The Role of Epicardial Adipose Tissue in Acute Coronary Syndromes, Post-Infarct Remodeling and Cardiac Regeneration.

Epicardial adipose tissue (EAT) is a fat deposit surrounding the heart and located under the visceral layer of the pericardium. Due to its unique features, the contribution of EAT to the pathogenesis of cardiovascular and metabolic disorders is extensively studied. Especially, EAT can be associated with the onset and development of coronary artery disease, myocardial infarction and post-infarct heart failure which all are significant problems for public health. In this article, we focus on the mechanisms of how EAT impacts acute coronary syndromes. Particular emphasis was placed on the role of inflammation and adipokines secreted by EAT. Moreover, we present how EAT affects the remodeling of the heart following myocardial infarction. We further review the role of EAT as a source of stem cells for cardiac regeneration. In addition, we describe the imaging assessment of EAT, its prognostic value, and its correlation with the clinical characteristics of patients.

Evaluation of Nitrosative/Oxidative Stress and Inflammation in Heart Failure with Preserved and Reduced Ejection Fraction.

Heart failure (HF) is a complex syndrome characterized by impaired cardiac function. Two common subtypes of HF include heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). In this study, we aimed to evaluate and compare the plasma levels of 3-nitrotyrosine (3-NT)-as a marker of nitrosative/oxidative stress and myeloperoxidase (MPO)-as an indicator of inflammation between HFpEF and HFrEF. Twenty-seven patients diagnosed with HFpEF and twenty-two with HFrEF were enrolled in this study. Additionally, forty-one patients were recruited for the control group. An echocardiographic assessment was conducted, followed by the collection of blood samples from all participants. Subsequently, the levels of 3-NT and MPO were quantified using the ELISA method. Comprehensive clinical characteristics and medical histories were obtained. Circulating levels of 3-NT were significantly higher in the HFpEF patients than in the control and the HFrEF groups. Nitrosative/oxidative stress is significantly intensified in HFpEF but not in HFrEF.

Multicenter registry of Impella-assisted high-risk percutaneous coronary interventions and cardiogenic shock in Poland (IMPELLA-PL).

BACKGROUND: Impella is a percutaneous mechanical circulatory support device for treatment of cardiogenic shock (CS) and high-risk percutaneous coronary interventions (HR-PCIs). IMPELLA-PL is a national retrospective registry of Impella-treated CS and HR-PCI patients in 20 Polish interventional cardiological centers, conducted from January 2014 until December 2021. AIMS: We aimed to determine the efficacy and safety of Impella using real-world data from IMPELLA-PL and compare these with other registries. METHODS: IMPELLA-PL data were analyzed to determine primary endpoints: in-hospital mortality and rates of mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months post-discharge. RESULTS: Of 308 patients, 18% had CS and 82% underwent HR-PCI. In-hospital mortality rates were 76.4% and 8.3% in the CS and HR-PCI groups, respectively. The 12-month mortality rates were 80.0% and 18.2%, and post-discharge MACCE rates were 9.1% and 22.5%, respectively. Any access site bleeding occurred in 30.9% of CS patients and 14.6% of HR-PCI patients, limb ischemia in 12.7% and 2.4%, and hemolysis in 10.9% and 1.6%, respectively. CONCLUSIONS: Impella is safe and effective during HR-PCIs, in accordance with previous registry analyses. The risk profile and mortality in CS patients were higher than in other registries, and the potential benefits of Impella in CS require investigation.

Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.

Biochemical and clinical evaluation of endothelial injury after distal or traditional transradial access in percutaneous interventions.

BACKGROUND: Distal transradial access (dTRA) has been proposed as an alternative to traditional transradial access (TRA) in cardiac catheterization. AIMS: The study aimed to compare these two transradial approaches: TRA and dTRA in terms of clinical and biochemical aspects. METHODS: Two hundred patients who qualified for the elective coronary procedure were included. The patients were assigned to one of the groups depending on their vascular access. The groups were compared in terms of perceived pain using the Visual Analogue Scale (VAS), time of gaining access, need for conversion, and local complications. Additionally, in forty patients circulating endothelial injury markers: endothelin 1 (ET-1), interleukin 8 (IL-8), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were assessed. RESULTS: Successful cannulation was obtained in 84 (100%) in the TRA group and in 98 (84%) subjects in the dTRA (P <0.001). dTRA was associated with higher level of pain perceived at the time of gaining vascular approach than TRA; median VAS score (interquartile range [IQR]): 4 (2-5) vs. 2 (2-4) (P = 0.04). The mean time (standard deviation [SD]) needed to cannulate the artery in dTRA was longer than in TRA: 81 (8) seconds vs. 50 (4) seconds (P = 0.04). ET-1 concentration was (SD) 2.08 (0.19) pg/ml [dTRA] vs. 2.00 (0.29) [TRA] pg/ml (P = 0.83); sVCAM-1: 12.71 (3.97) ng/ml vs. 12.86 (4.29) ng/ml (P = 0.98); IL-8: 8.81 (0.42) ng/ml vs. 9.15 (0.52) ng/ml (P = 0.62). Th number of complications after procedures did not differ between these two approaches. CONCLUSIONS: Cannulation of dTRA is associated with a lower success rate and higher pain perceived. dTRA is not inferior to TRA when safety issues and vascular injury are considered.

A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI.

BACKGROUND: Ischemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS). FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant. We tested the feasibility, safety and potential utility of FDY-5301 as a treatment to limit ischemia-reperfusion injury, in patients with first-time STEMI undergoing emergency PPCI. METHODS: STEMI patients (n = 120, median 62 years) presenting within 12 h of chest pain onset were randomized at 20 PPCI centers, in a double blind Phase 2 clinical trial, to receive FDY-5301 (0.5, 1.0 or 2.0 mg/kg) or placebo prior to reperfusion, to evaluate the feasibility endpoints. Participants underwent continuous ECG monitoring for 14 days after PPCI to address pre-specified cardiac arrhythmia safety end points and cardiac magnetic resonance imaging (MRI) at 72 h and at 3 months to assess exploratory efficacy end points. RESULTS: Intravenous FDY-5301 was delivered before re-opening of the infarct-related artery in 97% participants and increased plasma iodide levels ~1000-fold within 2 min. There was no significant increase in the primary safety end point of incidence of cardiac arrhythmias of concern. MRI at 3 months revealed median final infarct sizes in placebo vs. 2.0 mg/kg FDY-5301-treated patients of 14.9% vs. 8.5%, and LV ejection fractions of 53.9% vs. 63.2%, respectively, although the study was not powered to detect statistical significance. In patients receiving FDY-5301, there was a significant reduction in the levels of MPO, MMP2 and NTproBNP after PPCI, but no reduction with placebo. CONCLUSIONS: Intravenous FDY-5301, delivered immediately prior to PPCI in acute STEMI, is feasible, safe, and shows potential efficacy. A larger trial is justified to test the effects of FDY-5301 on acute ischemia-reperfusion injury and clinical outcomes. CLINICAL TRIAL REGISTRATION: CT.govNCT03470441; EudraCT 2017-000047-41.

Ticagrelor-Related Severe Dyspnoea: Mechanisms, Characteristic Features, Differential Diagnosis and Treatment.

With a growing number of patients on ticagrelor therapy after stent implantation, we observe many cases of side effects of the drug, mostly dyspnoea and bradycardia. In our article we present 2 patients, in which the symptoms were particularly severe. Then we describe possible mechanisms of these complications, explain how to carry out differential diagnosis, discuss when to switch ticagrelor to other antiplatelet drug and finally we present the way to deal with the symptoms.

Remote Ischemic Preconditioning in Renal Protection During Elective Percutaneous Coronary Intervention.

Remote ischemic preconditioning (RIPC) exerts protection in remote organs. The purpose of this study was to investigate the potential of RIPC to prevent contrast induced nephropathy. One hundred and twenty four patients were randomized to elective percutaneous coronary intervention with or without RIPC. RIPC was performed using three cycles of 5-min inflation to 200 mmHg of a standard upper arm blood pressure cuff. The time between the last inflation cycle and the coronary intervention was less than 2 h. The primary endpoint was the incidence of contrast-induced nephropathy based on the standard criteria of the serum creatinine (SC) and cystatin C (CC) levels. The rates of major cardiac and cerebral adverse events (MACCE) during 1 year follow-up were evaluated. We found that contrast-induced nephropathy assessed by SC occurred in 4.9% (3/61) patients with RIPC and in 12.1% (7/58) patients without it (p = 0.20). Nephropathy assessed by CC occurred in 1.7% (1/58) patients with RIPC and 3.5% (2/57) patients without it (p = 0.62). There was no coincidence between the diagnosis of contrast-induced nephropathy based on SC and CC (McNemar test 0.012, κ = 0.28); SC was a more sensitive marker of nephropathy than CC (ten and three cases, respectively). The MACCE rate during the year of follow-up tended to be lower with the ischemic preconditioning than without it, four vs. six cases, respectively. We conclude that RIPC prior to percutaneous coronary intervention has no major influence on the development of contrast-induced nephropathy and does not improve the one-year outcome.

Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I).

BACKGROUND: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein-mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. METHODS: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). RESULTS: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar. CONCLUSIONS: Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262.

Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction.

BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. DESIGN: The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 × ULN, total bilirubin >2 × ULN, serum creatinine ≥1.5×baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. SUMMARY: The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo.

[ST-elevation myocardial infarction caused by very late stent thrombosis]. / Ostry zawal serca z uniesieniem odcinka ST spowodowany bardzo pózna zakrzepica w stencie.

The case of a 46 year-old man suffering from diabetes mellitus and dyslipidaemia hospitalised with acute coronary syndrome with ST-segment elevation caused by very late in-stent thrombosis is presented.

The recurrence after ten years - "mother in-law variant" of tako-tsubo syndrome.

The recurrence of left ventricular apical ballooning (LVAB) or tako-tsubo syndrome seems to be rare. Little data exists regarding the recurrence of the disease, especially over the long-term follow-up. We present a case of relapse of LVAB after ten years.

[Severity of coronary artery disease in patients with acute coronary syndrome without ST segment elevation]. / Stopien zaawansowania choroby wiencowej u pacjentów z ostrym zespolem wienicowym bez uniesienia odcinka ST.

Risk stratification of patients presenting to the hospital with acute coronary syndrome (ACS) is usually based on ECG assessment, and several clinical and biochemical criteria, which are all intended to identify subjects with more severe disease, who might benefit from aggressive medical or interventional treatment. However, no one widely accepted jeopardy score is available. Our aim was to determine whether the initial ECG, biochemical data and past medical history correlate with the extent of coronary artery disease in patients with ACS thus identifying subjects with severe coronary artery disease (CAD) who may benefit from the early invasive strategy. Patients' data was prospectively collected and retrospectively analysed according to the result of angiography examination. Our cohort consisted of 220 consecutive patients hospitalised due to typical chest pain (> 5 min.) occurring at rest within the last 24 hours. Study group comprised of 115 patients, who were subsequently subjected to coronary angiography Blood for qualitative troponin I test (Cardiac STATus, Spectral Inc., NJ, USA), and other routine biochemistry tests was drawn and ECG was done on admission. Chi-square and Pearson correlation tests were used for statistical analysis, p < 0.05 being considered statistically significant. Stepwise forward regression analysis was used to identify variables predictive of significant coronary artery stenosis. We have identified 65 patients with significant and 5 patients with insignificant multivessel stenosis, 33 patients with significant and 7 patients with insignificant single vessel disease. Five patients had normal coronary arteries. Male sex was significantly more prevalent among patients with coronary artery disease than with normal arteries (71% vs. 40%, p = 0.02). No differences in biochemistry values were seen among the groups. There was a significant difference in the prevalence in ST segment depression (p = 0.03) among these patients and in the incidence of plasma fibrinogen levels of >380 mg% (p = 0.02), those findings being most frequently encountered in significant multi- and single-vessel disease subjects. Hypertension, myocardial infarction more than 10 days ago, history of smoking, hypercholesterolemia and diabetes were independent predictors of the presence of significant stenosis. Assessment of admitting ECG and troponin I together with patients medical history may allow for identification of ACS patients with significant CAD that may benefit from early invasive treatment.

[Clinical and angiographic correlates of coronary calcium scoring in multislice computed tomography (MSCT)]. / Zwiazek miedzy wskaznikiem uwapnienia tetnic wiencowych w wielorzedowej tomografii komputerowej a danymi klinicznymi i angiograficznymi.

BACKGROUND: The MSCT calcium scoring allows to identify patients with increased coronary event risk or at early stages of coronary artery disease (CAD). AIM: The aim of the study was to find the correlation of calcium score with various clinical features and degree of coronary stenosis. METHODS: 40 consecutive patients (10 women) with angiographically proven coronary artery disease were assessed for coronary calcium score by means of MSCT not later than 48 hours after the angiography. The acquisition parameters were as follows: 3.2 mm slice thickness, 1.6 mm increment, pitch 1.25, 120 kV, 200 mAs, rotation time of 500 ms, supine patients during single breath-hold. The calcium score was semiautomatically calculated taking into account the size and density higher than 130 Hounsfield units. The clinical features such as the presence of hypertension, diabetes, dyslipidaemia, obesity (body mass index), smoking, CCS angina score, previous myocardial infarction, CAD duration, degree of stenosis and diffused disease were also analysed by means of Spearman's test. RESULTS: The calcium score in the left anterior descending artery (LAD) 271 + 598 showed good correlation with the degree of stenosis in the LAD 69 +/- 37 (r = 0.591, p<0.0001) and angina score (median 2, p<0.001). It was also correlated as well as calcium score in the LMA 55 +/- 147 with the CAD duration of 9 +/- 9 years and diabetes (p<0.01). The CS in the RCA 102 +/- 362 was associated with the diabetes, dyslipidaemia and obesity with the p<0.03. The score in the LCX 282 +/- 797 was correlated with the degree of stenosis in every artery (p<0.001 for the LCX = 56 +/- 39). The total calcium score 675 +/- 1462 was associated with the angina score, CAD duration (p<0.001), diffused disease and the stenosis in the LAD and LCX (p<0.0001). CONCLUSION: The total and the LAD coronary calcium score may be associated with the severity of symptoms, degree of stenosis in the LAD and disease extent. The calcium deposits in the RCA may be more frequent in patients with metabolic disorders.

Severity of coronary artery disease in patients with acute coronary syndrome without ST segment elevation is related to baseline troponin I and ST-segment depression.

BACKGROUND: Risk assessment for patients admitted with acute coronary syndrome (ACS) is usually based on the past medical history, along with several clinical and biochemical criteria. We hypothesised that stratification of patients with ACS according to the presence of ST-segment depression and results of a qualitative troponin I test would identify subjects with more severe disease who may benefit from an earlier, more aggressive strategy. MATERIAL/METHODS: The study group consisted of 115 patients hospitalized for typical chest pain (>5 min) occurring within the last 24 hours, with coronary angiography. Blood was drawn for routine biochemistry and qualitative troponin I testing, and ECG was performed on admission. RESULTS: Patients were classified according to the presence of ST segment depression (ST) and the troponin I test results (T) into three categories: group A, consisting of 34 patients with ST+/T+; group B, consisting of 84 patients with either ST+/T- or ST-/T+; and group C, consisting of 7 subjects with ST-/T-. This stratification correlated significantly with the extent of coronary artery disease (p=0.0004). Significant coronary artery stenosis was significantly more prevalent in patients from groups A and B than in C (p<0.002). No difference in the patients' medical history, apart from more frequent AMI within the past 10 days in group A (p=0.009) was found between groups. CONCLUSIONS: Admission assessment of ECG and troponin I tests in patients with ACS may identify subjects with significant coronary artery disease, who are at high risk and could benefit from aggressive therapy.

Plasma fibrinogen and troponin I in acute coronary syndrome and stable angina.

We aimed to determine whether there is a stratification among patients with different stages of coronary artery disease with respect to plasma fibrinogen levels, and to assess diagnostic value of plasma fibrinogen in comparison to troponin I in patients with acute coronary syndrome. Fifty-one consecutive patients presenting to our department with acute coronary syndrome within the last 24 h and 52 patients with stable angina with no episode of unstable disease within the last month were analysed. Forty-nine patients with acute coronary syndrome in which both troponin I and fibrinogen levels were present were further evaluated. Blood was collected on admission for routine laboratory tests. Statistical analysis was done using Student's t-test, Pearson correlation and chi-square test, P<0.05 being considered statistically significant. Plasma fibrinogen levels (g/l) were significantly higher in patients presenting with unstable than with stable angina (3.87+/-1.2 vs. 3.26+/-0.65 P=0.002). We have found significant correlation between fibrinogen and troponin I levels in unstable patients (r=0.43, P=0.0015). In patients with acute coronary syndrome an increased inflammation and cardiac injury seem to coexist and correlate. These results seem to confirm the role of this acute phase protein in the pathophysiology of acute coronary syndrome.