CARDIOMIOPATIILE

Tipurile de CM: primare

Suferinte miocardice primitive sau secundare

Dilated cardiomyopathy: Dilatation and impaired contraction of the left or both ventricles. Caused by familial/genetic,
viral and/or immune, alcoholic/toxic, or unknown factors, or is associated with recognized cardiovascular disease.
Hypertrophic cardiomyopathy Left and/or right ventricular hypertrophy, often asymmetrical, which usually involves the
interventricular septum. Mutations in sarcoplasmic proteins cause the disease in many patients.
Restrictive cardiomyopathy Restricted filling and reduced diastolic size of either or both ventricles with normal or near-
normal systolic function. Is idiopathic or associated with other disease (e.g., amyloidosis, endomyocardial disease).
Arrhythmogenic right ventricular cardiomyopathy Progressive fibrofatty replacement of the right, and to some degree
left, ventricular myocardium. Familial disease is common.
Unclassified cardiomyopathy Diseases that do not fit readily into any category. Examples include systolic dysfunction
with minimal dilatation, mitochondrial disease, and fibroelastosis.
Specific Cardiomyopathies
Ischemic cardiomyopathy Presents as dilated cardiomyopathy with depressed ventricular function not explained by the
extent of coronary artery obstructions or ischemic damage.
Valvular cardiomyopathy Presents as ventricular dysfunction that is out of proportion to the abnormal loading conditions
produced by the valvular stenosis and/or regurgitation.
Hypertensive cardiomyopathy Presents with left ventricular hypertrophy with features of cardiac failure due to systolic
or diastolic dysfunction.
Inflammatory cardiomyopathy Cardiac dysfunction as a consequence of myocarditis.
Metabolic cardiomyopathy Includes a wide variety of causes, including endocrine abnormalities, glycogen storage
disease, deficiencies (such as hypokalemia), and nutritional disorders.
General systemic disease Includes connective tissue disorders and infiltrative diseases such as sarcoidosis and leukemia.
Muscular dystrophies Includes Duchenne, Becker-type, and myotonic dystrophies.
Neuromuscular disorders Includes Friedreich ataxia, Noonan syndrome, and lentiginosis. Sensitivity and toxic reactions
Includes reactions to alcohol, catecholamines, anthracyclines, irradiation, and others.
Peripartal cardiomyopathy First becomes manifest in the peripartum period, but it is likely a heterogeneous group.
 Tipurile de CM: secundare (specifice)

 Boli infiltrative: amiloidoza, Hurler, Hunter, Gaucher

 Tezaurismoze: hemocromatoza, Niemann-Pick, Fabry
 Toxica: medicamente, metale grele, agenti chimici
 Endomiocardica: fibroza endomiocardica, sdr. hipereozinofilic
 Inflamatorie – granulomatoasa: sarcoidoza
 Endocrine: DZ, hiper – hipotiroidism, feocromocitom, acromegalie
 Boli neuromusculare (ataxia Fridereich, distrofia musculara Duchenne)
 Deficite nutritionale: beri-beri, pelagra, scorbut, kwashiorkor
 Boli sistemice: LES, PR, PM-DM, SSP, PAN
 Chimioterapie: doxorubicina, ciclofosfamida; Radioterapia
Factorii genetici in CM

CARDIOMIOPATIA HIPERTROFICA
  Definitie. CM primara
caracterizata prin:

 HVS asimetrica sau

concentrica

 Cauza genetica: mutatii

ale genelor care codifica proteinele
sarcomerului

 Disfunctie VS
predominent diastolica

 Cardiomiopatia hipertrofica:

 75% din cazuri neobstructiva: HVS

 25% din cazuri obstructiva: HVS +

“stenoza aortica subvalvulara”

 Incidenta:

 0.2 – 0.5% din populatia generala

 M>F
Sir Russell Brock’s paper on “functional obstruction of the left ventricle” in 1957 (12) and Donald
Teare’s description of asymmetric myocardial hypertrophy in 1958: primele descrieri

HCM is a clinically heterogeneous but relatively common autosomal dominant genetic heart disease
(1:500 of the general population for the disease phenotype recognized by echocardiography) that probably is the most
frequently occurring cardiomyopathy. Data from the United States indicate that HCM is the most common cause of
sudden cardiac death in the young (including trained athletes) and is an important substrate for heart failure disability at
any age.o clinical study has demonstrated any convincing evidence for an effect of sex on disease expression, most
large series show a predominance of male subjects.

Incidenta mutatiilor
componentelor
sarcomerice in CMH
 cr. 1 cr. 15 cr. 19 cr. 15
cr. 11

cr. 3, 12 cr. 14
 11 gene
implicate

 80% forma
familiala autozomal
dominanta

 La
nturi grele ale miozinei: cr. 14q1

 20% forma sporadica

Genetic testing has also highlighted the phenomena of incomplete penetrance and age-related disease expression, and
as a result diagnostic criteria are once again being revised
The first disease locus to be identified was situated in the chromosome 14q1 region in a large French Canadian family
(36). The genes encoding the two cardiac myosin heavy chains (a and b) are arranged in tandem on chromosome 14
band q11.2-13, and further analysis involving this Canadian family revealed that each affected member had a missense
mutation in exon 13 of the b-myosin heavy-chain gene (38).
Since this discovery, numerous mutations in seven other genes that encode thick and thin filament sarcomeric
proteins have been reported (Fig. 29.4): cardiac troponin T (chromosome 1), cardiac troponin I (chromosome 19),
a-tropomyosin (chromosome 15), cardiac myosin-binding protein C (chromosome 11), the essential and regulatory
myosin light chains (chromosomes 3 and 12, respectively), and cardiac actin (chromosome 15) (36–67). In addition, a
locus on chromosome 7 has been identified in a large Irish family with HCM and Wolff-Parkinson-White syndrome
(90,91), and a further unconfirmed mutation in the gene encoding another sarcomeric protein, Titin (chromosome 2)
(68), has been reported.
2006:
HCM is caused by a variety of mutations encoding contractile proteins of the cardiac sarcomere. Currently, 11 mutant
genes are associated with HCM, most commonly -myosin heavy chain (the first identified) and myosinbinding protein
C. The other 9 genes appear to account for far fewer cases of HCM and include troponin T and I, regulatory and essential
myosin light chains, titin, -tropomyosin, -actin, -myosin heavy chain, and muscle LIM protein. This genetic diversity is
compounded by considerable intragenic heterogeneity, with 400 individual mutations now identified.
These most commonly are missense mutations but include insertions, deletions, and splice (split-site) mutations
encoding truncated sarcomeric proteins. The characteristic diversity of the HCM phenotype is attributable to the disease
causing mutations and probably to the influence of modifier genes and environmental factors.
In addition, nonsarcomeric protein mutations in 2 genes involved in cardiac metabolism have recently been reported to
be responsible for primary cardiac glycogen storage diseases in older children and adults with a clinical presentation
mimicking (or indistinguishable from) that of sarcomeric HCM. One of these conditions involves the gene encoding the
-2-regulatory subunit of the AMP-activated protein kinase (PRKAG2), associated with variable degrees of LV
hypertrophy and ventricular preexcitation. The other involves the gene encoding lysosome-associated membrane
protein 2 (LAMP-2), resulting in Danon-type storage disease. Clinical manifestations are limited largely to the heart,
usually with massive degrees of LV hypertrophy and ventricular preexcitation. These disorders are now part of a
subgroup of previously described infiltrative forms of LV hypertrophy such as Pompe disease, a glycogen storage disease
caused by -1,4 glycosidase (acid maltase deficiency) in infants, and Fabry’s disease, an X-linked recessive disorder of
glycosphingolipid metabolism caused by a deficiency of the lysosomal enzyme -galactosidase A, resulting in
intracellular accumulation of glycosphingolipids.
Undoubtedly, many other mutations causing cardiac hypertrophy by disrupting sarcomere, metabolic, and other genes
remain to be identified.
Anatomie
patologica
 HVS concentrica:
 33% din cazuri

VD

VS
  HVS asimetrica:
66% din cazuri
 varianta: HVS apicala

In Teare’s original series (13), myocardial

hypertrophy was asymmetric, involving the
interventricular septum more than the posterior
or free wall of the left ventricle (Fig. 29.1).
Subsequent studies have shown that, although
asymmetric septal hypertrophy is present in
approximately two-thirds of patients (70,71),
virtually any pattern can occur. Hypertrophy
confined to the left ventricular apex is
uncommon, except possibly in Japanese patients
(72). Isolated right ventricular hypertrophy is
unreported
Macroscopically, the cut surface of involved myocardium has a characteristic appearance reminiscent of a uterine
fibroid, with abnormally short and broad muscle fibers running in different directions
Sageata: patch of subendocardial thickening on the septum caused by repeated contact with the anterior leaflet of the
mitral valve

CMH:

 dezorganizarea
cardiomiocitara:
> 5% din masa totala a
miocardului
> 20% din zonele hipertrofiate
 dezorganizarea
miofibrilara
Miocard normal
Miocard din CMH

The cardinal microscopic feature of HCM is myocyte disarray. This is recognized by a loss of the normal parallel
arrangement of myocytes, with cells forming circles around foci of connective tissue. Individual myocytes may show
marked variation in diameter and nuclear size and have abnormal intercellular connections. Myofibrillar architecture
within cells is also disrupted—so-called myofibrillar disarray.
Myocyte disarray is described in congenital heart disease, hypertension, and aortic stenosis, but in HCM it is
typically more extensive, occupying 20% or more of at least one ventricular tissue block and more than 5% of
total myocardium at post mortem examination.
When LV wall thickness is mild, differential diagnosis with physiological athlete’s heart may arise. Furthermore,
individuals harboring a genetic defect for HCM do not necessarily express clinical markers of their disease such as LV
hypertrophy on echocardiogram, ECG abnormalities, or symptoms at all times during life, and ECG alterations can
precede the appearance of hypertrophy. Indeed, virtually any LV wall thickness, even when within normal limits, is
consistent with the presence of an HCM-causing mutant gene, and diagnosis can be made by laboratory DNA analysis.
Furthermore, recognition of LV hypertrophy may be age related with its initial appearance delayed well into adulthood
(adult morphological conversion). Most HCM patients have
the propensity to develop dynamic obstruction to LV outflow under resting or physiologically provocable conditions,
produced by systolic anterior motion of the mitral valve with ventricular septal contact.

CMH:

 dezorganizarea
cardiomiocitara:
> 5% din masa totala a miocardului
> 20% din zonele hipertrofiate

 dezorganizarea miofibrilara
The cardinal microscopic feature of HCM is myocyte disarray. This is recognized by a loss of the normal parallel
arrangement of myocytes, with cells forming circles around foci of connective tissue. Individual myocytes may show
marked variation in diameter and nuclear size and have abnormal intercellular connections. Myofibrillar architecture
within cells is also disrupted—so-called myofibrillar disarray.
Myocyte disarray is described in congenital heart disease, hypertension, and aortic stenosis, but in HCM it is
typically more extensive, occupying 20% or more of at least one ventricular tissue block and more than 5% of
total myocardium at post mortem examination.
When LV wall thickness is mild, differential diagnosis with physiological athlete’s heart may arise. Furthermore,
individuals harboring a genetic defect for HCM do not necessarily express clinical markers of their disease such as LV
hypertrophy on echocardiogram, ECG abnormalities, or symptoms at all times during life, and ECG alterations can
precede the appearance of hypertrophy. Indeed, virtually any LV wall thickness, even when within normal limits, is
consistent with the presence of an HCM-causing mutant gene, and diagnosis can be made by laboratory DNA analysis.
Furthermore, recognition of LV hypertrophy may be age related with its initial appearance delayed well into adulthood
(adult morphological conversion). Most HCM patients have
the propensity to develop dynamic obstruction to LV outflow under resting or physiologically provocable conditions,
produced by systolic anterior motion of the mitral valve with ventricular septal contact.
CMH – fibroza interstitiala

Disarray is often
associated with
myocardial fibrosis, ranging from extensive
scarring in the interventricular septum, free
wall of the left ventricle, and occasionally the
left ventricular papillary muscles (77) to a
more diffuse interstitial pattern

CMH –
anomaliile microcirculatiei
  pe vase < 1.5 mm

 Apare oriunde in
miocard
(descrisa initial in zone
cicatriciale sau hipertrofice)

The demonstration of abnormal small

intramural arteries (external
diameter less than 1,500 mm) within
fibrotic areas and in patients with
ventricular dilatation and reduced systolic function (79,80) (Fig. 29.3) has suggested that contiguous myocardial scarring
may be caused by myocardial ischemia. However, more recent data have shown that small-vessel disease may be just
as widespread in patients without extensive fibrosis and may occur in the absence of myocardial hypertrophy

-
 Fiziopatologia CMH

 Tulburarile functiei diastolice:

 Hipertrofia miocitara

 Dezordinea miocitara si miofibrilara

 Fibroza interstitiala

 Metabolism anormal al calciului

CM
 Ischemia miocardica H
 Ischemia miocardica:

 rezervei coronare de flux + boala microcirculatiei

 25% din pacienti au subdenivelari ST la Holter ECG

 40% au subdenivelari ST la efort
 Poate fi responsabila de MSC
CMH
 +/- obstructie intraventriculara cu gradient dynamic O

Diastolic Dysfunction
Several of the characteristic pathophysiologic features of HCM impair diastolic function, specifically, myocyte
hypertrophy, myocyte and myofibrillar disarray, abnormal intracellular calcium metabolism, myocardial fibrosis,
abnormal ventricular geometry, and myocardial ischemia (129–140). In a minority of patients, a restrictive
hemodynamic picture may predominate, with marked elevation of filling pressures, biatrial dilatation, and
predominantly right-sided signs, often in the absence of substantial myocardial hypertrophy (137,138). In the majority of
cases, a mixed picture with slow relaxation and elevated end diastolic pressures is observed. Invasive hemodynamic
studies have demonstrated a flat pressure-volume relationship with a response to off-loading similar to that seen in
patients with constrictive pericarditis, suggesting the presence of increased pericardial or possibly myocardial constraint
Myocardial Ischemia
Several studies have shown that patients with HCM have reduced coronary flow reserve and metabolic evidence for
myocardial ischemia during pacing and pharmacologic stress (119–125). It is likely that myocardial ischemia is the cause
of chest pain and dyspnea in many individuals, and limited data are available to suggest that myocardial ischemia
may be a trigger for fatal ventricular arrhythmia (126,127). However, the clinical evaluation of patients with chest
pain remains problematic. For example, whereas ST segment depression occurs in up to 40% of patients during
exercise (118), lactate production during atrial pacing is seen in more than one-half of those with negative results of
exercise tests. ST segment depression also occurs during ambulatory ECG monitoring in 25% of symptomatic young
patients (128), but its metabolic significance in unknown. A number of pathophysiologic mechanisms have been
suggested as causes of myocardial ischemia in patients with HCM (Table 29.1), but the predominant mechanism in
individual patients is usually impossible to determine.

Localizarea si fiziopatologia obstructiei in CMHO

 Proeminenta SIV in LVOT
 Miscare sistolica anterioara a foitei mitrale
anterioare
(SAM)
 Gradient intraventricular
 Insuficienta mitrala
 Ejectie rapida: VS hiperkinetic

Localizarea si fiziopatologia obstructiei in CMHO

Manifestari clinice in CMHO

Simptome:

 Asimptomatici

 Dispnee

 Angina (30% din adulti)

 Sincopa (15-25% din cazuri)

 Palpitatii si aritmii V sau SV

 MSC

Semne:

 “Pulsus bisferiens”

 Soc apexian hiperdinamic

 Galop presistolic

 SUFLU DE EJECTIE variabil:

 prin  volumului VS (efort, tahicardie, nitrit de amil, Valsalva, ortostatism)

 prin  volumului VS (PS mimetice, pozitia “pe vine”)

 Suflu de insuficienta mitrala

ECG

 HVS cu gradient alterat

 T negative in precordiale
 Unde Q septale: 25-50%
din cazuri
 P mitral
 Aritmii atriale sau
ventric.
 T negative gigante in V1-
V6 in CMH apicala
 diastola

sistola

Ecocardiografia

 Metoda diagnostica de electie

 HVS:
 Asimetrica: SeIV / PP > 1.5/1
 Concentrica
 Apicala
 Sept hipertrofiat hipokinetic
 Cavitate VS mica
 SAM a foitei Mi anterioare
 Inchidere mezosistolica a cuspelor aortice
CM hipertrofica
neobstructiva

Disfunctie diastolica severa

SAM in CMHO - eco

transthoracic
SAM in CMHO: TEE

CMHO – gradientul
intraventricular
CMHO forma apicala

Cateterismul cardiac:
gradientul
intraventricular
CMHO angio

CMHO – SAM angio

CMHO la RMN

Supravietuirea in CMHO in functie de

numarul factorilor de risc

Ff de risc ptr deces:

 AHC de MSC <
45 ani
 sincopa
 HVS extrema (>
30 mm)
 hipoTA la efort
 TV-NS la ex
Holter
 MSC sau TV
sustinuta
Ff de risc genetici:
 mutatii ale genei
 troponinei T

Tratamentul CMHO

 Evitarea efortului fizic: 40% din MSC se produc la efort

 Ameliorarea simptomelor = reducerea gradientului intraventricular

 Inotrop negative: -blocante, disopiramida, verapamil

 Embolizarea septala

 Pacing bicameral
  Miectomie chirurgicala

 Preventia mortii subite la pacientii cu risc inalt:

 Reducerea gradientului IV

 Amiodarona, defibrilator implantabil

Although some studies have suggested that up to 70% of patients improve with beta-blocker therapy, high doses are
frequently required and side effects may be limiting (28,162). Furthermore, little convincing evidence exists that beta-
blockers reduce the incidence of serious ventricular arrhythmias or sudden death (255). When beta-blockade alone is
ineffective, the addition of disopyramide can be effective in reducing gradients and improving symptoms (256–258).
Disopyramide should be titrated to patient’s symptoms and the emergence of side effects, aiming for a maintenance dose
of 400 to 600 mg daily. Data comparing beta-blockade and disopyramide are limited, but disopyramide may have a
superior effect on exercise tolerance (258). In some patients, particularly elderly patients, anticholinergic side effects
may preclude or limit the use of disopyramide. Recent data suggest that an alternative class I antiarrhythmic drug,
cibenzoline, which has fewer anticholinergic side effects, may be equally effective (259). Verapamil is also used to treat
symptoms in patients with outflow gradients, but its effect is unpredictable, and acute hemodynamic collapse is
described in patients with substantial gradients or severe diastolic dysfunction
Surgery should be considered in all patients with significant (i.e., greater than 50 mm Hg) outflow obstruction and
symptoms refractory to medical therapy (260–267). The principal aim of surgical intervention is to eliminate SAM of the
mitral valve and mitral leaflet–septal contact by widening the left ventricular outflow tract. The most commonly
performed procedure is a ventricular septal myotomy-myectomy (Morrow procedure) performed using a transaortic
approach. This procedure results in a significant reduction in outflow gradient in 95% of cases, reduced mitral
regurgitation, and long-term symptomatic improvement in up to 70% of patients (260–267). Operative mortality rate
figures in series reported elsewhere are of the order of 5% but are now probably less than 1% to 2% in centers with
experienced surgeons. Complications such as atrioventricular block and ventricular septal defects do occur but have
become less frequent with modification of surgical technique and the use of preoperative transesophageal
echocardiography (268). Aortic regurgitation may occur in patients postoperatively but is not usually of hemodynamic
significance
Valoarea prognostica a gradientului intraventricular in repaus > 30 mmHg
Alcoolizarea primei septale

Miotomia-miectomia Morrow in CMHO

Schematic
Diagram of a
Patient
Undergoing
Surgical Septal
Myectomy.
Before the
operation, there is
severe hypertrophy
of the basal
septum, with
systolic anterior
motion of the
mitral valve
(Panel A). This
results in severe
outflow tract
obstruction as well
as mitral
regurgitation.
During surgery
(Panel B), the
portion of the
basal septum that
projects into the
outflow tract is
removed by a
scalpel, resulting
in abolition of the
outflow
tract obstruction (Panel C). In addition, there is no longer systolic anterior motion of the mitral valve, and the mitral
regurgitation is abolished.

Miotomia-miectomia Morrow in CMHO

Preoperator postoperator

Efectul pacingului DDD asupra

gradientului in CMHO

Change in Doppler ultrasound–derived

resting left ventricular outflow tract
(LVOT) gradient from baseline (pre) to
follow-up assessment (post) in patients
with hypertrophic cardiomyopathy
undergoing surgery or pacemaker
insertion. Both groups (surgical
myectomy, left; dual-chamber pacing,
right ) show significant reductions in
resting gradient (p < 0.05). (From
Ommen SR, Nishimura RA, Squires RW,
et al: Comparison of dual-chamber pacing
versus septal myectomy for the treatment
of patients with hypertrophic obstructive
cardiomyopathy. J Am Coll Cardiol
34:191, 1999.)
Algoritm de tratament al CMH

CARDIOMIOPATIILE RESTRICTIVE

Definitie, clasificare etiologica

 Boli miocardice sau endomiocardice caracterizate prin reducerea umplerii diastolice a

unuia sau ambilor ventriculi cu functie sistolica normala sau aproape normala

 Sporadica sau familiala autozomal dominanta

 Clasificare:

 Primare (50% din cazuri):

  Idiopatica
 Fibroza endomiocardica Sdr.
hipereozinofilic
 Endocardita Loffler
 Secundare (50% din cazuri):

 Boli infiltrative: amiloidoza, (sarcoidoza, post iradiere, leucoze)

 Tezaurismoze (hemocromatoza, glicogenoze, boala Fabry)
 Boli metabolico-endocrine (carcinoidul, hipotiroidia, acromegalia)
 Identificarea cauzei are importanta terapeutica

CMR:
anatomie patologica

Depinde de etiologie

HE x 250
Hipertrofie miocitara usoara
HE x 40
Fibroza interstitiala marcata
Asociat fibroza endomiocardica;
Tromboza intracardiaca apicala

Fiziopatologie

 rigiditatii miocardului sau

endocardului

 rapida a presiunii de umplere

ventriculare

 Aspect caracteristic al curbei de presiune diastolice:

 “dip and plateau”

 Afectare
predominanta a VD (+/- VS)

 Dilatatie atriala
marcata cu cavitati
ventriculare normale

 Semne predominente
de IVD:  PVC

Diferente intre CMR si pericardita constrictive

CMR Pericardita constrictiva

Presiuni diastolice A-V Diferenta > 5 mmHg Diferenta < 5 mmHg
HTP (PAPs > 50 mmHg) sau
Platou diastolic al presiunii VD < 1/3 din presiunea sistolica > 1/3 din presiunea sistolica
Biopsia endomiocardica Anormala Normala
BNP >5xN N

Manifestari clinice

 Se coreleaza cu severitatea presiunii in atrii

 Intoleranta la efort

 Incapacitatea cresterii DC prin disfunctia diastolica

 Dispnee

 Astenie severa =  DC

 Semne de PVC mare:

 turgescenta jugulara, hepatomegalie, ascita, edeme, anasarca

 Instalare progresiva, greu reversibile

  Fibrilatie atriala = frecventa prin dilatatie atriala

 Aritmii ventriculare frecvente in faze avansate = cauza deces

 Complicatii tromboembolice la 1/3 din cazuri

 DIAGNOSTIC: ecocardiografie, cateterism cardiac, biopsie endomiocardica

CMR – aspect ecocardiografic

Tratamentul CMR

 Identificarea cauzelor tratabile (ex. hemocromatoza, carcinoid)

 Diuretice ptr reducerea PVC si a retentiei hidrosaline

 IECA determina hipoTA

 Digitalice: inutile patogenic, toxicitate crescuta

 Aritmii ventriculare grave:

 defibrilator implantabil,

 beta blocante sau

 transplant

 Transplant cardiac (nu in bolile sistemice)

Endocardita Loffler

 Caracteristica zonelor
temperate

 Eozinofilie sanguina si
miocardica
marcata

 M < 50 ani cu hipereozinofilie

 Etape clinice succesive:

 Necrotica

 Trombotica

 Fibrotica

Infiltrare miocardica extensiva

cu eozinofile

 Semne de IC congestiva
+ embolii
sistemice

 Tratament:
corticosteroizi,
hidroxiuree, transplant cardiac

Fibroza endomiocardica
 Caracteristica zonelor tropicale
 Eozinofilie usoara
 Fibroza endocardica apicala si subvalvulara
  Afectare biventriculara 50%; VS = 40%
 15-25% din decese cardiace ale zonei
 Afecteaza copii si adulti tineri
 Mortalitate la 2 ani: 35-50%

Amiloidoza miocardica

 CMR cea mai frecvent intalnita

in practica

 Boala infiltrativa multisistemica cu depunere de fibrile polipeptidice liniare in

interstitiul miocardic:

 Lanturi usoare de Ig (kappa sau lambda): forma AL = forma primara, varianta

de mielom

 Non Ig (proteina A): forma AA = forma secundara

 Forma familiala (AF): prealbumina (transtiretina)

 Forma senila (SSA): ANP-like sau transtiretina

 Aparitia manifestarilor clinice =

infiltrare severa

Amiloidoza
cutaneomucoasa

Amiloid: termenul lui Virchow

“amidon-like”

 manifestari neurologice
  Depunerea in rinichi = sdr. nefrotic

Amiloidoza miocardica
Afectarea cardiaca = 1/3 pts cu amiloidoza sistemica tip AL

 Afectarea anatomopatologica este prezenta si in lipsa manifestarilor clinice

 intereseaza miocardul V, A si eventual si valvele

 manifestari clinice: CMR, IC sistolica, hipoTA ortostatica, BAV

ECG: microvoltaj, tulburari de conducere AV sau BR

 Amiloidoza miocardica

Cardiac amyloidosis gives a distinctive appearance on two-

dimensional echocardiography and is associated with abnormal
LV and RV diastolic function. The findings of a normal or
small LV cavity size with markedly thickened myocardium
associated with a highly abnormal texture that is often described as “granular sparkling” in appearance is the classic
presentation (51) (Fig. 26.5A, Fig. 26.5B, Fig. 26.5C).
The sparkling granular appearance is thought to be caused by the acoustic mismatch between the highly reflective
amyloid deposits in the endocardium, myocardium, and pericardium and the normal tissue (357). Moreover, autopsy and
clinical biopsy series have demonstrated the presence of amyloid fibrils in the myocardium at the site of the granular
sparkling echoes. Ultrasonic tissue characterization has been used to identify patients with cardiac amyloidosis (358).
Global LV systolic function is usually preserved in early disease, whereas systolic function is usually impaired in
advanced disease. The interatrial septum and valve leaflets are also thickened. Both atria are enlarged, and small to
moderate pericardial effusions are usually present

Aspectul ecocardiografic in amiloidoza

Tratamentul amiloidozei

 Amiloidoza AL = prognostic c.m. infaust

 Agenti alkilanti: melfalan

 Imunosupresie: prednison

 Toxice ale fusului: colchicina

 Tratamentul IC:

 Evitarea digitalicelor (afinitate ptr fibrele de amiloid = toxicitate)

 Sensibilitate majora la Ca blocante

 Vdil si diureticele: efecte hipotensoare

 ANTICOAGULARE sistemica

 Transplant cardiac in formele fara afectare extracardiaca

 Transplant hepatic in formele cu transtiretina

The prognosis of cardiac amyloidosis is uniformly poor but does depend on the type of disease, with AL amyloidosis
having the worse prognosis (335,336,338,339,342). In a series of over 800 patents with primary amyloidosis over a 10-
year period, the median survival was 2.1 years (374). The treatment for cardiac amyloidosis (AL type) includes
alkylating agents, such as melphalan and prednisone (374).
There have been two randomized trials of chemotherapy showing benefit in AL amyloid (341,375,376). A trial of 100
patients with primary amyloidosis using melphalan, prednisone, and colchicine showed improvement of systemic disease
when the major features were not cardiac or renal (377). Colchicine has also been used to prevent amyloidosis associated
with familial Mediterranean fever (374); however, there is no evidence that it halts the progression of amyloid deposition
in primary amyloidosis. Dose-intensive melphalan with blood stem cell support is currently being evaluated (378).
Cardiac transplantation is generally not performed for patients with AL type amyloidosis, because this is a systemic
illness with progressive amyloidosis in other organs (281). However, it has been considered in select patients without
extracardiac disease (379,380). Liver transplantation has been suggested for the familial type (TTR variant) since the
circulating TTR is produced in the liver. Thus, the new liver replaces the variant TTR with a normal TTR. There is no
specific treatment for the senile type (381,382).
Avoidance of digoxin is recommended since digoxin-induced arrhythmias may occur because the digoxin may bind to
the amyloid fibrils (305,383). However, it has been used to control heart rate in patients with atrial fibrillation with
careful monitoring (336). Also, patients with cardiac amyloidosis may be sensitive to the negative inotropic effects of
calcium channel blockers either because of their abnormal binding to amyloid fibrils or the vasodilator effects (305,384).
Vasodilator agents and diuretics should be used judiciously because of the risk of postural hypotension. Pacemakers may
be useful to treat symptomatic high atrioventricular block (385), and anticoagulation should be considered because of the
risk of thrombus formation with atrial amyloid involvement and atrial standstill