The etiology of DCM is presented in Box 7.3. Symptoms Clinical presentation can be abrupt with acute pulmonary edema but more often pati ents present with symptoms of heart failure such as breathless- ness, in particular exertio nal dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and fatigue. Arrhythmias (e.g. AF, particularly with high alcohol intake) are also com- mon and patients are at risk for VT and sudden cardiac death (SCD). Diagnosis Diagnosis is established by physical examination, electrocardiography, chest X-ra y, and echocardiography (see also Box 7.4). \200 ECG may show evidence of LVH, previous myocardial infarction (MI), or arrhythmias. A sinus tachycardia is common with nonspeci \201 c T-wave changes and poor R wave in anterior ches t leads. Chest X-ray Echocardiography sizes as well as LV systolic and diastolic function a nd valvular function. There is usually biventricular dilatation with poor septal motion. Th ere may be mural thrombus in either or both ventricles. Often a small pericardial collectio n is found. Ejection fraction and fractional shortening are low. Dilatation of the ventricl es results in mitral and tricuspid regurgitation. Exercise testing oxygen consumption is us eful to assess functional capacity. Ambulatory ECG prognostically signi \201 cant ventricu lar arrhythmias. Cardiac catheterization patients with a dilated cardiomyopathy to do the f ollowing: \200 \200 \200 may show an enlarged cardiac size and pulmonary edema. allows accurate assessment of cardia c chamber with or without measurement of maximum ventilatory monitoring is essential to assess for the presence of should be performed with caution in all Exclude signi \201 cant coronary disease Assess severity of mitral regurgitation and pulmo nary artery pressures Ventricular biopsy: not routinely performed Treatment Management of DCM focuses on relieving symptoms and improving prognosis. Therapie s are designed to correct the maladaptive neuro- hormonal abnormalities involving the sympa thetic system and renin \200\223 angiotensin \200\223aldosterone axis. The management of he art failure is discussed in Chapter 5. DILATED CARDIOMYOPATHY 289 Box 7.3 Etiology of dilated cardiomyopathy Although originally considered to be idiopathic, experimental and clin- ical data now suggest that genetic, viral, and autoimmune factors p lay a role in its pathophysiology. Several genetic mutations have been identi \201 ed as the causative prob- lem in familial DCM, while certain viruses have been shown to cause sporadic cases of DCM. The following list is not exhaustive and there is some overlap with speci \201 c cardiomyopathies. \200 \200 \200 \200 \200 Inherited (may account for >25% of cases) Myocarditis (infective, autoimmune, toxic) Metabo lic (hemochromatosis, thyrotoxicosis). Nutritional (vitamin de \201 ciencies \200\224thiam ine [beriberi]) Persistent tachycardia (tachycardia-induced cardiomyopathy) DCM is essentially a diagnosis of exclusion, and potentially reversible causes, including c oronary artery disease, valvular heart disease and adult congenital heart disease, should b e sought. Careful attention should be paid to dietary history and alcohol consumption, as s ome reversibility is possible with modi \201 cation of these factors. Box 7.4 Additional investigations for DCM \200 \200 \200 \200 \200 \200 \200 Renal function Liver function tests Serum ferritin, iron, transferrin Thyroid function Vira l serology Infective screen (HIV, hepatitis C, enteroviruses) Autoantibodies CHAPTER 7 Diseases of the myocardium and pericardium 290 Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM) is characterized by maladapti ve left ventricular hypertrophy (LVH) inappropriate for the degree of afterload. Prevalence is thought to be 1 \200\2232 per 1000. The hypertrophy is classically localized to the proximal interventricular septum, resulting in a dynamic out \202 ow tract obstruction in association with systolic anterior motion ( SAM) of the mitral valve lea \202 ets (present in 35% of patients). However, there is considerable phenotypic variability and the hyper- trophy can be concentr ic, apical, or mid-cavitary, resulting in an intracavi- tary gradient (often in association with an apical aneurysm). In addition, genetic studies have demonstrated that affected fam ily members may have little or no cardiac hypertrophy despite the presence of a disease cau sing mutation (variable penetrance). The reason for this marked phenotypic variability is p oorly understood but is almost certainly multifactorial. HCM has also been associated with accessory atrioventricular pathways and conduction abnormalities in certain families. Etiology HCM is an autosomal dominant inherited cardiac condition. However, there is marked allelic and nonallelic heterogeneity with multiple mutations (more than 450) in at least 2 0 genes now identi \201 ed as causing the disease. Most of these mutations are in genes en coding proteins of the sarcomere. In contrast to mutations causing DCM, mutations frequentl y affect sar- comeric proteins involved in force generation as opposed to force trans- miss ion. This is, however, not consistent and some genes have different mutations causing both HCM and DCM. Other mutations have been found in genes encoding nonsarcomeric proteins. Histologically there is myo \201 brillar disarray and extensive \201 brosis. Small intra mural arterioles are also hypertrophied. The \201 ndings may be patchy but are concentrat ed in the septum. Subvalvular obstruction occurs between the anterior lea \202 et of the mitral valve and th e hypertrophied septum. The mitral valve apparatus moves anteriorly in systole (a combinati on of malaligned papillary muscles and Venturi effect of a high-velocity jet in the out \202 ow tract). The valve becomes thickened and mitral regurgitation occurs. Obstruction of the LV out \202 ow tract is not always present. It is possible to have asym metric septal hypertrophy (ASH) alone. Occasionally there is obstruction more evident towar d the apex rather than at the out \202 ow tract. Symptoms Patients often are asymptomatic and are increasingly picked up incidentally from t he wider use and availability of echocardiography or as part of fam- ily screening after id enti \201 cation of an affected family member. Symptoms, when they do occur, may include t he following: \200 Fatigue and breathlessness due to impaired diastolic \201 lling and decreased cardiac out put. Atrial transportation is very important for maintaining cardiac output; symptoms typic ally get much worse with AF. HYPERTROPHIC CARDIOMYOPATHY 291 Chest pain (angina) can result from increased cardiac work secondary to the LVH, a relative blood supply \200\223demand mismatch and plugging of intramural arterioles. High diastolic pressures increase the diastolic wall stress and impair diastolic coronary blood \202 ow . Atrial and ventricular arrhythmias are common and can result in palpitations, presyncope and syncope, or even sudden death. Presyncope and syncope can also occur due to increased o ut \202 ow tract obstruction during exercise, at times of relative intravascular dehydrati on, or from certain maneuvers (i.e., Valsalva). Approximately 10% \200\22315% of patients m ay eventually develop left ventricular dilatation and failure. Sudden cardiac death The risk of SCD in these patients is extremely dif \201 cult to deter mine because of the marked phenotypic variability, and most risk factors have low sensitivi ty and speci \201 city. The annual incidence of SCD across the entire population with HCM is about 1%. Markers of risk for SCD in HCM \200 \200 \200 \200 \200 \200 \200 Early age at diagnosis History of syncope Family history of SCD LV wall thickness >30 mm No nsustained VT on ambulatory ECG monitoring Abnormal blood pressure response to exercise Hig h-risk genetic mutations Diagnosis The diagnosis is established by physical examination, electrocardiography, and ec hocardiography. Close attention must be paid to family history and family members should be offered screening. A genetic diagnosis can now be made in select individuals who have a de \201 nite family h istory of HCM. Despite the marked genetic heterogeneity, a genetic diagnosis may be establi shed in 70% of patients with inherited HCM, allowing accurate screening of other family mem bers. Physical examination (see Fig. 7.1) Evidence of LVH may present with a forceful apical impu lse and an S4 heart sound. Out \202 ow tract obstruction is evident by a double apical imp ulse and ejection systolic murmur beginning in mid-systole, which may be aug- mented by pro vocation by maneuvers such as Valsalva or standing. A pansystolic murmur due to mitral regurgitation resulting from systolic anterior movement of the mitral valve may also be present. Investigations \200 ECG associated repolarization abnormalities. Features include \200 \200 \200 \200 is rarely normal but usually shows voltage criteria for LVH with LVH with ST and T wave change Deep Q waves in inferior and lateral leads (septal hypertroph y) Pre-excitation and WPW syndrome Ventricular ectopics CHAPTER 7 Diseases of the myocardium and pericardium 292 Jerky pulse. May have large tidal wave JVP: \200\234a \200\235 wave T Later may be small volume, collapsing Prominent artial thrust Double apex beat v \200\234a \200\235 wav Systolic thrill Mid-diastolic rubble if inflow obstruction 4 2 1 Harsh systolic ejection murmur starts well after S1 S2 reversed in severe HCM Figure 7.1 Clinical signs of hypertrophic cardiomyopathy. Reproduced with permission from S wanton RH (2003). Cardiology Pocket Consultant, 5th ed. Copyright Wiley-Blackwell 2003. Echocardiography measurement of chamber sizes and wall thicknesses. It also facilitates dem onstration of out \202 ow tract or intracavitary gradients. Features include the following : \200 is essential for diagnosis with accurate ASH: grossly thickened septum compared with posterior LV wall, with reduced septal motion S mall LV cavity with hypercontractile posterior wall Mid-systolic aortic valve closure or \202 uttering of the aortic valve lea \202 et tips SAM: systolic anterior movement of the mitral valve apparatus. There may be contact between the anterior mitral lea \202 et and s eptum in systole. Reduced diastolic closure rate of the anterior mitral valve lea \202 et \200 Cardiac MRI may be helpful in borderline cases. HYPERTROPHIC CARDIOMYOPATHY 293 Other investigations may help in risk strati \201 cation, although no one inves- tigation accurately predicts those at risk of SCD and negative tests do not exclude the risk of SCD. \200 Ambulatory ECG \200 Exercise testing exercise. Cardiac catheterization out \202 ow tract gradients. Electrophysiology testing assessment but EP studies may be useful to as sess suspected accessory AV pathways. Genetic testing gene in proband can be identi \201 e d. monitoring \200\224atrial and ventricular arrhythmias. \200\224functional capacity and blo od pressure response to \200\224coronary anatomy and intracavitary and \200\224VT studies have no proven role in risk \200\224only useful for screening family members if causative Treatment Approximately half of sudden deaths in HCM occur during or shortly after strenuou s exercise, thus patients should be advised against competitive sports. Unfortunately, this also means that a signi \201 cant proportion die unexpectedly without any obvious precipi tant. Treatment of symptoms usually consists of the following. B-Blockers B-Blockers reduce myocardial oxygen demand and improve diastolic \201 ll- ing, reducing chest pain and improving breathlessness. They are the main- stay of therapy for a ngina, dyspnea, and syncope. Large doses may be required. Calcium channel antagonists Calcium channel antagonists (verapamil and diltiazem) are usefu l as they are negative inotropes (reducing out \202 ow tract obstruction) and reduce heart rate during exercise. Use diltiazem cautiously with B-blockers. Avoid verapamil in patient s on B-blockers. Disopyramide Disopyramide is a negative inotrope antiarrhythmic agent that has been shown to reduce out \202 ow tract gradients. Unfortunately, its use is limited b y anticholinergic side effects. Antiarrhythmics Other antiarrhythmic drugs such as amiodarone and sotalol are useful for co ntrolling supraventricular arrhythmias but have not been shown to reduce the risk of SCD fr om ventricular arrhythmias. AF should be car- dioverted as soon as possible (using amiodaro ne to improve chances of success). Nonpharmacological treatments Surgical septal myotomy \200\223myectomy (Morrow procedure) d irectly debulks the proximal septum. This procedure is recommended in patients with severel y symptomatic heart failure (NYHA Class III or IV) or who have recurrent syncope despite me dical therapy and is the preferred debulking procedure over alcohol septal ablation. CHAPTER 7 Diseases of the myocardium and pericardium 294 There is a risk of high-degree AV block requiring permanent pacing (about 5%) and long-term complications include aortic regurgitation. Cardiac transplantation may be necessary in pa tients who develop left ventricular dilatation and systolic heart failure. Alcohol septal ablation involves injecting alcohol into the \201 rst or second septal per forator artery. This causes a localized infarct of the hypertro- phied proximal septum, red ucing LVOT gradient (see Table 7.1 for assess- ment of LVOT obstruction). However, a signi \201 cant number of patients (10% \200\22315%) require permanent pacing afterward from AV block, and the- oretically there is increased risk of ventricular arrhythmias due to creati on of further arrhythmic substrate. Dual-chamber pacing with short AV delay may be used in patients with sig- ni \201 cant obs truction and symptoms refractory to drug therapy and who are not candidates for surgical se ptal myectomy. By ensuring ventricular pre- excitation, LV contraction is desynchronized, r educing LVOT gradients. Maintaining RV capture especially during exercise is dif \201 cult and shorten- ing the AV delay too much impairs diastolic \201 lling. Implantable cardioverter de \201 brillators (ICDs) should be considered in patients who ha ve survived a cardiac arrest or who have presented with hemodynamically unstable VT. Althou gh not currently recommended in all HCM patients, the utility of ICDs, even for primary pre vention of SCD, is increasingly appreciated. Table 7.1 Dynamic maneuvers to assess LVOT obstruction Decreased LVOT obstruction (murmur softer and shorter) Increased LVOT obstruction (murmur louder and longer) i LV volume Squatting Handgrip Passive leg elevation Valsalva (after release) Mueller maneu ver (deep inspiration against a closed glottis) d Contractility B-Blockers (acute IV) i Aft erload Phenylephrine Handgrip d LV volume Sudden standing Valsalva (during) Sublingual GTN Hypovolemia Dehydration i Contractility B-Agonists (e.g., isoprenaline) d Afterload A-Blockade RESTRICTIVE CARDIOMYOPATHY 295 Restrictive cardiomyopathy Restrictive cardiomyopathy is a rare condition characterized by impaired diastolic function due to reduced ventricular compliance. It is very import- ant t o distinguish restrictive cardiomyopathy from constrictive pericarditis as the latter can b e treated surgically by stripping the pericardium from the myocardium. Etiology The etiology of truly idiopathic cases remains obscure. A few cases are familial a nd tend to be associated with skeletal muscle disease. Other cases are associated with syst emic diseases, in \201 ltration, or endomyocardial \201 brosis (see Box 7.5). Symptoms Patients often have severely limited exercise tolerance because of an inability to increase cardiac output as the stroke volume is relatively \201 xed. They are also limit ed by breathlessness and have evidence of right heart failure (peripheral edema). Diagnosis Physical examination In addition to signs of HF, a loud S3, S4, or both may be present. The re also may be prominent x and y descents of the JVP and venous pressure may increase on in spiration (Kussmaul sign). The apex beat will be palpable in contrast to constrictive peric arditis. Investigations \200 ECG voltages, and atrial arrhythmias. may be normal or at least demonstrate normal Echocard iography systolic function. Alternatively, systolic function may be reduced in advanced cas es. In \201 ltration may be evident by hypertrophied ventricles and thickened intra-atrial septum and the myocardium may appear speckled. Biatrial enlargement may also be present. A restrictive mitral in \202 ow pattern is seen on Doppler tracing. Laboratory test and rig ht heart catheterization may be necessary to help exclude constrictive pericarditis (differ ence in LVEDP and RVEDP >7 mmHg at end expiration makes constriction unlikely). CT and MRI may show P-mitrale or -pulmonale, reduced precordial QRS are aimed at determining causes of in \201 ltration. Left scanning are useful to look at pericardial disease. Treatment Treatment is aimed at the symptoms of HF and the underlying condition. Rate contr ol in atrial \201 brillation is important, as reducing ventricular \201 lling times wil l have signi \201 cant impact. CHAPTER 7 Diseases of the myocardium and pericardium 296 Box 7.5 Causes of restrictive cardiomyopathy Myocardial Nonin \201 ltrative \200 Idiopat hic \200 Scleroderma Endomyocardial \200 \200 \200 \200 \200 Endomyocardial \201 brosis Hypereosinophilic syndrome Metastatic malignancies Carcinoid I atrogenic (radiation, anthracyclines) In \201 ltrative \200 Amyloid \200 Sarcoid Storage diseases \200 Lysosomal storage diseases (Gaucher \200\231s, Hurler \200\231s, Fabry) Glycogen storage di sease Hemochromatosis \200 ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY 297 Arrhythmogenic right ventricular cardiomyopathy Arrhythmogenic right ventricular cardiomyop athy (ARVC) is a disease in which the normal right ventricular myocardium is replaced by a \201 bro-fatty in \201 ltrate. It was originally termed a dysplasia, re \202 ecting the idea that it was somehow a developmental defect, but further understanding has led to the appreciation that it is a continuing process and has subsequently been reclassi \201 ed as a cardiomyopathy. It can progress to right ventricular dilatation and failure, and in some cases there may also be left ventricular involvement. Etiology Half of cases are familial with an autosomal dominant pattern of inherit- ance. Di sease-causing genes have not been found, but several loci have been mapped to chromosomes 1 , 2, 3, 10, and 14. An autosomal reces- sive variant, which is characterized by ARVC, palmo plantar keratosis, and wooly hair (Naxos disease), has been mapped to chromosome 17. Symptoms Patients are usually asymptomatic and presentation is usually in the form of ventr icular arrhythmias with typical LBBB pattern indicating probable origin from the right vent ricle. Therefore, otherwise healthy young indi- viduals can present with cardiac arrest or SCD. Other patients present in later life with symptoms of HF with or without ventricular a rrhythmias and are misdiagnosed as having DCM. Diagnosis Diagnosis of affected individuals can be very dif \201 cult, especially during f amily screening, as standard noninvasive investigations have poor sensi- tivity. Only a min ority may have classic \201 ndings of typical right ventricular arrhythmias with LBBB pat tern, abnormal depolarization/repolarization abnormalities, particularly on right precordia l ECG leads, and evidence of structural abnormalities of the right ventricle. Right ventricular free wall abnormalities are best characterized by MRI, but this too has l imitations. Therefore, patients with suspected ARVC but negative investigations may need re peated studies. There are no established or proven speci \201 c risk factors for SCD. Markers of increased risk include young age at diagnosis, malignant family history, syncope, right ventricular dysfunction and left ventricular involve- ment, and presence of VT on ambulatory monitoring . Therefore, baseline investigations in addition to a carefully taken history should include the following: \200 \200 \200 \200 12 lead and signal-averaged ECG 24-hour ambulatory ECG monitoring Exercise testing Echocard iogram ( MRI scan) CHAPTER 7 Diseases of the myocardium and pericardium 298 Treatment There are no established best treatment options for patients with ARVC, and, as t he disease is progressive, antiarrhythmic options are used for symptomatic bene \201 t in patients with hemodynamically well-tolerated ven- tricular arrhythmias. Patients who have developed RV and LV dysfunction can be managed with standard treatments f or HF. In severe cases, transplantation may be an option. Antiarrhythmics B-Blockers alone or in combination with class I and III antiarrhythmics are the most effective in reducing symptomatic but well-tolerated ventricu- lar arrhythmias. S otalol and amiodarone have been shown to be most effective. Patients with more sustained ventricular arrhythmias may have drug therapy guided by their response during programmed electrical stimula- tion, but this has no proven bene \201 t in reducing the risk of SCD. Radiofrequency ablation A small subset of patients with drug-refractory arrhythmias who are felt to have fairly localized disease may be amenable to electrophysiological mapping and radiofrequency ablation. However, it must be remembered that ARVC is a progressive disease; this can only be viewed as a palliative procedure. Implantable cardioverter de \201 brillators In patients with life-threatening or drug-refr actory ventricular arrhythmias and widespread disease, ICDs probably offer the best protect ive measure against SCD. METABOLIC CARDIOMYOPATHY 299 Ischemic cardiomyopathy This is a condition in which coronary artery disease (CAD) causes a pic- ture that is often indistinguishable from DCM with or without a preceding history of angina or myocardial infarction. Often the degree of dysfunction is inconsistent with the e xtent of CAD. It is important to recognize patients with hibernating myocardium, as they will bene \201 t from revascularization. Valvular cardiomyopathy Patients with valvular heart disease will develop a cardiomyopathy depend- ent on the predominant valvular lesion. Often signi \201 cant improvement in cardi ac function can be seen after correction of the valve disease. Hypertensive cardiomyopathy Hypertension causes LVH in response to increased afterload, whi ch is compensatory and protective to a point. However, there are ultimately detrimental eff ects on systolic and diastolic ventricular function. Hypertension also leads to accelerated atherosclerosis and ischemic heart disease. Hyperten sive cardiomyopathy is the most common form of HF outside the Western world. Alcoholic cardiomyopathy Chronic alcohol excess is the most common cause of DCM in the West ern world. Proposed mechanisms include 1) direct toxic effect, 2) concomitant nutritional d e \201 ciencies (especially thiamine), and 3) rarely toxic effects of additives (cobalt). Unlike other forms of DCM, abstinence from alcohol early in the dis- ease process may stop progression or even result in signi \201 cant improve- ment in cardiac function. Metabolic cardiomyopathy Various abnormalities in metabolism can result in cardiomyopathy. Lysosomal and glycogen storage diseases can cause a form of restrictive cardiomyopathy. Hem ochromatosis also causes restrictive cardiomyop- athy by unknown mechanisms. Acquired errors of metabolism such as acromegaly result in biventricu- lar hypertrophy. Dia betes mellitus can cause cardiomyopathy with systolic and/or diastolic dysfunction even in the absence of signi \201 cant epicardial CAD. CHAPTER 7 Diseases of the myocardium and pericardium 300 Takotsubo cardiomyopathy ( \200\234broken heart syndrome \200\235) Takotsubo cardiomyopathy is a stress-induced cardiomyopathy whose presentation mimics an ST-elevation MI without ev idence of signi \201 cant epicardial coronary artery disease on angiogram. Its hallmark is apical bal- looning on left ventriculography (in a minority of patients there may be mid-v entricular ballooning instead). Originally described in Japan, it is becoming a more widely recognized syndrome. In series evaluating acute coronary syndromes, it accounts for about 1% \200\2232% of cases. The synd rome is much more common in women than in men and in a review of 7 series, postmenopausal w omen accounted for 82% \200\223100% of the reported cases. Pathogenesis Takotsubo cardiomyo pathy is typically triggered by acute medical illness or by an extreme emotional stressor. Although the exact pathophysiology is not known, it is hypothesized that the underlying mec hanism may include catecholamine excess resulting in microvascular spasm and resultant myo- cardial stunning, myocarditis, or coronary artery vasospasm. Clinical presentation Patient s typically present with sudden onset of substernal chest pain fol- lowing an extreme emoti onal stressor or critical illness. Occasionally patients will present with heart failure sy mptoms or in shock. The initial ECG typically reveals ST elevations (Box 7.6). Cardiac biomar- kers are often e levated. The degree of elevation is often mild and not con- sistent with degree of LV dysfu nction or hemodynamic compromise. Echocardiography reveals apical akinesis or dyskinesis. By de \201 nition, angiograms do not reveal any signi \201 cant epicardial coronary disease. Acute complications include tachy- and bradyarrhythmias, pulmonary edema, hypotension/shock, and transient LVOT obstruction. Treatment and prognosis Stress-in duced cardiomyopathy is typically a transient phenomenon and has a good prognosis. Patients who survive the acute episode typically have normalization of their left ventricular funct ion within 4 weeks. Treatment is therefore supportive. It is reasonable to initiate standard heart failure therapy with B-blockers, ACE-I, and diuretics if needed. Box 7.6 Diagnostic criteria of Takotsubo cardiomyopathy \200 Transient akinesis or dyskinesis of the apical and midventricular segments in association w ith regional wall motion abnormalities that extend beyond the distribution of a single epic ardial vessel Absence on angiography of obstructive coronary artery disease or evidence of acute plaque rupture New ST-segment elevation or T-wave inversion on ECG Absence of recent signi \201 cant head trauma, intracranial bleeding, pheochromocytoma, myocarditis, or hype rtrophic cardiomyopathy \200 MUSCULAR DYSTROPHIES 301 General system disease Systemic lupus erythematosus (SLE) can cause heart disease in many w ays. Approximately 10% of patients with SLE have evidence of myo- carditis. Patients with a ssociated antiphospholipid antibody syndrome have increased risk of valvular abnormalities and DCM due to throm- botic occlusions of the microcirculation without vasculitis. They als o have increased atherogenesis. Pulmonary hypertension due to pulmonary vasculitis is an uncommon cause of cardiomyopathy in patients with rheumatoid arthritis. Nutritional cardiomyopathy Thiamine is an important coenzyme in the hexose monophosphate sh unt. Infants breast-fed in areas with diets de \201 cient in thiamine develop mainly right ventricular failure between 1 and 4 months of age. Prompt correc- tion of the vitamin de \201 ciency results in rapid improvement in the cardiac abnormalities without long-term con sequence. Protein-calorie malnutrition (Marasmus, Kwashiorkor) results in thin- ning and atrophy of m uscle \201 bers and, ultimately, DCM. Careful treatment may result in marked improvement over several months provided the patient survives the initial period. Muscular dystrophies The large number of muscular dystrophies can be associated with either DCM or HCM, and this can be the most common cause of death in these patients. Myotonic dys trophy is associated with AV conduction abnormal- ities and arrhythmias rather than cardiom yopathy. All patients need careful long-term follow-up. CHAPTER 7 Diseases of the myocardium and pericardium 302 Neuromuscular disorders Cardiac involvement in Friedreich \200\231s ataxia is relatively co mmon although usually asymptomatic. It is most commonly associated with HCM, which is disti nct from the genetic variety by lack of myo \201 brillar disarray and malig- nant ventricu lar arrhythmias. Rarely, it is associated with DCM. Sensitivity or toxic reactions A large number of noninfectious agents can damage the myocar dium. The damage can be acute with evidence of an in \202 ammatory reaction, or there may be no in \202 ammation and necrosis, as in hypersensitivity reactions. Other agents lead to chronic changes with progressive \201 brosis and an ultimate picture similar to DCM. Numerous chemical and industrial agents can cause myocardial damage, as ca n radiation and excessive heat. Peripartum Peripartum cardiomyopathy is a form of DCM. Symptoms occur in the third trimeste r and the diagnosis is made in the peripartum period. Approximately half of patients will s how complete or near-complete reso- lution over the \201 rst 6 months postpartum. Of the remainder, some will continue to deteriorate and die or require transplantation, while othe rs will continue to experience chronic HF. Its diagnosis is established by excluding other causes of DCM; the cause is unknown (also see Chapter 10). MYOCARDITIS 303 Myocarditis Myocarditis is the process whereby the myocardium becomes in \202 amed by one of a large range of infectious agents. Unfortunately, the infectious agent is rarely identi \201 ed. Numerous bacteria, viruses, spirochetes, fungi, parasites, and rickettsia can ca use myocarditis (see Table 7.2). Etiology Damage can result from a number of mechanisms, including direct toxic effect on th e myocyte, production of a toxin (e.g., diphtheria), and immunologically mediated cell dama ge. Histological \201 ndings depend on a number of factors, including the infectious agen t, stage of disease, and the mechanism of damage. Damage can be focal or diffuse and is randomly distributed throughout the myocardium. Symptoms The clinical consequences of the damage can range from asymptomatic subclinical in fection to rapidly progressive and ultimately fatal HF. Long- term consequences are also va riable. Patients who were initially asymptomatic can present after a prolonged latency period with DCM or have complete recovery. Patients who pre- sent early, even with fulminant HF, can al so have complete recovery. Patients with nonfulminant presentations can gradually deteriora te and recover gradually. Diagnosis The diagnosis is often established by identifying the associated systemic illness . Isolation of the infectious agent is rarely achieved, although clearly supportive of the diagnosis if positive. Endomyocardial biopsy can be use- ful in con \201 rming the diagnos is but is frequently negative. Treatment Management of patients with myocarditis is largely supportive. Physical activity should be restricted, as in animal models exercise was found to be detrimental to cardiac f unction. Standard management of HF and eradication of the infectious agent are the mainstay of treat ment. Symptomatic arrhythmias should be controlled and B-blockers may be cardioprotective. Trials of immunosuppressive therapy in patients with myocarditis have been largely disappoi nting. The use of steroids in acutely ill patients could be considered, but any bene \201 t is unproven. CHAPTER 7 Diseases of the myocardium and pericardium 304 Table 7.2 Causes of myocarditis Viral (usually mild and self- limiting) Enterovirus (Coxsackie B) most common in Western co untries CMV Dengue Hepatitis EBV In \202 uenza Varicella HIV Spirochetal Lyme disease \200\224about 10% of patients have cardiac involvement Leptospiros is Syphilis \200\224direct involvement of myocardium with gummae is rare Protozoal Trypanos oma cruzi causes Chagas disease \200\224signi \201 cant public health problem in S. Americ a. HF may present 20 years after initial infection Fungal This is rare (typically occurs in patients with concomitant malignant disease or who are otherwise immunosuppressed) Actinomyces, Aspergillus, Candida, Cryptococcus, Histoplas ma Rickettsial Q fever rarely causes myocarditis Rocky Mountain spotted fever Scrub typhus Toxic/metabolic Anthracyclines Cocaine Catecholamines Carbon monoxide Hypocalcemia Hypersen sitivity \200\224eosinophilic in \201 ltration Bacterial Diptheria \200\224myocarditis occurs in up to 20% of diptheria infections Meningo coccus Mycoplasma Whipple \200\231s disease ETIOLOGY 305 Pericardial diseases Etiology The pericardium may be involved in the large number of diseas e processes listed in Table 7.3. In some patients, pericardial disease is the primary disea se process dominating the clinical picture, whereas in others it is a manifestation of a sy stemic disease. The most common causes are idiopathic (or viral), uremic, neoplastic, tuberculous pericardi tis, and acute myocardial infarction. The spectrum of pericardial disease is determined by the age and social circumstances of the patient. In an elderly North American and Western European population, the most common causes are ma lignancy, followed by uremia and myocar- dial infarction. In less privileged communities an d in developing countries, tuberculosis is still the predominant cause of pericardial disea se. Table 7.3 Etiology of pericardial diseases Infections Bacterial: Mycobacterium tuberculosis, Staphylococcus, Pneumococcus, Meningococcus, Mycopla sma Viral: Coxsackie, CMV, ECHO, EBV, in \202 uenza, HIV, mumps, parvo B19, rubella, varic ella Fungal: Histoplasmosis, blastomycosis Parasitic: Amoebiasis Collagen vascular diseases: systemic lupus erythematosus, polyarteritis nodosa, scleroderma , dermatomyositis Type 2 autoimmune disorders: rheumatic fever, autoreactive pericarditis, postmyocardial infarction, and postpericardiotomy syndromes Drug-induced: hydralazine, proc ainamide, penicillin, phenylbutazone Other autoimmune disorders: rheumatoid arthritis, anky losing spondylitis Autoimmune and hypersensitivity diseases Heart: acute myocardial infarction, myocarditis Lung: pulmonary infarction, pneumonia Pericardial involvement by disease in surrounding organs Malignant disease Primary: mesothelioma, sarcoma, \201 broma, lipoma Secondary: lung carcinoma, breast carc inoma, melanoma, lymphoma, leukemia Bleeding into the pericardium Trauma: penetrating and nonpenetrating Dissecting aortic aneurysm Hemorrhagic diathesis: le ukemia, scurvy Anticoagulants: warfarin Metabolic disorders Uremia, dialysis-related, myxedema, gout Miscellaneous Acute idiopathic pericarditis, radiation, sarcoidosis, amyloidosis, familial Mediterranean fever CHAPTER 7 Diseases of the myocardium and pericardium 306 Syndromes of pericardial disease Pericardial reaction to the various disease processes is l imited. The fol- lowing \201 ve clinical and pathological forms of pericarditis can thus be distinguished: 1. Acute pericarditis without effusion 2. Pericardial effusion with or wi thout tamponade 3. Constrictive pericarditis 4. Effusive \200\223constrictive pericarditis 5. Calci \201 c pericarditis without constriction ACUTE PERICARDITIS WITHOUT EFFUSION 307 Acute pericarditis without effusion ( \200\234Dry \200\235 pericarditis) Etiology Any of the causes listed in Table 7.3 may cause dry pericarditis. The clinical syn drome is commonly seen in acute viral pericarditis or after myocardial infarction. Pathology There is a \201 brinous exudate with an in \202 ammatory reaction involving th e visceral and parietal pericardium. The epicardium is also involved and this accounts for the ECG changes seen and the rise in cardiac enzymes (e.g., troponin I). Symptoms Sharp, stabbing, central chest pain is common, with radiation to the shoul- ders a nd upper arm. It is relieved by sitting up and leaning forward and is aggravated by lying d own. It may be accentuated by inspiration, cough, swallowing, or movement of the trunk. Fever, night sweats, and other constitutional symptoms may be present, depending on the underlying cause. Signs A pericardial friction rub is frequently heard. This is a super \201 cial, scratchy, grating sound that is best heard in the second to fourth intercostal spaces when pressure is exerted on the diaphragm of the stethoscope. Positioning the patient leaning forward and listening in held inspiration may bring it out. The rub is classically described as being triphasic. Usually at least two components are he ard because of atrial systole and ventricular systole. Occasionally a third component attri buted to rapid ventricular \201 lling is heard. ECG The patient is usually in sinus rhythm, but atrial \201 brillation may occur. In the early stages there is widespread ST-segment elevation with concavity directed upward, and P R segment deviation opposite the polarity of the P wave. After a few days the ST segments f ollowed by PR segments return to normal, and T waves become inverted. CXR The cardiac shadow is not enlarged in dry pericarditis. Differential diagnosis Acute pericarditis must be differentiated from myocardial infarction , spon- taneous pneumothorax, and pleurisy. CHAPTER 7 Diseases of the myocardium and pericardium 308 Diagnosis Diagnosis of acute pericarditis is based on typical symptoms of chest pain, peric ardial rub, and/or characteristic ECG changes. Management Treat the underlying cause. Good pain relief can be achieved by the use of nonsteroidal ant i-in \202 ammatory drugs (NSAIDs). PERICARDIAL EFFUSION TAMPONADE 309 Pericardial effusion tamponade Etiology Any of the causes listed in Table 7.3 may cause pericardial effusion. Large effusions are common with neoplastic, TB, uremic pericarditis, and myxedema. Pathology In addition to \201 brinous in \202 ammation, there is signi \201 cant \202 uid exudation. The pericardial \202 uid may be serous, serosanguineous, hemorrhagic, or purulent depending on the underlying cause. Hemorrhagic effusion is common in tuberculosis or neoplasia. Brownish \202 uid with an an chovy sauce appearance of the pus is highly suggestive of amoebic pericarditis. Clinical features Clinical presentation varies depending on the rate of accumulation of \202 uid, the amount of \202 uid that accumulates, and the stage at which the patient is \201 rst seen. Symptoms Chest pain may be typically pericardial (as described under Dry Pericarditis), or it may be dull and heavy from distension of the pericardium. Dyspnea is common, and orthopnea may occur later in the course of the disease. Cough may be present from compression of surrounding structures. Any constitutional symptoms depend on the cause of the disease. Signs Typically, precordial dullness extends beyond the apex beat (which may be impalpable) , and dullness is present to the right of the sternum. Dullness and bronchial breathing (Ew art \200\231s sign) at the left base posteriorly due to compression of the left lower lobe bronchus may be found. Cardiac tamponade should be considered in a patient with hypotension, raised JVP, and quiet heart sounds (Beck \200\231s triad). The primary defect in cardiac tamponade is interferen ce with diastolic \201 lling of the heart.