"le malattie cardiache infiltrative, diagnosi differenziale"

La Malattia di Fabry: conoscere per riconoscere17 giugno 2015, Udine

Le malattie cardiache infiltrative, diagnosi differenziale

Daniela MianiU.O. Scompenso cardiaco e Trapianti

S.O.C. Cardiologia - Dipartimento Cardiotoracico Ospedale Santa Maria della Misericordia di Udine

Definition• Infiltrative cardiomyopathies are characterized by the

deposition of abnormal substances that cause the ventricular walls to become progressively rigid, thereby impeding ventricular filling

• Some infiltrative cardiac diseases increase ventricular wall thickness (Table 1), while others cause chamber enlargement with secondary wall thinning (Table 2).

• In infiltrative disorder acculation of abnormal substances can be whitin myocytes with hypertrophy or in the myocardialinterstitium without myocyte hypertrophy

Physiopathology and Imaging• Infiltrative cardiomyopathy are characterized by

progressive diastolic dysfuncion that anticipate the finalsystolic dysfunction

• Doppler echocardiography assess the diastolic physiology• and atrial remodelling are the hall marks of restrictive

disease• CMR imaging and LGE provide incremental information:• Gadolinium causes magnetic hyperenhancement when

extracellular space is expanded• CMR is used to characterize the type of infiltrative disease

by the location and distribution of LGE.

Seward et al 2010 JACC;55:1769–79

Conditions Presenting With Increasaed LV Mass and Thic k Ventricular Walls

Seward et al 2010 JACC;55:1769–79

Conditions Presenting With Increasaed LV Mass and Thic k Ventricular Walls

Seward et al 2010 JACC;55:1769–79

Conditions With Dilated LV and Infarct Pattern

Seward et al 2010 JACC;55:1769–79

Conditions With Dilated LV and Infarct Pattern

Hypertrophic cardiomyopathy Hypertensive heart diseas e

Age at Presentation 17–18 yrs Adults

History and ClinicalMaybe asymptomatic, dyspnea,angina, syncope, sudden death History of hypertension

EchocardiographyAsymmetrical hypertrophy,small LV cavity, LVOT obstruction, normal EF

Symmetrical increase in LV wall thickness, mild LV dilation, normal EF

ECG ProfileIncreased QRS complex voltage, pseudo–delta wave, giant T-wave inversion

Increased QRS complex, nonspecific ST-T-wave changes

CMR LGEPatchy, midwall, junctions of the ventricular septum and RV

No pattern, predominantly subendocardial

BiopsyMyocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis

Enlarged myocytes with enlarged or replicated nuclei

Increasaed LV Mass and Thick Ventricular WallsDifferential

Ischemic cardiomyopathy Idiopathic dilated cardiomyopathy

Age at Presentation Adult Adult

History and Clinical

Coronary artery disease, congestive heart failure

Congestive heart failure, no known cardiovascular disease

Echocardiography

Dilated LV, regional hypokinesiscorresponding to perfusion territory, decreased systolic function

Dilated LV with global systolic dysfunction

ECG Profile

Multiform premature ventricular complexes, nonsustained ventricular tachycardia

Atrial fibrillation

CMR LGE

Subendocardial, different degrees of transmural extension, corresponds to perfusion territory No LGE, or if present, midwall and patchy

Biopsy

Conditions With Dilated LV and Infarct PatternDifferential

Amyloidosis• Systemic amyloidosis is a heterogeneus disorder

characterized by extracellular deposition of 8-10 nm fibrilsoriginate from the misfolding of an altered proteinprecursor in various tissues. The amorphous material iscalled amyloid.

• AL Amyloidosis can occure as primary disorder or secondary to hematologic malingnacy as multiple myeloma, Transthyretin (TTR) amyloidosis, systemicsenile amyloidosis, Systemic secondary amiloidosis

• Amyloid deposition can affect myocardium, valves, coronary vessels.

Differential diagnosis (DD)

• DD Is based on ECG , echocardiogram(Doppler) and cardiac RMN and histologicfindings from fat pad aspirate, salivary glands, gingiva and rectal biopsy, endomyocardialbiopsy

• DDIncludes: hypertrophic cardiomyopathy, hypertensive heart disease, infiltrativecardiomyopathy , storage diseases: DanonDisease and Fabry Disease.

Low voltage precordial leads on ECG

Low voltage precordial leads on ECG

Amyloidosis RMN

Amyloidosis RMN

Amyloidosis

Amyloidosis

EMB: colorazione Rosso Congo

BEM: birifrangenza al Rosso Congo

Danon Disease Background

• Danon Disease is a rare X linked dominantskeletal and cardiac muscle disease with mulisystemic clinical manifestations.

• young men present a clincal triade characterizedby skeletal and cardiac myopathy, cardiacconduction abnormalities, arrhythmias, and intelectual impairment

Background

• The disease is caused by mutations in LAMP-2 gene (Xq24), encoding for a lysosomal-associated membrane protein The product is involved in the fusion of lysosomes with other membranes and also acts as a receptor for proteins to be imported into lysosomes

• LAMP-2 deficiency leads to pathological glycogen storage in several tissues, such as retinal, hepatic and pulmonary tissue

CM, female 42y

• Symptomatic since 34yrs for palpitations

• Physical examination: normal.

• EKG: normal

• Echo: normal; RMN: normal

• Holter monitoring: BEV >30/h, > 50/h, couplets, NSVT max 6 beats.

• Genetic screening in 2005: LAMP2 +

CM, female 42y ECG

Sarcoidosis• Sarcoidosis is a multisystemic disease characterizerd by

the formation of granulomas in many tissues.

• Pulmonary involvement with hilar lymphadenopathy is the most frequent presentation

• Secondary skin involvement (erytema nodosus)• Cardiac involvement my be the presenting feature of

sarcoidosis• Cardiac sarcoidosis in autopsy series is present between

20% and 30% of cases

Clinical presentation• Dyspnea• Abnormal electrocardiogram• Asymptomatic abnormalities on echocardiography or at

MRI • Dyspnea� DD with dilated cardiomyopathy• Acute sarcoid myocarditis� DD idiopathic giant cell

myocarditis• ECG abnormalities: isolate complete heart block in young

person� DD with Lyme disease• ECG abnormalities: frequent ventricular arrhythmias �DD

with right ventricular cardiomyopathy.

Echocardiography, Cardiac MRI• Echo presents regional wall motion abnormalities• Areas of wall thinning in the septum (basal anterior

septum)• Cardiac MRI and PET are more sensitive and specific for

diagnosis• Cardiac MRI demostrates both scar and edema • Acute myocardial inflammation presents focal areas of

tickening and increased signal intensity on T2 weightedimages and early Gadolinium Enhancement in the basaland lateral segments.

FDG PET demonstrating diffuse, patchy, and intense FDG uptake throughout the left and right ventricular walls

Echocardiogram: mitral flow pattern

Conclusions

• Infiltrative cardiomyopthies (IF) are relatively raredisorders :

• morphologic characteristics are variable• IF Tend to be misdiagnosed• Clinical suspect, ECG, Echocardiography(Doppler) and Cardiac RMN in congiunction withclinical manifestations are foundamental inestablishing an accurate diagnosis and in theplanning of the appropriate treatment