658 CHAPTER 14 Cardiovascular disease HIV and the cardiovascular system The clinical effects of HIV on the heart are relatively u ncommon, relative to the impact of HIV infection on the lungs, gastrointestinal tract, cent ral nervous system, and skin. There are similarities in the pattern of CVD involvement in p eople living in developed and less-developed countries, but differences in the causative or ganisms implicated. The main presen- tations are (1) pericardial effusion; (2) cardiomyopat hy; (3) pulmonary hypertension; (4) large vessel aneurysms; and (5) metabolic complications associated with anti-retroviral drug use. Pericardial effusion Pericardial effusion is one of the early presenting features of HIV in fection in patients living in sub-Saharan Africa. Whereas in western countries, a large eff usion is usually idiopathic in 80 % of patients with acquired immune de \201 ciency syndro me (AIDS), the disease is caused by tuberculosis in over 80 % of Africans living with HIV. Purulent pericarditis is not uncommon, while involvement with Kaposi \200\231s sarcoma and B-cell lymphoma is rare. Treatment of tuberculous pericarditis is with a standard anti-tube rculous regime similar to that used in HIV-negative patients, and the short-term outcome is similar. The role of adjuvant steroids is uncertain. Cardiomyopathy Cardiomyopathy is found in 50 % of acutely ill hospitalized patients, and in 15 % of ambulatory asymptomatic patients living with HIV. Myocarditis is present in a prop ortion of the cases. In western series, the myocarditis is associated with cardiotropic vir us, whereas in Africa, preliminary data suggest that it may be associated with non-viral op portunistic infections such as toxoplasmosis, cryptococcosis, and Mycobacterium avium intra cellulare infection. HIV-positive patients with cardiomyopathy should be considered for end omyocardial biopsy to exclude a treatable cause of myocarditis. Otherwise, treat as for hea rt failure. Prognosis is poor, with a median survival of 100 days without anti-retroviral d rugs. Pulmonary hypertension HIV-associated pulmonary hypertension is estimated to be 1/200, much higher than the 1/200 000 found in the general population. Primary pulmonary hypertension is found in 0.5 % of hospitalized AIDS patients and is a cause of cor pulmonale and death. The pathogenesis is poorly understood. Arterial aneurysm HIV-related arterial aneurysm is a distinct clinical and pathological ent ity that is associated with advanced HIV disease. HIV-related aneurysms affect young patien ts (median age 30 years) with no risk factors for atheroscle- rosis, occur mainly in periph eral arteries (carotid, distal super \201 cial femoral, and popliteal sites), are usually multiple (1 \200\22310 per patient), and have been reported more frequently in black patien ts than in white individuals. The in \202 ammatory process involves the vasa vasorum of th e adventitia with sparing of the media and intima. The most frequent mode of presentation i s that of a painful mass of increasing size. The diagnosis is con \201 rmed by HIV AND THE CARDIOVASCULAR SYSTEM 659 duplex sonography or computed tomography (CT). Arterial angiography is performed to delinea te the extent of aneurysm. Serological testing for syphilis, typhoid, HIV, and autoimmune d isease is indicated. Treatment is by operative intervention for symptomatic aneurysm in pat ients with an acceptable surgical risk and anticipated life expectancy. Metabolic abnormalities The use of protease inhibitors and nucleoside reverse transcriptase inhibitors is associated with the following metabolic abnormalities: fat redistribution (l ipodystrophy), increased total cholesterol and triglycerides, decrease in high-density lipo protein (HDL), impaired glucose tolerance, and increased intra-abdominal fat. These changes translate into a small increase in the risk of myocardial infarction (MI) with the long-te rm use of anti-retroviral drugs. It is prudent to modify cardiovascular risk factors and tr eat the metabolic complications when they arise, according to standard guidelines in affect ed patients. 660 CHAPTER 14 Cardiovascular disease Chagas \200\231 disease and the heart Chagas \200\231 disease is a myocarditis of parasitic origin that is caused by the protozoa Trypanosoma cruzi . The disease is a major public he alth problem in South and Central America; 15 \200\22318 million people are infected with t he parasite, and 65 million people are at risk. Chagas \200\231 disease is transmitted by c ontamination of the bite wound of the \200\230assassin \200\231 or \200\230kissing \200 \231 reduviid bugs with the infected feces of the insect. Natural history The natural history of Chagas \200\231 disease is characterized by three ph ases: acute, latent, and chronic. Acute Chagas \200\231 disease occurs predominantly in chi ldren in less than 10 % of infected cases; it is fatal in 10 % of cases. It is characterize d by fever, lymphadenopathy, hepatosplenomegaly, and facial oedema. Acute myocarditis is co mmon and may be fatal. Rarely, menin- goencephalitis or convulsive seizures may occur, some times causing per- manent mental or physical defects or death. Recovery is usual, however, and the disease is quiescent for the next 10 to 15 years ( latent Chagas \200\231 disease ) . Chronic Chagas \200\231 disease may be asymptomatic, mild, or accom- panied by cardiomyop athy, megaoesophagus, and megacolon, with a fatal outcome. The late manifestations probably result from lymphocyte- mediated destruction of muscle tissue and nerve ganglions during t he acute stage of the disease. Trypanosoma cruzi may be found in degener- ated muscle cells , especially in the right atrium. The disease is characterized clinically by anginal chest pain, symptomatic conduction syste m disease; severe, protracted, congestive cardiac failure, often predominantly right sided, is the rule in advanced cases. Bifascicular block is present in more than 80 % of cases an d death from asystole and arrhythmia is common. Autonomic dysfunction is common. Apical ane urysms and left ventricular dilatation increase the risk of thromboembolism and arrhythmias . Diagnosis Chagas \200\231 disease is identi \201 ed by demonstration of trypanosomes in th e peripheral blood or leishmanial forms in a lymph node biopsy, or by animal inoculation or culture, xenodiagnosis (i.e. the patient is bitten by reduviid bugs bred in the laboratory ; the subsequent identi \201 cation of parasites in the intestine of the insect is proof o f infection in the human host), or sero- logic tests (e.g. Machado \200\223Guerreiro comple ment \201 xation test). The chest X-ray (CXR) demonstrates cardiomegaly. The ECG is abnor mal as a rule in the late course of the disease. The echocardiographic features in advanced cases are those of dilated cardiomyopathy; a left ventricular posterior wall hypokinesis a nd relatively preserved interventricular septum motion, associated with an apical aneurysm is distinctive. Radionuclide ventricu- lography may show ventricular wall motion abnormalit y in the absence of overall depression of global ventricular function. Perfusion scanning w ith thallium-201 may show \201 xed defects (corresponding to areas of \201 brosis) as w ell as evidence of reversible ischaemia. Gadolinium-contrast magnetic resonance imaging (MR I) can identify patients with more active myocardial disease. CHAGAS \200\231 DISEASE AND THE HEART 661 Treatment There is no speci \201 c therapy for Chagas \200\231 disease. Prolonged administ ration of nifurtimox, a nitrofurazone derivative, may effect parasitologic cure, but chroni c organ damage is irreversible. Heart failure, arrhythmias, and thromboembolism are treated with the usual measures. Prevention Reduviid bugs, the vectors for Chagas \200\231 disease, inhabit poorly construct ed houses and outbuildings. Spraying with 5 % G -benzene hexachloride is most effective in controlling the vector. Patching wall cracks and cementing over dirt \202 oors also helps to eliminate the vectors. 662 CHAPTER 14 Cardiovascular disease Cardiovascular syphilis Cardiovascular syphilis produces thoracic aneurysm, narrowing of th e coronary ostia, or aortic valvular insuf \201 ciency that usually appears 10 to 25 years after the initial infection. Involvement of the myocardium is rare. The introduction of pe nicillin has made the disease less common, but it remains an important cause of CVD in poor populations. Coronary disease Angina pectoris, rarely MI, cardiac aneurysm, or sudden death may result f rom involvement of the coronary ostia. Aortic insuf \201 ciency is nearly always present. The condition should be suspected when angina pectoris is encountered in young men, and whe n severe angina is associated with disproportionately mild aortic insuf \201 ciency. Glyce ryl trinitrate is often less effective in relieving symptoms. Attacks of angina decubitus a re not infrequent. The diagnosis is established by positive syphilis serology and coronary angiography. Successful surgical treatment may be achieved by endarterectomy of the coronar y ostia or by bypass grafting. Aortic insuf \201 ciency The presenting symptoms may be those of coronary insuf \201 cien cy or of left heart failure. The physical signs are the same as those of rheumatic aortic i nsuf \201 ciency. Pure insuf \201 ciency without any stenosis is the rule. Because of the unfolding and dilatation of the aorta, the murmurs are fre- quently better heard to the ri ght of the sternum. Occasionally, a musical ( \200\230cooing-dove \200\231) diastolic murmu r is produced by eversion or detachment of an aortic cusp. Syphilitic aortic aneurysm This involves the ascending aorta and the arch with equal freque ncy. Less commonly, the descending aorta is involved, and least commonly the abdominal aort a. It is not unusual for the aorta to be involved at more than one site in the same patient . Syphilitic aneurysms are usually saccular (vs. fusiform aneurysms of atherosclerosis). Sy philitic aneurysms can rupture, but never dissect. The clinical presentation is dependent o n compression of adja- cent structures and therefore varies with the portion of the aorta i nvolved. Ascending aorta aneurysms have been termed the \200\230aneurysms of signs \200\231: \200 compression of the superior vena cava (SVC) \200\224 distended non-pulsatile neck veins with oedema in their drainage area compression of the right main bronchus \200\224 lung complications \200 compression of t he right ventricular out \202 ow tract (RVOT) \200\224 signs of pulmonary stenosis erosion of the sternum \200\224 super \201 cial pulsating mass. Aortic arch aneurysms are known as the \200\230aneurysms of symptoms \200\231: \200 large airway compression \200\224 dry \200\230brassy \200\231 cough, dyspnoea \200 recurrent laryngeal nerve comp ression \200\224 hoarseness \200 oesophageal compression \200\224 dysphagia \200 comp ression of the sympathetic chain \200\224 Horner \200\231s syndrome \200 erosion of the vertebrae and compression of nerves \200\224 deep-seated continuous bone and root pain. CARDIOVASCULAR SYPHILIS 663 An aneurysm may be suspected clinically by unequal pulses and blood pressures in the upper limbs or by the presence of a tracheal tug. Not infrequently, an aneurysm is \201 rst det ected by CXR, and must be distin- guished from other masses. Linear calci \201 cation of t he aneurysmal sac and expansile pulsation on \202 uoroscopy are helpful signs when presen t. Aortic angiography is required for diagnosis. Treatment Benzathine penicillin G should be given in doses of 2.4 million units weekly for three successive weeks. When there is penicillin allergy, tetracycline 500 mg four times pe r day for 1 month may be administered. 664 CHAPTER 14 Cardiovascular disease Beri-beri (thiamine de \201 ciency) The coenzyme thiamine pyrophosphate (TPP) participates in carbohydrate metabolism through decarboxylation of A -keto acids. Thiamine also acts as a coenzyme to the apoenzyme transketolase in the pentose monophos- phate pathway for gluco se. Thiamine de \201 ciency may produce dry or wet beri-beri. Dry beri-beri manifests with peripheral neurologic and cerebral disturbances. The wet form is associated with cardiovas cular manifestations. Etiology Primary thiamine de \201 ciency arises from inadequate intake, particularly in pe ople subsisting on highly polished rice (e.g. in the Far East). Milling removes the husk, w hich contains most of the thiamine. Secondary thiamine de \201 ciency arises from (1) increased requirement, as in hyperthyroi dism, pregnancy, lactation, and fever; (2) impaired absorption, as in long-continued diarrh ea; (3) impaired utilization, as in severe liver disease; and (4) increased urinary excreti on, as in chronic furosemide therapy. A combination of decreased intake, impaired absorptio n and utilization, increased requirements, and possibly apoenzyme defect occurs in alcoholi sm. Highly concentrated dextrose infusions, coupled with low thiamine intake, may precipita te thiamine de \201 ciency. Cardiovascular (wet) beri-beri Cardiovascular (wet) beri-beri takes 2 forms \200\224 the m ore common high- output state or the rare low-output state ( Shoshin disease ). In the form er, before heart failure supervenes, there is tachycardia, a wide pulse pres- sure, sweatin g, and a warm skin. With heart failure, orthopnoea, pulmo- nary and peripheral oedema, and peripheral vasoconstriction causing cold and cyanosed extremities occur. Severe hypotension , lactic acidosis, very low systemic vascular resistance, and absence of oedema characteriz e the low-output state (Shoshin disease). In the latter, death occurs within a few hours or days, unless appropriate treatment is given. Even after several episodes of cardiovascular beri-beri, permanent myocardial damage is extremely rare. Infantile beri-beri Infantile beri-beri occurs in infants breast-fed by thiamine-de \201 c ient mothers, usually between the 2nd and 4th month of life. Cardiac failure, aphonia, and absent deep tendon re \202 exes are characteristic. Clinical features The diagnosis of beri-beri should always be considered in any case of hea rt failure in an alcoholic where the cause is not readily apparent. Neurologic symptoms suc h as paraesthesiae and weakness because of peripheral neuropathy, and Wernicke \200\231s en cephalopathy are occasionally present. Signs of a hyperkinetic circulatory state are manifested by warm hands, tachycardia, collap sing pulses, and raised jugular venous pressure (JVP). A wide pulse pressure with systolic hypertension is commonly found, but occasionally diastolic hypertension is also present ini tially, so that hypertensive BERI-BERI (THIAMINE DEFICIENCY) 665 heart failure may be suspected. The heart is almost invariably enlarged, with a gallop rhyt hm. Atrioventricular regurgitant murmurs may be present, and tricuspid insuf \201 ciency i s particularly common. Occasionally, right-sided heart failure dominates the clinical pictu re and there is disproportionate oedema and hepatomegaly. In Shoshin beri-beri, there is se vere heart failure with low cardiac output, orthopnoea, systemic congestion, and oliguria. The ECG \201 ndings are of crucial value in diagnosis. The most common \201 nding is a normal tracing, or one demonstrating right-axis deviation with clockwise rotation, when the patient is most severely ill. Less commonly, the initial ECG shows T-wave inversion over t he left or right ventricular precordial leads. In either event, daily tracings will show se rial changes, over either the right ventricle or left ventricle, or both. Thus, when the pa tient has apparently recovered completely, the ECG may actually be at its worst, showing ex pansive and deep T-wave inversion. The abnormal changes may persist for 24 hours, days, or even weeks following recovery, but complete return to normal is the rule. CXR: Radiologically, equally striking serial changes occur. Marked cardio- megaly with a pr ominent right ventricular out \202 ow and hilar congestion rapidly returns to normal in a week or two following appropriate treatment. Laboratory \201 ndings: Erythrocyte transketolase activity is diminished before and incre ases after the addition of thiamine pyrophosphate (TPP effect); a TPP effect > 15 % suggest s thiamine de \201 ciency. The blood sample must be taken in a heparin-coated vial, before administration of thiamine, and transported to the laboratory on ice. Elevated blood pyruv ate and lactate, and diminished urinary thiamine excretion (<50 g/day) are also found. Treatment Treatment is with thiamine 50 \200\223100 mg IV or IM immediately, and repeated d aily for 1 \200\2232 weeks. The response to thiamine is usually prompt and com- plete. Mark ed diuresis, decrease in heart rate and size, and clearing of pulmonary congestion may occu r in 12 to 48 hours. However, sudden death from pulmonary oedema may occur, so that it is p rudent to treat with digitalis and diuretics at the outset. 666 CHAPTER 14 Cardiovascular disease Tetanus Tetanus is caused by the endotoxin (tetanospasmin) from the anaerobic organism Clos tridium tetani . The portal of entry is usually a severe or untreated wound, often a neglec ted burn or, occasionally, a septic incom- plete abortion. In a few cases (15 \200\22330 % ), the portal of entry is never isolated. Public health immunization programs with tetanus toxoid have dramati- cally reduced the incidence of neonatal tetanus in many parts of the w orld, but there is still a signi \201 cant number of cases in adults. Features of special importance in the history are the period from injury to onset of sympto ms and the time interval between the onset of stiffness to the onset of spasms. In general, the shorter the period from injury to onset of symptoms and the shorter the time interval between symptoms and spasms, the more severe the tetanus will be. The most useful classi \201 cation of tetanus is simply: mild \200\224 stiffness and mild spasms \200 moderate \200\224 stiffness and/or spasms with dysphagia \200 severe \200\224 severe recurrent spasms and dysphagia autonomic overactivity. Sympathetic overactivity remains the major cause of death in patients with tetanus once ear ly deaths from respiratory obstruction and the deaths from mechanical failure have been eli minated. The syndrome of sym- pathetic overactivity results in tachycardia, marked \202 u ctuation of blood pressure (i.e. both hypotensive and hypertensive changes), excessive sali - vation, and sweating. This \202 uid loss may result in dehydration. The effect on the h eart can give rise to MI. A treatment approach that involves the use of extremely heavy sedation with intermittent po sitive pressure ventilation has proven to be successful in reducing mortality to 6 % in the authors \200\231 practice. RESTRICTIVE CARDIOMYOPATHY 667 Keshan disease Selenium is involved in the reoxidation of reduced glutathione and has close metabolic interrelationships with vitamin E. It is part of the enzyme glutathione peroxida se, which is thought to destroy peroxides derived from unsaturated fatty acids. De \201 ci ency has occurred in patients on long- term parenteral feeding. Several cases of fatal card iomyopathy have been attributed to selenium de \201 ciency. In China, a childhood cardiomy opathy known as Keshan disease, after the province in which it has been studied, has been a ttributed to selenium de \201 ciency and protection claimed for pro- phylactic dosing with 150 g selenium/day as selenomethionine. Selenium levels have also been found to be low in some patients with HIV-associated cardiomyopathy, with a response to selenium supplement ation. Restrictive cardiomyopathy Restrictive cardiomyopathy (which is discussed elsewhere in this book) is divided into a diffuse non-obliterative variety (e.g. amyloidosis, haemo- chromat osis) and an obliterative variety in which the endocardium and subendocardiun are \201 br osed (e.g. endomyocardial \201 brosis). Variants of restrictive obliterative cardiomyopat hy occur in temperate zones, described as Loef \202 er endocarditis , and in the tropical rainforest regions as endomyocardial \201 brosis (EMF) . Tropical EMF affects children in very low socio-economic groups; it is not restricted to speci \201 c racial groups, as Eu ropeans living in the tropics have also been affected. It has been suggested that Loef \202 er endocarditis and tropical EMF are part of a contin uum of the same disease, commencing with hypereosino- philia of whatever cause, resulting i n myocardial damage in three stages: a necrotic phase (eosinophilic myocarditis with arteri tis i.e. Loef \202 er endo- carditis) for the \201 rst few months of illness; a thrombot ic phase with early thickening of the myocardium with thrombosis after about 1 year of pre- sentation; and the late stage of \201 brosis (i.e. EMF). However, there are differences in the clinical presentation of tropical EMF and Loef \202 er endo- carditis: i.e. geograp hic, age (Loef \202 er endocarditis affects middle-aged men vs. tropical EMF which affects young people and children), pattern of ventricular involvement (tropical EMF affects mainl y right ventricle vs. Loef \202 er endocarditis affects either ventricle), and link with e osinophilia (Loef \202 er is associated with hypereosinophilia vs. link of tropical EMF wi th eosinophilia, which has not been established). 668 CHAPTER 14 Cardiovascular disease Endomyocardial \201 brosis Pathophysiology Fibrous tissue and the chordae adherent to the ventricular wall may bind down the papillary muscle. In the extreme stage, when there is o blitera- tive cardiomyopathy, the cavity of the ventricle is occupied entirely by \201 br ous tissue and superimposed thrombus. The disease may involve either or both ventricles and be complicated by pericarditis, with effusion and high diastolic pressure giving rise to p ulmonary and systemic venous congestion with AV valve incompetence. Symptoms and signs Typically, symptoms are suggestive of congestive cardiomyopathy, but sig ns resemble constrictive pericarditis. Like congestive cardiomyopathy, patients present wit h dyspnoea, orthopnoea, and peripheral oedema. Like constrictive pericarditis, pulsus parad oxus, a raised JVP with rapid \200\230x \200\231 and \200\230y \200\231 descents, an earl y third heart sound, hepatomegaly, and ascites are present. In contradistinction to constri ctive pericarditis, however, there is frequently a murmur of tricuspid and/or mitral regurg itation. Chronic, severe tricuspid regurgitation that is often seen in right-sided endomyoc ardial \201 brosis may cause bilateral proptosis. Diagnosis ECG is usually non-speci \201 cally abnormal, showing low-voltage QRS com- plexe s and ST \200\223T wave abnormalities, and may indicate right atrial enlarge- ment in the f orm of tall peaked P waves. CXR may demonstrate an enlarged cardiac silhouette similar to a pericardial effusion. Echocardiography shows increased ventricular wall thickness cavity o bliteration, and enlarged atria, with or without a small pericardial effusion. Cardiac cath eterization dem- onstrates the combination of restricted \201 lling and incompetence of t he AV valves. The right atrial pressure is elevated, with prominent systolic waves and stee p \200\230x \200\231 and \200\230y \200\231 descents. In severe obliterative cases, the p res- sures in the right atrium, right ventricle, and pulmonary arteries may be identical, a nd an intracardiac ECG may be required to locate the position of the tricuspid and pulmonar y valves. A dip and plateau ( \200\230square root \200\231) type of pressure pulse is frequ ently present in both ventricles. Ventriculography shows an enormously dilated right atrium and obliteration of the right ventricular apex. Endomyocardial biopsy of the right ventric le may be useful, by demonstrating an excess \201 brous tissue, a \201 nding that is hi ghly suggestive of endomyocardial \201 brosis. The distinguishing clinical, echocardiogra phic, and haemodynamic features between restrictive cardiomyopathy and constrictive pericar ditis are discussed under the section on constrictive pericarditis. However, in those forms of this syndrome where signi \201 cant cardiomegaly is absent, a distinction from constri ctive pericarditis may be impossible. The only means of making a diagnosis is then explorat ory thoracotomy . ENDOMYOCARDIAL FIBROSIS 669 Prognosis and treatment There is no speci \201 c treatment for endomyocardial \201 brosi s, and prognosis is poor (35 \200\22350 % 2-year mortality). Diuretics must be used with ca ution because of their ability to lower the preload upon which the non-compliant ventricles depend to maintain cardiac output. Digitalis is helpful in patients with atrial \201 bri llation. Afterload reducers may induce profound hypoten- sion, and are usually of no value. Operative excision of the \201 brotic endo- cardium ( endocardial resection ) and replac ement of one or both AV valves may lead to symptomatic improvement, but is associated with a high peri- operative mortality (15 \200\22325 % ) and no survival bene \201 t. Cardiac t ransplanta- tion is the de \201 nitive treatment for EMF. 670 CHAPTER 14 Cardiovascular disease Loef \202 er endocarditis Marked eosinophilia of any cause may be associated with endomyoc ardial disease. but the cause of eosinophilia in most patients with Loef \202 er endocar- ditis is unknown. The typical patient is a man in his 4th decade who lives in a temperate c limate and has the hypereosinophilic syndrome (i.e. persistent eosinophilia with (cid:116) 1500 eosiniphils/mm 3 for at least 6 months or until death, with organ involvement). Pathology Multi-organ disease involving the heart, lungs, bone marrow, and brain. Cardiac i nvolvement is often biventricular, with mural endocardial thickening of the in \202 ow por tions and apex of ventricles. There are histological features of eosinophilic myocarditis, mural thrombosis, and \201 brotic thickening of the endocardium. Symptoms and signs Constitutional symptoms (fever, weight loss), cough, and rash. Overt sym ptoms and signs of congestive heart failure are found in 50 % of patients. Cardiomegaly and the murmur of mitral regurgitation may be found even in patients without cardiac symptoms. Systemic embolism is frequent. Death is usually due to cardiac failure, often associated w ith renal, hepatic or respiratory failure. Diagnosis ECG most commonly shows non-speci \201 c ST \200\223T-wave changes, but atrial \201 brillation and right bundle branch block are common. CXR may reveal cardiomegaly and pulmonary congestion or pulmonary in \201 ltrates. Echocardiogram shows localized thickeni ng of the posterobasal left ven- tricular wall, with limited or absent motion of the poster ior lea \202 et of the mitral valve; enlarged atria, atrioventricular valve regurgitation; and usually preserved systolic function. Cardiac catheterization reveals the haemody- nami c features of a restrictive cardiomyopathy which are indistinguishable from tropical EMF ou tlined in b Restrictive cardiomyopathy, p. 667. The diagnosis is often con \201 rmed by en domyocardial biopsy . Management Medical therapy during the course of Loef \202 er endocarditis and surgical the rapy during later phases of \201 brosis may have a positive effect on symp- toms and surv ival. Corticosteroids are indicated for acute myocarditis, and together with hydroxyurea ma y improve survival. Some non-responders have responded to interferon . Routine cardiac ther apies with diuretics, digitalis, afterload reduction, and anticoagulation are important adj uncts. Surgical therapy offers palliation of symptoms once the \201 brotic stage has been reached. LOEFFLER ENDOCARDITIS 671 Further reading Chesler E ( 1992 ). Clinical cardiology . New York : Springer-Verlag . Fala se AO , Akinkugbe OO ( 2000 ). A Compendium of Clinical Medicine . 2 nd edn. Ibadan : Spectrum Books Limited . Nair R , Robbs JV , Naidoo NG , Woolgar J ( 2000 ). Clinical pro \201 le of HIV-related an eurysms . Eur J Vasc Endovasc Surg 20 : 235 \200\223 40 . Ntsekhe M , Mayosi BM ( 2009 ). Cardiac manifestations of HIV infection \200\224 the Afric an perspective . Nature Rev Cardiol 6 : 120 \200\223 27 . Potgieter PD ( 1990 ). Tetanus . In Potgieter PD , Linton DM , eds. Intensive Care Manual . Cape : CTP Book Printers , pp 99 \200\223 103 . Reddy KS ( 2002 ). Global perspective on cardiovascular disease . In S Yusuf , JA Cairns , AJ Camm , EL Fallen , BJ Gersh . Evidence-based Cardiology . London : BMJ Books , pp 91 \200\223 102 . Berkow R , Fletcher AJ ( 1987 ). The Merck Manual of Diagnosis and Therapy . Rahway : Merck Sharp & Dohme Research Laboratories . Wynne J , Braunwald E ( 2001 ). The cardiomyopathies and myocarditides . In Braunwald E , Z ipes DP , Libby P (eds). Heart Disease: a textbook of cardiovascular medicine . London : WB Saunders Company , pp 1751 \200\223 806 . This page intentionally left blank 673 Chapter 15 Heart disease in pregnancy Basic principles 674 Physiological changes in pregnancy 676 Normal \201 ndings in pregnan cy 678 General considerations in pregnancy 680 Pulmonary hypertension and pregnancy 682 Mar fan syndrome and pregnancy 683 Valvular heart disease in pregnancy 684 Mitral stenosis and pregnancy 686 Other valve lesions 687 Mechanical heart valves in pregnancy 688 Ischaemic he art disease 690 Hypertrophic cardiomyopathy 691 Peripartum cardiomyopathy 692 Arrhythmias i n pregnancy 694 Cardiac arrest in pregnancy 696 Endocarditis prophylaxis 696 674 CHAPTER 15 Heart disease in pregnancy Basic principles Cardiac disease in pregnancy is rare in the UK, Europe, and the devel- ope d world, but common in developing countries. In the UK, rheumatic heart disease is now extr emely rare in women of childbearing age and is con \201 ned to immigrants. Women with cong enital heart disease, having undergone corrective or palliative surgery in childhood, survi ve into adult- hood, and are encountered more frequently. These women may have complicated pregnancies. Women with metal prosthetic valves face dif- \201 cult decisions regarding a nticoagulation in pregnancy. Ischaemic heart disease (IHD) is becoming more common in pregn ancy, as the mean age of pregnancy increases and the smoking epidemic continues. Dissection of the aorta and its branches occurs more commonly in pregnancy, and pregnancy may cause a speci \201 c dilated cardiomyopathy \200\224 peripartum cardiomyopathy. Despite its relative rarity, cardiac disease is the leading cause of maternal death in the UK, being responsible for 48 deaths in the three years 2003 \200\2232005 inclusive. 1 The p redominant cardiac causes of maternal death in the UK are peripartum cardiomyopathy, myocar dial infarction (MI), and dissection of the aorta and its branches. Because of signi \201 cant physiological changes in pregnancy, symptoms such as palpitatio ns, and signs such as an ejection systolic murmur are very common and innocent \201 nding s. The care of the pregnant and parturient woman with heart disease requires a multidiscipl inary approach and formulation of an agreed and documented management plan encompassing man agement of both planned and emergency delivery. This chapter will cover the most important cardiac conditions relevant to pregnancy. 1 Nelson-Piercy C (2007). Cardiac disease. In: Lewis G (ed). The Con \201 dential Enquiry into Maternal and Child Health (CEMACH). Saving mothers \200\231 lives: reviewing maternal deaths to make motherhood safer 2003 \200\2232005. The Seventh Report on Con \201 dential Enquiries into Maternal Deaths in the UK. London: CEMACH. This page intentionally left blank 676 CHAPTER 15 Heart disease in pregnancy Physiological changes in pregnancy Cardiac output increases early in pregnancy, reaching a maximum by the mid-second trimester. This is achieved by an increase in both stroke volume and heart rate. There is peripheral vasodilation, and a fall in systemic and pulmonary vasc ular resistance. Although there is no increase in pulmonary capillary wedge pressure (PCWP), serum colloid o smotic pressure is reduced. The colloid oncotic pressure \200\223PCWP gradient is reduced b y 28 % , making pregnant women particularly susceptible to pulmonary oedema. Pulmonary oede ma will be precipitated if there is either an increase in cardiac preload (such as infusion of \202 uids), or increased pulmonary capillary permeability (such as in pre-eclampsia), or both. In late pregnancy, in the supine position, pressure of the gravid uterus on the inferior ve na cava (IVC) causes a reduction in venous return to the heart and a consequent fall in str oke volume and cardiac output. Turning from the lateral to the supine position may result i n a 25 % reduction in cardiac output. Pregnant women should therefore be nursed in the left or right lateral position wherever possible. If the mother has to be kept on her back, the pelvis should be rotated so that the uterus drops forward, and cardiac output as well as u teroplacental blood \202 ow are optimized. Reduced cardiac output is associated with redu ction in uterine blood \202 ow and therefore in placental perfusion; this can compromise the fetus. Labor is associated with further increases in cardiac output (15 % in the \201 rst stage and 50 % in the second stage). Uterine contractions lead to auto transfusion of 300 \200 \223500 mL of blood back into the circulation, and the sympathetic response to pain and anx iety further elevates heart rate and blood pressure. Cardiac output is increased more durin g contractions but also between contractions. Following delivery, there is an immediate rise in cardiac output due to the relief of IVC o bstruction, and contraction of the uterus that empties blood into the systemic circulation. Cardiac output increases by 60 \200\22380 % , followed by a rapid decline to pre-labor val ues within about one hour of delivery. Transfer of \202 uid from the extravascular space increases venous return and stroke volume further. Those women with cardiovascular compromi se are therefore most at risk of pulmonary oedema during the second stage of labor and the immediate post-partum period. See Fig. 15.1. PHYSIOLOGICAL CHANGES IN PREGNANCY 677 Physiological changes in the cardiovascular system in pregnancy i Cardiac output 40 % i Stroke volume i Heart rate 10 \200\22320 beats per minute d Blood pressure First and second trimester l Third trimester l Central venous pressure l Pulmonary capillary wedge pressure (PCWP) d Systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) 25 \200\22330 % d Serum colloid osmotic pressure 10 \200\22315 % ) n m i ) l ) l m m / l ( ) m p b ( ( ( t u p t u o c a t r d a r e a H C 3750 90 90 8 e m u o v e m u o v l e t a r l a m s a l P e k o r t S i Plasma volume 3500 3250 80 6 3000 80 2750 70 Heart rate Cardiac output and stroke volume 2500 70 60 4 4 Non- pregnant 2250 8 12 16 20 24 28 32 36 Post- delivery Gestation (weeks) Fig. 15.1 Physiological changes in pregnancy. Systemic and pulmonary vascular resistance fa ll during pregnancy. Blood pressure may fall in the second trimester, rising slightly in la te pregnancy. Note the cardiac output and stroke volume peak by 16 weeks \200\231 gestation . Reproduced with permission from Thorne SA (2004). Pregnancy in heart disease. Heart 90 : 450 \200\2236. 678 CHAPTER 15 Heart disease in pregnancy Normal \201 ndings in pregnancy On examination Findings may include: \200 bounding/coll apsing pulse \200 ejection systolic murmur (present in over 90 % pregnant women; may be quite loud, and audible all over the praecordium) third heart sound \200 relative sinus tachycardia \200 ectopics \200 peripheral oedem a. On electrocardiogaphy (ECG) These are partly related to changes in the position of the hear t: \200 atrial and ventricular ectopics \200 Q wave (small) and inverted T wave in lead III \200 ST-segment depression and T-wave inversion inferior and lateral leads \200 QR S axis leftward shift. Investigations \200 The amount of radiation received by the fetus during a maternal chest X-ray (CXR) is negligible and CXRs should never be withheld if clinically indicated i n pregnancy. Transthoracic and transoesophageal echocardiograms are also safe, with the usual precautions to avoid aspiration. Magnetic resonance imaging (MRI) is safe in pregnancy. \200 Routine investigation with el ectrophysiological studies and angiography is normally postponed until after pregnancy but should not be withheld in, for example, acute coronary syndromes. This page intentionally left blank 680 CHAPTER 15 Heart disease in pregnancy General considerations in pregnancy The heart has relatively less reserve than the respirat ory system. Women with heart disease may not be able to increase their cardiac output adequ ately to cope with pregnancy and delivery. The outcome and safety of pregnancy are related to the: presence and severity of pulmonary hypertension \200 presence of cyanosis \200 haemodyn amic signi \201 cance of the lesion \200 functional class as determined by the level of activity that leads to dyspnoea (New York Heart Association, NYHA). 1 Cardiac events such as stroke, arrhythmia, pulmonary oedema, and death complicating pregnan cies are predicted by: 2 \200 a prior cardiac event or arrhythmia \200 NYHA classi \201 cation > II \200 cyanosis \200 left ventricular ejection fraction (LVEF) <40 % \200 left heart obstruction (mitral valve area <2 cm 2 , aortic valve area <1.5 cm 2 , aortic valve gradient > 30 mmHg). Women with congenital heart disease are at increased risk of having a baby with congenital heart disease, and should therefore be offered detailed scanning for fetal cardiac anomalie s. Women with cyanosis (oxygen saturation <80 \200\22385 % ) have an increased risk of fetal g rowth restriction, fetal loss, and thromboembolism secondary to the reactive polycythaemia. Their chance of a live birth in one study was less than 20 % . 3 Women with the above risk factors for adverse cardiac or obstetric events should be managed and counseled by a multidisciplinary team, including cardiologists with expertise in pregn ancy, obstetricians, fetal medicine specialists, and pediatricians. Regular antenatal visit s and judicious monitoring to avoid or treat expediently any anemia or infection or cardiac decompensation are essential. There should be early involvement of obstetric anesthetists and a carefully documented plan for delivery. 1 McCaffrey FM, Sherman FS (1995). Pregnancy and congenital heart disease: The Magee Women \200\231s Hospital. J Mat Fet Med 4 : 152 \200\2239. 2 Siu SC, Sermer M, Colman JM, et al . (2001). Prospective multicenter study of pregnancy outcomes in women with heart disease. C irculation 104 : 515 \200\22321. 3 Presbitero P, Somerville J, Stone S, et al. (1994). Preg nancy in cyanotic congenital heart disease. Outcome of mother and fetus. Circulation 89 : 2 673 \200\2236. This page intentionally left blank 682 CHAPTER 15 Heart disease in pregnancy