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The contemporary study of acute myocarditis in South Africa - CAMISA
Thesis (PhD)--Stellenbosch University, 2022.
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| Format: | Thesis |
| Language: | English |
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867614134708731904 |
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| access_status_str | Open Access |
| author | Hassan, Karim Mohammed |
| author2 | Doubell, Anton Frans |
| author_browse | Doubell, Anton Frans Hassan, Karim Mohammed |
| author_facet | Doubell, Anton Frans Hassan, Karim Mohammed |
| author_sort | Hassan, Karim Mohammed |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/126319 |
| institution | Stellenbosch University (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:47:13.037Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2022 |
| publishDateRange | 2022 |
| publishDateSort | 2022 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/126319 The contemporary study of acute myocarditis in South Africa - CAMISA Hassan, Karim Mohammed Doubell, Anton Frans Herbst, Philippus George Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Cardiology. Myocarditis -- South Africa Cardiovascular system -- Magnetic resonance imaging Acute diseases -- South Africa UCTD Thesis (PhD)--Stellenbosch University, 2022. ENGLISH ABSTRACT: Despite the use of established criteria, the diagnosis of acute myocarditis (AM) can be difficult due to the heterogeneity of presentations, requiring specialised investigations including cardiovascular magnetic resonance imaging (CMR) and endomyocardial biopsy (EMB) for a definitive diagnosis. Viral infections are the commonest cause of AM in the developed world with parvovirus B19 (PVB19) the most frequently detected, although its clinical relevance and pathogenic role remains debated. In view of limited data on AM in both South Africa and Africa, we sought to determine the clinical presentations, aetiologies, causative viral pathogens and outcomes of patients with AM in South Africa. A case based, narrative review was used to highlight the contrasting clinical presentations, difficulties in diagnosis and possible varying patterns of AM on CMR and explore the knowledge gaps around the clinical relevance of PVB19. We prospectively recruited the largest cohort of AM patients outside of the developed world and found the mode of presentation locally to be similar to that seen in developed world, dominated by an infarct-like (IL) presentation (51.7%), followed by a heart failure (HF) presentation (34.8%), ventricular tachycardia (VT) (9%) and complete heart block (CHB) (4.5%). We compared the CMR findings of patients presenting with IL and HF symptoms and biopsy confirmed AM. The diagnostic sensitivity of CMR for identifying oedema on short-tau inversion recovery (STIR) imaging (91.3% vs 61.1%, p = 0.03) and making a definitive diagnosis of AM using the original Lake Louise criteria (LLC) (91.3% vs 55.6%, p = 0.01) were significantly higher in the IL than HF group. There was also a notable difference in the distribution pattern of late gadolinium enhancement (LGE). Despite an improved sensitivity for diagnosing AM in the HF group by using the updated LLC (up to 72.2%), we argued that this cohort would benefit most from access to early EMB to improve diagnostic yield. We developed a dynamic transthoracic echocardiography (TTE) protocol to aid the real-time guidance of EMB. Utilising this, with fluoroscopic guidance, there were no major complications reported in our 85 EMB procedures, mirroring complication rates found in high volume centres. We have demonstrated that the safety of EMB in low volume centres can be improved by the routine use of TTE guidance in addition to fluoroscopy. Viral myocarditis was also the most common form of AM locally, with 58.4% of AM patients having viral genomes detected on EMB. PVB19 was the most common virus locally (82.7% of patients with confirmed myocarditis), similar to developed world cohorts. However, PVB19 was also detected on EMB in 11 patients with no evidence of AM. This again questioned the pathogenic role of PVB19 in myocarditis, leading us to explore the use of high viral copy numbers as a predictor of clinical relevance. We found significantly higher PVB19 viral loads (VL) in patients with confirmed AM compared to those without (483 vs 226 copies/ml, p = 0.02) and determined the optimal cut off for clinical significance to be 316 copies/ml. The outcomes of local patients with AM was not benign with 30.3% developing the prespecified adverse outcome after an average follow up period of 24.1 months. Presentation with VT and CHB were predictors of adverse outcome with hazard ratios of 5.36 and 5.67 respectively. The detection of sustained VT at follow up in 62.5% of patients initially presenting with VT supported our practice of routine implantation of implantable cardioverter defibrillators (ICD) for secondary prevention in AM patients. AFRIKAANSE OPSOMMING: Die diagnose van akute miokarditis (AM) bly uitdagend ten spyte van die gebruik van gevestige kriteria om so ‘n diagnose te maak. Pasient presentering is dikwels hoogs heterogeen en die maak van ‘n definitiewe diagnose noop die gebruik van gespesialiseerde beeldingsmodaliteite, insluitend kardiale magnetiese resonansie (“CMR”) beelding en inwasiewe endomiokardiale biopsie (EMB). Virale infeksie is die mees algemene etiologie van miokarditis in die ontwikkelde wêreld met parvovirus B19 (PVB19) die enkel mees algemene virus wat tydens EMB geidentifiseer word. Die kliniese relevansie en patologiese rol van hierdie virus word steeds gedebateer. Die beperkte beskikbaarheid van data rakende AM in Afrika en Suid-Afrika het gedien as motivering om verdere navorsing te onderneem in die veld en om spesifiek die kliniese voordoening, etiologie, virale patogene en uitkomste van pasiente met AM in Suid-Afrika te bestudeer en beskryf. ‘n Gevalsgebaseerde, naratiewe oorsigsartikel is gebruik om die kontrasterende kliniese voordoening, problematiek rondom diagnose en moontlike varierende patrone van aantasting in AM met die gebruik van CMR toe te lig en gapings in ons kennis oor veral PVB19 te bespreek. Ons het daarvolgens die grootste prospektiewe kohort van AM pasiente buite die ontwikkelde wêreld gewerf en kon demonstreer dat die voordoeningspatrone van AM pasiente soorgelyk is as wat in die ontwikkelde wêreld gesien word. Akute koronêre sindroom - soortige (“IL”) presentering het gedomineer (51,7%), gevolg deur hartversaking (“HF”) presentering (34.8%), ventrikulêre tagikardie (VT) (9%) en derde graadse hartblok (“CHB”) (4.5%). Ons het die CMR bevindinge van pasiente met EMB bewysde AM en onderskeidelik IL en HF voordoenings vergelyk. Beide die diagnostiese sensitiwiteit van MRI om miokardiale edeem te identifiseer d.m.v. sogenaamde STIR (“Short Tau Inversion Revovery”) beelding (91.3% vs 61,1%, p = 0.01) en die vermoeë van CMR om ‘n definitiewe diagnose van AM te maak, deur die oorspronklike Lake Louise kriteria (“LCC”) te gebruik, was betekenisvol hoër in die IL vergeleke met die HF groep. Daar was ook ‘n opvallende verskil in die distribusie patroon van gadolinium kontras versterking laat na kontras administrering (“LGE”) gevind. Ten spyte van ‘n beter sensitiwiteit vir die diagnose van AM in die HF groep deur die gebruik van die opgedateerde LCC (tot en met 72.2%), is dit ons mening dat hierdie kohort sal baat by vroeë EMB om diagnostiese sekerheid te verhoog. Ons het ‘n dinamiese transtorakale eggokardiografie (“TTE”) protokol ontwikkel om deurgaanse EMB prosedurale monitering te verskerp ten einde die veiligheid van die prosedure te verbeter. Deur hierdie nuwe TTE moniteringstegniek te gebruik saam met fluoroskopie, het ons geen major komplikasies in ons kohort van 85 pasiente ondervind nie. Ons het dus gedemonstreer dat lae volume sentra wel die veiligheid van EMB kan verseker deur ‘n kombinasie van fluoroskopiese deurligting en deurgaanse TTE monitering te gebruik. Virale miokarditis was ook die algemeenste vorm van AM in ons studie en daar word geslaag om in 58.4% van pasiente wat EMB ondergaan, virale genomiese materiaal in hartspierweefsel te identifiseer. PVB19 was die algemeenste virale patogeen (82.7% van alle pasiente met bevestigde AM) wat soortgelyk is as wat in die ontwikkelde wêreld gesien word. PVB19 word egter ook in 11 pasiente sonder bewys van miokarditis bespeur wat weereens ‘n vraagteken plaas oor sy patologiese rol as direkte oorsaak van miokarditis. Ons ondersoek daarom die gebruik van virale kopie titers as moontlike voorspeller van die kliniese relevansie van ‘n PVB19 positiewe biopsie. Ons bevindinge demonstreer dat ‘n betekenisvolle hoër PVB19 virale lading teenwoordig is in pasiente met bevestigde AM as daarsonder (483 vs 226 kopië/ml, p = 0.02) en bepaal die optimale afsnypunt om relevansie teen te meet as 316 kopië/ml. Die uitkoms van ons pasiente met AM in ons kohort blyk nie benigne te wees nie, met 30.3% van pasiente wat voorafgespesifiseerde major komplikasies ondervind oor die opvolgperiode van 24.1 maande. ‘n Voordoening met VT en CHB voorspel ‘n swak uitkoms met risiko verhouding (“hazard ratio”) van 5.36 en 5.67 onderskeidelik. Die identifisering van volgehoue VT in 62.5% van pasiente wat met VT presenteer, valideer dan ook ons besluit om roetineweg implanteerbare kardioverter defibrillators (“ICD”) te implanteer in alle pasiente met AM wat met VT voordoen ten einde sekondêre voorkoming te bewerkstellig. Ons rapporteer data ingewin aan die hand van die grootste kohort van pasiente met klinies verdagte AM buite die ontwikkelde wêreld. Die studie verbeter ons insig oor die kliniese voordoening, aetiologie en virale patogene in ‘n lokale, Suid-Afrikaanse kohort en demonstreer dat lokale modes van presentering soortgelyk is as wat in ontwikkelde lande gesien word. Die patogeniese rol van PVB19 bly onseker, maar ons data ondersteun die gebruik van virale kopie titers om kliniese besluitneming toe te lig. Die uitkoms van locale pasiente met AM is nie benigne nie en dit onderskraag die noodsaaklikheid van voortgesette navorsing in hierdie veld. Doctoral 2022-11-21T10:28:48Z 2023-01-23T06:52:01Z 2022-11-21T10:28:48Z 2022-12 Thesis http://hdl.handle.net/10019.1/126319 en Stellenbosch University 145 pages : illustrations application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Myocarditis -- South Africa Cardiovascular system -- Magnetic resonance imaging Acute diseases -- South Africa UCTD Hassan, Karim Mohammed The contemporary study of acute myocarditis in South Africa - CAMISA |
| title | The contemporary study of acute myocarditis in South Africa - CAMISA |
| title_full | The contemporary study of acute myocarditis in South Africa - CAMISA |
| title_fullStr | The contemporary study of acute myocarditis in South Africa - CAMISA |
| title_full_unstemmed | The contemporary study of acute myocarditis in South Africa - CAMISA |
| title_short | The contemporary study of acute myocarditis in South Africa - CAMISA |
| title_sort | contemporary study of acute myocarditis in south africa camisa |
| topic | Myocarditis -- South Africa Cardiovascular system -- Magnetic resonance imaging Acute diseases -- South Africa UCTD |
| url | http://hdl.handle.net/10019.1/126319 |
| work_keys_str_mv | AT hassankarimmohammed thecontemporarystudyofacutemyocarditisinsouthafricacamisa AT hassankarimmohammed contemporarystudyofacutemyocarditisinsouthafricacamisa |