Prior Cerebrovascular Events Research Articles

Predictors, Incidence, and Outcomes of Patients Undergoing Transfemoral Transcatheter Aortic Valve Implantation Complicated by Stroke.

Stroke remains one of the most devastating complications of transcatheter aortic valve implantation (TAVI). The aim of this study was to identify the incidence, timing, temporal trends, and predictors of stroke after TAVI and evaluate the outcomes of patients with stroke. The CENTER-Collaboration is an international collaboration consisting of 3 national registries and 7 local registries or prospective clinical trials, selected through a systematic review. Accordingly, a total of 10 982 patients undergoing transfemoral TAVI between 2007 and 2018 were included in the current patient-level pooled analyses. A total of 261 patients (2.4%) experienced stroke during the first month after TAVI. The median time between TAVI and stroke was 1 day (interquartile range, 0-6 days). The stroke rate was comparable in procedures performed in the early years of TAVI (2007-2012) to those in the more recent years of TAVI (2013-2018; both 2.4%; P=1.0). Independent predictors of stroke at 30 days were a history of cerebrovascular events (odds ratio, 2.2; 95% CI, 1.4-3.6; P=0.0012) and a glomerular filtration rate of <30 mL/min per 1.73 m2 (odds ratio, 1.7; 95% CI, 1.0-2.8; P=0.05). Stroke occurring within the first 30 days after TAVI was associated with a 6-fold increase of 30-day mortality (odds ratio, 6.0; 95% CI, 4.4-8.1; P<0.001). Moreover, patients with stroke more frequently had documented new-onset atrial fibrillation (16% versus 3%; P<0.001) and major or life-threatening bleedings (12% versus 7%; P=0.002) at 30-day follow-up. In this large, global, patient-level analysis, the incidence of stroke after transfemoral TAVI was 2.4%. Prior cerebrovascular events and a low glomerular filtration rate independently predicted the occurrence of stroke after TAVI. The occurrence of stroke after TAVI was associated with a strikingly 6-fold increase of 30-day mortality; additionally, there was a 5-fold higher rate of new-onset atrial fibrillation in patients with stroke. URL: https://www.clinicaltrials.gov . Unique identifier: NCT03588247.

Long-term monitoring to detect atrial fibrillation with the indwelling implantable cardiac monitors

An increasing number of detection tools are available and several detection strategies have been described to pursue the diagnosis of atrial fibrillation to prevent ischemic stroke. Monitoring tools include standard electrocardiography, snapshot single-lead recordings with professional or personal devices (e.g. smartphone-based), Holter monitor, external devices with long-term recording capabilities, and cardiac implantable electronic devices, including pacemakers, implantable cardioverter defibrillators and insertable cardiac monitors. Insertable cardiac monitors have shown high sensitivity and specificity for the detection of atrial fibrillation, allow up to three years of continuous monitoring, do not require cooperation of the patient, are well tolerated, have a short device-related time delay between detection of atrial fibrillation and notification to the physician, provide information on atrial fibrillation burden and are minimally invasive. On the other hand, insertable cardiac monitors require a considerable use of resources to process the recordings and have a significant initial cost. Studies conducted with insertable cardiac monitors on patients with prior stroke and on patients with risk factors for stroke but no prior cerebrovascular events or atrial fibrillation have consistently shown a measurable incidence of atrial fibrillation at follow-up. However, the effectiveness of oral anticoagulations in reducing the incidence of ischemic stroke in patients with atrial fibrillation lasting less than 24 h, though reasonable, is currently unproven. The future of atrial fibrillation detection tools and atrial fibrillation detection strategies will be influenced by ongoing studies exploring whether oral anticoagulations reduce the incidence of stroke in patients with atrial fibrillation burden lower than 24 h.

Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack

BackgroundBiomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking. ObjectivesThis study evaluated whether patients with prior cerebrovascular events and elevated levels of oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), but without prior coronary artery disease (CAD), are at risk for recurrent stroke and CAD events following high-dose statin therapy. MethodsIn the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, OxPL-apoB levels were measured in 4,385 patients with stroke or transient ischemic attack at baseline and in 3,106 patients at 5 years following randomization to placebo or 80 mg atorvastatin. The primary endpoint was the time from randomization to a second nonfatal or fatal stroke. Secondary endpoints included first major coronary events and any cardiovascular event. ResultsPatients with recurrent stroke had higher baseline median OxPL-apoB levels than patients without (15.5 nmol/l vs. 11.6 nmol/l; p < 0.0001). After multivariable adjustment, elevated baseline OxPL-apoB predicted recurrent stroke (hazard ratio [HR]: 4.3; p < 0.0001), first major coronary events (HR: 4.0; p < 0.0001), and any cardiovascular event (HR: 4.4; p < 0.0001). These comparisons for any endpoint did not differ by treatment, shown as a nonsignificant interaction test. The net reclassification improvement, integrated discrimination improvement, and area under the receiver-operating characteristic curve (AUC) were all significantly improved by adding OxPL-apoB to the models, with ΔAUC +0.0505 (p < 0.0001) for recurrent stroke, ΔAUC +0.0409 (p < 0.0001) for first major coronary event, and ΔAUC +0.0791 (p < 0.0001) for any cardiovascular event. ConclusionsElevated OxPL-apoB levels predicted recurrent stroke and first major coronary events in patients with prior stroke or transient ischemic attack. The lack of statin–OxPL-apoB treatment interaction suggested that OxPLs might be statin-independent therapeutic targets to reduce risk of cardiovascular events. (Lipitor in the Prevention of Stroke, for Patients Who Have Had a Previous Stroke [SPARCL]; NCT00147602)

Impact of Cerebrovascular Events Older Than One Year on Ischemic and Bleeding Outcomes With Cangrelor in Percutaneous Coronary Intervention.

Cangrelor is a potent intravenous adenosine diphosphate-receptor antagonist that in the CHAMPION trials reduced the 48-hour and 30-day rates of ischemic events during percutaneous coronary intervention without an increase in severe bleeding. CHAMPION PCI (A Clinical Trial to Demonstrate the Efficacy of Cangrelor), CHAMPION PLATFORM (Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition), and CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention) were 3 randomized, double-blind, double-dummy trials in which cangrelor was compared with clopidogrel during percutaneous coronary intervention. The effect of cangrelor on ischemic events and bleeding was analyzed in the subgroup of patients with a history of cerebrovascular events at least 1 year prior to randomization; the Breslow-Day test was used to test for interaction of treatment effect in subgroups with and without such a history. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours. Among 24 910 randomized patients, 1270 patients (5.1%) had a cerebrovascular event >1 year old, including 650 assigned to cangrelor and 620 assigned to clopidogrel. Consistent with the overall trial results, the rate of the primary efficacy end point was 4.3% in the cangrelor group versus 5.3% in the clopidogrel group (odds ratio 0.80; 95% confidence interval 0.48-1.34; P=0.40; P for interaction =0.97), and the rate of GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe bleeding was 0.3% in both groups (P=0.97; P for interaction =0.81). Among patients in the CHAMPION trials with a prior cerebrovascular event at least 1 year before the percutaneous coronary intervention, the efficacy and bleeding profile of cangrelor compared with clopidogrel was similar to that in the overall trial.

Klebsiella Oxytoca: A Case of Antibiotic- Associated Hemorrhagic Colitis

A 74-year-old male with a prior cerebrovascular event and history of Clostridium difficile infection presents with bloody diarrhea for 1-2 weeks. He had been started on oral vancomycin a few days prior to presentation for a positive Clostridium difficile toxin. Cross-sectional imaging revealed pancolitis. Laboratory values were remarkable for a WBC count of 11.2 with 8% bands. Standard stool cultures and ova and parasites were negative. Repeat C. difficile toxin by PCR was also negative. His bloody diarrhea failed to improve after 1 week of oral vancomycin so flexible sigmoidoscopy was performed, revealing diffusely ulcerated erythematous rectosigmoid mucosa. Biopsies showed marked lymphoplasmacytic inflammatory infiltrates in the lamina propria with mild neutrophilic infiltrate concerning for ongoing infectious colitis. The patient's stool culture was tested for additional pathogens and was positive for Klebsiella oxytoca. Oral vancomycin was discontinued with cessation of bloody diarrhea. K. oxytoca can cause a rare form of antibiotic-associated hemorrhagic colitis [1]. K. oxytoca colonizes the gut in 2-10% of healthy individuals [2]. However, given its antibiotic resistance patterns, administration of certain antibiotics can lead to bacterial overgrowth and cytotoxin overproduction, thereby mediating mucosal damage in the colon. Although this is most frequently described after use of penicillin derivatives, literature review reveals three reported cases of late-onset quinolone associated K. oxytoca hemorrhagic colitis [3]. There are no reports of oral vancomycin associated hemorrhagic colitis. K. oxytoca is diagnosed on stool culture, but is not usually documented on standard microbiology reports given its presence as a normal colonizer. This hemorrhagic colitis is treated with cessation of offending antibiotics and usually resolves within 4 days [1]. We describe a case of K. oxytoca hemorrhagic colitis caused by oral vancomycin C. difficile therapy. Because K. oxytoca is not routinely reported on stool culture, clinicians should have a high index of suspicion for K. oxytoca in the differential diagnosis of patients with antibiotic-associated hemorrhagic colitis who were recently treated for C. difficile infection.Figure 1Figure 2

Aortic atheroma burden predicts acute cerebrovascular events after transcatheter aortic valve implantation: insights from volumetric multislice computed tomography analysis.

Embolisation of atheromatous debris during catheter manipulation is considered to underlie acute cerebrovascular events (CVE) after transcatheter aortic valve implantation (TAVI). However, the relationship between aorta atheroma burden and acute CVE after TAVI has not been established. We investigated the impact of aorta atheroma burden on acute CVE. Preoperative multislice computed tomographic (MSCT) images in 278 patients receiving TAVI were analysed. Total atheroma volume (TAV) was calculated by measuring aorta vessel and lumen areas in every 1 mm cross-sectional image. Acute CVE was observed in 16 patients. Patients having acute CVE were more likely to have a prior CVE (p=0.002), and to exhibit greater TAV in the ascending aorta (12.8±3.5 vs. 7.0±2.1 cm3, p<0.001) and the aortic arch (3.1±1.6 vs. 1.2±0.2 cm3, p<0.001). TAV in the ascending aorta >10.3 cm3 and in the aortic arch >2.9 cm3 predicted acute CVE. The incidence of acute CVE was highest (36.4%) if patients had a prior CVE and TAV in the ascending aorta and the aortic arch above cut-offs. Patients with acute CVE after TAVI had greater aorta atheroma burden. Our findings might underscore preoperative MSCT analysis of aorta atherosclerosis to identify high-risk patients for acute CVE, who might require an embolic protection device during TAVI.

Evolution in the eligibility criteria of randomized controlled trials for systemic cancer therapies.

Eligibility criteria in randomized controlled trials (RCTs) reduce inter-patient heterogeneity, but may reduce generalizability of results. Here, we explore temporal changes in eligibility criteria of practice-changing RCTs for systemic cancer therapies and in the proportion of patients excluded from these trials after application of eligibility criteria. An electronic search identified practice-changing RCTs published in six major journals between July 2010 and December 2012. Trial protocols were identified through journal websites and communication with authors or study sponsors. Eligibility criteria were extracted from protocols. The number of patients excluded after application of eligibility criteria was extracted from the CONSORT diagrams and text of publications. Changes in eligibility criteria over time were assessed by logistic regression and meta-regression was carried out to evaluate the impact of year of protocol on the proportion of patients who were excluded after screening. Eighty-six protocols written between 1987 and 2012 were included. Over time, there has been an increasing frequency of exclusion of patients with prior cerebrovascular events (OR 1.34, p=0.003), coagulation/bleeding disorders (OR 1.34, p=0.006), prior gastrointestinal bleeding (OR 1.33, p=0.01), cardiac co-morbidities (OR 1.24, p=0.004) and exclusion based on concurrent medication (OR 1.19, p=0.01). There has been a decrease in upper age limit usage (OR 0.83, p=0.01) and leukopenia (OR 0.83, p=0.009). The proportion of patients excluded from trials has increased from 9% prior to 2000 to 18% after 2010 (p-value for trend <0.001). RCTs have become less representative of cancer patients treated in routine practice with increased use of organ-specific and co-morbidity-based exclusion criteria.

A Nationwide Observational Study of the Israeli Experience with Ponatinib Outside Clinical Trials in Chronic Myeloid Leukemia

Ponatinib is an oral tyrosine kinase inhibitor (TKI) that has been designed to be effective also in patients who harbor the TKI-refractory threonine to isoleucine mutation at position 315 (T315I). In December 2014 the drug was granted an accelerated approval by the FDA, based on the promising results from the phase II PACE (Ponatinib Ph ALL and CML evaluation) trial. In this trial, 56% of previously treated patients who had resistance to or unacceptable side effects from dasatinib or nilotinib achieved a major cytogenetic response, including 70% of patients with the T315I mutation. Albeit the PACE trial convincingly demonstrated the efficacy of ponatinib, the wide use of the drug has been limited due to safety matters and in particular arterial thrombotic complications, reported in up to 17% of patients. Currently, there is very little real-life information regarding the use of ponatinib outside of clinical trials. The purpose of this study is to characterize patients with chronic myeloid leukemia (CML) who received ponatinib and to assess the effectiveness and safety profile of ponatinib outside of clinical trials.Between 4.2011 and 7.2015 (51 months) 24 patients with CML received ponatinib in 7 medical centers in Israel. We reviewed the medical records of these patients and asked their physicians to rank the quality of life of their patients on a 1 to 5 scale.Prior to ponatinib therapy, patients were treated for a median of 55 months (range: 1 to 215) with 1 to 3 different TKIs (median: 3). In addition 13 patients received at least one course of chemotherapy or interferon and 2 underwent allogeneic bone marrow transplantation.Screening for mutations at the DNA binding domain was performed at least once during the pre-ponatinib follow-up time in most patients (67%, N=16). Mutations were detected in 11 patients (69%) and the T315I mutation was detected in 8 of those.The median age when starting ponatinib was 44 years (rang: 23 to 79). Most patients had advanced disease and their disease was classified as either accelerated (21%, N=5) or blast crisis (41%, N=10) when they started ponatinib. Based on the medical history, 48% were at-risk to develop vascular complications either because of prior cerebrovascular event or myocardial infarction (18%) or because of vascular risk factors (30%). Baseline ECG and cardiac ECHO studies were available in 11 patients. Only two had signs of prior MI in ECG and none had significant structural or functional pathology.At time of analysis the median duration of follow up was 6 months (range <1 to 34 months), 4 patients died and 14 were still receiving ponatinib. Patients discontinued the treatment either because of major cardiovascular events (N=3), severe pancytopenia (N=1), planned bone-marrow transplantation (N=1) or because they were lost to follow-up (N=1). Seventeen patients were available for response assessment at time of analysis and the overall response rate was 77% (N=13). Five of six patients at chronic phase achieved either complete or major molecular response. Eight patients at accelerated phase or at blast crisis (8/11, 72%) achieved either hematological (5/11, 45%) or molecular response (3/11, 27%). Two of those, with hematological response, underwent allogeneic bone marrow transplantation. The median subjective scoring of ponatinib contribution to the quality of life of patients was 2.4 (range 1 to 5). Physicians that gave low scoring mentioned severe weakness, myalgia and cytopenias as a major concern.Conclusions: In real- life setting ponatinib is generally used as a last resort. In our cohort, it was almost exclusively given to patients who experienced failure to previous TKIs. The only exceptions were 2 patients who received ponatinib for suboptimal molecular response and achieved MMR when switched to ponatinib. Only one third of patients tolerated the recommended dose of 45mg. Yet, response rate was still relatively high, suggesting that a daily dose of 30mg might be appropriate.With only 6 months of follow-up we documented 3 cardiovascular events (12%) that prompted discontinuation of the drug and only one patient had a significant prior vascular risk.The high response rate and overall contribution to quality of life in patients with very few alternatives, who already experienced failure of other TKIs, support the use of this treatment for patients with advanced disease. DisclosuresRaanani:Novartis: Other: Advisory Board, Research Funding; BMS: Other: Advisory Board; Ariad: Other: Advisory Board; Pfizer: Other: Advisory Board. Lavie:Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Rozovski:Novartis: Other: Advisory board.

Safety of Catheter Ablation for AtrialFibrillation in Patients With PriorCerebrovascular Events.

This study sought to report on the safety of catheter ablation for atrial fibrillation (AF) in patients with prior cerebrovascular events (CVEs), at a large-volume tertiary care center over the course of the past 15 years. Many patients with drug-refractory AF have a history of a prior CVE. These patients are considered to be at high procedural risk for catheter ablation but data are scant. All consecutive patients undergoing AF ablation at the Cleveland Clinic were enrolled in a prospectively maintained data registry, which was used to identify patients with a prior CVE. Strict periprocedural anticoagulation protocols were in place. Extreme care was taken with sheath and catheter manipulation to prevent thrombus formation or air embolism. All thromboembolic and hemorrhagic events occurring periprocedurally and up to 3 months of follow-up were identified. Of 9,413 consecutive patients who underwent AF ablation, 247 patients with a prior CVE were identified (median age, 64 years; 40.1% female; median CHA2DS2-VASC score, 4). Anticoagulants used were warfarin (n= 192), dabigatran (n= 32), rivaroxaban (n= 15), and apixaban (n= 8). All patients received intravenous heparin before transseptal access (activated clotting time target during procedure, 350 to 400 seconds). The energy source was radiofrequency in 242 patients and cryoenergy in 5 patients. Acute procedural complications included 5 groin hematomas (1 requiring transfusion), 5 pericardial effusions with associated tamponade physiology in 2 (1 required pericardiocenthesis, 1 required surgery), and 1 arteriovenous fistula (managed conservatively). Importantly, none of the patients had a periprocedural thromboembolic event. Patients with a prior history of cerebrovascular events do not seem to be predisposed to a significant risk of clinical CVE recurrence when undergoing catheter ablation for AF without interruption of therapeutic anticoagulation.

Abstract 13454: The Impact of Prior Stroke on the Outcome of Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Introduction: Prior stroke has been identified as an independent correlate for post-procedure cerebrovascular events (CVE) in aortic stenosis (AS) patients undergoing surgical aortic valve replacement (SAVR). The present study aimed to evaluate the impact of prior cerebrovascular events on outcome in AS patients undergoing TAVR. Methods: Patients with severe AS undergoing TAVR between May 2007-March 2015 were included and categorized to patients with and without prior CVE defined as stroke and transit ischemic attack. Baseline, procedural characteristics, in-hospital outcomes, 1-month and 1-year mortality were compared, in accordance with the VARC-2 consensus. Results: A cohort of 662 consecutive patients with severe AS undergoing TAVR was included in the analysis. Of these, 120 patients had prior CVE, and 542 without. Balloon expandable valve was used in 70.7% and self-expandable valve in 29.3% of the patients. Trans-femoral access was used in 78% (571), and pre-TAVR balloon aortic valvuloplasty was performed in 87% (574). Patients with prior CVE had a higher mean STS score compared to those without prior CVE (10.1% versus 8.8%, respectively; p=0,006) and demonstrated higher rates of atherosclerotic disease involving the coronary, peripheral and carotid arteries. In-hospital minor stroke occurred more often in patients with prior CVE vs. those without CVE (3.3% vs. 0.7%; p=0.04). However, similar mortality rates were recorded at 1, 6, and 12 months (figure 1), and there were no significant differences in major stroke, bleeding, or post-procedure hospital stay between both groups. Conclusions: Prior history of CVE infers a higher risk for in-hospital minor stroke, yet no impact on other outcomes post TAVR. Patients with and without a history of prior CVE with severe aortic stenosis will similarly benefit from TAVR. Therefore, a history of CVE should not be considered an exclusion criterion.

Reperfusion therapy for ST-elevation acute myocardial infarction in Eastern Europe: the ISACS-TC registry.

Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition. We sought to evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of ST-segment elevation myocardial infarction (STEMI) and either received reperfusion therapy or remained without reperfusion in Eastern Europe. Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; NCT01218776) on STEMI patients admitted to 57 hospitals in Eastern European countries from January 2010 to February 2015. The primary endpoint was 30-day mortality. Of 7982 patients, 65 (0.8%) had a documented contraindication to reperfusion, 5973 (75.5%) received fibrinolysis ( n = 1032) or underwent primary percutaneous coronary intervention (p-PCI; n = 4941), and 1944 patients (24.6%) did not receive any reperfusion therapy. The overall unadjusted 30-day mortality rate was 7.9%. Thirty-day mortality rates were higher in non-reperfusion patients (16.0 vs. 5.0% in the p-PCI group and 7.4% in fibrinolysis group). The strongest factors associated with not attempting reperfusion therapy among these patients were female sex (OR 1.29 CI 1.07-1.56), age (OR 1.02; CI 1.01-1.03), prior MI (OR 1.79; CI 1.38-2.32), prior cerebrovascular events (OR 1.87; CI 1.30-2.68), chronic kidney disease (OR 1.76; CI 1.22-2.53), Killip class >1 (OR 1.31; CI 1.06-1.62), and time to admission >12 h (OR 15.9; CI 13.1-19.3). A substantial number of patients are still not offered any reperfusion therapy in many Eastern European countries with economy in transition, and this was associated with increased 30-day mortality. Time from symptoms onset to admission >12 h was the highest ranking among factors related to lack of reperfusion therapy. Quality improvement efforts should focus on minimizing delay to hospital admission among STEMI patients.

Residual Risk of Stroke and Death in Anticoagulated Patients According to the Type of Atrial Fibrillation: AMADEUS Trial.

Atrial fibrillation (AF) and heart failure frequently coexist and are associated with increased morbidity and mortality. We investigated the prognosis of anticoagulated patients with permanent AF and nonpermanent AF according to preexisting heart failure in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. The primary outcome was a composite of cardiovascular death and stroke or systemic embolism, analyzed using a Cox proportional hazards model, adjusted for baseline age, sex, diabetes mellitus, hypertension, creatinine, and previous cardiovascular diseases. The median follow-up was 11.6 months (interquartile range, 6.2-15.2). Nonpermanent AF was present in 2072 patients (46% of cohort), of which 339 (16%) had preexisting heart failure. A total of 2484 patients had permanent AF (54% of cohort), with a higher burden of heart failure including 730 patients (29%; P<0.001). Overall, death because of cardiovascular causes occurred in 57 patients and 45 had stroke or systemic embolism (1.4/100 person-years for each). Overall, the adjusted incidence of the composite outcome was higher in patients with permanent AF than in patients with nonpermanent AF. In multivariate analysis, permanency of AF, creatinine, prior cerebrovascular events, and previous coronary disease were independently associated with the primary outcome. The hazard ratio for permanent versus nonpermanent AF was 1.68 (95% confidence interval, 1.08-2.55; P=0.02). The presence of heart failure increased the risk of adverse outcomes in a similar way in both permanent and nonpermanent AF (interaction P value=0.76). The risk of cardiovascular death, stroke, or systemic embolism is higher in anticoagulated patients with permanent AF than in those with nonpermanent AF, regardless of preexisting heart failure.

Incidence of Myocardial Infarction and Vascular Death in Elderly Patients With Atrial Fibrillation Taking Anticoagulants: Relation to Atherosclerotic Risk Factors

Recent findings suggest that patients with atrial fibrillation (AF), in addition being at thromboembolic risk, are at risk of myocardial infarction (MI). Our aim was to investigate predictors of MI and cardiovascular death in a cohort of patients with AF who were taking anticoagulants. We prospectively followed up 1,019 patients with AF for a median of 33.7 months (3,223 person-years). All patients were treated with oral vitamin K antagonists. Primary outcome was a composite end point of cardiovascular events (CVEs) including fatal/nonfatal MI, cardiac revascularization, and cardiovascular death. The mean age of the patients was 73.2 years, and 43.8% were women. At follow-up, 111 CVEs (3.43%/y) had occurred: 47 fatal-nonfatal MI/revascularization and 64 cardiovascular deaths. In addition, 31 stroke/transient ischemic attacks (0.96%/y) were recorded. Patients experiencing CVEs were older (P < .001) and had a higher prevalence of metabolic syndrome (MetS) (P = .005), heart failure (P = .001), and prior cardiac (P < .001) and cerebrovascular events (P < .001). On a Cox proportional hazard analysis, age (hazard ratio [HR], 1.083; 95% CI, 1.053-1.113; P < .001), smoking (HR, 2.158; 95% CI, 1.193-3.901; P = .011), history of cerebrovascular (HR, 1.704; 95% CI, 1.119-2.597; P = .013) and cardiac (HR, 1.658; 95% CI, 1.105-2.489; P = .015) events, MetS (HR, 1.663; 95% CI, 1.107-2.499; P = .014), heart failure (HR, 1.584; 95% CI, 1.021-2.456; P = .040), and male sex (HR, 1.499; 95% CI, 1.010-2.223; P = .044) predicted CVEs. Patients with AF still experience a high rate of CVEs despite receiving anticoagulant treatment. MetS is a common clinical feature in patients with AF, which increases the risk of CVEs. A holistic approach is needed to reduce the cardiovascular risk in patients with AF. ClinicalTrials.gov; No.: NCT01882114; URL: www.clinicaltrials.gov.

ELEVATED LEVELS OF OXIDIZED PHOSPHOLIPIDS ON APOLIPOPROTEIN B-100 PREDICT RECURRENT CEREBROVASCULAR EVENTS: A STROKE PREVENTION BY AGGRESSIVE REDUCTION IN CHOLESTEROL LEVELS (SPARCL) SUBSTUDY

Biomarkers to predict recurrent stroke are lacking. Elevated levels of oxidized phospholipids on apolipoprotein B-100 lipoprotein (OxPL/apoB) predict increased risk in patients without and with prior cardiovascular events, but have not been evaluated in patients with prior cerebrovascular events.

Abstract 15680: Sinus Node Dysfunction in Associated With Higher Symptom Burden and Increased Risk of Progression to Permanent Atrial Fibrillation: Results From ORBIT-AF Registry

Background: Patients with sinus node dysfunction (SND) are at increased risk of atrial tachyarrhythmias, including atrial fibrillation (AF). Whether the presence of SND is also associated with worse outcomes among those with AF has not been well described. Methods: The ORBIT-AF registry enrolled patients with AF from a range of clinical practices across the US. SND was defined clinically, based on the presence of sinus bradycardia, severe sinus bradycardia, sinus arrest, sinoatrial exit block, or features of tachycardia-bradycardia syndrome. Descriptive statistics and multivariable logistic regression analysis were used to describe treatment patterns and outcomes for patients with and without SND and AF. Results: Overall, 1,710 (17.7%) patients had SND at enrollment. Patients with SND had lower left-ventricular ejection fractions, higher CHA 2 DS 2 -VASc risk scores, and more prior cerebrovascular events. Patients with SND had more severe symptoms (EHRA class IV: 17.5% vs. 13.9%; p=0.007) and poorer quality of life (median AFEQT 77.5 vs. 81.1; p=0.008) as compared to those without. SND patients were more frequently treated with oral anticoagulants (79.2% vs. 75.9%, p=0.004) and had more often received interventional therapy for AF (16.1% vs. 10.5%, p&lt;0.0001). There were no differences in the current AF management strategy between patients with SND and those without [rate control (69.7% vs. 67.7%), rhythm control (30.0% vs. 32.0%); P=0.11]. After adjustment, significantly more patients with SND had progressed from paroxysmal AF at baseline to persistent or permanent AF at any follow-up or persistent AF at baseline to permanent AF at any follow-up than those without (OR 1.23, 95% CI 1.01-1.49, p=0.035). Conclusion: Sinus node dysfunction is associated worse symptoms, lower quality of life, and higher risk of progression to permanent AF. However, SND is not associated with increased risk of all-cause hospitalization, incident stroke, or all-cause death.

Leaving no hole unclosed: left atrial appendage occlusion in patients having closure of patent foramen ovale or atrial septal defect.

To report procedural outcome of sequential occlusion of the left atrial appendage (LAA) and an interatrial septal communication and discuss possible indications. There are some patients who may have indications for both closure of patent foramen ovale (PFO) or atrial septal defect (ASD), as well as closure of the LAA. The optimal procedural strategy is not known. A retrospective review of LAA and PFO/ASD cases at our center was performed. Demographic, echocardiographic, and procedural data were recorded. Closure of LAA and then PFO/ASD (Group I: 11 patients), closure of both in the same setting (Group II: 3 patients), and closure of the PFO/ASD and then the LAA (Group III: 3 patients) was performed in a total of 17 patients. Average age was 63.5 ± 9.8 years. Most patients were hypertensive with prior cerebrovascular event in 52.9% of patients. Procedural success was 100%. Procedural adverse events were 2 episodes of tamponade (in Group I after first LAA procedure) treated with pericardiocentesis and 1 access-site hematoma (Group II) treated conservatively. Sequential (staged or during the same procedure) closure of the LAA and interatrial communications can be performed safely in a carefully selected patient population. This is also the first known report of LAA occlusion in patients with prior septal closure devices.

MRI in acute cerebral ischemia of the young

We focused on cerebral imaging findings in a large cohort of young patients with a symptomatic ischemic cerebrovascular event (CVE) to extract relevant pathophysiologic and clinical information. We analyzed the scans of 2,979 patients (aged 18-55 years) enrolled in the sifap1 project with clinical evidence of ischemic stroke (IS) or clinically defined TIA in whom MRI, including diffusion-weighted imaging, was obtained within 10 days of the CVE. Age groups were categorized as 18-34, 35-44, and 45-55 years. We compared age- and sex-specific proportions of infarct features, white matter hyperintensities, and old microbleeds. Acute infarcts were identified in 1,914 of 2,264 patients (84.5%) with IS and 101 of 715 patients (14.1%) with TIA. Among patients with IS, younger age was significantly associated with acute infarcts in the posterior circulation, while anterior circulation infarcts and acute lacunar infarcts were more frequent in older age groups. One or more old infarcts were present in 26.8% of IS and 17.1% of TIA patients. This rate remained high even after excluding patients with a prior CVE (IS, 21.7%; TIA, 9.9%). The prevailing type of old infarction was territorial in patients younger than 45 years and lacunar in those aged 45 years or older. The frequency of white matter hyperintensities (46.4%) and their severity was positively associated with age. Old microbleeds were infrequent (7.2%). Young adults show a high frequency of preexisting and clinically silent infarcts and a relative preference for acute ischemia in the posterior circulation. Findings suggesting small-vessel disease become apparent at age 45 years and older.

Cognitive Trajectory After Transcatheter Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) is known to be associated with silent cerebral injury, which could contribute to cognitive impairment. Considering its increasing use, thorough longitudinal investigation of cognitive trajectory after TAVI is pivotal. Repeatable battery for the assessment of neuropsychological status was performed before (E1), 3 days (E2), 3 months (E3), 1 (E4) year, and 2 years (E5) after TAVI. Baseline characteristics, procedural data, imaging parameters of brain injury (diffusion-weighted MRI), and the use of conceivable neuroprotective approaches were investigated for their effect on cognitive function. Cognitive performance was investigated in 111 patients (mean log EuroSCORE, 30±13%). Global cognitive function (repeatable battery for the assessment of neuropsychological status total score) increased transiently at E2 (P=0.02) and was comparable with baseline levels at E3, E4, and E5. Six patients (5.4%) demonstrated early cognitive decline. Persistence and late onset were seen infrequently (n=3, 2.7% and n=4, 3.6%, respectively). Hence, early cognitive decline was ruled out in 105 patients (94.6%), and a majority of patients (91%) demonstrated sustained cognitive performance throughout all investigated time points. Interestingly, only patient age (P=0.012), but not prior cerebrovascular events, cognitive status, direct TAVI, cerebral embolism in diffusion-weighted MRI, or the use of a cerebral embolic protection device was found to be independently associated with cognitive decline, linking higher age to cognitive impairment along the first 2 years after TAVI. Long-term cognitive performance was preserved in the great majority (91%) of patients throughout the first 2 years after TAVI, despite the high intrinsic risk for cognitive deterioration. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883285.

Association between asymptomatic carotid stenosis and cognitive function: A systematic review

Background: Asymptomatic carotid stenosis (CS), defined as the condition/INS; in which/INS; patients have carotid stenosis without a past history and current clinical evidence of any prior cerebrovascular event, and /INS;have traditionally been considered clinically silent. It is less clear whether asymptomatic CS itself is an independent risk factor for cognitive impairment.

Comparison of drug-eluting stent versus bypass surgery for patients with unprotected left main coronary artery disease and SYNTAX score &lt;33: Impact of second-generation drug-eluting stent

Purpose: Limited data are available on the clinical outcomes of second-generation DES (2nd DES) in patients with unprotected left main coronary artery (LMCA) lesions. We aimed to compare the clinical impact of 2nd DES with those of first-generation DES (1st DES) and coronary artery bypass graft (CABG) in patients with unprotected LMCA lesions and SYNTAX score <33. Methods: We identified 325 consecutive patients with unprotected LMCA lesions and SYNTAX score <33 between January 2003 and February 2012 and investigated 12-month clinical outcomes including all-cause death, cardiac death, target vessel revascularization (TVR), and major adverse cardiac and cerebrovascular events (MACCE) defined as all-cause death, myocardial infarction, TVR, and stroke. Previous PCI or CABG, hybrid LMCA stenting, and acute myocardial infarction were excluded. Results: Of the 325 patients, 112 underwent implantation of a 1st DES (Cypher, 111 patients; Taxus, 1 patient), 61 a 2nd DES (Endeavor, 26 patients; Xience, 13 patients; Nobori, 22 patients), and 152 CABG. There were no significant differences in baseline characteristics such as age, sex, hypertension, diabetes mellitus, dyslipidemia, peripheral artery disease, prior cerebrovascular event, renal failure, acute coronary syndrome, and SYNTAX score. The STS score of 1st DES was significantly lower than that of CABG (3.0 vs. 5.6, p<0.001) and was comparable to that of 2nd DES (3.0 vs. 4.3, p=0.17). The figure shows the clinical event rates. ![Figure][1] Clinical events over 12 months Conclusions: In patients with unprotected LMCA lesions and SYNTAX score <33, the clinical events rate of 2nd DES tended to be lower than those of 1st DES and were not significantly different from those of CABG. [1]: pending:yes