1. Restrictive Cardiomyopathy
Loryn S. Feinberg
Wednesday, April 20, 2005
Echocardiography Conference

2. Restrictive Cardiomyopathy
Definition
Characteristics
Clinical Presentation
Classification
Specific Diseases & Echo Findings
General Echo Features

3. 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

4. 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’ 61:1206

5. 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

6. Physical Examination
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
LV impulse: normal
S1, S2 normal, often S3 present
abrupt cessation of rapid ventricular filling
Regurgitant murmurs
Peripheral edema, ascites, pulsatile liver, HSM

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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 (Crohn’s, RA, Tb, FMF)
10% clinical cardiac involvement
Familial & Senile: overproduction of transthyretin [>50 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)

13. 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-> 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; 39:658.
Utility of echocardiography in evaluation of individuals with cardiomyopathy. Heart 2004;90

14. 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

15. 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->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

16. 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

17. Myocardial, Infiltrative
Gaucher’s
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
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

18. Metabolic Storage Diseases
Hemochromatosis
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

19. 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.

20. Fabry Disease
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

21. 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%

22. Endomyocardial Fibrosis: Echo 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
Regurgitation>stenosis
AF common

23. Endomyocardial Diseases
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
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

24. 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->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

25. 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

26. 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 > LV
Brosius FC III et al. Radiation heart disease. Am J Med 81’; 70.

27. 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

28. 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

29. 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

30. Advanced Restrictive Pattern
Ventricular compliance continues to decrease
Increased mitral early diastolic filling velocity (E) [> 1m/s]
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

31. 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

32. 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