Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality.

BACKGROUND: We aimed to determine whether serum levels of proteins related to changes in cardiac extracellular matrix (ECM) were associated with ischemic injury assessed by cardiac magnetic resonance (CMR) and mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: The concentrations of six ECM-related proteins (periostin, osteopontin, syndecan-1, syndecan-4, bone morphogenetic protein 7, and growth differentiation factor (GDF)-15) were measured in serum samples from patients on Day 1 and Month 4 after STEMI (n = 239). Ischemic injury was assessed by myocardial salvage index, microvascular obstruction, infarct size, and left ventricular function measured by CMR conducted during the initial admission (median 2 days after admission) and after 4 months. All-cause mortality was recorded after a median follow-up time of 70 months. RESULTS: Levels of periostin increased from Day 1 to Month 4 after hospitalization, while the levels of GDF-15, osteopontin, syndecan-1, and syndecan-4 declined. At both time points, high levels of syndecan-1 were associated with microvascular obstruction, large infarct size, and reduced left ventricular ejection fraction, whereas high levels of syndecan-4 at Month 4 were associated with a higher myocardial salvage index and less dilatation of the left ventricle. Higher mortality rates were associated with periostin levels at both time points, low syndecan-4 levels at Month 4, or high GDF-15 levels at Month 4. CONCLUSIONS: In patients with STEMI, we found an association between serum levels of ECM biomarkers and ischemic injury and mortality. The results provide new insight into the role ECM components play in ischemic injury following STEMI and suggests a potential for these biomarkers in prognostication after STEMI.

Changes in cardiac structure and function from 3 to 12 months after hospitalization for COVID-19.

BACKGROUND: Cardiac function may be impaired during and early after hospitalization for COVID-19, but little is known about the progression of cardiac dysfunction and the association with postacute COVID syndrome (PACS). METHODS: In a multicenter prospective cohort study, patients who had been hospitalized with COVID-19 were enrolled and comprehensive echocardiography was performed 3 and 12 months after discharge. Twenty-four-hour electrocardiogram (ECG) was performed at 3 and 12 months in patients with arrhythmias at 3 months. RESULTS: In total, 182 participants attended the 3 and 12 months visits (age 58 ± 14 years, 59% male, body mass index 28.2 ± 4.2 kg/m2 ). Of these, 35 (20%) had severe COVID-19 (treatment in the intensive care unit) and 74 (52%) had self-reported dyspnea at 3 months. From 3 to 12 months there were no significant overall changes in any measures of left or right ventricle (LV; RV) structure and function (p > .05 for all), including RV strain (from 26.2 ± 3.9% to 26.5 ± 3.1%, p = .29) and LV global longitudinal strain (from 19.2 ± 2.3% to 19.3 ± 2.3%, p = .64). Changes in echocardiographic parameters from 3 to 12 months did not differ by COVID-19 severity or by the presence of persistent dyspnea (p > .05 for all). Among patients with arrhythmia at 3 months, there was no significant change in arrhythmia burden to 12 months. CONCLUSION: Following COVID-19, cardiac structure and function remained unchanged from 3 to 12 months after the index hospitalization, irrespective of COVID-19 severity and presence of persistent dyspnea. These results suggest that progression of cardiac dysfunction after COVID-19 is rare and unlikely to play an important role in PACS.

Cardiac Dysfunction and Arrhythmias 3 Months After Hospitalization for COVID-19.

Background The extent of cardiac dysfunction post-COVID-19 varies, and there is a lack of data on arrhythmic burden. Methods and Results This was a combined multicenter prospective cohort study and cross-sectional case-control study. Cardiac function assessed by echocardiography in patients with COVID-19 3 to 4 months after hospital discharge was compared with matched controls. The 24-hour ECGs were recorded in patients with COVID-19. A total of 204 patients with COVID-19 consented to participate (mean age, 58.5 years; 44% women), and 204 controls were included (mean age, 58.4 years; 44% women). Patients with COVID-19 had worse right ventricle free wall longitudinal strain (adjusted estimated mean difference, 1.5 percentage points; 95% CI, -2.6 to -0.5; P=0.005) and lower tricuspid annular plane systolic excursion (-0.10 cm; 95% CI, -0.14 to -0.05; P<0.001) and cardiac index (-0.26 L/min per m2; 95% CI, -0.40 to -0.12; P<0.001), but slightly better left ventricle global strain (-0.8 percentage points; 95% CI, 0.2-1.3; P=0.008) compared with controls. Reduced diastolic function was twice as common compared with controls (60 [30%] versus 29 [15%], respectively; odds ratio, 2.4; P=0.001). Having dyspnea or fatigue were not associated with cardiac function. Right ventricle free wall longitudinal strain was worse after intensive care treatment. Arrhythmias were found in 27% of the patients, mainly premature ventricular contractions and nonsustained ventricular tachycardia (18% and 5%, respectively). Conclusions At 3 months after hospital discharge with COVID-19, right ventricular function was mildly impaired, and diastolic dysfunction was twice as common compared with controls. There was little evidence for an association between cardiac function and intensive care treatment, dyspnea, or fatigue. Ventricular arrhythmias were common, but the clinical importance is unknown. Registration URL: http://clinicaltrials.gov. Unique Identifier: NCT04535154.

Innate immune cell infiltration in melanoma metastases affects survival and is associated with BRAFV600E mutation status.

Little is known about the infiltrative pattern of innate immune cells in primary melanoma compared with their paired metastases and in BRAF-mutated tumors. Therefore, our aim was to characterize the inflammatory microenvironment in primary ulcerated and nonulcerated melanomas and paired metastases, to investigate the relation between inflammation and BRAF mutation in primary melanoma and paired metastases, and to evaluate the effect of the analyzed biomarkers on melanoma-specific survival. A total of 385 primary tumors and 96 paired metastases were stained with immunohistochemistry for BRAF, CD163+ macrophages, CD123+ plasmacytoid dendritic cells, CD66b+ neutrophils, and E-cadherin and estimated using objective computer-assisted image analysis. BRAF was semiquantitatively scored as either present or absent. In metastases of nonulcerated melanomas, we observed higher neutrophil (P=0.02) and macrophage (P=0.01) numbers. In the metastases of ulcerated melanomas, we found a higher number of macrophages (P<0.0001). Increase in the neutrophil numbers in the metastases was associated with poor patient survival after first relapse (hazard ratio=1.19, 95% confidence interval: 1.03-1.38, P=0.02). BRAF-positive primary tumors (P=0.02) and metastases (P=0.01) exhibited increased plasmacytoid dendritic cell numbers compared with BRAF-negative tumors. Lastly, primary melanomas in men had higher neutrophil numbers than women (P≤0.0001), and men had worse melanoma-specific survival (hazard ratio=1.52, 95% confidence interval: 1.04-2.21, P=0.03). Our data show that melanoma metastases are densely infiltrated with neutrophils, which affects survival. Our results also highlight the importance of recognizing the presence of inflammatory cells in the metastases as a prognostic marker, and that they may potentially be used to improve the precision of immunotherapy and BRAF targeted therapy.