Fibroblast Growth Factor 23: Potential Marker of Invisible Heart Damage in Diabetic Population.

Two-dimensional speckle-tracking echocardiography (2DSTE) detects myocardial dysfunction despite a preserved left ventricular ejection fraction. Fibroblast growth factor 23 (FGF23) has become a promising biomarker of cardiovascular risk. This study aimed to determine whether FGF23 may be used as a marker of myocardial damage among patients with diabetes mellitus type 2 (T2DM) and no previous history of myocardial infarction. The study enrolled 71 patients with a median age of 70 years. Laboratory data were analyzed retrospectively. Serum FGF23 levels were determined using a sandwich enzyme-linked immunosorbent assay. All patients underwent conventional echocardiography and 2DSTE. Baseline characteristics indicated that the median time elapsed since diagnosis with T2DM was 19 years. All subjects were divided into two groups according to left ventricular diastolic function. Individuals with confirmed left ventricular diastolic dysfunction had significantly lower levels of estimated glomerular filtration rate and higher values of hemoglobin A1c. Global circumferential strain (GCS) was reduced in the majority of patients. Only an epicardial GCS correlated significantly with the FGF23 concentration in all patients. The study indicates that a cardiac strain is a reliable tool for a subtle myocardial damage assessment. It is possible that FGF23 may become an early diagnostic marker of myocardial damage in patients with T2DM.

2D Strain Analysis in Myocarditis-Can We Be Any Closer to Diagnose the Acute Phase of the Disease?

BACKGROUND: The aim of present study was to assess left ventricular myocardial deformation detected by 2D STE in patients with suspected acute myocarditis (AM) early on admission in whom later cardiac magnetic resonance (CMR) evaluation was performed. METHODS: A total of 47 patients with suspected AM based on clinical practice were prospectively enrolled. Coronary angiography was performed on all patients to rule out significant coronary artery disease. CMR confirmed myocardial inflammation, oedema, and regional necrosis meeting the Lake Louise criteria in 25 patients (53%, oedema (+) subgroup). In the remaining patients, only LGE was confirmed in the sub-epicardial or intramuscular localization (22 patients, 47%, oedema (-) subgroup). Early on admission, echocardiography with measurements of global and segmental longitudinal strains (GLS), circumferential strains (GCS) at the endocardial (endocardial GCS) and epicardial (epicardial GCS) layers, transmural GCS, and radial strains (RS) were performed. RESULTS: Mild reduction of GLS, GRS, and transmural GCS values were found in patients with oedema (+) subgroup. The epicardial GCS turned out to be the diagnostic factor for oedema with a cut-off point of 13,0% (AUC 0.747, p = 0.0005). Twenty-two patients (all but three) with an acute phase of myocarditis and epicardial GCS -13.0% or less had oedema confirmed by CMR. CONCLUSIONS: 2D STE can help to set the diagnosis of AM in patients with acute chest pain with a normal coronary angiogram. The epicardial GCS can serve as a diagnostic factor for oedema in patients with early stage of AM. In patients presenting with signs of AM (oedema in CMR), the epicardial GCS is modified in comparison with a subgroup without oedema; therefore, this parameter could be used to improve the performance of ultrasound.

ST Segment Elevation in a Young Woman with Metaplastic Breast Carcinoma.

The 12-lead electrocardiogram (ECG) remains a key tool to diagnose ST elevation myocardial infarction (STEMI). However, a variety of other conditions aside from obstructive coronary disease, including hyperkalemia, myocarditis, pericarditis, and Takotsubo and Brugada syndrome, may also cause ST segment elevation, with an incidence rate of 3%-15% and mean age of 45 ± 14 years. A combination of a detailed past medical history, thorough physical examination, and additional imaging tests may allow physicians to make the correct diagnosis.In this report, we present a case of a 39-year-old woman with metaplastic breast cancer in the process of combined oncological treatment admitted to the emergency department because of general body weakness, chest pain, and accompanying hypotonia with an initial diagnosis of acute coronary syndrome.The ECG at presentation showed ST segment elevation, but owing to the observed neoplastic cachexia and frailty, she was medically managed and the diagnostics were extended to include transthoracic echocardiogram and computed tomography scan. The patient was found to have an external mass that infiltrated into the thoracic wall, pericardium, right ventricle, interventricular septum, and coronary arteries.In cancer patients with chest pain and ST segment elevation, STEMI should not be the only diagnosis taken into account. In our report, using a combination of available cardiac imaging methods, we were able to evaluate the stage of the lesion and coronary involvement.

Acute coronary syndrome versus acute myocarditis in young adults-value of speckle tracking echocardiography.

PURPOSE: Comparing myocarditis with an acute coronary syndrome (ACS)-like presentation and acute myocardial infarction (AMI) poses an important clinical challenge. The purpose of the study was to investigate the diagnostic value of the clinical, laboratory and especially echocardiographic characteristics including speckle tracking echocardiography (STE) of patients with ACS-like myocarditis and AMI. METHODS: We conducted a retrospective analysis comparing 69 symptomatic patients (≤ 45 years old), hospitalized at the Department of Interventional Cardiology (Medical University of Lodz, Poland) between April 2014 and June 2021 with an initial diagnosis of ST-segment elevation myocardial infarction. RESULTS: 37 patients with the cardiac magnetic resonance-confirmed acute myocarditis and 32 patients diagnosed with AMI based on the clinical presentation, electrocardiogram and the presence of a culprit lesion on the coronary angiography were analysed including echocardiography parameters. On STE analysis an average global longitudinal (GLS), radial and circumferential strain including three-layers observation were significantly lower (absolute value) in patients with AMI versus acute myocarditis (p<0.05). There was no significant difference in Endo/Epi ratio (p = 0.144) between the groups. An average GLS < (-17.5) represented the optimal cut-off value for the myocarditis diagnosis. CONCLUSION: In patients with AMI a significant reduction of global and three-layers strains compared to patients with myocarditis was detected. Furthermore, our analysis also confirmed the discriminative pattern of myocardial injury between the groups.

1,5-Anhydroglucitol as a Marker of Acute Hyperglycemia in Cardiovascular Events.

1,5-anhydroglucitol (1,5-AG) is a biomarker of acute hyperglycemia in diabetology and also in cardiodiabetology. It is used to monitor fluctuating glucose levels. 1,5-AG is a monosaccharide that is biochemically similar to D-glucose and originates from the nutrition. The presence of 1,5-AG in blood and tissue is nearly constant due to reabsorption in the renal proximal tubule. In acute hyperglycemia, renal reabsorption is inhibited by glucose and 1,5- AG is excreted in the urine, while its serum level decreases rapidly. 1,5-AG reflects glucose excursions over 1-3 days to 2 weeks. In this regard, low levels of serum 1,5-AG can be a clinical marker of short- term glycemic derangements such as postprandial hyperglycemia, which is an important risk factor for the pathogenesis of coronary artery disease (CAD) as low levels of 1,5-AG reflect severe plaque calcification in CAD and correlate with high-density lipoprotein cholesterol (HDL-C) levels. For these reasons, 1,5-AG may also be a marker for atherosclerosis; in fact an even better marker than HbA1c or fructosamine which are normally used. 1,5-AG may also be a predictor of cardiovascular disease, left ventricular dysfunction after acute coronary syndrome (ACS), and mortality after ACS. This articles reviews the current knowledge on 1,5-AG related to its use as predictor for cardiovascular events.

Fibroblast Growth Factor 23 and Cardiovascular Risk in Diabetes Patients-Cardiologists Be Aware.

Numerous clinical studies have indicated that elevated FGF23 (fibroblast growth factor 23) levels may be associated with cardiovascular (CV) mortality, especially in patients with chronic kidney disease. The purpose of this study was to examine the hypothesis that FGF23 may be a potent CV risk factor among patients with long-standing type 2 diabetes mellitus (T2DM). Research was performed utilizing patients with T2DM and regular outpatient follow-up care. Baseline characteristics determined by laboratory tests were recorded. Serum FGF23 levels were detected using a sandwich enzyme-linked immunosorbent assay. All patients underwent echocardiograms and 12-lead electrocardiograms. Data records of 102 patients (males: 57%) with a median age of 69 years (interquartile range (IQR) 66.0-74.0) were analyzed. Baseline characteristics indicated that one-third (33%) of patients suffered from ischemic heart disease (IHD), and the median time elapsed since diagnosis with T2DM was 19 years (IQR 14.0-25.0). The hemoglobin A1c, estimated glomerular filtration rate, and FGF23 values were, respectively, as follows: 6.85% (IQR 6.5-7.7), 80 mL/min/1.73 m2 (IQR 70.0-94.0), and 253.0 pg/mL (IQR 218.0-531.0). The study revealed that FGF23 was elevated in all patients, regardless of IHD status. Thus, the role of FGF23 as a CV risk factor should not be overestimated among patients with T2DM and good glycemic control.

Variations in Blood Platelet Proteome and Transcriptome Revealed Altered Expression of Transgelin-2 in Acute Coronary Syndrome Patients.

Proteomic analyses based on mass spectrometry provide a powerful tool for the simultaneous identification of proteins and their signatures. Disorders detection at the molecular level delivers an immense impact for a better understanding of the pathogenesis and etiology of various diseases. Acute coronary syndrome (ACS) refers to a group of heart diseases generally associated with rupture of an atherosclerotic plaque and partial or complete thrombotic obstruction of the blood flow in the infarct-related coronary artery. The essential role in the pathogenesis of ACS is related to the abnormal, pathological activation of blood platelets. The multifactorial and complex character of ACS indicates the need to explain the molecular mechanisms responsible for thrombosis. In our study, we performed screening and comparative analysis of platelet proteome from ACS patients and healthy donors. Two-dimensional fluorescence difference gel electrophoresis and nanoscale liquid chromatography coupled to tandem mass spectrometry showed altered expressions of six proteins (i.e., vinculin, transgelin-2, fibrinogen ß and γ chains, apolipoprotein a1, and tubulin ß), with the overlapping increased expression at the mRNA level for transgelin-2. Dysregulation in protein expression identified in our study may be associated with an increased risk of thrombotic events, correlated with a higher aggregability of blood platelets and induced shape change, thus explaining the phenomenon of the hyperreactivity of blood platelets in ACS.

Dysregulation in the Expression of Platelet Surface Receptors in Acute Coronary Syndrome Patients-Emphasis on P2Y12.

The pathological conditions caused by blood platelet activation constitute a fundamental core in the pathogenesis of Acute Coronary Syndrome (ACS). The hyperactivity of platelets in ACS is well-documented, but there is still little research into the molecular basis of phenotypic changes in platelet functionality. To expand the knowledge of this phenomenon, we analyzed the disturbances in the expression of several key platelet receptors and the aspect of regulating potential abnormalities. Platelet surface receptors are responsible for maintaining the hemostatic balance, platelet interaction with immune cells, and support of the coagulation cascade leading to occlusion of the vessel lumen. Due to their prominent role, platelet receptors constitute a major target in pharmacological treatment. Our work aimed to identify the molecular alteration of platelet surface receptors, which showed augmented mRNA expression of P2Y12, GP1BB, ITGA2B, and ITGB3 and increased protein concentrations of P2Y12 and GP IIb/IIIa in ACS. The upregulation of the P2Y12 level was also confirmed by confocal and cytometric visualization. Furthermore, we evaluated the expression of two microRNAs: miR-223-3p and miR-126-3p, which were suggested to regulate platelet P2Y12 expression. Results of our study present new insight into the molecular background of ACS.

Variations in the Gene Expression Profile in Atherosclerotic Patients with Non-Fatal ACS: A Preliminary Study.

The pathophysiology of atherosclerosis and acute coronary syndrome (ACS) is related to interactions between immune cells, endothelium, and blood platelets. An increasing number of reports confirm the link between excessive immune activation and cellular cross-talk with ACS incidence. Our genetic and proteomic analysis was performed on strictly selected atherosclerotic patients with non-fatal ACS without typical risk factors and healthy donors. Results showed changes in the gene expression levels of the various inflammatory factors derived from the peripheral blood cells that drive the over-activation of the immune system. The enhanced activation of the immune system may lead to the overexpression of the pro-inflammatory mediators, which causes self-perpetuating machinery of processes associated with thrombosis. In our preliminary study, we confirmed an altered expression of genes associated with the inflammation and overall interaction of the vascular microenvironment. Furthermore, 5 of 92 analyzed genes, CCL2, CCR2, CSF2, GZMB, and ICOS, were expressed only in patients with ACS. In conclusion, the augmented expression of the pro-inflammatory genes from the peripheral blood cells may be a crucial genetic factor leading to the occurrence of acute inflammation and thus be significant in ACS pathogenesis.

Symptomatic Young Adults with ST-Segment Elevation-Acute Coronary Syndrome or Myocarditis: The Three-Factor Diagnostic Model.

Myocarditis may mimic myocardial infarction (MI) due to a similar clinical presentation, including chest pain, electrocardiography changes, and laboratory findings. The purpose of the study was to investigate the diagnostic value of clinical, laboratory, and electrocardiography characteristics of patients with acute coronary syndrome - like myocarditis and MI. We analysed 90 patients (≤45 years old) with an initial diagnosis of ST-segment elevation myocardial infarction; 40 patients (44.4%), through the use of cardiac magnetic resonance, were confirmed to have myocarditis, and 50 patients (55.6%) were diagnosed with MI. Patients with myocarditis were younger and had fewer cardiovascular risk factors than those with MI. The cutoff value distinguishing between myocarditis and MI was defined as the age of 36 years. The history of recent infections (82.5% vs. 6%) and C-reactive protein (CRP) levels on admission (Me 45.9 vs. 3.4) was more associated with myocarditis. Further, the QTc interval was inversely correlated with the echocardiographic ejection fraction in both groups but was significantly longer in patients with MI. Non-invasive diagnostics based on clinical features and laboratory findings are basic but still essential tools for differentiation between MI and myocarditis. The three-factor model including the criteria of age, abnormal CRP, and history of recent infections might become a valuable clinical indication.

Screening Analysis of Platelet miRNA Profile Revealed miR-142-3p as a Potential Biomarker in Modeling the Risk of Acute Coronary Syndrome.

Transcriptome analysis constitutes one of the major methods of elucidation of the genetic basis underlying the pathogenesis of various diseases. The post-transcriptional regulation of gene expression is mainly provided by microRNAs. Their remarkable stability in biological fluids and their high sensitivity to disease alteration indicates their potential role as biomarkers. Given the high mortality and morbidity of cardiovascular diseases, novel predictive biomarkers are sorely needed. Our study focuses for the first time on assessing potential biomarkers of acute coronary syndrome (ACS) based on the microRNA profiles of platelets. The study showed the overexpression of eight platelet microRNAs in ACS (miR-142-3p; miR-107; miR-338-3p, miR-223-3p, miR-21-5p, miR-130b-3p, miR-301a-3p, miR-221-3p) associated with platelet reactivity and functionality. Our results show that the combined model based on miR-142-3p and aspartate transaminase reached 82% sensitivity and 88% specificity in the differentiation of the studied groups. Furthermore, the analyzed miRNAs were shown to cluster into two orthogonal groups, regulated by two different biological factors. Bioinformatic analysis demonstrated that one group of microRNAs may be associated with the physiological processes of platelets, whereas the other group may be linked to platelet-vascular environment interactions. This analysis paves the way towards a better understanding of the role of platelet microRNAs in ACS pathophysiology and better modeling of the risk of ACS.

Atrial Natriuretic Peptides, Right Atrial Infarction and Prognosis of Patients with Myocardial Infarction-A Single-Center Study.

Atrial natriuretic peptide (ANP) is secreted in response to the stretching of the atrial wall. Atrial ischemia most likely impairs the ability of atrial myocytes to produce ANP. Atrial infarction (AI) is rarely diagnosed but not infrequently associated with myocardial infarction (MI). The aim of the study was to assess the association between AI and the prognostic value of N-terminal proANP (NT-proANP) in patients with MI treated with primary percutaneous coronary intervention (PCI). We evaluated data of 100 consecutive patients. Plasma levels of NT-proANP were measured by the ELISA method. ECG recordings were interpreted to diagnose AI according to Liu's criteria. All patients were followed-up prospectively for 12 months for the manifestation of major adverse cardiovascular events (MACE), defined as unplanned coronary revascularization, stroke, reinfarction or all-cause death. AI was diagnosed in 36 patients. 14% of patients developed MACE. AI did not affect the incidence of MACE or any of its components, nor the patients' prognosis. NT-proANP revealed to be a strong predictor of death but was not associated with other adverse events. Conclusions: AI in patients with MI treated with primary PCI is not connected with their prognosis nor affects the usefulness of NT-proANP in predicting death during the 12-month follow-up.

Prognostic value of copeptin in patients with acute myocardial infarction treated with percutaneous coronary intervention: a prospective cohort study.

BACKGROUND: Ischemic myocardial injury leads to neurohormonal system activation and increased release of copeptin. Although diagnostic value of copeptin has been widely described, data on its prognostic performance in patients with myocardial infarction is inconclusive. The aim of this study was to asses if elevated copeptin concentration provides prognostic information for long-term adverse cardiac events in a cohort of first acute myocardial infarction patients treated with percutaneous coronary intervention. METHODS: Copeptin concentration was assessed in a cohort of 100 consecutive patients (39% women; mean age 63±7 years) presenting with first acute myocardial infarction and subjected to percutaneous coronary intervention. Samples were collected at the time of admission and on the 4th/5th day of hospitalisation. All patients were followed-up prospectively for 12 months for the occurrence of major adverse cardiovascular events defined as reinfarction, unscheduled coronary revascularisation and all-cause death. RESULTS: Elevated copeptin concentration on the 4th/5th day of hospitalisation was identified as a predictor of major adverse cardiovascular events (P=0.0445). The increase between copeptin level on admission and on day 4th/5th was associated with the requirement for unscheduled coronary revascularisation in receiver operating characteristics (ROC) analysis (AUC =0.639; 95% CI: 0.504-0.773; P=0.0430). In a multivariate analysis, copeptin concentration on the 4th/5th day of hospitalisation and left ventricular ejection fraction assessed by transthoracic echocardiography, were the only predictors for major adverse cardiac events during follow-up (P=0.024 and P=0.001, respectively). CONCLUSIONS: Copeptin seems to be a prognostic marker in patients with first myocardial infarction treated with percutaneous coronary intervention.

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).

FGF23: A Review of Its Role in Mineral Metabolism and Renal and Cardiovascular Disease.

FGF23 is a hormone secreted mainly by osteocytes and osteoblasts in bone. Its pivotal role concerns the maintenance of mineral ion homeostasis. It has been confirmed that phosphate and vitamin D metabolisms are related to the effect of FGF23 and its excess or deficiency leads to various hereditary diseases. Multiple studies have shown that FGF23 level increases in the very early stages of chronic kidney disease (CKD), and its concentration may also be highly associated with cardiac complications. The present review is limited to some of the most important aspects of calcium and phosphate metabolism. It discusses the role of FGF23, which is considered an early and sensitive marker for CKD-related bone disease but also as a novel and potent cardiovascular risk factor. Furthermore, this review gives particular attention to the reliability of FGF23 measurement and various confounding factors that may impact on the clinical utility of FGF23. Finally, this review elaborates on the clinical usefulness of FGF23 and evaluates whether FGF23 may be considered a therapeutic target.

Refractory Angina-Unsolved Problem.

The article discusses pharmacologic and interventional therapeutic options for patients with refractory angina. Refractory angina refers to long-lasting symptoms (≥3 months) due to established reversible ischemia in the presence of obstructive coronary artery disease, which cannot be controlled by escalating medical therapy with second-line and third-line pharmacologic agents, bypass grafting, or stenting. Due to an aging population, increased number of comorbidities, and advances in coronary artery disease treatment, incidence of refractory angina is growing. Although the number of therapeutic options is increasing, there is a lack of randomized clinical trials that could help create recommendations for this group of patients.

Remote Ischemic Preconditioning and Contrast-Induced Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention: A Randomized Clinical Trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired AKI and a serious complication of percutaneous coronary intervention. OBJECTIVE: The aim of the present study was to assess whether remote ischemic preconditioning (RIPC) reduces the incidence of CI-AKI. METHODS: We conducted a prospective, randomized, sham-controlled clinical study. The study included 101 patients admitted to the Intensive Cardiac Therapy Clinic of Medical University of Lodz for elective percutaneous coronary intervention. The participants were randomly assigned in a 1:1 ratio to either a control group (n = 51) or an RIPC group (n = 50). In the latter, RIPC was achieved before percutaneous coronary intervention by 4 cycles of 5-minute inflation of a cuff on the left upper arm to 200 mm Hg followed by 5-minute deflation. In the control group, a deflated cuff was placed on the left arm for 40 minutes. Serum creatinine concentration was measured to check for the presence of CI-AKI within 48 to 72 hours of percutaneous coronary intervention. Serum neutrophil gelatinase-associated lipocalin level was also measured within 3 hours. RESULTS: CI-AKI occurred in 2 patients from the RIPC group (4%) and 3 patients from the control group (5.9%), but the difference was not significant (P = 0.98). The patients who developed CI-AKI also demonstrated increased serum neutrophil gelatinase-associated lipocalin concentrations (the area under the receiver operator characteristic curve = 0.97; 95% CI, 0.938-1.00; P < 0.00) and the optimal cutoff point value was 118.9 ng/mL. CONCLUSIONS: The use of RIPC before elective percutaneous coronary intervention was not found to prevent CI-AKI. ClinicalTrials.gov identifier: NCT03761368. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Serum NGAL, KIM-1, IL-18, L-FABP: new biomarkers in the diagnostics of acute kidney injury (AKI) following invasive cardiology procedures.

PURPOSE: The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI. METHODS: The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography. RESULTS: 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4-221.0) vs. 201.8 (156.5-299.9) vs. 118.5 (73.4-198.7); p < 0.0001]. No significant correlations were observed between the decrease in eGFR or the increase in creatinine and biomarkers level. CONCLUSION: Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required.