INTEGRATED CASE WITH THERAPEUTICS: HEART I
CARDIOVASCULAR (ANGINA)
FACULTY COPY
PART A: MONDAY, NOVEMBER 6, 2000
10:30AM – 12:30PM
CHIEF COMPLAINT: "Pain on my chest" on and off for the past six months.
HISTORY: Mr. Solomon is a 58 year old insurance broker who presents tonight in the office following an episode of "chest pain" that he experienced earlier in the day during a gold game. Although he minimizes the severity of the pain and attributes it to being "out of shape," his wife insisted that he see a physician because he has had similar episodes during the past six months.
Mr. Solomon describes the pain as being more of a discomfort or heaviness. It is localized to "my breast bone" and does not radiate. Today, following a brief rest, the pain subsided and he returned to his golf game. Previous episodes of the heavy feeling tended to occur following large meals and one occasion, while dancing at a wedding. None of the episodes lasted more than "several minutes."
Although Mr. Solomon did not experience nausea or vomiting today, he notes many episodes in the past of feeling a burning sensation in his chest. He describes the sensation as being "like acid behind my breast bone." This feeling occurs most often late at night when he lays down. Usually he has had a large meal or drank alcohol. The sensation does not radiate.
When asked about how he feels about these episodes, he admits to being concerned about his health and longevity, considering his father died at age 52 of "heart problems." He says, Business is poor, my kid is always in trouble. "Who’s going to take care of things?"
Mr. Solomon smokes ½ to 1 pack of cigarettes per day. He drinks 2-3 cocktails per nights to "settle my nerves."
PHYSICAL EXAMINIATION: Mr. Solomon is a short, moderately obese man who appears somewhat anxious but is in no apparent distress. He is wearing clean casual shirt/pants. Vital sings: BP right arm 162/94; left arm 160/92. Weight 176lbs; Height 5’7". Respiratory rate is 16/minute. Temperature, 98.4º F.
Examination of cardiovascular system reveals a regular, apical heart rate of 86/minute. S1 is heard best at the apex; a loud S2 is heard best in the R2ICS and L parasternal border. A questionable S4 is heard at the apex. There are no murmurs or apical prominence. There is no peripheral edema.
Lungs are clear to percussion and auscultation. An indirect hernia is noted in the right inguinal region. The abdomen is examination is negative for abnormalities.
LABORATORY TESTS:
CBC: WBC = 5,600/mm3, hemoglobin = 15.2g/dL, hematocrit = 45%, platelet count = 320,000/mm3
Chemistries: Glucose 110mg/dL, Blood Urea Nitrogen (BUN) 11mg/dL, Creatinine 0.9mg/dL
Urinalysis: Specific gravity: 1.016; Protein, Glucose, Ketones = negative.
Chest X-ray: normal
EDUCATION OBJECTIVES
Define all unknown terms:
Cite the primary clinical problem (not the diagnosis)
Develop a general differential diagnosis of this clinical problem using categories of disease. Cite examples from each:
In general, what factors (data) would you take into consideration when determine a differential diagnosis of specific diagnosis:
Develop a specific differential diagnosis (higher probability causes of chest pain in this patient).
What is your diagnosis: Why?
What are the risk factors for this disease in this patient?
DIAGNOSTIC THINKING IN THE CASE OF MR. SOLOMON (QUESTIONS 8-12)
The development of a diagnostic strategy depends on the characteristics of the diagnostic tools that are used and the characteristics of the patient. The history, physical, laboratory studies, and supplemental tests all provide information that may enable the physician to reach a diagnosis. The operating characteristics of historical data, data from the physical exam, and further testing are described by the terms sensitivity, specificity, positive value, negative predictive value, and positive and negative likelihood ratio. (Refer to Dr. Richard S. Cooper’s IPM I lesson "How Do I Interpret A Diagnostic Test?")
Using English, define these operating characteristics (e.g. sensitivity: the proportion of cases with a disease that have a positive test.)
In considering Mr. Solomon’s presentation with "pain on my chest" what are the key parts of the history and physical that influence how you develop a differential diagnosis? Qualitatively, what is your impression of the sensitivity and specificity of the historical and physical exam findings?
What supplemental testing, if any, would you want in addition to the history, physical, and laboratory studies that are listed?
The characteristics of a patient determine how one interprets data obtained from that person. For example, a positive HIV test on a cloistered nun who has never had any sexual contact, blood exposure or other risk is almost certainly a false positive. In Mr. Solomon’s case, what characteristics, or risk factors, make you think it is likely that he has the diagnosis you consider most likely.
Given these characteristics, is there any point in supplemental diagnostic testing for Mr. Solomon? Would you believe a negative or positive test? Should be proceed directly to the "gold standard"?
What drug therapy would you consider prescribing to modify Mr. Solomon’s risk factors and to control his symptoms?
INTEGRATED CASE: CARDIOVASCULAR (ANGINA)
PART A: MONDAY, NOVEMBER 6, 2000
10:30AM – 12:30PM
EDUCATIONAL OBJECTIVES – FACULTY COPY
Define all unknown terms:
The students were told to use any source necessary to define all unknown terms in the case. The following texts are required: Medical dictionary, Robbin’s pathology text, Bate’s physical diagnosis text and Greene’s Clinical Medicine ("… is a work stimulated by and intended for medical students. Its is primarily designed to help bridge the chasm between the basic sciences and the wards. The format identifies the problems e.g. pruritus, cough – that patients describe and helps the student move through the history, physical examination and laboratory data to arrive at a diagnosis,") Harrison’s and Cecil’s textbooks of medicine are recommended.
Cite the primary clinical problem (not the diagnosis)
Chest discomfort or pain
Develop a general differential diagnosis of this clinical problem using categories of disease. Cite examples from each:
This objective is intended to help the students understand that a given clinical problem or complaint may have many different causes. Although the students may develop a long list of diseases, they should at least be aware that chest pain may arise from different organs or anatomical locations.
Cardiovascular: Angina
Acute myocardial infraction
Pericarditis
Aortic dissection
Gastrointestinal: Reflux esophagitis
Esophageal spasm
Esophageal rupture
Pulmonary: Pneumothroax
Pleuritis/pneumonia
Pulmonary embolus/infarction
Musculoskeletal: Traumatic injury
Costochondritis
Herpes zoster
Somatization: Anxiety
In general, what factors (data) would you take into consideration when determine a differential diagnosis of specific diagnosis:
Nature and characteristics of complaint, gender and age of patient, circumstances, risk factors for a disease, laboratory and radiologic test results.
Develop a specific differential diagnosis (higher probability causes of chest pain in this patient).
Angina/acute myocardial infarction
Reflux esophagitis/esophageal spasm
Muscular pain
Somatization
Angina: Repeated episodes of "heaviness" or chest discomfort during the previous 6 months. The discomfort seems to be brought on by exertion or eating, is relieved by rest and is localized to the center of the chest. Age, gender and risk factors support the diagnosis along with the characteristics of the complaint.
Acute myocardial infarction: Patient lacks "typical" crushing chest pain with or without radiation. Also lack other manifestations of AMI such as diaphoresis. Preliminary lab data lacks (delierately ) ECG or cardiac enzymes results.
Reflux esophagitis: Patient does not have episodes of symptoms compatible with reflux esophagitis, not uncommon for a man his age. These symptoms are used as "distractors" in this case to challenge the students to try and differentiate this disorder from CV problems. Esophageal spasm may be severe and centered in the chest although it may also bore to the back. This pain is also relieved by nitroglycerin
Musculo-skeletal injury: Used here as a distractor (golf game). Muscular skeletal pain often is localized along with point tenderness. Sometimes it mimics pleuritic pain during inspiration.
Somatization: One of the most common office complaints is a primary care setting is chest "pain" or discomfort. The complaint often reflects somatization. A point should be made that not all pain is organic; therfore, the physician should pursue psychosocial stresses which may be the initiator of this problem.
Rule out other possibilities:
No history or physical finding compatible with pericarditis.
Although the patient is hypertensive, description of chest discomfort and normal chest x-ray speak against the diagnosis of dissecting aorta.
History/physical findings lacking in support of esophageal rupture, pneumothorax (normal chest x-ray) and pulmonary infarction.
There is no historical data to suggest pleuritis/pneumonia (productive cough, fever, chills, pleuritic chest pain). Examination of the lungs is normal. Temp. is normal.
History/physical exam data do not support congestive heart failure.
Note: Ask the students to explain the nature of the S4 – hypertension.
What is your diagnosis: Why?
Angina Pectoris. The case is intended to represent a simple, "stable" angina wit other problems used to challenge the students to be discriminating. You may wish to ask the students at this time about the variants of angina pectoris. The lab data other than the cholesterol level, is normal. We want the students to look up the normal reference ranges for lab tests. ECGs will be touched on in the next phase of the case.
What are the risk factors for this disease in this patient?
Hypertension
Obesity
Hypercholesterolemia
Cigarette smoking
Family history of ischemic heart disease
Note: Please ask the students about determining levels of low density and hgih density lipoproteins in a patient with increased cholesterol levels.
DIAGNOSTIC THINKING IN THE CASE OF MR. SOLOMON (QUESTIONS 8-12)
The development of a diagnostic strategy depends on the characteristics of the diagnostic tools that are used and the characteristics of the patient. The history, physical, laboratory studies, and supplemental tests all provide information that may enable the physician to reach a diagnosis. The operating characteristics of historical data, data from the physical exam, and further testing are described by the terms sensitivity, specificity, positive value, negative predictive value, and positive and negative likelihood ratio. (Refer to Dr. Richard S. Cooper’s IPM I lesson "How Do I Interpret A Diagnostic Test?")
Using English, define these operating characteristics (e.g. sensitivity: the proportion of cases with a disease that have a positive test.)
Sensitivity is the proportion of patients with disease that have a positive test. Specificity is the proportion of patients without the disease that have a negative test. Positive predictive value is the frequency with which a positive test actually means that the patient has the condition.
Negative predictive value is the frequency with which a negative test actually means that the patient does not have the condition.
The likelihood ratio for a positive test is a ratio of the proportion of patients with the disease who have a positive test (the true positives) to those without the disease who have a positive test (the false positives).
The likelihood ratio for a negative test is the ratio of those with the disease who have a negative test (the false negatives) to those without the disease who have a negative test (the true negatives).
In considering Mr. Solomon’s presentation with "pain on my chest" what are the key parts of the history and physical that influence how you develop a differential diagnosis? Qualitatively, what is your impression of the sensitivity and specificity of the historical and physical exam findings?
Mr. Solomon presents with a history of chest pain that is related to exertion and gets better with rest. Chest pain or discomfort is a relatively sensitive question for coronary artery disease but not specific. Mr. Solomon also has a burning chest discomfort that occurs late at night, after large meals, when lying down. More specific details for angina as the diagnosis include the description of the pain as heaviness, the relation to exertion, the relief with rest. The details of the burning discomfort suggest gastroesophageal reflux disease (GERD)
Thus, the specificity of the diagnoses of angina and GERD are increased by the specific historical questions. The physical exam does not add much to either diagnostic possibility. In other words, the increased blood pressure is not particularly sensitive nor specific for the diagnosis of angina. The presence of hypertension, however, increases one’s concern that a patient may have angina given that hypertension is a known risk factor for coronary artery disease (see question 5).
What supplemental testing, if any, would you want in addition to the history, physical, and laboratory studies that are listed?
This questions is not entirely straightforward. It would be reasonable to obtain an exercise test and, depending on the result of that test, proceed with a cardiac catheterixation. One could easily argue, however, given the multiple risk factors and the high prior probability of coronary artery disease, that a negative exercise test may well be considered a false negative and one would go ahead with a catheterization anyway. If that is one’ reasoning, then the exercise test would be a waste of time and money.
The characteristics of a patient determine how one interprets data obtained from that person. For example, a positive HIV test on a cloistered nun who has never had any sexual contact, blood exposure or other risk is almost certainly a false positive. In Mr. Solomon’s case, what characteristics, or risk factors, make you think it is likely that he has the diagnosis you consider most likely.
Answer to 11 and 12: The point of this question is to review the risk factors for coronary artery disease in Mr. Solomon and then discuss how they influence one’s interpretation of the data obtained. Mr. Solomon is a male smoker with hypertension, hypercholestrolemia, obesity, and a family history of coronary artery disease.
This all leads into the point made at the end of question 4: the historical data and the risk factors make the prior probability so high that Mr. Solomon has angina, going directly to cardiac catheterization may well be the most reasonable course if one’s goal is to prove that the chest discomfort is angina and related to coronary artery disease. If Mr. Solomon is averse to invasive testing, a treadmill test might be useful to get a sense of the severity of the coronary artery disease. (i.e. if he drops his pressure with exercise then one would be concerned about left main obstruction and argue more forcefully about the need for a catheterization) and as therapeutic maneuver (e.g., if Mr. Solomon does not have EKG changes until he reaches a high double product, one could consider beginning a gentle exercise program as part of his therapeutic regimen.)
Given these characteristics, is there any point in supplemental diagnostic testing for Mr. Solomon? Would you believe a negative or positive test? Should be proceed directly to the "gold standard"?
See answer above in question 11.
What drug therapy would you consider prescribing to modify Mr. Solomon’s risk factors and to control his symptoms?
Anti-hypertensive medication to lower blood pressure (specific agents yet to be covered in the therapeutics lectures-defer)
An HMG-CoA reductase inhibitor to lower cholesterol
HMG-CoA reductase inhibitors block the rate limiting enzyme for the synthesis of cholesterol. Serum cholesterol levles fall not only from a reduced synthetic rate but from an up-regulation of LDL receptors in hepatocytes and an increased rate of LDL catabolism from the circulating pool. The HMG-CoA inhibitors (lovastatin, simvastatin, pravastatin), have been shown in clinical trials to reduce the rate of progression of coronary artherosclerotic lesion and to increase the frequency of regression. These agents have also been shown to reduce the risk of death due to coronary artery disease and risk of nonfatal myocardial infarction. The goal of this therapy (combined with dietary restrictions) is to reduce serum cholesterol to <190 mg/dL.
Aspirin
Since aspirin reduces the risk of heart attack (coronary thrombosis) in patients with coronary artery disease there is a strong indication for daily aspirin (160 mg/day) therapy. Aspirin causes irreversible inhibition of platelet cyclooxygenase, decreased thromboxane A2 production and decreased platelet aggregation. Then aspirin is given as prophylactic therapy to reduce the risk of intracoronary thrombosis and would probably have little effect on Mr. Solomon’s angina.
Sublingual nitroglycerine
Organic nitrates are excellent drugs for the treatment of stable angina. The organic nitrates
(R-O-NO2) combine with cysteine (R-SH) in the vessel wall to form a nitrosothiol that releases nitric oxide (NO). The organic nitrates decrease ventricular wall stress (oxygen demand) by reducing both preload and afterload {wall stress = (P x r)/ (2 x wall thickness)} This results from a primary action on venous capacitance vessels with a more minor effect on aterioles. Organic nitrates may also exert favorable effects on oxygen supply. The reduced ventricular pressure during both diastole and systole will decrease extravascular coronary resistance (compressive forces). Organic nitrates also dilate collateral vessels and will cause a small dilation of stenotic coronary arteries when the stenosis is eccentric.
Long-acting nitrates
If sublingual nitrodlycerine worked well but Mr. Solomon wanted something that prevented his attacks then you could consider switching to a nitroglycerine patch, or isosorbide dinitrate. Continuous nitrate therapy is not recommended due to the depletion of cysteine in the vascular smooth muscle and the development of tolerance. A nitrate-free interval of at least 8 hours is recommended between repeated doses.
Beta-blockers and or calcium channel blockers.
If organic nitrate therapy alone was inadequate to control Mr. Solomon’s angina, then the combination of an organic nitrate and beta-blocker or an organic nitrate with a calcium channel antagonist (verapamil, diltiazem, long acting dihydrophyridine derivative) would provide greater protection against ischemia. Triple therapy consisting of an organic nitrate, beta-blocker and calcium channel blocker might also be considered. The short acting dihydropyridine derivatives (nifedipine) have been shown to increase mortality in patients with coronary artery disease and should not be prescribed.