groups (proteinuria, renal dysfunction, myocardial ischaemia). Diabetes mellitus \200 Tight glycaemic control is recommended. \200 Patients should be treated as per established guidelines. \200 Thiazolinediones have been associated with in creased \202 uid overload and symptomatic HF, and are therefore contraindicated in patien ts in NYHA functional class III \200\223IV and should be used with caution in less symptoma tic patients (NYHA I \200\223II). Given the close association of HF and renal dysfunction, renal function should be monitored in patients on metformin, which may require discontinuation in acute exacerbations associa ted with acute or chronic renal failure. Renal impairment \200 Common in HF; prevalence increase with increasing HF severity, age, diabetes mellitus, hypertension \200 Strongly linked to poorer prognosis \200 Always lo ok for potentially reversible causes. COPD \200 Common in HF (20 \200\22330 % ). \200 Associated with increased morbidity and mortality. \200 Although it may be dif \201 cult, attempt to quantify the relative contribution of each component to the symptoms of the patient, since it may affect optimal management. The majority of COPD patients will tolerate B -blockers well. Anemia \200 Anemia of chronic disease is common in HF, with reported prevalence varying widely (up to 70 % ). Anemia confers increased morbidity and mortality. \200 Correction of chronic anemia has n ot been established as routine treatment in HF, and blood transfusion is not recommended unless the patient is compromised . Erythropoietin treatment has been trialed but remains of unproven bene \201 t. Gout \200 Common in HF, given the use of loop diuretics and high prevalence of renal dysfunction. Hyperuricaemia is an independent risk factor of poor prognosis in HF. \200 Avoid NSAIDs/s teroids and treat acute attacks with colchicine. \200 Prophylactic treatment with allopur inol is recommended to prevent recurrence. This page intentionally left blank 414 CHAPTER 7 Heart failure Palliative care for heart failure \200 Patients with clinical features of advanced HF, wh o experience refractory symptoms despite optimal treatment, should be referred for a structured palliati ve care assessment. Symptoms and compromised quality of life, however, prevail throughout the course of HF and should therefore be speci \201 cally addressed with pallia tive care measures. Palliative care for HF should be integrated into comprehensive HF care to improve decision making and supportive care: \200 communication \200 education \200 psychological and spiritual needs \200 symptom management. Worsening heart failure When a patient is seen with worsening heart failure, it is importan t to try and ascertain the cause. The most frequent reasons for symptom deterio- ration are shown next. Causes of worsening heart failure Non-cardiac \200 Non-compliance (lifestyle changes, med ication) \200 Newly prescribed drugs \200 Renal dysfunction \200 Infection \200 Pul monary embolus \200 Anemia. Cardiac \200 Atrial \201 brillation \200 Other tachyarr yhthmias \200 Bradycardia/heart block \200 Worsening valve disease \200 Myocardial is chaemia (including infarction). WORSENING HEART FAILURE 415 Table 7.11 Summary of common side-effects of drugs used in heart failure Drugs Complications Diuretics Common : postural hypotension, gout, urinary urgency Serious : electrolyte imbalance (hypokalaemia, hypomagnesia, hyponatraernia), arrhythmia ACE-Is Common : cough, hypotension including postural Serious : worsening renal function, renal infarction in renal artery stenosis, angio-oedema B-blockers Common : tiredness, bradycardia, coldness Serious : asthmatic attack, exacerbation of heart failure, heart block Spironolactone Common : gynaecomastia, tiredness, rashes Serious : hyperkalaemia, hypotraemia Digoxin Common : nausea Serious : life-threatening arrhythmias Common : hypotension including postural Angiotensin-II receptor antagonists Serious : worsening renal function, renal infarction in renal artery stenosis Amiodarone Common : photosensitivity, nausea, thyroid dysfunction, sleep disturbance, corneal microdep osits Serious : thyrotoxic storm, pro-arrhythmia, pulmonary/hepatic \201 brosis Inotropes Common : nausea, palpitation Serious : arrhythmia, cardiotoxicity 416 CHAPTER 7 Heart failure High-output heart failure In high-output states, the only way that the oxygen demands of th e peripheral tissues can be met is by an increase in cardiac output. If there is underlying heart disease, the heart is unable to augment the cardiac output in the long term, and HF results. Causes of high-output states \200 Anemia \200 Acquired arteriovenous \201 stula \200 Haemangioma \200 Hereditary haemorrhagic Thyrotoxicosis \200 Beri-beri heart disease \200 Paget \200\231s disease of the bone \200 Fibrous dysplasia \200 Polycythaemia rubra vera \200 Carcinoid syndrome \200 Mu ltiple myeloma telangiectasia Hepatic haemangioendothelioma \200 Pregnancy \200 Acromegaly Anemia When the hemoglobin levels fall below 8 gm/dL, the anemia produces a high cardiac ou tput. However, even when severe, anemia rarely causes HF or angina in patients with normal hearts. Look for an underlying cardiac problem or valve disease. Try to determine the etiol ogy for the anemia. Patient should be on bed rest and transfused with packed red blood cell s accompanied with IV diuretics. Systemic arteriovenous \201 stulas The increase in cardiac output depends on the size of the \201 stula. The Branham sign consists of slowing of the heart rate after manual compr ession of the \201 stula. It also raises arterial blood pressure. Surgical repair or exci sion is the ideal treatment. Pregnancy (see b Heart disease in pregnancy, Chapter 15, p. 67 3) Thyrotoxicosis Raised levels of thyroxine produce increased heart rate and cardiac contrac- tility, reduction in systemic vascular resistance, and enhanced sympathetic activation. Th yrotoxicosis does not usually precipitate HF unless there is reduced cardiac reserve. Atria l \201 brillation occurs in about 10 % of patients, exacerbating the HF. Respiratory musc le weakness may contribute to the dyspnoea. Beri-beri (see b Beri-beri (thiamine deifciency ), p. 664) Paget \200\231s disease There is a linear relationship between the extent of bone involveme nt and rise in cardiac output. Involvement of about 15 % of the skeleton is required before the rise is seen, and patients may tolerate the early stages well for years. Concomitant v alvular disease or iachaemic heart disease results in decompensation. Successful treatment of Paget \200\231s disease with bisphospho- nates may reverse the rise in cardiac output ov er several months. 417 Chapter 8 Heart muscle diseases Classi \201 cation 418 Dilated cardiomyopathy 420 Dilated cardiomyopathy: treatment 422 Hy pertrophic cardiomyopathy 424 Hypertrophic cardiomyopathy: investigations 428 Hypertrophic cardiomyopathy: treatment 430 Restrictive cardiomyopathy 432 Cardiac amyloidosis 434 Cardia c amyloidosis: treatment 436 Fabry disease 438 Arrhythmogenic right ventricular cardiomyopa thy (ARVC) 440 ARVC: management 442 Left ventricular non-compaction 444 Ischaemic cardiomyo pathy 446 Valvular cardiomyopathy 446 Hypertensive cardiomyopathy 446 Alcoholic cardiomyopa thy 446 Metabolic cardiomyopathy 447 Takotsubo cardiomyopathy 447 Peripartum cardiomyopathy 447 Cardiomyopathy in systemic disease 448 Nutritional cardiomyopathy 448 Sensitivity or t oxic reactions 448 Neuromuscular disorders 448 Muscular dystrophies 450 Myocarditis 452 Vir al myocarditis 453 Rickettsial myocarditis 453 Bacterial myocarditis 454 Spirochetal myocar ditis 454 Protozoal myocarditis 455 Fungal myocarditis 455 Toxic and metabolic myocarditis 456 418 CHAPTER 8 Heart muscle diseases Classi \201 cation Heart muscle diseases include a diverse range of cardiomyopathies and m yocardites. Cardiomyopathies have been previously classi \201 ed as dis- eases of unknown cause and were therefore distinct from more speci \201 c causes of heart muscle disease su ch as ischaemia, hypertension, and val- vular heart disease. However, a better understandin g of their etiology and pathophysiology has led to this distinction becoming obsolete. De \201 nition Cardiomyopathies can be de \201 ned as a heterogeneous group of diseases o f the myocardium, characterized by mechanical and/or electrical dysfunc- tion that typicall y (though not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and a re due to a variety of causes that are fre- quently genetic. Cardiomyopathies are either co n \201 ned to the heart or are part of generalized systemic disorders, often leading to ca rdiovascular death or progressive heart failure-related disability (Fig. 8.1 ). 1 Cardiomyopathies can be classi \201 ed according to the predominant organ involvement. Pri mary cardiomyopathies are those con \201 ned to the heart muscle and can be further subdiv ided into genetic and acquired forms. Secondary cardiomyopathies occur as part of a variety of generalized sys - temic diseases, often with multi-organ involvement, which also demon- strate myocardial pathology. Primary cardiomyopathies Primary cardiomyopathies are predominantly con \201 ned to the he art only. They can be further classi \201 ed into genetic and acquired groups, though over lap exists with certain forms of cardiomyopathy, in particular dilated cardiomyopathy. Secondary cardiomyopathies Secondary cardiomyopathies are typically part of generalized mul tisystem diseases. Cardiac manifestations may be an isolated feature, though multiple organ involvement is more common. Conversely, if no evidence of myo- cardial disease is found, r egular surveillance for cardiac involvement with history, examination and non-invasive inve stigations is important. Fig. 8.2 lists examples of conditions associated with secondary ca rdiomyopathy but is not exhaustive. 1 Maron BJ, Towbin JA, Thiene G, et al (2006). Contemporary de \201 nitions and classi \201 cation of the cardiomyopathies. An American Heart Association Scienti \201 c Statemen t From the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Qua lity of Care and Outcomes Research and Functional Genomics and Translational Biology Interd isciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 113 : 1 807 \200\22316. CLASSIFICATION 419 Primary cardiomyopathies Genetic Mixed Acquired \227\217 Inflammatory \200\224myocardites \227\217 Stress induced \200\224 \200 \230tako-tsubo \200\231 \227\217 Peripartum \227\217 Tachycardia induced \227\217 Nutrit ional deficiency \227\217 Toxic \200\224alcohol, chemotherapeutics etc \227\217 Muscular dystrophies DCM \227\217 HCM \227\217 ARVC \227\217 LVNC \227\217 Glycogen and lysosomal storage di sease \227\217 Mitochondrial myopathies DCM \227\217 Restrictive \200\223amyloidosis, sarcoidosis Fig. 8.1 Primary cardiomyopathies can be divided into genetic and acquired causes of heart muscle disease. 1 DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; ARVC = a rrhythmogenic right ventricular myopathy; LVNC = left ventricular non-compaction. INFILTRATIVE Amyloidosis Gaucher \200\231s and Hurler \200\231s disease ENDOCRINE STORAGE Diabetes Thyroid disease Phaeochromo- cytoma Fabry disease Haemochromatosis Secondary cardiomyopathies TOXICITY NEUROMUSCULAR Muscular dystrophies Friedreich \200\231s ataxia Alcohol Radiation Anthracyclines AUTO-IMMUNE NUTRITION Beri-beri Kwashiorkor SLE Rheumatoid arthritis Fig. 8.2 Secondary cardiomyopathies can be a feature of many generalized systemic diseases. 420 CHAPTER 8 Heart muscle diseases Dilated cardiomyopathy Dilated cardiomyopathy (DCM) is characterized by cardiac chamber enl argement and impaired systolic dysfunction, although diastolic dys- function is almost alwa ys also present. The prevalence is 5 \200\2238 per 100 000 and it is 3 times more frequent in black and male than white and female individuals. Symptoms Clinical presentation may be abrupt, with acute pulmonary oedema, sys- temic or pu lmonary emboli, or even sudden death, but more often patients present with progressive symp toms of congestive cardiac failure (CCF) including exertional dyspnoea, orthopnoea, paroxys mal nocturnal dysp- noea, and fatigue. Right upper quadrant discomfort, nausea, and anorexi a may relate to hepatic congestion. Syncope is an ominous symptom and should be regarded to represent a potentially fatal arrhythmia unless sub- sequent investigation indicates other wise. Diagnosis Diagnosis is established by physical examination, electrocardiography, chest X-ra y (CXR), and echocardiography. \200 A raised jugular venous pressure (JVP), displaced car diac apex, and added heart sounds are sensitive clinical markers of heart failure. Crackles in the lungs and swollen ankles are relatively non-speci \201 c, especially in the octoge nerain population. Electrocadiography (ECG) may show evidence of sinus tachycardia, atrial \201 brillation ( AF), or frequent ventricular extra-systoles. Voltage criteria for cardiac chamber enlargeme nt, bundle branch block, non- speci \201 c T-wave changes, and poor R-wave progression in the anterior chest leads are common. CXR may show an enlarged cardiac size and pulmonary oedema (upper lobe venous diversion, in terstitial oedema, pleural effusions and Kerley B lines). Echocardiography (ECHO) is currently regarded to be the gold standard investigation for diagnosing left ventricular (LV) dysfunction. Bi-atrial and bive ntricular enlargement are common, and patients with chronic LV volume overload may also exh ibit mild left ventricular hypertrophy (LVH). Indices of systolic (and diastolic function) are impaired. The atrioventricular (AV) valves are commonly incompetent, due to annular dil atation. ECHO may reveal complications of dilated cardiomyopathy such as intramural thrombu s, and is invaluable in the identi \201 cation of alternative causes of heart failure, suc h as hypertensive heart disease, previous myocardial infarction (MI), valvular heart diseas e, pericardial disease, and intracardiac shunts. Exercise testing with or without measurement of maximum ventilatory oxygen consumption, is useful to assess functional capacity and prognosis. Ambulatory ECG monitoring is essential to identify the presence of paroxysmal AF and non-sustained ventricular tachycardia (VT), which have important therapeu tic and prognostic implications respectively. DILATED CARDIOMYOPATHY 421 There is rarely any indication for cardiac catheterization in patients with dilated cardiomyopathy, with the exception of excluding coronary artery disease. Etiology of dilated cardiomyopathy Although originally considered to be idiopathic, experimental and clinical data now suggest that genetic, viral, and autoimmune factors play a role in its pathophysiology. Several ge netic mutations have been identi \201 ed as the causative problem in familial DCM, while c ertain viruses have been shown to cause sporadic cases of DCM. The following list is not ex haus- tive and there is some overlap with speci \201 c cardiomyopathies. \200 Inherited (may account for > 25 % of cases) \200 Myocarditis (infective, autoimmune, toxic) \200 Metabolic (haemochromatosis, thyrotoxicosis) \200 Nutritional (vitamin de \201 ciencies \200\224 thiamine (beri-beri)) \200 Persistent tachycardia (tachymyopathy) DCM is essent ially a diagnosis of exclusion, and potentially reversible causes including coronary artery disease, valvular heart disease, and adult congenital heart disease should be sought. Care ful attention should also be paid to dietary history and alcohol consumption, as some rever sibility is possible with modi \201 cation of these factors. Additional investigations for DCM \200\224 the \200\230cardiomyopathy screen \200\231 \200 Renal function \200 Liver function tests (LFTs) \200 Serum ferritin, iron, transf errin, B 12 , and folate \200 Thyroid function \200 Viral serology \200 Infective scr een (HIV, hepatitis C, enteroviruses) \200 Autoantibodies 422 CHAPTER 8 Heart muscle diseases Dilated cardiomyopathy: treatment Management of DCM focuses on relieving symptoms and impro ving prog- nosis and quality of life. Pulmonary and peripheral congestion are effectively t reated with diuretics. Prognostically important pharmaceutical therapies inhibit the malada ptive neurohormonal process involving the sympathetic system and rein \200\223angiotensin \200\223aldosterone axis. The acute management of heart failure is discussed in b Chapter 7 , p.367. Diuretics Loop diuretics, are useful in relieving symptoms caused by pulmonary and peripher al congestion. Careful monitoring of electrolytes is important, as intravascular depletion may cause urea to rise, and hypokalaemia is common. Hypokalaemia may be counteracted by the co-administration of a potas- sium-sparing diuretic such as amiloride or spironolactone. S pironolactone is an aldosterone antagonist. The recent RALES (Randomized Aldactone Evaluati on Study) trial (see b p. 106) demonstrated that the use of low-dose spironolactone can red uce mortality in patients with severe CCF. Angiotensin-converting enzyme inhibitors There is overwhelming scienti \201 c evidence tha t angiotensin-converting enzyme inhibitors (ACE-Is) improve symptoms and outcomes in patien ts with heart failure, irrespective of symptoms. First-dose hypotension used to be a concer n but this is rarely observed with newer ACE-Is and usually only in patients who are relati vely intravascularly depleted due to the concomitant use of high-dose diuretics. Side-effec ts include a dry cough, which may affect up to 20 % of patients and is due to increased lev els of bradykinin. Angioedema is a rare but potentially life-threatening complica- tion of ACE-Is. Angiotensin receptor 1 antagonists (ARBs) can be used as an alternative in patients who experience a dry cough. Contra-indications to ACE-I include established bilateral renovascular disease, severe aort ic stenosis, pregnancy, and a baseline potassium > 6 mmol/L. ACE-Is should be prescribed wi th caution in individuals with a resting systolic blood pressure <90 mm Hg or basline creat inine > 200 mol/L. Beta-blockers Beta-blockers also provide symptomatic and prognostic bene \201 t and are re commended in all patients with dilated cardiomyopathy unless there are speci \201 c contra indications. Beta-blockers are effective through several mechanisms, which include a reduct ion of myocardial oxygen consump- tion, enhanced LV \201 lling, inhibition of the apoptot ic effects of catechol- amines on cardiac myocytes, treatment of cardiac arrhythmias, and u pregulation of beta-1 receptors. Given the potentially negative inotropic effects, the drug s are initiated in low doses, which are titrated up gradually. They should not be started i n patients with overt heart failure. DILATED CARDIOMYOPATHY: TREATMENT 423 Aldosterone antagonists Alodosterone antagonists improve symptoms and prognosis and are rec - ommended in patients who continue to remain in NYHA (New York Heart Association) class II I despite adequate doses of ACE-Is and beta- blockers. The most important complication is h yperkalaemia due to the concomitant use of ACE-I. Painful gynaecomastia is a recognized sid e- effect, particularly in males taking digoxin and anti-androgens. Antiarrhythmic agents Antiarrhythmics agents have not been shown to reduce the incidence of sudden cardiac death (SCD) in patients with DCM. AF is a common arrhythmia in DCM and may be associated with symptoms of cardiac decompensation. Most individuals are rate controlled with B -blockers, although digoxin may be used as additive treatment in individuals who co n- tinue to exhibit rapid heart rates despite satisfactory doses of B -blocker. Maintenance of sinus rhythm is usually unsuccessful in the long term. Anticoagulation Patients with DCM are prone to thromboembolic complications and should be a nticoagulated with warfarin regardless of underlying rhythm. Device therapy \200 Cardiac resynchronization therapy (CRT) utilizes biventricular pacing to combat intraventricular and interventricular dys-synchony associated with ventricular co nduction defects. CRT has been shown to be associated with signi \201 cant improvements in functional capacity and rates of rehospitalization from heart failure ( b see p. 404). CRT is generally reserved for individuals with wide QRS complexes (particularly left bundle br anch block (LBBB)) who have an ejection fraction (EF) of <35 % and are in NYHA class III de spite optimal medical therapy. \200 Implantable cardioverter de \201 brillators (ICDs) a re effective in preventing arrhythmogenic SCD and are recommended in all victims of aborted SCD and those w ith sustained VT. An ICD may be implanted for prophylactic reasons in all individuals with an EF<35 % who are in NYHA class II or III. Cardiac transplantation Orthotopic cardiac transplantation using an allograft can be consid ered in patients who are severely symptomatic despite maximal medical therapy. The limited availability of donor organs still restricts its role. As a result, there is considerable i nterest in using organs from other species (xenografts). However, technical hurdles still r emain before this can be considered a viable option. The arti \201 cial heart is another a rea that has received much interest and publicity, and clinical trials are soon to be condu cted. 424 CHAPTER 8 Heart muscle diseases Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy (HCM) is characterized by unexplain ed LVH and has a prevalence of 1 in 500. HCM is a heterogeneous disorder in terms of clinic al manifestation, cardiac morphology, and natural history. Whereas the vast majority of aff ected individuals have a relatively normal life span, HCM is most recognized for being the commonest cause of exercise-related SCD in young individuals under 35 years of age. Genetics HCM exhibits marked allelic and non-allelic heterogeneity, with multiple mutations in at least 12 genes encoding sarcomeric contractile protein. The majority of the mutation s ( > 70 % ) are in the B -myosin heavy chain, troponin T and myosin-binding protein C gene s (see Table 8.1 ). Table 8.1 The frequency of sarcomeric gene mutations in HCM Mutation Frequency ( % ) B -myosin heavy chain 40 Myosin-binding protein C 25 Troponin I <10 Troponin T <5 A -Tropomyosin <5 Myosin light chain <1 A -Myosin heavy chain <1 Titin <0.5 Actin <0.5 Pathophysiology The macroscopic hallmark of HCM is LVH, which usually affects the inter- ve ntricular septum in an asymmetric fashion; however, almost any pattern of LVH is possible, including concentric LVH as seen in individuals with hypertension, and hypertrophy localize d to only 1 or 2 myocardial seg- ments. The magnitude of LVH is also variable and can range from very severe LVH ( > 30 mm) to very mild LVH (13 \200\22315 mm). There are also recogn ized familial cases where the only manifestation of the disorder is an abnormal ECG. Indivi duals with HCM often exhibit elongated mitral valve lea \202 ets. Histologically, there is evidence of myocyte disarray, myo- cardial scarring, and abnormal intramyocardial arteriol es. Together, these abnormalities manifest as: \200 hyperdynamic systolic function, which may be associated with \200 left ventricular out \202 ow tract (LVOT) obstruction due t o systolic anterior motion (SAM) of the anterior mitral valve lea \202 et (present in 725 % of patien ts at rest but up to 70 % during exercise) HYPERTROPHIC CARDIOMYOPATHY 425 impaired myocardial relaxation and raised \201 lling pressures \200 myocardial ischaemi a, and \200 propensity to potentially fatal supraventricular tachycardia (SVT) and VT/VF (ventricular \201 brillation). LVOT obstruction occurs as a consequence of forward motion of the anterior mitral lea \202 et towards the hypertrophied proximal interventricular septum in systole. There are two ma in postulated mechanisms, which include (1) anterior displacement of the papillary muscles and (2) the so-called Venturi effect, created by rapid ejection of blood across a narrow LV OT, which \200\230sucks \200\231 the anterior mitral valve lea \202 et against the septum . See also Table 8.2. Symptoms Patients with HCM are often asymptomatic and often identi \201 ed inciden- tally during routine medical examination, an abnormality on the ECG, or through family screening following the diagnosis in a \201 rst-degree relative. Recognized symptoms may include: fatigue and breathlessness due to impaired diastolic \201 lling and decreased cardiac output. Atrial transportation is very important for maintaining cardiac o utput, and symptoms typically deteriorate with AF \200 chest pain (angina) may result fro m increased cardiac work secondary to the LVH, a relative blood supply \200\223demand misma tch, and narrowing of intramural arterioles. High diastolic pressures increase the diastoli c wall stress and impair diastolic coronary blood \202 ow palpitations, pre-syncope, and syncope may occur due to atrial and ventricular arrhythmias or mechanical obstruction to cardiac output in those patients with left ventricular out \202 ow pressure gradients sudden death may be the initial presentation \200 approximately 5 % of patients may event ually develop progressive left ventricular dilatation and failure, due to ongoing myocardia l \201 brosis and chronic small-vessel ischaemia. Physical examination Look for LVH (a forceful apical impulse and an S 4 heart sound). Out \202 ow tract obstruction is evident by a double apical impulse and ejection systolic murmu r beginning in mid-systole, which may be augmented by provoca- tion by maneuvers such as Va lsalva or squatting. A pansystolic murmur due to mitral regurgitation resulting from the SA M of the mitral valve may also be present. 426 CHAPTER 8 Heart muscle diseases Table 8.2 Dynamic maneuvers to assess LVOT obstruction Decreased LVOT obstruction (murmur softer and shorter) Increased LVOT obstruction (murmur louder and longer) i LV volume d LV volume Squatting Sudden standing Handgrip Valsalva (during) Passive leg elevation Sublingual glyceryl trinitrate (GTN) Valsalva (after release) Hypovolaemia Mueller maneuver (deep inspiration against a closed glottis) Dehydration d Contractility i Contractility Beta-blockers (acute IV) Beta-agonists (e.g. isoprenaline) i Afterload d Contractility A -Blockade Phenylephrine Handgrip This page intentionally left blank 428 CHAPTER 8 Heart muscle diseases Hypertrophic cardiomyopathy: investigations ECG ECG is abnormal in > 95 % of cases. Isolate d Sokolow \200\223Lyon criterion for LVH is identi \201 ed in only 2 % of cases. Features include: \200 ST- and T-wave abnormalities \200 LVH with Romhilt \200\223Estes points \200\231 score > 5 \200 pathological Q waves in inferior and lateral leads (septal hypert rophy) \200 deep T-wave inversions (particularly in anterior and inferior leads in the apical form of HCM) pre-excitation and Wolff \200\223Parkinson \200\223White (WPW) syndrome \200 ventricular ectopics \200 atrial \201 brillation. Echocardiography Echocardiography continues to remain the gold standard investigation due t o its widespread availability. The investigation is usually for detection of the presence, magnitude, and distribution of LVH, as well as identi- fying patients with basal LVOT obstr uction. Recognized echocardiographic features include: \200 asymmetric septal hypertrophy (ASH): grossly thickened septum compared with posterior LV wall, with reduced septal motio n; however, almost any pattern of LVH is possible small LV cavity \200 SAM: systolic anterior movement of the mitral valve apparatus \200 mid-systolic aortic valve closure or \202 uttering of the aortic valve lea \202 et tips impaired diastolic function and left atrial enlargement. Cardiac magnetic resonance imaging (MRI) Cardiac MRI is extremely helpful for identifying a pical HCM, evaluating the anterolateral free wall, and demonstrating evidence of myocardial scarring and \201 brosis. Other investigations Other investigations may help in risk strati \201 cation, although no single investigation accurately predicts those at risk of SCD, and negative tests do not e ntirely exclude the risk of SCD: \200 ambulatory ECG monitoring \200\224 AF and ventricu lar tachycardia arrhythmias. Non-sustained VT is a risk factor for SCD exercise testing \200\224 functional capacity and blood pressure response to exercise. A \202 at blood pressure response during exercise (failure of the systolic blood pressure to rise by 25 mmHg from rest to peak exercise, or a paradoxical drop in systolic blood pressu re during exercise) is a recognized risk marker for SCD there is no role for cardiac catheterization in the diagnosis of HCM, although coronary ang iography may be performed in adult patients with angina to exclude co-existent coronary art ery disease (CAD) HYPERTROPHIC CARDIOMYOPATHY: INVESTIGATIONS 429 there is no role for electrophysiology studies in the diagnosis of HCM. Ventricular stimula tion studies have a poor predictive accuracy for the identi \201 cation of high-risk patie nts; however, radiofrequency ablation of accessory pathways and atrial \202 utter circuit s may be therapeutically important genetic testing is being utilized increasingly; however, a genetic diagnosis is currently only possible in 60 \200\22370 % of cases. Genetic testing is partic ularly useful for cascade screening of family members if a causative gene in the proband ca n be identi \201 ed. 430 CHAPTER 8 Heart muscle diseases Hypertrophic cardiomyopathy: treatment Approximately half of sudden deaths in HCM occur dur ing or shortly after strenuous exercise, and therefore patients should be advised against c om- petitive sports of a high-dynamic and high-intensity nature. The management of HCM incl udes (1) amelioration of symptoms including abolition of LVOT obstruction; (2) treatment of arrhythmias; (3) identi \201 cation of individuals at risk of SCD, with a view to implant ation of ICD; and (4) screening \201 rst-degree relatives for the disorder. Treatment for symptoms B -blockers B -blockers are the mainstay of therapy for angina, dysp noea, giddiness, and syncope. They reduce myocardial oxygen demand and improve diastolic \201 lling, and are effective in the treatment of angina and exertional dyspnoea. Large dos es may be required. Calcium-channel antagonists Calcium-channel antagonists (verapamil and diltiazem) are as ef fective as B -blockers and may be used in patients in whom B -blockers are not toler- ated or are contraindicated. Management of arrhythmias Beta-blockers and amiodarone are the anti-arrhythmic agents of ch oice in the management of supraventricular arrhytyhmias. None of these agents have been sho wn to reduce the risk of SCD. AV re-entrant tachy- cardia and atrial \202 utter are usual ly amenable to radiofrequency ablation. Sustained VT is treated with amiodarone but such pa tients are candidates for ICD; the amiodarone reduces the frequency of non-sustained ven- t ricular tachycardia (NSVT) and the need for recurrent anti-tachycardia pacing. Patients wit h AF should be anticoagulated with warfarin. Abolition of left ventricular out \202 ow obstruction Left ventricular out \202 ow obstru ction is treated pharmacologically, surgically, or by alcohol-induced trancoronary septal a blation. \200 Drugs : the drugs of choice include B -blockers or verapamil. Disopyramide, a negatively inotropic agent may be added in those with large symptomatic pre ssure gradients. Surgical myomectomy : surgical septal myotomy \200\223myectomy (Morrow procedure) directly debulks the proximal septum. It has been shown to relieve obstruction i n 90 % of cases and symptoms in 70 % over 5 years. The procedure is complicated by a risk o f high-degree AV block, requiring permanent pacing, and long-term complications include aor tic regurgitation. \200 Transcoronary septal ablation : alcohol septal ablation involves chemical infarction of the proximal portion of the interventricular septum by injection of alcohol into the \201 rst or second septal perforator artery. Initially, results have bee n promising; however, a signi \201 cant number of patients (10 \200\22325 % ) are rendered with complete heart block, necessitating permanent pacing. Unfortunately, there remain con cerns HYPERTROPHIC CARDIOMYOPATHY: TREATMENT 431 about the procedure in terms of the long-term impact of MI, notably adverse LV remodeling o f potentially sinister arrhythmias. Cardiac pacing : dual-chamber pacing with short AV delay has been shown to improve symptoms and abolish gradients in a small proportion of patients. In previous trials, most patients were asymptomatic for only short periods and therefore the procedure is only reserved for patients with severe symptomatic obstruction who are unsuitable for surgery or transcoronar y septal ablation. Sudden cardiac death The only effective therapy to prevent SCD is an ICD. De \201 nitive ( secondary) indications for an ICD include previous aborted SCD or haemodynamically unstable VT. Risk strati \201 cation in patients who are relatively asymptomatic and do not fall into t his category is less straightforward. There are currently several established risk factors; however, all have a relatively low sensitivity or speci \201 city to predict SCD in isola tion. The box below lists established risk factors for SCD. Each risk factor has a positive predi ctive accuracy of 20 \200\22325 % ; however, the negative predicitive accuracy of these ris k factors exceeds 90 % ; therefore the absence of any of these risks allows reassurance in most patients. Due to the relatively Iow positive predictive accuracy of any one of the fac tors in isolation, current practice indicates that at least two or more of these risk facto rs should be present to warrant ICD implantation for the purposes of primary prevention. Markers of risk for SCD in hypertrophic cardiomyopathy \200 Markers of risk for SCD in HC M \200 Unheralded syncope \200 Family history of SCD from HCM \200 Severe LVH ( > 30 mm) \200 Severe left ventricular out \202 ow obstruction ( > 60 mmHg) \200 Non-sustain ed VT on ambulatory ECG monitoring \200 Abnormal ( \202 at or decreasing) blood pressure response to exercise. 432 CHAPTER 8 Heart muscle diseases Restrictive cardiomyopathy Restrictive cardiomyopathy is a rare condition characterized by impaired diastolic function due to reduced ventricular compliance. It is very impor- tant t o distinguish restrictive cardiomyopathy from constrictive pericar- ditis, as the latter ca n be 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. Symptoms Patients often have severely limited exercise tolerance due to an inability to inc rease cardiac output, as their stroke volume is relatively \201 xed. They are also limite d by breathlessness and have evidence of right heart failure (peripheral oedema). Diagnosis Physical examination In addition to signs of CCF, a loud S 3 , S 4 , or both may be present. There also may be prominent x and y descents of the JVP, and venous pres- sure may increase on inspiration (Kussmaul sign). The apex beat will be palpable, in contrast to constrictive pericarditis. Investigations \200 ECG may show P mitrale or P pulmonale, reduced precordial QRS voltages, and atrial arrhythmias. Echocardiography may be normal, or at least demonstrate normal systolic function. Alternati vely, systolic function may be reduced in advanced cases. In \201 ltration may be evident by hypertrophied ventricles, and thickened intra-atrial septum, and the myocardium may appe ar speckled. Bi-atrial enlargement may also be present. A restrictive mitral in \202 ow pa ttern is seen on Doppler tracing. Laboratory test are aimed at determining causes of in \201 ltration. Left and right heart catheterization may be necessary to help to exclude constrictive pericarditis (a difference in left (LVEDP) and right (RVEDP) end-diastolic pressures > 7 mmHg at end-expiration makes constriction unlikely). Computed tomography (CT) and MRI scanning are useful to look at pericardial disease. Treatment Treatment is aimed at the symptoms of CCF and the underlying condi- tion. Rate co ntrol in AF is important, as reducing ventricular \201 lling times will have signi \201 cant impact. Patients with amyloid are very sensitive to digoxin. RESTRICTIVE CARDIOMYOPATHY 433 Causes of restrictive cardiomyopathy Myocardial \200 Non-in \201 ltrative \200 Idiopat hic \200 Scleroderma \200 In \201 ltrative \200 Amyloid \200 Sarcoid \200 Storag e diseases \200 Lysosomal storage disease (Gaucher \200\231s, Hurler \200\231s, Fabry) \200 Glycogen storage disease \200 Haemochromatosis. Endomyocardial \200 Endomyocardia l \201 brosis \200 Hypereosinophilic syndrome \200 Metastatic malignancies \200 Car cinoid \200 Iatrogenic (radiation anthracyclines). 434 CHAPTER 8 Heart muscle diseases Cardiac amyloidosis Amyloidosis is a clinical disorder characterized by extracellular depos ition of insoluble \201 bril proteins. Amyloid deposition can occur in connective tissue or blood vessels, and in a variety of organs including the heart, kidney, liver, and nervou s system. Cardiac amyloidosis is de \201 ned clinically by signs of myocardial or conducti on system dysfunction, due to involvement of the heart by amyloid deposition either as part of systemic amyloidosis or as a localized process. Classi \201 cation Systemic AL amyloidosis is the commonest form of clinical amyloid disea se. AL \201 brils consist of monoclonal immunoglobulin light chains and can be derived fr om any B-cell dyscrasia (e.g. myeloma, lymphoma), though benign monoclonal gammopathies are commonest. The disorder occurs equally in males and females over the age of 50 years, and usually in \201 ltrates multiple organs. Cardiac involvement occurs in up to 90 % of patie nts with AL amyloidosis, with approximately 50 % suffering diastolic heart failure. Systemic AA amyloidosis is a consequence of any chronic in \202 ammatory condition that fe atures a sustained acute phase response causing elevated production of serum amyloid A prot ein. Cardiac involvement is rare, but renal disease is the predominant \201 nding, with p roteinuria and renal failure. ATTR cardiac amyloidosis is a form of hereditary systemic amyloidosis with autosomal domina nt inheritance due to a mutation in the transthy- retin molecule (ATTR). The most common AT TR amyloid cardiomyop- athy is due to the Val122Ile mutation (substitution of isoleucine fo r valine at position 122) and is more prevalent in African-Carribean individuals, causing l ate-onset cardiomyopathy and progressive severe heart failure. Senile systemic amyloidosis is a slowly progressive in \201 ltrative cardiomy- opathy. The