Point-of-Care Testing for Multiple Cardiac Markers Based on a Snail-Shaped Microfluidic Chip

Existing methods for detecting cardiac markers are difficult to be applied in point-of-care testing (POCT) due to complex operation, long time consumption, and low sensitivity. Here, we report a snail-shaped microfluidic chip (SMC) for the multiplex detection of cTnI, CK-MB, and Myo with high sensitivity and a short detection time. The SMC consists of a sandwich structure: a channel layer with a mixer and reaction zone, a reaction layer coated with capture antibodies, and a base layer. The opening or closing of the microchannels is realized by controlling the downward movement of the press-type mechanical valve. The chemiluminescence method was used as a signal readout, and the experimental conditions were optimized. SMC could detect cTnI, CK-MB, and Myo at concentrations as low as 1.02, 1.37, and 4.15. The SMC will be a promising platform for a simultaneous determination of multianalytes and shows a potential application in POCT.

Coronary computed tomography angiography vs.standard of care for evaluation of NSTE-ACS: a systematic review and meta-analysis

Background Non-ST elevation acute coronary syndrome (NSTE-ACS) is one of the common cardiac emergencies that pose a diagnostic challenge, especially in the absence of EKG changes or elevation in cardiac markers. Coronary computed tomography angiography (CT) has an established role in the evaluation of stable chest pain with ESC giving it class I recommendation. The role of CCTA in the management of NSTE-ACS is less clear. Purpose To evaluate the hypothesis of CT efficacy in identifying and managing patients with NSTE-ACS in comparison to the standard of care (SOC). Methods We searched MEDLINE, EMBASE, and Cochrane Central for randomized controlled trials (RCT) that compared initial CT utilization vs SOC in patients presenting with acute chest pain with suspected or confirmed NSTE-ACS. SOC arm included initial evaluation and triaging by treating physician including but not limited to clinical observation, serial cardiac markers, stress testing, and invasive coronary angiography (ICA). Studies with follow-up data of 1 month or more were included. Outcomes evaluated were incidence of rehospitalization/ER visits post index visit, referral to ICA, and presence of significant lesion during ICA requiring revascularization. Results A total of 6,862 patients (3,663 in the CT arm and 3,199 in the SOC) were analyzed from 13 RCTs. No statistically significant difference was noted between two intervention arms with regards to repeat hospital visits [Odds ratio (OR): 1.02; 95% CI: 0.85–1.24; P=0.82; I2=0%], and referral to ICA (OR: 1.32: 95% CI: 0.95–1.83; P=0.10; I2=66). CT was however more likely to uncover significant lesions requiring revascularization compared to SOC arm (OR: 1.77; 95% CI: 1.32–2.37; P=0.0001; I2=23%]. Conclusion Our meta-analysis showed that in patients with suspected NSTE-ACS, CT is associated with similar rates of ICA referral and re-admissions albeit being more likely to uncover hemodynamically significant lesions that require revascularization. These findings are consistent with the finding of the recently published VERDICT trial that showed comparable efficacy between coronary CT and ICA. Further studies evaluating the long term cardiovascular outcomes are warranted. FUNDunding Acknowledgement Type of funding sources: None.

Changes of resting cardiac marker levels due to sport adaptation

Background In acute and chronic heart diseases some cardiac necroenzymes and peptide fragments are essential during the diagnosis and following the progression of the diseases. Previous literature data are available about elevation of these cardiac markers after exhausting physical activity, but we do not have information about the resting levels in athletes. Methods In part of the extended cardiology screening of athletes in our institute, we analyzed the levels of hsTroponinT, CKMB, LDH and NT-proBNP from blood samples. All the samples were collected at least 12 hours after the last trainings or competitions. The results of the athletes were compared with a healthy sedentary non-athlete control group. After the blood collection all subject underwent echocardiography examinations and cardiopulmonary exercise testing. Depending on normality, groups were compared with two-tailed Student's t-test or Mann-Whitney U-test. Statistical analysis was processed in RStudio development environment. Results Results of 335 athletes from different sports (male: 162, age: 18.9±5.9 years, training: 15.8±5.9 hours/week) and 53 sedentary non-athletes (male: 23, age: 19.8±3.2 years, training: 2.7±2.3 hours/week) were compared. In athletes, increased level of hsTroponinT was found in 3.3% (n=11), of CKMB in 5.7% (n=18), of LDH in 2.7% (n=9) and of NT-proBNP in 1.2% (n=4). In the control group no elevation was found regarding the CKMB and hsTroponinT, while slightly elevated values of LDH and NT-proBNP were revealed in 1–1 cases. In athletes we measured higher CKMB (17.5±6.8 vs 12.3±3.4 U/l, p<0.001) and LDH values (323.7±63.3 vs 286.0±51.1 U/l, p<0.001), and lower values of NT-proBNP (27.2±29.2 vs 49 8±38.7 pg/ml, p<0.001) compared to the control group, while in the hsTroponinT levels (4.3±1.4 vs 5.6±6.3 ng/l, p=0.33) no significant changes were measured. In term of the examined laboratory parameters significant correlation was found with maximal relative aerob capacity (CKMB: r=0.23, p<0.001; LDH: r=0.18, p<0.001; hsTroponinT: r=0.23, p<0.001; NT-proBNP: r=−0.22, p<0.001), but no correlation was found with age. Significant correlation was found between NT-proBNP levels and echocardiographic measurements of ventricular diameters and left ventricular wall thickness (LVEDD r=−0.15, p<0.03; LVESD r=−0.18, p<0.03; RVD: r=−0.15, p<0.02; IVS: r=−0.22, p<0.001; PWD r=−0.27, p<0.001), CKMB levels correlated with left ventricular wall thickness (IVS: r=0.11, p<0.05; PWD r=0.14, p<0.02). Conclusions Based on our results, in connection with the sports adaptation of the heart, the resting levels of the cardiac markers also show significant changes, these changes are correlated with aerobic endurance and structural sport adaptation parameters as well. Our study draws attention to the importance of different assessment of cardiac markers in athletes. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary (K 135076).Supported by the ÚNKP-20-3-I-SE-41 New National Excellence Program of the Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation fund.

Cardioprotective Potential of Garlic Oil and Its Active Constituent, Diallyl Disulphide, in Presence of Carvedilol during Chronic Isoprenaline Injection-Mediated Myocardial Necrosis in Rats

In isoprenaline (ISO)-induced myocardial infarcted rats, garlic oil (GO) and its main ingredient, diallyl disulfide (DADS), were examined for cardioprotective effects when used with carvedilol (CAR). GO, DADS and CAR were given to rats in their respective groups, either alone or together, with the addition of isoprenaline (3 mg/kg/day, subcutaneously) during the last 10 days of treatment. At the end of 14 days of treatment, blood samples were collected, the hearts were excised under anesthesia and weighed. Heart tissue homogenate was used to measure superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Furthermore, the serum activities of cardiac markers, including lactate dehydrogenase, creatine kinase, and cardiac troponin, were checked. Moreover, inflammatory markers including tumor necrosis factor alpha, interleukin one beta, interleukin six, and kappa bp65 subunit were assessed. Rats that received GO, DADS, and CAR exhibited a significant increase in the cardiac antioxidant enzyme activities with a simultaneous decrease in serum cardiac markers enzymes and inflammatory markers. The TBARS were significantly reduced in rats that received treatment. The addition of carvedilol to GO or DADS significantly elevated antioxidant activities and decreased the release of cardiac enzymes into blood circulation. Both DADS and GOl were almost similar in efficacy, indicating the potential role of DADS in garlic oil-mediated cardioprotection. Combining GO or DADS with CAR increased CAR’s cardioprotective impact and protected rats from developing ISO-induced myocardial infarction.

Myoglobin Offers Higher Accuracy Than Other Cardiac-Specific Biomarkers for the Prognosis of COVID-19

Although sporadic studies have shown that myoglobin may have better prognostic performance than other cardiac markers in COVID-19, a comprehensive comparative study is lacking. Herein, we retrospectively analyzed the clinical and laboratory data of COVID-19 patients admitted to the Guanggu Campus of Wuhan Tongji Hospital from February 9, 2020 to March 30, 2020, intending to compare the prognostic accuracy of three commonly used cardiac markers on COVID-19 mortality. Our results revealed that abnormal increases in myocardial biomarkers were associated with a significantly increased risk of in-hospital mortality with COVID-19. Interestingly, myoglobin, a non-cardiac-specific biomarker, also expressed in skeletal myocytes, had even higher prognostic accuracy than cardiac-specific biomarkers such as high-sensitivity troponin I (hs-TnI) and creatine kinase-MB (CK-MB). More importantly, multivariate Cox analysis showed that myoglobin, rather than hs-TnI or CK-MB, was independently prognostic for in-hospital mortality in COVID-19. These results were further confirmed by subgroup analyses of patients with severe and critical illnesses and those without a history of cardiovascular disease. Our findings suggest that myoglobin may be a reliable marker of illness reflecting general physiological disturbance and help to assess prognosis and treatment response in patients with COVID-19.