a heart-healthy diet to prevent the progression of endothelial dysfunction. Medications including their dosages, indications, and side effects should be discussed to improve patient compliance. Referrals to nonphysician providers such as psychotherapists and physical therapists should also be discussed. The idea of nurse-run clinics for these patients similar to those conducted for heart failure patients should be considered to improve care and decrease costs.
CONCLUSION
Patients who carry this diagnosis often report poor quality of life despite their excellent prognosis.5 Their exercise tolerance can be quite hindered by chest discomfort, affecting all aspects of their life. These patients may be seen frequently in medical and cardiology clinics and emergency departments. Frequently, these patients undergo numerous noninvasive tests for coronary disease, which yield no further information. They also report problems with interpersonal relationships and an inability to explain why they are symptomatic although they have normal coronary arteries. Clearly, the large number of persons with this diagnosis and its impact on quality of life should lead to further research in the field, especially to identify potential causes of cardiac syndrome X and to test the effectiveness of existing or new treatment modalities.
References