Optical coherence tomography, intravascular ultrasound or angiography guidance for distal left main coronary stenting. The ROCK cohort II study.

OBJECTIVES: to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid-term outcome accordingly. BACKGROUND: Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited. METHODS: ROCK II is a multicenter, investigator-driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal-LM stenting. The primary study endpoint was target-lesion failure (TLF) including cardiac death, target-vessel myocardial infarction and target-lesion revascularization. We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non-inferiority of OCT versus IVUS. RESULTS: A total of 730 patients, 377 with intravascular-imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one-year rate of TLF was 21.2% with angiography and 12.7% with intravascular-imaging (p = 0.039), with no difference between OCT and IVUS (p = 0.26). Intravascular-imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23-0.93: p = 0.03). Propensity-score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one-year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p = 0.03 for IVUS or OCT vs. angiography). No between-group significant differences in the rate of individual components of TLF were found. CONCLUSIONS: Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.

Antithrombotic strategies in elderly patients with atrial fibrillation revascularized with drug-eluting stents: PACO-PCI (EPIC-15) registry.

BACKGROUND: We sought to investigate the antithrombotic regimens applied and their prognostic effects in patients over 75 years old with atrial fibrillation (AF) after revascularization with drug-eluting stents (DES). METHODS: Retrospective registry in 20 centers including patients over 75 years with AF treated with DES. A primary endpoint of MACCE and a co-primary endpoint of major bleeding by ISTH criteria were considered at 12 months. RESULTS: A total of 1249 patients (81.1 ±â€¯4.2 years, 33.1% women, 66.6% ACS, 30.6% complex PCI) were included. Triple antithrombotic therapy (TAT) was prescribed in 81.7% and dual antithrombotic therapy (DAT) in 18.3%. TAT was based on direct oral anticoagulants (DOAC) in 48.4% and maintained for only 1 month in 52.2%, and DAT included DOAC in 70.6%. Primary endpoint of MACCE was met in 9.6% and primary endpoint of major bleeding in 9.4%. TAT was significantly associated with more bleeding (10.2% vs. 6.1%, p = 0.04) but less MACCE (8.7% vs. 13.6%, p = 0.02) than DAT and the use of DOAC was significantly associated to less bleeding (8% vs. 11.1%, p = 0.03) and similar MACCE (9.8% vs. 9.4%, p = 0.8). TAT over 1 month or with VKA was associated with more major bleeding but comparable MACCE rates. CONCLUSIONS: Despite advanced age TAT prevails, but duration over 1 month or the use of other agent than Apixaban are associated with increased bleeding without additional MACCE prevention. DAT reduces bleeding but with a trade-off in terms of ischemic events. DOAC use was significantly associated to less bleeding and similar MACCE rates.

Parametric Modeling of Biomimetic Cortical Bone Microstructure for Additive Manufacturing.

In this work we present a novel algorithm for generating in-silico biomimetic models of a cortical bone microstructure towards manufacturing biomimetic bone via additive manufacturing. The software provides a tool for physicians or biomedical engineers to develop models of cortical bone that include the inherent complexity of the microstructure. The correspondence of the produced virtual prototypes with natural bone tissue was assessed experimentally employing Digital Light Processing (DLP) of a thermoset polymer resin to recreate healthy and osteoporotic bone tissue microstructure. The proposed tool was successfully implemented to develop cortical bone structure based on osteon density, cement line thickness, and the Haversian and Volkmann channels to produce a user-designated bone porosity that matches within values reported from literature for these types of tissues. Characterization of the specimens using a Scanning Electron Microscopy with Focused Ion Beam (SEM/FIB) and Computer Tomography (CT) revealed that the manufacturability of intricated virtual prototype is possible for scaled-up versions of the tissue. Modeling based on the density, inclination and size range of the osteon and Haversian and Volkmann´s canals granted the development of a dynamic in-silico porosity (13.37⁻21.49%) that matches with models of healthy and osteoporotic bone. Correspondence of the designed porosity with the manufactured assessment (5.79⁻16.16%) shows that the introduced methodology is a step towards the development of more refined and lifelike porous structures such as cortical bone. Further research is required for validation of the proposed methodology model of the real bone tissue and as a patient-specific customization tool of synthetic bone.

The Pt-Cr everolimus-eluting stent with bioabsorbable polymer in the treatment of patients with acute coronary syndromes. Results from the SYNERGY ACS registry.

OBJECTIVES: We investigated the safety and efficacy of the bioabsorbable polymer-coated, everolimus-eluting coronary stent (SYNERGY) stent in a real-world study population with acute coronary syndromes (ACS). BACKGROUND: A number of clinical trials support the overall efficacy and safety of the SYNERGY stent. However, a recent trial (TIDES-ACS) in the context of ACS reported worrying figures of infarction and definite/probable stent thrombosis in the SYNERGY control arm. METHODS: This is a multicenter registry (10 centers) including consecutive patients with ACS (unstable angina, non-ST elevated myocardial infarction, ST elevated myocardial infarction) who underwent percutaneous revascularization with the implantation of SYNERGY stent. The primary endpoint was the composite of cardiac death, myocardial infarction and target lesion revascularization at 12 months. RESULTS: A total of 1008 patients were included with age 65.4 ±â€¯14.8 years, 23.8% females and a 24.5% diabetics. Regarding presentation, a 15.2% with unstable angina, 43% with non-ST elevated myocardial infarction and 41.8% with ST elevated myocardial infarction. Primary outcome was met in 3% (7% in SYNERGY TIDES-ACS arm, P superiority <0.01 and 6.3% in OPTIMAX TIDES-ACS arm, P superiority <0.01). Cardiac death was 1.3% (1.6%, p = 0.8 and 0.5%, P superiority =0.1 respectively). Myocardial infarction was 1.6% (4.6%, p < 0.01 and 1.8%, P superiority = 0.9 respectively). Target lesion revascularization was 1% (3.4%, p < 0.01 and 5.4%, P superiority <0.01 respectively). Definite or probable thrombosis was 0.9% (2.8%, p ≤ 0.01 and 1.1%, P superiority = 0.8 respectively). CONCLUSIONS: The results of this registry show a very good safety and efficacy profile at 12 months for the SYNERGY stent in patients with ACS. SUMMARY: A recent trial (TIDES-ACS) in the context of acute coronary syndromes (ACS) reported worrying figures of infarction and definite/probable stent thrombosis in the SYNERGY stent control arm. We investigated the safety of SYNERGY stent in a real-world study population with ACS applying the same inclusion/exclusion criteria as used in the TIDES-ACS trial. Primary endpoint was the composite of cardiac death, myocardial infarction and TLR at 12 months. A total of 1008 patients have been included. Primary outcome was met in 3% (7% in SYNERGY TIDES-ACS arm, P superiority <0.01 and 6.3% in OPTIMAX TIDES-ACS arm, P superiority <0.01).

Multivessel disease in patients over 75years old with ST elevated myocardial infarction. Current management strategies and related clinical outcomes in the ESTROFA MI+75 nation-wide registry.

BACKGROUND: In elderly patients with ST elevated myocardial infarction (STEMI) and multivessel disease (MVD the outcomes related with different revascularization strategies are not well known. METHODS: Subgroup-analysis of a nation-wide registry of primary angioplasty in the elderly (ESTROFA MI+75) with 3576 patients over 75years old from 31 centers. Patients with MVD were analyzed to describe treatment approaches and 2years outcomes. RESULTS: Of 1830 (51%) with MVD, 847 (46%) underwent multivessel revascularization either in acute (51%), staged (44%) or both procedures (5%). Patients with previous myocardial infarction and those receiving drug-eluting stents or IIb-IIIa inhibitors were more prone to be revascularized, whereas older patients, females and those with Killip III-IV, renal failure and higher ejection fraction were less likely. Survival free of cardiac death and infarction at 2years was better for those undergoing multivessel PCI (85.8% vs. 80.4%, p<0.0008), regardless of Killip class. Multivessel PCI was protective of cardiac death and infarction (HR 0.60, 95% CI 0.40-0.89; p=0.011). Complete revascularization made no difference in outcomes among those patients undergoing multivessel PCI. The best prognosis corresponded to those undergoing multivessel PCI in staged procedures (p<0.001). A propensity score matching analysis (514 patients in each group) yielded similar results. CONCLUSIONS: In elderly patients with STEMI and MVD, multivessel PCI was related with better outcomes especially after staged procedures. Among those undergoing multivessel PCI, anatomically defined completeness of revascularization had not prognostic influence. SUMMARY: We sought to investigate the revascularization strategies applied and their prognostic implications in patients aged over 75years with ST elevated myocardial infarction showing multivessel disease. Of 1830 patients, 847 (46%) underwent multivessel PCI either in acute (51%), staged (44%) or both procedures (5%). Multivessel PCI was independent predictor of cardiac death and infarction with the best prognosis corresponding to those undergoing staged procedures.

Phylogenetic analyses indicate little variation among reticuloendotheliosis viruses infecting avian species, including the endangered Attwater's prairie chicken.

Reticuloendotheliosis virus infection, which typically causes systemic lymphomas and high mortality in the endangered Attwater's prairie chicken, has been described as a major obstacle in repopulation efforts of captive breeding facilities in Texas. Although antigenic relationships among reticuloendotheliosis virus (REV) strains have been previously determined, phylogenetic relationships have not been reported. The pol and env of REV proviral DNA from prairie chickens (PC-R92 and PC-2404), from poxvirus lesions in domestic chickens, the prototype poultry derived REV-A and chick syncytial virus (CSV), and duck derived spleen necrosis virus (SNV) were PCR amplified and sequenced. The 5032bp, that included the pol and most of env genes, of the PC-R92 and REV-A were 98% identical, and nucleotide sequence identities of smaller regions within the pol and env from REV strains examined ranged from 95 to 99% and 93 to 99%, respectively. The putative amino acid sequences were 97-99% identical in the polymerase and 90-98% in the envelope. Phylogenetic analyses of the nucleotide and amino acid sequences indicated the closest relationship among the recent fowl pox-associated chicken isolates, the prairie chicken isolates and the prototype CSV while only the SNV appeared to be distinctly divergent. While the origin of the naturally occurring viruses is not known, the avian poxvirus may be a critical component of transmission of these ubiquitous oncogenic viruses.

Secondary forms of Takotsubo cardiomyopathy: A whole different prognosis.

BACKGROUND: Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. METHODS: We performed an analysis including patients with TKS between 2003-2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as 'primary forms' and (b) physical factors (asthma, surgery, trauma, etc.) as 'secondary forms'. RESULTS: Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14-10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01-2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06-3.22, p=0.02). CONCLUSION: Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.

H5N2 avian influenza outbreak in Texas in 2004: the first highly pathogenic strain in the United States in 20 years?

In early 2004, an H5N2 avian influenza virus (AIV) that met the molecular criteria for classification as a highly pathogenic AIV was isolated from chickens in the state of Texas in the United States. However, clinical manifestations in the affected flock were consistent with avian influenza caused by a low-pathogenicity AIV and the representative virus (A/chicken/Texas/298313/04 [TX/04]) was not virulent for experimentally inoculated chickens. The hemagglutinin (HA) gene of the TX/04 isolate was similar in sequence to A/chicken/Texas/167280-4/02 (TX/02), a low-pathogenicity AIV isolate recovered from chickens in Texas in 2002. However, the TX/04 isolate had one additional basic amino acid at the HA cleavage site, which could be attributed to a single point mutation. The TX/04 isolate was similar in sequence to TX/02 isolate in several internal genes (NP, M, and NS), but some genes (PA, PB1, and PB2) had sequence of a clearly different origin. The TX/04 isolate also had a stalk deletion in the NA gene, characteristic of a chicken-adapted AIV. By analyzing viruses constructed by in vitro mutagenesis followed by reverse genetics, we found that the pathogenicity of the TX/04 virus could be increased in vitro and in vivo by the insertion of an additional basic amino acid at the HA cleavage site and not by the loss of a glycosylation site near the cleavage site. Our study provides the genetic and biologic characteristics of the TX/04 isolate, which highlight the complexity of the polygenic nature of the virulence of influenza viruses.

Characterization of recent H5 subtype avian influenza viruses from US poultry.

In the US, the isolation of H5 subtype avian influenza (AI) viruses has been uncommon in commercial chickens and turkeys, although sporadic isolations have been made from the live bird markets or its supply chain since 1986. In 2002, two different outbreaks of H5 AI occurred in commercial chicken or turkey operations. The first occurred in Texas and was identified as a H5N3 subtype AI virus. The second outbreak was caused by a H5N2 virus isolated from a turkey farm in California. In this study we analyzed recent H5 subtype AI viruses from different avian species and different sources in the US. Most recent H5 subtype isolates shared a high sequence identity and phylogenetically assorted into a separate clade from the Pennsylvania/83 lineage isolates. However, no established lineage was found within this clade and the recent H5 subtype isolates seemed to be the result of separate introductions from the wild bird reservoir. The Texas H5N3 isolate shared the lowest homology with the other recent isolates in the haemagglutinin gene and had a unique haemagglutinin cleavage site sequence of REKR/G (other recent isolates have the typical avirulent motif, RETR/G). Furthermore, this isolate had a 28 amino acid deletion in the stalk region of the neuraminidase protein, a common characteristic of chicken adapted influenza viruses, and may indicate that this virus had actually been circulating in poultry for an extended period of time before it was isolated. In agreement with genetic evidence, the Texas H5N3 isolate replicated better than other H5 isolates in experimentally infected chickens. The outbreak in Texas with a more chicken-adapted H5N3 virus underscores the importance of ongoing surveillance and control efforts regarding the H5 subtype AI virus in the US.