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Cardiomyopathy 

Cardiomyopathy
Chapter:
Cardiomyopathy
Author(s):

Ali Khavandi

DOI:
10.1093/med/9780199654901.003.0004
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date: 29 November 2020

4.1 Primary cardiomyopathy

  • Patients with primary disorders of the myocardium tend to have a genetic component

  • The conditions fall broadly under five categories (Figure 4.1):

    • Dilated cardiomyopathy (DCM)

    • Hypertrophic cardiomyopathy (HCM)

    • Restrictive cardiomyopathy (RCM)

    • Arrythmogenic cardiomyopathy (ACM)

    • Unclassified cardiomyopathy (UCM or left ventricular non-compaction)

  • An inflammatory cardiomyopathy may also exist and is defined as inflammation of the myocardium and its structures by infectious or non-infectious agents.

Figure 4.1 Classification of cardiomyopathies based on a report of the World Health Organization and International Society and Federation of Cardiology. DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; RCM, restrictive cardiomyopathy; ACM, arrhythmic cardiomyopathy; UCM, unclassified cardiomyopathy.

Figure 4.1
Classification of cardiomyopathies based on a report of the World Health Organization and International Society and Federation of Cardiology. DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; RCM, restrictive cardiomyopathy; ACM, arrhythmic cardiomyopathy; UCM, unclassified cardiomyopathy.

Reproduced from Richardson et al. Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the definition and classification of cardiomyopathies. Circulation 1996; 93: 841–2, with permission of Wolters Kluwer Health.

4.2 Hypertrophic cardiomyopathy

Four cardinal features are key to diagnosis:

  1. 1. Unexplained hypertrophy of the left ventricle

  2. 2. Cardiac myocyte disarray

  3. 3. Familial occurrence

  4. 4. Association with sudden cardiac death.

  • Concentric, asymmetric, and apical patterns of hypertrophy are all well recognized

  • The presence of left ventricular outflow tract obstruction (LVOTO), although not essential for diagnosis, occurs in around a quarter of patients with clinical and prognostic implications.

Genetics

  • Hypertrophic cardiomyopathy is an inherited disorder with mutation of the sarcomeric proteins

  • Sarcomere is the contractile apparatus within the myocardial cells

  • Mutation leads to myocyte disarray and fibrosis, myocardial hypertrophy, and small vessel coronary artery disease.

  • Autosomal dominant mode of inheritance is most common, with increasing penetrance with age

  • Most common mutation is the gene for β‎-myosin heavy chain but many other mutations have been implicated (see Box 4.1)

  • Prevalence is estimated at 1 in 500

  • Only 60% are estimated to have a detectable mutation in sarcomeric genes

  • Some patients have phenocopies of HCM, i.e. a phenotype suggestive of HCM but an alternative underlying condition (e.g. Fabry’s disease, glycogen storage disorder, disorders of metabolism)

  • Phenocopies tend to have extra-cardiac manifestations and an increased incidence of conduction disease, cavity dilation, and heart failure.

Pathophysiology

  • Diastolic dysfunction (several mechanisms):

    • Normal calcium uptake required for early diastole is disrupted

    • Hypertrophy and interstitial fibrosis decrease compliance and cause the failure of passive relaxation

  • Small vessel ischaemia:

    • Changes occur in the microcirculation, with reduced arteriolar luminal size and capillary density

    • There is also a reduction in coronary flow reserve

  • LVOT obstruction:

    • Outflow tract obstruction occurs in 25% of patients (it can occur in the mid cavity and apex as well as at the sub-aortic level)

    • Systolic anterior motion of the mitral valve caused by abnormal mitral apparatus and abnormal haemodynamics leads to further obstruction as well as a degree of mitral regurgitation.

Clinical presentation

  • Asymptomatic:

    • Screening due to family history or abnormal ECG

  • Angina:

    • Small vessel coronary disease

  • Breathlessness:

    • Diastolic dysfunction due to left ventricular hypertrophy (LVH)

  • Raised pulmonary pressures:

    • Ischaemia ± mitral regurgitation

  • Dizziness/syncope:

    • Left ventricular tract obstruction

    • Ventricular arrhythmia

Physical signs include:

  • Rapid upstroke to pulse

  • Forceful left ventricle at apex (‘double impulse’)

  • Mid-late systolic murmur (no carotid radiation), which can be provoked with exercise or valsalva manoeuvre.

Diagnosis

Echocardiography

See Box 4.2.

  • Caution should be used to distinguish HCM from athlete’s heart in young, fit individuals

  • Athletes tend to have milder degrees of left ventricular hypertrophy (LVH) (septal thickness of 13–14 mm), the LV cavity tends to be enlarged, and diastolic parameters are normal or enhanced.

Guidelines are applicable only to first-degree relatives of index cases with confirmed hypertrophic cardiomyopathy, all of whom have a 50% probability of carrying the mutation. Diagnosis is established in the presence of one major criterion, or two minor echocardiographic criteria, or one minor echocardiographic plus two minor electrocardiographic criteria. Other causes of left ventricular hypertrophy (e.g. athletic training and hypertension) may confound diagnosis.

LV, left ventricular; SAM, systolic anterior motion of the mitral valve. Reproduced from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright 2009 with permission of Oxford University Press.

ECG

See Box 4.3.

Reproduced from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright 2009 with permission of Oxford University Press.

Cardiac magnetic resonance imaging

  • Permits accurate assessment of left ventricular hypertrophy and left ventricular mass

  • Late gadolinium studies are helpful in distinguishing from other forms of cardiomyopathy.

Screening investigations

  • Patients screened for HCM with echocardiography if family history or symptoms:

    • Pre-pubescent children only if symptomatic, have a high risk family history, undertake competitive sport, or there are high levels of parental anxiety

    • Adolescents: annual review from early adolescence, as clinical manifestations occur during puberty

    • In later life, five-yearly screening of relatives due to incidence of late onset HCM.

Prognosis and outcome

  • Clinical course is variable—annual mortality estimated at 1% for asymptomatic patients; 5% for symptomatic (overall 2–3%). See Box 4.4

  • Symptoms tend to be due to left ventricular outflow tract obstruction (LVOTO) and diastolic dysfunction due to LVH

  • Left ventricular thinning also occurs secondary to abnormal haemodynamics, leading to myocyte loss and fibrosis.

Risk stratification for patients with confirmed HCM

  • Risk stratification should be performed annually

  • Echocardiography to assess LV thickness and LVOTO

  • Exercise testing: inadequate Bp response defined as <20 mmHg rise in response to exercise

  • 24-h Holter monitor:

    • ≥ 3 beats of VT at rate of ≥ 120 bpm

    • Presence of AF (refer for formal anticoagulation)

    • Consider implantable loop recorder if suspicious history for malignant arrhythmia.

Management

Aims of management

  • Alleviate symptoms

  • Prevent complications, e.g. atrial fibrillation

  • Reduce risk of SCD.

Medical therapy

  • Asymptomatic patients:

    • Mild LVH—no treatment

    • Severe LVH—verapamil to improve relaxation and diastolic dysfunction

  • Symptomatic patients:

    • Calcium antagonists (verapamil or diltiazem) or BBs act as negative inotropes and reduce systolic LVOT gradient

    • Diuretics should be used with caution as patients can be very volume sensitive

    • Disopyramide can be used to alter calcium kinetics in the myocytes and is associated with reduced symptoms and reduced systolic pressure gradient

    • Amiodarone to reduce the burden of atrial fibrillation; formal anticoagulation should be strongly considered.

Additional therapy

  • Septal myectomy:

    • Marrow procedure is treatment for patients with refractory symptoms and obstructive HCM

    • Good long-term results but remodeling and cavity dilation seen in 15–20%

    • Complications include pacemaker implantation (3%) and ventricular septal defect (VSD; 1%)

  • Septal ablation:

    • Septal ablation is performed with LVOT gradient >30–50 mmHg (rest); 60–100 mmHg (with provocation)

    • The site of injection is identified by contrast echocardiography and alcohol injected into the first or second septal perforator leading to a limited infarction

    • In a third of cases, the pressure gradient disappears immediately; two thirds in weeks/months

    • Complications include pacemaker implantation (3–5%)

  • Implantable cardiac defibrillator implantation:

    • Implantable cardiac defibrillator implantation is indicated in patients at high risk of SCD

    • There is no evidence that medical therapy reduces the risk of SCD.

Special considerations

  • Pregnancy:

    • Cardiomyopathy generally well tolerated with low maternal mortality if asymptomatic with no high risk features

    • Joint cardiac and obstetric care is recommended

  • Exercise:

    • Patients with HCM should not undertake competitive sport

    • Burst exertion (e.g. sprints) and isometric exercise (e.g. weight lifting) should be discouraged

  • Elderly patients:

    • Elderly patients with HCM should be distinguished from those with non-genetic hypertensive heart disease. Hypertrophy tends to be milder in hypertensive disease

    • In the absence of a genotype, the presence of LVOTO, a disproportionate level of hypertrophy compared to the degree of hypertension, or an unusual pattern of hypertrophy, suggests HCM.

4.3 Dilated cardiomyopathy

  • Dilated cardiomyopathy (DCM) is a chronic heart muscle disease with cavity enlargement and impaired systolic function of the left or both ventricles

  • The diagnosis is made once other specific cardiomyopathies have been excluded (see Table 4.1)

  • Around 30–40% of cases are genetically transmitted

  • Prevalence of familial DCM is likely underestimated due to poor disease expression and a variability of phenotype for the same genetic abnormality leading to a number of presentations, e.g. arrhythmia, stroke, conduction system disease, and sudden cardiac death

  • Inheritance is commonly autosomal dominant but recessive, X-linked and mitochondrial forms are recognized

  • Proteins affected include dystrophin, desmin, cardiac actin, β‎ myosin heavy chain, cardiac troponins C and T, and lamin A/C proteins

  • Some environmental factors may unmask incomplete genetic penetrance, e.g. alcohol excess

  • Other causative factors include anthrocyclines, malnutrition, thiamine, and protein deficiencies

  • In patients with no family history, the mechanism is felt to be an acute myocarditis, e.g. secondary to a viral insult

  • There follows chronic inflammation and a possible exaggerated immune response leading to LV remodeling and dysfunction.

Table 4.1 Diagnostic criteria for dilated cardiomyopathy

Diagnostic criteria

Exclusion criteria

LV ejection fraction <45%

Blood pressure >160/100

Fractional shortening <25%

Coronary artery disease (>50% luminal stenosis)

Chronic alcohol excess

LV End-diastolic diameter >117% of predicted (age and body surface area corrected)

Clinical sustained and rapid tachycardia Systemic disease

Pericardial disease

Congenital heart disease

Cor pulmonale

Reproduced from ‘Guidelines for the study of familial dilated cardiomyopathies’, L. Mestroni, B. Maisch, W. J. McKenna, et al., Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy, Eur. Heart J., 20, 93–102, copyright 1999 with permission of Oxford University Press.

Clinical course and prognosis

  • The course is heterogenous

  • Better outcomes are associated with young age, shorter clinical history, improvement in LV function with medical therapy, a worse NYHA class on presentation, and a history of hypertension

  • Demonstrable genetic mutations are associated with a worse prognosis.

Diagnostic testing

  • Neurohormones:

    • Brain natriuretic peptide (BNP) relates to myocardial stretch

    • A value twice the upper limit of normal range is predictive of long-term mortality

  • ECG:

    • Atrial fibrillation and prologation of QTc are associated with increased mortality and heart failure progression

    • Prolongation of QRS duration (>120–150 ms) implies dyssynchrony and allows consideration for cardiac resynchronization therapy (CRT)

    • Ventricular arrhythmias detected on Holter monitoring are associated with increased mortality and allow consideration of implantable defibrillator (ICD)

  • Cardiopulmonary exercise testing:

    • Assessment of anaerobic threshold and ventilatory efficiency are reliable markers of mortality as well as part of the assessment for cardiac transplantation

  • Echocardiographic assessment of ejection fraction:

    • ≤30% indicates severe LV systolic impairment

    • 30–45%, moderate

    • >45% mild

    • >60% is normal

  • Cardiac MRI:

    • Cardiac MRI is the gold standard test for LV size, function, myocardial mass, and regional wall motion

    • Late gadolinium enhancement imaging can be helpful to identify scar and other patterns of uptake

  • Cardiac catheterization:

    • Cardiac catheterization excludes coronary artery disease and invasive assessments of cardiac output, pulmonary capillary wedge pressure, and trans-pulmonary gradient

  • Endomyocardial biopsy:

    • Endomyocardial biopsy is usually non-specific in DCM.

Management and prognosis

  1. 1. Treatment for heart failure:

    • ACE inhibitors/ARBs

    • Beta blockers (BBs)

    • Aldosterone antagonists

    • Heart rate controlling drugs such as If channel blockers should be considered

  2. 2. Discontinuation of cardiotoxics, e.g. alcohol, anthrocyclines

  3. 3. Assessment for device therapy:

    • Risk assessment for SCD (Box 4.5)

    • QRS >120 ms and NYHA >Class II for consideration of CRT

  4. 4. Exercise training/cardiac rehabilitation

  5. 5. Left ventricular assist device as bridge to transplant or to recovery

  6. 6. Cardiac transplantation.

NSVT: non-sustained ventricular tachycardia.

Risk assessment for SCD in DCM

See Box 4.5.

  • First-degree relatives of patients with DCM should be screened with ECG and echocardiography for early detection

  • Tests should be performed every 3–5 years

  • Medical therapy with ACE inhibitors and BBs improve pump function in 50% of patients; normalization occurs in 16%

  • Death occurs in around one-fifth of cases probably secondary to SCD; the remainder have terminal heart failure

  • Five-year survival is estimated at 30–35%

  • Optimized medical therapy has improved LV ejection fraction, NYHA class, risk for SCD, and transplant-free survival.

4.4 Restrictive cardiomyopathy

  • In restrictive cardiomyopathy (RCM) there is abnormal diastolic function due to rigid or thickened ventricular walls leading to elevated right- and left-sided filling pressures

  • Unlike constrictive cardiomyopathy, there is dissociation between the right and left chambers with respiration, i.e. there is ventricular discordance.

Classification

Primary RCM

  1. i. Loffler’s endocarditis (acute)

  2. ii. Endomyocardial fibrosis (chronic)

  3. iii. Idiopathic.

  • Pathophysiology is associated with inflammation (hypereosinophilia)

  • This is secondary to a chronic inflammatory process, e.g. parasitic infection, autoimmune disease, eosinophilic leaukaemia

  • It is rare in the Western world but endemic in African and South American countries.

Secondary RCM

This is due to specific material deposition within the myocardium by infiltrative disease, e.g. amyloid, storage disorders, or replacement by other molecules.

Loeffler endocarditis

Pathophysiology

  • Due to presence of a sustained hypereosinophilia secondary to an autoimmune state, parasitic infection, or an eosinophilic leukaemia leading to tissue infiltration

  • Eosinophilic endomyocardial fibrosis occurs secondary to an inflammatory response from cytotoxic and growth factor release

  • The severe eosinophilia also leads to a hyperviscosity syndrome

  • Myocardial fibrosis occurs at the left and/or right ventricular apices. It extends to the outflow tracts and involves the chordae leading to mitral and or tricuspid regurgitation

  • Histology demonstrates acute eosinophilic myocarditis.

Clinical features

  • Patients can present with weight loss, fever, cough, a rash. and congestive cardiac failure

  • Systemic embolization frequently occurs. causing renal and neurological complications

  • Cardiac dysfunction occurs in >50% of patients and mitral/tricuspid regurgitation is commonly seen

  • Death is secondary to congestive cardiac failure.

Diagnosis

  • CXR:

    • Radiological evidence of heart failure, biatrial dilatation

  • ECG:

    • Non-specific ST segment abnormality; AF common

  • Echo:

    • Localized apical thickening with chordal involvement

    • Mitral/tricuspid regurgitation

    • Biatrial enlargement

    • Preserved systolic function

    • Restrictive filling patterns

    • Reduction in mitral and tricuspid inflow velocities with inspiration

  • Cardiac catheterization:

    • High LV end-diastolic pressure

    • Thick obliterated ventricle

    • Mitral/tricuspid regurgitation

  • Biopsy:

    • Eosinophilic endomyocardial fibrosis.

Management

Treat the underlying cause: steroids for autoimmune disease, anti-parasitics for infection, disease modifying drugs for rheumatoid arthritis, chemotherapy for eosinophilic leaukaemia.

  • Heart failure management:

    • Diuretics (with caution as can lower filling pressures further by hypovolaemia)

    • ACE inhibitors/ARBs

    • BBs

    • Digoxin for AF

  • Anticoagulation:

    • LMWH/warfarin is mandatory

  • Surgery:

    • Endocardial decortication can be used in medically stable patients

  • Prognosis:

    • Death at 6–12 months from diagnosis; better if underlying disease can be treated.

Endomyocardial fibrosis

  • Endomyocardial fibrosis involves intense endocardial thickening leading to similar presentation to Loeffler endocarditis

  • Fibrosis leads to both restriction and constriction (if both ventricles affected)

  • There are three types: left ventricular (40%), right ventricular (10%), and biventricular (50%)

  • There are two forms:

    • African form: age 30–40 years with male:female ratio of 2:1. Secondary to parasitic disease (filarisis)

    • European form: age 30–50 years with male:female ratio of 1:2; secondary to autoimmune disease, particularly associated with glomerulonephritis, rheumatoid arthritis

  • Pathophysiology is similar to Loffler endocarditis but is less acute

  • Clinical course is chronic. Diagnostic tests give similar results to Loffler endocarditis.

Management

  • Heart failure treatment is as above but BBs are used with caution as bradycardias are poorly tolerated in patients with small ventricles and high filling pressures, giving significant diastolic dysfunction

  • Endocardial decortication is used, with or without mitral/tricuspid valve replacement

  • Transplantation is usually excluded due to pulmonary hypertension.

Prognosis

  • Patients remain stable for years but can deteriorate suddenly.

Differential diagnosis

  • Post-viral constrictive pericarditis

  • Carcinoid of the right ventricle

  • Amyloidosis.

Secondary restrictive cardiomyopathy

Amyloid heart disease

  • Amyloid is deposition of a soluble extracellular protein as an insoluble fibril causing loss of tissue architecture and function:

    • Acquired amyloid (AL or 1°) is deposition of fibril proteins from immunoglobulin light chains produced by plasma cells. It is associated with myeloma or monoclonal gammopathies

    • Secondary amyloid (AA) is associated with chronic inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, and familial Mediterranean fever. The amyloid fibrils consist of protein A. Nephrotic syndrome and renal failure are common at presentation

    • Senile systemic amyloidosis (TTR amyloid) involves the deposition of a fibril precursor of the protein transthyretin. Heart failure, heart block, and atrial fibrillation are recognized manifestations. It is slowly progressive and has a better prognosis than acquired forms

    • Hereditary amyloid is typically autosomal dominant. It is a mutation in any of the fibril precursor proteins for transthretin, apolipoprotein AI or AII, lysozyme, fibrinogen Aa chain, gelsolin, and cystatin C

  • Cardiac amyloid is mainly seen in primary, senile systemic (TTR), and certain hereditary forms

  • Cardiovascular involvement is seen in AA forms of the disease but is an unfavorable marker if present

  • Amyloid fibrils deposit within the myocardium, papillary muscles, valves, conduction tissue, and in the vessels

  • Suspicion of amyloid should be raised if there is

    • Cardiac disease in the presence of established AL amyloid ± plasma cell dyscrasia

    • Ventricular dysfunction/arrhythmia in patients with long-standing connective tissue disease or chronic inflammatory disorder

    • Any restrictive cardiomyopathy without explanation

    • Thickened ventricle on echocardiography but low-voltage ECG

    • Heart failure of unknown cause or refractory to treatment.

Investigations

See Table 4.2.

Table 4.2 Investigations for cardiac amyloid

12-lead ECG

  • Low voltage (though this is not always seen)

  • Varying degrees of atrioventricular block

  • Interventricular conduction delay/bundle branch block

  • Left-axis deviation

  • Poor R-wave progression*

Holter

  • Atrial fibrillation

  • Other tachyarrhythmia or bradyarrhythmia

Two-dimensional echocardiography

  • Concentric or asymmetric thickening of the left ventricular wall

  • Occasional thickening of the right ventricle

  • Thickened interatrial septum*

  • Sparkling/granular appearance of myocardium*

  • Thickened valves and/or papillary muscles

  • Left atrial or biatrial dilation

  • Diastolic dysfunction in early disease (E/A reversal)

  • Restrictive physiology (E >> A)

  • Pericardial effusion

  • Systolic impairment with normal end-diastolic volume

Histology

Apple-green birefringence under polarized light microscope after staining with Congo red* Immunoperoxidase stains to differentiate light chains/transthyretin/protein A, etc.

Cardiac catheterization

Raised filling pressures

Protein electrophoresis

Serum and urine electrophoresis for presence of monoclonal protein in patients with suspected AL amyloidosis

Genetic testing

Commercially available to detect common mutations

* Features considered relatively more specif c for amyloidosis.

Reproduced from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright 2009 with permission of Oxford University Press.

Management

  • Management aims at treatment of the underlying condition—hence identification of subtype is crucial

  • Treatment of heart failure is mainly with diuretics

  • ACE inhibitors/ARBs should be used with caution due to the frequency of hypotension

  • Digoxin is contraindicated as it binds to amyloid fibrils

  • BBs can promote AV blockade so should be used with caution

  • Ventricular arrhythmias can predict SCD

  • Cardiac transplantation is relatively contra-indicated in AL amyloid.

Prognosis

  • Prognosis for AL amyloid is very poor

  • Systemic senile amyloid is slowly progressive and requires no specific treatment

  • Reactive AA amyloid may improve with anti-inflammatory treatments.

Sarcoid heart disease

  • Sarcoid is a multisystem disorder characterized by deposition of non-caseating granuloma

  • It most commonly affects the lungs and lymphatics

  • Cardiac involvement is seen in around a quarter of cases, affecting mainly the LV free wall and septum

  • Right-sided and atrial involvement is recognized

  • Sarcoid should be considered in

    • Young people presenting with conduction disease

    • Patients with unexplained DCM and AV block and features of abnormal wall thickness, regional wall motion abnormality, or apical/septal perfusion defects that improve with stress nuclear imaging

    • Patients with sustained VT with no obvious cause

    • Pateients with RCM of unknown cause

    • Presumed ARVC or AV block in patients with chronic respiratory disease.

Clinical presentation

  • Arrhythmia/conduction abnormality

  • Heart failure

  • Pericardial effusions, constriction, and valvular disease recognized

  • SCD can be first presentation

  • Isolated cardiac involvement is rare—presentation usually follows systemic manifestation of the disease.

Diagnosis

  • Investigations can include:

    • Serum ACE

    • 12-lead ECG

    • Holter monitoring

    • Chest X-ray

    • Echocardiography

    • Myocardial perfusion imaging

    • Cardiac MR

    • Cardiac catheterization

    • Endomyocardial biopsy

  • See Table 4.3 for guidelines on diagnosis.

Table 4.3 Guidelines for diagnosis based on study report on diffuse pulmonary disease for Japanese Ministry of Health and Welfare, 1993

Histology

Endomyocardial biopsy demonstrating epitheloid granulomata without caseating granulomata

Clinical

Exclusion of other aetiologies and the presence of complete RBBB, LAD, AV block, VT, ventricular ectopy on ambulatory ECG plus one of the following:

  1. 1. Abnormal wall motion, regional wall thinning of dilatation of the left ventricle

  2. 2. Perfusion abnormality on perfusion imaging

  3. 3. Abnormal intracardiac pressure, low cardiac output, abnormal wall motion or reduced left ventricular ejection fraction

  4. 4. Evidence of interstitial fibrosis or cellular inflammation

Adapted from Hiraga H, Yuwai K, Hiroe M. et al., ‘Guideline for diagnosis of cardiac sarcoidosis’, published in ‘Cardiac sarcoidosis’, Abdul R. Doughan, Byron R. Williams, Heart 92, 282–288, copyright 2006 with permission of BMJ Publishing.

Management

  • Early treatment with corticosteroids is first-line treatment

  • Other treatments include chloroquine, hydoxychloroquine, and methotrexate

  • Resolution of arrhythmia and conduction disease can be seen, as well as some resolution in LV function

  • Treatment should be started prior to standard heart failure treatment if possible

  • Pacemaker implantation should be performed in patients with high-grade AV block

  • Defibrillators should be used in patients who survive cardiac arrest or have refractory ventricular arrhythmia

  • Pacemaker/ICD implantation and steroid treatment improve prognosis

  • Catheter ablation can be used to treat recurrent VT

  • Transplantation is rare.

4.5 Storage diseases

  • Storage diseases are inborn errors of metabolism resulting in the abnormal accumulation of the substrate or byproduct in tissues (see Table 4.4)

  • Intracellular deposition distinguishes them from infiltrative disease, where deposition is within the interstitium

  • Within the myocytes, the presence of these metabolites is toxic, causing either concentric (HCM-like phenotype) or eccentric (DCM-like phenotype) changes

Table 4.4 Summary of cardiovascular manifestations of some inborn errors of metabolism.

Mechanism

Genetics

Presentation

Diagnosis

Management

H aemachromatosis

Iron overload and deposition

Mutation on HFE gene encoding for transferrin receptor. AR inheritance with variable penetrance.

Liver, pancreas, joints and heart affected. Heart failure, SVTs, AV blockade, raised atrial pressures (restrictive filling)

  • Echo: normal LV thickness

  • CMR

  • Histology: stainable iron within the sarcoplasm

  • Regular phlebotomy Serial EMB±CMR, FBC and iron studies to assess treatment.

  • Standard heart failure and arrhythmia management Screening of first-degree relatives

GSD Type II (Pompe's Disease)

Acid α‎ galactosidase (acid maltase) deficiency

AR inheritance

Within first few months—failure to thrive, hypotonia, macroglossia, hepatomegaly

  • CXR: cardiomegaly Raised cardiac enzymes ECG: short PR, LAD, high voltage QRS

  • Enzyme assay of muscle or skin fibroblasts shows no acid maltase activity Echo: bilateral ventricular hypertrophy; HCM phenotype ± SAM

Previously poor prognosis with death. New treatment with recombinant acid maltase (acid α‎ galactosidase) enzyme replacement now promising.

GSD Type III (Corbi or Farbe's disease)

Amylo-1,6,-glucosidase deficiency causing phosphorylase limit dextran accumulation

AR inheritance with variable phenotype

Fasting hypoglycaemia and hepatomegaly. Many patients asymptomatic but recurrent sustained VT and SCD seen

Echo: HCM-type phenotype ± SAM. CMR: late gadolinium suggestive of late fibrosis

GSD Type IV

Amylo 1,4-1,6 transglucosidase deficiency with accumulation of polyglucosan bodies in the liver

Liver dysfunction, skeletal myopathy and heart failure

GSD = glycogen storage disorders.

Anderson-Fabry’s disease

  • Fabry’s disease is an X-linked genetic disorder causing a deficiency in α‎-galactosidase

  • It leads to a deposition of glycosphingolipids (particularly globotriaosylcermide) in the skin, endothelium, kidneys, liver, pancreas, and central nervous system

  • Patients may present a multi-system disease (see section on ‘Cardiovascular presentations’) with obstructive airways disease, proteinuria, end-stage renal disease, or stroke

  • Cardiovascular deposition is within the myocardium, conduction tissue, valves, and vascular endothelium.

Cardiovascular presentations

  • Patients present with heart failure, conduction disease, arrhythmia and angina

  • It is an incidental finding on echocardiography with unexplained LVH

  • Endothelial involvement is associated with subendocardial ischaemia

  • LVH and reduced coronary flow reserve may also be the cause of angina

  • Renal involvement increases the incidence of hypertension and hypercholesterolaemia and leads to premature coronary artery disease

  • Increased prevalence of smoking in this population also contributes to this higher risk of premature coronary artery disease

  • Stroke is seen as a consequence of deposition within the cerebral endothelium.

Extra-cardiac features

  • Cutaneous:

    • Angiokeratomas

    • Lympoedema

  • Neurological:

    • Tinnitus

    • Vertigo

    • Headache

    • TIA/stroke

    • Chronic arm and leg pain

    • Fabry crisis (severe acute pain precipitated by emotional or physical stress)

  • Gastrointestinal:

    • Diarrhea

    • Abdominal discomfort or vomiting

  • Renal:

    • Proteinuria

    • Renal failure.

Investigations

  • Echocardiography reveals increased wall thickness (concentric and septal patterns) with associated systolic anterior motion of the mitral valve and LVOTO

  • Systolic function is preserved whilst mild–moderate diastolic dysfunction is seen

  • Restriction is rare

  • Thickened papillary muscles and mitral valve leaflets occur in over 50% of patients

  • The diagnosis is made by demonstration of reduced α‎-galactosidase activity in the plasma or peripheral leukocytes

  • 6% of patients with ‘late-onset HCM’ have Fabry’s disease

  • Women have relatively high levels of α‎-galactosidase which can limit the assay in its use (women express varying phenotypes due to random inactivation of an X-chromosome)

  • Genetic testing can be helpful.

Management

  • Treatment is with enzyme replacement therapy, which can reduce the overall tissue and serum load of glycosphingolipids leading to a reduction in pain symptoms, renal complications, and improved quality of life

  • There is currently limited evidence in the regression of cardiac disease

  • Anginal symptoms should be treated with antiplatelet agents and calcium antagonists

  • BBs are used with caution due to the incidence of conduction disease and bradycardia

  • Heart failure is treated with standard treatments; transplant can be considered in severe cases.

Post-radiation disease

  • Radiation damage can affect any part of the heart (see Table 4.5) and is seen after treatment for lymphoma as well as breast, lung, and testicular malignancy

  • Symptoms are associated with the area affected

  • Regular assessment with 12-lead ECG, echocardiography, exercise testing, Holter monitoring, and cardiac MR is useful for occult disease

  • Newer radiotherapy techniques involve smaller doses as well as shielding

  • Cardiovascular risk assessment and aggressive treatment can reduce the risk of coronary disease

  • The use of cardiotoxic chemotherapy with radiotherapy should be avoided.

Table 4.5 Summary of cardiac complications from radiation

Structure

Mechanism

Clinical features

Myocardial

  • Damage occurs due to microcirculatory damage and free radical toxicity.

  • Acute inflammation of small/medium sized arteries is followed by latent phase of thrombosis and ischaemia. Myocyte death and fibrosis follows.

  • Clinically overt cardiomyopathy (restrictive CM) is uncommon.

  • Anthrocycline induced DCM-like phenotype does occur with more frequency when associated with radiation exposure.

Pericardial

  • Early complications are associated with radiation induced necrosis of tumour masses adjacent to the heart. Treatment is usually continued with no long-term sequelae.

  • Late presentation is due to a chronic constrictive pericarditis and presence of a chronic pleural effusion

  • Acute symptoms of pericarditis—fever, chest pain.

  • Chronic constriction leads to right-sided heart failure. Pericardectomy is treatment of choice in intractable cases.

Conduction disease

Sick sinus syndrome and AV block have been reported

Valve disease

Around a third of patients had valve demonstrable valve disease (mainly aortic) post radiation therapy

Coronary artery disease

Ostial left main stem and left anterior descending disease can be seen in patients who have had mediastinal radiotherapy. Often, other risk factors for CAD are present

Reproduced from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright 2009 with permission of Oxford University Press.

4.6 Arrhythmogenic cardiomyopathy

The WHO classification

  • A group of heart muscle disorders characterized by structural and functional abnormalities of the right ventricle due to localized or diffuse atrophy, with replacement of the myocardium by fatty and fibrous tissue

  • Areas affected are the outflow tract, apex, and subtricuspid areas of the free wall

  • The septum is spared

  • There is replacement of myocardial tissue with fibro-fatty infiltrates (mainly diffuse) with increase wall thickness

  • Saccular aneurysms are present in 50% of cases

  • Genetic predisposition plays a part—familial component in 30–50% of cases with several genes implicated (autosomal dominant and recessive).

Clinical presentation

  • Exercise-induced symptomatic VT of RV origin (LBBB pattern)

  • Palpitations/syncope/pre-syncope

  • Sudden cardiac death

  • Some patients present with heart failure and ventricular arrhythmia and misdiagnosed as DCM.

Diagnosis

  • The ECG is abnormal in 90% of cases with the presence of an epsilon wave being a distinct marker of disease (Figure 4.2)

  • Imaging (echocardiography, cardiac MR and RV angiography) demonstrates RV dilatation, segmental or regional wall motion abnormality. and the presence of saccular aneurysms

  • Diagnosis based on two major criteria, one major plus two minor criteria, or four minor criteria (Box 4.6).

Figure 4.2 ECG lead in V1 with T wave inversion and epsilon-wave (arrows) in a patient with arrhythmogenic right ventricular cardiomyopathy.

Figure 4.2
ECG lead in V1 with T wave inversion and epsilon-wave (arrows) in a patient with arrhythmogenic right ventricular cardiomyopathy.

Reproduced from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright Oxford University Press 2009.

LBBB, left bundle branch block; LV, left ventricle; RBBB, right bundle branch block; RV, right ventricle. Reproduced from ‘Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy’, Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. W. J. McKenna, G. Thiene, A. Nava et al., British Heart Journal, 71, 215–218, copryight 1994 with permission from BMJ Publishing Group Ltd.

Management

  • Use standard heart failure treatment with ACE inhibitors/ARBs, BBs, aldosterone antagonists, and digoxin (see Table 4.6)

  • Transplantation should be considered in those patients with refractory symptoms despite full standard therapy

  • ICD use may be limited due to the abnormal RV myocardium giving low endocardial signals and increased pacing thresholds

  • Catheter ablation can be used but new foci arise in around half of cases

  • Sustained VT refractory to drug treatment may require transplantation.

Table 4.6 Arrhythmia management

Good systolic function Non-life-threatening arrhythmias

Medical therapy with amiodarone, beta blockers or propafenone

Reduced systolic function

Amiodarone, beta blockers or class I agents

Syncope, cardiac arrest, documented VT/VF and a family history of sudden cardiac death

Implantable defibrillator

Prognosis and outcome

  • Biventricular dysplastic involvement leading to a DCM is rare

  • Progressive right ventricular failure occurs in some patients

  • Untreated sustained or non-sustained VT may be well tolerated but can degenerate to VF in 1–2% of cases.

4.7 Unclassified cardiomyopathy

  • Unclassified cardiomyopathy is also known as left ventricular non-compaction (LVNC)

  • It is a genetic-based disease where there is a two-layer myocardium: a thin compacted layer adjacent to the epicardium and a thicker non-compacted layer adjacent to the endocardium.

Aetiology

  • The myocardium is a loose network of fibres separated by deep recesses during embryogeneisis

  • At weeks 5–8, these fibres compact down, with the intratrabecular recesses becoming capillary networks

  • LVNC is the arrest of normal myocardial maturation by unknown mechanisms

  • Isolated LVNC has been associated with a Z protein seen in cardiac muscle on the X chromosome; autosomal dominant inheritance is more commonly seen.

Pathophysiology

  • Subendocardial ischaemia due to compression of intramural coronary vessels may cause areas of ischaemia and fibrosis

  • It leads to remodeling and dilatation causing systolic impairment, and substrate for arrhythmia

  • Excess trabeculation limits myocardial compliance and causes diastolic dysfunction

  • Thromboembolism (cerebral, mesenteric, or pulmonary) is seen due to stagnation of blood within the trabeculae.

Clinical presentation

  • Patients present at any age with heart failure, arrhythmia, or thromboembolic complications

  • It can also be an incidental finding or be observed as part of family screening for SCD

  • ECG can show high-voltage QRS and repolarization abnormality and shifts in QRS axis

  • High-quality transthoracic echo, with or without the use of contrast, or cardiac MR is used to confirm the diagnosis.

Diagnostic criteria

  • The ratio of N/C ≥2 in adults (N/C ≥1.4 in children) where N and C are the maximal end-systolic thickness of the non-compacted and compacted layer respectively

  • The ratio of the depth of the intratrabecular recesses and overall wall thickness is also significantly high

  • Other features include:

    1. 1. Prominent and excessive trabeculation in the non-compacted layer

    2. 2. Deep intratrabecular recesses that fill completely with blood

    3. 3. Localization of the non-compacted regions at the apex, lateral, and inferior walls

  • Although left ventricular dilatation and systolic impairment is seen, it is not essential for diagnosis

  • LVNC can be misdiagnosed as apical HCM, DCM, apical thrombus, or apical infarction.

Management

  1. 1. Standard heart failure treatment is used for LV dysfunction

  2. 2. Arrythmia management: ICD implantation is used for patients with:

    • Sustained VT

    • Recurrent unexplained syncope

    • LV ejection fraction <35% on optimal medical therapy with non-sustained VT on Holter monitor

  3. 3. Thromboprophylaxis: formal anticoagulation in patients with ventricular dilatation and systolic impairment, or previous embolic event

  4. 4. Cardiac transplantation in patients refractory to treatment.

Prognosis and outcome

  • Initially felt to have high mortality but increase in diagnosis rates has demonstrated patients at lower risk

  • Timely detection, appropriate treatment, and ICD implantation may also improve prognosis.

4.8 Inflammatory myocardial disease

  • Inflammatory cardiomyopathy is characterized by myocarditis in association with cardiac dysfunction

  • The underlying cause may be idiopathic, autoimmune, or infectious (Box 4.7).

Reproduced from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright 2009 with permission of Oxford University Press.

Pathophysiology

  • There are various hypotheses regarding the mechanism of myocarditis

  • It may be secondary to a virus triggered inflammation in those patients with a genetic predisposition to myocardial inflammation

  • The virus can cause a direct toxic effect or cause a secondary immune response, which can persist despite elimination of the virus

  • Alternatively there may also be persistent chronic infection driving a continued inflammatory response. This could be in the form of antibodies cross-reacting with myocardial antibodies or the release of cardiodepressive cytokines causing myocardial dysfunction.

Clinical presentation

  • Patients present with heart failure, chest discomfort, palpitations, syncope, or SCD

  • There can be a temporal relationship with a viral infection, although this is quite often subclinical

  • Acute fulminant myocarditis: acute and rapid onset with severe LV dysfunction which may need inotropic or mechanical support

  • Acute non-fulminant myocarditis: usually presents with chest pain, non-specific ECG changes, and a rises in serum troponin and C reactive protein

  • The coronary arteries are normal

  • Echo shows preserved systolic function but may demonstrate regional wall motion abnormality

  • Pericardial effusion and wall oedema is seen on echo and cardiac MR

  • In both clinical scenarios, arrhythmias can be seen. Patients can present with SCD.

Management

  • Secondary causes of heart failure should be excluded

  • Standard heart failure treatment including ICD and LVAD, either as bridge to recovery or transplantation

  • If patients improve they should be closely monitored with serial echo, ECG, and Holter monitoring

  • If there is progressive LV dysfunction, immunomodulatory treatment and transplantation should be considered

  • Endomyocardial biopsy and immunohistology may be necessary to help with aetiology (Figure 4.3)

  • Immunomodulatory treatment strategies are dependent on the absence of viral persistence by immunohistology

  • Persistent inflammation due to an autoimmune response in the absence of any virus may respond to immunosuppression.

Figure 4.3 Endomyocardial biopsy and immunohistology may help with aetiology.

Figure 4.3
Endomyocardial biopsy and immunohistology may help with aetiology.

Reproduced with permission from The ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright Oxford University Press 2009.

Prognosis and outcome

  • No clinical parameter predicts outcome

  • The presence of viral persistence and chronic inflammation is associated with an adverse prognosis

  • 5-year survival is estimated at around 35%; initial presentation of fulminant myocarditis and heart failure is associated with a better outcome.

HIV cardiomyopathy

  • Cardiac involvement can be seen in 50% of HIV positive patients (usually sub-clinical)

  • The pathogenesis is felt to be a result of either continued infection by HIV-1 of the myocardial cells, further opportunistic infection of the myocardium by other organisms, or as a result of nucleoside analogue treatment

  • Management is with standard heart failure treatment but caution should be used given the interactions with protease inhibitors.

Chagas disease

  • Chagas disease is a protazoal myocarditis after infection with Trypanosoma cruzi

  • It is endemic in south and central America and is transmitted by realuvid bug, but an be from animal reservoirs, blood transfusion, and vertical transmission

  • Patients present with fatigue, fluid retention, conduction disease, progressive left ventricular dysfunction, ventricular arrhythmia, sudden cardiac death, and thrombo-embolic disease

  • Investigations include the Machado-Guerreiro complement fixation test, indirect immunofluorescence or ELISA, 12-lead ECG, and echocardiography

  • Echo can demonstrate global LV systolic dysfunction but can show septal sparing, posterior wall hypokinesia, and apical aneurysm formation.

Treatment

  1. 1. Antiparasitics, e.g. benzidazole, which reduces but does not eradicate the organism

  2. 2. Heart failure treatment

  3. 3. Antiarrhythmics, e.g. amiodarone

  4. 4. Anticoagulation.

Lyme disease

  • Lyme disease is an infection with a tick borne spirochete, Borrelia burgdorferi

  • Patients present with erythema migrans and general malaise

  • Cardiac and neurological features occur after weeks and months

  • It is more common in females but men tend to suffer more complications

  • Cardiac sequelae include conduction disease, myo-pericarditis, and a self-limiting cardiomyopathy

  • Other complications include cranial nerve palsies and a migratory polyarthiritis

  • Diagnosis is made on the basis of the history of tick bite, clinical findings, and serological studies

  • Treatment should be in an expert centre

  • The antibiotic of choice is doxycycline

  • Intravenous ceftriaxone is used for 2–4 weeks if there are cardiac or neurological signs.

4.9 Secondary myocardial diseases

Ischaemic cardiomyopathy

  • Ischaemic cardiomyopathy is the most common cause for heart failure in the Western world

  • There is conflicting data on the benefits of revascularization

  • The mechanism of injury can be due to:

    • Myocardial infarction—irreversible damage; neurohormonal activation can lead to further adverse remodeling

    • Myocardial ischaemia—stunning and hibernation

  • Viability assessments can help distinguish between those areas of myocardium that are dead and those that are alive and may improve by revascularization.

Management

  • Management uses standard heart failure treatment with medical and device therapy

  • Revascularization can be considered. In patients with anginal symptoms there is data to support improved symptoms and prognosis with severe left ventricular dysfunction and three-vessel coronary artery disease

  • In patients without chest pain revascularization is contentious. A number of small studies have shown improvement in left ventricular function, symptoms, and prognosis with surgical revascularization (CABG). The current AHA/ACC guidelines (see Further Reading section) recommend CABG being offered to patients with:

    • Proven significant regions of hibernation

    • Left main stem/equivalent disease

    • Severe three-vessel coronary disease

  • Surgery in this group is, however, high risk, particularly in those with an LV end-diastolic diameter of >7 cm.

Hypertensive cardiomyopathy

  • Hypertension-induced LVH is independently associated with ventricular dysfunction, arrhythmia, and sudden cardiac death.

Pathophysiology

  • The condition involves enlargement and proliferation of cardiac myocytes and interstitial fibrosis

  • An increase in collagen content leads to ventricular non-compliance and diastolic dysfunction

  • The abnormal myocardial microcirculation fails to enlarge at the same rate as the increase in muscle mass

  • This, together with endothelial dysfunction and perivascular fibrosis, leads to ischaemic symptoms despite normal epicardial coronary arteries.

Clinical presentation

  • Patients may complain of chest pain and breathlessness (from diastolic dysfunction) but some remain asymptomatic

  • There is high prevalence of atrial fibrillation

  • Frequent ventricular ectopics are seen; sustained VT is unusual but some patients do present with SCD.

Management

  • Treatment with antihypertensives can reduce the degree of LVH hence reducing cardiovascular risk

  • ACE inhibitors/ARBs are the treatment of choice (in combination with standard antihypertensives).

Alcoholic cardiomyopathy

  • Ethanol at a level of >90 g daily for >5 years is felt to unmask a genetic predisposition to dilated cardiomyopathy via a direct toxic effect on myocytes and function

  • Two phases of the disease are recognized:

    1. i. Initial asymptomatic phase with isolated LV cavity enlargement and diastolic dysfunction

    2. ii. Clinically overt phase with signs and symptoms of heart failure and LV systolic dysfunction

  • Incidence of arrhythmia such as AF and non-sustained VT are similar to those patients with DCM

  • SCD rates are also comparable but this figure can be attenuated by abstinence

  • Standard heart failure treatment improves ventricular function

  • Therapy is more effective when the patient abstains from alcohol.

Metabolic cardiomyopathy

  • Metabolic cardiomyopathy is myocardial dysfunction secondary to a derangement in metabolism

  • It includes nutritional disorders such as thiamine deficiency, which is a cause of cardiomyopathy worldwide

  • The most common metabolic disorder is diabetes.

Beri-beri (Vitamin B1 deficiency)

  • Thiamine deficiency (Vitamin B1) is prevalent in Asia due to the consumption of thiamine-deplete polished rice

  • Diagnostic criteria include:

    • Cardiomyopathy whilst in normal sinus rhythm

    • Dependant oedema

    • Signs of a neuritis and/or pellagra

    • A history of over three months of thiamine deficiency

  • Patients have a reduced serum thiamine, raised pyruvate and lactate, and a low red cell transketolase

  • Patients present with either high-output cardiac failure and a peripheral neuropathy (‘dry’ beri-beri) or fatigue, malaise, and oedema (‘wet’ beri-beri)

  • Other features include an anaemia, painful glossitis, and hyperkeratinized skin lesions

  • Treatment is with intravenous followed by oral thiamine deficiency and is associated with good recovery.

Diabetic cardiomyopathy

  • Diabetes affects ventricular function independent of its effect on the coronary arteries and concurrent hypertension

  • Prevalence of heart failure is higher and patients have a poorer prognosis

  • Patients tend to have more extensive coronary disease as well as small vessel disease

  • There is thickening of the basement membrane, myocellular atrophy and hypertrophy with myocardial and interstitial fibrosis leading to ventricualr dysfunction

  • Standard heart failure treatment may attenuate remodeling and improve prognosis

  • Optimal glycaemic control is mandatory.

Takotsubo cardiomyopathy

  • Takotsubo cardiomyopathy is characterized by LV dysfunction with severe impairment of the apical and mid segments and sparing of basal segments

  • It predominately affects women (usually in their sixties) and is often triggered by emotional or physical stress

  • Patients present with chest pain or breathlessness

  • ECG demonstrates ST elevation, usually in the anterior chest leads, and patients are commonly treated for STEMI/ACS, but normal coronary arteries are seen on cardiac catheterization

  • LV angiography and echocardiography show the characteristic features of severe LV impairment with sparing of the basal segments (‘apical ballooning’)

  • Some patients have basal segment involvement (‘reverse Takotsubo’)

  • Low–moderate tropinin elevation is seen

  • The pathophysiology is incompletely understood—catecholamines appear central, either via vasospasm or other toxic effect. The result is significant but usually transient LV dysfunction

  • Treatment with aspirin, ACE inhibitors/ARBs and BBs and nitrates is used to reduce afterload, heart rate, and vasospasm

  • Clinical outcomes are generally good, with resolution of LV dysfunction in hours/days

  • Treatment can be stopped at 3–6 months but recurrence can occur in around 5% of patients.

Tachycardiomyopathy

  • Incessant arrhythmia, such as SVT or AF (heart rates 180–200 bpm), can lead to LV dysfunction

  • The restoration of sinus rhythm improves left ventricular function

  • Heart rate reduction: BBs and ivabradine have demonstrated prognostic benefit in patients with heart failure

  • Catheter ablation to restore sinus rhythm has been beneficial in restoring LV function in patients with incessant tachycardia.

Muscular dystrophy cardiomyopathy

  • Primary disorders of skeletal muscle may affect cardiomyocytes

  • There are many disorders associated with myocardial disease (Table 4.7)

  • Skeletal deformity of the chest also leads to raised pulmonary pressures, leading to secondary cardiomyopathy

  • Patients with muscular dystrophy should be periodically monitored with ECG, Holter monitoring, and echocardiography.

Table 4.7 Cardiac manifestations in muscular dystrophies

Type

Inheritance

Mechanism of disease expression

Extracardiac manifestations

Cardiac manifestations

Duchenne

X-linked

Absence of dystrophin leads to disruption of the mechanical link between the sarcolemma and the extracellular matrix

Childhood onset Progressive proximal myopathy

Dilated cardiomyopathy

Becker

X-linked

Dystrophin present but at reduced levels

Onset age >12 years with slowly progressive proximal myopathy

Dilated cardiomyopathy

Emery-Dreifuss

X- linked AD, rarely AR

Loss of emerin (inner nuclear protein) Lamins A and C (nuclear envelope proteins)

Ankle, elbow and neck contractures Slowly progressive myopathy

Absent/reduced p waves refractory to atrial pacing; require V pacing AF/A flutter Massive atrial dilatation requiring anticoagulation Dilated cardiomyopathy SCD

Myotonic (Type A)

AD

Abnormal expansion of trinucleotide repeat sequence on myotonin protein kinase gene (DMPK) which modifies actin cytoskeleton. Demonstrates genetic anticpation

Myotinia Facial, pharyngeal and distal limb muscles Diabetes and thyroid dysfunction Cataracts

Conduction disease—may require pacing AF/flutter Ventricular arrhythmia SCD LV dilatation ± systolic impairment Mitral valve prolapse Left ventricular hypertrophy

Adapted from the ESC Textbook of Cardiovascular Medicine 2nd edition, ed. John Camm, Thomas Lüscher and Patrick Serruys, copyright 2009 with permission of Oxford University Press.

Peripartum cardiomyopathy

  • Peripartum cardiomyopathy occurs in around 1/3000–1/10000 pregnancies

  • It is defined as left ventricular systolic impairment with the following:

    1. 1. Presentation one month prior to delivery or five months post partum

    2. 2. Absence of pre-existing cardiac disease

    3. 3. No other cause for cardiac dysfunction

  • Aetiology is unclear, with hypotheses including an inflammatory component, malnutrition, or a familial DCM that is unmasked by the cardiovascular burden of pregnancy

  • There are some features that predispose patients to developing the disease (Box 4.8)

  • Physical examination can be difficult as third heart sound and systolic murmurs can be heard as part of normal pregnancy

  • ECG: sinus tachycardia and left axis deviation are normal for pregnancy

  • Echocardiography is the investigation of choice. The definition of LV systolic dysunction is LVEF <45% or fractional shortening of <30% with an end-diastolic diameter of 2.7 cm/m2 body surface area.

Data from ‘Peripartum cardiomyopathy: a condition intensivists should be aware of’, E. de Beus, W. N. van Mook, G. Ramsay et al., Intensive Care Med., 29, 167–74, copyright 2003 with kind permission from Springer Science and Business Media; and ‘A review of peripartum cardiomyopathy’, P. R. James, Int. J. Clin. Pract. 58, 363–5, copyright 2004 with permission from John Wiley and Sons.

Management

  • Standard heart failure therapy is used, e.g. diuretics and supportive measures including intra-aortic balloon pumps for cardiogenic shock

  • ACE inhibitors/ARBs are contraindicated in the first trimester—they cause oligohydramnios

  • Thrombo-prophylaxis: increased risk from prolonged bed rest, diuretic use, and impaired left ventricular function.

Prognosis and outcome

  • Mortality and transplant rates are around 7%. Most patients have resolution of systolic function

  • Death is usually from pump failure

  • Counselling is important after the event:

    • Subclinical LV systolic dysfunction exists and another pregnancy is likely to cause decompensation thus risk of recurrence must be emphasized

    • Incidence of complication is higher, e.g. maternal death, foetal prematurity, and loss

    • Women with completely normalized LV function are at low risk but heart failure will occur in 20% of those patients with residual LV impairment

  • All patients with previous peripartum cardiomyopathy need close monitoring in the event of subsequent pregnancies.

4.10 Cardiac transplantation

  • Cardiac transplantation is the final option for those patients with progressive heart failure despite optimal medical and device therapy

  • Patients considered for transplantation should not only have severe disease, but should have no significant co-morbidity

  • As well as major surgery, physical and psychological suitability for long-term immunosuppression should be considered

  • Primary indication worldwide is split equally between cardiomyopathy of ischemic and non-ischaemic origin

  • The most commonly performed procedure is orthotopic transplant where the heart is replaced by the donor’s.

Indications for cardiac transplantation

  • Advanced heart failure refractory to maximum tolerated medical/device or surgical treatment with

    • Expected mortality of >25%

    • Limiting symptoms attributable to heart failure

  • Life-threatening acute heart failure unresponsive to treatment

  • Refractory life-threatening arrhythmia

  • Intractable angina not ameanable to revascularization.

Contraindications to transplantation

  • Irreversible pulmonary hypertension (raised pulmonary pressures, raised transpulmonary gradient)

  • Irreversible hepatic or lung dysfunction (FEV1 <50% predicted)

  • Cerebrovascular disease

  • Active infection

  • Systemic disease, e.g. amyloid, vasculitis, sarcoid

  • Inability to comply with immunosuppresion

  • Continued alcohol/substance misuse.

Relative contraindications

  • Age >70 years

  • Renal dysfunction with eGFR <40 ml/min

  • Diabetes with end-organ damage

  • Peripheral vascular disease not amenable to revascularization

  • Malignancy

  • Learning difficulties/dementia

  • Hep B/C or HIV

  • BMI >30

  • Recent pulmonary embolism (within three months)

  • Active peptic ulcer disease

  • Osteoporosis

  • Current smoker.

Further reading

Camm AJ, Lüscher TF, and Serruys PW (eds). The European Society of Cardiology Textbook of Cardiovascular Medicine. Oxford University Press, 2009.Find this resource:

Dubrey SW, Hawkins PN, Falk RH. Systemic disorders in heart disease: Amyloid diseases of the heart: assessment, diagnosis, and referral. Heart, 2011; 97: 75–84.Find this resource:

Eagle KA, Guyton RA, Davidoff R, et al. Guideline Update for Coronary Artery Bypass Graft Surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). ACC/AHA, 2004.Find this resource:

Elliott P. Cardiomyopathy: diagnosis and management of dilated cardiomyopathy. Heart, 2000; 84: 106.Find this resource:

Gardner RS, Mconagh TA, Walker NL. Heart Failure. Oxford Specialist Handbooks in Cardiology. Oxford University Press, 2007.Find this resource:

Linhart A, Elliott P. The heart in Anderson-Fabry disease and other lysosomal storage disorder. Heart, 2007; 93: 528–35.Find this resource:

Maron BJ, McKenna WJ, Danielson GK, et al. ACC/ESC Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents and the European Society of Cardiology Committee for Practice Guidelines (Committee to Develop an Expert Consensus Document on Hypertrophic Cardiomyopathy). Eur Heart J, 2003; 24: 1965–91.Find this resource:

McKenna WJ, Thiene G, and Nava A. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Br Heart J, 1994; 71: 215–8.Find this resource:

Mestroni L, Maisch B, and McKenna WJ. Guidelines for the Study of Familial Dilated Cardiomyopathies. Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy. Eur Heart J, 1999; 20, 93–102.Find this resource:

Richardson P, McKenna W, Bristow M, et al. Classification of cardiomyopathies based on a report of the World Health Organization and International Society and Federation of Cardiology. Circulation, 1996; 93: 841–2.Find this resource: