INTRODUCTION
CASE IN DETAIL
DB was diagnosed with acute myocardial infarction when she presented at hospital 3 months ago with a 2-day history of epigastric discomfort, nausea and general malaise. Her admission was further complicated by an episode of diabetic hyperosmolar coma, which was managed with hydration and parenteral insulin. She was discharged from hospital 9 weeks ago after a hospital stay of 3 weeks. Post discharge she experienced angina on exertion. She could walk 50 metres on flat ground before experiencing retrosternal chest discomfort. Subsequent coronary angiography revealed triple-vessel disease.
She was scheduled for revascularisation therapy through angioplasty and stenting 1 week ago. The treatment had to be postponed due to severe dyspnoea on second presentation. The dyspnoea was present at rest, with associated orthopnoea and episodes of paroxysmal nocturnal dyspnoea. These symptoms have been present in varying degrees of severity over the past 3 months. Currently her ischaemic heart disease is managed with isosorbide mononitrate 60 mg daily, quinapril 5 mg daily and aspirin 150 mg daily. She has a significant risk factor profile for coronary artery disease, which includes:
1. a family history of ischaemic heart disease, with her mother dying of an acute myocardial infarction at the age of 67 and father dying of the same at the age of 65
2. a smoking history of 50 pack-years. She stopped smoking 10 years ago.
3. hypercholesterolaemia managed with pravastatin 10 mg daily. The patient does not know her previous or current cholesterol levels.
4. hypertension diagnosed 1 year ago and managed with diltiazem 240 mg daily. She denies any side effects associated with this medication. The local pharmacist monitors her blood pressure at monthly intervals. She cannot remember the most recent blood pressure reading.
5. diabetes mellitus, which was diagnosed 4 years ago. Initially she was managed on a diet and the oral hypoglycaemic agent metformin. But metformin was very soon stopped due to its adverse effects, including nausea, diarrhoea and rash. Subsequently she was commenced on gliclazide. Three months ago this was stopped due to erratic blood sugar control, and she was commenced on insulin therapy. She is currently maintained on the following insulin regimen:
She monitors her blood sugar levels four times a day. She does not comply with the diabetic diet.
Usually her blood sugar levels fall between 8 and 10 mmol/L. She denies ever experiencing hypoglycaemic episodes and is unaware of the usual warning signs of hypoglycaemia.
She suffers from the multiple end-organ complications associated with diabetes:
1. Ocular complications—an ophthalmologist reviews her eyes every year. She has bilateral cataracts and is awaiting excision. She is unaware of any other ocular complication and denies any visual impairment.
2. Renal complications—she has her urine tested by her general practitioner every month and is currently unaware of any nephropathy. But she complains of recurrent polydipsia, polyuria and nocturia, symptoms that may suggest renal failure.
3. Macrovascular complications—she has peripheral vascular disease and has a claudication distance of 10 metres. She has never had a stroke.
4. She complains of postural dizziness, a symptom that may suggest autonomic neuropathy.
DB denies any paraesthesias or loss of peripheral sensation. She also denies any foot complications such as callosities, corns or ulcers.
She also suffers from asthma, which was diagnosed many years ago, and emphysema, diagnosed 8 years ago.
Her airway symptoms are worst in the winter. Perfumes and pollen are known precipitants of her asthma attacks. She denies nocturnal cough. She has never been admitted to hospital with exacerbation of airway disease. She monitors her peak flow weekly and it varies around 150–200 L/min. Her airway disease is currently managed with nebulised salbutamol and ipratropium bromide four times a day and salmeterol via a metered dose inhaler twice a day. She has been managed on variable doses of prednisolone previously, but she cannot recall the maximum or minimum doses that she has been on.
Prednisolone causes easy bruising but she denies any other side effects associated with this therapy, including pathological fractures and weight gain. She cannot remember whether she has had her bone density assessed.
She was diagnosed with carcinoid tumour of the left lung 8 years ago when she presented with resistant wheezing, dyspnoea and cyanotic spells. She denies any facial flushing or diarrhoea during that presentation. The diagnosis was made after imaging studies followed by bronchoscopy and biopsy. She is managed with regular endobronchial laser therapy at 2-yearly intervals and her last treatment episode was 1 year ago.
She has had persistent diarrhoea for 3 months. On average she has 6–10 bowel movements a day. The diarrhoea is watery in nature and she denies any associated blood loss. She denies any abdominal pain, nausea, vomiting or anorexia. She has previously tried several antidiarrhoeal agents without much success.
She also suffers from painful muscle cramps occasionally, which are treated with quinine bisulfate as required.
Her current medications in summary are diltiazem, isosorbide mononitrate, pravastatin, insulin, salbutamol, ipratropium bromide, salmeterol and quinine bisulfate.
This woman’s allergies include metformin and penicillin, both of which cause rash.
Her family history also includes one brother aged 81 suffering from Alzheimer’s disease and one sister aged 69 suffering from rheumatoid arthritis and breast cancer.
She has previously worked as a chef and is currently on a pension. She finds this income barely enough to meet her needs.
She consumes alcohol only very occasionally.
She has been married for 51 years and her husband, aged 74, is well and supportive. She is usually independent with activities of self-care, but has been experiencing difficulties lately due to the dyspnoea. She lives in a house where there are no steps to negotiate. She has been driving until about 3 weeks ago.
She has a son aged 47 and a daughter aged 44 years; both are well, married and living apart from their parents, and she has four grandchildren. She has regular contact with them.
The dietary history I obtained suggests satisfactory nutrition but with inappropriately high joule and lipid intake.
She has poor sleep hygiene, with initial and terminal insomnia. She has about 5 hours of sleep each day but denies daytime somnolence.
She has had the occasional feeling of depression but has never sought medical help and denies any current depressive feelings.
At home she spends most of her spare time knitting.
I felt that she had very poor insight into the multiple disease conditions that she suffers from.
ON EXAMINATION
DB was alert and cooperative. She had an estimated body mass index of 30. Her cognitive function was well preserved, with a Mini-Mental State score of 29/30. She was breathing oxygen via nasal prongs at a rate of 2 L per minute.
Her blood pressure was 148/68 mmHg and there were postural drops of 20 mmHg systolic and 20 mmHg diastolic. Her respiratory rate was 20 at rest. She was afebrile.
Examination of the cardiovascular system showed a jugular venous pressure elevation to a level 5 cm above the angle of Louis. Her apex beat was not palpable. There were two heart sounds and both were normal with no added sounds. There was bilateral pitting ankle oedema to the level of the knee.
In the examination of her respiratory system I noticed a moist cough, but no sputum was available for inspection. She was using accessory muscles of respiration. She had oropharyngeal crowding. The percussion note was resonant throughout and the breath sounds were vesicular, with polymorphic wheezes audible in the lower zones bilaterally. In addition there were coarse inspiratory crepitations in the lung bases bilaterally. The forced expiratory timing was prolonged to 7 seconds.
Gastrointestinal examination showed no oral candidiasis. Her abdomen was obese and soft, and there was no organomegaly or masses. Bowel sounds were well audible.
Neurological examination showed a visual acuity of 6/9 in the right side and 6/24 in the left with correction. Fundoscopy showed multiple flame-shaped bleeds with cottonwool spots and increased tortuosity of the retinal vasculature. The rest of the cranial nerve examination was unremarkable.
Upper limb examination showed normal tone, power, reflexes and coordination bilaterally. There was diminished pinprick sensation in the periphery up to the level of the wrist. Other sensory modalities were normal.
Lower limb examination showed normal motor function and coordination, with impaired pinprick sensation up to the level of the knees bilaterally. Other sensory modalities were preserved. The plantar response was flexor bilaterally and Romberg’s test was negative.
Musculoskeletal examination was unremarkable and there were no areas of bony tenderness.
There was no lymphadenopathy. The diabetic foot examination was unremarkable except for the abovementioned sensory impairment.
In summary, this is a 72-year-old obese woman with triple-vessel coronary artery disease, multiple coronary risk factors and a recent myocardial infarction, presenting for angioplasty and stenting of the coronary stenoses. This admission has been complicated by recalcitrant dyspnoea. She also suffers from persisting diarrhoea, diabetes mellitus with end-organ damage, hypertension, hyperlipidaemia, carcinoid tumour of the lung, asthma, emphysema and occasional depression.
Currently her major problems are dyspnoea and coronary ischaemia.
In approaching her management I have identified four problems that need initial attention:
I believe this woman’s dyspnoea to be multifactorial. The possible differential diagnoses include pulmonary oedema, pulmonary sepsis, infective exacerbation of her airway disease, poorly controlled asthma, carcinoid syndrome and pulmonary embolus. To exclude the above causes I would like to see the results of the following investigations:
1. Chest X-ray, looking for pulmonary congestion, consolidation, hyperinflation and/or cardiomegaly
2. Arterial blood gases, looking for hypoxia and carbon dioxide retention
3. Full blood count, to exclude anaemia or leucocytosis
4. Lung function studies in the form of a flow–volume loop or spirometry, to ascertain the presence of obstructive or restrictive lung pathology
6. If the above investigations are not diagnostic, a ventilation-perfusion scan is indicated, to look for areas of mismatch.
To treat her symptoms I would first optimise her airway therapy and stabilise her airway function. I would administer a short course of systemic steroid therapy, starting with 25 mg prednisolone daily to achieve early control of her airway inflammation. I would also commence regular inhaled steroids in the form of fluticasone via an Accuhaler device at a dose of 500 mg twice daily. I would stop the long-acting bronchodilator and manage her with regular nebulised salbutamol and ipratropium bromide administered 4–6 times a day. I would monitor her serial spirometry results while in hospital and stop the systemic steroid therapy as soon as possible once airway stability was achieved, because of her diabetes and obesity. While she was on systemic steroids I would closely monitor her blood sugar level four times a day and step up her diabetic therapy according to need.
I would also optimise her left ventricular function and relieve pulmonary congestion with regular diuretic therapy in the form of frusemide and ACE inhibitor therapy, the diuretic dose to be titrated according to the response. I would monitor her potassium level closely. I would continue her ACE inhibitor therapy and consider increasing the dose of quinapril to 10 mg daily while closely observing the renal function indices.
If there was evidence to suggest infection, I would commence antibiotic therapy as guided by the chest X-ray and sputum microscopy and culture.
Questions and answers
Q: Would you please interpret this chest X-ray?
A: This is a frontal projection, posteroanterior view chest X-ray of DB done on (insert date). It shows diaphragmatic flattening suggesting pulmonary hyperinflation, which is characteristic of emphysema. It also shows increased translucency in the peripheral lung fields, further confirming emphysema. She has an increased cardiothoracic ratio, estimated at about 60–70%, together with prominent hilar shadows suggesting congested main pulmonary vessels and a diffuse, patchy infiltrate, all features suggesting pulmonary congestion secondary to left heart failure.
I would like to look at her lateral-view chest X-ray, results of a recent echocardiogram and results of the lung function tests to confirm my findings.
Q: She has been treated with high-dose frusemide therapy, 120 mg mane and 80 mg nocte, but she is still symptomatic. What would you do now?
A: She remains in symptomatic cardiac failure despite being managed with high-dose diuretic and ACE inhibitor therapy. To augment the diuretic treatment, I would add a thiazide diuretic to her regimen, commencing while she is still in hospital, and place her on a fluid restriction of 1 L/day and a low-salt diet. I would follow her up with observation for clinical improvement of her symptoms and signs, monitoring the urine output and daily weighing.
I would expedite coronary revascularisation once her clinical status was stable, because with the restored blood flow the hypoperfused ‘hibernating’ myocardium could be brought in to augment the ventricular contraction.
If her clinical status deteriorates, she might benefit from a short course of intravenous inotropic therapy, given via a centrally placed venous catheter. The agent I would use is dobutamine.
Q: Would you please interpret these lung function test results?
A: This lung function test report shows severe obstructive airway disease with impaired gas exchange. This confirms the clinical and radiological findings of emphysema. I would like to test further for reversibility of airway obstruction with a bronchodilator challenge, and perform arterial blood gases, looking for hypoxia and carbon dioxide retention.
Q: What do you think about the choice of angioplasty for coronary revascularisation in this woman?
A: This woman has triple-vessel coronary artery stenosis, cardiac failure and diabetes mellitus. I would like to see the angiogram to ascertain the severity of the coronary disease and to see whether there is significant disease in the left main coronary artery. Her prognosis is guarded by the fact that she has cardiac failure as well as diabetes mellitus. The best modality of coronary revascularisation for this patient is coronary artery bypass grafting. But given her severe airway disease, obesity, diabetes and poor functional status, it is doubtful whether she would survive general anaesthesia and major surgery. Therefore I would attempt to treat her with coronary angioplasty. But diabetic patients usually have low rates of maintenance of coronary patency after angioplasty. Stenting the treated stenosis will help maintain its patency for a longer period of time. Best medical therapy (see box) is another option I would consider in this case. However, adding further agents to her list of medications may lead to polypharmacy and associated issues with poor compliance.
Antiangina medical therapy
For resistant cases, consider adding the following:
Q: How would you optimise her coronary risk factor profile?
A: First I would like to reassess her coronary risk factor profile. She was marginally hypertensive at the time of my examination. But she is already on considerably high doses of antihypertensive agents. I would continue to monitor her blood pressure while she was in hospital before altering her antihypertension therapy. To evaluate her usual blood sugar control, I would like to see her glycosylated haemoglobin level done during this admission. Guided by this measure and the recent blood sugar levels, I would optimise her insulin regimen to strictly control her blood sugar level. I would like to know her fasting serum lipid profile to see whether she would need review of her anticholesterol therapy.
Significant weight reduction would certainly improve this woman’s overall prognosis, but it would be a serious challenge!
Q: Her latest serum total cholesterol level is 6.1 mmol/L and triglyceride level 2 mmol/L. Would you change her therapy?
A: Because of her existing ischaemic heart disease I would like to have her total cholesterol level maintained below 4.5 mmol/L. I would provide her with further advice on lipid-lowering dietary habits, encourage her to engage in low-impact physical exercise and also increase the dose of pravastatin to 20 mg/day.
Q: How would you manage her diarrhoea?
A: Initially I would like to ascertain the exact cause of this woman’s diarrhoea. The differential diagnoses I would consider are as follows:
1. Infectious causes such as Campylobacter, Salmonella, E. coli or parasitic agents such as Giardia
2. Medication-induced diarrhoea (excessive diuretics)
3. Osmotic diarrhoea due to lactose/disaccharide intolerance. I would fast her for 12 hours to see whether the diarrhoea settled, as is the case with osmotic diarrhoea.
4. Endocrine or metabolic causes, such as diabetic autonomic neuropathy, hyperthyroidism and carcinoid syndrome
5. Inflammatory causes, such as ulcerative colitis or collagenous colitis
6. Malabsorption syndrome or chronic bacterial overgrowth
7. Villous adenoma.
If all the above were excluded, it could be considered irritable bowel syndrome. To evaluate the exact cause I would like to see the results of the following investigations:
1. Microscopy and culture of stool, looking for leucocytes, pathogenic bacteria, parasites, ova and cysts
2. Stool test for Clostridium difficile toxin
3. Stool electrolytes and pH and osmolality. An acidic pH may suggest carbohydrate malabsorption and an osmotic gap of > 50 mOsm/L might confirm this finding.
4. If the above tests were unrevealing I would like to perform faecal fat quantification, looking for evidence of malabsorption
6. I would further like to ascertain the level of activity of this patient’s carcinoid syndrome by performing a 24-hour urinary quantification of 5-hydroxyindole acetic acid (5-HIAA) and look for any hyperthyroidism by performing thyroid function tests.
Q: All the above tests were non-diagnostic. What would you do?
A: Diabetic autonomic neuropathy or irritable bowel syndrome are the likely diagnoses in this case, and I would start treating her with a trial of antidiarrhoeal therapy in the form of loperamide chloride or diphenoxylate.
Q: How would you manage her steroid-related complications?
A: This woman has diabetes mellitus, of which the control is complicated by steroid therapy. I would endeavour to minimise the duration of systemic steroid therapy. I would also perform bone densitometry, looking for evidence of osteoporosis. I would vaccinate this woman against the influenza virus every year and against Pneumococcus every 5 years.
Q: Please interpret this bone densitometry report.
A: It shows a Z score of –2.7 and a T score of –2. This is highly suggestive of osteoporosis. I would treat this woman with calcium supplements in the form of calcium carbonate or caltrate, vitamin D supplements in the form of calcitriol, and bisphosphonate therapy in the form of daily oral etidronate or monthly intravenous pamidronate. I would warn the patient about the erosive oesophagitis that etidronate can cause and advise her to take the medication before breakfast every day and not to lie supine for at least half an hour after ingestion of the drug.
Q: Do you think her carcinoid syndrome is well managed?
A: Her 5-HIAA level is normal, and therefore it is likely that she currently has no carcinoid syndrome.
Q: If this woman were to develop symptomatic carcinoid syndrome, how would you manage it?
A: Carcinoid syndrome usually presents with facial flushing, dyspnoea, wheezing, weight loss and persistent diarrhoea. I would check her serum serotonin level and also do a hepatic ultrasound scan, looking for hepatic metastases, to determine the level of disease activity. Symptomatic management is achieved with the use of antiserotonin agents such as cyproheptadine. If the symptoms were severe, I would use octreotide to treat her. Definitive therapy involves removal of the tumour bulk. As this woman has been satisfactorily managed with laser therapy in the past, I would use further laser therapy to reduce the bulk of the tumour.
Q: How are you going to improve this woman’s quality of life?
A: Adequate control of the airway disease and coronary revascularisation will most definitely improve her symptoms and will also improve her exercise tolerance. I would commence her on a cardiorespiratory rehabilitation program with regular physiotherapy to expedite her recovery. I would formulate a program of weight loss with the help of the dietitian. I would consult the occupational therapist with a view to assessing her functional capacity and providing necessary support.
