Restrictive cardiomyopathy Flashcards
Definition
an abnormally stiffened myocardium (because o fibrosis or an infiltrative process) leading to impaired diastolic relaxation, but systolic contractile function is typically normal or near normal
Typical example of HF with preserved EF
Presentation
signs of heart failure
Dyspnea- exertional Orthopnea Fatigue Pulmonary edema pulmonary rales, Loud S3 Heart size may be normal or enlarged Similar to constrictive pericarditis , jugular venous distention may paradoxically worsen with inspiration (the Kussmaul sign) because the sti ened RV cannot accommodate the increased venous return
(Decreased cardiac output )
Presentation
Features of RV failure
Systemic congestion (o ten more prominent than pulmonary congestion in this syndrome) leads to Raised JVP Hepatomegaly Edema Ascites
Presentation
Other findings
Presentation similar to constrictive pericarditis
Atrial fibrillation in 75% of patients
Other arrhythmias - including AV block + atrial + ventricular origin
ECG
Non specific T wave + ST changes
Pathological Q waves , in the abscence of previous MI
LVH
May have sinus tachycardia,Afib,AV block
In amyloidosis : microvoltage of QRS complex
Xray
Heart size is often normal or even small with signs of pulmonary congestion
May be enlarged in late stage amyloidosis or hemochromatosis
Echo
Normal systolic function
Dilated atria may be present
Myocardial hypertrophy may be present ( increased wall thickness)
Helps to differentiate from restrictive pericarditis
This whould show thickened pericardium
RCM : Big atria , small ventricles
e wave + a wave , the amplitude of e wave compared to amplitude of a wave >2
BULLET POINTS
abnormally rigid (but not necessarily thickened) ventricles with impaired diastolic filling but usually normal, or near normal, systolic unction
Clinical mani estations o cardiac involvement are most common in which type of amyloidosis?
primary (AL) form
of amyloidosis and typically relate to the development of restrictive cardiomyopathy because
of the infiltrating amyloid protein. Diastolic dysfunction is the prominent cardiac abnormality; systolic dysf unction may also develop later in the disease. Orthostatic hypotension is
present in about 10% o patients, likely contributed to by amyloid deposition in the autonomic nervous system and peripheral blood vessels. Infiltration of amyloid into the cardiac conduction system can cause arrhythmias and conduction impairments, which can result in
syncope or sudden death
Pathophysiology
Reduced compliance o the ventricles in restrictive cardiomyopathy, whether due to inf ltration or f brosis, results in an upward shi t o the passive ventricular f lling curve , leading to abnormally high diastolic pressures. This has two major consequences:
(1) elevated systemic and pulmonary venous pressures, with signs o right- and le t-sided
vascular congestion, and
(2) reduced ventricular cavity size with decreased f lling, stroke volume, and cardiac output
The most useful diagnostic tools to differentiate restrictive cardiomyopathy from constrictive pericarditis
transvenous endomyocardial biopsy, computed tomography (CT), and MRI
For example, in restrictive cardiomyopathies, transvenous endomyocardial biopsy
may demonstrate the cause of the condition (e.g., the presence of amyloid fibrils in amyloidosis, or iron deposits in patients with hemochromatosis [a condition of iron overload]).
CT or MRI scans accurately identify the thickened pericardium present in most patients
with constrictive pericarditis, a finding that is not present in states causing restrictive cardiomyopathy.
Treatment of restrictive pericarditis
of underlying cause
For example, phlebotomy and iron chelation therapy may be helpful in the early stages of hemochromatosis. Symptomatic therapy or all etiologies includes :
- salt restriction
- cautious use of diuretics to improve symptoms of systemic and pulmonary congestion.
Unlike the dilated cardiomyopathies, vasodilators are not helpful because systolic function is usually preserved.
Maintenance of sinus rhythm (e.g., converting atrial
fibrillation i it occurs) is important to maximize diastolic
filling and forward cardiac output. Some
restrictive cardiomyopathies are prone to intraventricular thrombus formation, thus warranting chronic oral anticoagulant therapy.
In the case o primary (AL) amyloidosis, chemotherapy followed by autologous bone marrow stem cell transplantation has proved efective in
selected patients with early cardiac involvement
Examples of Restrictive Cardiomyopathy
Noninfiltrative
Idiopathic
Scleroderma
Infiltrative
Amyloidosis
Sarcoidosis
Storage diseases Hemochromatosis Glycogen storage diseases Endomyocardial disease Endomyocardial fibrosis Hypereosinophilic syndrome Metastatic tumors Radiation therapy
Endocrine + Metabolic diseases
Carcinoid
Hypothyroidism
Acromegaly
Cardiotoxicity Rx therapy (breast cancer ,Hodgkin) Antitracyclines HCQ Metisergida Serotoninergic agents
Genetic Sporadic /familial autosomal dominant (Tn,Ttn,actin,lamin,DSP,desmin,BAC cochaperon 3,filamia C) Endomyocardial fibrosis Loffler Endocarditis Idiopathic
Physiopathology from lecture
Restrictive cardiomyopathy is characterised by loss of elasticity of ventricular walls -> alteration of diastolic filling of one or both ventricles
- 🠕 stiffness of the myocardium /endocardium
- rapid 🠕 in ventricular filling pressure
- Specific pattern of diastolic pressure curve :
‘‘dip and plateau’’ - Predominant involvement of RV (+/- VS)
- Marked atrial dilatation with normal ventricular cavities
Predominantly , signs of RVF : 🠕 CVP
Clinical manifestations
They correlate with the severity of atrial pressure 🠕
LV failure
Exercise intolerance :inability to 🠕 CO due to diastolic dysfunction
Dyspnea
Severe asthenia = 🠗 CO
Signs of high CVP ( central venous pressure)
- Jugular vein distention .hepatomegaly , ascites edema,anasarca
- Progressive development , hardly reversible
Atrial fibrilation = frequent ventricular arrhythmias = cause of death
Advanced stages - frequent ventricular arrhythmias = cause of death
1/3 of cases - thromboembolic events
Lab tests and investigations
BNP > 400 pg/ml NT-pro BNP > 2000 pg/ml Changes with specific pathologies - High creatinine,urea,changes with protein electrophoresis in amyloidosis - High sideremia in hemochromatosis
Diagnosis
- Echocardiography
- Cardiac magnetic resonance
- Cardiac catheterization , endomyocardial biopsy
MRI & complementary tests
can the patient underogo MRI with gandolinium enhanchement? If he can then we will preform MRI to evaluate for signs of infiltrative or inflammatory causes of restrictive cardiomyopathy.If they are present on the MRI then we think about sarcoididosis , amyolidosis or any other infiltrative cardiomyopathy. If not we should go forward to genetic test to find a pathogenic gene out of those variants associated with restrictive cardiomyopathy.If we identify it then we know that the restrictive cardiomyopathy has a restrictive cause.If not -> endomyocardial biopsy , if and only if that possible diagnosis change management of the case,bcz endomyocardial biopsy is a dangerous maneuver so we should only do it if the outcome changes the management of the case.
if we cant preform MRI -> 2 options according to the age.
if pt >= 50yo -> obtain bone tracing cardiac schintigraphy to evaluate common cause stress creatinine? amyloidosis
If the test is negative or the pt < 50yo -> genetic test
Cardiac MRI
Shows the normal ventricular volumes , normal EF and severe dilatation of atria
May sustain an etiology of RCM
Exemples :
T2 sequence may apeciate iron deposits and establish Hemochromatosis diagnostic
T1 relaxation time are changed in amyloidosis and Fabry disease
The late gadolinium enhancement (LGE) may show fibrosis , scar tissue, infiltration
Posterobasal – Fabry disease
Endocardial distribution diffuse with LVH – amyloidosis
Management of RCM
Identifying the treatable causes (ex. hemochromatosis, carcinoid)
sYMPTOMATIC TREATMENT OF RHF
Diuretics for lowering the CVP and alleviating the hydro-saline retention
ACE -> hypotension
Digitalis: pathogenically useless, high toxicity
Severe ventricular arrhythmias:
Implantable cardioverter defibrillator,
Beta-blockers or
transplant
Cardiac transplant (not in systemic diseases)
Loffler Endocarditis
in hyperEo situations (primary / secondary / idiopathic >1500/mm3
Marked blood and myocardial eosinophilia
Successive clinical stages :
1. Necrotic (silent)
2.Thrombotic
3. Fibrotic (most significant)
Signs of congestive HF + systemic thromboembolic events
Cardiac MRI for diagnosis
Treatment: Monoclonal antibodies, corticosteroids, hydroxyurea, antiparasitics, cardiac transplant
Extensive myocardial infiltration
with eosinophils
Endomyocardial fibrosis
Encountered in tropical regions Light eosinophilia Apical and subvalvular subendocardial fibrosis Biventricular involvement 50%; LV = 40% 15-25% of cardiac deaths in the are Diagnosed in children and young adults 2 year mortality: 35-50%
Cardiac amyloidosis
most frequent
most frequently encountered RCM in practice Multisystem infiltrative disease with deposition of linear polypeptide fibrils in the myocardial interstitium: Ig light chain (kappa or lambda): AL type = primary form, myeloma variant Familial form (AF): prealbumine (transthyretine) Senile form (SSA): ANP-like or transthyretine Clinical manifestations = severe infiltration of myocardium
Clinical manifestations
Cardiac amyoidosis
Polineuropathy Orthostatic hypotension Big tongue Big liver Digestive disturbances
Cutaneomucous amyloidosis
Amiloid: Virchow’s term
“amidon-like”
neurological manifestations
Kidney deposits
= Nephrotic sdr
we have to assess renal function -> creatinine and urea
Heart transplant is not useful , but you mahe an isolated form just affecting the heart and this is an aspect where heart transplant might be useful
Echocardiography
Amyloidosis
parasternal long axis view
parasternal short axis view
Small LV , with LVH , IVS >15mm
White LV walls “granular sparkling” -> deposits of amyloide in the walls
IAS infiltration , Valves infiltration
Dilated atria
Restrictive diastolic dysfunction
LV small with LVH ( in the short axis view) with IVS > 15mm
Management of amyloidosis
AL Amyloidosis = worst prognosis
Transplant + chimiotherapy
Alkylating agents: melphalan
Immunosupressive drugs: prednisone
Fusion toxic: colchicine
HF treatment:
Avoidance of digitalis (affinity for amyloid fibres = toxicity)
Major sensitivity to CCB
Vasodilator agents and diuretics : risk of hypotension
Systemic ANTICOAGULATION
Heart transplant in forms without extracardiac involvement
Liver transplantation in transthyretin forms
The prognosis of cardiac amyloidosis is uniformly poor but does depend on the type of disease, with AL amyloidosis having the worse prognosis .
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).
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
Afib in emergency room hemodynamically stable
Assess the risk of thromboembolism ->Transesophageal echo to exlude the presence of thrombus in LV appendage
after electrical cardioversion do we give anticoagulation treatment ?
we assess the CHADVASC score if we have CHADVASC = 4 -> this is class I indication for anticoagulation
How long do you anticoagiulate a person with first episode of atrial fibrillation
if chadvasc = 4
if he still develops Afib
in elderly people who are asymptomatic -> Holter ECG to ask ecgs during palpitations
AT LEAST 1 MONTH, some of the them need more
Why at least 1 month?
Bcz the electrical + mechanical events after a conversion are not simultaneous.You will p waves on ecg but doesnt mean that the atria contracts vigorously , efficiently so it takes some time to recover from stem point of efficient atrial contraction.
what can we do when the patient has ventricular rather than atrial arrhythmias?
severe ventricular arrhythmias means sustained ventricular arrhythmias, arrhythmias that encompose the risk of sudden cardiac death:
Beta blockers
Implantable cardioverter defibrillator will treat severe ventricular arrhythmias not atrial since they are not life threatening
transplant
Cardia transplant ( not in systemic diseases)
can we do heart transplant in systemic diseases?
No , bcz in systemic diseases the heart will develop diseases as the old heart so its useless
Cardiac amyloidosis
Cardiac involvement = 1/3 pts with type AL systemic amyloidosis
Anatomopathological changes are present even in the absence of clinical manifestations
it involves V, A myocardium and, eventually, valves
clinical manifestations: RCM, systolic HF, orthostatic hypotension,
Low QRS voltage complexes especially in the limbs
sometimes even smaller than p waves
pathognomonic sign : infiltrative myocardial disease
V1,V2,V3 Q waves
previous MI or due to infiltration of amyloide into the septum + replacement of the normal myocardium with fibrous tissue and with amyloide which will lead to less of electric potential
V4-V6
R waves no more Q waves
no ST changes
This is an aspect -> pathognomonic for amyloidosis since the large p waves make us think about enlarged atrium with the small QRS complexes due to deposis of amyloidosis + restrictive cardiomyopathy
echocardiographic aspect of amyloidosis
LV with very thick walls
small cavity with enlarged of both atrium
Heart transplant
is only adequate without extracardiac involvement so in forms that amyloidosis is just localized at the heart level or in the heart
in pts with RCM with very dilated atria
due to amyloidosis will develop atrial fibrillation this is the way in which we will meet a drug…drop with diminished AV rate,we must avoid digitalis bcz it has affinity for amyloid fibers + will lead to toxicity
so we give β blockers
we will always prefare β blockers instead of digitalis in any pts with HF
we avoid vasodilators + diuretics -> risk of HTN
we will use systemic snticoagulation since it is in a form with increased risk of thrombus formation + thromboembolic events
1/3 of pts with RCM might be asymptomatic due to
thromboembolic events and this subtype in the case of amyloidosis is more frequently associated with thromboembolic events so we need systemic anticoagulation
