Restrictive Cardiomyopathy Loryn S. Feinberg Wednesday

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Restrictive Cardiomyopathy

• Loryn S. Feinberg
• Wednesday, April 20, 2005
• Echocardiography Conference

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Restrictive Cardiomyopathy

• Definition
• Characteristics
• Clinical Presentation
• Classification
• Specific Diseases Echo Findings
• General Echo Features

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Definition

• Idiopathic or systemic myocardial disease
  characterized by
• Impaired ventricular filling
• Elevated diastolic pressures
• Normal or reduced diastolic volume of
  ventricle(s)
• Normal/near normal systolic function until
  advanced stages

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Clinical Echo Characteristics

• Nondilated ventricle
• Normal to increased wall thickness
• Rigid ventricular walls
• Severe diastolic dysfunction
• Restrictive filling
• Elevated diastolic filling pressures
• Dilated atria, elevated RA pressure
• Pulmonary hypertension
• Inability to ? CO with exercise
• due to impaired filling
• Right sided failure

Benotti, JR et al. Clinical profile of
restrictive cm. Circ 80 611206
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Clinical Presentation

• Signs of pulmonary and systemic congestion in
  absence of cardiomegaly
• Dyspnea
• PND, orthopnea
• Peripheral edema
• Palpitations
• Fatigue, weakness, exercise intolerance
• Thromboembolic complications (up to 1/3 with
  idiopathic RCM)
• Cardiac conduction disturbances
• Amyloid , sarcoid, hemochromatosis
• AF common in IRCM amyloidosis
• Advanced Stage
• Marked elevation in CVP
• Hepatosplenomegaly, ascites, anasarca

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Physical Examination

• Pulse normal or low amplitude/tachycardic low
  SV
• JVP elevated with prominent x and y descents
• Kussmauls sign JVP fails to fall or ?es w/
  inspiration
• Increased resistance to
• RA filling during inspiration
• LV impulse normal
• S1, S2 normal, often S3 present
• abrupt cessation of rapid ventricular filling
• Regurgitant murmurs
• Peripheral edema, ascites, pulsatile liver, HSM

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Differentiation from Constrictive Pericarditis
Adapted from Hursts The Heart, 10th ed. 2004
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• Secondary restrictive physiology may occur in
  advanced stages of dilated, hypertrophic,
  hypertensive, ischemic heart disease

Kushwaha et al. 336 (4) 267, Table 1     January
23, 1997
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Myocardial, Non-infiltrative

• Idiopathic
• Sporadic , AD, or AR
• Familial type part of spectrum of familial HCM?
• Different phenotypic expression of same genetic
  disease
• May be associated with distal skeletal myopathy,
  occasionally heart block fibrosis of SA AV
  nodes
• Manifests at any age childrens prognosis worse,
  adults course protracted
• Incidence? in elderly,
• women ? men
• Survival time variable, mean 9 years
• Disease of exclusion

Marked patchy interstitial fibrosis
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Idiopathic Restrictive CM 2D Echo features

• Biatrial enlargement
• Thrombi in atrial appendages
• Cavity size/wall thickness normal
• Normal or reduced global systolic function
• Right ventricle eventually enlarges depending on
  degree of PH
• May have patchy, granular sparkling appearance

Non-dilated, non-hypertrophied ventricles with
dilated atria
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Myocardial, Non-infiltrative

• Scleroderma
• Myocardial fibrosis, contraction band necrosis
  dense bands through myofibers often seen after
  ischemiai w. reperfusion
• Often patchy, may be biventricular
• Microvascular occlusions ? ischemia
• Fibrinous pericarditis, effusions
• Ventricular conduction abnormalities
• Heart block, SVTs, VT, pseudoinfarction patterns
  on ECG
• Pulmonary hypertension leading cause of
  morbidity/mortality

Fibrous tissue replacement Thinned papillary
muscles LV wall
Braunwald, Heart Disease 6th edition
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Myocardial, Infiltrative

• Amyloid
• Primary light chain immunoglobulin
  overproduction from monoclonal plasma cells
  (multiple myeloma)
• 50 clinical cardiac involvement
• Secondary fragments of serum amyloid A protein
• Chronic inflammatory conditions (Crohns, RA, Tb,
  FMF)
• 10 clinical cardiac involvement
• Familial Senile overproduction of
  transthyretin gt50 mutations
• Familial usually AD, associated with ascending
  peripheral autonomic neuropathy
• 5 clinical cardiac involvement

Dx endomyocardial or fat biopsy Left prominent
interstitium, expansion by acellular,
eosinophilic substance. Uneven size myocardial
cells, vacuolated Right affinity for sulfated
alcian blue (histochemical equivalent of congo
red stain)
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Myocardial, Infiltrative

• Amyloid
• Deposits may be interstitial widespread
• Myocardial Dysfunction
• Diffuse infiltration of myocardium with stiff
  beta-pleated fibrils ?impaired relaxation,
  diastolic dysfunction
• Replacement of functional myocardium with
  amyloid-gt systolic dysfunction
• Stiff Heart Syndrome restrictive filling
  present impaired systolic function
• Deposits may localize to
• Conduction tissue heart block, ventricular
  arrhythmias
• Valves regurgitation
• Pericardium constriction
• Coronaries ischemia
• Prognosis poor, median survival two years
• Diastolic function found to be a stronger
  predictor of cardiac death than LV wall thickness
  or systolic function
• Cardiac transplantation not usually performed

Swanton, RH et al. Systolic and diastolic
ventricular function in cardiac amyloidosis. Am J
Cardiol 1977 39658. Utility of
echocardiography in evaluation of individuals
with cardiomyopathy. Heart 200490
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Amyloid 2D Echo features

• Ventricular cavities may be small, normal, or
  moderately dilated
• Atrial appendage thrombi
• Dilated atria IVC
• Normal or increased wall thickness
• Prognostic variable
• Survival range 2.4 yrs if NL(12 mm)
• 0.4 yrs if markedly ? (?15 mm)
• Variable (but often depressed) systolic function
• Involvement of pericardium, valves, coronaries
• Granular, sparkling appearance is characteristic

BiV hypertrophy, biatrial enlargement, mild,
diffuse valve thickening
Cueto-Garcia L, et al. Echo findings in systemic
amyloidosis. JACC 85 6 Katritsis, D et al.
Primary restrictive CM clinical and pathologic
characteristics. JACC 91 18
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Myocardial, Infiltrative

• Sarcoidosis
• Affects young/middle age adults, no gender
  prediliction
• Noncaseating granulomas in lungs, spleen, lymph
  nodes, skin, liver, parotid glands, heart
• Infiltration of conduction system, LV (upper
  septum), pulmonary artery
• Autopsy Cardiac involvement in 25, Clinically
  5
• Cardiac manifestations restrictive cm-gtdilated
• Conduction abnormalities, high-grade AV block, VT
• Patchy distribution
• Biopsy sensitivity of 20-30
• Sudden cardiac death in 17 with extensive
  cardiac granulomas
• Cardiac transplantation may be appropriate for
  intractable heart failure or arrhythmias

Griffin BP Manual of CV Medicine 2004
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Sarcoidosis Echo features

• Systolic function usually normal initially
• Diffuse HK focal abnormalities of WM
• Basal septum affected, apex spared
• Pulmonary involvement frequent
• Pulmonary hypertension, RHF
• LV aneurysms
• Valvular regurgitation
• Septum or LV free wall may appear hyperechogenic

Valantine H et al. Sarcoidosis a pattern of
clinical and morphological presentation. Br Heart
J 87 57 Fahy, J et al. Doppler echo detection in
patients with pulmonary sarcoidosis. Chest 96
109
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Myocardial, Infiltrative

• Gauchers
• Most common lysosomal storage disease
• Deficiency in beta-glucocerebrocidase enzyme
• Accumulation of cerebroside in many organs,
  usually bm, spleen, liver, brain
• More rare pulmonary cardiovascular involvement
• Cerebroside accumulation in interstitium of LV -gt
  restrictive cm
• Often subclinical
• Pulmonary hypertension from pulmonary capillary
  occlusion
• Calcification thickening of valves, pericardial
  effusion
• Hurlers Syndrome
• Mucopolysaccharide accumulation leads to severe
  skeletal deformities, hepatosplenomegaly, mental
  retardation
• Cardiac involvement evident between 1-5 years of
  age
• Mucopolysaccharide deposition in myocardial
  interstitium, valves, coronary arteries, aorta

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Metabolic Storage Diseases

• Hemochromatosis
• Five types, AD or AR
• Iron deposition in multiple organs (heart, liver,
  skin, pancreas, pituitary, joints)
• Dilatedgtrestrictive cardiomyopathy
• Systolic dysfunction indicates a poor prognosis
• Conduction disturbances common, e.g., SSS
• SVT VT occur in 1/3 of patients
• Granular or sparkling appearance may be seen on
  echo
• Atrial enlargement
• Treatment with repeated phlebotomy or chelation
  (desferrioxamine) may reverse LV dysfunction
• Cardiac transplantation can be considered

Hursts The Heart, 10th edition
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Fabry Disease (angiokeratoma corporis
diffusum,ceramide trihexosidosis, or
Anderson-Fabry disease )

• X-linked disorder of glycosphingolipid metabolism
• Due to deficiency of lysosomal ceramide (?-
  galactosidase)
• Intracellular accumulation deposition of
  glycolipids in heart, skin, kidneys
• First symptoms manifest by age 10
• Peripheral neuropathy, hypohidrosis, skin lesions
  (angiokeratomas), renal dysfunction

Nagueh, SF. Fabry disease. Heart 2003 89819.
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Fabry Disease

• Accumulation occurs in myocardium, vascular, and
  valvular endothelium
• May develop LVH (concentric) with hypertrophic
  CM, restrictive CM, or dilated CM
• Conduction abnormalities, ARgtMR, premature CAD,
  aortic root dilation, premature stroke
• Cardiac manifestations may not occur until age 30
• Echo findings are similar to amyloid
• LV mass correlates with disease severity
• Full expression in males, incomplete in females
• Screening for plasma alpha-galactosidase A levels
  in patients with unexplained concentric LVH
  should be considered
• Recombinant alpha-galactosidase causes regression
  of cardiac dysfunction

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Endomyocardial Diseases

• Endomyocardial Fibrosis
• (Davies Disease)
• Tropics
• 10-20 of deaths due to HF in equitorial Africa
• Children, young adults
• No gender prediliction
• Intense endocardial fibrotic thickening of apex
  subvalvular regions of ventricle(s)? obstruction
  to blood inflow, regurgitation, restrictive
  physiology
• Histology granulation tissue, collagen,
  connective tissue lines endocardium
• Affects both (50), left (40), right (10)
  ventricles
• Two year mortality up to 50

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Endomyocardial FibrosisEcho Features

• Inferobasal LV wall thickening
• Endocardial thrombus deposition
• Apical obliteration
• Biventricular involvement in ½ of patients
• Ventricular cavities vary in size but often
  obliterated by extensive endocardial thickening
• Large atria
• Papillary muscle involvement AV valve apparatus
  with valve deformity common
• Regurgitationgtstenosis
• AF common

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Endomyocardial Diseases

• Loefflers endocarditis
• eosinophilic cardiomyopathy
• Temperate climates
• Activated eosinophils may release cardiotoxic
  intracytoplasmic granules
• Middle age, usually men
• Intense eosinophilia, nervous system bone
  marrow involvement, skin rash, constitutional
  symtpms
• Restrictive cardiac disease (often
  biventricular), fibrinoid vasculitis of
  coronaries
• Valvular involvement leads to regurgitation or
  stenosis of AV valves
• Thromboembolic phenomena
• Mural atrial thrombi
• LV thrombi in absence of WMA
• Gradual apical obliteration apex fills with
  echogenic mass

Tai PC Lancet 87 1 Wood MJ et al Utility of
Echo in the Eval of Ind with CM Heart 2004 90
Thrombus deposition in RV/LV apices
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Endomyocardial Diseases

• Carcinoid Heart Disease
• Late complication of carcinoid syndrome from
  metastatic carcinoid tumors
• 50 of patients
• TR most common finding
• Pathognomonic fibrous plaque-like deposits
• Pulmonary inactivation of serotonin, bradykinin,
  etc..
• LV involvement uncommon
• If present, likely r-gtl shunt
• Endocardium of valve cusps/leaflets,cardiac
  chambers, intima of PA/aorta
• Plaques smooth muscle cells embedded in
  mucopolysaccharides collagen
• Lack elastic components

Pellikka PA et al. Carcinoid heart disease
clinical and echo spectrum in 74 patinets.Circ
93 87
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Carcinoid Syndrome

• Echo findings in 2/3 of patients
• Thickened, retracted, immobile tricuspid
  pulmonary valves
• RA/RV enlargement
• RA wall thickening on TEE
• Pulmonary outflow obstruction may occur
• TR/PR on doppler
• Rarely see metastatic tumors to heart
• Valvular lesions do not regress with therapy

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Endomyocardial Diseases

• Radiation carditis
• Can manifest decades after thoracic radiotherapy
• Can involve many cardiac structures
• Coronary arteries ostial stenoses
• Valves stenosis
• Pericardium constrictive pericarditis
• Myocardium, endocardium
• Interstitial fibrosis of RV gt LV

Brosius FC III et al. Radiation heart disease. Am
J Med 81 70.
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Endomyocardial Diseases

• Metastatic cancer (lung, breast, melanoma,
  leukemia, lymphoma)
• Drug toxicity
• Anthracylines dilated CM endomyocardial
  fibrosis
• Risk of restrictive cm markedly increased with
  concurrent irradiation
• Diastolic abnormalities do not appear to be
  dose-related
• Drugs causing endomyocardial fibrosis
• Methylsergide
• Serotonin
• Busulfan
• Ergotamine
• Mercurial agents

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Doppler Echo findings Early in Disease Course

• Impaired diastolic filling
• Doppler of LV inflow
• Reduced E velocity, increased A velocity
• Prolonged isovolumic relaxation time
• Decreased early diastolic deceleration slope
• Pulmonary vein inflow
• Reduced diastolic filling phase
• Normal systolic filling phase
• Decreased ratio of systolic to diastolic PV flow

Zile et al. Circ 02 105
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Pseudonormalization

• LA pressure rises
• Increased pressure gradient from LA to LV at MV
  opening
• E and A velocities may remain relatively normal
• Pulmonary venous inflow
• Systolic filling normal or decreased
• Diastolic is normal or increased
• Increased resistance to LV filling ? in
  velocity and duration of atrial flow reversal in
  lower resistance PV

Otto, Textbook of Clinical Echo 3rd edition
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Advanced Restrictive Pattern

• Ventricular compliance continues to decrease
• Increased mitral early diastolic filling velocity
  (E) gt 1m/s
• Deceleration slope becomes more rapid
• A velocity reduced due to increased LVEDP
  reduced atrial contractile function lt.5 m/s
• Increased EA ratio (gt2)
• Mitral deceleration time shortens (lt150 ms)
• Isovolumic relaxation time shortens ? 70 ms
• PV flow shows increased diastolic phase, reduced
  systolic phase Pva increases further in
  duration velocity

E/A 2.4
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Myocardial Tissue Doppler Signals

• Displays the velocities of the myocardium during
  contraction and relaxation
• Can assist in assessment and grading of diastolic
  function
• Sm myocardial velocity during systole
• Em myocardial velocity during early filling
• Am myocardial velocity during filling due to
  atrial contraction
• In restrictive pattern, Em is diminutive
• Helpful in differentiating constriction from
  restriction

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Cardiac MR

• Can aid in distinguishing between the
  cardiomyopathies
• Hemochromatosis produces low signal intensity due
  to iron deposition
• May differentiate primary restrictive CM from
  amyloidosis based on tissue characterization
• May detect mass lesions due to sarcoid granuloma
  or scar
• Can aid in differentiating constrictive from
  restrictive disease

Celetti et al, AJC 99 83
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