Download Echo in Restrictive Cardiomyopathy

Restrictive Cardiomyopathy
Loryn S. Feinberg
Wednesday, April 20, 2005
Echocardiography Conference
Restrictive Cardiomyopathy
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Definition
Characteristics
Clinical Presentation
Classification
Specific Diseases & Echo Findings
General Echo Features
Definition
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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
Clinical & Echo Characteristics
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Nondilated ventricle
Normal to increased wall thickness
Rigid ventricular walls
– Severe diastolic dysfunction
– Restrictive filling
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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’ 61:1206
Clinical Presentation
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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
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– AF common in IRCM & amyloidosis
Advanced Stage
– Marked elevation in CVP
 Hepatosplenomegaly, ascites, anasarca
Physical Examination
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Pulse: normal or low amplitude/tachycardic [low SV]
JVP: elevated with prominent x and y descents
Kussmaul’s sign: JVP fails to fall or ↑es w/ inspiration
– Increased resistance to
RA filling during inspiration
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LV impulse: normal
S1, S2 normal, often S3 present
– abrupt cessation of rapid ventricular filling
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Regurgitant murmurs
Peripheral edema, ascites, pulsatile liver, HSM
Differentiation from Constrictive
Pericarditis
Restrictive CM
Constrictive Pericarditis
History
Systemic disease involving myocardium,
mm, amyloid, cardiac transplant
Acute pericarditis, cardiac surgery, chest
trauma, systemic disease involving
pericardium
Chest X-ray
Absence of calcification, massive atrial
enlargement
Helpful when calcification persists,
moderate atrial enlargement
ECG
BBBs, AV block
Abnormal repolarization
CT/MRI
Normal pericardium
Helpful if thickened (>4 mm) pericardium
Hemodynamics
Helpful if unequal diastolic pressures;
concordant effect of respiration on
diastolic pressures
Diastolic equilibration; dip and plateau
Biopsy
Fibrosis, hypertrophy, infiltration
Normal
Adapted from Hurst’s The Heart, 10th ed. 2004
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
Myocardial, Non-infiltrative
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Idiopathic
– Sporadic , AD, or AR
– Familial type: part of spectrum of
familial HCM?
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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
Idiopathic Restrictive CM:
2D Echo features
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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
Myocardial, Non-infiltrative
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Scleroderma
– Myocardial fibrosis, contraction band
necrosis [dense bands through
myofibers often seen after ischemiai
w. reperfusion]
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Often patchy, may be biventricular
– Microvascular occlusions →
ischemia
– Fibrinous pericarditis, effusions
– Ventricular conduction abnormalities
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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
Myocardial, Infiltrative
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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
(Crohn’s, RA, Tb, FMF)
 10% clinical cardiac involvement
– Familial & Senile: overproduction of
transthyretin [>50 mutations]
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Familial usually AD, associated with
ascending peripheral & autonomic
neuropathy
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‹ 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)
Myocardial, Infiltrative
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Amyloid
– Deposits may be interstitial & widespread:
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Myocardial Dysfunction:
– Diffuse infiltration of myocardium with stiff beta-pleated fibrils →impaired relaxation,
diastolic dysfunction
– Replacement of functional myocardium with amyloid-> systolic dysfunction
– Stiff Heart Syndrome: restrictive filling present & impaired systolic function
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Deposits may localize to:
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Conduction tissue: heart block, ventricular arrhythmias
Valves: regurgitation
Pericardium: constriction
Coronaries: ischemia
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– Prognosis poor, median survival two years
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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; 39:658.
Utility of echocardiography in evaluation of individuals with cardiomyopathy. Heart 2004;90
Amyloid: 2D Echo features
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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
Myocardial, Infiltrative
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Sarcoidosis
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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->dilated
 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
Sarcoidosis: Echo features
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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
Myocardial, Infiltrative
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Gaucher’s
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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 -> restrictive cm
– Often subclinical
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Pulmonary hypertension from pulmonary capillary occlusion
Calcification & thickening of valves, pericardial effusion
Hurler’s 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
Metabolic Storage Diseases
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Hemochromatosis
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Five types, AD or AR
Iron deposition in multiple organs (heart, liver,
skin, pancreas, pituitary, joints)
Dilated>restrictive 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
Hurst’s The Heart, 10th edition
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; 89:819.
Fabry Disease
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Accumulation occurs in myocardium, vascular, and valvular
endothelium
May develop LVH (concentric) with hypertrophic CM,
restrictive CM, or dilated CM
– Conduction abnormalities, AR>MR, 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
Endomyocardial Diseases
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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%
Endomyocardial Fibrosis:
Echo Features
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Inferobasal LV wall thickening
Endocardial thrombus deposition
– Apical obliteration
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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
– Regurgitation>stenosis
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AF common
Endomyocardial Diseases
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Loeffler’s 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
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Mural & atrial thrombi
LV thrombi in absence of WMA
Gradual apical obliteration; apex fills with
echogenic mass
Tai PC Lancet 87’; 1;
Thrombus deposition in RV/LV apices
Wood MJ et al; Utility of Echo in the Eval of Ind with CM; Heart 2004; 90
Endomyocardial Diseases
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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->l 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
Carcinoid Syndrome
– Echo findings in 2/3 of patients
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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
Endomyocardial Diseases
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Radiation carditis
– Can manifest decades after thoracic radiotherapy
– Can involve many cardiac structures
Coronary arteries: ostial stenoses
 Valves: stenosis
 Pericardium: constrictive pericarditis
 Myocardium, endocardium:
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– Interstitial fibrosis of RV > LV
Brosius FC III et al. Radiation heart disease. Am J Med 81’; 70.
Endomyocardial Diseases
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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
Doppler Echo findings:
Early in Disease Course
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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
Pseudonormalization
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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
Advanced Restrictive Pattern
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Ventricular compliance continues to
decrease
Increased mitral early diastolic filling
velocity (E) [> 1m/s]
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Deceleration slope becomes more rapid
A velocity reduced due to increased
LVEDP & reduced atrial contractile
function [<.5 m/s]
Increased E:A ratio (>2)
Mitral deceleration time shortens (<150
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
Myocardial Tissue Doppler Signals
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Displays the velocities of the myocardium
during contraction and relaxation
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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
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Helpful in differentiating constriction from
restriction
Cardiac MR
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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
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Can aid in differentiating constrictive from restrictive
disease
Celetti et al, AJC 99’ 83