Myocardial Fibrosis in ART-Treated Women with HIV in South Africa: Preliminary Insights From the MUTIMA Study

Presenting Author(s)

• 

  Olukayode O. Aremu, PhD

  Postdoctoral Research Fellow
  University of Cape Town
  Cape Town, Western Cape, South Africa

Primary Author(s)

• 

  Olukayode O. Aremu, PhD

  Postdoctoral Research Fellow
  University of Cape Town
  Cape Town, Western Cape, South Africa

Co-Author(s)

• PS

  Petronella P. Samuels, BSc

  University of Cape Town
  Cape Town, Western Cape, South Africa
• 

  Morne F. Kahts, MD, MBA

  Radiology Registrar
  Groote Schuur Hospital & University of Cape Town
  Cape Town, Western Cape, South Africa
• NT

  Natasha Taylor-Meyer, MSc

  Research Coordinator
  University of Cape Town
  Capetown, Western Cape, South Africa
• MA

  Marguerite Adriaanse, MD

  Medical Officer
  University of Cape Town
  Capetown, Western Cape, South Africa
• SS

  Sango Skelem, RN

  Research Nurse
  Groote Schuur Hospital, Cape Town
  Capetown, Western Cape, South Africa
• SJ

  Stephen Jermy, MSc

  Research Fellow
  University of Cape Town
  Cape Town, Western Cape, South Africa
• LS

  Lidia Szczepaniak, PhD

  Consultant
  MRS Consulting in Biomedical Research
  Albuquerque, New Mexico, United States
• BA

  Boni Ale, MD

  Director, Health Data Acumen
  Nairobi, Kenya, Nairobi Area, Kenya
• MZ

  Markella V. Zanni, MD

  Professor of Medicine
  Massachusetts General Hospital
  Boston, Massachusetts, United States
• CL

  Chris Longenecker, MD, PhD

  Professor of Medicine
  University of Washington Medical Center, United States
• NN

  Ntobeko A. Ntusi, MD, PhD

  President and CEO
  South African Medical Research Council
  Cape Town, Western Cape, South Africa

Background: Antiretroviral therapy (ART) has made HIV a chronic illness, extending the lifespan of women with HIV (WWH) in sub-Saharan Africa (SSA). Simultaneously, rates of cardiovascular disease (CVD) are increasing in WWH². Myocardial l fibrosis causes diastolic dysfunction, arrhythmia, and heart failure. Cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and T1 mapping can identify focal and diffuse cardiac fibrosis noninvasively. We investigated the extent of myocardial fibrosis in ART-treated WWH in South Africa using multiparametric CMR.

Methods: We conducted a cross-sectional study of ART-treated WWH aged >40 years in South Africa. All participants underwent CMR on a 3T Siemens Skyra scanner. Imaging included cine sequences for biventricular volumes and function, T1 and T2 mapping for myocardial tissue characterisation, extracellular volume fraction (ECV) quantification, and LGE imaging for focal fibrosis. Postprocessing assessed chamber volumes, ejection fraction, myocardial mass, fibrosis, inflammation and myocardial strain. Clinical metadata were collected. Continuous variables were expressed as mean ± standard deviation (SD) and indexed to body surface area (BSA) where appropriate. Myocardial fibrosis was defined as focal LGE and/or increased native T1 time or ECV (Cut off: Native T1 times - 1210 ± 40 ms; ECV -: < 27%).

Results: Forty-six ART-treated WWH (mean age 50 ± 6 years, BSA 1.86 ± 0.2 m²) with no known CVDs were included. Mean systolic and diastolic blood pressures were 134 ± 21 mmHg and 82 ± 14 mmHg, respectively. LV and RV volumes were within normal limits (LVEDVi 72 ± 11 ml/m²; LVESVi 29 ± 7 ml/m², RVEDVi 71 ± 13 ml/m²), with preserved ejection fractions (LVEF 60 ± 5%, RVEF 58 ± 7%) and LV mass index (40 ± 8 g/m²), as depicted in Table1. Left and right atrial volumes were 65 ± 15 ml and 55 ± 18 ml, respectively. Native T1 times (1238 ± 42 ms), and ECV (29 ± 2.8%) were elevated. T2 times (41 ± 4 ms) were normal. Mean LGE mass was 15 ± 9.7 g, corresponding to 38 ± 10% volume proportion (Figure 1). Peak global longitudinal strain was impaired (–16 ± 2.8%) as shown in Table 2.



Conclusion: In this cohort of ART-treated WWH, biventricular systolic function was preserved, yet there was an evidence of a substantial burden of myocardial fibrosis and deformation abnormalities. The combination of myocardial fibrosis and impaired myocardial strain suggests ongoing subclinical myocardial injury, highlighting the need for early detection and tailored cardiovascular risk management in WWH.

Table 1: Demographics, clinical and functional parameters in WWH

Demographic, clinical and functional parameters	Patients (n=46)
Age, years	50 ± 6.4
BSA, m2	1.86 ± 0.2
Systolic Blood Pressure, mmHg	134 ± 20.9
Diastolic Blood Pressure, mmHg	82 ± 13.5
LVEDVi, ml/m2	72 ± 11.3
LVESVi, ml/m2	29 ± 7.0
LVSVi, ml/m2	43 ± 8.2
Max LAV, ml	65 ± 14.8
LVEF, %	60 ± 5.1
LVMI, g/m2	40 ± 8.1
RVEDVi, ml/m2	71 ± 12.8
RVESVi, ml/m2	32 ± 14.6
RVSVi, ml/m2	40 ± 6.6
Max RAV, ml	55 ± 17.7
RVEF, %	58 ± 6.7

Continuous data are mean ± SD. Values are indexed to body surface area. LVEDVI, left ventricular end-diastolic volume index; LVESVI, left ventricular end-systolic volume index; LVSVI, left ventricular systolic volume index; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; LA, Left atrium; RVEDVI, right ventricular end-diastolic volume index; RVESVI, right ventricular end-systolic volume index; RVSVi, right ventricular systolic volume index; RVEF, right ventricular ejection fraction; RA, right atrium.Table 2: CMR tissue characteristics in WWH

CMR tissue characteristics	Patients (n=46)
LGE mass (g)	15 ± 9.7
LGE percentage (%)	38 ± 9.8
T1 relaxation times, ms	1238 ± 42
T2 relaxation times, ms	41 ± 3.6
ECV, %	29 ± 2.8
Peak radial systolic strain, %	35 ± 6.6
Peak circumferential systolic strain, %	-20 ± 2.3
Peak longitudinal systolic strain, %	-16 ± 2.8
Peak radial systolic strain rate, s-1	1.6 ± 0.5
Peak circumferential systolic strain rate, s-1	-0.8 ± 0.2
Peak longitudinal systolic strain rate, s-1	-0.9 ± 1.7
Peak radial diastolic strain rate, s-1	-1.0 ± 1.7
Peak circumferential diastolic strain rate, s-1	0.8 ± 0.6
Peak longitudinal diastolic strain rate, s-1	0.9 ± 0.2

Continuous data are mean ± SD, ECV, extracellular volume fractionFigure 1. Patterns of late gadolinium enhancement in WWH. Normal, Healthy control with no LGE; Diffuse, Diffuse whole heart enhancement; Patchy, Patchy midwall enhancement; LSM, Linear septal midwall enhancement; LCM, Linear circumferential enhancement.