Hyalotekite, (Ba,Pb,K)(4)(Ca,Y)(2)Si-8(B,Be)(2)(Si,B)(2)O28F, a Tectosilicate Related to Scapolite: New Structure Refinement, Phase Transitions and a Short-Range Ordered 3B Superstructure

Hyalotekite, a framework silicate of composition (Ba,Pb,K)(4)(Ca,Y)(2)Si-8(B,Be)(2) (Si,B)(2)O28F, is found in relatively high-temperature(greater than or equal to 500 degrees C) Mn skarns at Langban, Sweden, and peralkaline pegmatites at Dara-i-Pioz, Tajikistan. A new paragenesis at Dara-i-Pioz is pegmatite consisting of the Ba borosilicates leucosphenite and tienshanite, as well as caesium kupletskite, aegirine, pyrochlore, microcline and quartz. Hyalotekite has been partially replaced by barylite and danburite. This hyalotekite contains 1.29-1.78 wt.% Y2O3, equivalent to 0.172-0.238 Y pfu or 8-11% Y on the Ca site; its Pb/(Pb+Ba) ratio ranges 0.36-0.44. Electron microprobe F contents of Langban and Dara-i-Pioz hyalotekite range 1.04-1.45 wt.%, consistent with full occupancy of the F site. A new refinement of the structure factor data used in the original structural determination of a Langban hyalotekite resulted in a structural formula, (Pb1.96Ba1.86K0.18)Ca-2(B1.76Be0.24)(Si1.56B0.44)Si8O28F, consistent with chemical data and all cations with positive-definite thermal parameters, although with a slight excess of positive charge (+57.14 as opposed to the ideal +57.00). An unusual feature of the hyalotekite framework is that 4 of 28 oxygens are non-bridging; by merging these 4 oxygens into two, the framework topology of scapolite is obtained. The triclinic symmetry of hyalotekite observed at room temperature is obtained from a hypothetical tetragonal parent structure via a sequence of displacive phase transitions. Some of these transitions are associated with cation ordering, either Pb-Ba ordering in the large cation sites, or B-Be and Si-B ordering on tetrahedral sites. Others are largely displacive but affect the coordination of the large cations (Pb, Ba, K, Ca). High-resolution electron microscopy suggests that the undulatory extinction characteristic of hyalotekite is due to a fine mosaic microstructure. This suggests that at least one of these transitions occurs in nature during cooling, and that it is first order with a large volume change. A diffuse superstructure observed by electron diffraction implies the existence of a further stage of short-range cation ordering which probably involves both (Pb,K)-Ba and (BeSi,BB)-BSi.

[Meningitis (I)--differential diagnosis; aseptic and chronic meningitis].

Meningitis is the most common serious manifestation of infection of the central nervous system. Inflammatory involvement of the subarachnoid space with meningeal irritation leads to the classical triad of headache, fever, and meningism, and to a pleocytosis of the cerebrospinal fluid (CSF). Meningitis is clinically categorized into an acute and chronic disease based on the acuity of symptoms. Acute meningitis develops over hours to days, while in chronic meningitis symptoms evolve over days or even weeks. Aseptic meningitis, in which no bacterial pathogen can be isolated by routine cultures, can mimic bacterial meningitis, but the disease has a much more favorable prognosis. Many cases of aseptic meningitis are caused by viruses, primarily enteroviruses, but bacteria and noninfectious etiologies also cause meningitis with negative cultures. Symptoms of meningeal inflammation with CSF pleocytosis that persist for more than 4 weeks define the chronic meningitis syndrome. The diagnosis is based on the patient history, clinical evidence of meningitis, CSF examination, and often imaging studies. The differential diagnosis is broad, and the predominant CSF cell type can provide clues as to the underlying disease. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. In patients with chronic meningitis, a definite diagnosis is often not available or delayed for days, in which case empiric therapy may have to be initiated. It is important to cover the treatable causes of meningitis, for which the outcome is poor if treatment is delayed.

HDL Cholesterol Is Not Associated with Lower Mortality in Patients with Kidney Dysfunction

In the general population, HDL cholesterol (HDL-C) is associated with reduced cardiovascular events. However, recent experimental data suggest that the vascular effects of HDL can be heterogeneous. We examined the association of HDL-C with all-cause and cardiovascular mortality in the Ludwigshafen Risk and Cardiovascular Health study comprising 3307 patients undergoing coronary angiography. Patients were followed for a median of 9.9 years. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine-cystatin C (eGFRcreat-cys) equation. The effect of increasing HDL-C serum levels was assessed using Cox proportional hazard models. In participants with normal kidney function (eGFR>90 ml/min per 1.73 m(2)), higher HDL-C was associated with reduced risk of all-cause and cardiovascular mortality and coronary artery disease severity (hazard ratio [HR], 0.51, 95% confidence interval [95% CI], 0.26-0.92 [P=0.03]; HR, 0.30, 95% CI, 0.13-0.73 [P=0.01]). Conversely, in patients with mild (eGFR=60-89 ml/min per 1.73 m(2)) and more advanced reduced kidney function (eGFR<60 ml/min per 1.73 m(2)), higher HDL-C did not associate with lower risk for mortality (eGFR=60-89 ml/min per 1.73 m(2): HR, 0.68, 95% CI, 0.45-1.04 [P=0.07]; HR, 0.84, 95% CI, 0.50-1.40 [P=0.50]; eGFR<60 ml/min per 1.73 m(2): HR, 1.18, 95% CI, 0.60-1.81 [P=0.88]; HR, 0.82, 95% CI, 0.40-1.69 [P=0.60]). Moreover, Cox regression analyses revealed interaction between HDL-C and eGFR in predicting all-cause and cardiovascular mortality (P=0.04 and P=0.02, respectively). We confirmed a lack of association between higher HDL-C and lower mortality in an independent cohort of patients with definite CKD (P=0.63). In summary, higher HDL-C levels did not associate with reduced mortality risk and coronary artery disease severity in patients with reduced kidney function. Indeed, abnormal HDL function might confound the outcome of HDL-targeted therapies in these patients.

Predictors of adverse events among patients undergoing primary percutaneous coronary intervention: insights from a pooled analysis of the COMFORTABLE AMI and EXAMINATION trials

Aims: The aim of this study was to identify predictors of adverse events among patients with ST-elevation myocardial infarction (STEMI) undergoing contemporary primary percutaneous coronary intervention (PCI). Methods and results: Individual data of 2,655 patients from two primary PCI trials (EXAMINATION, N=1,504; COMFORTABLE AMI, N=1,161) with identical endpoint definitions and event adjudication were pooled. Predictors of all-cause death or any reinfarction and definite stent thrombosis (ST) and target lesion revascularisation (TLR) outcomes at one year were identified by multivariable Cox regression analysis. Killip class III or IV was the strongest predictor of all-cause death or any reinfarction (OR 5.11, 95% CI: 2.48-10.52), definite ST (OR 7.74, 95% CI: 2.87-20.93), and TLR (OR 2.88, 95% CI: 1.17-7.06). Impaired left ventricular ejection fraction (OR 4.77, 95% CI: 2.10-10.82), final TIMI flow 0-2 (OR 1.93, 95% CI: 1.05-3.54), arterial hypertension (OR 1.69, 95% CI: 1.11-2.59), age (OR 1.68, 95% CI: 1.41-2.01), and peak CK (OR 1.25, 95% CI: 1.02-1.54) were independent predictors of all-cause death or any reinfarction. Allocation to treatment with DES was an independent predictor of a lower risk of definite ST (OR 0.35, 95% CI: 0.16-0.74) and any TLR (OR 0.34, 95% CI: 0.21-0.54). Conclusions: Killip class remains the strongest predictor of all-cause death or any reinfarction among STEMI patients undergoing primary PCI. DES use independently predicts a lower risk of TLR and definite ST compared with BMS. The COMFORTABLE AMI trial is registered at: http://www.clinicaltrials.gov/ct2/show/NCT00962416. The EXAMINATION trial is registered at: http://www.clinicaltrials.gov/ct2/show/NCT00828087.

Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial

BACKGROUND Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. METHODS We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. FINDINGS Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014). INTERPRETATION In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study. FUNDING Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

Ten year clinical follow-up after Sirolimus-eluting stent implantation

BACKGROUND: Little is known on the "very" long-term incidence of major adverse cardiac events (MACE), target-lesion revascularization (TLR), target-vessel revascularization and stent thrombosis after sirolimus-eluting stent (SES) implantation. We present the first study to provide a 10-year clinical follow-up in an unselected patient population who underwent SES implantation. METHODS AND RESULTS: We ran a systematic 10-year clinical follow-up in a series of 200 consecutive patients treated with unrestricted SES implantation between April 2002 and April 2003 in two Swiss hospitals. Outcomes and follow-up were obtained in all 200 patients. The cumulative 10-year MACE rate was 47% with all-cause death of 20%, cardiac death of 9%, myocardial infarction of 7%, TLR and target-vessel revascularization of 8% and 11% respectively. Academic Research Consortium-defined "definite and probable" stent thrombosis-rate was 2.5%. TLR risk was maximal between 3 to 6 years. New lesion revascularization increased throughout the study period. CONCLUSION: Incidence of TLR was maximal 3 to 6 years after SES implantation and decreased thereafter. MACE and non-TLR revascularization rates steadily increased during the complete follow-up underlining the progression of coronary artery disease.

Major challenges in clinical management of TB/HIV co-infected patients in Eastern Europe compared with Western Europe and Latin America.

INTRODUCTION Rates of both TB/HIV co-infection and multi-drug-resistant (MDR) TB are increasing in Eastern Europe (EE). Data on the clinical management of TB/HIV co-infected patients are scarce. Our aim was to study the clinical characteristics of TB/HIV patients in Europe and Latin America (LA) at TB diagnosis, identify factors associated with MDR-TB and assess the activity of initial TB treatment regimens given the results of drug-susceptibility tests (DST). MATERIAL AND METHODS We enrolled 1413 TB/HIV patients from 62 clinics in 19 countries in EE, Western Europe (WE), Southern Europe (SE) and LA from January 2011 to December 2013. Among patients who completed DST within the first month of TB therapy, we linked initial TB treatment regimens to the DST results and calculated the distribution of patients receiving 0, 1, 2, 3 and ≥4 active drugs in each region. Risk factors for MDR-TB were identified in logistic regression models. RESULTS Significant differences were observed between EE (n=844), WE (n=152), SE (n=164) and LA (n=253) for use of combination antiretroviral therapy (cART) at TB diagnosis (17%, 40%, 44% and 35%, p<0.0001), a definite TB diagnosis (culture and/or PCR positive for Mycobacterium tuberculosis; 47%, 71%, 72% and 40%, p<0.0001) and MDR-TB prevalence (34%, 3%, 3% and 11%, p <0.0001 among those with DST results). The history of injecting drug use [adjusted OR (aOR) = 2.03, (95% CI 1.00-4.09)], prior TB treatment (aOR = 3.42, 95% CI 1.88-6.22) and living in EE (aOR = 7.19, 95% CI 3.28-15.78) were associated with MDR-TB. For 569 patients with available DST, the initial TB treatment contained ≥3 active drugs in 64% of patients in EE compared with 90-94% of patients in other regions (Figure 1a). Had the patients received initial therapy with standard therapy [Rifampicin, Isoniazid, Pyrazinamide, Ethambutol (RHZE)], the corresponding proportions would have been 64% vs. 86-97%, respectively (Figure 1b). CONCLUSIONS In EE, TB/HIV patients had poorer exposure to cART, less often a definitive TB diagnosis and more often MDR-TB compared to other parts of Europe and LA. Initial TB therapy in EE was sub-optimal, with less than two-thirds of patients receiving at least three active drugs, and improved compliance with standard RHZE treatment does not seem to be the solution. Improved management of TB/HIV patients requires routine use of DST, initial TB therapy according to prevailing resistance patterns and more widespread use of cART.

Biolimus-eluting stent with biodegradable polymer improves clinical outcomes in patients with acute myocardial infarction

OBJECTIVE To investigate clinical outcomes of coronary intervention using a biolimus-eluting stent (BES) compared with a sirolimus-eluting stent (SES) in patients with acute myocardial infarction (AMI) in the Limus Eluted from A Durable versus ERodable Stent (LEADERS) coating trial at the final 5-year follow-up. METHODS The LEADERS trial is a multicentre all-comer study, where patients (n=1707) were randomised to percutaneous intervention with either BES containing biodegradable polymer or SES containing durable polymer. Out of 1707 patients enrolled in this trial, 573 patients had percutaneous coronary intervention for AMI (BES=280, SES=293) and were included in the current analysis. Patient-oriented composite endpoint (POCE, including all death, all myocardial infarction (MI) and all revascularisations), major adverse cardiac events (MACE, including cardiac death, MI and clinically indicated target vessel revascularisation) and stent thrombosis were assessed at 5-year follow-up. RESULTS The baseline clinical, angiographic and procedural characteristics were well matched between BES and SES groups. In all patients with AMI, coronary intervention with a BES, compared with SES, significantly reduced POCE (28.9% vs 42.3%; relative risk (RR) 0.61, 95% CI 0.47 to 0.82, p=0.001) at 5-year follow-up. There was also a reduction in MACE rate in the BES group (18.2% vs 25.9%; RR 0.67, 95% CI 0.47 to 0.95, p=0.025); however, there was no difference in cardiac death and stent thrombosis. In patients with ST-elevation MI (STEMI), coronary intervention with BES significantly reduced POCE (24.4% vs 39.3%; RR 0.55, 95% CI 0.36 to 0.85, p=0.006), MACE (12.6% vs 25.0%; RR 0.47, 95% CI 0.26 to 0.83, p=0.008) and cardiac death (3.0% vs 11.4%; RR 0.25, 95% CI 0.08 to 0.75, p=0.007), along with a trend towards reduction in definite stent thrombosis (3.7% vs 8.6%; RR 0.41, 95% CI 0.15 to 1.18, p=0.088), compared with SES. CONCLUSIONS BES, compared with SES, significantly improved safety and efficacy outcomes in patients with AMI, especially those with STEMI, at 5-year follow-up. TRIAL REGISTRATION NUMBER NCT 00389220.

Psychosocial aspects in cardiac rehabilitation: From theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology

A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality of life (HRQoL) and prognosis in patients with established CHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system. Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention, integrating counselling for PSRFs and coping with illness should be included within comprehensive CR. Patients with clinically significant symptoms of distress should be referred for psychological counselling or psychologically focused interventions and/or psychopharmacological treatment. To conclude, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.

Stent thrombosis in early-generation drug-eluting stents versus newer-generation everolimus-eluting stent assorted by LVEF.

OBJECTIVE Everolimus drug-eluting stents (EES) are superior to early-generation drug-eluting stents (DES), releasing sirolimus (SES) or paclitaxel (PES) in preventing stent thrombosis (ST). Since an impaired LVEF seems to increase the risk of ST, we aimed to investigate the difference in outcome of patients with varying LVEF using EES versus early-generation DES. METHODS In a prospective cohort study, we compared the risk of ST in patients in three LVEF subgroups: normal (LVEF >50%), mildly impaired (LVEF >40% and ≤50%) and moderate-severely impaired (LVEF ≤40%). Within these various LVEF groups, we compared EES with SES and PES after adjustment for baseline differences. RESULTS We assessed a cohort of 5363 patients, with follow-up of up to 4 years and available LVEF. Overall definite ST occurred in 123 (2.3%) patients. ST rates were higher in the LVEF moderate-severely impaired group compared with the normal LVEF group (2.8% vs 2.1%; HR 1.82; CI 1.10 to 3.00). Especially early ST (EST) was more frequent in the moderate-severely impaired LVEF group (HR 2.20; CI 1.06 to 4.53). Overall rates of definite ST were lower in patients using EES compared with patients using SES or PES in all LVEF groups. Interaction terms were not statistically significant. ST rates were higher in the moderate-severely impaired LVEF group compared with the normal LVEF group when using SES or PES, but not significantly different when using EES. CONCLUSIONS EES was associated with a lower risk of definite ST compared with early-generation DES. This lower risk was independent of LVEF, even though ST rates were higher in patients with a moderate-severely impaired LVEF. TRIAL REGISTRATION NO MEC-2013-262.

Clinical results with the Resolute zotarolimus-eluting stent in total coronary occlusions.

Aims: We conducted a pooled post hoc analysis (RESOLUTE All Comers and RESOLUTE International) of patients who had the Resolute® zotarolimus-eluting stent (R-ZES) implanted in revascularised total occlusions (TO) compared with patients treated with R-ZES for non-occluded lesions. Methods and results: Patients were divided into three groups: chronic TO (CTO; n=256), non-chronic TO (n=292), and no occlusion (n=2,941). Clinical and safety outcomes assessed through two years included target lesion failure (TLF: cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation) and Academic Research Consortium definite or probable stent thrombosis. The rate of TLF at two years was not significantly different among patients in the CTO (9.1%), TO (9.8%), and no occlusion (10.4%) groups (log-rank p=0.800); neither were the components of TLF. Definite or probable stent thrombosis occurred more frequently in the TO group (2.8% vs. 1.2% in the CTO and 1.1% in the group with no occlusion, p=0.027). There were 10 late and six very late stent thrombosis events. Conclusions: Apart from a higher rate of stent thrombosis in patients with TO, patients with totally occluded coronary arteries who receive revascularisation with an R-ZES have clinical outcomes comparable to those who receive a similar stent in non-occluded lesions.

Differences in coronary risk factors, procedural characteristics, mortality and stent thrombosis between two all-comers percutaneous coronary intervention registries from Europe and Japan: a patient-level data analysis of the Bern-Rotterdam and j-Cypher registries

Aims: The reported rate of stent thrombosis (ST) after drug-eluting stent (DES) implantation varies among registries. To investigate differences in baseline characteristics and clinical outcome in European and Japanese all-comers registries, we performed a pooled analysis of patient-level data. Methods and results: The j-Cypher registry (JC) is a multicentre observational study conducted in Japan, including 12,824 patients undergoing SES implantation. From the Bern-Rotterdam registry (BR) enrolled at two academic hospitals in Switzerland and the Netherlands, 3,823 patients with SES were included in the current analysis. Patients in BR were younger, more frequently smokers and presented more frequently with ST-elevation myocardial infarction (MI). Conversely, JC patients more frequently had diabetes and hypertension. At five years, the definite ST rate was significantly lower in JC than BR (JC 1.6% vs. BR 3.3%, p<0.001), while the unadjusted mortality tended to be lower in BR than in JC (BR 13.2% vs. JC 14.4%, log-rank p=0.052). After adjustment, the j-Cypher registry was associated with a significantly lower risk of all-cause mortality (HR 0.56, 95% CI: 0.49-0.64) as well as definite stent thrombosis (HR 0.46, 95% CI: 0.35-0.61). Conclusions: The baseline characteristics of the two large registries were different. After statistical adjustment, JC was associated with lower mortality and ST.

4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention)

OBJECTIVES The aim of the study was to investigate 4-year outcomes and predictors of repeat revascularization in patients treated with the Resolute zotarolimus-eluting stent (R-ZES) (Medtronic, Minneapolis, Minnesota) and XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Abbott Park, Illinois) in the RESOLUTE (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention) All-Comers trial. BACKGROUND Data on long-term outcomes of new-generation drug-eluting stents are limited, and predictors of repeat revascularization due to restenosis and/or progression of disease are largely unknown. METHODS Patients were randomly assigned to treatment with the R-ZES (n = 1,140) or the EES (n = 1,152). We assessed pre-specified safety and efficacy outcomes at 4 years including target lesion failure and stent thrombosis. Predictors of revascularization at 4 years were identified by Cox regression analysis. RESULTS At 4 years, the rates of target lesion failure (15.2% vs. 14.6%, p = 0.68), cardiac death (5.4% vs. 4.7%, p = 0.44), and target vessel myocardial infarction (5.3% vs. 5.4%, p = 1.00), clinically-indicated target lesion revascularization (TLR) (7.0% vs. 6.5%, p = 0.62), and definite/probable stent thrombosis (2.3% vs. 1.6%, p = 0.23) were similar with the R-ZES and EES. Independent predictors of TLR were age, insulin-treated diabetes, SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) score, treatment of saphenous vein grafts, ostial lesions, and in-stent restenosis. Independent predictors of any revascularization were age, diabetes, previous percutaneous coronary intervention, absence of ST-segment elevation myocardial infarction, smaller reference vessel diameter, SYNTAX score, and treatment of left anterior descending, right coronary artery, saphenous vein grafts, ostial lesions, or in-stent restenosis. CONCLUSIONS R-ZES and EES demonstrated similar safety and efficacy throughout 4 years. TLR represented less than one-half of all repeat revascularization procedures. Patient- and lesion-related factors predicting the risk of TLR and any revascularization showed considerable overlap. (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention [RESOLUTE-AC]; NCT00617084).

Lack of association between dual antiplatelet therapy use and stent thrombosis between 1 and 12 months following resolute zotarolimus-eluting stent implantation.

AIM The optimal duration of dual antiplatelet therapy (DAPT) following the use of new generation drug-eluting stents is unknown. METHODS AND RESULTS The association between DAPT interruption and the rates of stent thrombosis (ST) and cardiac death/target-vessel myocardial infarction (CD/TVMI) in patients receiving a Resolute zotarolimus-eluting stent (R-ZES) was analysed in 4896 patients from the pooled RESOLUTE clinical programme. Daily acetylsalicylate (ASA) and a thienopyridine for 6-12 months were prescribed. A DAPT interruption was defined as any interruption of ASA and/or a thienopyridine of >1 day; long interruptions were >14 days. Three groups were analysed: no interruption, interruption during the first month, and >1-12 months. There were 1069 (21.83%) patients with a DAPT interruption and 3827 patients with no interruption. Among the 166 patients in the 1-month interruption group, 6 definite/probable ST events occurred (3.61%; all long DAPT interruptions), and among the 903 patients in the >1-12 months (60% occurred between 6 and 12 months) interruption group, 1 ST event occurred (0.11%; 2-day DAPT interruption). Among patients with no DAPT interruption, 32 ST events occurred (0.84%). Rates of CD/TVMI were 6.84% in the 1-month long interruption group, 1.41% in the >1-12 months long interruption group, and 4.08% in patients on continuous DAPT. CONCLUSION In a pooled population of patients receiving an R-ZES, DAPT interruptions within 1 month are associated with a high risk of adverse outcomes. Dual antiplatelet therapy interruptions between 1 and 12 months were associated with low rates of ST and adverse cardiac outcomes. Randomized clinical trials are needed to determine whether early temporary or permanent interruption of DAPT is truly safe. CLINICAL TRIALSGOV IDENTIFIERS NCT00617084; NCT00726453; NCT00752128; NCT00927940.

Clinical role of atrial arrhythmias in patients with arrhythmogenic right ventricular dysplasia

BACKGROUND: The clinical role of atrial fibrillation/atrial flutter (AF-AFl) and variables predicting these arrhythmias are not well defined in patients with arrhythmogenic right ventricular dysplasia (ARVD). We hypothesized that transthoracic echocardiography (TTE) and 12-lead electrocardiography (ECG) would be helpful in predicting AF-AFl in these patients. METHODS AND RESULTS: ECGs and TTEs of 90 patients diagnosed with definite or borderline ARVD (2010 Task Force Criteria) were analyzed. Data were compared in (1) patients with AF-AFl and (2) all other patients. A total of 18 (20%) patients experienced AF-AFl during a median follow-up of 5.8 years (interquartile range 2.0-10.4). Kaplan-Meier analysis revealed reduced times to AF-AFl among patients with echocardiographic RV fractional area change <27% (P<0.001), left atrial diameter ≥24.4 mm/m(2)(parasternal long-axis, P=0.001), and right atrial short-axis diameter ≥22.1 mm/m(2)(apical 4-chamber view, P=0.05). From all ECG variables, P mitrale conferred the highest hazard ratio (3.37, 95% confidence interval 0.92-12.36, P=0.067). Five patients with AF-AFl experienced inappropriate implantable cardioverter-defibrillator (ICD) shocks compared with 4 without AF-AFl (36% vs. 9%, P=0.03). AF-AFl was more prevalent in heart-transplant patients and those who died of cardiac causes (56% vs. 16%, P=0.014). CONCLUSIONS: AF-AFl is associated with inappropriate ICD shocks, heart transplantation, and cardiac death in patients with ARVD. Evidence of reduced RV function and atrial dilation helps to identify the ARVD patients at increased risk for AF-AFl.