Gut microbiota-derived metabolite trimethylamine N-oxide and biomarkers of inflammation are linked to endothelial and coronary microvascular function in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD), which is an umbrella term used for ulcerative colitis (UC) and Crohn's disease (CD), is associated with an increased risk for atherosclerotic cardiovascular disease (CVD). We aimed to investigate the association of local and systemic biomarkers of inflammation and gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) with endothelial and coronary microvascular dysfunction in IBD. METHODS: A total of 56 patients with IBD (20 with UC and 36 with CD) and 34 age and gender matched controls were included. For all participants, samples were collected to analyze faecal calprotectin, and TMAO concentrations. Ultrasound-based examinations were done to measure flow-mediated vasodilatation (FMD) and coronary flow velocity reserve (CFVR). RESULTS: Patients with IBD had lower CFVR (2.07 (1.82-2.40)) and FMD (8.7 ± 3.7) as compared to controls (2.30 (2.07-2.74), p = 0.005 and 11.9 ± 6.8, p = 0.03). In patients with IBD, TMAO concentration (r = -0.30, p = 0.03), C-reactive protein (r = -0.29, p = 0.03) and WBC count (r = -0.37, p = 0.006) had a significant negative correlation with CFVR, and TMAO (ß = -0.27, 95 % CI: -0.23 to -0.02) and WBC count (ß = -0.31, 95 % CI: -0.56 to -0.06) were significant predictors of CFVR after multivariate adjustment. None of the biomarkers of inflammation or TMAO showed significant correlations with FMD. In patients with UC, TMAO showed a significant correlation with both CFVR (r = -0.55, p = 0.01) and FMD (r = -0.60, p = 0.005) while only WBC count had a statistically significant correlation with CFVR (r = -0.49, p = 0.004) in patients with CD. CONCLUSIONS: Gut microbiota-derived metabolite TMAO and biomarkers of systemic inflammation are associated with measures of endothelial/coronary microvascular dysfunction in patients with IBD.

Coronary microvascular dysfunction is common in patients hospitalized with COVID-19 infection.

BACKGROUND AND AIMS: Microvascular disease is considered as one of the main drivers of morbidity and mortality in severe COVID-19, and microvascular dysfunction has been demonstrated in the subcutaneous and sublingual tissues in COVID-19 patients. The presence of coronary microvascular dysfunction (CMD) has also been hypothesized, but direct evidence demonstrating CMD in COVID-19 patients is missing. In the present study, we aimed to investigate CMD in patients hospitalized with COVID-19, and to understand whether there is a relationship between biomarkers of myocardial injury, myocardial strain and inflammation and CMD. METHODS: 39 patients that were hospitalized with COVID-19 and 40 control subjects were included to the present study. Biomarkers for myocardial injury, myocardial strain, inflammation, and fibrin turnover were obtained at admission. A comprehensive echocardiographic examination, including measurement of coronary flow velocity reserve (CFVR), was done after the patient was stabilized. RESULTS: Patients with COVID-19 infection had a significantly lower hyperemic coronary flow velocity, resulting in a significantly lower CFVR (2.0 ± 0.3 vs. 2.4 ± 0.5, p < .001). Patients with severe COVID-19 had a lower CFVR compared to those with moderate COVID-19 (1.8 ± 0.2 vs. 2.2 ± 0.2, p < .001) driven by a trend toward higher basal flow velocity. CFVR correlated with troponin (p = .003, r: -.470), B-type natriuretic peptide (p < .001, r: -.580), C-reactive protein (p < .001, r: -.369), interleukin-6 (p < .001, r: -.597), and d-dimer (p < .001, r: -.561), with the three latter biomarkers having the highest areas-under-curve for predicting CMD. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with COVID-19 and is related to the severity of the infection. CMD may also explain the "cryptic" myocardial injury seen in patients with severe COVID-19 infection.

Soluble low density lipoprotein receptor-related protein-1 levels in the differential diagnosis of myopericarditis versus acute coronary syndrome.

INTRODUCTION: Differential diagnosis of myopericarditis (MPC) versus acute coronary syndromes (ACS) can be difficult in the emergency room (ER). Low density lipoprotein receptor-related protein-1 (LRP-1) is a transmembrane receptor with diverse biological functions. LRP-1 is increased after viral infections as a defense mechanism. sLRP-1 (soluble form) can be measured in the serum. We study the diagnostic sLRP-1 levels in patients with MPC, ACS and healthy controls. METHODS: The study included consecutive patients who were admitted between the dates of 1.1.2018 and 1.1.2019 with the diagnosis of MPC or ACS. All patients reported to the ER with chest pain (CP) and elevated cardiac troponin levels. Control group (n = 61) was selected from healthy subjects. In addition to routine laboratory work up, serum sLRP-1 concentrations were measured on admission. RESULTS: sLRP-1 levels were significantly higher in MPC, compared to controls (p = 0.005) and ACS (p = 0.001). Median (IQR) sLRP-1 levels in MPC, controls and ACS were 7.39 (22.42), 2.27 (1.74), 2.41 (0.98) µg/ml, respectively (p = 0.004). Among the covariates: sLRP-1, age, gender, HDL-C and LDL-C; only sLRP-1 differentiated a diagnosis of MPC versus ACS (OR = 1684, p = 0,046, CI for OR (1008-2812). The area under the curve (AUC) was measured as 0.79 [CI 0.62-0.95] in ROC analysis, p = 0.001; sLRP-1 had 69% sensitivity and 85% specificity for diagnosis of MPC with a cut-off value of 4.3 µg/ml. CONCLUSION: sLRP-1 is a potential biomarker in the differential diagnosis of MPC versus ACS in ER. Future studies are needed to evaluate and develop the utility of sLRP-1 as a diagnostic and prognostic biomarker in MPC.

Post-cardiac injury syndrome after a concealed accessory pathway ablation.

The incidence of pericardial effusion for supraventricular tachycardias is less than 1%, and its combination with pleural effusion is rare. We present a case of severe pericardial and pleural effusion after a left-sided concealed accessory pathway ablation. The 480 cc of pericardial fluid was drained with the pericardial drainage system due to cardiac tamponade with hemodynamic compromise. The chest X-ray and thorax computed tomography showed moderate left-sided pleural effusion after pericardiocentesis. We considered the inflammatory response as the pathophysiology of the situation; we started ibuprofen 800 mg t.i.d. and colchicine 0.5 mg o.d. At a 3-week follow-up, her X-ray revealed the resolution of pleural effusion, and the echocardiography showed no pericardial effusion. .

Coronary flow velocity reserve is reduced in patients with an exaggerated blood pressure response to exercise.

Coronary artery disease and cardiovascular mortality are increased in patients with an exaggerated blood pressure response to exercise. The exact cause of this increase remains unknown, but previous studies have indicated the presence of endothelial dysfunction in peripheral arteries and subclinical atherosclerosis in these patients. The present study aimed to clarify whether coronary microvascular dysfunction is also present in patients with exaggerated blood pressure response to exercise. A total of 95 patients undergoing exercise testing were consecutively enrolled. Flow-mediated vasodilatation and carotid intima-media thickness were measured using standardized methods. A transthoracic echocardiography examination was performed to measure coronary flow velocity reserve. Patients with an exaggerated blood pressure response to exercise had significantly lower coronary flow velocity reserve than the controls (2.06 (1.91-2.36) vs. 2.27 (2.08-2.72), p = 0.004), and this difference was caused by a reduction in hyperemic flow velocity (57.5 (51.3-61.5) vs. 62.0 (56.0-73.0), p = 0.004) rather than a difference in basal flow (26.5 (22.3-29.8) vs. 26.0 (24.0-28.8), p = 0.95). Patients with an exaggerated blood pressure response to exercise also had a significantly greater carotid intima-media thickness and significantly lower flow-mediated vasodilatation than controls. However, an exaggerated blood pressure response to exercise remained a significant predictor of coronary microvascular dysfunction after adjusting for confounders (OR: 3.60, 95% CI: 1.23-10.54, p = 0.02). Patients with an exaggerated blood pressure response to exercise show signs of coronary microvascular dysfunction, in addition to endothelial dysfunction and subclinical atherosclerosis. This finding might explain the increased risk of coronary artery disease and cardiovascular mortality in these patients.