The Cardica C-Port System: clinical and angiographic evaluation of a new device for automated, compliant distal anastomoses in coronary artery bypass grafting surgery--a multicenter prospective clinical trial

OBJECTIVES: The C-Port System (Cardica, Inc, Redwood City, Calif) integrates in one tool all functions necessary to enable rapid automated distal coronary anastomoses. The goal of this prospective, nonrandomized, and multicenter study is to determine the safety and efficacy of this novel anastomotic system. METHODS: Five centers enrolled 133 patients awaiting elective coronary artery bypass grafting surgery. Outcome variables were intraoperative device performance, incidence of device-related adverse events, predischarge and 6-month angiographic graft patency, and 12-month clinical outcome. Independent core laboratories performed qualitative and quantitative angiographic and computed tomographic assessments. RESULTS: The C-Port was used to perform a vein-to-coronary anastomosis in 130 patients. Intraoperative conversion to a hand-sewn anastomosis was necessary in 11 patients because of inadequate target site preparation, inappropriate target vessel selection, or both. Inadequate blood flow related to poor runoff required conversion in 3 additional patients. Three patients died before discharge of causes unrelated to the device. At discharge, 113 patients had a C-Port implant in place, and 104 C-Port anastomoses were studied by means of angiography, resulting in 100 FitzGibbon A, 3 FitzGibbon B, and 1 FitzGibbon 0 classifications. At 6 months, one additional patient died of a device-unrelated cause, and 98 patients were evaluated by means of angiography (n = 89). Overall patency (FitzGibbon A) was 92.1%. Three C-Port anastomoses were rated FitzGibbon B, and 4 were rated FitzGibbon 0. At 12 months, 107 (98.2%) of 109 alive patients were followed up, without any reports of device-related major adverse cardiac events. CONCLUSIONS: The C-Port System allows for a rapid, reliable, and compliant distal anastomosis and yields favorable 6-month angiographic and 12-month clinical results when compared with published studies.

Impact of vessel size on angiographic and clinical outcomes of revascularization with biolimus-eluting stent with biodegradable polymer and sirolimus-eluting stent with durable polymer the LEADERS trial substudy

OBJECTIVES: We assessed the impact of vessel size on outcomes of stenting with biolimus-eluting degradable polymer stent (BES) and sirolimus-eluting permanent polymer stent (SES) within a randomized multicenter trial (LEADERS). BACKGROUND: Stenting of small vessels might be associated with higher rates of adverse events. METHODS: "All-comer" patients (n = 1,707) were randomized to BES and SES. Post-hoc-stratified analysis of angiographic and clinical outcomes at 9 months and 1 year, respectively, was performed for vessels with reference diameter 2.75 mm. RESULTS: Of 1,707 patients, 429 patients in the BES group with 576 lesions and 434 patients in the SES group with 557 lesions had only small vessels treated (50.6% of the patient cohort). In patients with small vessels there was no significant difference in overall major adverse cardiac events (MACE) rate (12.1% vs. 11.8%; p = 0.89) or target lesion revascularization (TLR) rate (9.6% vs. 7.4%; p = 0.26) between BES and SES. The MACE and TLR rates in the small-vessel patient population were higher than in the large-vessel population. The TLR rate was 9.6% versus 2.6%, and MACE rate was 12.1% versus 7.1% for small versus large vessels in the BES arm (TLR: hazard ratio [HR] = 3.724, p = 0.0013; MACE: HR = 1.720, p = 0.0412). In the SES arm, TLR was 7.4% versus 5.1%, and MACE was 11.8% versus 10.3% in small versus large vessels (TLR: HR = 1.435, p = 0.2594; MACE: HR = 1.149, p = 0.5546). CONCLUSIONS: Prevalence of small vessel disease is high in an "all-comer" population with higher TLR and MACE rates. The BES and SES seem equivalent in treatment outcomes of small vessels in this "all-comer" patient population.

The evolutionary diversification of parrots supports a taxon pulse model with multiple trans-oceanic dispersal events and local radiations

Vicariance is thought to have played a major role in the evolution of modern parrots. However, as the relationships especially of the African taxa remained mostly unresolved, it has been difficult to draw firm conclusions about the roles of dispersal and vicariance. Our analyses using the broadest taxon sampling of old world parrots ever based on 3219 bp of three nuclear genes revealed well-resolved and congruent phylogenetic hypotheses. Agapornis of Africa and Madagascar was found to be the sister group to Loriculus of Australasia and Indo-Malayasia and together they clustered with the Australasian Loriinae, Cyclopsittacini and Melopsittacus. Poicephalus and Psittacus from mainland Africa formed the sister group Of the Neotropical Arini and Coracopsis from Madagascar and adjacent islands may be the closest relative of Psittrichas from New Guinea. These biogeographic relationships are best explained by independent colonization of the African continent via trans-oceanic dispersal from Australasia and Antarctica in the Paleogene following what may have been vicariance events in the late Cretaceous and/or early Paleogene. Our data support a taxon pulse model for the diversification of parrots whereby trans-oceanic dispersal played a more important role than previously thought and was the prerequisite for range expansion into new continents. (C) 2009 Elsevier Inc. All rights reserved

Amplatzer left atrial appendage occlusion: single center 10-year experience

OBJECTIVES To report a 10-year single center experience with Amplatzer devices for left atrial appendage (LAA) occlusion. BACKGROUND Intermediate-term outcome data following LAA occlusion are scarce. METHODS Short- and intermediate-term outcomes of patients who underwent LAA occlusion were assessed. All procedures were performed under local aesthesia without transesophageal echocardiography. Patients were discharged on acetylsalicylic acid and clopidogrel for 1-6 months. RESULTS LAA occlusion was attempted in 152 patients (105 males, age 72 ± 10 years, CHA2 DS2 -Vasc-score 3.4 ± 1.7, HAS-BLED-score 2.4 ± 1.2). Nondedicated devices were used in 32 patients (21%, ND group) and dedicated Amplatzer Cardiac Plugs were used in 120 patients (79%, ACP group). A patent foramen ovale or atrial septal defect was used for left atrial access and closed at the end of LAA occlusion in 40 patients. The short-term safety endpoints (procedural complications, bleeds) occurred in 15 (9.8%) and the efficacy endpoints (death, stroke, systemic embolization) in 0 patients. Device embolization occurred more frequently in the ND as compared to the ACP group (5 patients or 12% vs. 2 patients or 2%). Mean intermediate-term follow up of the study population was 32 months (range 1-120). Late deaths occurred in 15 patients (5 cardiovascular, 7 noncardiac, 3 unexplained). Neurologic events occurred in 2, peripheral embolism in 1, and major bleeding in 4 patients. The composite efficacy and safety endpoint occurred in 7% and 12% of patients. CONCLUSION LAA closure may be a good alternative to oral anticoagulation. This hypothesis needs to be tested in a randomized clinical trial to ensure that all potential biases of this observational study are accounted for.

Transcatheter aortic valve implantation and bleeding: incidence, predictors and prognosis

Peri-procedural bleeding complications are feared adverse events in patients undergoing transcatheter aortic valve implantation (TAVI). Little is known about the implications of peri-procedural bleeding on clinical outcome. In a prospective single-center registry of consecutive patients undergoing TAVI, we investigated incidence, predictors and clinical consequences of life-threatening and major bleeding as defined by the Valve Academic Research Consortium. Among 389 consecutive patients undergoing TAVI by a transfemoral (79.2%), transapical (19.6%) or trans-subclavian (1.3%) approach between July 2007 and October 2011, life-threatening or major peri-procedural bleeding events occurred in 64 (16.4%) and 125 patients (32.1%), respectively. Patients with peri-procedural bleeding events had a higher logistic EuroSCORE, more advanced renal disease, and were more symptomatic as assessed by New York Heart Association functional class at baseline as compared to patients with no bleeding. Life-threatening bleeding was associated with a higher all-cause (17.2 vs. 5.6 vs. 3.0%, p < 0.001) and cardiovascular mortality (10.9 vs. 5.6 vs. 2.5%, p = 0.02) at 30 days compared to patients with major bleeding or no bleeding. Multivariate analysis identified transapical access (OR 2.6, 95% CI 1.4-4.8; p = 0.002), glomerular filtration rate <30 ml/min (OR 2.3, 95% CI 1.1-4.7, p = 0.031), and diabetes (OR 1.8, 95% CI 1.001-3.2, p = 0.049) as independent predictors of life-threatening, peri-procedural bleeding. Life-threatening bleeding complications in patients undergoing TAVI are associated with increased mortality. Renal impairment, diabetes, and transapical approach were identified as independent risk factors for life-threatening bleeding events.

Subclinical thyroid dysfunction and cardiovascular outcomes among prospective cohort studies

The association between subclinical thyroid dysfunction and cardiovascular outcomes has been recently clarified with the publication of three individual participant data (IPD) analyses from the Thyroid Studies Collaboration. We identified original cohort studies with a systematic review and pooled individual data from over 70'000 participants to obtain a more precise estimate of the risks of cardiovascular outcomes associated with subclinical thyroid dysfunction. Subclinical hypothyroidism and subclinical hyperthyroidism, defined as normal thyroxine (FT4) levels with increased or decreased Thyroid-Stimulating Hormones (TSH or thyrotropin) respectively, are associated with increased risk of cardiovascular outcomes compared to euthyroid state, particularly in those with a more pronounced thyroid dysfunction. Specifically, subclinical hypothyroidism is associated with an increased risk of coronary heart disease (CHD) events, CHD mortality and heart failure (HF) events in individuals with higher TSH levels, particularly in those with TSH levels ≥10.0 mIU/L. Conversely, subclinical hyperthyroidism is associated with an increased risk of total mortality, CHD mortality, HF and atrial fibrillation, particularly in those with suppressed TSH levels <0.10 mIU/L. Pending ongoing randomized controlled trials, these observational findings allow identifying potential TSH thresholds for thyroid medication initiation based on risk of clinical outcomes, although clinical decision based solely on observational data need caution. The impact of thyroid replacement among the elderly with subclinical hypothyroidism is currently studied in a multicenter international randomized controlled trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial, TRUST trial).

Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients.

Repetitive transcranial magnetic stimulation (rTMS) is a recent putative treatment for affective disorders. Several studies have demonstrated antidepressant effects of rTMS in younger patients; we aimed to assess its effect in older outpatients with treatment-resistant major depression. Twenty-four outpatients (mean age=62 years, S.D.=12) with major depression were randomized for sham or real stimulation and received 10 daily rTMS sessions (20 Hz, 2-s trains, 28-s intertrain intervals, 100% of motor threshold) in addition to the antidepressant medication. For sham stimulation, the coil was tilted 90 degrees. Depression severity was assessed using the Hamilton Depression Rating Scale, the Beck Depression Inventory, items from the NIMH self-rated symptom scale, and a visual analog depression scale. Mini-Mental Status Examination performance, memory, and executive and attentional functions were measured to control for cognitive side effects. Depression ratings revealed significant antidepressant effects within 2 weeks in both sham and real stimulation groups; however, there were no between-group differences. Treatment with rTMS was safe; adverse events were rare and not more prevalent in either group, and cognitive assessment did not show any deterioration. We were unable to demonstrate any additional antidepressant effects of real stimulation in elderly patients with treatment-resistant major depression. Therapeutic effects of rTMS in this clinically challenging patient group remain to be demonstrated.

Risk of very early recurrent cerebrovascular events in symptomatic carotid artery stenosis

OBJECT The risk of recurrence of cerebrovascular events within the first 72 hours of admission in patients hospitalized with symptomatic carotid artery (CA) stenoses and the risks and benefits of emergency CA intervention within the first hours after the onset of symptoms are not well known. Therefore, the authors aimed to assess (1) the ipsilateral recurrence rate within 72 hours of admission, in the period from 72 hours to 7 days, and after 7 days in patients presenting with nondisabling stroke, transient ischemic attack (TIA), or amaurosis fugax (AF), and with an ipsilateral symptomatic CA stenosis of 50% or more, and (2) the risk of stroke in CA interventions within 48 hours of admission versus the risk in interventions performed after 48 hours. METHODS Ninety-four patients were included in this study. These patients were admitted to hospital within 48 hours of a nondisabling stroke, TIA, or AF resulting from a symptomatic CA stenosis of 50% or more. The patients underwent carotid endarterectomy (85 patients) or CA stenting (9 patients). At baseline, the cardiovascular risk factors of the patients, the degree of symptomatic CA stenosis, and the type of secondary preventive treatment were assessed. The in-hospital recurrence rate of stroke, TIA, or AF ipsilateral to the symptomatic CA stenosis was determined for the first 72 hours after admission, from 72 hours to 7 days, and after 7 days. Procedure-related cerebrovascular events were also recorded. RESULTS The median time from symptom onset to CA intervention was 5 days (interquartile range 3.00-9.25 days). Twenty-one patients (22.3%) underwent CA intervention within 48 hours after being admitted. Overall, 15 recurrent cerebrovascular events were observed in 12 patients (12.8%) in the period between admission and CA intervention: 3 strokes (2 strokes in progress and 1 stroke) (3.2%), 5 TIAs (5.3%), and 1 AF (1.1%) occurred within the first 72 hours (total 9.6%) of admission; 1 TIA (1.1%) occurred between 72 hours and 7 days, and 5 TIAs (5.3%) occurred after more than 7 days. The corresponding actuarial cerebrovascular recurrence rates were 11.4% (within 72 hours of admission), 2.4% (between 72 hours and 7 days), and 7.9% (after 7 days). Among baseline characteristics, no predictive factors for cerebrovascular recurrence were identified. Procedure-related cerebrovascular events occurred at a rate of 4.3% (3 strokes and 1 TIA), and procedures performed within the first 48 hours and procedures performed after 48 hours had a similar frequency of these events (4.5% vs. 4.1%, respectively; p = 0.896). CONCLUSIONS The in-hospital recurrence of cerebrovascular events was quite low, but all recurrent strokes occurred within 72 hours. The risk of stroke associated with a CA intervention performed within the first 48 hours was not increased compared with that for later interventions. This raises the question of the optimal timing of CA intervention in symptomatic CA stenosis. To answer this question, more data are needed, preferably from large randomized trials.

Geochronology of metasomatic events

In order to date any geological event, suitable mineral geochronometers that record that and only that event must be identified and analyzed. In the case of metasomatism, recrystallisation is a key process that controls both the petrology and the isotopic record of minerals. It can occur both in the form of complete neocrystallisation (e.g. in a vein) and in the form of pseudomorphism, whereby dissolution/reprecipitation at the submicroscopic scale plays a central role. Recrystallisation may be complete or not, raising the possibility that relicts of a pre-metasomatic assemblage may be preserved. Because recrystallisation is energetically less costly at almost any temperature than diffusion, and because radiogenic isotopes (except 4He) never diffuse faster than major elements forming the mineral structure, there is a strong causal link between petrographic relicts and isotopic inheritance (as demonstrated for zircon, monazite, titanite, amphibole, K-feldspar, biotite, and muscovite). Metasomatic assemblages commonly contain such mixtures between relicts and newly formed phases, whose geochronology is slightly more complex than that of simple, ideal systems, but can be managed by techniques that have become routine in the last decade and which are described in this chapter. Because of its crucial role in controlling the isotope systematics, the petrogenesis of a mineral needs to be understood in extreme detail, especially using microchemical analyses and micro-imaging techniques, before mineral ages can be correctly interpreted. As the occurrence of recrystallization is limited by the availability of water, minerals act as “geohygrometers” that allow constraints to be placed on the nature and age of fluid circulation episodes, especially metasomatic events.

A randomized clinical trial of Behavioral Activation (BA) therapy for improving psychological and physical health in dementia caregivers: results of the Pleasant Events Program (PEP).

Dementia caregiving is associated with elevations in depressive symptoms and increased risk for cardiovascular diseases (CVD). This study evaluated the efficacy of the Pleasant Events Program (PEP), a 6-week Behavioral Activation intervention designed to reduce CVD risk and depressive symptoms in caregivers. One hundred dementia family caregivers were randomized to either the 6-week PEP intervention (N = 49) or a time-equivalent Information-Support (IS) control condition (N = 51). Assessments were completed pre- and post-intervention and at 1-year follow-up. Biological assessments included CVD risk markers Interleukin-6 (IL-6) and D-dimer. Psychosocial outcomes included depressive symptoms, positive affect, and negative affect. Participants receiving the PEP intervention had significantly greater reductions in IL-6 (p = .040), depressive symptoms (p = .039), and negative affect (p = .021) from pre- to post-treatment. For IL-6, clinically significant improvement was observed in 20.0% of PEP participants and 6.5% of IS participants. For depressive symptoms, clinically significant improvement was found for 32.7% of PEP vs 11.8% of IS participants. Group differences in change from baseline to 1-year follow-up were non-significant for all outcomes. The PEP program decreased depression and improved a measure of physiological health in older dementia caregivers. Future research should examine the efficacy of PEP for improving other CVD biomarkers and seek to sustain the intervention's effects.

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies.

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

The FReedom from Ischemic Events-New Dimensions for Survival (FRIENDS) registry: design of a prospective cohort study of patients with advanced peripheral artery disease.

BACKGROUND Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes. METHODS/DESIGN The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up. DISCUSSION The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

High intestinal cholesterol absorption is associated with cardiovascular disease and risk alleles in ABCG8 and ABO: evidence from the LURIC and YFS cohorts and from a meta-analysis.

OBJECTIVES This study sought to determine whether high intestinal cholesterol absorption represents a cardiovascular risk factor and to link ABCG8 and ABO variants to cardiovascular disease (CVD). BACKGROUND Plant sterol-enriched functional foods are widely used for cholesterol lowering. Their regular intake yields a 2-fold increase in circulating plant sterol levels that equally represent markers of cholesterol absorption. Variants in ABCG8 and ABO have been associated with circulating plant sterol levels and CVD, thereby suggesting atherogenic effects of plant sterols or of cholesterol uptake. METHODS The cholestanol-to-cholesterol ratio (CR) was used as an estimate of cholesterol absorption because it is independent of plant sterols. First, we investigated the associations of 6 single nucleotide polymorphisms in ABCG8 and ABO with CR in the LURIC (LUdwisghafen RIsk and Cardiovascular health study) and the YFS (Young Finns Study) cohorts. Second, we conducted a systematic review and meta-analysis to investigate whether CR might be related to CVD. RESULTS In LURIC, the minor alleles of rs4245791 and rs4299376 and the major alleles of rs41360247, rs6576629, and rs4953023 of the ABCG8 gene and the minor allele of rs657152 of the ABO gene were significantly associated with higher CR. Consistent results were obtained for rs4245791, rs4299376, rs6576629, and rs4953023 in YFS. The meta-analysis, including 6 studies and 4,362 individuals, found that CR was significantly increased in individuals with CVD. CONCLUSIONS High cholesterol absorption is associated with risk alleles in ABCG8 and ABO and with CVD. Harm caused by elevated cholesterol absorption rather than by plant sterols may therefore mediate the relationships of ABCG8 and ABO variants with CVD.