Human immunodeficiency virus (HIV) infected persons on antiretroviral therapy (ART) have been shown to have functionally and structurally altered ventricles and may be related to cardiovascular inflammation. Mounting evidence suggests that the myocardium of HIV infected individuals may be abnormal before ART is initiated and may represent subclinical HIV-associated cardiomyopathy (HIVAC). The influence of ART on subclinical HIVAC is not known. Newly diagnosed, ART naïve persons with HIV infection were enrolled along with HIV uninfected, age- and sex-matched controls. All participants underwent comprehensive cardiovascular assessment, including contrasted cardiovascular magnetic resonance (CMR) with multiparametric mapping on a 1.5T CMR system. The HIV group was started on ART (tenofovir/lamivudine/dolutegravir) and prospectively evaluated 9 months later. Cardiac tissue characterisation was compared in, and between groups using the appropriate statistical tests for the cross sectional data and the paired, prospective data respectively. Seventy-three ART naïve HIV infected individuals (32 ± 7 years, 45% female) and 22 healthy non-HIV subjects (33 ± 7 years, 50% female) were enrolled. Compared with non-HIV healthy subjects, the global native T1 (1008 ± 31 ms vs 1032 ± 44 ms, p = 0.02), global T2 (46 ± 2 vs 48 ± 3 ms, p = 0.006), and the prevalence of pericardial effusion (18% vs 67%, p < 0.001) were significantly higher in the HIV infected group at diagnosis. Global native T1 (1032 ± 44 to 1014 ± 34 ms, p < 0.001) and extracellular volume (ECV) (26 ± 4% to 25 ± 3%, p = 0.001) decreased significantly after 9 months on ART and were significantly associated with a decrease in the HIV viral load, decreased high sensitivity C-reactive protein, and improvement in the CD4 count (p < 0.001). Replacement fibrosis was significantly higher in the HIV infected group than controls (49% vs 10%, p = 0.02). The prevalence of late gadolinium enhancement did not change significantly over the 9-month study period (49% vs 55%, p = 0.4). Subclinical HIVAC may already be present at the time of HIV diagnosis, as suggested by the combination of subclinical myocardial oedema and fibrosis found to be present before administration of ART. Markers of myocardial oedema on tissue characterization improved on ART in the short term, however, it is unclear if the underlying pathological mechanism is halted, or merely slowed by ART. Mid- to long term prospective studies are needed to evaluate subtle myocardial changes over time and to assess the significance of subclinical myocardial fibrosis.

There is a growing interest in the role of biomarkers in differentiating hypertensive emergency from hypertensive urgency. This study aimed to determine the diagnostic utility of lactate dehydrogenase (LDH), high-sensitivity cardiac troponin T (hscTnT), and N-terminal prohormone of brain-type natriuretic peptide (NT-proBNP) for identifying hypertensive emergency. A diagnosis of hypertensive emergency was made based on a systolic blood pressure of ≥180 mmHg and/or a diastolic blood pressure of ≥110 mmHg with acute hypertension-mediated organ damage. The predictive value of LDH, hscTnT, NT-proBNP, and models of these biomarkers for hypertensive emergency was determined using the area under the receiver operator characteristic curve (AUC). There were 66 patients (66.7% male) with a hypertensive emergency and 16 (31.3% male) with hypertensive urgency. LDH, NT-proBNP, and hscTnT were significantly higher in hypertensive emergency. Serum LDH > 190 U/L and high creatinine were associated with hypertensive emergency. LDH had an AUC ranging from 0.87 to 0.92 for the spectrum of hypertensive emergencies, while hscTnT had an AUC of 0.82 to 0.92, except for neurological emergencies, in which the AUC was 0.72. NT-proBNP was only useful in predicting acute pulmonary edema (AUC of 0.89). A model incorporating LDH with hscTnT had an AUC of 0.92 to 0.97 for the spectrum of hypertensive emergencies. LDH in isolation or combined with hscTnT correctly identified hypertensive emergency in patients presenting with hypertensive crisis. The routine assessment of these biomarkers has the potential to facilitate the timely identification of hypertensive emergencies, especially in patients with subtle and subclinical target organ injury.

HIV associated cardiomyopathy (HIVAC) is a poorly understood entity that may progress along a continuum. We evaluated a group of persons newly diagnosed with HIV and studied the evolution of cardiac abnormalities after ART initiation. We recruited a group of newly diagnosed, ART naïve persons with HIV and a healthy, HIV uninfected group. Participants underwent comprehensive cardiovascular evaluation, including cardiovascular magnetic resonance imaging. The HIV group was started on ART and re-evaluated 9 months later. The cardiovascular parameters of the study groups were compared at diagnosis and after 9 months. The ART naïve group’s (n = 66) left- and right end diastolic volume indexed for height were larger compared with controls (n = 22) (p < 0.03). The left ventricular mass indexed for height was larger in the naïve group compared with controls (p = 0.04). The ART naïve group had decreased left- and right ventricular ejection fraction (p < 0.03) and negative, non-linear associations with high HIV viral load (p = 0.02). The left ventricular size increased after 9 months (p = 0.04), while the systolic function remained unchanged. The HIV group had a high rate of non-resolving pericardial effusions. HIV infected persons demonstrate structurally and functionally altered ventricles at diagnosis. High HIV viral load was associated with left- and right ventricular dysfunction. Cardiac parameters and pericardial effusion prevalence did not show improvement with ART. Conversely, a concerning trend of increase was observed with left ventricular size. These subclinical cardiac abnormalities may represent a stage on the continuum of HIVAC that can progress to symptomatic disease if the causes are not identified and addressed.

Increased aortic stiffness is an important predictor of cardiovascular disease (CVD). It remains controversial whether HIV infected persons have increased aortic stiffness at the time of HIV diagnosis. An explorative, case-control study was performed using carotid-femoral pulse wave velocity (PWV) in a newly diagnosed, antiretroviral treatment (ART)-naïve cohort with modest baseline cardiovascular risk. We recruited 85 newly diagnosed adults without known CVD from health care facilities in South Africa (43 female; mean age 33). Median CD4 count was 285, IQR 156–393 cells/µL. Twenty two HIV uninfected controls were recruited from the same facilities (8 female; mean age 33). PWV was measured using the Vicorder module (Skidmore Medical, United Kingdom) using a corrective factor of 0.8. The HIV infected group’s mean PWV measured 11% higher than controls (5.88 vs 5.28 m/s; P = .02). Median aortic distensibility in HIV infected persons was 18% lower than controls (0.37 vs 0.45 mm Hg⁻¹; P = .009). Multivariate analysis revealed that the difference in PWV between groups remained significant when corrected for age, sex, mean blood pressure and kidney function (mean difference 0.52 m/s; P = .01). Mean blood pressure, estimated glomerular filtration rate, HIV infection per se, age and male sex were important associations with increased PWV. Our study provides evidence for increased aortic stiffness in ART naïve adults already demonstrable at the time of HIV diagnosis. The cohort’s young age and recent HIV diagnosis makes atherosclerosis a less likely explanation for the difference. Alternative, potentially reversible, explanations that require further research include vasomotor tone abnormalities and endothelial dysfunction.

HIV-associated cardiomyopathy (HIVAC) is a poorly understood group of diseases with a poor prognosis once ventricular dysfunction is present. Cardiovascular magnetic resonance has revealed a previously unappreciated burden of asymptomatic myocardial abnormalities in people living with HIV, including abnormalities already present at the time of HIV diagnosis. These abnormalities include thickened, inflamed ventricles that bear resemblance to cases of symptomatic HIVAC that are reported on in this article. Our understanding and the significance of asymptomatic HIV-associated myocardial pathology will be explored as early disease on a continuum towards more advanced cardiomyopathy. The need for prospective research in persons naïve to anti-retroviral therapy is emphasised as it may provide key findings to better understand this elusive disease process.

Aims: Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. We prospectively evaluated the hearts of newly diagnosed people living with human immunodeficiency virus (PLWH) using cardiac biomarkers, compared them with human immunodeficiency virus (HIV)-uninfected controls, and correlated our prospective findings with cardiovascular magnetic resonance imaging (CMR). Methods and results: Newly diagnosed, antiretroviral therapy (ART)-naïve PLWH were recruited along with HIV-uninfected, age-matched, and sex-matched controls. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), and galectin-3, as well as a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in and between groups. Compared with controls (n = 22), hs-cTnT (4.0 vs. 5.1 ng/L; P = 0.004), NT-proBNP (23.2 vs. 40.8 ng/L; P = 0.02), and galectin-3 (6.8 vs. 9.0 ng/mL; P = 0.002) were all significantly higher in the ART-naïve group (n = 73). After 9 months of ART, hs-cTnT (5.1 vs. 4.3 ng/L; P = 0.02) and NT-proBNP (40.8 vs. 28.5 ng/L; P = 0.03) both decreased significantly and a trend of decrease was seen in sST2 (16.5 vs. 14.8 ng/L; P = 0.08). Galectin-3 did not demonstrate decrease over time (9.0 vs. 8.8 ng/mL; P = 0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and extracellular volume were NT-proBNP (rs ≥ 0.4, P < 0.001) and galectin-3 (rs ≥ 0.3, P < 0.01). Conclusions: Our cardiac biomarker data support the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis, and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.