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Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC), Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults (≥18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies.Results: Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classi­fication. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (-1.21 mL/min/1.73 m2 vs -3.32 mL/min/1.73 m2) or plasma globotriaosylceramide (-1.05 nmol/mL vs -2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the 0.2-mg/kg EOW and weekly groups. Tachycardia, fatigue, and hypotension were experienced by two or more patients overall. Anti–agalsidase alfa antibodies were detected in 11.4% of patients and neutralizing antibodies in 6.8%. Infusion-related reactions did not appear to be correlated with antibody status.Conclusion: No efficacy or safety differences were found when the approved EOW dosage of agalsidase alfa was increased to weekly administration. Exploratory analyses for 0.4 mg/kg weekly showed similar results. Keywords: adverse events, exercise tolerance, left ventricular hypertrophy, lysosomal storage disorder, quality of life, renal function

To quantify heterogeneous tissue at the periphery of areas of fibrosis (gray zone) in patients with hypertrophic cardiomyopathy (HCM) with the use of two different techniques. Cardiac magnetic resonance with late gadolinium enhancement analysis was performed in 33 patients with HCM. Gray zone was evaluated with the use of two different techniques previously described in patients after myocardial infarction. LGE was present in 25 (78%) patients. There was no significant difference in total LGE mass at two different cut-off values [53.8 g (interquartile range, IQR 43.5-77.8 g) vs. 53.8 g (IQR 37.8-64.5 g), respectively, P = 0.49]. Significant difference in gray zone mass assessed with the use of two techniques was demonstrated (19.1 +/- 7.3 g vs. 50.8 +/- 47.8 g; P = 0.003). There was a strong correlation between total LGE and gray zone mass (r = 0.789, P = 0.0001 for first method and r = 0.951, P < 0.0001 for the second one, respectively). However, significant variability of gray zone mass (and extent expressed as % of left ventricular mass) in patients with similar LGE size/extent was observed. Moreover, LGE mass varied greatly in patients with similar gray zone size. Neither left ventricular mass, nor with maximal wall thickness correlated with extent of gray zone assessed with both methods. The studied techniques provided similar results with regard to total LGE but significant differences were observed in gray zone mass. Two patients may have similar extent (or absolute mass) of LGE, but strikingly discrepant gray zone size. [ABSTRACT FROM AUTHOR]

Background: In patients with HCM at high risk of SCD, an ICD should be considered as a standard of care. Current risk approximation algorithms recommended by ESC 2014 criteria indicate that SCD risk is not stable. The aim of the study was to investigate how the calculated SCD risk in HCM patients with an ICD implanted in the past changed over time. Methods: We analyzed 64 HCM patients with ICD for primary prevention, referred for ICD re-implantation, and 32 HCM patients referred for a first-time ICD placement during the same period. The 5-year-SCD risk was assessed for suitable patients using the recommended ESC calculator. Results: The first-time group had a higher 5-year-SCD risk than those referred for ICD re-implantation: 7.50 (IQR 5.98−10.46) vs. 4.88 (IQR 3.42−7.25), p < 0.05. Out of the patients with an initial calculated risk below 4%, the risk increased in 22% of cases, reaching the 4−6% range. In 78% of patients, the risk remained stable and low. In 31% of patients with an initial calculated SCD risk ≥ 6%, the risk decreased over time to below 6%, and in 14% of the cases, below 4%. Conclusions: SCD risk in HCM patients is usually stable or gets lower. Our data suggest it is important to re-evaluate the risk profile for patients with HCM when ICD re-implantation is considered.

Combination of the polyimide 6FDA-mPD (6FDA = 4,4'-hexafluoroisopropylidene diphthalic anhydride and mPD = m-phenylenediamine) and crystallites of the metal-organic frameworks (MOFs) MIL-101(Cr) or MOF-199 (HKUST-1, Cu-BTC) produces mixed-matrix membranes (MMMs) with excellent dispersion and compatibility of the MOF particles within the polymer matrix. Permeation tests of a binary CO2/CH4 (50/50) gas mixture showed a remarkable increase of CO2 permeabilities for MIL-101(Cr)@6FDA-mPD and significantly higher selectivities for MOF-199@6FDA-mPD. The CO2 permeability increased from 10 (neat polymer) to 50 Barrer for the 24 wt% MIL-101(Cr)@6FDA-mPD membrane (with essentially constant selectivity) due to the high pore volume of MIL-101(Cr). The CO2/CH4 selectivity increased from 54 to 89 from the neat 6FDA-mPD polymer to the 24 wt% MOF-199@6FDA-mPD membrane, apparently due to the high CO2 adsorption capacity of MOF-199.

Nano/microsized MIL-101Cr was synthesized by microwave heating of emulsions for the use as a composite with Matrimid mixed-matrix membranes (MMM) to enhance the performance of a mixed-gas-separation. As an example, we chose CO 2 /CH 4 separation. Although the incorporation of MIL-101Cr in MMMs is well-known, the impact of nanosized MIL-101Cr in MMMs is new and shows an improvement compared to microsized MIL-101Cr under the same conditions and mixed-gas permeation. In order to reproducibly obtain nanoMIL-101Cr microwave heating was supplemented by carrying out the reaction of chromium nitrate and 1,4-benzenedicarboxylic acid in heptane-in-water emulsions with the anionic surfactant sodium oleate as emulsifier. The use of this emulsion with the phase inversion temperature (PIT) method offered controlled nucleation and growth of nanoMIL-101 particles to an average size of <100 nm within 70 min offering high apparent BET surface areas (2,900 m 2 g -1 ) and yields of 45%. Concerning the CO 2 /CH 4 separation, the best result was obtained with 24 wt.% of nanoMIL-101Cr@Matrimid, leading to 32 Barrer in CO 2 permeability compared to six Barrer for the neat Matrimid polymer membrane and 21 Barrer for the maximum possible 20 wt.% of microMIL-101Cr@Matrimid. The nanosized filler allowed reaching a higher loading where the permeability significantly increased above the predictions from Maxwell and free-fractional-volume modeling. These improvements for MMMs based on nanosized MIL-101Cr are promising for other gas separations., (Copyright © 2019 Gruber, Nuhnen, Lerch, Nießing, Klopotowski, Herbst, Karg and Janiak.)

3-Triazolylquinoxalines can be readily synthesized by applying two complementary synthetic protocols starting from heterocyclic π nucleophiles or (hetero)aryl glyoxylic acids in a consecutive four- or five-component reaction. Conceptually, the sequential use of a single cuprous salt for alkynylation and Cu-catalyzed alkyne-azide cycloaddition (CuAAC) in a one-pot fashion sets the stage for activation-alkynylation-cyclocondensation-CuAAC or glyoxylation-alkynylation-cyclocondensation-CuAAC sequences in good yields. The diversity-oriented generation of differently substituted 3-triazolylquinoxalines is an excellent entry to tunable emission solvatorchromic fluorophores with triazole ligation. The electronic structure, corroborated by DFT and TD-DFT calculations, rationalizes the charge transfer character of relevant absorptions and large Stokes shifts as well as the electronic innocence of the triazole substituents., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

To investigate the safety and efficacy of an early platelet function testing (PFT)-guided de-escalation of dual antiplatelet treatment (DAPT) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVS). Early DAPT de-escalation is a new non-inferior alternative to 12-months DAPT in patients with biomarker positive ACS treated with stent implantation. In this post-hoc analysis of the TROPICAL-ACS trial, which randomized 2610 ACS patients to a PFT-guided DAPT de-escalation (switch from prasugrel to clopidogrel) or to control group (uniform prasugrel), we compared clinical outcomes of patients (n = 151) who received a BVS during the index PCI. The frequency of the primary endpoint (cardiovascular death, myocardial infarction, stroke or BARC ≥ 2 bleeding) was 8.8% (n = 6) in the de-escalation group vs. 12.0% (n = 10) in the control group (HR 0.72, 95% CI 0.26-1.98, p = 0.52) at 12 months. One early definite stent thrombosis (ST) occurred in the control group (day 19) and 1 possible ST (sudden cardiovascular death) in the de-escalation group (day 86), both despite prasugrel treatment and in a background of high on-treatment platelet reactivity assessed at day 14 after randomization (ADP-induced platelet aggregation values of 108 U and 59 U, respectively). A PFT-guided DAPT de-escalation strategy could potentially be a safe and effective strategy in ACS patients with BVS implantation but the level of platelet inhibition may be of particular importance. This hypothesis-generating post-hoc analysis requires verification in larger studies with upcoming BVS platforms.

Background: Atrial fibrillation (AF) is a common complication in patients with hypertrophic cardiomyopathy (HCM) and may contribute to high cardiovascular morbidity and mortality. Therefore, it is important to assess parameters associated with AF in HCM patients., Hypothesis: The aim of the study was to evaluate AF prevalence in patients with HCM and to investigate risk factors for AF., Methods: Five hundred and forty-six HCM patients aged below 65 were included into analysis. Clinical and echocardiographic parameters were analyzed., Results: In 141 patients (25.8%) AF episodes were recorded. The following factors were identified as risk factors for AF in patients with HCM: age ≥ 45 years (OR 2.38, CI 1.40-4.05, P = 0.001), past history of presyncope or syncope (OR 2.25, CI 1.35-3.74, P = 0.002), non-sustained ventricular tachycardia (nsVT) (OR 2.70, CI 1.60-4.57, P < 0.001), left atrium diameter during first assessment (OR 1.065, CI 1.03-1.11, P = 0.001), left atrium diameter at the last assessment before AF occurrence (OR 1.10, CI 1.06-1.14, P < 0.001) and left ventricular ejection fraction at the last assessment before AF occurrence (CI 0.96, CI 0.94-0.98, P = 0.001)., Conclusions: We confirm that AF is a common complication for patients with HCM. Identification of patients with high risk for AF and implementation of preventive strategies may reduce AF occurrence and its complications., (© 2018 Wiley Periodicals, Inc.)

Three selenoether-functionalized ionic liquids (ILs) of N-[(phenylseleno)methylene]pyridinium (1), N-(methyl)- (2) and N-(butyl)-N'-[(phenylseleno)methylene]imidazolium (3) with bis(trifluoromethanesulfonyl)imide anions ([NTf2]) were prepared from pyridine, N-methylimidazole and N-butylimidazole with in situ obtained phenylselenomethyl chloride, followed by ion exchange to give the desired compounds. The crystal structures of the bromide and tetraphenylborate salts of the above cations (1-Br, 2-BPh4 and 3-BPh4) confirm the formation of the desired cations and indicate a multitude of different supramolecular interactions besides the dominating Coulomb interactions between the cations and anions. The vaporization enthalpies of the synthesized [NTf2]-containing ILs were determined by means of a quartz-crystal microbalance method (QCM) and their densities were measured with an oscillating U-tube. These thermodynamic data have been used to develop a method for assessment of miscibility of conventional solvents in the selenium-containing ILs by using Hildebrandt solubility parameters, as well as for modeling with the electrolyte perturbed-chain statistical associating fluid theory (ePC-SAFT) method. Furthermore, structure-property relations between selenoether-functionalized and similarly shaped corresponding aryl-substituted imidazolium- and pyridinium-based ILs were analyzed and showed that the contribution of the selenium moiety to the enthalpy of vaporization of an IL is equal to the contribution of a methylene (CH2) group. An incremental approach to predict vaporization enthalpies of ILs by a group contribution method has been developed. The reaction of these ILs with zinc acetate dihydrate under microwave irradiation led to ZnSe nanoparticles of an average diameter between 4 and 10 nm, depending on the reaction conditions.

The anti-neuroinflammatory meroterpenoid citreohybridonol was isolated for the first time from a sponge-derived fungus Penicillium atrovenetum. In this study, in addition to isolation and structure featuring, its unambiguous absolute configuration was determined exclusively by single crystal X-ray diffraction. The C-17-keto tautomer was clearly observed in X-ray analysis. The substance crystallises in the monoclinic space group P2 1 with a = 10.7496(5) Å, b = 14.3286(7) Å, c = 17.4909(8) Å, β = 103.235(2)°, V = 2622.5(2) Å 3 , Z = 2, D calcd  = 1.280 g/cm 3 . The chirality of the asymmetric carbon atoms was as follows: C3 (S), C5 (R), C6 (S), C8 (S), C9 (R), C10 (R), C13 (R), C14 (R).

Background: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT)., Methods: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22., Findings: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (p non-inferiority =0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], p superiority =0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; p non-inferiority =0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23)., Interpretation: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI., Funding: Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

: Platelet aggregation monitoring in patients after stent implantation is a promising way of preventing stent thrombosis and bleeding. The aim of the study was to verify whether clopidogrel (ADPtest) and aspirin (ASPItest) response measured by Multiplate (Dynabyte, Munich, Germany) analyzer in elective percutaneous coronary implantation patients predict the risk of stent thrombosis or other ischemic adverse events and bleeding. In this prospective, observational study 697 elective percutaneous coronary implantation patients were analyzed. The median ASPItest was 86 AU min. In 69 patients (9.9%), an ASPI result of more than 203 AU min was observed. The median ADP-dependent platelet aggregation was 212 AU min. In 36 (5.2%) patients, the result was at least 468 AU min. Cox regression analysis showed the prognostic factors of definite or probable stent thrombosis and cardiac death at 1 year were higher ASPItest result [odds ratio (OR) 1.006, 95% confidence interval (CI) 1.004-1.008, P < 0.001], ASPItest more than 203 AU min (OR 7.61, 95% CI 2.83-20.43, P < 0.001), higher ADPtest result (OR 1.005, 95% CI 1.003-1.007, P < 0.001) and ADPtest at least 468 AU min (OR 12.54, 95% CI 4.56-35.53, P < 0.001). In turn, ADPtest 188 AU min or less predicted GUSTO scale major and moderate bleeding (OR 4.15, 95% CI 1.12-15.32, P = 0.033). There was also a strong trend toward higher rate of major and moderate bleeding for the ASPItest less than 35 AU min (lowest quintile) - (OR 3.04, 95% CI 0.96-9.58, P = 0.058). Lower creatinine clearance and lower hemoglobin level were associated with both ischemic and bleeding complications. The results of this study show that impaired platelet response to clopidogrel and aspirin measured by the Multiplate analyzer results in increased risk of stent thrombosis and cardiac death. Furthermore, the study showed that increased response to clopidogrel is related to major and moderate bleeding events.

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 (β = 37.6; 95% CI: 16.5-58.8; p = 0.001) and hypertension (β = 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., Competing Interests: The authors declare no conflict of interest.

Background: The presence of late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcome and the extent of LGE predicts the increased risk of sudden cardiac death (SCD). Limited data exist regarding the distribution of LGE. We attempted to verify whether the presence of LGE outside the interventricular insertion points carries additional risk for patients with HCM., Methods: In this prospective study, 328 patients with HCM, who underwent cardiac magnetic resonance (CMR) were enrolled. Five major risk factors for SCD were assessed in all patients. The median follow-up was 37 months., Results: LGE was detected in 226 (68.9%) patients. In 70 (21.3%) patients it was present only at the interventricular insertion points - LGE (+) group, while in 156 (47.6%) it was noted in other locations - LGE (++) group. Primary endpoint defined as SCD or appropriate implantable cardioverter-defibrillator intervention occurred in 14 (4.3%) patients, one in LGE (+) and 13 in LGE (++). In multivariable analysis including five traditional risk factors and left ventricular ejection fraction <50%, only the presence of LGE outside the insertion points was a significant predictor of SCD/aborted SCD (HR 10.01, 95% CI 1.21-83.86, p=0.033). The performance of the multivariable sudden cardiac death risk model was improved by the addition of LGE (++) to the traditional risk factors (likelihood ratio p=0.005). The Kaplan-Meier curves showed better event-free survival in the LGE (-) and LGE (+) patient groups compared to the LGE (++) group., Conclusions: In HCM patients, presence of LGE outside interventricular insertion points is associated with increased risk of sudden cardiac death or its equivalent as well as overall mortality. Cardiac fibrosis as a substrate for SCD in HCM may be identified on CMR and serve as an imaging biomarker of increased risk., (Copyright © 2016. Published by Elsevier Ltd.)

To assess the anatomical background and significance of incomplete invasive coronary angiography (ICA) and to evaluate the value of coronary computed tomography angiography (CTA) in this scenario. The current study is an analysis of high volume center experience with prospective registry of coronary CTA and ICA. The target population was identified through a review of the electronic database. We included consecutive patients referred for coronary CTA after ICA, which did not visualize at least one native coronary artery or by-pass graft. Between January 2009 and April 2013, 13,603 diagnostic ICA were performed. There were 45 (0.3 %) patients referred for coronary CTA after incomplete ICA. Patients were divided into 3 groups: angina symptoms without previous coronary artery by-pass grafting (CABG) (n = 11,212), angina symptoms with previous CABG (n = 986), and patients prior to valvular surgery (n = 925). ICA did not identify by-pass grafts in 21 (2.2 %) patients and in 24 (0.2 %) cases of native arteries. The explanations for an incomplete ICA included: 11 ostium anomalies, 2 left main spasms, 5 access site problems, 5 ascending aorta aneurysms, and 2 tortuous take-off of a subclavian artery. However, in 20 (44 %) patients no specific reason for the incomplete ICA was identified. After coronary CTA revascularization was performed in 11 (24 %) patients: 6 successful repeat ICA and percutaneous intervention and 5 CABG. Incomplete ICA constitutes rare, but a significant clinical problem. Coronary CTA provides adequate clinical information in these patients.

Objectives: To determine immediate and long-term clinical outcome, as well prognostic factors in patients who underwent repeat percutaneous mitral balloon valvuloplasty (PMBV)., Background: Repeat PMBV may be a method of treatment for symptomatic patients with restenosis after successful initial PMBV, but data regarding its long term safety and efficacy are scarce., Methods: The study group consisted of 67 patients (mean age 52.1 ± 10.5 years). All PMBV procedures were performed using the Inoue balloon system., Results: Repeat PMBV resulted in significant increase in MVA from 1.17 ± 0.16 cm(2) to 1.63 ± 0.22 cm(2) (P < 0.001). Good immediate result (MVA ≥1.5 cm(2) , mitral regurgitation ≤2) was obtained in 52 (77.6%) patients and was not predicted by any analyzed factors. During follow-up (mean time 4.9 ± 2.9 years) six patients died, nine underwent mitral valve replacement, four-third PMBV, and four developed heart failure. The 3-, 5-, and 8-year good functional results (survival free of mitral valve replacement, third PMBV or heart failure ≥ NYHA III) by Kaplan-Meier estimates were 89.3, 75.6, and 52.6%, respectively. These results were significantly superior in patients with good immediate results and echo score <7. In the entire population multivariate Cox regression analysis identified echo score <7 and absence of prior surgical commissurotomy as the independent predictors of event-free survival., Conclusions: Repeat PMBV is safe and provides good immediate results in patients with restenosis after successful first procedure. Long-term results of repeat PMBV are satisfactory and related mainly to the echo score and quality of the procedure., (Copyright © 2010 Wiley-Liss, Inc.)

Aim: There is no consensus regarding the technique of quantification of late gadolinium enhancement (LGE). The aim of the study was to compare different methods of LGE quantification in patients with hypertrophic cardiomyopathy (HCM)., Methods: Cardiac magnetic resonance was performed in 33 patients with HCM. First, LGE was quantified by visual assessment by the team of experienced readers and compared with different thresholding techniques: from 1SD to 6SD above mean signal intensity (SI) of remote myocardium, above 50% of maximal SI of the enhanced area (full-width at half maximum, FWHM) and above peak SI of remote myocardium., Results: LGE was present in 25 (78%) of patients. The median mass of LGE varied greatly depending on the quantification method used and was highest with the utilization of 1SD threshold [75.5 g, interquartile range (IQR): 63.3-112.3g] and lowest for FWHM method (8.4 g, IQR: 4.3-13.3g). There was no difference in mass of LGE as assessed with 6SD threshold and FWHM when compared to visual assessment (p=0.19 and p=0.1, respectively); all other thresholding techniques provided significant differences in the median LGE size when compared to visual analysis. Results for all thresholds, except FWHM were significantly correlated with visual assessment with the strongest correlation for 6SD (rho=0.956, p<0.0001)., Conclusions: LGE quantification with the use of a threshold of 6SD above the mean SI of the remote myocardium provided the best agreement with visual assessment in patients with HCM., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Background: Percutaneous alcohol septal ablation (ASA) becomes an alternative option of treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy (HOCM). The procedure relieves left ventricular outflow tract obstruction, but produces a myocardial scar in patients who already have a substrate for life-threatening ventricular arrhythmia., Objectives: To examine the effect of ASA on the occurrence of non-sustained ventricular tachycardia (nsVT) on 24 h ambulatory Holter monitoring in HOCM patients., Methods: Sixty-one consecutive patients (34 males, mean age 48 years), who underwent ASA between 1997 and 2003 were analyzed. Holter recordings were performed in each patient before and after ablation., Results: Follow-up ranged from 60 to 125 months (median 116 months). The mean number of Holter recordings per patient was 2.7 (range 1-11) before and 8.3 (range 2-23) after ASA (p < 0.001). Non-sustained ventricular tachycardia occurred in 14 patients before and 27 patients after ASA (23 vs. 44%, p = 0.01). The percentage of Holter recordings with nsVT before and after ablation was similar (14.5 vs. 15.7%, p = 0.56, respectively). No difference was observed between the number of nsVT per Holter recording before and after ablation (0.21 vs. 0.24%, p = 0.65, respectively). The percentage of patients with nsVT after ASA was comparable to the proportion of patients with nsVT in a control group consisting of 705 patients with hypertrophic cardiomyopathy under follow-up at our institution (44.3 vs. 43.2%, p = 0.91). There was no significant difference in percentage of Holter recordings with nsVT with respect to sex, amount of alcohol used during ASA, peak creatine phosphokinase level, and gradient reduction at rest., Conclusion: Alcohol septal ablation affected neither the percentage of Holter recordings with nsVT nor the number of nsVT episodes per Holter recording among HOCM patients.

Aims: Despite proven benefits of cardiac rehabilitation (CR), currently proposed CR models are not acceptable for many heart failure (HF) patients. The purpose of this study was to evaluate a new model of home-based telemonitored cardiac rehabilitation (HTCR) using walking training compared with an outpatient-based standard cardiac rehabilitation (SCR) using interval training on a cycle ergometer., Methods and Results: The study included 152 HF patients (aged 58.1 + or - 10.2 years, NYHA class II and III, ejection fraction < or = 40%) who were randomized to HTCR (n = 77) or SCR (n = 75). All patients underwent 8 weeks of CR. Both groups were comparable in terms of demographic and clinical characteristics and medical therapy. The effectiveness of CR was assessed by changes in NYHA class, peak oxygen consumption, 6-min walking test distance, and SF-36 score. Cardiac rehabilitation resulted in a significant improvement of all parameters in both groups. All patients in the HTCR group completed the 8 weeks of CR, whereas 15 patients in the SCR group (20%) discontinued CR., Conclusion: In patients with HF, HTCR is equally as effective as SCR and provides a similar improvement in quality of life. Adherence to CR seems to be better for HTCR. Home-based telemonitored cardiac rehabilitation may be a useful alternative form of CR in patients with HF.

Object: Global cerebral edema is an independent risk factor for early death and poor outcome after subarachnoid hemorrhage (SAH). In the present study, the time course of brain edema formation, neurological deficits, and neuronal cell loss were investigated in the rat filament SAH model., Methods: Brain water content and neurological deficits were determined in rats randomized to sham (1-, 24-, or 48-hour survival), SAH by endovascular perforation (1-, 24-, or 48-hour survival), or no surgery (control). The neuronal cell count (CA1-3) was quantified in a separate set of SAH (6-, 24-, 48-, or 72-hour survival) and shamoperated animals., Results: Brain water content increased significantly 24 (80.2 +/- 0.4% [SAH] vs 79.2 +/- 0.1% [sham]) and 48 hours (79.8 +/- 0.2% [SAH] vs 79.3 +/- 0.1% [sham]) after SAH. The neuroscore was significantly worse after SAH (33 +/- 15 [24 hours after SAH] vs 0 +/- 0 points [sham]) and correlated with the extent of brain edema formation (r = 0.96, p < 0.001). No hippocampal damage was present up to 72 hours after SAH., Conclusions: Brain water content and neurological dysfunction reached a maximum at 24 hours after SAH. This time point, therefore, seems to be optimal to test the effects of therapeutic interventions on brain edema formation. Neuronal cell loss was not present in CA1-3 up to 72 hours of SAH. Therefore, morphological damage needs to be evaluated at later time points.

Background: Hyponatremia is a common electrolyte disorder reported to be a predictor of poor prognosis among hospitalized patients, but individuals with high levels also tend to have less favorable outcomes. This study investigated whether sodium level on admission is predictive of in-hospital outcome in patients with ST-elevation myocardial infarction (STEMI) treated with primary angioplasty., Material/methods: Included were 1858 patients admitted with STEMI for primary angioplasty. Sodium level was measured on admission and analyzed as hypo- versus normonatremia and by grouping patients into sodium quintiles. The relationships between sodium level and in-hospital mortality as well as the composite of death or heart failure were assessed., Results: Ninety-six patients had hyponatremia on admission. The hypo- and normonatremic groups were comparable with respect to baseline characteristics and in-hospital management. Hyponatremics had higher rates of in-hospital mortality (13.5% vs. 3.8%, p<0.001) composite of death and heart failure (27.8% vs. 18.4%, p=0.022). After adjustment for covariates, hyponatremia independently correlated with in-hospital mortality (HR: 3.89, 95%CI: 1.59-9.56, p=0.003) and the combined endpoint (HR: 1.73, 95%CI: 1.01-2.99, p=0.047). Patients in the lowest and highest sodium quintiles were 3.27 (95%CI: 1.34-8.02, p=0.009) and 2.65 (95%CI: 1.07-6.60, p=0.036) times more likely to die during hospitalization than those in the 2nd quintile (best survival). In the adjusted model, only patients in the lowest quintile had significantly increased risk of in-hospital death (HR: 6.35, 95%CI: 1.83-21.72, p=0.004)., Conclusions: Hyponatremia is a simple laboratory marker independently associated with increased risk of death in STEMI patients treated with primary angioplasty.

Objective: After a subarachnoid hemorrhage (SAH), the primary cause of mortality is secondary brain injury occurring within the first 48 hours after the initial bleeding. Because of the unknown pathophysiology of these early events, therapeutic approaches are scarce. Because mild hypothermia (33 degrees C) is among the strongest neuroprotectants known so far, the aim of this study was to investigate acute and delayed effects of hypothermia if applied after SAH., Methods: Male Sprague-Dawley rats were subjected to SAH and randomly assigned to the following groups: 1) SAH under normothermia, 2) SAH followed by 2 hours of hypothermia starting 1 hour after the bleeding, and 3) SAH followed by 2 hours of hypothermia starting 3 hours after the bleeding. Cerebral blood flow and intracranial pressure were continuously measured up to 6 hours after SAH. Mortality, neurological deficits, and body weight were assessed from postoperative day 1 to day 7. Brain water content and morphological brain damage were quantified 24 hours and 7 days after SAH, respectively., Results: Mild hypothermia reduced intracranial pressure (P < 0.001) and posthemorrhagic neurological deficits (P < 0.05) and improved postoperative weight gain significantly (P < 0.05). Mortality, cerebral blood flow, and the formation of cerebral edema were not significantly influenced by mild hypothermia., Conclusion: The current results show that mild hypothermia (33 degrees C) exhibits sustained neuroprotection if applied up to 3 hours after SAH. Overall, mild hypothermia seems to be an effective neuroprotective strategy after SAH and should therefore be evaluated as a treatment option for SAH in patients.

Background: Hemoglobin (Hb) levels may interact with inflammatory activation, but it is unknown whether the interaction has any impact on clinical outcomes in acute coronary syndromes. The aim of this study was to assess the relationship between admission Hb levels, leukocytosis and clinical outcomes of ST-elevation myocardial infarction (STEMI) treated with primary angioplasty. Methods and Results The study group comprised 1,904 (1,380 men) patients with STEMI treated with primary percutaneous coronary intervention, enrolled in a prospective registry. The primary endpoint of in-hospital death occurred in 90 (4.7%) patients. According to univariate analysis, extreme values of Hb (for 1(st) and 5(th) vs mid quintiles respectively: hazard ratio (HR) =7.1, P<0.001 and HR =3.2, P=0.024) and leukocytosis above median (HR =2.09, P=0.001) significantly correlated with in-hospital death. After dividing patients into high and low white blood cell (WBC) count groups, a U-shaped relationship of Hb levels and mortality was observed for patients with higher leukocytosis (1(st) and 5(th) vs mid quintiles respectively: HR =8.1, P=0.001 and HR =4.4, P=0.022), whereas in patients with lower WBC count higher mortality was related solely to the lowest Hb quintile (HR =6.9, P=0.010 vs mid quintile). Conclusion Higher mortality associated with higher Hb levels in STEMI patients treated with primary angioplasty is limited to patients with increased leukocytosis.

Background: In hypertrophic obstructive cardiomyopathy, percutaneous transluminal septal myocardial ablation (PTSMA) improves functional capacity in the short term. However, long term functional capacity is unknown., Aim: To assess the long term exercise capacity of patients with hypertrophic obstructive cardiomyopathy undergoing PTSMA., Methods: Twenty three patients (56.5% male, mean age 44.5+/-13.6 years) who underwent PTSMA were included. All patients had also undergone a symptom limited cardiopulmonary exercise treadmill test before the procedure, then after 3 months (early follow-up) and after a mean 7.2+/-1.0 years (long term follow-up)., Results: Before PTSMA, mean maximal pressure gradient in the left outflow tract (LVOTGmax) was 82+/-29 mmHg, 17 patients had NYHA functional class> or = III and peak oxygen uptake (pVO2) was 18+/-4 ml/kg/min. PTSMA led to a reduction in mean LVOTGmax (to 29+/-19 mmHg, p<.0001), improvement of heart failure symptoms (NYHA> or =III in 1 patient, p<.0001) and an increase of pVO2 (to 22+/-6 ml/kg/min, p=.0002) at short term. LVOTGmax, functional class and pVO2 did not change significantly during long term follow-up compared to early follow-up. However, there was a continuous improvement in percentage predicted pVO2 over time., Conclusions: In patients with hypertrophic obstructive cardiomyopathy and symptoms of heart failure, PTSMA leads to stable long term improvement of objectively measured exercise capacity.

Following an accidental finding of a large atrial lead-related thrombus in a 33-year-old woman with suspected prothrombotic disorder, a conservative treatment with low molecular weight heparin injections and close transthoracic and transesophageal echocardiographic monitoring was used. It led to a complete resolution of the thrombus in 4 weeks without the need for a high-risk operation in this patient.

Vasogenic brain edema is one of the major determinants for mortality following subarachnoid hemorrhage (SAH). Although the formation of vasogenic brain edema occurs on the microvascular level by opening of endothelial tight junctions and disruption of the basal lamina, microvascular changes following experimental SAH are poorly characterized. The aim of the present study was therefore to investigate the time course of blood-brain barrier (BBB) dysfunction and basal lamina damage following SAH as a basis for the better understanding of the pathophysiology of SAH. SAH was induced in Sprague-Dawley rats by an endovascular filament. Animals were sacrificed 6, 24, 48, and 72 h thereafter (n=9 per group). Microvascular basal lamina damage was quantified by collagen type IV immunostaining. Western blotting was used to quantify collagen IV protein content and bovine serum albumin (BSA) extravasation as a measure for basal lamina damage and blood-brain barrier disruption, respectively. BSA Western blot revealed significant (p<0.05) BBB opening in the cerebral cortex ipsilateral to the hemorrhage beginning 6 h and peaking 48 h after SAH. Significant (p<0.05) basal lamina damage occurred with gradual increase from 24 to 72 h. Basal lamina damage correlated significantly with BBB dysfunction (r=-0.63; p=0.0001). Microvascular damage as documented by collagen IV degradation and albumin extravasation is a long lasting and ongoing process following SAH. Due to its delayed manner microvascular damage may be prone for therapeutic interventions. However, further investigations are needed to determine the molecular mechanisms responsible for basal lamina degradation and hence damage of the microvasculature following SAH.