Evolution of myocardial oedema and fibrosis in HIV infected persons after the initiation of antiretroviral therapy: a prospective cardiovascular magnetic resonance study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Characterizing myocardial edema and fibrosis in hypertensive crisis with cardiovascular magnetic resonance imaging.

A hypertensive crisis is associated with an increased risk of cardiovascular events. Although altered cardiac structure, function, and myocardial architecture on cardiovascular magnetic resonance (CMR) have been associated with increased adverse events in hypertensive patients, the studies did not include patients with hypertensive crisis. Our study aimed to determine myocardial tissue characteristics in patients with hypertensive crisis using CMR imaging. Participants underwent comprehensive CMR imaging at 1.5T. The imaging protocol included cine-, T2-weighted-, contrasted- and multi-parametric mapping images. Blood and imaging biomarkers were compared in hypertensive emergency and hypertensive urgency. Predictors of myocardial edema was assessed using linear regression. The predictive value of T1- and T2 mapping for identifying hypertensive emergency (from urgency) was assessed with receiver operator characteristics curves. Eighty-two patients (48.5 ± 13.4 years, 57% men) were included. Hypertensive emergency constituted 78%. Native T1 was higher in patients with LVH compared to those without (1056 ± 33 vs. 1013 ± 40, P < 0.001), and tended to be higher in hypertensive emergency than urgency (1051 ± 37 vs. 1033 ± 40, P = 0.077). T2-w signal intensity (SI) ratio and T2 mapping values were higher in hypertensive emergency (1.5 ± 0.2 vs. 1.4 ± 0.1, P = 0.044 and 48 ± 2 vs. 47 ± 2, P = 0.004), and in patients with than without LVH (1.5 ± 0.2 vs. 1.4 ± 0.1, P = 0.045 and P = 0.030). A trend for higher extracellular volume was noted in hypertensive emergency compared to urgency (25 ± 4 vs. 22 ± 3, P = 0.050). Native T1 correlated with T2 mapping (rs = 0.429, P < 0.001), indexed LV mass (rs = 0.493, P < 0.001), cardiac troponin (rs = 0.316, P < 0.001) and NT-proBNP (rs = 0.537, P < 0.001), while T2 correlated with cardiac troponin (rs = 0.390, P < 0.001), and NT-proBNP (rs = 0.348, P < 0.001). Non-ischemic LGE pattern occurred in 59% and was 21% more prevalent in the hypertensive emergency group (P = 0.005). Our findings demonstrate that hypertensive crisis is associated with distinct myocardial tissue alterations, including increased myocardial edema and fibrosis, as detected on CMR. Patients with hypertensive emergency had a higher degree of myocardial oedema than hypertensive urgency. Further research is necessary to explore the prognostic value of these findings.

Antiretroviral therapy and HIV-associated cardiovascular disease: a prospective cardiac biomarker and CMR tissue characterization study.

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.

Subclinical cardiovascular remodelling in HIV-infection: A multimodal case study of 2 serodiscordant, monozygotic twins.

Cardiovascular abnormalities are increasingly recognised among people newly diagnosed with HIV, but subclinical pathology may be challenging to diagnose. We present a case study of subtle cardiovascular changes in identical twins, one without HIV-infection and the other recently diagnosed with HIV (serodiscordant). We hypothesise that cardiovascular parameters would be similar between the twins, unless non-genetic (environmental) factors are at play. These differences likely represent occult pathology secondary to the effects of early HIV-infection. A 25-year-old female incidentally diagnosed with HIV, and her HIV-uninfected identical twin, living with her since birth, underwent comprehensive cardiovascular assessments. The HIV-positive twin exhibited a globular left ventricle (LV), larger LV volumes, decreased LV strain, peak atrial longitudinal strain (PALS) and higher native T1 and T2 mapping values compared to her sister. Cardiac biomarkers high sensitivity cardiac troponin T and N-terminal proBNP, as well as the novel markers of fibrosis and remodelling, galectin-3 and soluble-ST2, were higher in the HIV-infected twin. Given the twins' shared environment and genetic makeup, these differences likely stem from HIV-infection. Our study supports previous findings and suggests potential screening markers for HIV-associated cardiovascular disease, including PALS. Further research is warranted to explore PALS' utility in this context.

Myocardial Tissue Characterization in Patients with Hypertensive Crisis, Positive Troponin, and Unobstructed Coronary Arteries: A Cardiovascular Magnetic Resonance-Based Study.

Hypertensive crisis can present with cardiac troponin elevation and unobstructed coronary arteries. We used cardiac magnetic resonance (CMR) imaging to characterize the myocardial tissue in patients with hypertensive crisis, elevated cardiac troponin, and unobstructed coronary arteries. Patients with hypertensive crisis and elevated cardiac troponin with coronary artery stenosis <50% were enrolled. Patients with troponin-negative hypertensive crisis served as controls. All participants underwent CMR imaging at 1.5 Tesla. Imaging biomarkers and tissue characteristics were compared between the groups. There were 19 patients (63% male) with elevated troponin and 24 (33% male) troponin-negative controls. The troponin-positive group was older (57 ± 11 years vs. 47 ± 14 years, p = 0.015). The groups had similar T2-weighted signal intensity ratios and native T1 times. T2 relaxation times were longer in the troponin-positive group, and the difference remained significant after excluding infarct-pattern late gadolinium enhancement (LGE) from the analysis. Extracellular volume (ECV) was higher in the troponin-positive group (25 ± 4 ms vs. 22 ± 3 ms, p = 0.008) and correlated strongly with T2 relaxation time (rs = 0.701, p = 0.022). Late gadolinium enhancement was 32% more prevalent in the troponin-positive group (82% vs. 50%, p = 0.050), with 29% having infarct-pattern LGE. T2 relaxation time was independently associated with troponin positivity (OR 2.1, p = 0.043), and both T2 relaxation time and ECV predicted troponin positivity (C-statistics: 0.71, p = 0.009; and 0.77, p = 0.006). Left ventricular end-diastolic and left atrial volumes were the strongest predictors of troponin positivity (C-statistics: 0.80, p = 0.001; and 0.82, p < 0.001). The increased T2 relaxation time and ECV and their significant correlation in the troponin-positive group suggest myocardial injury with oedema, while the non-ischaemic LGE could be due to myocardial fibrosis or acute necrosis. These CMR imaging biomarkers provide important clinical indices for risk stratification and prognostication in patients with hypertensive crisis.

Cardiac Morphology, Function, and Left Ventricular Geometric Pattern in Patients with Hypertensive Crisis: A Cardiovascular Magnetic Resonance-Based Study.

(1) Background: Altered cardiac morphology and function are associated with increased risks of adverse cardiac events in hypertension. Our study aimed to assess left ventricular (LV) morphology, geometry, and function using cardiovascular magnetic resonance (CMR) imaging in patients with hypertensive crisis. (2) Methods: Patients with hypertensive crisis underwent CMR imaging at 1.5 Tesla to assess cardiac volume, mass, function, and contrasted study. Left ventricular (LV) function and geometry were defined according to the guideline recommendations. Late gadolinium enhancement (LGE) was qualitatively assessed and classified into ischemic and nonischemic patterns. Predictors of LGE was determined using regression analysis. (3) Results: Eighty-two patients with hypertensive crisis (aged 48.5 ± 13.4 years, and 57% males) underwent CMR imaging. Of these patients, seventy-eight percent were hypertensive emergency and twenty-two percent were urgency. Diastolic blood pressure was higher under hypertensive emergency (p = 0.032). Seventy-nine percent (92% of emergency vs. 59% of urgency, respectively; p = 0.003) had left ventricular hypertrophy (LVH). The most prevalent LV geometry was concentric hypertrophy (52%). Asymmetric LVH occurred in 13 (22%) of the participants after excluding ischemic LGE. Impaired systolic function occurred in 46% of patients, and predominantly involved hypertensive emergency. Nonischemic LGE occurred in 75% of contrasted studies (67.2% in emergency versus 44.4% in urgency, respectively; p < 0.001). Creatinine and LV mass were independently associated with nonischemic LGE. (5) Conclusion: LVH, altered geometry, asymmetric LVH, impaired LV systolic function, and LGE are common under hypertensive crisis. LVH and LGE more commonly occurred under hypertensive emergency. Longitudinal studies are required to determine the prognostic implications of asymmetric LVH and LGE in hypertensive crisis.

Clinical Profile of Patients with Hypertensive Emergency Referred to a Tertiary Hospital in the Western Cape Province of South Africa.

BACKGROUND: Despite advances in managing hypertension, hypertensive emergencies remain a common indication for emergency room visits. Our study aimed to determine the clinical profile of patients referred with hypertensive emergencies. METHODS: We conducted an observational study involving patients aged ≥18 years referred with hypertensive crisis. A diagnosis of hypertensive emergencies was based on a systolic blood pressure (BP) ≥180 mmHg and/or a diastolic BP ≥110 mmHg, with acute hypertension-mediated organ damage (aHMOD). Patients without evidence of aHMOD were considered hypertensive urgencies. Hypertensive disorders of pregnancy and unconscious patients were excluded from the study. RESULTS: Eighty-two patients were included, comprising 66 (80.5%) with hypertensive emergencies and 16 (19.5%) with hypertensive urgencies. The mean age of patients with hypertensive emergencies was 47.9 (13.2) years, and 66.7% were males. Age, systolic BP, and duration of hypertension were similar in the hypertensive crisis cohort. Most patients with hypertensive emergencies reported nonadherence to medication (78%) or presented de novo without a prior diagnosis of hypertension (36%). Cardiac aHMOD (acute pulmonary edema and myocardial infarction) occurred in 66%, while neurological emergencies (intracranial hemorrhage, ischemic stroke, and hypertensive encephalopathy) occurred in 33.3%. Lactate dehydrogenase (LDH) (P < 0.001), NT-proBNP (P=0.024), and cardiac troponin (P<0.001) were higher in hypertensive emergencies compared to urgencies. LDH did not differ in the subtypes of hypertensive emergencies. CONCLUSION: Cardiovascular and neurological emergencies are the most common hypertensive emergencies. Most patients reported nonadherence to medication or presented de novo without a prior diagnosis of hypertension.

The Role of Cardiac Biomarkers in the Diagnosis of Hypertensive Emergency.

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.

Altered cardiac structure and function in newly diagnosed people living with HIV: a prospective cardiovascular magnetic resonance study after the initiation of antiretroviral treatment.

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.

Pulse wave velocity demonstrates increased aortic stiffness in newly diagnosed, antiretroviral naïve HIV infected adults: A case-control study.

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.

The hidden continuum of HIV-associated cardiomyopathy: A focussed review with case reports.

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.