Long-term success of a multi-electrode substrate mapping and ablation strategy versus a classic single tip mapping and ablation strategy for ventricular tachycardia ablation in patients with ischemic cardiomyopathy.

INTRODUCTION: Over the past years, mapping and ablation techniques for the treatment of ventricular tachycardia (VT) have evolved rapidly. High Density (HD) substrate mapping is now routine and pre-procedural imaging is increasingly used. The additional value of these techniques for long-term VT-free survival is not clear. METHODS: We compared baseline and procedural characteristics, procedural success, safety and outcome of mapping and ablation of ventricular tachycardia in patients with ischemic heart disease between two groups. (1) Low Density (LD) group: VT mapping and ablation with a 4 mm single tip catheter (2) HD group: HD substrate mapping with the Pentaray (Biosense Webster, USA) or HD Grid (Abbott, USA) catheter and ablation with a 4 mm single tip catheter. RESULTS: VT ablation was performed in 133 patients (71 patients in LD group and 62 patients in HD group). The median follow-up was 5.0 years in LD group and 2.0 years in HD group. One-, two-, and five-year VT recurrence rates were 47%, 56%, and 65% in the LD group versus 39%, 50%, and 55% in the HD group (log-rank test for VT recurrence p = .70). One-, two-, and five-year ICD shock recurrence rates were 14%, 18%, and 24% in the LD group versus 8%, 15%, and 19% in the HD group (log-rank test for ICD-shock p = .79). All-cause mortality, cardiac (non-arrhythmic), and arrhythmic death, were similar in both groups. Severe procedural complications (tamponade, stroke, or procedural death) occurred in four patients (5%, 1 vascular, 3 tamponade) in the LD group versus two patients (3%, both tamponade) in the HD group (NS). In univariate and multivariable analysis, only a higher LVEF was significantly associated with VT-free survival. HD mapping was not significantly associated with VT-free survival. Anterior infarct location and age were significantly associated with ICD recurrent shock in both univariate and multivariable analyses. CONCLUSIONS: In patients with ischemic cardiomyopathy, a HD substrate mapping, and ablation strategy did not lead to higher VT-free survival and shock-free survival compared to a single tip mapping and ablation strategy. In this study, only LVF is an independent predictor for VT recurrence. Anterior infarct location and age predict recurrent ICD shocks.

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.

The effect of transcatheter aortic valve implantation approaches on mortality.

OBJECTIVES: We aimed to evaluate the effect of transcatheter aortic valve implantation (TAVI) approaches on mortality and identify effect modifiers and predictors for mortality. BACKGROUND: Alternative access routes to transfemoral (TF) TAVI include the surgical intra-thoracic direct-aortic (DA) and transapical (TA) approach. TA TAVI has been associated with a higher mortality rate. We hypothesized that this is related to effect modifiers, in particular the left ventricular ejection fraction (LVEF). METHODS: This multicentre study derived its data from prospective registries. To adjust for confounders, we used propensity-score based, stabilized inverse probability weighted Cox regression models. RESULTS: In total, 5,910 patients underwent TAVI via TF (N = 4,072), DA (N = 524), and TA (N = 1,314) access. Compared to TF, 30-day mortality was increased among DA (HR 1.87, 95%CI 1.26-2.78, p = .002) and TA (HR 3.34, 95%CI 2.28-4.89, p < .001) cases. Compared to TF, 5-year mortality was increased among TA cases (HR 1.50, 95%CI 1.24-1.83, p < .001). None of the variables showed a significant interaction between the approaches and mortality. An impaired LVEF (≤35%) increased mortality in all approaches. CONCLUSIONS: The surgical intra-thoracic TA and DA TAVI are both associated with a higher 30-day mortality than TF TAVI. TA TAVI is associated with a higher 5-year mortality than TF TAVI. The DA approach may therefore have some advantages over the TA approach when TF access is not feasible.

Efficacy and Safety of the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation and Concomitant Aspirin Therapy: A Meta-Analysis of Randomized Trials.

BACKGROUND: Current guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study-based meta-analysis of published randomized controlled trials. METHODS: A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis. RESULTS: This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67-0.91; vascular death: HR, 0.85; 95% CI, 0.76-0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69-1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26-0.56). CONCLUSIONS: This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy.

Long-term results of carotid stenting and risk factors in patients with severe carotid artery stenosis undergoing subsequent cardiac surgery.

AIMS: To identify risk factors for composite outcome of mortality, stroke or myocardial infarction in patients with severe carotid stenosis undergoing staged carotid artery stenting (CAS) with subsequent cardiac surgery. METHODS AND RESULTS: In this prospective observational study, we enrolled 643 consecutive patients with both symptomatic (i.e., with history of stroke) and asymptomatic severe carotid artery disease, who required cardiac surgery. Generally, cardiac surgery was planned 30 days after the CAS procedure. The composite outcome consisted of death, stroke and myocardial infarction. The composite outcome rate was 26.3% at 5 years and 47% at 8 years after CAS. Age ≥ 80 years (hazard ratio [HR] = 1.89; 95%CI, 1.18-3.03; P = 0.008), history of stroke (HR = 1.66, 1.16-2.37; P = 0.006), chronic obstructive pulmonary disease (HR = 1.86; 1.07-3.24; P = 0.03) and kidney disease (HR = 1.83, 1.11-3.04; P = 0.02) were independent risk factors for the composite outcome during long-term follow-up. CONCLUSIONS: In this study with staged CAS followed by cardiac surgery, we confirm previously reported event-free survival rates and identify several risk factors for the composite outcome. Future studies are needed to confirm the importance of the identified risk factors and to assess their predictive ability.

Association of Traditional Cardiovascular Risk Factors With Venous Thromboembolism: An Individual Participant Data Meta-Analysis of Prospective Studies.

BACKGROUND: Much controversy surrounds the association of traditional cardiovascular disease risk factors with venous thromboembolism (VTE). METHODS: We performed an individual level random-effect meta-analysis including 9 prospective studies with measured baseline cardiovascular disease risk factors and validated VTE events. Definitions were harmonized across studies. Traditional cardiovascular disease risk factors were modeled categorically and continuously using restricted cubic splines. Estimates were obtained for overall VTE, provoked VTE (ie, VTE occurring in the presence of 1 or more established VTE risk factors), and unprovoked VTE, pulmonary embolism, and deep-vein thrombosis. RESULTS: The studies included 244 865 participants with 4910 VTE events occurring during a mean follow-up of 4.7 to 19.7 years per study. Age, sex, and body mass index-adjusted hazard ratios for overall VTE were 0.98 (95% confidence interval [CI]: 0.89-1.07) for hypertension, 0.97 (95% CI: 0.88-1.08) for hyperlipidemia, 1.01 (95% CI: 0.89-1.15) for diabetes mellitus, and 1.19 (95% CI: 1.08-1.32) for current smoking. After full adjustment, these estimates were numerically similar. When modeled continuously, an inverse association was observed for systolic blood pressure (hazard ratio=0.79 [95% CI: 0.68-0.92] at systolic blood pressure 160 vs 110 mm Hg) but not for diastolic blood pressure or lipid measures with VTE. An important finding from VTE subtype analyses was that cigarette smoking was associated with provoked but not unprovoked VTE. Fully adjusted hazard ratios for the associations of current smoking with provoked and unprovoked VTE were 1.36 (95% CI: 1.22-1.52) and 1.08 (95% CI: 0.90-1.29), respectively. CONCLUSIONS: Except for the association between cigarette smoking and provoked VTE, which is potentially mediated through comorbid conditions such as cancer, the modifiable traditional cardiovascular disease risk factors are not associated with increased VTE risk. Higher systolic blood pressure showed an inverse association with VTE.

Systematic comparison of routine laboratory measurements with in-hospital mortality: ICU-Labome, a large cohort study of critically ill patients.

BACKGROUND: In intensive care unit (ICU) patients, many laboratory measurements can be deranged when compared with the standard reference interval (RI). The assumption that larger derangements are associated with worse outcome may not always be correct. The ICU-Labome study systematically evaluated the univariate association of routine laboratory measurements with outcome. METHODS: We studied the 35 most frequent blood-based measurements in adults admitted ≥6 h to our ICU between 1992 and 2013. Measurements were from the first 14 ICU days and before ICU admission. Various metrics, including variability, were related with hospital survival. ICU- based RIs were derived from measurements obtained at ICU discharge in patients who were not readmitted to the ICU and survived for >1 year. RESULTS: In 49,464 patients (cardiothoracic surgery 43%), we assessed >20·106 measurements. ICU readmissions, in-hospital and 1-year mortality were 13%, 14% and 19%, respectively. On ICU admission, lactate had the strongest relation with hospital mortality. Variability was independently related with hospital mortality in 30 of 35 measurements, and 16 of 35 measurements displayed a U-shaped outcome-relation. Medians of 14 of 35 ICU-based ranges were outside the standard RI. Remarkably, γ-glutamyltransferase (GGT) had a paradoxical relation with hospital mortality in the second ICU week because more abnormal GGT-levels were observed in hospital survivors. CONCLUSIONS: ICU-based RIs for may be more useful than standard RIs in identifying ICU patients at risk. The association of variability with outcome for most of the measurements suggests this is a consequence and not a cause of a worse ICU outcome. Late elevation of GGT may confer protection to ICU patients.

Kidney measures with diabetes and hypertension on cardiovascular disease: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Whether the association of chronic kidney disease (CKD) with cardiovascular risk differs based on diabetes mellitus (DM) and hypertension (HTN) status remains unanswered. METHODS: We investigated 11,050 participants from the Atherosclerosis Risk in Communities Study (fourth examination (1996-1998)) with follow-up for cardiovascular outcomes (coronary disease, heart failure and stroke) through 2009. Using the Cox regression models, we quantified cardiovascular risk associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) in individuals with and without DM and/or HTN and assessed their interactions. RESULTS: Individuals with DM and HTN generally had higher cardiovascular risk relative to those without at all the levels of eGFR and ACR. Cardiovascular risk increased with lower eGFR and higher ACR regardless of DM and HTN status (e.g. adjusted hazards ratio (HR) for eGFR 30-44 vs. 90-104 ml/min/1.73 m(2), 2.32 (95% CI, 1.66-3.26) in non-diabetics vs. 1.83 (1.25-2.67) in diabetics and 2.45 (2.20-5.01) in non-hypertensives vs. 1.51 (1.27-1.81) in hypertensives and corresponding adjusted HR for ACR 30-299 vs. <10 mg/g, 1.70 (1.45-2.00) vs. 1.34 (1.10-1.64) and 1.42 (1.10-1.85) vs. 1.57 (1.36-1.81), respectively). Only the ACR-DM interaction reached significance, with a shallower relative risk gradient among diabetics than among non-diabetics (p = 0.02). Analysis of individual cardiovascular outcomes showed similar results. CONCLUSION: Although individuals with DM and HTN generally had higher cardiovascular risk relative to those without these complications, both low eGFR and high ACR were associated with cardiovascular diseases regardless of the presence or absence of DM and HTN. These findings reinforce the importance of CKD in cardiovascular outcomes.

Association of kidney disease measures with ischemic versus hemorrhagic strokes: pooled analyses of 4 prospective community-based cohorts.

BACKGROUND AND PURPOSE: Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke. METHODS: We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression. RESULTS: Among 29,595 participants (mean age, 61 [SD 12.5] years; 46% men; 17% black), 1261 developed stroke (12% hemorrhagic) during 280,549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95% confidence interval, 1.01-1.68) and 0.92 (0.47-1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27-2.07) for ischemic and 2.57 (1.37-4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure. CONCLUSIONS: Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations.

Association of mild to moderate chronic kidney disease with venous thromboembolism: pooled analysis of five prospective general population cohorts.

BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. METHODS AND RESULTS: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Trøndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Tromsø study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria ≥30 mg/g, (versus no CKD) was 1.54 (95% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well. CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis.

BACKGROUND: Hypertension is the most prevalent comorbidity in individuals with chronic kidney disease. However, whether the association of the kidney disease measures, estimated glomerular filtration rate (eGFR) and albuminuria, with mortality or end-stage renal disease (ESRD) differs by hypertensive status is unknown. METHODS: We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and ESRD associated with eGFR and albuminuria in individuals with and without hypertension. FINDINGS: We analysed data for 45 cohorts (25 general population, seven high-risk, and 13 chronic kidney disease) with 1,127,656 participants, 364,344 of whom had hypertension. Low eGFR and high albuminuria were associated with mortality irrespective of hypertensive status in the general population and high-risk cohorts. All-cause mortality risk was 1·1-1·2 times higher in individuals with hypertension than in those without hypertension at preserved eGFR. A steeper relative risk gradient in individuals without hypertension than in those with hypertension at eGFR range 45-75 mL/min per 1·73 m(2) led to much the same mortality risk at lower eGFR. With a reference eGFR of 95 mL/min per 1·73 m(2) in each group to explicitly assess interaction, adjusted HR for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) was 1·77 (95% CI 1·57-1·99) in individuals without hypertension versus 1·24 (1·11-1·39) in those with hypertension (p for overall interaction=0·0003). Similarly, for albumin-creatinine ratio of 300 mg/g (vs 5 mg/g), HR was 2·30 (1·98-2·68) in individuals without hypertension versus 2·08 (1·84-2·35) in those with hypertension (p for overall interaction=0·019). We recorded much the same results for cardiovascular mortality. The associations of eGFR and albuminuria with ESRD, however, did not differ by hypertensive status. Results for chronic kidney disease cohorts were similar to those for general and high-risk population cohorts. INTERPRETATION: Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension. FUNDING: US National Kidney Foundation.

Single-beat global atrial mapping facilitates the treatment of short-lived atrial tachycardias and infrequent premature atrial contractions.

BACKGROUND: Short runs of atrial tachycardias (ATs) and infrequent premature atrial contractions (PACs) are difficult to map and ablate using sequential electrophysiology mapping techniques. The AcQMap mapping system allows for highly accurate mapping of a single atrial activation. OBJECTIVES: We aimed to test the value of a novel dipole charge density-based high-resolution mapping technique (AcQMap) in the treatment of brief episodes of ATs and PACs. METHODS: Data of all patients undergoing catheter ablation (CA) using the AcQMap mapping system were reviewed. RESULTS: Thirty-one out of 219 patients (male n = 8; female n = 23) had short runs of ATs (n = 23) and PACs (n = 8). The mean procedural time was 155.3 ± 46.6 min, with a mean radiation dose of 92.0 (IQR 37.0-121.0) mGy. Total radiofrequency application duration 504.0 (271.0-906.0) s. Left atrial localization of ATs and PACs was identified in 45.1% of the cases, right atrium localization in 45.1%, and septal origins in 9.8% of the cases. Acute success was achieved in 30/31 (96.8%), and recurrence during the follow-up developed in six patients (19.4%), including four patients with PACs and two patients with short-lived ATs. One patient presented procedure-related groin hematoma as minor complication. CONCLUSION: Brief episodes of highly symptomatic ATs and infrequent PACs can be mapped using charge density mapping and successfully ablated with high acute and long-term success rates.

Elevated albuminuria associated with increased risk of recurrent venous thromboembolism: results of a population-based cohort study.

This study examined the risk of recurrent venous thromboembolism (VTE) in patients with elevated albuminuria. In 1997-1998, inhabitants of Groningen, the Netherlands, aged 28-75 years (n=85,421), were invited to participate in the PREVEND (Prevention of REnal and Vascular ENd stage Disease) Study, an observational, population-based cohort study. Albuminuria was measured and VTE occurrence was monitored in responding subjects (n=40,856). Patients with first VTE between study entry and January 2009, identified through databases of the national registry of hospital discharge diagnoses, death certificates, regional anticoagulation clinic and medical records, were used for analysis. Of 351 subjects with first VTE, 37 subjects developed a recurrence during a median follow-up period of 3.3 (interquartile range, 1.1-6.4) years. The annual incidence of recurrence in subjects with elevated albuminuria (≥ 20 mg/l) was 5.00% [95% confidence interval (CI); 2.16-9.85], compared to 2.38% (95%CI; 1.59-3.41) in subjects with normal albuminuria (<20 mg/l). Hazard ratio for recurrence was 1.95 (95%CI; 0.89-4.30) after adjustment for age and sex. This hazard ratio was 3.35 (95%CI; 1.18-9.47) in patients with first unprovoked, and 1.12 (95%CI; 0.25-5.01) in those with a first provoked event. This study showed that subjects with elevated albuminuria who experience an unprovoked VTE are at an increased risk of recurrence, independent of age and sex.

Increased risk of arterial thromboembolism after a prior episode of venous thromboembolism: results from the Prevention of REnal and Vascular ENd stage Disease (PREVEND) Study.

Large population-based studies are needed to establish the magnitude and duration of the recently suggested association between arterial and venous thromboembolism. In 1997-98, all inhabitants of Groningen, the Netherlands, aged 28-75 years (n = 85 421), were invited to participate in a study that followed and monitored responding subjects (n = 40 856) for venous and arterial thromboembolism until 2009. Thromboembolism was verified with national registries of hospital discharge diagnoses and death certificates, anticoagulation clinic and medical records. During a median follow-up of 10·7 years, 549 participants developed venous thromboembolism and 3283 developed arterial thromboembolism. Annual incidence of arterial thromboembolism after venous thromboembolism was 2·03% [95% confidence interval (CI), 1·48-2·71], compared to 0·87% (95% CI, 0·84-0·90) in subjects without venous thromboembolism. The hazard ratio (HR) of arterial thromboembolism after venous thromboembolism was 1·40 (95% CI, 1·04-1·88) after adjustment for age, sex and cardiovascular risk factors. This risk was highest during the first year after venous thromboembolism [annual incidence, 3·00% (95% CI, 1·64-5·04); adjusted HR, 2·01 (95% CI, 1·19-3·40)] and after an unprovoked event [annual incidence, 2·53% (95% CI, 1·68-3·66); adjusted HR, 1·62 (95% CI, 1·11-2·34)]. This study showed that subjects with venous thromboembolism are at increased risk for arterial thromboembolism, particularly in the first year after venous thromboembolism and after an unprovoked event.

Age and association of kidney measures with mortality and end-stage renal disease.

CONTEXT: Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. OBJECTIVE: To evaluate possible effect modification (interaction) by age of the association of eGFR and albuminuria with clinical risk, examining both relative and absolute risks. DESIGN, SETTING, AND PARTICIPANTS: Individual-level meta-analysis including 2,051,244 participants from 33 general population or high-risk (of vascular disease) cohorts and 13 CKD cohorts from Asia, Australasia, Europe, and North/South America, conducted in 1972-2011 with a mean follow-up time of 5.8 years (range, 0-31 years). MAIN OUTCOME MEASURES: Hazard ratios (HRs) of mortality and end-stage renal disease (ESRD) according to eGFR and albuminuria were meta-analyzed across age categories after adjusting for sex, race, cardiovascular disease, diabetes, systolic blood pressure, cholesterol, body mass index, and smoking. Absolute risks were estimated using HRs and average incidence rates. RESULTS: Mortality (112,325 deaths) and ESRD (8411 events) risks were higher at lower eGFR and higher albuminuria in every age category. In general and high-risk cohorts, relative mortality risk for reduced eGFR decreased with increasing age; eg, adjusted HRs at an eGFR of 45 mL/min/1.73 m2 vs 80 mL/min/1.73 m2 were 3.50 (95% CI, 2.55-4.81), 2.21 (95% CI, 2.02-2.41), 1.59 (95% CI, 1.42-1.77), and 1.35 (95% CI, 1.23-1.48) in age categories 18-54, 55-64, 65-74, and ≥75 years, respectively (P <.05 for age interaction). Absolute risk differences for the same comparisons were higher at older age (9.0 [95% CI, 6.0-12.8], 12.2 [95% CI, 10.3-14.3], 13.3 [95% CI, 9.0-18.6], and 27.2 [95% CI, 13.5-45.5] excess deaths per 1000 person-years, respectively). For increased albuminuria, reduction of relative risk with increasing age was less evident, while differences in absolute risk were higher in older age categories (7.5 [95% CI, 4.3-11.9], 12.2 [95% CI, 7.9-17.6], 22.7 [95% CI, 15.3-31.6], and 34.3 [95% CI, 19.5-52.4] excess deaths per 1000 person-years, respectively by age category, at an albumin-creatinine ratio of 300 mg/g vs 10 mg/g). In CKD cohorts, adjusted relative hazards of mortality did not decrease with age. In all cohorts, ESRD relative risks and absolute risk differences at lower eGFR or higher albuminuria were comparable across age categories. CONCLUSIONS: Both low eGFR and high albuminuria were independently associated with mortality and ESRD regardless of age across a wide range of populations. Mortality showed lower relative risk but higher absolute risk differences at older age.

Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate.

CONTEXT: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation more accurately estimates glomerular filtration rate (GFR) than the Modification of Diet in Renal Disease (MDRD) Study equation using the same variables, especially at higher GFR, but definitive evidence of its risk implications in diverse settings is lacking. OBJECTIVE: To evaluate risk implications of estimated GFR using the CKD-EPI equation compared with the MDRD Study equation in populations with a broad range of demographic and clinical characteristics. DESIGN, SETTING, AND PARTICIPANTS: A meta-analysis of data from 1.1 million adults (aged ≥ 18 years) from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts. Data transfer and analyses were conducted between March 2011 and March 2012. MAIN OUTCOME MEASURES: All-cause mortality (84,482 deaths from 40 cohorts), cardiovascular mortality (22,176 events from 28 cohorts), and end-stage renal disease (ESRD) (7644 events from 21 cohorts) during 9.4 million person-years of follow-up; the median of mean follow-up time across cohorts was 7.4 years (interquartile range, 4.2-10.5 years). RESULTS: Estimated GFR was classified into 6 categories (≥90, 60-89, 45-59, 30-44, 15-29, and <15 mL/min/1.73 m(2)) by both equations. Compared with the MDRD Study equation, 24.4% and 0.6% of participants from general population cohorts were reclassified to a higher and lower estimated GFR category, respectively, by the CKD-EPI equation, and the prevalence of CKD stages 3 to 5 (estimated GFR <60 mL/min/1.73 m(2)) was reduced from 8.7% to 6.3%. In estimated GFR of 45 to 59 mL/min/1.73 m(2) by the MDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73 m(2) by the CKD-EPI equation and had lower incidence rates (per 1000 person-years) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.27-0.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P < .001). Net reclassification improvement was similarly positive in most subgroups defined by age (<65 years and ≥65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. CONCLUSION: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

Aspirin Alone Versus Dual Antiplatelet Therapy After Transcatheter Aortic Valve Implantation: A Systematic Review and Patient-Level Meta-Analysis.

Background In patients undergoing transcatheter aortic valve implantation without an indication for oral anticoagulation, it is unclear whether single or dual antiplatelet therapy (DAPT) is necessary to minimize both the bleeding and thromboembolic risk. In this patient-level meta-analysis, we further investigate the effect of aspirin alone compared with DAPT for preventing both thromboembolic and bleeding events after transcatheter aortic valve implantation. Methods and Results We conducted a systematic review of all available randomized controlled trials comparing aspirin with DAPT. In total, 1086 patients were included across 4 eligible trials. The primary outcomes were the composite of all-cause mortality, major or life-threatening bleeding, stroke or myocardial infarction (first composite outcome), and the same composite excluding bleeding (second composite outcome), both tested at 30 days and 3 months. The first composite outcome occurred significantly less in the aspirin-alone group at 30 days (10.3% versus 14.7%, odds ratio [OR], 0.67; 95% CI, 0.46-0.97, P=0.034) and 3 months (11.0% versus 16.5%, hazard ratio [HR], 0.66; 95% CI, 0.47-0.94, P=0.02), compared with the DAPT group. The second composite outcome occurred in 5.5% and 6.6% at 30 days (OR, 0.83; 95% CI, 0.50-1.38, P=0.47) and in 6.9% and 8.5% at 3 months in the aspirin-alone group compared with the DAPT group (HR, 0.82; 95% CI, 0.52-1.29, P=0.39), respectively. Conclusions In patients without an indication for oral anticoagulation undergoing transcatheter aortic valve implantation, aspirin alone significantly reduced the composite of thromboembolic and bleeding events, and does not increase the composite of thromboembolic events after transcatheter aortic valve implantation, compared with DAPT.

Factor V Leiden Does Not Modify the Phenotype of Acute Coronary Syndrome or the Extent of Myocardial Necrosis.

Background The prothrombotic defect factor V Leiden (FVL) may confer higher risk of ST-segment-elevation myocardial infarction (STEMI), compared with non-ST-segment-elevation acute coronary syndrome, and may be associated with more myocardial necrosis caused by higher thrombotic burden. Methods and Results Patients without history of cardiovascular disease were selected from 2 clinical trials conducted in patients with acute coronary syndrome. FVL was defined as G-to-A substitution at nucleotide 1691 in the factor V (factor V R506Q) gene. Odds ratios were calculated for the association of FVL with STEMI adjusted for age and sex in the overall population and in the subgroups including sex, age (≥70 versus <70 years), and traditional cardiovascular risk factors. The peak biomarker levels (ie, creatine kinase-myocardial band and high-sensitivity troponin I or T) after STEMI were contrasted between FVL carriers and noncarriers. Because of differences in troponin assays, peak high-sensitivity troponin levels were converted to a ratio scale. The prevalence of FVL mutation was comparable in patients with STEMI (6.0%) and non-ST-segment-elevation acute coronary syndrome (5.8%). The corresponding sex- and age-adjusted odds ratio was 1.06 (95% CI, 0.86-1.30; P=0.59) for the association of FVL with STEMI. Subgroup analysis did not show any differences. In patients with STEMI, neither the median peak creatine kinase-myocardial band nor the peak high-sensitivity troponin ratio showed any differences between wild-type and FVL carriers (P for difference: creatine kinase-myocardial band=0.33; high sensitivity troponin ratio=0.54). Conclusions In a general population with acute coronary syndrome, FVL did not discriminate between a STEMI or non-ST-segment-elevation acute coronary syndrome presentation and was unrelated to peak cardiac necrosis markers in patients with STEMI. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00391872 and NCT01761786.