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Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy
Thesis (PhD)--Stellenbosch University, 2022.
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Stellenbosch : Stellenbosch University
2022
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| _version_ | 1867614105183977472 |
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| access_status_str | Open Access |
| author | Robbertse, Pieter-Paul Strauss |
| author2 | Herbst, Philip G |
| author_browse | Herbst, Philip G Robbertse, Pieter-Paul Strauss |
| author_facet | Herbst, Philip G Robbertse, Pieter-Paul Strauss |
| author_sort | Robbertse, Pieter-Paul Strauss |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2022. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/126333 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:46:44.579Z |
| 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:10019.1/126333 Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy Robbertse, Pieter-Paul Strauss Herbst, Philip G Doubell, Anton F. Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine: Cardiology. Cardiovascular system -- Diseases Antiretrovirals HIV-positive persons UCTD Thesis (PhD)--Stellenbosch University, 2022. ENGLISH ABSTRACT: HIV-associated cardiovascular disease (CVD) exists on a spectrum, is poorly understood, and may be highly heterogenous. In low- and middle income countries, HIV-associated cardiomyopathy (HIVAC) remains prevalent; yet, little research is available on antiretroviral treatment (ART) naïve persons from these regions. The study of subclinical CVD may increase our appreciation of HIV-related pathology. Purpose and methods The dissertation’s purpose was to explore subclinical HIV-associated CVD. Our experience with the diagnosis and management of symptomatic HIVAC, and the questions that arose from this, served as motivation for the development of this prospective research project assessing for subclinical HIVAC in people living with HIV (PLWH). Cardiovascular magnetic resonance imaging (CMR), supplemented by additional modalities, was employed in a cohort study of newly diagnosed, ART naïve PLWH in South Africa. Contemporary, HIV uninfected persons were recruited as a control group. Cardiovascular findings were compared between the research groups at enrolment and at 9 months after the initiation of ART. Key findings Distinct similarities exist between symptomatic and subclinical HIVAC, characterised by dilated and thickened left ventricles (LV), decreased systolic function, and tissue characterisation suggesting myocardial oedema. ART improved but did not normalise these abnormalities. The finding of inflammation in our asymptomatic cohort suggests that HIVAC exists along a spectrum, ranging from asymptomatic cardiac inflammation to end stage dilated cardiomyopathy. Inflammation is therefore likely to be the central pathology as supported by CMR imaging biomarkers, biochemical markers of inflammation, and highly prevalent pericardial effusions in our HIV cohort. The cross-sectional analysis of the cohort study revealed altered structure, function, tissue characteristics, biochemical signatures, and aortic stiffness in PLWH compared with controls. The features of dilated ventricles in PLWH with increased LV mass and deceased biventricular systolic function were associated with myocardial tissue abnormalities. These included elevated native T1, T2, and extracellular volume mapping (ECV). Furthermore, PLWH had a high prevalence of cardiac fibrosis and aortic stiffness, already present at the time of HIV diagnosis. Significant associations with the HIV viral load were demonstrable between the LV and right ventricular (RV) ejection fractions and markers of myocardial oedema. Cardiac biochemical biomarkers of myocardial stretch, remodelling, and fibrosis showed promise as surrogates for CMR imaging biomarkers. The prospective data of PLWH showed that, despite the decrease in systemic inflammation and myocardial oedema, the LV size and systolic function did not improve. Coupled with tissue characterisation evidence of persistent myocardial fibrosis, this suggests irreversible cardiac injury, partially to ART. Conclusion At the time of HIV diagnosis, the hearts of PLWH demonstrated subclinical abnormalities. ART improved, but did not completely normalise these abnormalities. Myocardial oedema and fibrosis were present, supporting the current inflammatory hypothesis of HIV. The subclinical myocardial abnormalities resemble cases of symptomatic HIVAC, and may represent a stage in the evolution towards more advanced CVD. In the absence of long-term clinical outcomes, the aortic stiffness and cardiac biomarker findings suggest increased cardiovascular risk in our cohort. This body of work provides robust data that lays the foundation for further research on the cardiovascular risk and clinical outcomes of subclinical CVD in PLWH. AFRIKAANSE OPSOMMING: Agtergrond MIV-geassosieerde kardiovaskulêre siekte (“CVD”)* bestaan op ‘n spektrum, word nie volledig verstaan nie, en kan hoogs heterogeen wees. Ten spyte daarvan dat MIV-geassosieerde kardiomiopatie (“HIVAC”) steeds algemeen voorkom in ontwikkelende lande, is beperkte navorsing rakende antiretrovirale behandelings(“ART”)-naïewe persone uit hierdie streke beskikbaar. ‘n Ondersoek na subkliniese CVD kan ons begrip van MIV-geassosieerde patologie verbeter. Doelwitte en Metodes Die doelwit van die dissertasie was om subkliniese MIV-geassosieerde CVD te ondersoek. Ons ervaring met die diagnose en behandeling van pasiënte met simptomatiese HIVAC, asook gepaardgaande onsekerhede deur ons geïdentifiseer, het gelei tot die ontwikkeling van hierdie prospektiewe navorsingsprojek wat mense met MIV (“PLWH”) assesseer vir subkliniese HIVAC. Tydens ‘n kohortstudie van nuut-gediagnoseerde, ART-naïewe PLWH in Suid-Afrika is daar gebruik gemaak van kardiale magnetiese resonansie-beelding (“CMR”), ondersteun deur addisionele modaliteite. ‘n Kontrolegroep is saamgestel uit tydgenote sonder MIV. Kardiovaskulêre bevindinge van die navorsingsgroepe is met mekaar vergelyk met die aanvang van die studie, sowel as 9 maande na die inisiëring van ART. Kernbevindinge Die studie het sekere ooreenkomste tussen simptomatiese en subkliniese HIVAC aangedui, naamlik gedilateerde en verdikte linkerventrikels (LV), verminderde sistoliese funksie, en weefselkarakteristiek wat miokardiale edeem suggereer. ART het die abnormaliteite verbeter, maar nie laat normaliseer nie. Die bevinding van inflammasie in ons asimptomatiese kohort suggereer dat HIVAC op ‘n spektrum bestaan wat wissel van asimptomatiese hartinflammasie tot eindstadium gedilateerde kardiomiopatie. Inflammasie is dus waarskynlik die sentrale patologie. Hierdie bevinding word ondersteun deur CMR beelding-biomerkers, biochemiese merkers van inflammasie, en die hoë prevalensie van perikardiale effusies in ons MIV-kohort. In vergelyking met die kontrolegroep, dui die deursnee-analise van die kohortstudie op veranderde struktuur, funksie, weefselkarakteristiek, biochemiese kenmerke, en aortastyfheid in PLWH. Die verskynsel van gedilateerde ventrikels in PLWH met verhoogde LV massa en verminderde biventrikulêre sistoliese funksie was geassosieer met miokardiale weefselabnormaliteite. Hierdie sluit verhoogde prekontras T1, T2, en ekstrasellulêre volume kartering (“ECV”) in. Daarbenewens is ‘n hoë prevalensie van hartfibrose en verhoogde aortastyfheid waargeneem ten tye van die MIV-diagnose. Betekenisvolle assosiasies met die MIV-virale telling is aangetoon tussen die uitwerpfraksies van die LV en regterventrikel (RV) en merkers van miokardiale edeem. Die gebruik van kardiale biochemiese biomerkers van strek, hermodellering, en fibrose as surrogaat-merkers vir CMR beelding-biomerkers blyk belowend te wees. Die prospektiewe data van PLWH het getoon dat, ten spyte van die afname in sistemiese inflammasie en miokardiale edeem, die LV grootte en sistoliese funksie nie verbeter het nie. Tesame met die weefselkarakteristiek-bewyse van volgehoue miokardiale fibrose, suggereer hierdie onomkeerbare hartbesering wat slegs gedeeltelik op ART reageer. Gevolgtrekking Ten tye van die MIV-diagnose het die harte van PLWH subkliniese abnormaliteite gewys. ART het die abnormaliteite laat verbeter, maar volledige normalisering is nie waargeneem nie. Miokardiale edeem en fibrose was teenwoordig, en ondersteun die huidige inflammatoriese hipotese van MIV. Die subkliniese miokardiale abnormaliteite toon ooreenkomste met simptomatiese HIVAC en mag a fase in die evolusie na meer gevorderde CVD verteenwoordig. In die afwesigheid van langtermyn kliniese uitkomste, suggereer beide die aortastyfheid en kardiale biomerker data die verhoogde kardiale risiko van die kohort. Hierdie studie verskaf sterk data wat die grondslag lê vir toekomstige navorsing in die vakgebied. *Afkortings word gebruik soos dit in die Engelse weergawe van die manuskrip verskyn. Doctoral 2022-11-19T17:10:43Z 2023-01-23T06:52:42Z 2022-11-19T17:10:43Z 2022-12 Thesis http://hdl.handle.net/10019.1/126333 en_ZA Stellenbosch University application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Cardiovascular system -- Diseases Antiretrovirals HIV-positive persons UCTD Robbertse, Pieter-Paul Strauss Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| title | Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| title_full | Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| title_fullStr | Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| title_full_unstemmed | Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| title_short | Prospective evaluation of the presence, profile and evolution of asymptomatic cardiovascular disease in treatment naïve, HIV infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| title_sort | prospective evaluation of the presence profile and evolution of asymptomatic cardiovascular disease in treatment naive hiv infected patients using cardiac magnetic resonance imaging after initiation on antiretroviral therapy |
| topic | Cardiovascular system -- Diseases Antiretrovirals HIV-positive persons UCTD |
| url | http://hdl.handle.net/10019.1/126333 |
| work_keys_str_mv | AT robbertsepieterpaulstrauss prospectiveevaluationofthepresenceprofileandevolutionofasymptomaticcardiovasculardiseaseintreatmentnaivehivinfectedpatientsusingcardiacmagneticresonanceimagingafterinitiationonantiretroviraltherapy |