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CLZ - induced
CLZ - induced
cardiotoxiciy
cardiotoxiciy
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Part (1)
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Dr.Mohamed Saeed
Consultant Physician
Treatment-resistant schizophrenia (TRS) :
is defined as failure to respond to 2 or more antipsychotic
medications given in full therapeutic doses for 6 wks or more
Prevalence :
about 30% of schizo. patients respond poorly to antipsychotic
medication and those who show ‘total non-response’ is ~ 7%.
CLZ - advantages : ( CLZ is such Great Medicine )
- Among people with TRS , Clz is the gold-standard medicine and
The most effective one
- low risk of EPS - Doesn't induce hyperprolactinemia
- significantly reduce suicidal behavior in pts with schizophrenia
However, CLZ have a wide spectrum of S/E :
- some are common and fortunately benign
- while others are rare but serious and threatening pt’s life as :
CLZ-induced Cardiotoxicity,which is our topic today
Introduction:
CLZ + TRS
CLZ + TRS
§
Myocarditis :
Myocarditis :
- is the most common and serious cardiac disorders
seen early after initiating CLZ R/ .
§
Definition
Definition :
- It is defined as inflammation of the myocardium
causing myocyte injury and can result in H.F
S/E OF CLZ ON CVS
-Tachycardia - QT-prolongation - orthostatic hypotension
- Myocarditis - - Reduced H.R variability - pulmonary embolism
- cardiomyopathy - sudden cardiac death
- Metabolic syndrome
Incidence:
- Until recently the incidence was <_ 1.0 %
- Nowadays it is estimated to be about 3% of those initiated on CLZ therapy.
Onset :
- According to reports, more than 85% of the cases occur in the first 2 months
- up to 75% of cases within the 1st 3 weeks
- OF note, there is a peak between days 14 -22
(Published online:;CNS drugs-14 August 2017)
CLZ –
CLZ –
Induced
Induced
Myocarditis
Myocarditis
- 2
- 2
Number of Days Receiving CLZ before Onset of Suspected CLZ – Induced Myocarditis
among 106 Pts in Australia from 1993 : 2003
H&E-stained sections of the L.V from CLZ-
treated for 21 days and control rats.
(A) There is no myocardial inflammation in control
rats (score 0).
(B) There are inflammatory lesions in the myocardium
after 10 mg/ kg/d CLZ (score 2).
(C) There are larger inflammatory lesions in the myocardium
after administration of 15 mg/kg/d (score 3).
(D) There are extensive inflammatory lesions in
the myocardium after administration of
25mg/kg/d (score 4).
Egyptian Journal
Sciences Forensic of
822014) 4, 75
of rats treated with CK-MB Serum levels of
clozapine in doses of 10, 15 and 25
mg/kg/d, for 21 days
of rats treated with LDH Serum levels of lactate
clozapine in doses of 10, 15 and 25 mg/kg/d
for 21 days
Histological Evidences of CIM
Histological Evidences of CIM
q symptoms and Signs of :
- R.T Infection or - U.T infection or - GIT Infection
- Develop before cardiac manifestations
- It is a part of the syndrome of hypersensitivity myocarditis
q Fever :
- Present in about 75%. - it is one of the earliest symptoms
q Tachycardia :
- occurs benignly in 90% with clz R/ ; but if it is :
- At rest and persistent - HR 120 min or - increase by > 30
min may indicate the presence of myocarditis
q Hypotension :
- Present in about 30%
- A sudden drop in systolic B.P ,Usually around day 5 and the pt. may
report chest pain
q Chest pain :
- Present in about 50%, often described as "stabbing" in character
- May accompanied by SOB and dyspnea
q Symptoms and signs and of H.F or myocardial infarction :
- Basal crepitations 3
rd
-heart sounds - peripheral edema -raised
J.V.P
C-P of Myocarditis
1) Eosinophilia :
1) Eosinophilia :
-
-
Present in 62% of cases
Present in 62% of cases
- in some cases onset delayed
- in some cases onset delayed
several days after troponin raise
several days after troponin raise
2) CRP :
2) CRP :
> 100 mg- L : in 72 %
> 100 mg- L : in 72 %
3) Troponin I or T :
3) Troponin I or T :
-Raised to > 2 ULN in 90%
-
Troponin( I/T) > 2 ULN or CRP > 100
mg/ L : Present in almost 100% of
cases with signs or
symptoms of
infectious illness
4)
C.K myocardial band (CK-MB) :
C.K myocardial band (CK-MB) :
- Raised in 4–58% of cases
5) Creatine kinase (CK) :
5) Creatine kinase (CK) :
-
-
Raised
Raised 15% of cases .
Investigations -1
Investigations -1
7) Echocardiography
7) Echocardiography
-
It is one of the most helpful tools for diagnosing myocarditis
It is one of the most helpful tools for diagnosing myocarditis
-
-
L.V dysfunction
L.V dysfunction
is Present in 62% ; of cases ,
is Present in 62% ; of cases ,
including
including
a reduction of the
a reduction of the
LV ejection fraction (LVEF) :
LV ejection fraction (LVEF) :
-
-
Normal range : 52% to 72%
Normal range : 52% to 72%
-
-
Mildly abnormal : 41% to 51 %
Mildly abnormal : 41% to 51 %
-
-
Moderately abnormal : 30% to 40%
Moderately abnormal : 30% to 40%
-
-
Less than 30% Severely abnormal
Less than 30% Severely abnormal
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Investigations - 8/9
Investigations - 8/9
-Sensitivity 81%;
- specificity 71%
T2-weighted images :
demonstrate the presence
of patchy focal edema in
the sub epicardium of the
infero-lateral wall
8) Cardiac magnetic resonance
- Considered the gold standard
for diagnosis of myocarditis
- It will shows infiltration of
Myocytes with inflammatory
eosinophilic cells
- My show associated myocyte
necrosis
9) Endomyocardial biopsy
CLZ-induced of Evolution Typical
myocarditis
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