Julie Ma, M.D.

Introduction

The evaluation of non-cardiac chest pain, defined as chest pain in patients with angiographically normal coronary arteries, is estimated to carry an annual health care cost of $750 million.¹ Approximately 10%-30% of patients undergoing cardiac catheterization in the investigation of chest pain are found to have normal coronary arteries.² While non-cardiac chest pain carries a good prognosis, these patients have frequent office visits, emergency room evaluations, hospital admissions and repeat catheterizations for their unexplained pain.

Non-cardiac chest pain is especially difficult to diagnose in the diabetic patient who often presents with atypical symptoms and are more likely to have silent infarctions than are their non-diabetic counter-parts.³ Thus, while it is important to consider noncardiac etiologies of chest pain, it is especially prudent to suspect an acute coronary syndrome when this patient population presents with chest discomfort even if atypical.

Case Report

A 62-year-old female with a history of NIDDM, dilated cardiomyopathy and ventricular tachycardia status post AICD placement presented to the emergency room with dyspnea, intermittent substernal chest and midepigastric pain for five days. She described the pain as similar to her past "angina", with an intermittent "aching pressure" associated with loss of appetite, nausea, vomiting and diarrhea. An electrocardiogram showed right bundle branch block with left axis deviation unchanged from an electrocardiogram obtained at her last admission.

One month earlier, the patient had been hospitalized for similar symptoms. Myocardial infarction was ruled out and she was discharged with GERD treatment at that time. Review of the patient's history revealed that she had been admitted eleven times in the previous year with similar symptoms. Endoscopy performed one year ago revealed mild gastritis and cardiac catheterization was normal.

The patient was taking captopril, furosemide, lansoprazole, sotalol and warfarin. Review of systems was negative for fever, headache, cough, hemoptysis, hematemesis, melena and dysuria. The patient was treated for unstable angina in the emergency room with aspirin and intravenous nitroglycerin without significant improvement in her pain. Her blood pressure was 96/60 mm Hg, the pulse was 68, the respirations were 15, the temperature was 36.9 and the oxygen saturation was 96 percent on 2 liters of oxygen by nasal cannula. The jugular venous pressure was 8 cm; the lungs had bibasilar rales, and the cardiac exam showed a regular rate and rhythm with a displaced apical impulse. The abdominal examination was unremarkable and rectal exam showed brown stool with occult blood test negative. Laboratory data included a normal white cell count and differential, normal liver function tests, PT/INR of 54.3 and 5.1. Urinalysis showed a bland sediment and chest radiograph was significant for cardiomegaly and pulmonary congestion.

The patient was admitted to the CICU for atypical chest pain. Treatment with intravenous morphine and famotidine were initiated. The patient ruled out for myocardial infarction. The patient continued to require large doses of intravenous morphine to control her pain and her nausea persisted. A right upper quadrant ultrasound revealed a hypoechoic and thickened galbladder wall consistent with acute cholecystitis. The patient was evaluated by General Surgery and was felt to be a poor candidate for cholecystectomy due to her severe cardiac disease and coagulopathy. The patient was managed with intravenous morphine and antibiotics with eventual resolution of her pain.

Discussion

This case illustrates the importance of considering non-cardiac etiologies for recurrent chest pain and the difficulty of making such a diagnosis especially in the diabetic patient. Due to the high mortality and morbidity of myocardial infarction, patients presenting with chest pain should always be considered to have an acute coronary syndrome until proved otherwise. This is especially true in the diabetic population where symptoms tend to be more atypical and patients present more often with silent ischemia.³

The most common cause of non-cardiac chest pain is gastroesophageal reflux disease. In addition, musculoskeletal etiologies are frequently seen in the primary care setting. However, acute cholecystitis and related hepatobiliary disorders should also be considered as they can mimic an acute myocardial infarction or ischemia in symptomatology, electrocardiographic changes, and even left ventricular segmental wall motion abnormalities.⁴

In this case, several unusual features of this patient's history and presentation as well as the recurrent nature of her symptoms after ischemia had been ruled out suggested an alternative diagnosis than a cardiac etiology. With a five-day history of pain at rest, one would expect to have found electrocardiographic changes consistent with ischemia or infarction. In addition, the nature of her pain, with radiation to the back is somewhat atypical for myocardial ischemia.⁵ The patient's description of her pain as similar to that which had brought her to the emergency room several times prior to this admission suggest that the patient's symptoms at that time were most likely caused by cholecystitis rather than ongoing intermittent ischemia. In addition, the patient was confirmed to have had normal coronaries by catheterization less than five years prior to this admission with multiple admissions in the recent past for similar symptoms. This should have signaled that there was a possible non-cardiac source of her pain. The association between gastrointestinal symptoms, including nausea and vomiting, and acute coronary syndromes is well established.⁶ This is particularly true for inferior myocardial events and among diabetics and women. Thus, these presenting symptoms could not be used to sway the diagnosis towards a non-cardiac event. However, the persistence of the patient's symptoms despite heparin and large quantities of nitroglycerin and morphine suggested as alternative diagnosis than cardiac ischemia.

The normal liver function tests and white blood cell count were surprising in light of the etiology of her symptoms and contributed to the delay in diagnosis. It is also unclear whether her coagulopathy was secondary to underlying infection and possible sepsis or from her medication. This laboratory data did persuade the decision to continue with medical management rather than surgical intervention.

The clinical approach to patient with chest pain of unclear origin includes the systematic exclusion of different diagnostic possibilities. These include pain from the chest wall, pleura or mediastinum, as well as diseases of the gastrointestinal tract. Musculoskeletal etiologies of chest pain are common accounting for approximately 15% of all cases of non-cardiac chest pain.⁵ After the exclusion of coronary syndromes, musculoskeletal etiologies can usually be diagnosed by history and physical examination, with point tenderness the major physical finding and a history of pain of insidious onset related to unaccustomed physical activity. Pulmonary etiologies of non-cardiac chest pain, including pneumonia, pneumothorax and pneumomediastinum, are less common and can usually be identified by exam and chest radiograph.⁷

Gastroenterologic causes of chest pain are the most common causes of non-cardiac chest pain and can be difficult to separate from a cardiac etiology. Peptic ulcer disease, incarcerated hiatal hernia, cholecystitis and pancreatitis may all present with chest pain instead of classic epigastric and right upper quadrant discomfort. Esophageal disease has long been considered a common source of non-cardiac chest pain produced by motility disorders such as achalasia, diffuse esophageal spasm and nutcracker esophagus or high amplitude esophageal contrac-tions.¹ Gastroesophageal reflux disease is the other major esophageal cause of non-cardiac chest pain. A study of patients with non-cardiac esophageal chest pain found GERD to be the cause in 40%, motility disorders in 20% and a combination of both, either simultaneously or separately, in 40%.⁸ If there is a strong suspicion for peptic ulcer disease or reflux esophagitis, esophagogastroduodenoscopy may be helpful in the diagnosis. In addition, an abdominal ultrasound to rule out hepatobiliary disease may also be warranted as seen in this case. Once these etiologies have been excluded, prolonged ambulatory esophageal pH monitoring has become a widely available technique to rule out reflux.¹Approximately 40% of patients with non cardiac chest pain have an abnormal degree of acid reflux on 24 hour pH monitoring or a correlation between their symptoms and reflux events.² It should be noted that reflux confirmed by pH monitoring does not necessarily mean that it is the etiology of the patient's symptoms. However, a normal study may help exclude reflux as a cause of non-cardiac chest pain while a positive study may be used to support reflux disease as the etiology of their pain.

The management of chest pain of unclear etiology is more complicated in patients with diabetes because of their higher incidence of heart disease, their tendency to present with atypical symptoms, as well as there predisposition to infection. As has been emphasized earlier, acute coronary syndromes should be ruled out in all diabetic patients presenting with chest pain and its associated symptoms. However, particularly in elderly patients with diabetes, noncardiac causes of chest pain can also cause serious morbidity and often require early diagnosis and treatment. Thus the clinician should remain vigilant to other etiologies of chest pain once a cardiac source has been ruled out. This patient's clinical course illustrates this point and emphasizes the importance of including hepatobiliary diseases in the differential diagnosis of atypical chest pain.