Cardiology — Long Cases

2 Cardiology—Long Cases Chu-Pak Lau, A. John Camm, Kai-Hang Yiu, Wai-Hong Chen, and Bernard Man-Yung Cheung 2.1 Acute chest pain (acute myocardial infarction) History A 65-year-old man presented to the accident and emergency department after an acute onset of chest pain. The pain started 2 hours earlier while he was jogging in the park, and lasted up to the time of hospital attendance. He described it as a compress- ing discomfort in the retrosternal region and was accompanied by sweating and ill-defined weakness. He denied having chest pain or exertional breathlessness prior to this episode. He had a long history of diabetes mellitus and had smoked approximately 1 to 1.5 packs per day of cigarettes for the past 30 years. Physical examination His blood pressure was 125/85, and his pulse rate was 92 per minute. The jugular venous pressure was not elevated. The apex was in the normal position. The first heart sound was soft and a fourth heart sound was audible. A grade 2/6 ejection systolic murmur was heard over the apex. All other systems were normal.

22 Problem-Based Medical Case Management Case 2.1 Investigations Chest X-ray: normal cardiothoracic ratio and mediastinal width. ECG: sinus thythm and 1-2 mm ST-elevation over the leads V2 to V5. Questions 1. What blood tests should be obtained before proceeding to further management? * Serial assays of serum markers of cardiac damage should be performed to confirm the diagnosis of myocardial infarction. Creatine kinase-MB (CK-MB) isoenzyme has been the most frequently employed biomarker for myocardial infarction but is limited by its non-specificity (also found in skeletal muscles, small intestine, uterus, etc.). Cardiac troponin I and T are more sensitive and specific for myocardial injury and are the preferred method for diagnosing acute myocardial infarction. However, it takes 3—6 hours after the onset of myocardial infarc- tion for these markers to become detectable; they are therefore not useful to guide acute management in the majority of cases. Other blood tests include electrolytes, urea, creatinine, glucose, lipids, complete blood counts, prothrombin time, and activated partial thromboplastin time. 2. What reperfusion therapy should be given? For patients with ST-elevation myocardial infarction presenting within 3 hours of symptom onset, there is no preference for mechanical reperfusion or fibrinolysis if both can be performed in a timely fashion (medical contact-to-balloon angioplasty time < 90 minutes; medical contact-to-needle time < 30 minutes). 3. What are the absolute contraindications to fibrinolytic therapy? Fibrinolytic therapy is contraindicated after any previous intracranial haemorrhage, known structural cerebrovascular lesions (e.g., arteriovenous malformation), malignant intracra- nial neoplasm, and ischaemic stroke within 3 months. It should not be used in suspected aortic dissection, active bleeding or

Case 2.1 Cardiology 23 bleeding diathesis and within 3 months of a significant closed head injury or facial trauma. 4, What complications do you suspect if a new pansystolic murmur appears together with new development or worsening of congestive heart failure? How can they be differentiated? « Rupture of the interventricular septum or a papillary muscle. The murmur of ruptured interventricular septum is usually best heard at the lower left sternal border and accompanied by a thrill, whereas a mitral regurgitation murmur is usually heard at the apex and radiates to the axilla. Ventricular septal defect is associated with anterior infarct and mitral regurgitation usually follows inferior infarcts. Definitive diagnosis relies on the use of echocardiography with colour flow Doppler imaging and/ or insertion of a pulmonary artery balloon catheter. During echocardiography, a septal defect and left-to-right shunt can be readily visualized just as it is possible to recognize mitral regurgitation and ruptured papillary muscle. In septal rupture, right heart catheterization can detect oxygen step-up in the right ventricle. 5. What are the clinical variables that affect a patient’s mortal- ity risk before administration of fibrinolytic therapy? Elderly, hypotension, tachycardia, congestive heart failure, anterior infarct, diabetes, low body weight, and delay in receiv- ing fibrinolysis. 6. What measures are beneficial in secondary prevention of acute myocardial infarction? + These include interventions to modify risk factors: smoking cessation, cholesterol lowering with statins, antiplatelet therapy with aspirin, angiotensin converting enzyme inhibitor, and beta-blocker. Cardiac rehabilitation programmes (incorporating exercise and education) are important. Pitfalls and tips ' » Some patients experience repetitive cycles of spontaneous rep- erfusion and re-occlusion before persistent thrombotic occlu- sion is established. The time of symptom onset may thus be

24 Problem-Based Medical Case Management Case2.2 erroneously judged to be earlier, leading to the erroneous con- clusion “outside the 12-hour window” to benefit from fibrino- Iytic therapy. » Atypical presentations of acute myocardial infarction (ST-elevation) include: — Syncope Indigestion Atypical location of the pain Sudden mania or psychosis Apprehension and nervousness — Dyspnoea ¢ Aninitial normal ECG does not exclude infarction but failure of ECG infarct patterns to evolve throughout despite persistence of suspicious ST-elevation makes myocardial infarction highly unlikely. 1 | 2.2 A patient with progressive exertional dyspnoea (dilated cardiomyopathy) History A 48-year-old female secretary presented with a 2-month history of gradually worsening fatigue, breathlessness on exertion, and ankle swelling. The breathlessness was worse when she lay flat. She had one normal pregnancy 20 years earlier and her last men- struation was 2 years ago. There was no history of hypertension, diabetes, hyperlipidaemia, myocardial infarction, stroke or other cardiovascular disease, and she had never had chest pains. She had always been a non-smoker and non-drinker. Her father died of lung cancer (at age 60) and her mother of heart disease (at age 48). Her older brother, aged 50 years, was being treated for chronic heart failure. Until the time of presentation, she had not been taking any drugs.

Case 2.2 Cardiology 25 Physical examination Patient was tachypnoeic. There was no anaemia, clubbing, jaun- dice or cyanosis. Her blood pressure was 120/76 mm Hg and her heart rate was regular, at 104 per minute. Jugular venous pressure was raised; prominent v wave. There was bilateral leg oedema. Cardiac apex: 6th intercostal space, ante- rior axillary line, heaving. On auscultation: 3rd heart sound, pan- systolic murmur at the apex, left sternal border and axilla. There were inspiratory crackles in both lung bases. The liver was enlarged and pulsatile. Investigations » Normal blood count, ESR ¢ Normal urea and electrolytes « Liver function tests: mild elevations in AST and ALT and mild decrease in albumin ¢ Normal cardiac enzymes « ECG: sinus tachycardia » Posteroanterior chest X-ray: large cardiac shadow, with a car- diothoracic ratio of 0.7, increased lung markings, prominent vascular markings especially in the upper lobe and blunting of costophrenic angles » Echocardiography: dilatation of the cardiac chambers, global hypokinesia, with mild to moderate mitral and tricuspid regurgitation * Left ventricular ejection fraction: 35% + From the retrograde tricuspid flow velocity, the right ventricu- lar systolic pressure was estimated to be 40 mmHg. (Normal <30 mmHg) Questions 1. What other investigations can be undertaken to reach a diagnosis? ¢ Thyroid function test.

26 Problem-Based Medical Case Management Case 2.2 * Antibody viral titres are useful when acute myocarditis is suspected. « HIV test in suspected cases. ¢ Serum ferritin (haemochromatosis). * Drug screen (illicit drugs such as cocaine). ¢ Thallium scan to detect myocardial ischaemia. Cardiac catheterization can help to document pressures in the chambers, cardiac function, and the presence of coronary artery disease. ¢ Endomyocardial biopsy might be useful for diagnostic and prognostic purposes. Skeletal muscle biopsy if primary muscle disease is suspected. 2. What are the causes of heart failure? e The vast majority of patients with chronic heart failure are elderly, and have hypertension and/or ischaemic heart disease. Previous myocardial infarction, valvular heart diseases, car- diomyopathies, and high output failure (e.g., thyrotoxicosis and anaemia) are also causes of heart failure. ¢ In the absence of an underlying cause, (e.g., ischaemic heart disease, congenital heart disease or valvular heart disease), the cause is intrinsic to the myocardium and is termed cardiomyo- pathy; described as dilated, hypertrophic, arrhythmogenic right ventricular dysplastic, obliterative or restrictive. Recognized provocative/aetiological causes include: high cardiac output (thyrotoxicosis, volume overload, peripartum), viral and rarely other infections/infestations, amyloidosis, alcoholism, drugs (e.g., doxorubicin) and infiltrative (iron). 3. How do you treat the heart failure in this patient? « While in hospital, sit patient up and give oxygen. ¢ Loop diuretic, e.g., frusemide. « Start angiotensin converting enzyme inhibitor. ¢ Replace potassium or add a potassium-sparing diuretic (e.g., amiloride) if necessary. « Consider initiating a beta-blocker when patient is stable. ¢ Consider adding spironolactone. ¢ Give digoxin if the patient is in atrial fibrillation. .

Case 2.2 Cardiology 27 Give specific treatment depending on aetiology, e.g., treat thyo- toxicosis, give thiamine. + Inadilated heart, QRS may be prolonged, in which case, cardiac resynchronization therapy (CRT) by biventricular pacing may be considered. 4. Why might this patient have dilated cardiomyopathy? o Her heart is dilated and she does not have hypertension, valvu- lar heart disease, or coronary artery disease or its risk factors. The family history of premature heart disease is consistent with cardiomyopathy; about 30% of patients have a genetic basis. More investigations (including endomyocardial biopsy) can be undertaken to ascertain the diagnosis but the heart failure treat- ment would be unaltered. 5. What is the prognosis of dilated cardiomyopathy? « The prognosis depends on the cause. In general, heart failure is associated with a poor prognosis, with only about half of all patients surviving after 5 years. The US Myocarditis Treatment Trial showed that most patients with postviral and idiopathic lymphocytic myocarditis spontaneously improve, and that immunosuppressive therapy does not increase the extent of improvement, although it can be tried as a last resort. Dilated cardiomyopathy is a major reason for cardiac transplantation. * Several uncommon causes may be amenable to specific thera- pies: sarcoidosis; haemochromatosis; Lyme’s carditis; systemic autoimmune disease; coronary vasculitis; Chagas’ disease. 6. What are other causes of exertional dyspnoea? * Besides heart disorder, it is important to consider respiratory diseases and anaemia. ¢ B-type natriuretic peptide may be measured in plasma; a high level is associated with heart failure. This is especially useful for distinguishing respiratory from cardiac causes of dyspnoea. 7. Can viruses cause dilated cardiomyopathy? * Viruses, parasites, protozoan, and fungi can all cause myo- carditis. Viral myocarditis is quite common and often sub- clinical. Non-specific ECG abnormalities are often present in patients with viral infections, which revert to normal upon

28 Problem-Based Medical Case Management Case2.3 convalescence. Coxsackie B, hepatitis C, and the human immu- nodeficiency viruses are known to be associated with myocardi- tis, but many other different viruses could be involved. The end result is infiltration of NX cells, macrophages, and T lympho- cytes in the myocardium, with apoptosis, necrosis, and fibrosis. 8. Is dilated cardiomyopathy hereditary? « If the cause is viral, then it is not hereditary. At least about a quarter of the cases have a family history. Screening the rela- tives may reveal LV enlargement that may progress to cardio- myopathy. A number of genes are implicated; the best known are codes for dystrophin. 2.3 Exercise induced syncope (hypertrophic obstructive cardiomyopathy) History A 40-year-old man with good past health presented with 3 episodes of exertion-related syncope last year. He had a positive family history of sudden death: both his father and grandfather died in their early thirties. He also complained of gradually decreasing exercise tolerance for the past 3 years. He had no chest pain, pal- pitation or ankle oedema. He was a gymnastics instructor and had never smoked; nor did he drink alcohol. He did not have a history of rheumatic fever in childhood. Physical examination He had a normal blood pressure, and his pulse rate was 60 per minute. The apex was displaced, but no thrill was detected. There was a pansystolic murmur at the apex radiating to axilla and an ejection systolic murmur at the aortic area radiating to the neck. All other systems were normal.

Case 2.3 Cardiology 29 Questions 1 What differential diagnoses can be offered? What clinical features support these? 2. Exercise induced syncope can be due to hypertrophic obstruc- tive cardiomyopathy, severe aortic stenosis, exercise induced arrhythmias and critical coronary artery disease. Differentiation between hypertrophic obstructive cardiomyopa- thy and aortic stenosis: in hypertrophic obstructive cardiomyo- pathy, the pulse has a normal volume that stops abruptly during mid-systole and the aortic second sound is normal. Clinically, how do you determine the severity of aortic stenosis? 3. History of syncope, angina, and heart failure suggest critical aortic stenosis. A systolic thrill, slow rising, small volume pulse, and soft aortic second sound are features of severity. Displaced apex is a late event often associated with heart failure. What are the different types of hypertrophic cardiomyopa- thy? How can one differentiate them clinically? Obstructive type: jerky pulse and murmur. Obstruction can be dynamic (examine on standing). Non-obstructive; occurs often in Asians; the hypertrophy can be limited to the apical region. In elderly females, there may be concentric left ventricular hypertrophy with diastolic failure. How do you investigate this patient? ECG: left ventricular hypertrophy with ST-T changes. Echocardiogram: left ventricular hypertrophy, —septal-to- posterior wall thickness ratio > 1.5, impaired septal motion with speckled appearance, systolic anterior movement (SAM) of mitral valve (Venturi effect). Doppler to define subaortic gradient. Cardiac catheterization: associated coronary artery disease, intra-cavity gradient and cavity obliteration on angiography. Holter: associated atrial and ventricular arrhythmias. Electrophysiology study: inducible ventricular arthythmias for risk stratification (controversial).

30 Problem-Based Medical Case Management Case2.3 5. Patient is a part-time gymnastics instructor, so how will you advise him if the diagnosis is correct? e May need to consider job change to avoid vigorous exertion. Competitive sports should be avoided. 6. How do you treat this patient? Medical: beta-blocker, calcium channel blocker such as vera- pamil, anti-arrhythmic agents for associated atrial fibrillation. e Non-drug treatment: — Implantable cardiac defibrillator if significant ventricular arrhythmia is documented. — Dual chamber pacing that alters the septal activation can reduce outflow gradient (may provide symptomatic improve- ment especially in elderly). — Surgical myomectomy (or catheter-based alcohol septal ablation) to relieve outflow tract obstruction. 7. What are the causes of exercise induced syncope in this patient? « Exercise induced syncope can be due to dynamic (outflow obstruction), reflex vasodilation or exercise induced atrial or ventricular arrhythmias. Pitfalls and tips ¢ Remember to ask for family history; draw a family tree if possible. * In the history, clarify the nature of syncope (light-headedness, faintness, loss of consciousness or vertigo). e Decreasing exercise tolerance (increasing breathlessness versus tiredness). » Examine the patient either standing or during the strain phase of the Valsalva manoeuvre (these reduce the left ventricular volume, accentuating outflow obstruction murmurs).

Case 2.4 Cardiology 31 2.4 Fever for three months (infective endocarditis) History A 40-year-old man complained of fever and fleeting joint pains for 3 months. He had a history of febrile illness in childhood with a heart murmur detected at that time, but did not receive monthly injection of penicillin. He was treated as for rheumatoid arthritis (as his serum was positive for rheumatoid factor) but his joint pains failed to resolve. He enjoyed good exercise tolerance (> 4 flights of stairs) and did not have any dental procedures performed recently. Physical examination He had Osler’s nodes but no splinter haemorrhages nor Janeway lesions. Precordium examination revealed the apex beat to be at the 5Sth intercostal space in the mid-clavicular line, a soft first heart sound, and a grade 3/6 pan-systolic murmur at apex radiating to the axilla. Neurological examination, fundoscopy, and urinalysis were normal. There was no splenomegaly. Questions 1. What investigations will you perform to establish the diagnosis? * Persistent bacteraemia as revealed by 3 positive blood cultures will establish the diagnosis. ¢ Other evidence of infection includes raised white cell count, ESR, and CRP. * Status of cardiac disease can be established by echocardiogra- phy; vegetation is better appreciated by transoesphageal echo. ° Establish a baseline for treatment, e.g., haemoglobin, renal function, chest X-ray.

32 Problem-Based Medical Case Management Case 2.4 2. How do you treat his infective endocarditis? ¢ Start high-dose intravenous bactericidal antibiotics for the most likely flora, e.g., soluble penicillin 3 Mega units intravenously every 4 hours for 4 weeks and gentamicin 60 mg every 8 hours for 2 weeks for streptococcus infection. ¢ Modify antibiotics according to culture and sensitivity results. * Monitor patient: temperature (fever may take 1 week to resolve), changing murmur and cardiac symptoms, urine, ESR, renal function, echocardiogram. 3. What are the common pathogens causing infective endocarditis? e Streptococcus viridans (dental sepsis), Streptococcus bovis (exclude cancer of colon), and staphylococcus (main-lining drug addicts or indwelling catheters) and Gram negative organ- isms (gynaecological causes or after urinary catheterization). 4. What are the diagnostic criteria for rheumatic fever? « Carditis, subcutaneous nodules, chorea, arthritis, and erythema marginatum are major Jones criteria. Minor criteria include fever, raised ESR, and prolonged PR interval on ECG. Evidence of recent streptococcal infection is an important clue. 5. What is the relationship of the febrile episode (in childhood) to this admission? Febrile illness in childhood could represent an episode of rheu- matic fever. 6. What is the cause of haematuria in infective endocarditis? * Emboli, glomerulonephritis, and history of urinary catheterization. 7. What are the problems with high-dose penicillin? * Allergy, anaemia, encephalopathy, potassium overload. 8. What is the significance of the serum being positive for rheumatoid factor? * A manifestation of immune complex phenomena.

Case 2.5 Cardiology 33 2.5 A patient with high blood pressure (malignant hypertension) History A 30-year-old man with no known history of hypertension pre- sented with acute onset of chest pain at rest and was found to have a blood pressure of 230/140 mmHg in the accident and emergency department. He gave no history of nocturia, paroxysmal headache, palpitations or sweating. There was no angina pectoris, heart failure, or history of cerebrovascular disease. He smoked 1 packet of cigarettes a day for 10 years and drinks beer on occasion. His father had hypertension at the age of 70. Physical examination Blood pressure was equal in both arms and the pulse was 80 per minute—regular and of normal volume and character. All peripheral pulses were present and there was no radio-femoral delay. Jugular venous pressure was not elevated and no periph- eral oedema was present. The apex was not displaced. The aortic second heart sound was loud and there were no basal crack- les. Liver was not palpable and there were no carotid or renal bruits. Fundoscopy showed arteriovenous nipping, soft “cotton wool” exudates, and flame-shaped haemorrhages, and the optic disc was pink and swollen with blurred margins. Neurological examination was normal. Questions 1. What investigations will you perform on this patient? « Urine should be tested for protein, blood, and glucose, and an ECG to detect left ventricular hypertrophy and myocar- dial infarction. Chest X-ray to detect cardiomegaly and heart failure. Blood tests are needed to determine renal function, fasting glucose, lipids, and cardiac enzymes. Ultrasound of kidneys and Doppler examination of renal arteries and an

34 Problem-Based Medical Case Management Case 2.5 echocardiography to assess left ventricular mass and func- tion should be considered. It is advisable to measure 24-hour urinary protein and creatinine (in those having abnormal dipstix findings or elevated creatinine). In patients aged < 40 years, consider measuring urinary vanillyl mandelic acid (especially in the presence of other congenital abnormalities or a history of familial endocrine tumours), cortisol, and renin aldosterone levels. Patients with either neurological signs or papilloedema usually require a computer tomogram or MRI scan of the brain. 2. What are the causes of hypertension? * 10% have secondary causes such as renal or endocrine dis- eases (Cushing’s, Conn’s, phaeochromocytoma, acromegaly), anatomical causes (coarctation, renal artery stenosis), sleep apnoea, and drugs (steroids). ¢ 90% are primary, with no single cause identifiable. There is usually a combination of genetic (family history) and environ- mental factors (overweight, excessive salt or alcohol, lack of exercise). 3. What is malignant hypertension? * Severe elevation of blood pressure (> 220/120 mmHg) along with fundal haemorrhage and/or papilloedema occurs in about 1% of all hypertensive patients. Target organ damage occurs in the brain, heart, and kidneys. * Brain: there is loss of autoregulation with dilatation of arteri- oles, causing cerebral oedema which manifests as hypertensive encephalopathy, with headache, nausea, decreased conscious- ness, and convulsions. * Heart: left ventricular hypertrophy, angina, myocardial infarc- tion, and heart failure. ¢ Kidney: proteinuria, microscopic haematuria, red blood cell casts, and renal failure. 4. How do you determine whether renal disease is responsible for hypertension or vice versa? ° History or an investigation suggestive of pre-existing renal disease is helpful, but usually, whether renal disease or

Case 2.5 Cardiology 35 5. by hypertension developed first is difficult to ascertain. Ultrasound showing bilateral small kidneys is suggestive of chronic paren- chymal disease. In patients suspected to have a treatable renal disease, a biopsy may be performed. What are the histological findings of renal disease induced hypertension? Nephrosclerosis: macroscopically, the kidneys are shrunken and scarred. Microscopically, there is obsolescence of glo- meruli, interstitial fibrosis, arterial intimal fibroplasia, and hya- linization in small arteries. The histological appearances are not specific to hypertension-induced kidney disease. . What is the treatment of malignant hypertension? Malignant hypertension is a medical emergency and requires hospital admission and immediate lowering of blood pressure. Oral treatment such as beta-blocker, diuretics, calcium blocker, and angiotensin receptor blocker can be used. Intravenous therapy is indicated for some cases, when com- plicated by aortic dissection, encephalopathy, heart failure, and pre-eclampsia. Nitroprusside or labetalol can be given as an intravenous infusion. Labetalol must be given with caution if left ventricular function is poor and is contraindicated in asthma. Phentolamine is given in phaeochromocytoma because alpha-blockade is essential. Hydralazine is given for pre-eclampsia. Blood pressure must be lowered in a controlled manner; too rapid reduction in blood pressure may result in cerebral infarction. Fluid balance must be carefully managed to avoid either hypo- volaemia or overload. When should you refer to a specialist? Patients with secondary hypertension, young hypertensive (e.g., < 40 years), persons suspected to have secondary hypertension who are not overweight, have no family history of hypertension, as well as patients in whom severe hypertension was difficult to control could benefit from specialist referral.

36 Problem-Based Medical Case Management Case 2.6 Pitfalls and tips ¢ Very high systolic blood pressures can be missed if the cuff is not inflated to exceed the systolic blood pressure. Measure with palpation method first. « In a female patient, pre-eclampsia in pregnancy needs to be excluded. * In contrast to malignant hypertension, uncomplicated hyperten- sion is asymptomatic. There are no symptoms characteristic of hypertension, but untreated hypertension can lead to compli- cations such as stroke, myocardial infarction, and cardiac and renal failure. ¢ Blood pressure fluctuates, so multiple readings are needed. » Ambulatory blood pressure and home blood pressure readings complement clinic readings. « Compliance may be a problem when multiple medications are needed to control blood pressure, and poor compliance leads to poor blood pressure control. 2.6 Advice on pregnancy (mitral stenosis) History A 32-year-old woman was noted to have an International Normalized Ratio (INR) of 5.5 during a routine follow-up for chronic rheumatic heart disease. She was diagnosed as having mitral stenosis ~10 years earlier. After a transient episode of right-sided weakness and slurring of speech 3 years ago, she was started on warfarin treatment. She did not notice any bleeding in the few days prior to her clinic visit. She denied altered compli- ance to warfarin, recent concomitant drug use, and major changes in her diet intake. She also reported a stable exercise capacity of about 3 flights of stairs. There was no gum bleeding, haemopty- sis or melaena. Five years ago, she had a normal pregnancy and delivered a girl without complications. She and her husband were planning for a second child.

Case 2.6 Cardiology 37 Physical examination A large bruise was noted in the right antecubital fossa where venepuncture had been performed. Her pulse was irregularly irregular at 82 per minute. The blood pressure was 125/85. The jugular venous pressure was not elevated. The apex was in the 5th intercostal space at the mid-clavicular line and had a tapping quality. There was a mild left parasternal heave. The first heart sound was loud and an opening snap was audible. The pulmonic second sound was accentuated. A grade 3/6 mid-diastolic murmur was heard over the apex. All other systems were normal. Investigations Chest X-ray showed evidence of left atrial and right ventricular enlargement. Electrocardiogram showed atrial fibrillation with a ventricular rate of 86/min. Echocardiography revealed pliable and non-calcified mitral valve leaflets consistent with rheumatic valve disease. The mitral valve area and systolic pulmonary arte- rial blood pressure were estimated to be 1.2 cm’ and 55 mmHg, respectively. Questions 1. What should be the appropriate management of this woman with a high INR? * For patients with INR greater than the therapeutic range by 0.5 but < 5.0 and without significant bleeding, lower the dose or omit a dose and resume therapy at a lower dose when the INR approaches the desired range. e If the INR is between 5 and 9 and there is no bleeding, the next 1 or 2 doses of warfarin can be omitted. Recheck INR in 2-3 days’ time. Therapy can be restarted at a lower dosage when the INR is within the therapeutic range. If the patient is at increased risk of bleeding (e.g., active gastric ulceration, prior cerebral haemorrhage), the next dose of warfarin is omitted and vitamin K, 1-2.5 mg can be given orally.

38 Problem-Based Medical Case Management Case 2.6 » If the INR is > 9, or there is significant bleeding, vitamin K, 3-5 mg should be given orally and repeated as necessary. Wartfarin can be resumed at a Jower dose when the INR reaches the therapeutic level. ¢ In situations of serious bleeding or INR > 20, infusion of fresh frozen plasma supplemented with slow intravenous infu- sion of 10 mg vitamin K, should be administered. Additional vitamin K, may be given at 12-hour intervals. For this patient, warfarin should be stopped, INR checked in 2 days, and warfa- rin reinitiated at a reduced dose. 2. The patient desires to have a planned pregnancy. What advice can you offer to her regarding anticoagulant therapy? » Warfarin crosses the placenta and can give rise to embryopa- thy, central nervous system abnormalities, and foetal bleed- ing if there is first-trimester exposure. Heparin does not cross the placenta and is the preferred anti-coagulant in pregnant women. However, there have been reports on heparin (both unfractionated and low-molecular-weight) failure leading to serious maternal complications in patients with mechanical heart valves. Different options exist but the following seems to be most widely practised: unfractionated (or low-molecular- weight heparin, less data) in the first trimester, switching to warfarin in the second trimester until ~38-week gestation, then changing to unfractionated or low-molecular-weight heparin with planned labour at ~40 weeks. 3. What effects will pregnancy have on the cardiac status of this patient and what are the therapeutic options? * A majority of patients with moderate to severe mitral stenosis exhibit worsening of 1 or more New York Heart Association classes during pregnancy, secondary to physiological increase in heart rate and blood volume, decreased serum colloid osmotic pressure, and increased propensity to atrial arrhythmias from increased left atrial pressure. * The therapeutic approach during pregnancy should aim to reduce the heart rate and decrease the left atrial pressure. This can be achieved by restricting physical activities and administering beta-blockers. Digoxin is useful in controlling ventricular rate

Case 2.6 Cardiology 39 in atrial fibrillation. Blood volume can be reduced by restriction of salt intake and judicious use of oral diuretics. o Mitral valve repair or replacement during pregnancy should be considered only in cases with severe mitral stenosis (mitral valve area < 1.0 cm?) refractory to optimal medical manage- ment. The chance of foetal wastage is high. There have been increasing reports on the use of percutaneous balloon mitral valvuloplasty in pregnant patients with mitral stenosis. In the majority, improvement is achieved without adverse effects on the mother or foetus. For this patient, the mitral stenosis is of moderate severity, but there is evidence of pulmonary hyperten- sion. However, her exercise capacity seems to be stable. In this case, pursuing medical therapy with a fall-back to percutaneous balloon mitral valvuloplasty in the 2nd trimester of pregnancy can be offered.