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IMHOTEP The African Cardiomyopathy and Myocarditis Registry Programme
Dr. Sarah Kraus University of Cape Town/Groote Schuur Hospital
South Africa PASCAR MauriAus 2015
Cardiomyopathy
The cardiomyopathies pose the greatest challenge of all the cardiovascular
diseases (CVDs) in Africa because of their greater prevalence in socieAes sAll
plagued by diseases of famine and pesAlence; the difficulty in diagnosis,
which oPen requires specialized cardiological inves;ga;ons that are lacking
in resource-poor environments; the lack of access to effec;ve interven;ons;
and the high mortality associated with these oPen irreversible disorders of
heart muscle
Akinkugbe, O.O., G.D. Nicholson, and J.K. Cruickshank, Heart disease in blacks of Africa and the Caribbean. Cardiovasc Clin, 1991. 21(3): p. 377-91
The African Cardiomyopathy and MyocardiAs Registry Programme
Registry Database
Research Clinical PracAce
CollaboraAon
Academic learning
Facilitate change in health policies
Development of key clinical services
Advancement of our understanding of the geneAc basis of cardiovascular disease
EducaAon & training Clinical PracAce
The African Cardiomyopathy and MyocardiAs Registry Programme
Registry Database
Research Clinical PracAce
EducaAon & training
Be`er outcomes for paAents with cardiomyopathy and myocardiAs
Clinical PracAce
Research IMHOTEP Study
Hypertrophic cardiomyopathy
Four fundamental research quesAons
1. What is the aeAology of cardiomyopathy in Africans? 2. What are the geneAc factors that contribute to cardiomyopathy in
Africans?
3. What is the prevalence of myocardiAs in paAents presenAng with cardiomyopathy in Africa?
4. What is the outcome and factors influencing prognosis in Africans with cardiomyopathy?
IMHOTEP Study
Hypotheses
1. Cardiomyopathy is caused by familial (geneAc) and non-familial (secondary) factors
2. There is an overlap in the molecular geneAc causes of different
morpho-funcAonal types of cardiomyopathy 3. MyocardiAs is present in a significant proporAon of cases where it
serves as a triggering factor in familial cases and a causa;ve factor in non-familial cases
4. The outcome of cardiomyopathy is influenced by geneAc and non-
geneAc factors.
IMHOTEP Study
ObjecAves
Pan-African mulA-centre prospecAve cohort study 1. To phenotype and classify adults and children with
cardiomyopathy into familial and non-familial disease according to the ESC criteria
2. To conduct geneAc studies of causal genes in familial disease, and
geneAc associaAon studies for suscepAbility genes in cases of non-familial disease
3. To establish the prevalence of myocardiAs using CMR and histology at two centres in SA
4. Determine the outcome of cardiomyopathy in Africans.
IMHOTEP Study
COHORT
Prevalent cases (exis;ng cases)
Groote Schuur Cardiomyopathy Clinic +
South African ARVC Registry +
Study of Familial Dilated Cardiomyopathy
Incident cases (new cases)
All newly diagnosed cases of
cardiomyopathy or myocardiAs
12 month Pilot Phase at Groote Schuur Hospital
Pilot Phase at Red Cross Childrens
Hospital
MulAple sites throughout Africa
IMHOTEP Study
Progress: Development RaAonale design of the registry and development of the research protocol
Development of: Case report forms Consent and assent forms PaAent InformaAon sheets ARVC, DCM, HCM
UCT Human Ethics Commi`ee approval October 2014 Development of the OpenClinica database
Data Management Plan and Standard OperaAng Procedures Clinical algorithms
IMHOTEP Study
Unique opportuni;es
CompaAble for children and adults Inclusion of all morphofuncAonal types of
cardiomyopathy and myocardiAs Detailed phenotyping for geneAcs studies Physician friendly
Progress: Recruitment
Prevalent cases
GSH Cardiomyopathy Clinic 32 cases
+ South African ARVC Registry 141 cases under review
+ Study of Familial Dilated
Cardiomyopathy 150 cases under review
Incident cases
Pilot phase: 1 February 2015 22 cases
IMHOTEP Study
Prevalent Incident IDCM
SDCM
FDCM
HCM
ARVC
Cardiomyopathy Clinic
Clinical PracAce IMHOTEP Study
Dilated cardiomyopathy with LBBB
3 stage invesAgaAve approach
NON-INVASIVE
INVASIVE
GENETIC
Diagnos;c and/or e;ologic uncertainty Exclusion of coronary artery disease Transplanta;on assessment Arrhythmias
Iden;fy Familial CMO Family screening Gene;c diagnosis
Confirm diagnosis of cardiomyopathy Exclude alterna;ve causes of heart failure Establish a phenotype DCM, HCM, RCM, ARVC, LVNC, Other E;ological diagnosis Risk assessment for SCD
IMHOTEP Study
3 stage invesAgaAve approach
NON-INVASIVE
INVASIVE
GENETIC
CORE INVESTIGATIONS History & ExaminaAon CXR ECG Echocardiogram Blood invesAgaAons
Family history
IMHOTEP Study
3 stage invesAgaAve approach
NON-INVASIVE
INVASIVE
GENETIC
EXTENDED INVESTIGATIONS TOE Angiography EMB EP study
Extend Family Pedigree Gene;c counseling Family screening Genotyping
EXTENDED INVESTIGATIONS SAECG 24 hour Holter EST Imaging: CMR, CT, MIBI
CORE INVESTIGATIONS History & ExaminaAon CXR ECG Echocardiogram Blood invesAgaAons
IMHOTEP Study
CARDIOMYOPATHY DIAGNOSTIC ALGORITHM!
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IMHOTEP
STAGE 1: NON-INVASIVE CORE INVESTIGATIONS!!
History!! Drug and toxin exposure, including alcohol!! Hypertension!! Pregnancy! !! Exercise!! Recent viral illness!! Systemic symptoms!! Co-morbid conditions!
Examination!! Weight & height (BMI, BSA)!! Dysmorphism!! Cardiovascular findings!! Proximal myopathy!! Six-minute walk test!
ECG !CXR!Echocardiogram!
Mandatory to determine phenotype and exclude alternative causes!
Blood investigations (depending on phenotype)!DCM: !
HIV, CK, Ferritin, TSH, blood glucose, cholesterol, *Eosinophil count, *Inflammatory markers!*Autoimmune screen!
RCM:!Eosinophil count, ferritin!
STAGE 1: NON-INVASIVE EXTENDED INVESTIGATIONS!!
DCM: ! 24-hour ambulatory ECG !! Imaging CMR!
HCM:! 24-hour ambulatory ECG!! Exercise stress test!
! Imaging: CMR, CTA, MIBI!ARVC:! SAECG!! 24-hour ambulatory monitoring!! Imaging: CMR!RCM: ! Imaging: CMR!LVNC:! Imaging: CMR!
! !
Suspected cardiomyopathy!! !! !
Three stage investigative approach!
STAGE 1: NON-INVASIVE!!Confirm diagnosis of cardiomyopathy!!Exclude alternative causes!
Systemic arterial hypertension !Coronary artery disease!Pericardial diseases!Congenital heart disease!Pulmonary disease with cor pulmonale!Valvular heart disease, including RHD!!
Establish morphofunctional phenotype!Dilated cardiomyopathy (DCM)!Hypertrophic cardiomyopathy (HCM)!Restrictive cardiomyopathy (RCM)!Arrhythmogenic right ventricular cardiomyopathy (ARVC)!Left ventricular noncompaction (LVNC)!!
Etiological diagnosis!!Risk assessment for SCD!!
CLINICAL SYMPTOMS!!Symptoms of heart failure!! Reduced effort tolerance!
Orthopnoea!Paroxysmal nocturnal dyspnoea!Leg and/or abdominal swelling!
Palpitations!Presyncope!Syncope!Chest pain !Asymptomatic but positive family history of cardiomyopathy
CARDIOMYOPATHY DIAGNOSTIC ALGORITHM!!!!!
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IMHOTEP
STAGE 3: GENETICS!!Detailed family history and construction of a family pedigree!
! POSITIVE family history!
! Clinical screening of first degree relatives
STAGE 2: INVASIVE INVESTIGATIONS!!
Indications for TRANSOESOPHAGEAL ECHOCARDIOGRAM:! Exclusion of left atrial thrombus prior to cardioversion/EPS ! Poor transthoracic views where CMR is not available! Perioperative during septal myectomy in HCM! To detect surgical complications (VSD, AR, residual
LVOTO) in HCM!!Indications for CARDIAC CATHETERIZATION:! Exclusion of coronary artery disease! Haemodynamic assessment and angiography!
- Diagnostic!- Assessment for transplantation!!
Indications for ENDOMYOCARDIAL BIOPSY!CLASS I, LEVEL OF EVIDENCE B! New onset heart failure of < 2 weeks duration, a normal
sized or dilated LV, and haemodynamic compromise ! New onset HF with a dilated ventricle, 2 weeks - 3 months
of symptoms, new ventricular arrhythmias or Mobitz type 2 second-degree HB or third-degree HB, or who fail to respond to usual care within 1-2 weeks !
ADDITIONAL INDICATIONS:! Diagnostic purposes that will alter management!
- E.g. RCM: giant cell myocarditis, amyloidosis!- E.g. Cardiac sarcoidosis!- E.g. ARVC !
Post-transplantation!- organ rejection!!
Indications for ELECTROPHYSIOLOGICAL STUDY:! Assessment for ventricular arrhythmias - VT stimulation
test! Atrial or ventricular arrhythmias - for possible ablation
procedure!
STAGE 2: INVASIVE !!This stage should be undertaken at institutions that have the facilities and expertise!!Patients should be considered for extended invasive testing !! Diagnostic and/or etiologic uncertainty ! Exclusion of coronary artery disease ! Transplantation assessment ! SCD risk assessment! Arrhythmias!!