Unsupervised machine learning demonstrates the prognostic value of TAPSE/PASP ratio among hospitalized patients with COVID-19.

BACKGROUND: The ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) is a validated index of right ventricular-pulmonary arterial (RV-PA) coupling with prognostic value. We determined the predictive value of TAPSE/PASP ratio and adverse clinical outcomes in hospitalized patients with COVID-19. METHODS: Two hundred and twenty-nine consecutive hospitalized racially/ethnically diverse adults (≥18 years of age) admitted with COVID-19 between March and June 2020 with clinically indicated transthoracic echocardiograms (TTE) that included adequate tricuspid regurgitation (TR) velocities for calculation of PASP were studied. The exposure of interest was impaired RV-PA coupling as assessed by TAPSE/PASP ratio. The primary outcome was in-hospital mortality. Secondary endpoints comprised of ICU admission, incident acute respiratory distress syndrome (ARDS), and systolic heart failure. RESULTS: One hundred and seventy-six patients had both technically adequate TAPSE measurements and measurable TR velocities for analysis. After adjustment for age, sex, BMI, race/ethnicity, diabetes mellitus, and smoking status, log(TAPSE/PASP) had a significantly inverse association with ICU admission (p = 0.015) and death (p = 0.038). ROC analysis showed the optimal cutoff for TAPSE/PASP for death was 0.51 mm mmHg-1 (AUC = 0.68). Unsupervised machine learning identified two groups of echocardiographic function. Of all echocardiographic measures included, TAPSE/PASP ratio was the most significant in predicting in-hospital mortality, further supporting its significance in this cohort. CONCLUSION: Impaired RV-PA coupling, assessed noninvasively via the TAPSE/PASP ratio, was predictive of need for ICU level care and in-hospital mortality in hospitalized patients with COVID-19 suggesting utility of TAPSE/PASP in identification of poor clinical outcomes in this population both by traditional statistical and unsupervised machine learning based methods.

HIV and Global Cardiovascular Health.

PURPOSE OF REVIEW: Because of effective combination antiretroviral therapy, people living with HIV (PLWH) are living longer but developing chronic age-related conditions including cardiovascular disease (CVD), the leading cause of death globally. This review aims to discuss the epidemiology, mechanisms, and clinical considerations of CVD in PLWH from a global perspective. RECENT FINDINGS: PLWH are at greater risk for CVD at chronologically younger ages than those without HIV. Potential underlying mechanisms for CVD in PLWH include systemic inflammation, comorbidities, immune-mediated, or treatment-related mechanisms. There is also risk factor variation based on geographical location, including non-traditional CVD risk factors. CVD is prevalent in PLWH and increasing on a global scale. Further understanding the unique epidemiology, risk factors, and treatment of CVD in this population will improve the care of PLWH.

Prominent Longitudinal Strain Reduction of Basal Left Ventricular Segments in Patients With Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-19 (COVID-19) has been associated with overt and subclinical myocardial dysfunction. We observed a recurring pattern of reduced basal left ventricular (LV) longitudinal strain on speckle-tracking echocardiography in hospitalized patients with COVID-19 and subsequently aimed to identify characteristics of affected patients. We hypothesized that patients with COVID-19 with reduced basal LV strain would demonstrate elevated cardiac biomarkers. METHODS AND RESULT: Eighty-one consecutive patients with COVID-19 underwent speckle-tracking echocardiography. Those with poor quality speckle-tracking echocardiography (n = 2) or a known LV ejection fraction of <50% (n = 4) were excluded. Patients with an absolute value basal longitudinal strain of <13.9% (2 standard deviations below normal) were designated as cases (n = 39); those with a basal longitudinal strain of ≥13.9% were designated as controls (n = 36). Demographics and clinical variables were compared. Of 75 included patients (mean age 62 ± 14 years, 41% women), 52% had reduced basal strain. Cases had higher body mass index (median 34.1; interquartile range 26.5-37.9 kg/m2 vs median 26.9, interquartile range, 24.8-30.0 kg/m2, P = .009), and greater proportions of Black (74% vs 36%, P = .0009), hypertensive (79% vs 56%, P = .026), and diabetic patients (44% vs 19%, P = .025) compared with controls. Troponin and N-terminal pro-brain natriuretic peptide levels trended higher in cases, but were not significantly different. CONCLUSIONS: Reduced basal LV strain is common in patients with COVID-19. Patients with hypertension, diabetes, obesity, and Black race were more likely to have reduced basal strain. Further investigation into the significance of this strain pattern is warranted.

Multimodality Imaging for Cardiac Evaluation in Patients with COVID-19.

PURPOSE OF REVIEW: A growing number of cardiovascular manifestations resulting from the novel SARS-CoV-2 coronavirus (COVID-19) have been described since the beginning of this global pandemic. Acute myocardial injury is common in this population and is associated with higher rates of morbidity and mortality. The focus of this review centers on the recent applications of multimodality imaging in the diagnosis and management of COVID-19-related cardiovascular conditions. RECENT FINDINGS: In addition to standard cardiac imaging techniques such as transthoracic echocardiography, other modalities including computed tomography and cardiac magnetic resonance imaging have emerged as useful adjuncts in select patients with COVID-19 infection, particularly those with suspected ischemic and nonischemic myocardial injury. Data have also emerged suggesting lasting COVID-19 subclinical cardiac effects, which may have long-term prognostic implications. With the spectrum of COVID-19 cardiovascular manifestations observed thus far, it is important for clinicians to recognize the role, strengths, and limitations of multimodality imaging techniques in this patient population.

Imaging Assessment of Endothelial Function: An Index of Cardiovascular Health.

Endothelial dysfunction is a key early mechanism in a variety of cardiovascular diseases and can be observed in larger conduit arteries as well as smaller resistance vessels (microvascular dysfunction). The presence of endothelial dysfunction is a strong prognosticator for cardiovascular events and mortality, and assessment of endothelial function can aid in selecting therapies and testing their response. While the gold standard method of measuring coronary endothelial function remains invasive angiography, several non-invasive imaging techniques have emerged for investigating both coronary and peripheral endothelial function. In this review, we will explore and summarize the current invasive and non-invasive modalities available for endothelial function assessment for clinical and research use, and discuss the strengths, limitations and future applications of each technique.

Effect of Sex on Coronary Endothelial Dysfunction in People Living With HIV.

Background Impaired coronary endothelial function (CEF) predicts cardiovascular events and occurs in people living with HIV (PLWH). Women compared with men living with HIV have worse cardiovascular outcomes, but prior CEF studies included few women. The authors aimed to compare CEF in women with HIV versus without HIV, investigate sex differences in CEF and PCSK9 (proprotein convertase subtilisin/kexin type 9) (a proinflammatory biomarker), and evaluate whether increased serum levels of PCSK9 are associated with CEF in PLWH. Methods and Results Magnetic resonance imaging was performed to measure CEF (as percent change in coronary cross-sectional area and coronary blood flow during isometric handgrip exercise, an endothelial-dependent stressor) and serum PCSK9 levels were measured in 106 PLWH and 76 people without HIV. CEF was significantly reduced in women with versus without HIV (cross-sectional area change -0.5%±9.7 versus 9.5%±3.2, respectively). After adjustment for age, body mass index, and menopausal status, women with HIV still had reduced CEF (percentage of cross-sectional area: ß -8.3 [-13 to -3.6], P=0.001) compared with women without HIV. PCSK9 was elevated in women living with HIV versus without (306 ng/mL [200-412 ng/mL] versus 180 ng/mL [154-223 ng/mL], P<0.001), and no sex differences in either CEF or PCSK9 were detected in PLWH. Elevated PCSK9 was associated with impaired CEF in PLWH; however, no significant sex differences in the association were detected. Conclusions Among PLWH, coronary endothelial dysfunction is present in women and comparable to men. PCSK9 is higher in women with versus without HIV and a significant inverse relationship between PCSK9 and CEF was shown. Future studies should determine whether PLWH would benefit from interventions to improve endothelial function.

Coronary Endothelial Dysfunction in People Living With HIV Is Related to Body Fat Distribution.

BACKGROUND: People living with HIV (PLWH) on antiretroviral therapy (ART) are at increased risk of atherosclerotic disease. Abnormal adipose distribution is common in PLWH and may contribute to atherosclerosis. Because coronary artery endothelial function (CEF) is impaired in early atherosclerosis, predicts future cardiovascular events, and is reduced in PLWH, we investigated associations between body fat distribution and CEF in PLWH. SETTING: Prospective cohort study. METHODS: PLWH on stable ART underwent MRI to quantify CEF, measured as change in coronary cross-sectional area from rest to that during isometric handgrip exercise, an endothelial-dependent stressor. Abdominal visceral and subcutaneous fat area (axial L4 level) and liver fat fraction were quantified using MRI. Linear regression was used to determine associations between CEF and independent variables. RESULTS: Among 84 PLWH (52 ± 11 years; 33% women), mean cross-sectional area change was 0.74 ± 11.7%, indicating impaired CEF. On univariable regression analysis, CEF was inversely related to waist circumference (R = -0.31, P = 0.014), hip circumference (R = -0.27, P = 0.037), and subcutaneous fat area (R = -0.25, P = 0.031). We did not observe significant relationships between CEF and liver fat fraction, waist/hip ratio, or visceral fat area. On multivariable regression adjusted for age, sex, and race, CEF was associated with waist circumference, hip circumference, subcutaneous fat, and liver fat fraction. CONCLUSION: Waist and hip circumference and subcutaneous fat area are associated with impaired CEF, an established metric of abnormal vascular health in PLWH on stable ART, and may contribute to the increased rate of heart disease in this population.

Endothelial thrombomodulin downregulation caused by hypoxia contributes to severe infiltration and coagulopathy in COVID-19 patient lungs.

BACKGROUND: Thromboembolism is a life-threatening manifestation of coronavirus disease 2019 (COVID-19). We investigated a dysfunctional phenotype of vascular endothelial cells in the lungs during COVID-19. METHODS: We obtained the lung specimens from the patients who died of COVID-19. The phenotype of endothelial cells and immune cells was examined by flow cytometry and immunohistochemistry (IHC) analysis. We tested the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the endothelium using IHC and electron microscopy. FINDINGS: The autopsy lungs of COVID-19 patients exhibited severe coagulation abnormalities, immune cell infiltration, and platelet activation. Pulmonary endothelial cells of COVID-19 patients showed increased expression of procoagulant von Willebrand factor (VWF) and decreased expression of anticoagulants thrombomodulin and endothelial protein C receptor (EPCR). In the autopsy lungs of COVID-19 patients, the number of macrophages, monocytes, and T cells was increased, showing an activated phenotype. Despite increased immune cells, adhesion molecules such as ICAM-1, VCAM-1, E-selectin, and P-selectin were downregulated in pulmonary endothelial cells of COVID-19 patients. Notably, decreased thrombomodulin expression in endothelial cells was associated with increased immune cell infiltration in the COVID-19 patient lungs. There were no SARS-CoV-2 particles detected in the lung endothelium of COVID-19 patients despite their dysfunctional phenotype. Meanwhile, the autopsy lungs of COVID-19 patients showed SARS-CoV-2 virions in damaged alveolar epithelium and evidence of hypoxic injury. INTERPRETATION: Pulmonary endothelial cells become dysfunctional during COVID-19, showing a loss of thrombomodulin expression related to severe thrombosis and infiltration, and endothelial cell dysfunction might be caused by a pathologic condition in COVID-19 patient lungs rather than a direct infection with SARS-CoV-2. FUNDING: This work was supported by the Johns Hopkins University, the American Heart Association, and the National Institutes of Health.

The Role of Multimodality Imaging in HIV-Associated Cardiomyopathy.

Despite marked advances in therapeutics, HIV infection remains a leading cause of morbidity and mortality worldwide. HIV infection is associated with cardiovascular complications including myocardial dysfunction. The description of HIV-associated cardiomyopathy (HIVAC) has evolved over time from a predominantly dilated cardiomyopathy with systolic dysfunction to one of subclinical diastolic dysfunction. Multimodality cardiovascular imaging plays an integral role in our understanding of the etiology and pathogenesis of HIVAC. Such imaging is also essential in the evaluation of individuals with chronic HIV disease who present with cardiac symptoms, especially of heart failure. In the present review, we will highlight current evidence for the role of multimodality imaging in establishing the diagnosis, etiology and pathophysiology of HIVAC as well as guiding treatment and assessing prognosis.

Myocardial Work Efficiency, A Novel Measure of Myocardial Dysfunction, Is Reduced in COVID-19 Patients and Associated With In-Hospital Mortality.

Background: Although troponin elevation is common in COVID-19, the extent of myocardial dysfunction and its contributors to dysfunction are less well-characterized. We aimed to determine the prevalence of subclinical myocardial dysfunction and its association with mortality using speckle tracking echocardiography (STE), specifically global longitudinal strain (GLS) and myocardial work efficiency (MWE). We also tested the hypothesis that reduced myocardial function was associated with increased systemic inflammation in COVID-19. Methods and Results: We conducted a retrospective study of hospitalized COVID-19 patients undergoing echocardiography (n = 136), of whom 83 and 75 had GLS (abnormal >-16%) and MWE (abnormal <95%) assessed, respectively. We performed adjusted logistic regression to examine associations of GLS and MWE with in-hospital mortality. Patients were mean 62 ± 14 years old (58% men). While 81% had normal left ventricular ejection fraction (LVEF), prevalence of myocardial dysfunction was high by STE; [39/83 (47%) had abnormal GLS; 59/75 (79%) had abnormal MWE]. Higher MWE was associated with lower in-hospital mortality in unadjusted [OR 0.92 (95% CI 0.85-0.99); p = 0.048] and adjusted models [aOR 0.87 (95% CI 0.78-0.97); p = 0.009]. In addition, increased systemic inflammation measured by interleukin-6 level was associated with reduced MWE. Conclusions: Subclinical myocardial dysfunction is common in COVID-19 patients with clinical echocardiograms, even in those with normal LVEF. Reduced MWE is associated with higher interleukin-6 levels and increased in-hospital mortality. Non-invasive STE represents a readily available method to rapidly evaluate myocardial dysfunction in COVID-19 patients and can play an important role in risk stratification.

Noninvasive detection of impaired pulmonary artery endothelial function in people living with HIV.

OBJECTIVE: People living with HIV (PLWH) have an increased risk of pulmonary vascular disease and pulmonary hypertension. Endothelial cell dysfunction is thought to contribute, but human studies have been limited by the invasive nature of conventional measures of pulmonary artery endothelial function (PAEF). We report here a noninvasive MRI approach to measure nitric oxide mediated PAEF by quantifying changes in pulmonary artery area and blood flow during isometric handgrip exercise (IHE), an endothelial nitric oxide dependent stressor. We used this to test the hypothesis that PLWH have impaired PAEF, even before development of pulmonary hypertension. DESIGN: A prospective cohort study. METHODS: We enrolled 25 HIV-positive viral-suppressed individuals on stable antiretroviral therapy without known or suspected pulmonary hypertension and 19 matched seronegative control individuals (HIV-negative). Pulmonary artery area and blood flow changes in response to IHE were measured with noncontrast MRI. Data previously collected during nitric oxide-synthase inhibition were analysed to determine the role of nitric oxide in the pulmonary artery response to IHE. RESULTS: Seronegative individuals exhibited the anticipated PA vasodilatory response to IHE, but this was completely absent in HIV-positive individuals who exhibited an impaired area change (-1.1 ±â€Š1.2 vs. +7.7 ±â€Š2.2%, HIV-positive vs. HIV-negative, mean ±â€ŠSEM, respectively, P = 0.002) and blood flow response (0.2 ±â€Š2.3 vs. 13.5 ±â€Š4.8%, P = 0.005). The pulmonary artery vasodilatory effect of IHE in healthy individuals was fully blocked by nitric oxide-synthase, demonstrating this pulmonary artery response is predominantly nitric oxide mediated. CONCLUSION: Using noninvasive MRI methods to quantify PAEF, we observed significantly impaired PAEF in PLWH compared with matched HIV-negative controls. Noninvasive PAEF testing may be useful in evaluating early HIV-related pulmonary vascular disease.

Prevalence and Clinical Correlates of Echo-Estimated Right and Left Heart Filling Pressures in Hospitalized Patients With Coronavirus Disease 2019.

OBJECTIVES: The prevalence of elevated right and left heart filling pressures in coronavirus disease 2019 is not well characterized. We aimed to characterize the prevalence of pulmonary hypertension and concurrent elevated left heart filling pressure in hospitalized patients with coronavirus disease 2019. We hypothesized that a significant proportion of coronavirus disease 2019 patients has evidence of pulmonary hypertension associated with elevated left heart filling pressure on transthoracic echocardiography. DESIGN: Retrospective cohort study. SETTING: Academic tertiary-care center. PATIENTS: Hospitalized coronavirus disease 2019 patients who underwent clinical transthoracic echocardiography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure variable of interest was right ventricular systolic pressure, calculated using the American Society of Echocardiography guidelines. Pulmonary hypertension was defined as right ventricular systolic pressure greater than 40 mm Hg. Left heart filling pressure was estimated with Nagueh's method for pulmonary artery occlusion pressure using E/e' ratio, and normal was considered pulmonary artery occlusion pressure less than 16 mm Hg. Clinical characteristics and outcomes were compared between the patients with and without pulmonary hypertension. A total of 73 patients (median age 66 yr [57-75 yr]; 46% women) were included. Median right ventricular systolic pressure was 39 mm Hg (interquartile range, 32-50 mm Hg), and 36 patients (49.3%) had evidence of pulmonary hypertension. Patients with pulmonary hypertension were more likely to require ICU admission (86% vs 65%; p = 0.035) and have acute respiratory distress syndrome (72% vs 49%; p = 0.0053) than those without. In-hospital mortality was 26% for those with pulmonary hypertension compared with 14% for those without (p = 0.19). Patients with pulmonary hypertension had higher median-estimated pulmonary artery occlusion pressure (17.4 mm Hg [12.7-21.3 mm Hg] vs 12.1 mm Hg [10.0-14.1 mm Hg]; p = 0.0008), and elevated left heart filling pressure was present in 59% of those with pulmonary hypertension. CONCLUSIONS: Pulmonary hypertension is common in hospitalized patients with coronavirus disease 2019 and is associated with poor clinical outcomes. Left ventricular filling pressure is elevated in over half of those with pulmonary hypertension and may represent a target to reduce right ventricular afterload and potentially improve outcomes in coronavirus disease 2019.