RestrictiveRestrictive CardiomyopathyCardiomyopathy

Loryn S. FeinbergLoryn S. FeinbergWednesday, April 20, 2005Wednesday, April 20, 2005

Echocardiography ConferenceEchocardiography Conference

Restrictive CardiomyopathyRestrictive Cardiomyopathy

DefinitionDefinition CharacteristicsCharacteristics Clinical PresentationClinical Presentation ClassificationClassification Specific Diseases & Echo FindingsSpecific Diseases & Echo Findings General Echo FeaturesGeneral Echo Features

DefinitionDefinition

Idiopathic or systemic Idiopathic or systemic myocardial disease myocardial disease characterized by:characterized by:– Impaired ventricular fillingImpaired ventricular filling– Elevated diastolic Elevated diastolic

pressures pressures – Normal or reduced diastolic Normal or reduced diastolic

volume of ventricle(s)volume of ventricle(s)– Normal/near normal Normal/near normal

systolic function until systolic function until advanced stagesadvanced stages

Clinical & Echo CharacteristicsClinical & Echo Characteristics

Nondilated ventricleNondilated ventricle Normal to increased wall thicknessNormal to increased wall thickness Rigid ventricular wallsRigid ventricular walls

– Severe diastolic dysfunctionSevere diastolic dysfunction– Restrictive fillingRestrictive filling

Elevated diastolic filling pressures Elevated diastolic filling pressures Dilated atria, elevated RA Dilated atria, elevated RA

pressure pressure Pulmonary hypertensionPulmonary hypertension Inability to ↑ CO with exercise Inability to ↑ CO with exercise

due to impaired fillingdue to impaired filling Right sided failureRight sided failure

Benotti, JR et al. Clinical profile of restrictive cm. Circ 80’ 61:1206Benotti, JR et al. Clinical profile of restrictive cm. Circ 80’ 61:1206

Clinical PresentationClinical Presentation

Signs of pulmonary and systemic congestion in absence of cardiomegalySigns of pulmonary and systemic congestion in absence of cardiomegaly– DyspneaDyspnea– PND, orthopneaPND, orthopnea– Peripheral edemaPeripheral edema– PalpitationsPalpitations– Fatigue, weakness, exercise intoleranceFatigue, weakness, exercise intolerance

Thromboembolic complicationsThromboembolic complications (up to 1/3 with idiopathic RCM) (up to 1/3 with idiopathic RCM) Cardiac conduction disturbancesCardiac conduction disturbances

– Amyloid , sarcoid, hemochromatosisAmyloid , sarcoid, hemochromatosis– AF common in IRCM & amyloidosisAF common in IRCM & amyloidosis

Advanced StageAdvanced Stage– Marked elevation in CVPMarked elevation in CVP

Hepatosplenomegaly, ascites, anasarcaHepatosplenomegaly, ascites, anasarca

Physical ExaminationPhysical Examination

Pulse: normal or low amplitude/tachycardic [low SV]Pulse: normal or low amplitude/tachycardic [low SV] JVP: elevated with prominent x and JVP: elevated with prominent x and yy descents descents Kussmaul’s sign: JVP fails to fall or ↑es w/ inspirationKussmaul’s sign: JVP fails to fall or ↑es w/ inspiration

– Increased resistance toIncreased resistance toRA filling during inspirationRA filling during inspiration

LV impulse: normalLV impulse: normal S1, S2 normal, often S3 present S1, S2 normal, often S3 present

– abrupt cessation of rapid ventricular fillingabrupt cessation of rapid ventricular filling Regurgitant murmursRegurgitant murmurs Peripheral edema, ascites, pulsatile liver, HSMPeripheral edema, ascites, pulsatile liver, HSM

Differentiation from Constrictive Differentiation from Constrictive PericarditisPericarditis

Adapted from Hurst’s The Heart, 10Adapted from Hurst’s The Heart, 10 thth ed. 2004 ed. 2004

Restrictive CMRestrictive CM Constrictive PericarditisConstrictive Pericarditis

HistoryHistory Systemic disease involving myocardium, Systemic disease involving myocardium, mm, amyloid, cardiac transplantmm, amyloid, cardiac transplant

Acute pericarditis, cardiac surgery, chest Acute pericarditis, cardiac surgery, chest trauma, systemic disease involving trauma, systemic disease involving pericardiumpericardium

Chest X-rayChest X-ray Absence of calcification, massive atrial Absence of calcification, massive atrial enlargementenlargement

Helpful when calcification persists, Helpful when calcification persists, moderate atrial enlargementmoderate atrial enlargement

ECGECG BBBs, AV blockBBBs, AV block Abnormal repolarizationAbnormal repolarization

CT/MRICT/MRI Normal pericardiumNormal pericardium Helpful if thickened (>4 mm) pericardiumHelpful if thickened (>4 mm) pericardium

HemodynamicsHemodynamics Helpful if unequal diastolic pressures; Helpful if unequal diastolic pressures; concordant effect of respiration on concordant effect of respiration on diastolic pressuresdiastolic pressures

Diastolic equilibration; dip and plateauDiastolic equilibration; dip and plateau

BiopsyBiopsy Fibrosis, hypertrophy, infiltrationFibrosis, hypertrophy, infiltration NormalNormal

Kushwaha et al. 336 (4): 267, Table 1 January 23, 1997

Secondary restrictive Secondary restrictive physiology may occur in physiology may occur in advanced stages of advanced stages of dilated, hypertrophic, dilated, hypertrophic, hypertensive, ischemic hypertensive, ischemic heart diseaseheart disease

Myocardial, Non-infiltrativeMyocardial, Non-infiltrative

IdiopathicIdiopathic– Sporadic , AD, or ARSporadic , AD, or AR– Familial type:Familial type: part of spectrum of part of spectrum of

familial HCM?familial HCM? Different phenotypic expression of Different phenotypic expression of

same genetic diseasesame genetic disease May be associated with distal skeletal May be associated with distal skeletal

myopathy, occasionally heart block myopathy, occasionally heart block [fibrosis of SA & AV nodes][fibrosis of SA & AV nodes]

– Manifests at any age [childrens’ Manifests at any age [childrens’ prognosis worse, adults’ course prognosis worse, adults’ course protracted]protracted]

IncidenceIncidence in elderly, in elderly, women women men men

– Survival time variable, mean 9 yearsSurvival time variable, mean 9 years– Disease of exclusionDisease of exclusion Marked patchy interstitial fibrosis

Idiopathic Restrictive CM:Idiopathic Restrictive CM: 2D Echo features2D Echo features

Biatrial enlargementBiatrial enlargement Thrombi in atrial Thrombi in atrial

appendagesappendages Cavity size/Cavity size/wall thicknesswall thickness

normal normal Normal or reduced global Normal or reduced global

systolic functionsystolic function Right ventricle eventually Right ventricle eventually

enlarges [depending on enlarges [depending on degree of PH]degree of PH]

May have patchy, granular May have patchy, granular sparkling appearancesparkling appearance

Non-dilated, non-hypertrophied ventricles with dilated atriaNon-dilated, non-hypertrophied ventricles with dilated atria

Myocardial, Non-infiltrativeMyocardial, Non-infiltrative

SclerodermaScleroderma– Myocardial fibrosis, contraction band Myocardial fibrosis, contraction band

necrosis [dense bands through necrosis [dense bands through myofibers often seen after ischemiai myofibers often seen after ischemiai w. reperfusion]w. reperfusion]

Often patchy, may be biventricularOften patchy, may be biventricular– Microvascular occlusions → Microvascular occlusions →

ischemiaischemia– Fibrinous pericarditis, effusions Fibrinous pericarditis, effusions – Ventricular conduction abnormalitiesVentricular conduction abnormalities

Heart block, SVTs, VT, Heart block, SVTs, VT, pseudoinfarction patterns on ECGpseudoinfarction patterns on ECG

– Pulmonary hypertensionPulmonary hypertension leading leading cause of morbidity/mortalitycause of morbidity/mortality

Fibrous tissue replacement:

Thinned papillary muscles & LV wall

Braunwald, Heart Disease; 6th edition

Myocardial, InfiltrativeMyocardial, Infiltrative

AmyloidAmyloid– Primary:Primary: light chain immunoglobulin

overproduction from monoclonal plasma cells (multiple myeloma)

50%50% clinical cardiac involvement clinical cardiac involvement

– Secondary:Secondary: fragments of serum amyloid A protein

Chronic inflammatory conditions Chronic inflammatory conditions (Crohn’s, RA, Tb, FMF)(Crohn’s, RA, Tb, FMF)

10%10% clinical cardiac involvement clinical cardiac involvement

– Familial & Senile:Familial & Senile: overproduction of overproduction of transthyretin [>50 mutations]transthyretin [>50 mutations]

Familial usually AD, associated with Familial usually AD, associated with ascending peripheral & autonomic ascending peripheral & autonomic neuropathyneuropathy

‹ ‹ 5% clinical cardiac involvement5% 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, InfiltrativeMyocardial, Infiltrative

AmyloidAmyloid– Deposits may be interstitial & widespread:Deposits may be interstitial & widespread:

Myocardial Dysfunction:Myocardial Dysfunction: – Diffuse infiltration of myocardium with stiff beta-pleated fibrils →impaired relaxation, Diffuse infiltration of myocardium with stiff beta-pleated fibrils →impaired relaxation,

diastolic dysfunction diastolic dysfunction – Replacement of functional myocardium with amyloid-> systolic dysfunctionReplacement of functional myocardium with amyloid-> systolic dysfunction– Stiff Heart Syndrome: restrictive filling present & impaired systolic function Stiff Heart Syndrome: restrictive filling present & impaired systolic function

Deposits may localize to:Deposits may localize to: Conduction tissue: heart block, ventricular arrhythmiasConduction tissue: heart block, ventricular arrhythmias Valves: regurgitationValves: regurgitation Pericardium: constrictionPericardium: constriction Coronaries: ischemiaCoronaries: ischemia

– Prognosis poor, median survival two yearsPrognosis poor, median survival two years Diastolic function found to be a stronger predictor of cardiac death than LV wall Diastolic function found to be a stronger predictor of cardiac death than LV wall

thickness or systolic function thickness or systolic function Cardiac transplantationCardiac transplantation not usually performed 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

AmyloidAmyloid: 2D Echo features: 2D Echo features

Ventricular cavitiesVentricular cavities may be small, may be small, normal, or moderately dilatednormal, or moderately dilated

Atrial appendageAtrial appendage thrombi thrombi Dilated atria & IVCDilated atria & IVC Normal or increased wall thicknessNormal or increased wall thickness

– Prognostic variablePrognostic variable Survival range 2.4 yrs if Survival range 2.4 yrs if

NL(≤12 mm)NL(≤12 mm) 0.4 yrs if markedly 0.4 yrs if markedly ( (15 15

mm)mm) Variable (but often depressed) Variable (but often depressed)

systolic functionsystolic function Involvement of pericardium, valves, Involvement of pericardium, valves,

coronariescoronaries Granular, sparkling appearance is Granular, sparkling appearance is

characteristiccharacteristic

Cueto-Garcia L, et al. Echo findings in systemic amyloidosis. JACC 85; 6Cueto-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; 18Katritsis, D et al. Primary restrictive CM: clinical and pathologic characteristics. JACC 91; 18

BiV hypertrophy, biatrial enlargement,BiV hypertrophy, biatrial enlargement,

& mild, diffuse valve thickening& mild, diffuse valve thickening

Myocardial, InfiltrativeMyocardial, Infiltrative

SarcoidosisSarcoidosis– Affects young/middle age adults, no gender Affects young/middle age adults, no gender

predilictionprediliction– Noncaseating granulomas in lungs, spleen, lymph Noncaseating granulomas in lungs, spleen, lymph

nodes, skin, liver, parotid glands, heartnodes, skin, liver, parotid glands, heart– Infiltration of conduction system, LV (upper septum), Infiltration of conduction system, LV (upper septum),

pulmonary arterypulmonary artery– AutopsyAutopsy: Cardiac involvement in 25%, Clinically: 5%: Cardiac involvement in 25%, Clinically: 5%– Cardiac manifestations: restrictive cm->dilatedCardiac manifestations: restrictive cm->dilated

Conduction abnormalities, high-grade AV Conduction abnormalities, high-grade AV block, VTblock, VT

– Patchy distributionPatchy distribution Biopsy sensitivity of 20-30%Biopsy sensitivity of 20-30%

– Sudden cardiac death in 17% with extensive cardiac Sudden cardiac death in 17% with extensive cardiac granulomasgranulomas

– Cardiac transplantation may be appropriate for Cardiac transplantation may be appropriate for intractable heart failure or arrhythmiasintractable heart failure or arrhythmias

Griffin BP; Manual of CV Medicine 2004Griffin BP; Manual of CV Medicine 2004

SarcoidosisSarcoidosis: Echo features: Echo features

Systolic function usually normal initiallySystolic function usually normal initially Diffuse HK & focal abnormalities of WMDiffuse HK & focal abnormalities of WM

– Basal septum affected, apex sparedBasal septum affected, apex spared Pulmonary involvement frequentPulmonary involvement frequent

– Pulmonary hypertension, RHFPulmonary hypertension, RHF LV aneurysms LV aneurysms Valvular regurgitationValvular regurgitation Septum or LV free wall may appear Septum or LV free wall may appear

hyperechogenichyperechogenic

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

Myocardial, InfiltrativeMyocardial, Infiltrative

Gaucher’sGaucher’s– Most common lysosomal storage diseaseMost common lysosomal storage disease– Deficiency in beta-glucocerebrocidase enzymeDeficiency in beta-glucocerebrocidase enzyme– Accumulation of cerebroside in many organs, usually bm, spleen, liver, brainAccumulation of cerebroside in many organs, usually bm, spleen, liver, brain– More rareMore rare: pulmonary & cardiovascular involvement: pulmonary & cardiovascular involvement

Cerebroside accumulation in interstitium of LV -> restrictive cmCerebroside accumulation in interstitium of LV -> restrictive cm– Often subclinicalOften subclinical

Pulmonary hypertension from pulmonary capillary occlusionPulmonary hypertension from pulmonary capillary occlusion Calcification & thickening of valves, pericardial effusionCalcification & thickening of valves, pericardial effusion

Hurler’s SyndromeHurler’s Syndrome– Mucopolysaccharide accumulation leads to severe skeletal deformities, Mucopolysaccharide accumulation leads to severe skeletal deformities,

hepatosplenomegaly, mental retardationhepatosplenomegaly, mental retardation– Cardiac involvement evident between 1-5 years of ageCardiac involvement evident between 1-5 years of age– Mucopolysaccharide deposition in myocardial interstitium, valves, coronary arteries, aortaMucopolysaccharide deposition in myocardial interstitium, valves, coronary arteries, aorta

Metabolic StorageMetabolic Storage DiseasesDiseases

HemochromatosisHemochromatosis– Five types, AD or ARFive types, AD or AR– Iron deposition in multiple organs (heart, liver, Iron deposition in multiple organs (heart, liver,

skin, pancreas, pituitary, joints)skin, pancreas, pituitary, joints)– Dilated>restrictive cardiomyopathyDilated>restrictive cardiomyopathy

Systolic dysfunction indicates a poor Systolic dysfunction indicates a poor prognosisprognosis

– Conduction disturbances common, e.g., SSSConduction disturbances common, e.g., SSS SVT & VT occur in 1/3 of patientsSVT & VT occur in 1/3 of patients

– Granular or sparkling appearance may be seen Granular or sparkling appearance may be seen on echoon echo

Atrial enlargementAtrial enlargement

– Treatment with repeated phlebotomy or chelation Treatment with repeated phlebotomy or chelation (desferrioxamine) may reverse LV dysfunction(desferrioxamine) may reverse LV dysfunction

– Cardiac transplantation can be consideredCardiac transplantation can be considered

Hurst’s The Heart, 10Hurst’s The Heart, 10thth edition edition

Fabry Disease (angiokeratoma corporis diffusum,Fabry Disease (angiokeratoma corporis diffusum,ceramide trihexosidosis, ceramide trihexosidosis,

or Anderson-Fabry disease )or Anderson-Fabry disease )

– X-linked disorder of glycosphingolipid X-linked disorder of glycosphingolipid metabolismmetabolism

Due to deficiency of lysosomal ceramide (Due to deficiency of lysosomal ceramide (- - galactosidase)galactosidase)

Intracellular accumulation & deposition of Intracellular accumulation & deposition of glycolipids in heart, skin, kidneysglycolipids in heart, skin, kidneys

First symptoms manifest by age 10First symptoms manifest by age 10– Peripheral neuropathy, hypohidrosis, Peripheral neuropathy, hypohidrosis,

skin lesions (angiokeratomas), renal skin lesions (angiokeratomas), renal dysfunctiondysfunction

Nagueh, SF. Fabry disease. Heart 2003; 89:819.Nagueh, SF. Fabry disease. Heart 2003; 89:819.

Fabry DiseaseFabry Disease

Accumulation occurs in myocardium, vascular, and valvular Accumulation occurs in myocardium, vascular, and valvular endotheliumendothelium

May develop LVH (concentric) with hypertrophic CM, restrictive CM, May develop LVH (concentric) with hypertrophic CM, restrictive CM, or dilated CMor dilated CM

– Conduction abnormalities, AR>MR, premature CAD, aortic root Conduction abnormalities, AR>MR, premature CAD, aortic root dilation, premature strokedilation, premature stroke

– Cardiac manifestations may not occur until age 30Cardiac manifestations may not occur until age 30– Echo findings are similar to amyloidEcho findings are similar to amyloid

LV mass correlates with disease severityLV mass correlates with disease severity Full expression in males, incomplete in femalesFull expression in males, incomplete in females Screening for plasma alpha-galactosidase A levels in patients with Screening for plasma alpha-galactosidase A levels in patients with

unexplained concentric LVH should be consideredunexplained concentric LVH should be considered Recombinant alpha-galactosidase causes regression of cardiac Recombinant alpha-galactosidase causes regression of cardiac

dysfunctiondysfunction

Endomyocardial DiseasesEndomyocardial Diseases

Endomyocardial Fibrosis Endomyocardial Fibrosis (Davies Disease)(Davies Disease)

– TropicsTropics– 10-20% of deaths due to HF in equitorial 10-20% of deaths due to HF in equitorial

AfricaAfrica– Children, young adultsChildren, young adults– No gender predilictionNo gender prediliction– Intense endocardial fibrotic thickening of Intense endocardial fibrotic thickening of

apex & subvalvular regions of apex & subvalvular regions of ventricle(s)→ obstruction to blood inflow, ventricle(s)→ obstruction to blood inflow, regurgitation, restrictive physiologyregurgitation, restrictive physiology

– Histology:Histology: granulation tissue, collagen, granulation tissue, collagen, connective tissue lines endocardiumconnective tissue lines endocardium

– Affects both (50%), left (40%), right (10%) Affects both (50%), left (40%), right (10%) ventriclesventricles

– Two year mortality up to 50%Two year mortality up to 50%

Endomyocardial Fibrosis:Endomyocardial Fibrosis:Echo FeaturesEcho Features

Inferobasal LV wall thickeningInferobasal LV wall thickening Endocardial thrombus depositionEndocardial thrombus deposition

– Apical obliterationApical obliteration Biventricular involvement in ½ of patientsBiventricular involvement in ½ of patients Ventricular cavities vary in size but often obliterated by Ventricular cavities vary in size but often obliterated by

extensive endocardial thickeningextensive endocardial thickening Large atriaLarge atria Papillary muscle involvement & AV valve apparatus with valve Papillary muscle involvement & AV valve apparatus with valve

deformity commondeformity common– Regurgitation>stenosisRegurgitation>stenosis

AF commonAF common

Endomyocardial DiseasesEndomyocardial Diseases

Loeffler’s endocarditis Loeffler’s endocarditis [eosinophilic cardiomyopathy][eosinophilic cardiomyopathy]

– Temperate climatesTemperate climates– Activated eosinophils may release cardiotoxic Activated eosinophils may release cardiotoxic

intracytoplasmic granules intracytoplasmic granules – Middle age, usually menMiddle age, usually men– Intense eosinophilia, nervous system & bone Intense eosinophilia, nervous system & bone

marrow involvement, skin rash, constitutional marrow involvement, skin rash, constitutional symtpmssymtpms

– Restrictive cardiac disease (often Restrictive cardiac disease (often biventricular), fibrinoid vasculitis of coronariesbiventricular), fibrinoid vasculitis of coronaries

– Valvular involvement leads to regurgitation or Valvular involvement leads to regurgitation or stenosis of AV valvesstenosis of AV valves

– Thromboembolic phenomenaThromboembolic phenomena Mural & atrial thrombiMural & atrial thrombi LV thrombi in absence of WMALV thrombi in absence of WMA Gradual apical obliteration; apex fills with Gradual apical obliteration; apex fills with

echogenic massechogenic mass

Tai PC Lancet 87’; 1; Tai PC Lancet 87’; 1;

Wood MJ et al; Utility of Echo in the Eval of Ind with CM; Heart 2004; 90Wood MJ et al; Utility of Echo in the Eval of Ind with CM; Heart 2004; 90

Thrombus deposition in RV/LV apicesThrombus deposition in RV/LV apices

Endomyocardial DiseasesEndomyocardial Diseases

Carcinoid Heart Disease Carcinoid Heart Disease – Late complication of carcinoid syndrome from Late complication of carcinoid syndrome from

metastatic carcinoid tumorsmetastatic carcinoid tumors 50% of patients50% of patients TR most common findingTR most common finding

– Pathognomonic fibrous plaque-like deposits Pathognomonic fibrous plaque-like deposits Pulmonary inactivation of serotonin, bradykinin, Pulmonary inactivation of serotonin, bradykinin,

etc..etc..– LV involvement uncommonLV involvement uncommon

If present, likely r->l shuntIf present, likely r->l shunt Endocardium of valve cusps/leaflets,cardiac Endocardium of valve cusps/leaflets,cardiac

chambers, intima of PA/aorta chambers, intima of PA/aorta Plaques: smooth muscle cells embedded in Plaques: smooth muscle cells embedded in

mucopolysaccharides & collagenmucopolysaccharides & collagen– Lack elastic componentsLack elastic components

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

Carcinoid SyndromeCarcinoid Syndrome

– Echo findings in 2/3 of patientsEcho findings in 2/3 of patients

Thickened, retracted, immobile tricuspid & pulmonary valvesThickened, retracted, immobile tricuspid & pulmonary valves RA/RV enlargementRA/RV enlargement RA wall thickening on TEERA wall thickening on TEE Pulmonary outflow obstruction may occurPulmonary outflow obstruction may occur TR/PR on doppler TR/PR on doppler Rarely see metastatic tumors to heartRarely see metastatic tumors to heart

– Valvular lesions do not regress with therapyValvular lesions do not regress with therapy

Endomyocardial DiseasesEndomyocardial Diseases Radiation carditisRadiation carditis

– Can manifest decades after thoracic radiotherapyCan manifest decades after thoracic radiotherapy– Can involve many cardiac structuresCan involve many cardiac structures

Coronary arteries: ostial stenosesCoronary arteries: ostial stenoses Valves: stenosisValves: stenosis Pericardium: constrictive pericarditis Pericardium: constrictive pericarditis Myocardium, endocardium:Myocardium, endocardium:

– Interstitial fibrosis of RV > LVInterstitial fibrosis of RV > LV

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

EndomyocardialEndomyocardial DiseasesDiseases

Metastatic cancer (lung, breast, melanoma, leukemia, lymphoma)Metastatic cancer (lung, breast, melanoma, leukemia, lymphoma) Drug toxicity:Drug toxicity:

– Anthracylines: dilated CM & endomyocardial fibrosisAnthracylines: dilated CM & endomyocardial fibrosis Risk of restrictive cm markedly increased with concurrent Risk of restrictive cm markedly increased with concurrent

irradiationirradiation Diastolic abnormalities do not appear to be dose-relatedDiastolic abnormalities do not appear to be dose-related

Drugs causing endomyocardial fibrosisDrugs causing endomyocardial fibrosis– MethylsergideMethylsergide– SerotoninSerotonin– BusulfanBusulfan– ErgotamineErgotamine– Mercurial agentsMercurial agents

Doppler Echo findings: Doppler Echo findings: Early in Disease CourseEarly in Disease Course

Impaired diastolic fillingImpaired diastolic filling– Doppler of LV inflowDoppler of LV inflow

Reduced E velocity, increased A Reduced E velocity, increased A velocityvelocity

Prolonged isovolumic relaxation timeProlonged isovolumic relaxation time Decreased early diastolic deceleration Decreased early diastolic deceleration

slopeslope– Pulmonary vein inflowPulmonary vein inflow

Reduced diastolic filling phaseReduced diastolic filling phase Normal systolic filling phaseNormal systolic filling phase

– Decreased ratio of systolic to Decreased ratio of systolic to diastolic PV flowdiastolic PV flow

Zile et al. Circ 02’; 105Zile et al. Circ 02’; 105

PseudonormalizationPseudonormalization

LA pressure risesLA pressure rises– Increased pressure gradient from LA to LV Increased pressure gradient from LA to LV

at MV openingat MV opening– EE and and AA velocities may remain relatively velocities may remain relatively

normalnormal Pulmonary venous inflowPulmonary venous inflow

– Systolic filling normal or decreasedSystolic filling normal or decreased– Diastolic is normal or increasedDiastolic is normal or increased– Increased resistance to LV filling : Increased resistance to LV filling : in in

velocity and duration of atrial flow reversal velocity and duration of atrial flow reversal in lower resistance PVin lower resistance PV

Otto, Textbook of Clinical Echo; 3Otto, Textbook of Clinical Echo; 3rdrd edition edition

Advanced Restrictive PatternAdvanced Restrictive Pattern

Ventricular compliance continues to Ventricular compliance continues to decreasedecrease

Increased mitral early diastolic filling Increased mitral early diastolic filling velocity (velocity (EE) [> 1m/s]) [> 1m/s]

– Deceleration slope becomes more rapidDeceleration slope becomes more rapid AA velocity reduced due to increased velocity reduced due to increased

LVEDP & reduced atrial contractile LVEDP & reduced atrial contractile function [<.5 m/s]function [<.5 m/s]

Increased E:A ratio (>2)Increased E:A ratio (>2) Mitral deceleration time shortens (<150 Mitral deceleration time shortens (<150

ms)ms) Isovolumic relaxation time shortens [Isovolumic relaxation time shortens [ 70 70

ms]ms] PV flow shows increased diastolic phase, PV flow shows increased diastolic phase,

reduced systolic phase & Pva increases reduced systolic phase & Pva increases further in duration & velocityfurther in duration & velocity

E/A 2.4E/A 2.4

Myocardial Tissue Doppler SignalsMyocardial Tissue Doppler Signals

Displays the velocities of the myocardium Displays the velocities of the myocardium during contraction and relaxation during contraction and relaxation

Can assist in assessment and grading of Can assist in assessment and grading of diastolic functiondiastolic function

– Sm:Sm: myocardial velocity during myocardial velocity during systolesystole

– Em:Em: myocardial velocity during myocardial velocity during early fillingearly filling

– Am:Am: myocardial velocity during myocardial velocity during filling due to atrial contractionfilling due to atrial contraction

In restrictive pattern, Em In restrictive pattern, Em is diminutiveis diminutive

Helpful in differentiating constriction from Helpful in differentiating constriction from restrictionrestriction

Cardiac MRCardiac MR

Can aid in distinguishing between the cardiomyopathiesCan aid in distinguishing between the cardiomyopathies– Hemochromatosis produces low signal intensity due to iron Hemochromatosis produces low signal intensity due to iron

depositiondeposition– May differentiate primary restrictive CM from amyloidosis based on May differentiate primary restrictive CM from amyloidosis based on

tissue characterization tissue characterization – May detect mass lesions due to sarcoid granuloma or scarMay detect mass lesions due to sarcoid granuloma or scar

Can aid in differentiating constrictive from restrictive Can aid in differentiating constrictive from restrictive diseasedisease

Celetti et al, AJC 99’ 83Celetti et al, AJC 99’ 83