In-Hospital Levels of Circulating MicroRNAs as Potential Predictors of Left Ventricular Remodeling Post-Myocardial Infarction.

Background and Objectives: Biochemical and molecular regulation of both adaptive and pathological responses of heart tissue to ischemic injury is widely investigated. However, it is still not fully understood. Several biomarkers are tested as predictors of left ventricle (LV) remodeling after myocardial infarction (MI). The aim of this study was to assess the relationship between selected microRNAs (miRNAs) and LV function and morphology in patients after MI. Materials and Methods: Selected miRNAs related to heart failure were assessed in the acute phase of MI: miR-150-3p, miR-21-5p, miR-19b-3p, miR-155-5p, miR-22-5p. Echocardiography with 3D imaging was performed at baseline and after 6 months. Remodeling was defined as >20% increase in LV end-diastolic volume, whereas reverse remodeling was defined as >10% reduction in LV end-systolic volume. Results: Eighty patients entered the registry. Remodeling occurred in 26% and reverse remodeling was reported in 51% of patients. In the presented study, none of the analyzed miRNAs were found to be a significant LV remodeling predictor. The observed correlations between miRNAs and other circulating biomarkers of myocardial remodeling were relatively weak. Conclusions: Our analysis does not demonstrate an association between the analyzed miRNAs and LV remodeling in patients with MI.

Thrombus containing lesions strategies during primary percutaneous coronary interventions in ST-segment elevation myocardial infarction: insights from ORPKI National Registry.

In the era of potent P2Y12 inhibitors, according to current guidelines, treatment with glycoprotein IIb/IIIa inhibitors (GPIs) should be limited to bail-out and/or highly thrombotic situations. Similarly, the recommendation for aspiration thrombectomy (AT) is downgraded to very selective use. We examine the prevalence, and predictors of GPI and AT use in STEMI patients referred to primary percutaneous coronary intervention (PCI). Data on 116,873 consecutive STEMI patients referred to primary PCI in Poland between 2015 and 2020 were analyzed. GPIs were administered in 29.3%, AT was used in 11.6%, and combined treatment with both in 6.1%. There was a mild trend toward a decrease in GPI and AT usage during the analyzed years. On the contrary, there was a rapid growth of the ticagrelor/prasugrel usage rate from 6.5 to 48.1%. Occluded infarct-related artery at baseline and no-reflow during PCI were the strongest predictors of GPI administration (OR 2.3; 95% CI 2.22-2.38 and OR 3.47; 95% CI 3.13-3.84, respectively) and combined usage of GPI and AT (OR 4.4; 95% CI 4.08-4.8 and OR 3.49; 95% CI 3.08-3.95 respectively) in a multivariate logistic regression model. Similarly, the administration of ticagrelor/prasugrel was an independent predictor of both adjunctive treatment strategies. In STEMI patients in Poland, GPIs are selectively used in one in four patients during primary PCI, and the combined usage of GPI and AT is marginal. Despite the rapid growth in potent P2Y12 inhibitors usage in recent years, GPIs are selectively used at a stable rate during PCI in highly thrombotic lesions.

The Impact of Age on the Physiological Assessment of Borderline Coronary Stenoses.

Background and Objectives: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through ischemia assessment via one of the recommended methods of invasive evaluation. This study aimed to assess whether clinical factors influence the risk of a positive result in invasive myocardial ischemia assessment and if these potential factors change with the patient's age and the consistency of ischemia assessment. Materials and Methods: Data were collected retrospectively on all consecutive patients hospitalized in the University Hospital in Krakow between 2020 and 2021, on whom physiological assessments of coronary circulation were performed. Patients were divided into two groups: patients aged 60 or younger and patients older than 60. Results: Despite the older patients having more risk factors for CAD, their physiological assessment results of borderline lesions were similar to those of the younger patients. Positive fractional flow reserve (FFR) assessments were obtained from almost 50% of vessels. In the younger patients, cigarette use and type 2 diabetes mellitus increased the risk of a positive FFR result by 3.5 and 2.5 times, respectively. In the older patients, male gender and peripheral vascular disease significantly increased the risk of a positive FFR by 2.5 and 2 times, respectively. Conclusions: Clinical characteristics of patients undergoing physiological assessment of borderline coronary stenosis varied significantly by age. Refining the definition of borderline lesions to include age, gender, and other factors may improve the identification of patients who would benefit from physiological assessment and coronary revascularization.

Does the incidence of infectious endocarditis show seasonal patterns? - a single center retrospective study.

I n t r o d u c t i o n: Seasonal variation has been observed for bacterial and viral infections (e.g., COVID-19 [1]), but also for numerous cardiac problems. However, little information is available on the seasonality of infectious endocarditis (IE), a rare disease that is usually linked to a bacterial origin. Data from the Polish population are lacking. Materials and M e t h o d s: Our retrospective study focused on the identification of patients with IE, who were hospitalized at the University Hospital in Krakow between 2005-2022. For this purpose, we searched the medical records system using the ICD-10 code. We decided to divide our patients into four groups (winter, spring, summer, autumn), based on the date of admission to the hospital. Comparison of the distribution of IE incidents by season was performed with the ch2 test. R e s u l t s: One hundred and ten patients were included in the study (median age 62.5 years (range 20-94), 72 men (65.45%)). The left native valve IE was diagnosed in 49% of the patients, the prosthetic valve IE in 16%, the right valve IE in 27% and the implantable cardiac electronic devices IE in 12% of the subjects. The outcomes comprised of cardiac surgery (n = 53), embolism (n = 16), death (n = 15) and metastatic infections (n = 5). No differences in the incidence of IE by season were observed. C o n c l u s i o n s: In the preliminary observation of IE cases of patients admitted to the University Hospital in Krakow, Poland no seasonal pattern of IE was detected. Therefore, IE should be taken into account in the differential diagnosis at any time of the year.

MicroRNA composition of plasma extracellular vesicles: a harbinger of late cardiotoxicity of doxorubicin.

BACKGROUND: The use of doxorubicin is associated with an increased risk of acute and long-term cardiomyopathy. Despite the constantly growing number of cancer survivors, little is known about the transcriptional mechanisms which progress in the time leading to a severe cardiac outcome. It is also unclear whether long-term transcriptomic alterations related to doxorubicin use are similar to transcriptomic patterns present in patients suffering from other cardiomyopathies. METHODS: We have sequenced miRNA from total plasma and extracellular vesicles (EVs) from 66 acute lymphoblastic leukemia (ALL) survivors and 61 healthy controls (254 samples in total). We then analyzed processes regulated by differentially expressed circulating miRNAs and cross-validated results with the data of patients with clinically manifested cardiomyopathies. RESULTS: We found that especially miRNAs contained within EVs may be informative in terms of cardiomyopathy development and may regulate pathways related to neurotrophin signaling, transforming growth factor beta (TGFß) or epidermal growth factor receptors (ErbB). We identified vesicular miR-144-3p and miR-423-3p as the most variable between groups and significantly correlated with echocardiographic parameters and, respectively, for plasma: let-7g-5p and miR-16-2-3p. Moreover, vesicular miR-144-3p correlates with the highest number of echocardiographic parameters and is differentially expressed in the circulation of patients with dilated cardiomyopathy. We also found that distribution of particular miRNAs between of plasma and EVs (proportion between compartments) e.g., miR-184 in ALL, is altered, suggesting changes within secretory and miRNA sorting mechanisms. CONCLUSIONS: Our results show that transcriptomic changes resulting from doxorubicin induced myocardial injury are reflected in circulating miRNA levels and precede development of the late onset cardiomyopathy phenotype. Among miRNAs related to cardiac function, we found vesicular miR-144-3p and miR-423-3p, as well as let-7g-5p and miR-16-2-3p contained in the total plasma. Selection of source for such studies (plasma or EVs) is of critical importance, as distribution of some miRNA between plasma and EVs is altered in ALL survivors, in comparison to healthy people, which suggests that doxorubicin-induced changes include miRNA sorting and export to extracellular space.

Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study.

BACKGROUND: Pleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status. METHODS: Biochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension. RESULTS: Clinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM. CONCLUSIONS: Our preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.

Biotransformation of organic nitrates by glutathione S-transferases and other enzymes: An appraisal of the pioneering work by William B. Jakoby.

Organic nitrates (R-ONO2; R, organic residue) such as nitroglycerin are used as drugs in part for more than a century. Their pharmacological use is associated with clinically relevant tolerance which is reportedly known since 1888. The underlying mechanisms of both, the mechanisms of action and the main pharmacological effect, which is vasodilatation and reduction of blood pressure, and the development of tolerance, which means increasing need of drug amount in sustained long-term therapy, are still incompletely understood. William B. Jakoby and associates were the first to report the biotransformation of organic nitrates, notably including nitroglycerin (i.e., glycerol trinitrate; GTN), by glutathione S-transferase (GST)-catalyzed conjugation of glutathione (GSH) to the nitrogen atom of one of the three nitrate groups of GTN to generate glutathione sulfenyl nitrite (glutathione thionitrate, S-nitroglutathione; GSNO2). Jakoby's group was also the first to suggest that GSNO2 reacts with a second GSH molecule to produce inorganic nitrite (ONO-) and glutathione disulfide (GSSG) without the catalytic involvement of GST. This mechanism has been adopted by others to the biotransformation of GTN by mitochondrial aldehyde dehydrogenase (mtALDH-(CysSH)2) which does not require GSH as a substrate. The main difference between these reactions is that mtALDH forms an internal thionitrate (mtALDH-(CysSH)-CysSNO2) which releases inorganic nitrite upon intra-molecular reaction to form mtALDH disulfide (mtALDH-(CysS)2). Subsequently, ONO- and GSNO2 are reduced by several proteins and enzymes to nitric oxide (NO) which is a very potent activator of soluble guanylyl cyclase to finally relax the smooth muscles thus dilating the vasculature. GSNO2 is considered to rearrange to GSONO which undergoes further reactions including GSNO and GSSG formation. The present article is an appraisal of the pioneering work of William B. Jakoby in the area of the biotransformation of organic nitrates by GST. The two above mentioned enzymatic reactions are discussed in the context of tolerance development to organic nitrates, still a clinically relevant pharmacological concern.

Experience with Optical Coherence Tomography Enhanced by a Novel Software (Ultreon™ 1.0 Software)-The First One Hundred Cases.

Introduction: Optical coherence tomography (OCT) intravascular imaging including the latest version Ultreon™ 1.0 Software (Abbott Vascular, Santa Clara, CA, USA), not only improve patients prognosis, but also facilitates improved percutaneous coronary intervention (PCI). Objectives: The aim of the study was to compare procedure related decision making, procedural indices, clinical outcomes according to the extent of stent expansion and assess risk factors of underexpansion in patients treated with PCI using OCT. Methods: The study comprised 100 patients, which were divided in groups according to the extent of stent expansion: <90 (29 patients) and ≥90% (71 patients). Comparison of OCT parameters, selected clinical and procedural characteristics was performed between groups. We assessed clinical outcomes during the follow-up: major adverse cardiovascular events and risk factors of stent underexpansion. Results: Patients from the stent underexpansion group were treated more often in the past with percutaneous peripheral interventions (p=0.02), no other significant differences being noted in general characteristics, procedural characteristics or clinical outcomes comparing both groups. Significant predictors of stent underexpansion assessed by simple linear univariable analysis included: hypercholesterolemia, obstructive bronchial diseases and treatment with inhalators, family history of cardiovascular disease, PCI of other than the left main coronary artery, stent and drug-eluting stent implantation, PCI without drug-eluting balloon, paclitaxel antimitotic agent, greater maximal stent diameter and lower mean Euroscore II value. Univariable logistic regression analysis revealed a correlation between stent underexpansion and greater creatinine serum concentration before [OR: 0.97, 95%CI: 0.95-0.99, p=0.01] and after PCI [OR: 0.98, 95%CI: 0.96-0.99, p=0.02]. Conclusions: Based on the presented analysis, the degree of stent expansion is not related to the selected procedural, OCT imaging indices and clinical outcomes. Logistic regression analysis confirmed such a relationship for creatinine level.

The growing need for reliable online health information during lockdown in Europe: An infodemiologic analysis of myocardial infarction management in the COVID-19 era.

I n t r o d u c t i o n: The COVID-19 pandemic has put healthcare systems worldwide under huge strain, resulting in a significant loss of their capacity and availability. Patients have become more reluctant to contact their doctors or call an ambulance in case of myocardial infarction (MI) symptoms onset. It has been accompanied by a significant decrease in the number of coronary angiography and PCI procedures performed. O b j e c t i v e s: The aim of the study is to evaluate the role of online health information in the patient- dependent phase of MI management during the COVID-19 lockdown in Europe. Methods: We analyzed Google Trends data on the popularity of phrases related to MI symptoms, respiratory tract infection, urological complaints, and terms unrelated to health, for the period of the first COVID-19 lockdown, along with the data from the corresponding weeks from 2017-2019 in seven European countries. R e s u l t s: The search volume for particular symptoms of myocardial infarction increased in all studied countries, compared to the analogous period from 2017-2019, with a significant increase in for chest pain, shortness of breath, fear, and palpitations in most countries. These changes have not been accompanied by increased interest in terms related to respiratory tract infection symptoms and urological complaints. C o n c l u s i o n s: Our findings suggest that during lockdown, patients with MI symptoms may have tried to manage their complaints on their own, using information from the Internet. This demonstrates the growing role of the Internet in the patient's decision-making process in the emergency situation, indicating a growing need for reliable and freely available online information provided by healthcare professionals.

Microvascular angina (Cardiac Syndrome X) from a historical overview, epidemiology, pathophysiology to treatment recommendations - a minireview.

Microvascular angina (MVA) is a condition characterized by the presence of angina-like chest pain, a positive response to exercise stress tests, and no significant stenosis of coronary arteries in coronary angiography, with absence of any other specific cardiac diseases. The etiology of this syndrome is still not known and it is probably multifactorial. Coronary microvascular dysfunction is proposed as the main pathophysiological mechanism in the development of MVA. Altered somatic and visceral pain perception and autonomic imbalance, in addition to myocardial ischemia, has been observed in subjects with MVA, involving dynamic variations in the vasomotor tone of coronary microcirculation with consequent transient ischemic episodes. Other theories suggest that MVA may be a result of a chronic inflammatory state in the body that can negatively influence the endothelium or a local imbalance of factors regulating its function. This article presents the latest information about the epidemiology, diagnostics, etiopathogenesis, prognosis, and treatment of patients with MVA.

Long-Term Prognostic Significance of High-Sensitive Troponin I Increase during Hospital Stay in Patients with Acute Myocardial Infarction and Non-Obstructive Coronary Arteries.

Background and Objectives: A topic already widely investigated is the negative prognostic value regarding the extent of high sensitive troponin I (hs-TnI) increases among patients with myocardial infarction (MI) and obstructive coronary atherosclerosis compared to a group of patients with MI and non-obstructive coronary atherosclerosis (MINOCA). Thus, the aim of this study was to evaluate the prognostic value concerning the extent of hs-TnI increase on clinical outcomes among patients with a MINOCA working diagnosis. Materials and Methods: We selected 337 consecutive patients admitted to hospital with a working diagnosis of MINOCA. The patients were divided in three groups according to the extent of hs-TnI increase during hospitalization (increase ≤5-times above the limit of the upper norm, >5 and ≤20-times, and >20-times). The study endpoints included all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE; cerebral stroke and transient ischemic attacks, MI, coronary artery revascularization, either percutaneous coronary intervention or coronary artery bypass grafting and all-cause mortality). Results: During the mean follow-up period of 516.1 ± 239.8 days, using Kaplan-Meier survival curve analysis, significantly higher mortality rates were demonstrated among patients from the group with the greatest hs-TnI increase compared to the remaining groups (p = 0.01) and borderline values for MACCE (p = 0.053). Multivariable cox regression analysis did not confirm hs-TnI among factors related to increased MACCE or all-cause mortality rates. Conclusion: While a relationship between clinical outcomes and the extent of the hs-TnI increase among patients with a MINOCA working diagnosis remains, it does not seem to be not as strong as it is in patients with obstructive coronary atherosclerosis.

Past strong experiences determine acute cardiovascular autonomic responses to acoustic stress.

BACKGROUND: Stress is a major risk factor for cardiovascular (CV) disease. We hypothesized that past strong experiences might modulate acute CV autonomic responses to an unexpected acoustic stimulus. A i m: The study's aim was to compare acute CV autonomic responses to acoustic stress between students with and without a past strong experience associated with the acoustic stimulus. MATERIALS AND METHODS: Twenty five healthy young volunteers - medical and non-medical students - were included in the study. CV hemodynamic parameters, heart rate (HR), and blood pressure (BP) variability were assessed for 10 min at rest and for 10 min after two different acoustic stimuli: a standard sound signal and a specific sound signal used during a practical anatomy exam (so-called "pins"). RESULTS: Both sounds stimulated the autonomic nervous system. The "pins" signal caused a stronger increase in HR in medical students (69 ± 10 vs. 73 ± 13 bpm, p = 0.004) when compared to non-medical students (69 ± 6 vs. 70 ± 10, p = 0.695). Rises in diastolic BP, observed 15 seconds after sound stressors, were more pronounced after the "pins" sound than after the standard sound signal only in medical students (3.1% and 1.4% vs. 3% and 4.4%), which was also reflected by low-frequency diastolic BP variability (medical students: 6.2 ± 1.6 vs. 4.1 ± 0.8 ms2, p = 0.04; non-medical students: 6.0 ± 4.3 vs. 4.1 ± 2.6 ms2, p = 0.06). CONCLUSIONS: The "pins" sound, which medical students remembered from their anatomy practical exam, provoked greater sympathetic activity in the medical student group than in their non-medical peers. Thus, past strong experiences modulate CV autonomic responses to acute acoustic stress.

Novel antidiabetic drugs in diabetic kidney disease accompanying type 2 diabetes - a minireview.

Intensive hypoglycemic treatment is the strongest preventive strategy against the development of microvascular complications of type 2 diabetes (T2DM), including diabetic nephropathy. However, some antidiabetic drugs, i.e. sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have an additional renoprotective effect beyond glucose control by itself. Similar, both SGLT-2i and GLP1-RA have been demonstrated to decrease the risk of adverse cardiovascular (CV) events in CV outcome trials. Nevertheless, there are relevant differences in CV and renal effects of SGLT-2i and GLP1-RA. First, SGLT2i reduced the incidence and progression of albuminuria and prevented loss of kidney function, while predominant renal benefits of GLP1-RA were driven by albuminuria outcomes. Second, the risk of heart failure (HF) hospitalizations decreased on SGLT2i but not on GLP1-RA, which gives priority to SGLT2i in T2DM and HF, especially with depressed EF. Third, either GLP1-RA (reducing predominantly atherosclerosis-dependent events) or SGLT-2i, should be used in T2DM and established atherosclerotic CV disease (ASCVD) or other indicators of high CV risk. In this review, we have briefly compared clinical practice guidelines of the American Diabetes Association (2020 and 2021 versions), Polish Diabetes Association (2020) and the European Society of Cardiology/European Association for the Study of Diabetes (2019), with a focus on the choice between SGLT-2i and GLP1-RA in patients with diabetic kidney disease.

Depressed systemic arterial compliance and impaired left ventricular midwall performance in aortic stenosis with concomitant type 2 diabetes: a retrospective cross-sectional study.

BACKGROUND: Degenerative aortic stenosis (AS), a disease of the elderly, frequently coexists with concomitant diseases, including type 2 diabetes (T2DM) which amplifies the cardiovascular (CV) risk. T2DM affects left ventricular (LV) structure and function via hemodynamic and metabolic factors. In concentric LV geometry, typical for AS, indices of LV midwall mechanics are better estimates of LV function than ejection fraction (EF). Effects of T2DM coexisting with AS on circumferential LV midwall systolic function and large artery properties have not been reported so far. Our aim was to compare characteristics of AS patients with and without T2DM, with a focus on LV midwall systolic function and arterial compliance. METHODS: Medical records of 130 electively hospitalized patients with moderate or severe isolated degenerative AS were retrospectively analyzed. Exclusion criteria included clinical instability, atrial fibrillation, coronary artery disease and relevant non-cardiac diseases. From in-hospital echocardiography and blood pressure, we calculated LV midwall fractional shortening (mwFS), circumferential end-systolic LV wall stress (cESS) and valvulo-arterial impedance (Zva), estimates of LV afterload, as well as systemic arterial compliance. RESULTS: Patients with (n = 50) and without T2DM (n = 80) did not differ in age, AS severity, LV mass and LV diastolic diameter. T2DM patients exhibited elevated cESS (247 ± 105 vs. 209 ± 84 hPa, p = 0.025) and Zva (5.8 ± 2.2 vs. 5.1 ± 1.8 mmHg per mL/m2, p = 0.04), and lower stroke volume index (33 ± 10 vs. 38 ± 12 mL/m2, p = 0.01) and systemic arterial compliance (0.53 ± 0.16 vs. 0.62 ± 0.22 mL/m2 per mmHg, p = 0.01). mwFS (11.9 ± 3.9 vs. 14.1 ± 3.7%, p = 0.001), but not EF (51 ± 14 vs. 54 ± 13%, p = n.s.), was reduced in T2DM. mwFS and cESS were inversely interrelated in patients both with (r = - 0.59, p < 0.001) and without T2DM (r = - 0.53, p < 0.001) By multiple regression, higher cESS (p < 0.001) and T2DM (p = 0.02) were independent predictors of depressed mwFS. CONCLUSIONS: In AS, coexistent T2DM appears associated with reduced systemic arterial compliance and LV dysfunction at the midwall level, corresponding to slightly depressed myocardial contractility.

Distinct associations between plasma osteoprotegerin, homoarginine and asymmetric dimethylarginine in chronic kidney disease male patients with coronary artery disease.

High plasma osteoprotegerin (OPG) and asymmetric dimethylarginine (ADMA) and low homoarginine (hArg) predict adverse renal and cardiovascular (CV) outcomes. In patients with chronic kidney disease and stable coronary artery disease, plasma OPG correlated with hArg (r = - 0.37, P = 0.03) and the hArg/ADMA molar ratio (r = - 0.46, P = 0.009), which was maintained upon adjustment for renal function. Elevated OPG levels and decreased hArg/ADMA ratios independently predicted 4-year composite CV and renal endpoints (CV death or progression to dialysis). Thus, high OPG and low hArg/ADMA ratio, albeit interrelated, appear to independently contribute to adverse clinical outcome.

Platelet Reactivity And Circulating Platelet-Derived Microvesicles Are Differently Affected By P2Y12 Receptor Antagonists.

Background: Platelet-derived microvesicles (PMVs), shed from platelet surface membranes, constitute the majority of circulating microvesicles and have been implicated in procoagulant, pro-inflammatory and pro-atherosclerotic effects. Our aim was to compare plasma PMVs numbers in relation to platelet reactivity during dual antiplatelet therapy (DAPT) with various P2Y12 adenosine diphosphate (ADP) receptor antagonists. Methods: In pre-discharge men treated with DAPT for an acute coronary syndrome, plasma PMVs were quantified by flow cytometry on the basis of CD62P (P-selectin) and CD42 (glycoprotein Ib) positivity, putative indices of PMVs release from activated and all platelets, respectively. ADP-induced platelet aggregation was measured by multiple-electrode aggregometry. Results: Clinical characteristics were similar in patients on clopidogrel (n=16), prasugrel (n=10) and ticagrelor (n=12). Platelet reactivity was comparably reduced on ticagrelor or prasugrel versus clopidogrel (p<0.01). Compared to clopidogrel-treated patients, CD42+/CD62P+ PMVs counts were 3-4-fold lower in subjects receiving ticagrelor (p=0.001) or prasugrel (p<0.05), while CD42+ PMVs were significantly reduced on ticagrelor (by about 6-fold, p<0.001), but not prasugrel (p=0.3). CD42+/CD62P+ PMVs numbers correlated positively to the ADP-induced aggregation on clopidogrel (p<0.01) or prasugrel (p<0.05), which was absent in ticagrelor users (p=0.8). CD42+ PMVs counts were unrelated to platelet reactivity (p>0.5). Conclusions: Higher antiplatelet potency of prasugrel and ticagrelor versus clopidogrel is associated with decreased plasma CD42+/CD62P+ PMVs numbers. However, in contrast to thienopyridines, the association of reduced CD42+/CD62P+ PMVs counts with ticagrelor use appears independent of its anti-aggregatory effect. Despite similar platelet-inhibitory activity of ticagrelor and prasugrel, only the treatment with ticagrelor seems associated with lower total PMVs release. Our preliminary findings may suggest a novel pleiotropic effect of ticagrelor extending beyond pure anti-aggregatory properties of the drug.

Association between low-grade chronic inflammation and depressed left atrial compliance in heart failure with preserved ejection fraction: A retrospective analysis.

BACKGROUND: A novel paradigm of diastolic heart failure with preserved ejection fraction (HFpEF) proposed the induction of coronary microvascular dysfunction by HFpEF comorbidities via a systemic pro-inflammatory state and associated oxidative stress. The consequent nitric oxide deficiency would increase diastolic tension and favor fibrosis of adjacent myocardium, which implies not only left ventricular (LV), but all-chamber myocardial stiffening. Our aim was to assess relations between low-grade chronic systemic inflammation and left atrial (LA) pressure-volume relations in real-world HFpEF patients. METHODS: We retrospectively analyzed medical records of 60 clinically stable HpEFF patients in sinus rhythm with assayed high-sensitive C-reactive protein (CRP) during the index hospitalization. Subjects with CRP >10 mg/L or coexistent diseases, including coronary artery disease, were excluded. LV and LA diameters and mitral E/E' ratio (an index of LA pressure) were extracted from routine echocardiographic records. A surrogate measure of LA stiffness was computed as the averaged mitral E/e' ratio divided by LA diameter. RESULTS: With ascending CRP tertiles, we observed trends for elevated mitral E/e' ratio (p <0.001), increased relative LV wall thickness (p = 0.01) and higher NYHA functional class (p = 0.02). The LA stiffness estimate and log-transformed CRP levels (log-CRP) were interrelated (r = 0.38, p = 0.003). On multi- variate analysis, the LA stiffness index was independently associated with log-CRP (ß ± SEM: 0.21 ± 0.07, p = 0.007) and age (ß ± SEM: 0.16 ± 0.07, p = 0.03), which was maintained upon adjustment for LV mass index and relative LV wall thickness. CONCLUSIONS: Low-grade chronic inflammation may contribute to LA stiffening additively to age and regardless of the magnitude of associated LV hypertrophy and concentricity. LA stiffening can exacerbate symptoms of congestion in HFpEF jointly with LV remodeling.

Endothelial dysfunction is independent of inflammation and altered CCR7 T cell expression in patients with ankylosing spondylitis.

OBJECTIVES: The accumulation of CCR7 (chemokine receptor 7) positive cells in the vessel wall may be involved in endothelial dysfunction and subsequent accelerated atherogenesis. CCR7 plays a crucial role in T cell and monocyte migration/homing and in priming of naive T lymphocytes in non-lymphoid tissues in chronic inflammatory diseases. Our objective was to investigate the endothelial function and inflammation-driven expression of CCR7 on T lymphocytes in patients with ankylosing spondylitis (AS). METHODS: We performed flow cytometry to assess the distribution of peripheral blood T cell subpopulations in the context of serum inflammatory markers (TNF-α, IL-6, sICAM-1) and asymmetric dimethylarginine (ADMA) in 38 patients with AS with active disease, and in 20 healthy controls. RESULTS: Patients with AS demonstrated higher ADMA (0.74±0.2 µmol/l vs. 0.64±0.15 µmol/l; p=0.03), as well as elevated inflammatory markers (TNFα, IL-6, sICAM-1) and increased proportions of circulating CCR7-positive lymphocytes largely attributable to elevated CD8+ naive T cells (47.1±17 vs. 34.3±13.1%; p=0.005). However, ADMA did not correlate with either CCR7-positive lymphocytes or inflammatory markers. CONCLUSIONS: We found an increased percentage of peripheral CCR7 T cells accompanied by endothelial dysfunction in patients with AS. The lack of direct associations between ADMA and inflammation may suggest the presence of other pathogenic mechanisms contributing to accelerated atherogenesis and increased cardiovascular risk in AS.

No Association of Proton Pump Inhibitor Use with Fasting or Postload Glycaemia in Patients with Cardiovascular Disease: A Cross-Sectional Retrospective Study.

Background: Proton pump inhibitor (PPI) use was reportedly associated with an excess of adverse cardiovascular (CV) events, thus making their systemic effects relevant to public health. PPIs reduce gastric acid secretion, causing increased gastrin release. Gastrin stimulates ß-cell neogenesis and enhances insulin release, exerting an incretin-like effect. Our aim was to assess, if PPI usage is associated with altered glycaemia in patients with CV disease. Methods: We retrospectively analyzed medical records of 102 subjects (80 with ischemic heart disease) who underwent a routine oral glucose tolerance test while hospitalized in a cardiology department. Fasting and 2-h postload glucose levels were compared according to PPI use for ≥1 month prior to admission. Results: Compared to 51 subjects without PPIs, those on a PPI were older, more frequently male, had a lower body-mass index and a tendency to a worse renal function. PPI users and non-users exhibited similar glucose levels at baseline (5.6 ± 0.9 vs. 5.5 ± 1.1 mmol/l, P = 0.5) and 2-hrs post glucose intake (9.8 ± 3.0 vs. 9.9 ± 3.4 mmol/l, P = 0.9). This was consistent across subgroups stratified by gender or diabetes status. The results were substantially unchanged after adjustment for different characteristics of subjects with and without PPIs. Conclusions: PPI use does not appear associated with altered glycaemia in subjects with CV disease. Unchanged glucose tolerance despite PPI usage may result from simultaneous activation of pathways that counteract the putative PPI-induced incretin-like effect.

Patient after renal transplantation with syncope: Role of echocardiography in upright position.

In Doppler echocardiography, testing left ventricular outflow tract (LVOT) gradient in the supine position (as is done in everyday practice) does not reflect the pathophysiology of this dynamic abnormality during the daily activities that trigger the symptoms (eg, syncope). LVOT obstruction is a dynamic phenomenon, strongly dependent on the left ventricular cavity size, geometric configuration of hypertrophy, load variability, contractility, and mitral apparatus abnormalities. LVOT gradient may develop not only in hypertrophic cardiomyopathy but also in various heart diseases. Recent investigations show that LVOT gradient should be measured also in the standing position. Here, we report the case of patient after renal transplantation, who developed LVOT gradient during orthostatic test. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:616-620, 2017.