Clinical features, etiology, and survival in patients with restrictive cardiomyopathy: A single-center experience.

BACKGROUND: Numerous prognostic factors have been proposed for cardiac amyloidosis (CA). The knowledge about other subtypes of restrictive cardiomyopathy (RCM) is scant. AIMS: This study aimed to elucidate the etiology and prognostic factors of RCM as well as assess cardiac biomarkers: high-sensitive troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and soluble suppression of tumorigenicity 2, as mortality predictors in RCM. METHODS: We enrolled 36 RCM patients in our tertiary cardiac department. All patients were screened for CA. Genetic testing was performed in 17 patients without CA. RESULTS: Pathogenic or likely pathogenic gene variants were found in 86% of patients, including 5 novel variants. Twenty patients died, and 4 had a heart transplantation during the study. Median overall survival was 29 months (8-55). The univariate Cox models analysis indicated that systolic and diastolic blood pressure, GDF-15, hs-TnT, NT-proBNP, left ventricular stroke volume, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e'), tricuspid annulus plane systolic excursion, early tricuspid valve annular systolic velocity, the presence of pulmonary hypertension, and pericardial effusion influenced survival (P <0.05). A worse prognosis was observed in patients with GDF-15 >1316 pg/ml, hs-TnT >42 ng/l, NT-proBNP >3383 pg/ml, and pericardial effusion >3.5 mm (Kaplan-Meier analysis, log-rank test, P <0.001). CONCLUSIONS: Genetic testing should be considered in every RCM patient where light-chain amyloidosis has been excluded. Survival remains poor regardless of etiology. Increased concentrations of GDF-15, hs-TNT, NT-proBNP, and pericardial effusion are associated with worse prognosis. Further studies are warranted.

Host body mass, not sex, affects ectoparasite loads in yellow-necked mouse Apodemus flavicollis.

We investigated the presence and potential causes of sex bias in ectoparasite infestations in the yellow-necked mouse Apodemus flavicollis. We compared the natural tick and flea burdens of male and female mice in a temperate beech forest and assessed whether the observed differences were driven by host sex or body mass. We found that males were more heavily infested by ticks compared to female mice. However, this difference was driven by host body mass, and not sex itself. Host body mass positively correlated with flea loads, but there was no evidence of sex bias in flea abundance. In addition, the abundance of both ticks and fleas infesting yellow-necked mice changed over time, both seasonally (month to month) and annually (year to year). Our results underscore the importance of the sexual size dimorphism and the parasite taxon as the primary factors that influence the occurrence of sex-biased parasitism in small mammals.

A new model for predicting adverse outcomes in arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive disease leading to ventricular arrhythmias and heart failure. Determining optimal time for heart transplantation (HTx) is challenging; therefore, it is necessary to identify risk factors for disease progression. OBJECTIVES: The study aimed to identify predictors of end­stage heart failure and to evaluate the role of biomarkers in predicting adverse outcomes in ARVC. PATIENTS AND METHODS: A total of 91 individuals with ARVC (59 men; mean [SD] age, 47 [16] years) were included. In all patients, information on medical history was collected, electrocardiography and echocardiography were performed, and serum levels of selected biomarkers (soluble form of the ST2 protein [sST2], galectin­3 [Gal­3], extracellular matrix metalloproteinases [MMP­2 and MMP­9], N­terminal pro-B­type natriuretic peptide [NT­proBNP], and high­sensitivity troponin T [hs­TnT]) were measured. Thereafter, the participants were followed for the primary end point of death or HTx, as well as the secondary end point of major arrhythmic events (MAEs), defined as sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter­defibrillator intervention. RESULTS: During the median (interquartile range) follow­up of 36.4 (29.8-41.2) months, 13 patients (14%) reached the primary end point of death or HTx, and 27 (30%) experienced MAEs. The patients who achieved the primary end point had higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT, but not of Gal-3 and MMP-9. Three factors turned out to be independent predictors of death or HTx: higher NT­proBNP concentration (≥890.3 pg/ml), greater right ventricular end­diastolic area (≥39 cm2), and a history of atrial tachycardia. None of the biomarkers predicted MAEs. CONCLUSIONS: An NT­proBNP concentration greater than or equal to 890.3 pg/ml, right ventricular end-diastolic area of 39 cm2 or greater, and a history of atrial tachycardia were identified as risk factors for death or HTx in ARVC. Higher levels of sST2, MMP­2, NT­proBNP, and hs­TnT were associated with reaching the primary end point of death or HTx. The biomarkers had no value in predicting ventricular arrhythmias.

From trees to fleas: masting indirectly affects flea abundance on a rodent host.

Mast seeding causes strong fluctuations in populations of forest animals. Thus, this phenomenon can be used as a natural experiment to examine how variation in host abundance affects parasite loads. We investigated fleas infesting yellow-necked mice in beech forest after 2 mast and 2 non-mast years. We tested 2 mutually exclusive scenarios: (1) as predicted by classical models of density-dependent transmission, an increase in host density will cause an increase in ectoparasite abundance (defined as the number of parasites per host), versus (2) an increase in host density will cause a decline in flea abundance ("dilution," which is thought to occur when parasite population growth is slower than that of the host). In addition, we assessed whether masting alters the relationship between host traits (sex and body mass) and flea abundance. We found a hump-shaped relationship between host and flea abundance. Thus, the most basic predictions are too simple to describe ectoparasite dynamics in this system. In addition, masting modified seasonal dynamics of flea abundance, but did not affect the relationship between host traits and flea abundance (individuals with the highest body mass hosted the most fleas; after controlling for body mass, parasite abundance did not vary between sexes). Our results demonstrate that pulses of tree reproduction can indirectly, through changes in host densities, drive patterns of ectoparasite infestation.

Upconversion FRET quantitation: the role of donor photoexcitation mode and compositional architecture on the decay and intensity based responses.

Lanthanide-doped colloidal nanoparticles capable of photon upconversion (UC) offer long luminescence lifetimes, narrowband absorption and emission spectra, and efficient anti-Stokes emission. These features are highly advantageous for Förster Resonance Energy Transfer (FRET) based detection. Upconverting nanoparticles (UCNPs) as donors may solve the existing problems of molecular FRET systems, such as photobleaching and limitations in quantitative analysis, but these new labels also bring new challenges. Here we have studied the impact of the core-shell compositional architecture of upconverting nanoparticle donors and the mode of photoexcitation on the performance of UC-FRET from UCNPs to Rose Bengal (RB) molecular acceptor. We have quantitatively compared luminescence rise and decay kinetics of Er3+ emission using core-only NaYF4: 20% Yb, 2% Er and core-shell NaYF4: 20% Yb @ NaYF4: 20% Yb, 5% Er donor UCNPs under three photoexcitation schemes: (1) direct short-pulse photoexcitation of Er3+ at 520 nm; indirect photoexcitation of Er3+ through Yb3+ sensitizer with (2) 980 nm short (5-7 ns) or (3) 980 nm long (4 ms) laser pulses. The donor luminescence kinetics and steady-state emission spectra differed between the UCNP architectures and excitation schemes. Aiming for highly sensitive kinetic upconversion FRET-based biomolecular assays, the experimental results underline the complexity of the excitation and energy-migration mechanisms affecting the Er3+ donor responses and suggest ways to optimize the photoexcitation scheme and the architecture of the UCNPs used as luminescent donors.

Quantitative Comparison of the Light-to-Heat Conversion Efficiency in Nanomaterials Suitable for Photothermal Therapy.

Functional colloidal nanoparticles capable of converting between various energy types are finding an increasing number of applications. One of the relevant examples concerns light-to-heat-converting colloidal nanoparticles that may be useful for localized photothermal therapy of cancers. Unfortunately, quantitative comparison and ranking of nanoheaters are not straightforward as materials of different compositions and structures have different photophysical and chemical properties and may interact differently with the biological environment. In terms of photophysical properties, the most relevant information to rank these nanoheaters is the light-to-heat conversion efficiency, which, along with information on the absorption capacity of the material, can be used to directly compare materials. In this work, we evaluate the light-to-heat conversion properties of 17 different nanoheaters belonging to different groups (plasmonic, semiconductor, lanthanide-doped nanocrystals, carbon nanocrystals, and metal oxides). We conclude that the light-to-heat conversion efficiency alone is not meaningful enough as many materials have similar conversion efficiencies─in the range of 80-99%─while they significantly differ in their extinction coefficient. We therefore constructed their qualitative ranking based on the external conversion efficiency, which takes into account the conventionally defined light-to-heat conversion efficiency and its absorption capacity. This ranking demonstrated the differences between the samples more meaningfully. Among the studied systems, the top-ranking materials were black porous silicon and CuS nanocrystals. These results allow us to select the most favorable materials for photo-based theranostics and set a new standard in the characterization of nanoheaters.

Engineering the Compositional Architecture of Core-Shell Upconverting Lanthanide-Doped Nanoparticles for Optimal Luminescent Donor in Resonance Energy Transfer: The Effects of Energy Migration and Storage.

Förster Resonance Energy Transfer (FRET) between single molecule donor (D) and acceptor (A) is well understood from a fundamental perspective and is widely applied in biology, biotechnology, medical diagnostics, and bio-imaging. Lanthanide doped upconverting nanoparticles (UCNPs) have demonstrated their suitability as alternative donor species. Nevertheless, while they solve most disadvantageous features of organic donor molecules, such as photo-bleaching, spectral cross-excitation, and emission bleed-through, the fundamental understanding and practical realizations of bioassays with UCNP donors remain challenging. Among others, the interaction between many donor ions (in donor UCNP) and many acceptors anchored on the NP surface and the upconversion itself within UCNPs, complicate the decay-based analysis of D-A interaction. In this work, the assessment of designed virtual core-shell NP (VNP) models leads to the new designs of UCNPs, such as …@Er, Yb@Er, Yb@YbEr, which are experimentally evaluated as donor NPs and compared to the simulations. Moreover, the luminescence rise and decay kinetics in UCNP donors upon RET is discussed in newly proposed disparity measurements. The presented studies help to understand the role of energy-transfer and energy migration between lanthanide ion dopants and how the architecture of core-shell UCNPs affects their performance as FRET donors to organic acceptor dyes.

A quality of life, clinical and biochemical improvements after catheter ablation of persistent arrhythmia in patients with structural heart disease and arrhythmia-mediated cardiomyopathy.

BACKGROUND: Arrhythmia-mediated cardiomyopathy (AMC) is an essential clinical situation that is commonly underdiagnosed. Successful arrhythmia control leads to improvement in health-related quality of life (HRQoL) and heart failure (HF) symptoms in patients with structural heart disease (SHD). AIMS: The study aimed to evaluate the impact of catheter ablation (CA) of persistent arrhythmia on HRQoL, biochemical and clinical parameters HF in patients with SHD and AMC. METHODS: Patients with SHD, on optimal medical treatment, with persistent arrhythmia and strong suspicion of AMC, scheduled for CA were prospectively enrolled. Study procedures included: HRQoL measurement (the Minnesota Living with Heart Failure Questionnaire [MLHFQ] and the EuroQol Research Foundation [EQ-5D-3L] questionnaire), biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], troponin T [TnT], matrix metalloproteinase-9 [MMP-9], soluble suppression of tumorigenesis-2 [sST2], tissue inhibitor of matrix metalloproteinase-1 [TIMP-1]), transthoracic echocardiography and clinical assessment. RESULTS: At 6 months, 30/35 (86%) patients were free of persistent arrhythmia. Patients who underwent successful CA had a significant improvement in HRQoL: MLHFQ (median [interquartile range, IQR], -22 [-28; -11]; P <0.001), EQ5D-3L score (mean [standard deviation], 21.8 (16.8); P <0.001); EQ5D-3L index (median [IQR], 0.09 (0.05; 0.18); P <0.001). A significant decrease in injury bio markers was observed: NT-proBNP (median [IQR], -414 [-1397; -318] pg/ml; P <0.001), TnT (median [IQR], -2.27 (-8.52; 0.55) ng/l; P <0.01) but not in fibrosis biomarkers: (median [IQR], sST2: 2.20 [-5.4; 4.3] ng/ml; P = 0.741, MMP-9: 34 [-376; 283] ng/ml; P = 0.881, TIMP-1: 11.1 [-17.1; 31.9] ng/ml; P = 0.215). There was a significant increase of left ventricular ejection fraction (LVEF) (mean [SD], 9.8 [5.9] %; P <0.01). CONCLUSIONS: Successful CA significantly improved clinical status, LVEF, and HRQoL of patients with SHD and AMC.

Th17/Treg imbalance in patients with primary hyperaldosteronism and resistant hypertension.

INTRODUCTION: Inflammation plays a pivotal role in blood pressure regulation. Data on experimental models of hypertension and hypertensive patients reflect the imbalance between T regulatory (Treg) and Th17 effector cells (Th17). OBJECTIVES: The aim of this study was to quantify peripheral blood Treg lymphocytes and Th17 subsets in individuals with primary hyperaldosteronism (PHA) and resistant hypertension (RHT) presenting with elevated blood pressure levels and augmented cardiovascular risk when compared with normotensive controls (CTRL). PATIENTS AND METHODS: Twenty CTRL participants, 21 patients with PHA, and 20 patients with RHT were enrolled. Plasma renin and angiotensin II, serum aldosterone concentration, ambulatory blood pressure monitoring (ABPM), echocardiography, clinical data, and phenotype of peripheral blood cells were assessed. RESULTS: There were no statistically significant differences in terms of age and sex between the groups. Similar systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in ABPM were observed in individuals with PHA and RHT. PHA patients had lower angiotensin II and 4­fold higher aldosterone concentrations than CTRL patients. Both, PHA and RHT were associated with cardiac hypertrophy and coronary artery disease. RHT patients presented a significantly higher CD4+IL­17A+ T cell number when compared with PHA and CTRL ones. The number of CD4+CD25+FOXP3+ T cells did not differ between patients with secondary hypertension and normotensive controls. Finally, positive correlations between the data on 24 h SBP and the content of CD4+IL­17A+ and CD4+CD25+FOXP3+ in the PHA were found. CONCLUSIONS: Elevated 24 h SBP in PHA was associated with the increased numbers of CD4+IL­17 and CD4+CD25+FOXP3+ T cells.

Validated Simple HPLC-UV Method for Mycophenolic Acid (MPA) Monitoring in Human Plasma. Internal Standardization: Is It Necessary?

The aim of the work was to prepare a simple but reliable HPLC-UV method for the routine monitoring of mycophenolic acid (MPA). Sample preparation was based on plasma protein precipitation with acetonitrile. The isocratic separation of MPA and internal standard (IS) fenbufen was made on Supelcosil LC-CN column (150 × 4.6 mm, 5 µm) using a mobile phase: CH3CN:H2O:0.5M KH2PO4:H3PO4 (260:700:40:0.4, v/v). UV detection was set at 305 nm. The calibration covered the MPA concentration range: 0.1-40 µg/mL. The precision was satisfactory with RSD of 0.97-7.06% for intra-assay and of 1.92-5.15% for inter-assay. The inaccuracy was found between -5.72% and +2.96% (+15.40% at LLOQ) and between -8.82% and +5.31% (+19.00% at LLOQ) for intra- and inter-assay, respectively, fulfilling acceptance criteria. After a two-year period of successful application, the presented method has been retrospectively calibrated using the raw data disregarding the IS in the calculations. The validation and stability parameters were similar for both calculation methods. MPA concentrations were recalculated and compared in 1187 consecutive routine therapeutic drug monitoring (TDM) trough plasma samples from mycophenolate-treated patients. A high agreement (r2 = 0.9931, p < 0.0001) of the results was found. A Bland-Altman test revealed a mean bias of -0.011 µg/mL (95% CI: -0.017; -0.005) comprising -0.14% (95% Cl: -0.39; +0.11), whereas the Passing-Bablok regression was y = 0.986x + 0.014. The presented method can be recommended as an attractive analytical tool for medical (hospital) laboratories equipped with solely basic HPLC apparatus. The procedure can be further simplified by disapplying an internal standard while maintaining appropriate precision and accuracy of measurements.

Standardization of Methodology of Light-to-Heat Conversion Efficiency Determination for Colloidal Nanoheaters.

Localized photothermal therapy (PTT) has been demonstrated to be a promising method of combating cancer, that additionally synergistically enhances other treatment modalities such as photodynamic therapy or chemotherapy. PTT exploits nanoparticles (called nanoheaters), that upon proper biofunctionalization may target cancerous tissues, and under light stimulation may convert the energy of photons to heat, leading to local overheating and treatment of cancerous cells. Despite extensive work, there is, however, no agreement on how to accurately and quantitatively compare light-to-heat conversion efficiency (ηQ) and rank the nanoheating performances of various groups of nanomaterials. This disagreement is highly problematic because the obtained ηQ values, measured with various methods, differ significantly for similar nanomaterials. In this work, we experimentally review existing optical setups, methods, and physical models used to evaluate ηQ. In order to draw a binding conclusion, we cross-check and critically evaluate the same Au@SiO2 sample in various experimental conditions. This critical study let us additionally compare and understand the influence of the other experimental factors, such as stirring, data recording and analysis, and assumptions on the effective mass of the system, in order to determine ηQ in a most straightforward and reproducible way. Our goal is therefore to contribute to the understanding, standardization, and reliable evaluation of ηQ measurements, aiming to accurately rank various nanoheater platforms.

Primary aldosteronism is highly prevalent in patients with hypertension and moderate to severe obstructive sleep apnea.

STUDY OBJECTIVES: It has been suggested that there might be a pathophysiological link and overlap between primary aldosteronism (PA) and obstructive sleep apnea (OSA). Therefore, in a prospective study, we evaluated the frequency of PA in hypertensive patients suspected of having OSA. METHODS: We included 207 consecutive hypertensive patients (mean age 53.2 ± 12.1 years, 133 M, 74 F) referred for polysomnography on the basis of one or more of the following clinical features: typical OSA symptoms, resistant or difficult-to-treat hypertension, diabetes, or cardiovascular disease. PA was diagnosed based on thew saline infusion test. RESULTS: Moderate-to-severe OSA was diagnosed in 94 patients (45.4% of the whole group). PA was diagnosed in 20 patients with OSA (21.3%) compared with 9 patients in the group without OSA (8.0%; P = .006). PA was also frequent in patients in whom symptoms of OSA were a sole indication for PA screening (15.4%) and in patients with and without resistant hypertension (24.5% and 17.8%, respectively). Most patients with PA and OSA were diagnosed with bilateral adrenal hyperplasia (18 patients, 90%). There were no major differences in clinical characteristics between patients with OSA with PA and those without PA. In multivariate models, moderate-to-severe OSA predicted the presence of PA (odds ratio 2.89, P = .018). CONCLUSIONS: Patients with clinically important moderate-to-severe OSA are characterized by a relatively high frequency of PA. Our results support the recommendations to screen patients with moderate-to-severe OSA for PA, regardless of the presence of other indications for PA screening.

Galectin-3 plasma levels in adult congenital heart disease and the pressure overloaded right ventricle: reason matters.

Aim: To assess galectin-3 (Gal-3) levels and their relationship with clinical status and right ventricular (RV) performance in adults with RV pressure overload of various mechanisms due to congenital heart disease. Materials & methods: A cross-sectional study was conducted. Patients underwent clinical examination, blood testing and transthoracic echocardiography. Results: The study included 63 patients with congenitally corrected transposition of the great arteries, 41 patients with Eisenmenger syndrome and 20 healthy controls. Gal-3 concentrations were higher in patients compared with controls (7.83 vs 6.11 ng/ml; p = 0.002). Biomarker levels correlated with age, New York Health Association class, N-terminal probrain natriuretic peptide and RV function only in congenitally corrected transposition of the great arteries patients. Conclusion: Gal-3 profile in congenital heart disease patients and pressure-overloaded RV differs according to the cause of pressure overload.

microRNA-451a prevents activation of matrix metalloproteinases 2 and 9 in human cardiomyocytes during pathological stress stimulation.

Matrix metalloproteinases (MMP) are important for cardiac remodeling. Recently, microRNA (miR)-451a has been found to inhibit the expression of both MMP-2 and MMP-9 in human malignancies, but its role in cardiomyocytes has not been explored. We hypothesized that miR-451a modulates MMP-2 and MMP-9 levels in human cardiomyocytes. The role of miR-451a on regulation of MMP-2 and MMP-9 was evaluated in two separate pathological models using Cor.4U human inducible pluripotent stem cell-derived cardiomyocytes (hiPS-CMs): 1) endothelin-1 (ET-1), and 2) 48-h hypoxia (1% O2). Both models were transfected with synthetic miR-451a mimics or scramble control. Expression of both mRNA and miR was determined by quantitative real-time polymerase chain reaction and protein activity by (MMP-2/9) activity assay. Bioinformatic analyses were performed using Targetscan 7.1 and STRING 10.5. hiPS-CMs stimulated by hypoxia increased both MMP-2 and MMP-9 expression levels compared with normoxia (P < 0.05), whereas ET-1 stimulation only increased the MMP-9 level compared with vehicle controls (P < 0.05). miR-451a mimics prevented the increase of MMP-2 and MMP-9 expression in both models. Protein activity of MMP-2 and MMP-9 was confirmed to be lower following treatment with miR-451a mimic compared with scramble-controls. Six of 28 predicted gene transcripts of miR-451a were linked to MMP-2 and MMP-9; Macrophage migration inhibitory factor (MIF) was the only predicted target of miR-451a that was increased by ET-1 and hypoxia and reduced following miR-451a mimic transfection. miR-451a prevent the increase of MMP-2 and MMP-9 in human cardiomyocytes during pathological stress. The modulation by miR-451a on MMP-2 and MMP-9 is caused by MIF.

Fluorescent electrospun PMMA microfiber mats with embedded NaYF4: Yb/Er upconverting nanoparticles.

Functional upconverting nanoparticles (UCNPs) can offer new possibilities in fluorescent applications as they exhibit desired characteristic properties like large shift between the fluorescent emission signal and the infrared excitation wavelength, multi- and narrow-band absorption and emission in visible and near infrared - Vis/NIR, together with excellent photostability and low toxicity as opposed to semiconducting quantum dots. The upconversion luminescence emission or quenching characteristics of UCNPs can be altered upon exposure to physical or chemical environmental factors providing thus a functionality that can be utilized for sensing or imaging. Furthermore their functionalization with suitable indicator dyes or recognition elements can extend the range of luminescence response and ratiometric sensing to specific analytes. Synergistically, electrospun nano- and microfibers offering large surface area can enhance the functionality of UCNPs by retaining the fluorescence efficiency and improving the overall responsivity due to dramatically increased surface. For the optimization of this hybrid material system the controllable incorporation of UCNPs is required especially at increased concentration conditions needed for high brightness. Herein, we report the fabrication, morphological and optical characterization of electrospun polymer-based nanocomposite fibers, consisting of poly(methyl methacrylate) (PMMA) and upconverting lanthanide doped nanoparticles of the type NaYF4 : 20% Yb3+/2% Er3+ @ NaYF4. Morphological studies regarding the uniformity and aggregation effects of the UCNP inclusion within the fibers have been implemented followed by upconversion emission characterization by pulsed near-infrared excitation. The study and optimization of such nanocomposite fibrous systems could provide useful insights for the development of efficient upconverting electrospun fiber mats for a number of imaging and sensing applications.

Circulating biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy assessed by cardiac magnetic resonance.

BACKGROUND: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice. OBJECTIVE: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM. METHODS: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis. RESULTS: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r = 0.32, p = 0.012), LV mass indexed for the body surface area (LVMI) (r = 0.27, p = 0.036) and maximal wall thickness (MWT) (r = 0.31, p = 0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r = 0.58, p < 0.0001), LVMI (r = 0.48, p = 0.0001), MWT (r = 0.31, p = 0.015) and late gadolinium enhancement (LGE) mass (r = 0.37, p = 0.003). There were positive correlations between NT-proBNP levels and LVM (r = 0.33, p = 0.01), LVMI (r = 0.41, p = 0.001), MWT (r = 0.42, p < 0.001) and LGE mass (r = 0.44, p < 0.001). CONCLUSIONS: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.

Factors related to on-treatment platelet aggregation assessed by multiple electrode aggregometry in percutaneous coronary intervention patients on clopidogrel and aspirin.

INTRODUCTION: There is ongoing controversy concerning the clinical value of platelet function monitoring in patients undergoing percutaneous coronary interventions (PCI). Patients at risk of high on-treatment platelet aggregation (HPR) may benefit most from such monitoring. AIM: To define the factors related to HPR on aspirin and clopidogrel, looking at a wider spectrum of variables than those assessed in some previous studies. MATERIAL AND METHODS: We assessed platelet function in 908 patients on clopidogrel and aspirin after PCI using the multielectrode aggregometry system Multiplate to define which clinical, procedural and laboratory factors are related to on-treatment platelet aggregation in response to aspirin and clopidogrel either as linear values or using established cutoff values for HPR. RESULTS: We found that in PCI patients on clopidogrel and aspirin, age (OR per year 1.06; 95% CI: 1.024-1.097; p = 0.001), gender (OR = 0.319; 95% CI: 0.139-0.731; p = 0.007), active smoking (OR = 2.57; 95% CI: 1.29-5.15; p = 0.008), diabetes (ß = 37.6; 95% CI: 16.5-58.8; p = 0.001) and hypertension (ß = 26.9; 95% CI: 6.73-47.1; p = 0.009) are independently linked to platelet aggregation values treated as linear values and as dichotomous variables at the accepted cutoffs. The same is true for stented segment length (OR per mm 1.033; 95% CI: 1.010-1.057; p = 0.009) and stent inflation pressure (OR per atmosphere 0.862; 95% CI: 0.772-0.963; p = 0.002). CONCLUSIONS: The study shows that, contrary to some earlier data, in the tested cohort women are better clopidogrel responders, but more often aspirin low-responders. Older age, active smoking, diabetes and hypertension all predispose to HPR. A novel finding is that stented segment length is an independent predictor of lower response both to aspirin and clopidogrel, possibly as a marker of more diffuse atherosclerosis.