Marker Of Myocardial Ischemia Research Articles

Hydrogel-Integrated Heart-on-a-Chip Platform for Assessment of Myocardial Ischemia Markers.

Organ-on-a-chip platform scans offer a controllable environment and a physiological similarity to mimic human pathophysiology. In this study, a single-channel PDMS microchip was fabricated, characterized, and optimized to obtain a heart-on-a-chip platform, which is integrated with a hydrogel scaffold suitable for cardiomyocyte growth inside its channel. Single-channel chips with a size of 20 × 12 mm and a channel height ranging from 60 to 100 μm were produced using photolithography and soft lithography techniques. A gelatin-embedded alginate network-based hydrogel was further augmented with 3% (v/v) collagen type I. Pore sizes were in the range of 74-153 μm for H9C2 implantation and biomimicry. The hydrogels are characterized both on PDMS surfaces and in capillaries. The primary feature distinguishing this study from previous microchip studies is that it mimics the cell microenvironment much better using different hydrogel formulations instead of creating a 2D cell culture by passing fluids, such as fibronectin, for cell adhesion. Instead of using complex microchip designs, the chip system we created intends to provide a physiologically relevant copy by using a 3D cell culture to its advantage and a simple, single-channel architecture. The microchip study was combined with cardiomyocytes to create the heart-on-a-chip system and tested under normoxic and hypoxic conditions to create a myocardial ischemia model inside this channel. As a result, this heart-on-a-chip platform was shown to be utilized for the detection of several small-size biomarkers such as adenosine, ADP, lactic acid, l-isoleucine, l-glutamic acid, and oxidized glutathione via LC-MS/MS from control conditions and a myocardial ischemia model. Cell-embedded and hydrogel matrix-supported versions of this heart-on-a-chip system were successfully prepared and shown to provide powerful outputs with myocardial ischemia markers. In light of this research, these outputs aim to develop simple and biologically effective organ-on-a-chip systems for future research.

Ischemia-induced alterations in the electrocardiogram of salmonid fish

Cardiovascular diseases such as coronary arteriosclerosis are widespread and constitute severe health and welfare problems for both farmed and wild salmonid fish. However, effective tools for rapid screening and analysing heart diseases in fish do not currently exist. Electrocardiogram (ECG) recordings are widely used for screening and diagnosing numerous cardiac pathologies in humans, but the use of ECG techniques to diagnose and characterize cardiac abnormalities in fish is still in its infancy. In this study, we induced myocardial ischemia in anaesthetized rainbow trout by surgical coronary artery ligation. Additionally, we experimentally manipulated the fish's heart rate and environmental oxygen availability by altering gill water flow and oxygen saturation (i.e., no flow, normoxic flow and hyperoxic flow), and analyzed changes in the ECG profile in detail. The main ECG abnormalities observed in fish with ligated coronaries in normoxia were atrioventricular blocks, prolonged QRS duration, reduced QRS amplitude and changes in the ST-segment such as the presence of early repolarization pattern. Furthermore, when gill water flow was stopped, fish exhibited pronounced hypoxic bradycardia, which alleviated all ECG abnormalities in coronary ligated fish. This is the first study to provide a detailed characterization of electrocardiographic markers of myocardial ischemia in fish. Our study shows that hypoxic bradycardia improves cardiac electrical conductivity, presumably by reducing mismatches in myocardial oxygen supply and demand. Yet, the importance of avoiding hypoxic bradycardia in experimental and biomedical studies on anaesthetized fish is highlighted as it can potentially lead to incorrect ECG interpretations.

Electrocardiograms Do Not Detect Myocardial Ischemia in Patients With Williams Syndrome and Nonsyndromic Elastin Arteriopathy With Coronary Artery Stenosis

Coronary artery stenosis (CAS) may affect up to 27% of patients with Williams syndrome (WS), which may lead to myocardial ischemia. Patients with WS face a 25- to 100-fold greater risk of sudden cardiac death, frequently linked to anesthesia. Assessing CAS requires either imaging while under general anesthesia or intraoperative assessment, with the latter considered the gold standard. Our study aimed to identify electrocardiogram (ECG) markers of myocardial ischemia in patients with WS or nonsyndromic elastin arteriopathy and documented CAS. We retrospectively reviewed patients with WS/elastin arteriopathy who underwent supravalvar aortic stenosis surgery and CAS assessment from January 1, 2006 to April 30, 2021. A pediatric electrophysiologist, not aware of the patients' CAS status, reviewed their preoperative ECGs for markers of ischemia. We assessed associations of study parameters using Wilcoxon rank-sum and Fisher's exact tests. Of 34 patients, 62% were male, with a median age of 20 months (interquartile range: 8 to 34). CAS was present in 62% (21 of 34), 76% of whom (16 of 21) were male. There were no ECG indicators of myocardial ischemia in patients with CAS. In conclusion, CAS was present in >1/2 the children with WS/elastin arteriopathy who underwent repair of supravalvar aortic stenosis. CAS in WS/nonsyndromic elastin arteriopathy does not appear to exhibit typical ECG-detectable myocardial ischemia. ECGs are not a useful screening tool for CAS in WS/elastin arteriopathy. Given the high anesthesia-related cardiac arrest risk, other noninvasive indicators of CAS are needed.

Changes in circulating ApoJ-Glyc levels in patients with suspected acute coronary syndrome: The EDICA trial

BackgroundMyocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. ObjectiveThis proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). MethodsIn suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). Results404 patients were recruited; 291 were given a clinical diagnosis of “non-ischemic” chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with “non-ischemic” patients (66 [46–90] vs. 73 [56–95] μg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. ConclusionsCirculating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with “non-ischemic” patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.

SEX DIFFERENCES IN PULSE WAVE AND SUBENDOCARDIAL VIABILITY RATIO IN HYPERTENSIVE PATIENTS

Objective: Myocardial ischemia represents the main cause of morbidity and mortality in hypertensive patients in both women and men, although some difference in pathophysiology and in the exposure to risk factors may explain the lower global cardiovascular risk of women. Sex differences in the structure and function of the cardiovascular system may affect the aortic pressure wave and the functional balance in myocardial perfusion determined by central aortic pressure, which may lead to myocardial ischemia and type 2 myocardial infarction. Design and method: In a population of 318 treated hypertensive patients (162 females, 156 males) referring to a single Hypertension centre (University of Trieste, Italy), we measured peripheral blood pressure and performed arterial applanation tonometry (PulsePen, DiaTecne, Italy) to determine central blood pressure waveform, aortic pulse wave velocity (PWV), augmentation index (AIx), pulse wave separation analysis with timing and amplitude of forward (fT, fP) and backward reflected (bT, bP) waves, and the subendocardial viability ratio (SEVR), i.e. the ratio between diastolic and systolic pressure-time index, as a risk marker of myocardial ischemia. Results: Despite similar peripheral systolic and diastolic blood pressure values, heart rate and PWV between sexes, females showed a longer forward pressure wave duration (119.8±38.6 vs 105.0±30.4 ms, p<0.0001) and lower amplitude (52.7±19,4 vs 57.1±19.3 mmHg, p = 0.039) compared to males. Backward pressure waved were similar in timing and amplitude between males and females. The difference in forward wave caused a marked higher AIx (19.5±12.4 vs 11.9±14.9, p<0.0001) and a lower SEVR (101.6±24.4 vs 108.5±27.7, p = 0.018) in women compared to men. Conclusions: Hypertensive women and men showed significant differences in forward pressure wave, causing a significant increase in AIx and a decreased SEVR in women compared to men. This may have important implications in sex-specific risk and myocardial ischemia.

Safety of intracoronary iopromide solution for experimental pharmaco-cold ex vivo preservation of donor heart

Objective: To evaluate the effect of intracoronary iopromide (Ultravist®, Bayer, AG, Leverkusen, Germany) during pharmaco-cold ex vivo preservation of a donor heart on the restoration of heart pumping function and cardiomyocyte metabolism in the early post-transplant period.Methods: Black-and-white calves aged 3 months were used as an experimental model. In the control group, pharmaco-cold preservation of the donor heart was performed by injecting 2 liters of custodiol (Custodiol®, Dr. Franz Köhler Chemie GmbH, Bensheim, Germany) into the aortic root. The hearts were then stored in an appropriate solution at 0 to 1°C for 2 hours. In the experimental group (n = 6), a solution of iopromide and custodiol were injected into the aortic root at a ratio of 50:50 under a pressure of 70-80 mm Hg for 5 minutes after 120 minutes of preservation. Then the coronary bed was washed with 1 liter of custodiol at a pressure of 40 mm Hg and orthotopic heart transplantation was performed. In the post-transplant period, the parameters of central hemodynamics, myocardial oxygen consumption, and the levels of myocardial ischemia markers (troponin I, creatine phosphokinase-MB, lactate dehydrogenase) were assessed.Results: Twelve orthotopic heart transplantations were performed during the study. In 120 minutes after the restoration of spontaneous cardiac activity, the level of cardiac output was 5.11 [4.99; 5.41] L/min and 5.77 [4.97; 6.62] L/min (p = 0.0009) in the control and experimental groups, respectively. Changes in the concentration of lactate dehydrogenase, troponin I and lactate in the blood flowing from the coronary sinus were significantly higher in the early reperfusion period. However, no statistically significant difference was observed between the groups (p > 0.05). Myocardial oxygen consumption was significantly reduced at reperfusion. However, the initial values were restored by reperfusion minute 60 without any significant intergroup difference (p > 0.05).Conclusion: We established the safety of intracoronary iopromide administration for pharmaco-cold ex vivo preservation of the donor heart. Intracoronary administration of iopromide solution does not affect the restoration of the pumping function of the heart or metabolism in cardiomyocytes in the early post-transplant period. Received 6 May 2022. Revised 14 June 2022. Accepted 11 July 2022. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Contribution of the authorsConception and study design: M.O. Zhulkov, D.A. Sirota, I.S. ZykovData collection and analysis: M.O. Zhulkov, I.S. Zykov, A.K. Sabetov, H.A. Agaeva, A.G. Makaev, D.M. Osintsev, A.E. Kalendarev, A.P. Nadeev, V.E. Kliver, A.R. Tarkova, M.A. Ovchinnikova, N.A. Karmadonova, D.V. KhomushkuStatistical analysis: M.O. Zhulkov, A.G. MakaevDrafting the article: M.O. ZhulkovCritical revision of the article: M.O. Zhulkov, D.A. Sirota, I.S. Zykov, A.V. FomichevFinal approval of the version to be published: M.O. Zhulkov, D.A. Sirota, I.S. Zykov, A.K. Sabetov, H.A. Agaeva, A.G. Makaev, D.M. Osintsev, A.E. Kalendarev, A.P. Nadeev, V.E. Kliver, A.R. Tarkova, M.A. Ovchinnikova, A.V. Fomichev, N.A. Karmadonova, D.V. Khomushku

Evaluating Ischemia-Modified Albumin as an Early Biomarker for Hypertensive Disorders During Pregnancy: A Case-Control Study.

Background Ischemia-modified albumin (IMA) is looked upon as a newer marker of myocardial ischemia. There is a paucity of literature however with regardto studies correlating levels of IMA in patients with hypertensive disorders of pregnancy. The present study therefore aimed at estimating the levels of IMA in patients with gestational hypertension and assessing its utility in predicting hypertensive disorders of pregnancy. Methods The present study was a hospital-based case-control study conducted in the Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Nagpur. IMA was estimated in 30 controls (Group I) and 20 cases of gestational hypertension (Group II) using a spectrophotometric assay detecting free unbound Cobalt left behind. The clinical data and lab results were presented as mean ± SD. Student's t-test was applied and Pearson's correlation coefficient was calculated. A value of p < 0.05 was taken as statistically significant. The ROC (Receiver Operator Characteristic) curve was used to establish the cut-off of serum IMA levels in pregnancy-induced hypertension (PIH). Results There was no significant difference in age and period of gestation (POG) at the time of sample collection between the groups. There was a significant difference in the systolic and diastolic blood pressures (BPs) of both groups. The mean level of serum IMA was significantly higher in cases of gestational hypertension (0.88 ± 0.14 absorbance units {ABSU}) as compared to controls (0.69 ± 0.08 ABSU) (p<0.001). On correlation analysis, the systolic and diastolic BPs were found to be highly positively correlated with serum IMA levels (p<0.001). ROC curve analysis suggested that at a cut-off of 0.73 ABSU, IMA has 85% sensitivity and 80% specificity for predicting gestational hypertension. Conclusion Statistically significant results of serum IMA levels obtained in gestational hypertension which falls on the lesser severe spectrum of the diseaseimply that serum IMA can be used for early diagnosis of gestational hypertension and impending Pre-eclampsia (PE) and Eclampsia.

ApoJ-Glyc, an early marker of myocardial ischaemia, rapidly maps improved myocardial perfusion in STEMI patients undergoing successful primary PCI

Abstract Background Previous studies using experimental models and clinical retrospective samples have pointed to a potential role of glycosylated apolipoprotein J (ApoJ-Glyc) as a marker for the early detection of myocardial ischaemia. Ischaemia induces intracellular accumulation of non-glycosylated ApoJ that mirrors the reduction in ApoJ-Glyc serum levels in patients presenting with ST-segment elevation myocardial infarction (STEMI). Purpose The EDICA (Early Detection of Myocardial Ischaemia in Suspected Acute Coronary Syndromes by Apo J-Glyc as a Novel Pathologically based Ischaemia Biomarker) clinical trial assessed the performance of ApoJ-Glyc as a biomarker for the early detection of myocardial ischaemia in patients attending the A&amp;E department with chest pain suggestive of acute coronary syndrome. Here, we report the observed changes in ApoJ-Glyc concentration in STEMI patients at baseline and after primary percutaneous coronary intervention (PPCI). Methods The EDICA trial, a multi-centre (10 sites), international, in vitro diagnostic study, assessed 404 patients attending the A&amp;E department with suspected ACS. Of these, 291 patients had a final diagnosis of “non-ischaemic” event and 113 of “ischaemic” event. The main inclusion criterion was chest pain of suspected cardiac origin. Blood samples were obtained for the simultaneous assessment of high sensitivity-troponin and ApoJ-Glyc on admission (time 0) and at 1h and 3h thereafter. Two different glycosylated variants of ApoJ (ApoJ-GlycA2 and ApoJ-GlycA6) were analyzed with a novel ELISA in serum samples. Of the “ischaemic” patients, 33 had STEMI, of whom 85% underwent PPCI. Results As expected, in the presence of myocardial ischaemia, time 0 ApoJ-GlycA2 and ApoJ-GlycA6 serum levels decreased by 34% and 48%, respectively in STEMI patients, compared with non-ischaemic patients, i.e. ApoJ-GlycA2 in STEMI: 66 [52–95] μg/ml vs. non-ischaemic: 100 [72–131] μg/ml; P=0.0002; ApoJ-GlycA6 STEMI: 38 [34–67] vs. non-ischaemic: 73 [56–95] μg/ml; P&amp;lt;0.0001. ApoJ-GlycA6 showed a discriminating ability for the presence of STEMI with a 67% sensitivity and a 83% specificity (AUC=0.747, cut-off of 50μg/ml). In STEMI patients in whom PPCI successfully restored TIMI 3 flow, ApoJ-Glyc levels increased rapidly and significantly compared with time 0 levels (ApoJ-GlycA2: P=0.02 and P=0.003 for 1h and 3h; ApoJ-GlycA6: P=0.02 and P=0.002 for 1h and 3h) and compared to patients in whom PPCI was not performed (Table 1). Conclusions ApoJ-Glyc concentrations are reduced in STEMI patients on admission and increase rapidly after improved perfusion with PPCI, pointing to a potential role of this biomarker in the early detection of reversible ischaemia and the mapping of reversible changes. The mechanisms whereby ApoJ-Glyc levels rapidly and markedly increase after PPCI are speculative at present and deserve further investigation, together with the potential prognostic value of ApoJ-Glyc in this setting. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission 2020-EIC-SMEInstrument Phase 2; Spanish Ministry of Science, Innovation and Universities

Results of a study of the effectiveness of direct coronary oxygen persufflation as a donor heart conditioning method

Objective: to evaluate the technical feasibility as well as functional, metabolic and structural integrity of donor heart myocardium after 4 hours of direct intracoronary oxygen persufflation in an experiment. Materials and methods. Mini-pig siblings aged 3 months with a body weight of 23–36 kg were used as the experimental model. In the control group (n = 8), donor hearts were cold preserved by injecting 2 liters of Bretschneider cardioplegic solution (Custodiol®, Germany, HTK) into the aortic root. In the experimental group (n = 8), modified HTK solution (with 40 mg/L hyaluronidase added) was used to initiate cardioplegia, then moistened carbogen (95% O2, 5% CO2) was injected into the ascending aorta, maintaining 40–45 mm Hg aortic root pressure. The hearts were stored in an mHTK solution at 0–4 °С. After 3 hours of donor heart preservation, orthotopic heart transplantation (OHTx) was performed. In the post-transplant period, we studied central hemodynamic parameters, myocardial oxygen consumption, level of myocardial ischemia markers (troponin I, TnI; creatine phosphokinase-MB, CPKMB; lactate dehydrogenase, LDH), and histological signs of structural cellular injury. Results. Sixteen OHTx surgeries were performed during the study. At 120 minutes after restoration of spontaneous cardiac activity, cardiac output was 2.99 [4.85; 3.17] L/min and 2.48 [2.04; 2.92] L/min (p &gt; 0.05) in the control and experimental groups, respectively. Changes in LDH, TnI and lactate levels in the blood flowing from the coronary sinus were significantly higher in the early reperfusion period. However, there was no statistically significant difference between the groups (p &gt; 0.05). Myocardial oxygen consumption in the control and experimental groups was 8.2 [7.35; 9.35] ml-O2/min/100 g and 7.7 [6.75; 10.12] ml-O2/min/100 g, respectively (p &gt; 0.05). Morphological examinations also showed no significant myocardial ischemia injury in the persufflation group compared to the control group. Conclusion. The experiment showed the technical feasibility and safety of direct intracoronary oxygen persufflation for 4 hours at the ex vivo donor heart conditioning stage. At the same time, experimental data showed no significant advantages of coronary persufflation over the standard protocol of cold preservation of donor heart with Bretschneider cardioplegic solution.

T Wave Alternans Preceding ST Segment Depression as a Sign of Myocardial Ischemia During Treadmill Test

We observed a case where T wave alternans preceded classical ischemic ST segment depression during treadmill stress test. T wave alternans is considered to suggest increased susceptibility to ventricular arrhythmias. Our case suggests that T wave alternans can also be a marker of myocardial ischemia and can precede classical ischemic ST segment depression during treadmill stress test.

Assessment of troponin I level in patients with acute myocardial infarction and its impact on clinical outcome

Introduction: Coronary Artery disease is one of the major causes of Mortatlity I the world that included Myocardial ischemia and infarction. Cardiac toponins are (troponin- I and Troponin -T) the markers of myocardial ischemia and they are the sign of Myocardial damage. They can provide important diagnostic and prognostic information. Aim : In the present study the correlation of clinical presentation, complication and outcome with reference of different level (mild, moderate and severe) of elevated troponin enzyme level was studied. Material and method: 100 patientspresented with acute myocardial infarct ion were studied for clinical presentation (hemodynamics, heart failure, mechanical complication, angina, shock) and ICCU stay and total hospital stay, recurrent angina, heart failure, re-infarct, morbidity and mortality was recorded. Their cardiac troponin- I level was measured and corelated accordingly in group 1 (mild elevation: cTnIlevel baseline (0.004) totentimes), group 2 (moderate elevation: cTnIlevel ten times to hundredtimes) and group 3 (severe elevation: cTnIlevel morethan hundredtimes). RESULTS: Significantly greater number of patients with recurrent angina were having severely elevated Troponin-I level. Relocation of patient in ICCU was more with patient with severely elevated level. Severity of cardiac failure and Troponin-I levels were found to be significantly associated with each other.

The Value of Stress Echocardiography Imaging and Functional Parameters in Patients with aVR Lead ST-Segment Elevation during an Exercise Stress Test to Detect Significant Left Main Stenosis.

To evaluate the role of functional and imaging parameters during exercise stress echocardiography (SE) in the presence of ST-segment elevation (ST-E) in aVR leads to predict significant left main/left main equivalent/or ostial left anterior descending (LAD) stenosis (LM+). The study population included 548 patients with ECG and echo markers of myocardial ischemia, in whom diagnostic coronary angiography was performed. We analyzed the patients' clinical characteristics, ECG changes, wall motion score index (WMSI) by stress echocardiography (SE), as well as functional capacity during exercise (METs) and Duke treadmill score. aVR ST-segment elevation was found in 60/548 (11%) patients, whereas aVR ST-E was found in 23/57 patients with left main LM stenosis (Sn 40%, Sp 92%, PPV 38%, NPV 93%). When aVR ST-E was combined with other functional/imaging parameters, patients with aVR ST-E and LM+ had significantly worse functional capacity in METs (5.0±2.2 vs. 6.7±2.3, P=0.005), lower Duke score (-6.8±6.8 vs. -3.6±4.1, P=0.049), and higher deterioration of WMSI (0.51±0.24 vs. 0.39±0.24, P=0.046). Significant multivariable predictors of the left main (LM) stenosis were aVR ST-E and positive SE in LAD territory in the whole group of patients, and Delta WMSI, Duke score and METs achieved in patients presented with aVR ST-E during exercise. The aVR ST-segment alone has intermediate sensitivity in detecting significant LM stenosis in patients referred to SE testing for chest pain. When combined with other functional and imaging parameters, including poor exercise functional capacity in METs, lower Duke score or greater WMA in the territory of LAD, its diagnostic power to detect LM significantly increases.

Association of Maternal Serum Ischemia Modified Albumin (IMA) with Placental Histopathological Changes and Fetomaternal Outcome: A Prospective Case Control Study in Normotensive and Pre-eclamptic Women.

Ischemia and oxidative stress leads to generation of hydroxyl free radicals and modification of 'N-terminus' of human serum albumin. This modified albumin molecule, known as Ischemia Modified Albumin (IMA), is elevated in early stages of ischemia. It has recently been approved by US Food and Drug Administration (US FDA) for its clinical use, as early marker of myocardial ischemia in cardiology. IMA is a novel marker of ischemia and is elevated in other clinical conditions associated with ischemia like pulmonary embolism, uncontrolled type II diabetes mellitus, acute decompensated heart failure, preeclampsia, recurrent pregnancy losses and IUGR. Role of IMA in birth asphyxia in perinatology is of current interest and needs further research. A prospective case control study was conducted in a tertiary center in North India for one year. Total 80 pregnant women between 34 and 40weeks were recruited and allocated in two groups. Case group comprised of 40 pre-eclamptic pregnant women and control group comprised of 40 normotensive pregnant women. Comparison and association of maternal serum IMA levels with fetomaternal outcome and number and types of placental histopathological changes was done in two groups. In preeclampsia group mean serum IMA (115.23 ± 49.51) was significantly higher as compared to the normotensive group (79.21 ± 14.35). The optimum cut off value of IMA to detect a case was 94.5IU/ml (sensitivity 65%, specificity 87.5%, PPV 83.9%, NPV 71.4% and diagnostic accuracy of 76.3). Pre-eclamptic women, had significantly higher incidence of PTVD, lower fetal birth weight and placental histopathological changes as compared to normotensive group. 83.8% of the women with raised IMA levels were pre-eclamptic. Raised IMA levels were significantly associated with higher incidence of PTVD, birth weight ≤ 2kg and hypoxic histopathological lesions of chorangiosis, intervillous fibrin and hyalinization. Determination of maternal serum IMA levels early in pregnancy can predict preeclampsia and avoid future severe preeclampsia related complications. It might be useful to optimize both maternal and fetal/neonatal outcomes.

Intravenous metoprolol during ongoing STEMI ameliorates markers of ischemic injury: a METOCARD-CNIC trial electrocardiographic study.

Besides its protective effect against neutrophil-mediated injury at reperfusion, intravenous (IV) metoprolol was recently shown to reduce the progression of ischemic injury in a pig model of ST-segment elevation myocardial infarction (STEMI). Here, we tested the hypothesis that IV metoprolol administration in humans with ongoing STEMI blunts the time‑dependent progression of ischemic injury assessed by serial electrocardiogram (ECG) evaluations before reperfusion. The METOCARD-CNIC trial randomized 270 anterior STEMI patients to IV metoprolol or control before reperfusion by percutaneous coronary intervention (PCI). In 139 patients (69 IV metoprolol, 70 controls), two ECGs were available (ECG-1 before randomization, ECG-2 pre-PCI). Between-group ECG differences were analyzed using univariate and multivariate regression models. No significant between-group differences were observed on ECG-1. On ECG-2, patients who received IV metoprolol had a narrower QRS than those in the control group (84ms vs. 90ms, p = 0.029), a lower prevalence of QRS distortion (10% vs. 26%, p = 0.017), and a lower sum of anterior and total ST-segment elevation (10.1mm vs. 13.6mm, p = 0.014 and 10.4mm vs. 14.0mm, p = 0.015, respectively). Adjusted analysis revealed similar results. Significant associations were observed between ECG-2 variables and cardiac magnetic resonance imaging measurements (extent of myocardial edema, infarct size, microvascular obstruction, and left-ventricular ejection fraction) after STEMI. In summary, IV metoprolol administration before reperfusion ameliorates ECG markers of myocardial ischemia in anterior STEMI patients. These data confirm that IV metoprolol is able to reduce ischemic injury and highlight the ability of ECG analysis to provide relevant real-time information on the effect of cardioprotective therapies before reperfusion.

The Correlation between Cardiac Enzymes and Cardiotrophin-1 Levels in Patients with Acute Coronary Syndrome

Background In the current era, there is always search for better cardiovascular biomarkers to early diagnose the disease. Objectives We aimed to investigate the association between a novel biomarker, cardiothropin-1 (CT-1), and standard markers of myocardial ischemia in patients with acute coronary syndrome (ACS) in Turkey. Patients and Methods In this prospective cohort study, patients who were admitted to our institution between July 2012 and July 2013 with the diagnosis of ACS were included. The standard markers of myocardial [...]

Firefighters and COVID-19: An Occupational Health Perspective.

Firefighters and COVID-19: An Occupational Health Perspective.

MO924GROWTH DIFFERENTIATION FACTOR 15 PREDICTOR VALUE IS SUPERIOR TO TROPONIN I IN THE EVALUATION OF KIDNEY TRANSPLANT CANDIDATES

Abstract Background and Aims Elevation of cardiac troponin has been shown to be a marker of myocardial ischemia and other cardiovascular pathologies frequently present in patients with CKD. Pretransplant cardiac troponin I (cTNI) has demonstrated its predictor value of survival after kidney transplant in previous studies. Growth differentiation factor 15 (GDF-15) is a biomarker induced by oxidative stress currently studied as a predictor of mortality and cardiovascular events (CVE) in multiple scenarios, including patients with chronic kidney disease. The aim of this study is to compare the utility of cTNI and GDF-15 to predict posttransplant mortality and CVE in a cohort of kidney transplant recipients. Method We included 359 kidney transplants performed between 2005 and 2015. cTNI and GDF-15 were measured on stored serum samples obtained pretransplant. Information about patients was extracted from the prospectively maintained database of renal transplant recipients at our center. Results Receptors had a median age of 54.1 and were 67.4% male. 22% were diabetic before the transplant, whereas 9.5% and 8.1% had prior history of coronary and peripheral artery disease. 16.5% transplants were performed preemptively. Median GDF-15 was 5346.4 (IQR= 4071.83-6786.32) pg/ml and median cTNI was 5.6 (IQR= 3.11-10.67) ng/l. After follow up, 77 (21.45%) patients died. During this period, incidence of cerebrovascular accident, acute coronary syndrome and mayor adverse cardiovascular events (MACE) was 6.38%, 12.68% and 20.56% respectively. Patients were stratified in tertiles according to GDF-15 and cTNT levels. In the univariate analysis, higher levels of GDF-15 significantly related to overall mortality, cardiovascular mortality, cerebrovascular accident, acute coronary syndrome and major adverse cardiovascular events. Higher cTNI related to cardiovascular mortality, acute coronary syndrome and MACE, but not overall mortality (Log Rank p=0.4). (Fig 1). By multivariate cox regression analysis, including both biomarkers and clinical characteristics (age, diabetes, prior coronary and peripheral artery disease and pretransplant renal replacement therapy), the relation between overall survival and GDF-15 remained significant for the highest tertile (HR 2.2 CI95% (1.2-4.1), p = 0.01). Similarly, GDF-15 relation with cerebrovascular accidents and MACE remained significant after the adjustment by these characteristics [HR 9.7 CI95% (2.2-43.1), p = 0.003 and HR 2.7 CI95% (1.4-5.1), p = 0.002] for the highest risk tertile. On the contrary, posttransplant acute coronary syndrome was only related to cTNI tertiles and previous coronary artery disease in the multivariate model [HR 3.2 CI95% (1.5-7.3), p = 0.003 for the highest cTNI tertile]. Conclusion Our study highlights the potential utility of GDF-15 as a predictor of mortality and cardiovascular events after kidney transplant and its superiority compared to cTNI. In our study, cardiac troponin showed a stronger relation with acute coronary events, probably due to its specific production in myocardial tissue. Altogether, these two molecules could be used in conjunction with clinical characteristics to create prognostic models to better stratify patient’s risk prior organ allocation, predict mortality and cardiovascular adverse events after transplant and ideally find strategies to minimize them. Large-scale, multicenter validation using these biomarkers would be the next step to prove its utility among kidney transplant candidates.

Post-mortem CMR in a model of sudden death due to myocardial ischemia: validation with connexin-43.

We sought to evaluate the effectiveness of post-mortem cardiac magnetic resonance (PM-CMR) for the identification of myocardial ischemia as cause of sudden cardiac death (SCD) when the time interval between the onset of ischemia and SCD is ≤ 90 min. PM-CMR was performed in 8 hearts explanted from pigs with spontaneous death caused by occlusion of the left anterior descending coronary artery: 4 with SCD after ≤ 40 min of coronary occlusion and 4 between 40 and 90 min. PM-CMR included conventional T1 and T2-weighted image and T1, T2, and T2* mapping techniques. Imaging data were compared and validated with immunohistochemical evaluation of the altered proportion and redistribution of phosphorylated versus non-phosphorylated connexin 43 (CX43 and npCX43, respectively), an established molecular marker of myocardial ischemia. At T2-weighted images, the ischemic core was hypointense (core/remote ratio 0.67 ± 0.11) and surrounded by and hyperintense border zone. Compared to remote myocardium, the ischemic core had higher T1 (p = 0.0008), and lower T2 (p = 0.007) and T2* (p = 0.002). Cytoplasmatic npX43 and the npCX43/CX43 ratio were significantly higher in animals deceased > 40 min than in others. PM-CMR can reliably detect early signs of myocardial damage induced by ischemia, based on conventional pulse sequences complemented by a novel ad hoc application of quantitative mapping techniques. • Post-mortem MRI may help to understand cause of sudden cardiac death. • Post-mortem MRI allows detection of signs of myocardial ischemia as cause of sudden cardiac death within 90 and 40 min following coronary occlusion as demonstrated in a pig model of myocardial ischemia. • Signs of myocardial ischemia using conventional and mapping MRI technique are associated with the immunohistochemical changes of phosphorylated and dephosphorylated connexin-43 which is an established molecular marker of myocardial ischemia.

Non-invasive myocardial work is reduced during transient acute coronary occlusion.

During ischemia a close relationship exists between sub-endocardial blood flow and myocardial function. Strain parameters can capture an impairment of regional longitudinal function but are load dependent. Recently, a novel non-invasive method to calculate Myocardial Work (MW) showed a strong correlation with invasive work measurements. Our aim was to investigate the ability of non-invasive MW indices to identify the ischaemic risk area during transient acute coronary occlusion (TACO). The study population comprises 50 individuals with critical coronary stenosis (CCS). Echocardiography recordings were obtained before coronary angiography, during TACO and after revascularization to measure global longitudinal strain (GLS), Myocardial Work Index (MWI), Myocardial Constructive Work (MCW), Myocardial Wasted work (MWW), Myocardial work efficiency (MWE). Compared to baseline, we found a significant reduction of GLS (p = 0.005), MWI, MCW and MWE (p<0.001) during TACO. The non-invasive measurement of MW parameters is a sensitive and early marker of myocardial ischemia during TACO.

Relation of hs-CRP and Glycogen phosphorylase BB in Acute Myocardial Infarction Patients

Background: Inflammation has important role in the pathophysiology of atherosclerosis and acute myocardial infraction and hs-CRP is an inflammatory marker. GPBB is a marker of myocardial necrosis or myocardial ischmia i.e. the initial phase of AMI. The aim of this study was to know the levels of GPB and the relation between hs-CRP and GPBB in AMI patients. Materials & methods: This study was conducted in the Cardiology of J.A. Hospital and Department of biochemistry, G.R. Medical College, Gwalior. Patients were admitted with severe chest pain out of which 100 were included in this study. 50 normal healthy individuals were also selected. Blood samples were collected at the admission time for the analysis of hs-CRP and GPBB. All patients underwent thorough clinical examination and investigations. Estimation of GPBB and hs-CRP were done by ELISA method and other routine parameters done by enzymatic method. Results: The mean level of GPBB in patients was 46.92ng/mL while in controls it was 13.88ng/mL. The mean level of hs-CRP in patients was 4.38mg/L while in controls it was 1.34mg/L. There was highly significant difference of GPBB and hs-CRP in control group and AMI group. The finding of results showed that hs-CRP and GPBB was positively correlated. The levels of FBG, Triglyceride, Cholesterol, LDL, and VLDL were significantly increased and HDL was decreased in AMI group when compare controls. Conclusion: Our results demonstrate that there was positive correlation of hs-CRP and GPBB in AMI patients. So along with GPBB, hs-CRP is also additional marker of myocardial ischemia and AMI.