Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

Use of PET/CT to detect myocardial inflammation and the risk of malignant arrhythmia in chronic Chagas disease.

BACKGROUND: Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD. METHODS AND RESULTS: Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed 18F-FDG and 68Ga-DOTATOC uptake, 68Ga-DOTATOC corrected SUVmax was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%). CONCLUSION: 18F-FDG and 68Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and 68Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Case Report: Malignant Ventricular Arrhythmias Mimicking Acute Coronary Syndrome in Chagas Disease.

Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.