Inflammatory cytokines differ between patients with high versus low CHA2DS2-VASc scores in sinus rhythm-a possible mechanism for adverse cardiovascular events.

Background: The CHA2DS2-VASc score was shown to predict systemic thromboembolism and mortality in certain groups of patients in sinus rhythm (SR). Previous data showed that patients in SR with high CHA2DS2-VASc score have higher plasma levels of inflammatory markers such as sP-selectin and C-reactive protein. We further investigated this group. Methods: Blood samples were collected from consecutive patients in SR. Plasma was extracted and stored at -80 °C. Concentrations of a panel of soluble markers IL-1ß, IL-6, IL-8, IL-10, TNF-α and VEGF were measured by Magnetic Luminex Performance Assay. The PLF4 cytokine blood level was measured by ELISA. Results: 66 patients were enrolled (age 53 ± 18 years, 60% women). Patients with high CHA2DS2-VASc scores (n = 23) had significantly higher median IQR concentrations of TNF-α [10.34 (8.55,14.92) vs. 7.69 (6.06, 9.85) pg/ml, p = 0.009] and a trend towards higher levels of IL-1ß [0.59 (0.4,0.8) vs. 0.44 (0.31, 0.62) pg/ml, p = 0.07] and IL-8 [5.92 (4.5,9.4) vs. 5.04 (3.63, 6.04) pg/ml, p = 0.07], compared to the group with low scores (n = 43). Median IQR concentrations of VEGF, IL-6, IL-10 and PF4 did not significantly differ between the CHA2DS2-VASc score groups. Conclusion: Patients in SR with high versus low CHA2DS2-VASc scores have high plasma concentrations of systemic inflammation cytokines. The already proven high levels of sP-selectin, that promotes release of inflammatory cytokines from leukocytes, is in line with these results. This pro-inflammatory state in patients with high CHA2DS2-VASc scores, may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score even without atrial fibrillation.

Comparison of Factors Associated with Inflammation, Thrombosis, and Platelet Reactivity as well as Turnover between Patients with High versus Low CHA2DS2-VASc without Atrial Fibrillation.

BACKGROUND: The CHA2DS2-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF). OBJECTIVES: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA2DS2-VASc score in SR. METHODS: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA. RESULTS: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA2DS2-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA2DS2-VASc group (45, interquartile ratio [IQR] 36-49) vs. 37 (IQR 28-46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7-9.3) vs. 1.6 (IQR 0.78-5.4), P < 0.001; NLR 2.7 (IQR 2.1-3.8) vs. 2.1 (IQR 1.6-2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups. CONCLUSIONS: Patients in SR with high CHA2DS2-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score.

Acute myocardial infarction in the Covid-19 era: Incidence, clinical characteristics and in-hospital outcomes-A multicenter registry.

BACKGROUND: We aimed to describe the characteristics and in-hospital outcomes of ST-segment elevation myocardial infarction (STEMI) patients during the Covid-19 era. METHODS: We conducted a prospective, multicenter study involving 13 intensive cardiac care units, to evaluate consecutive STEMI patients admitted throughout an 8-week period during the Covid-19 outbreak. These patients were compared with consecutive STEMI patients admitted during the corresponding period in 2018 who had been prospectively documented in the Israeli bi-annual National Acute Coronary Syndrome Survey. The primary end-point was defined as a composite of malignant arrhythmia, congestive heart failure, and/or in-hospital mortality. Secondary outcomes included individual components of primary outcome, cardiogenic shock, mechanical complications, electrical complications, re-infarction, stroke, and pericarditis. RESULTS: The study cohort comprised 1466 consecutive acute MI patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with STEMI: 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. Although STEMI patients admitted during the Covid-19 period had fewer co-morbidities, they presented with a higher Killip class (p value = .03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122-292) in 2018 to 290 minutes (IQR 161-1080, p < .001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint in the multivariable regression model (OR 1.65, 95% CI 1.03-2.68, p value = .04). Furthermore, the rate of mechanical complications was four times higher during the Covid-19 era (95% CI 1.42-14.8, p-value = .02). However, in-hospital mortality remained unchanged (OR 1.73, 95% CI 0.81-3.78, p-value = .16). CONCLUSIONS: STEMI patients admitted during the first wave of Covid-19 outbreak, experienced longer total ischemic time, which was translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events, compared with parallel period.

Measurements of immature platelet fraction and inflammatory markers in atrial fibrillation patients - Does persistency or ablation affect results?

PURPOSE: Atrial fibrillation (AF) is associated with platelet hyperactivity and a higher proportion of immature platelets. We aimed to examine whether immature platelet fraction (IPF) and inflammatory markers differ between AF types and whether they are affected by ablation. METHODS: A prospective study included patients with atrial fibrillation/flutter (AFL). We excluded patients with hematologic, inflammatory, or acute coronary states. Blood samples for IPF, white blood cells (WBC), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP) were collected at baseline, within one-hour postablation in those undergoing ablations, and the day after ablation. IPF was measured by an autoanalyzer (Sysmex 2100 XE). RESULTS: One hundred and four patients were included (paroxysmal AF-63, persistent AF-36, AF and AFL-7, AFL alone-5), (Mean age 67.7 ± 12.8 years, 54.8% male, CHA2 D2 -VASC2 3.2 ± 1.8). Seventy-two patients underwent ablation (cryoballoon AF ablation-60, AFL radiofrequency ablation-5, both-7). There was no difference between paroxysmal and persistent AF regarding baseline markers. There was a significant change in the following parameters after ablation: WBC (baseline 6.9 ± 2.0, 1-h post 8.0 ± 2.4, and 1-day post 9.0 ± 2.8 ×109 /L), NLR (2.9 ± 2.2, 3.0 ± 2.4, 4.2 ± 2.9, respectively), and CRP (3.6 ± 3.7, 3.6 ± 3.5, 12.4 ± 9.0 mg/L, respectively) (P < .05 for all). However, there were no differences in immature platelet count (8.6 ± 4.8, 8.5 ± 4.9, 8.4 ± 5.2 ×109 /L) or IPF (4.6 ± 3.2, 4.7 ± 3.3, 4.9 ± 3.6%) from baseline to postablation (p = NS). CONCLUSIONS: AF persistency does not affect IPF and inflammation. In patients undergoing cryoablation of AF, there is a postablation inflammatory process; however, platelet activation is probably not affected.

Neutrophil Gelatinase-Associated Lipocalin for the Early Prediction of Acute Kidney Injury in ST-Segment Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention.

INTRODUCTION AND OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI). METHODS: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range. RESULTS: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p < 0.001) and 24 h (142 ± 41 vs. 93 ± 36; p < 0.001). Per ROC curve analysis, an optimal cutoff value of NGAL (>120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801-0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013-1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001-1.036; p = 0.04). CONCLUSIONS: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.