Etiology and Phenotypes of Cardiomyopathy in Southern Africa: The IMHOTEP Multicenter Pilot Study

Sarah M Kraus^{1

2

3

4}, Jacqui Cirota^{1

3}, Shahiemah Pandie^{1

3}, Kandathil Thomas⁵, Mookenthottathil Thomas⁵, Makoali Makotoko⁶, Albertino Damasceno⁷, Sarah Yiga⁶, Louwra Greyling⁶, Hermanus A Hanekom⁷, Angela Mateus⁸, Celia Novela⁸, Nakita Laing⁹, Unita September^{1

3}, Zita Kerbelker¹, Tessa Suttle¹, Emily Chetwin¹, Francis E Smit⁷, Gasnat Shaboodien^{2

3}, Ashley Chin¹, Karen Sliwa^{1

2}, Freedom Gumedze¹⁰, Stefan Neubauer¹¹, Leslie Cooper¹², Hugh Watkins^{4

11}, Ntobeko A B Ntusi^{1

2

3}; IMHOTEP Investigators

Affiliations

¹ Department of Medicine, The Cardiac Clinic, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
² The Cardiovascular Genetics Laboratory, Department of Medicine, Cape Heart Institute, University of Cape Town (UCT), Cape Town, South Africa.
³ South African Medical Research Council Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, University of Cape Town, Cape Town, South Africa.
⁴ Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
⁵ Division of Cardiology, Nelson Mandela Academic Hospital and Walter Sisulu University, Mthatha, South Africa.
⁶ Division of Cardiology, Universitas Hospital and University of the Free State, Bloemfontein, South Africa.
⁷ Department of Cardiothoracic Surgery, Robert W.M. Frater Cardiovascular Research Centre, University of the Free State, Bloemfontein, South Africa.
⁸ Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique.
⁹ Division of Human Genetics, Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Statistics, University of Cape Town, Cape Town, South Africa.
¹¹ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹² Mayo Clinic, Jacksonville, Florida, USA.

PMID: 39817068
PMCID: PMC11733814
DOI: 10.1016/j.jacadv.2024.100952

Etiology and Phenotypes of Cardiomyopathy in Southern Africa: The IMHOTEP Multicenter Pilot Study

Sarah M Kraus et al. JACC Adv. 2024.

. 2024 May 8;3(12):100952.

doi: 10.1016/j.jacadv.2024.100952. eCollection 2024 Dec.

Authors

Affiliations

¹ Department of Medicine, The Cardiac Clinic, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
² The Cardiovascular Genetics Laboratory, Department of Medicine, Cape Heart Institute, University of Cape Town (UCT), Cape Town, South Africa.
³ South African Medical Research Council Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, University of Cape Town, Cape Town, South Africa.
⁴ Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
⁵ Division of Cardiology, Nelson Mandela Academic Hospital and Walter Sisulu University, Mthatha, South Africa.
⁶ Division of Cardiology, Universitas Hospital and University of the Free State, Bloemfontein, South Africa.
⁷ Department of Cardiothoracic Surgery, Robert W.M. Frater Cardiovascular Research Centre, University of the Free State, Bloemfontein, South Africa.
⁸ Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique.
⁹ Division of Human Genetics, Department of Medicine, University of Cape Town, Cape Town, South Africa.
¹⁰ Department of Statistics, University of Cape Town, Cape Town, South Africa.
¹¹ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
¹² Mayo Clinic, Jacksonville, Florida, USA.

PMID: 39817068
PMCID: PMC11733814
DOI: 10.1016/j.jacadv.2024.100952

Abstract

Background: Cardiomyopathies are an important cause of heart failure in Africa yet there are limited data on etiology and clinical phenotypes.

Objectives: The IMHOTEP (African Cardiomyopathy and Myocarditis Registry Program) was designed to systematically collect data on individuals diagnosed with cardiomyopathy living in Africa.

Methods: In this multicenter pilot study, patients (age ≥13 years) were eligible for inclusion if they had a diagnosis of cardiomyopathy or myocarditis. Cases were grouped and analyzed according to phenotype; dilated cardiomyopathy (DCM) including myocarditis and peripartum cardiomyopathy, hypertrophic cardiomyopathy (HCM), arrhythmogenic cardiomyopathy (ACM), and restrictive cardiomyopathy (RCM).

Results: A total of 665 unrelated index cases (median age 35 [27-44] years; 51.1% female) were recruited at 3 centers in South Africa and 1 center in Mozambique. DCM (n = 478) was the most common type of cardiomyopathy, accounting for 72% of the cohort; ACM (n = 78), HCM (n = 70), and RCM (n = 39) were less frequent. While the age of onset and sex distribution of HCM and ACM were similar to European and North American populations, DCM and RCM had a younger age of onset and occurred more frequently in women and those with African ancestry. Causes of cardiomyopathy were diverse; familial (27%), nonfamilial/idiopathic (36%), and secondary (37%) etiologies were observed.

Conclusions: In the largest study of cardiomyopathy to-date on the African continent, we observe that DCM is the dominant form of cardiomyopathy in Southern Africa. The age of onset was significantly younger in African patients with notable sex and ethnic disparities in DCM.

Keywords: Africa; South Africa; cardiomyopathy; dilated cardiomyopathy; heart failure; myocarditis.

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Conflict of interest statement

The study was jointly funded by the 10.13039/501100001322South African Medical Research Council, the Medical Research Council United Kingdom (via the Newton Fund), and GSK Africa Non-Communicable Disease Open Lab. Dr Ntusi was supported by funding from the 10.13039/501100001322South African Medical Research Council, 10.13039/501100001321National Research Foundation, and the Lily and Ernst Hausmann Trust. Dr Kraus was supported by research fellowship funding from the Mauerberger Foundation Fund. Drs Watkins and Neubauer were supported by the Oxford 10.13039/501100013373NIHR Biomedical Research Centre and by the British Heart Foundation Centre of Research Excellence. Dr Shaboodien was supported by funding from the 10.13039/501100001321National Research Foundation and the Medical Research Council of South Africa. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

**Figure 1**
IMHOTEP Pilot Study Recruitment Recruitment according to (A) site, (B) study arm, and (C) diagnostic classification. ACM = arrhythmogenic cardiomyopathy; DCM = dilated cardiomyopathy; HCM = hypertrophic cardiomyopathy; RCM = restrictive cardiomyopathy.

**Figure 2**
Age at First Presentation and Sex According to Phenotype Age and sex in (A) IMHOTEP and (B) EORP (adapted from *Charron et al, Eur Heart J 2018;39(20):1784-1793*). ACM = arrhythmogenic cardiomyopathy; DCM = dilated cardiomyopathy; EORP = EURObservational Research Programme; HCM = hypertrophic cardiomyopathy; IMHOTEP = African Cardiomyopathy and Myocarditis Registry Program; RCM = restrictive cardiomyopathy.

**Figure 3**
Ethnic Variation in DCM Ethnic variation in DCM for (A) age, (B) sex, and (C) etiology. DCM = dilated cardiomyopathy.

**Figure 4**
**Phenotypes and Etiology** ABVC = arrhythmogenic biventricular cardiomyopathy; ACM = arrhythmogenic cardiomyopathy; ARVC = arrhythmogenic right ventricular cardiomyopathy; DCM = dilated cardiomyopathy; FH+ = positive family history; HCM = hypertrophic cardiomyopathy; HIVAC = human immunodeficiency virus-associated cardiomyopathy; LVNC = left ventricular noncompaction; PPCM = peripartum cardiomyopathy; RCM = restrictive cardiomyopathy.

**Central Illustration**
**The IMHOTEP Multicenter Pilot Study on Cardiomyopathies in Southern Africa** ABVC = arrhythmogenic biventricular cardiomyopathy; ACM = arrhythmogenic cardiomyopathy; ARVC = arrhythmogenic right ventricular cardiomyopathy; DCM = dilated cardiomyopathy; EMF = endomyocardial fibrosis; HCM = hypertrophic cardiomyopathy; HIVAN = human immunodeficiency virus-associated cardiomyopathy; LVNC = left ventricular noncompaction/left ventricular hypertrabeculation; RCM = restrictive cardiomyopathy.

See this image and copyright information in PMC

References

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Etiology and Phenotypes of Cardiomyopathy in Southern Africa: The IMHOTEP Multicenter Pilot Study

Affiliations

Etiology and Phenotypes of Cardiomyopathy in Southern Africa: The IMHOTEP Multicenter Pilot Study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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