Primary Outcome Of Death Research Articles

Abstract 11097: Racial Differences in Clinical Outcomes in Elderly Patients With Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is associated with stroke and death, but the effect of race on these outcomes is not known. Methods: Medicare administrative data from 2010-2011 were used to identify patients with newly diagnosed AF who were categorized based on race as white, black and Hispanic. Racial differences in the primary outcome of death and secondary outcomes of stroke and the composite of stroke and death were assessed using Cox proportional hazard models. Results: Among 517,941 patients with newly diagnosed AF, 452,986 (87%) were whites, 36,425 (7%) were blacks and 28,530 (6%) were Hispanics. The mean age was 79 ± 8 years and 40.5% were males. Over a mean follow-up period of 0.9 years per patient, 68,250 (15.1%) whites, 7665 (20%) blacks and 4814 (16.9%) Hispanics died. Stroke was diagnosed in 6,509 (1.4%) whites, 843 (2.3%) blacks and 507 (1.8%) Hispanics. Compared to whites, blacks had a significantly higher hazard of death (Hazard Ratio [HR] =1.43; 95% CI 1.40-1.47; p<0.001), stroke (HR=1.69; 95% CI 1.57-1.81; p<0.001), and the composite outcome (HR= 1.46; 95% CI 1.43-1.49; p<0.001). After controlling for pre-existing co-morbidities, the higher hazard of death (HR 0.99; 95% CI 0.97-1.01; p=0.41) and the composite outcome (HR=1.02; 95% CI 0.99-1.04; p=0.135) in blacks were eliminated and the relative hazard of stroke (HR=1.44; 95% CI 1.34-1.55; p<0.001) was reduced compared to the whites. Similarly, Hispanics had a higher risk of death (HR= 1.13; 95% CI 1.10-1.17; p<0.001), stroke (HR=1.26; 95% CI, 1.15-1.38; p<0.001) and the composite outcome (HR= 1.15; 95% CI 1.12-1.18; p<0.001), as compared to whites. The relative hazard of death and the composite outcome were noted to be lower in Hispanics, compared to whites, after controlling for pre-existing co- morbidities (HR= 0.93; 95% CI 0.92-0.96; p<0.001 and HR= 0.95; 95% CI 0.92-0.97; p<0.001 respectively). The relative hazard of stroke was also attenuated (HR=1.15; 95% CI 1.05-1.26; p=0.002). Conclusions: In an elderly Medicare population with newly diagnosed AF, the risks of death and stroke are higher in blacks and Hispanics, as compared to whites. This is likely due to increased co-morbidities in blacks and Hispanics.

Improving infant outcome with a 10 min Apgar of 0

ObjectiveAsystole at birth and extending through 10 min is rare, with current international recommendations stating it may be appropriate to consider discontinuation of resuscitation in this clinical scenario. These recommendations...

RR6. High-Risk Carotid Endarterectomy (CEA) Beyond the SAPPHIRE Trial and Development of a Risk Index to Define Patients At Risk for Adverse Outcomes After CEA, From the Vascular Study Group of New England (VSGNE)

Recently we defined several independent high-risk criteria that were inclusive and exclusive of the SAPPHIRE (Stenting with Angioplasty and Protection in Patients at High Risk for Endarterectomy) trial. The objective of this study was to create a risk index that may predict patients at high risk for carotid endarterectomy (CEA). Data on 3,098 CEAs between 2003 and 2011 at 20 Vascular Study Group of New England (VSGNE) centers were used for this study. SAPPHIRE general inclusion criteria and primary outcomes of death, stroke, or myocardial infarction were used, as were other previously reported high-risk criteria. Factors that were associated with the primary outcome by analysis of variance (P < .10) and not linearly dependent, as determined by a Pearson's correlation analysis, were further assessed for an independent association by multivariate logistic regression. A risk index model was developed for these significant predictors using an integer score as a reliable formula. Multivariate analysis (P < .05) found the following independently significant risk factors (95% confidence interval): age in years (1.0-1.1; P < .001), preadmission nursing home (1.2-6.6; P = .020), congestive heart failure (CHF; 1.4-2.8; P < .001), diabetes (1.1-1.3; P < .001), chronic obstructive pulmonary disease (COPD; 1.2-1.5; P < .001), any previous cerebrovascular disease (CVD; 1.1-1.9; P = .003), and contralateral internal carotid artery stenosis (1.0-1.2; P = .001). The predictors are age in years (40-49: 0 points; 50-59: 2 points; 60-69: 4 points; 70-79: 6 points; 80-89: 8 points), living in a nursing home (4 points), any CVD (2 points), CHF (5 points), COPD (3 points), diabetes (2 points), degree of contralateral stenosis (<50%: 0 points; 50-69%: 1 point; 70-near occlusion: 2 points; occlusion: 3 points). Lowest-risk CEA was defined as 0 points with an estimated risk of 2.7%, highest-risk CEA was defined as >13 points, representing adverse outcome rate of 22.5%. The SAPPHIRE high-risk CEA definition is not accurate. We propose a new, evidence-based definition of high-risk CEA. The CEA risk index model may assist clinicians in appropriate patient selection. Future studies should aim at validation of this risk index model.

Efficacy and safety of mineralocorticoid receptor antagonist therapy in heart failure with reduced ejection fraction

oBjECTIVES: To summarize the efficacy and safety of mineralocorticoid receptor antagonists (MRAs) compared with placebo for the treatment of heart failure with reduced ejection fraction (HFrEF) by assessing clinically relevant end points of randomized controlled trials. METhoDS: The Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ACP Journal Club, DARE and International Pharmaceutical Abstracts databases were searched from inception to June 2014. Three authors independently reviewed and identified relevant articles. Included were randomized, doubleblinded, placebo-controlled trials that investigated spironolactone or eplerenone in adult patients with HFrEF regardless of etiology or symptomatology. RESulTS: The search strategy identified 726 articles; three met the inclusion criteria and included a total of 11,032 participants. The primary outcome of death from any cause was statistically significantly reduced with MRAs over placebo (risk ratio [RR] 0.81 [95% CI 0.74 to 0.88]; P<0.001). Hyperkalemia (serum potassium ≥6.0 mmol/L) was significantly higher with MRA therapy (RR 1.41 [95% CI 1.16 to 1.72]; P<0.001). Other clinically relevant safety outcomes were not consistently reported. With respect to efficacy, MRAs reduced cardiovascular mortality (RR 0.80 [95% CI 0.73 to 0.87]; P<0.001) and hospitalizations due to heart failure (RR 0.76 [95% CI 0.64 to 0.90]; P=0.001), but not all-cause hospitalization (RR 0.91 [95% CI 0.79 to 1.06]; P=0.23). CoNCluSIoNS: The present review highlights the benefit of MRAs across the spectrum of HFrEF despite a higher incidence of hyperkalemia. Therefore, MRA therapy should not be withheld from appropriately selected patients with HFrEF because the risk of adverse events does not appear to exceed the overall benefit in mortality reduction.

Primary Supratentorial Haemorrhage - Surgery or no Surgery in an Indian Setup.

Rise of hypertension among younger age group has increased the prevalence of intracranial haemorrhage. Conflicting reviews regarding the mode of treatment has been a concern to the treating physicians especially in a developing country like India. This study was undertaken to underline the importance of management and propose a local protocol for primary supra-tentorial haemorrhage. Patients presenting with primary supratentorial (ST) haemorrhage fulfilling inclusion criteria are included in the study. Decompression craniotomy done in all the patients and the patient particulars noted. The primary outcome of death is correlated with various particulars and statistical analysis done with SPSS version 16. Mean age of presentation was 54.2 years, ranging from 38-71years. Male comprised 82.1% (23 patients). Seven out of eight patients with Glasgow coma scale (GCS) ≤7 (87.5%) expired whereas only 3 out of 20 (15%) patients with GCS >7 expired. 50% of the patients with intracranial haemorrhage (ICH) in temporo-pari et al., (2/4) or in basal ganglia with cortical extension (5/10) expired whereas the mortality in cases of ICH in parietal lobe and frontal lobes were 25% (1/4) and 20% (2/10) respectively. Clot volume ≤100ml had a mortality of 19% (4/21) whereas the mortality was as high as 85.7% (6/7) with clot volume >100ml. Emergency Craniotomy and Evacuation of the Hematoma could be a feasible option in between 40 ml to 100ml of Primary ST ICH without intra-ventricular extension. In cases of intra-ventricular extension of haematoma surgery is less helpful. Midline shift of 5 mm or more might be a poor prognostic factor.

Usefulness of the Seattle Heart Failure Model to Identify Adults With Congenital Heart Disease at High Risk of Poor Outcome

Our objective was to determine whether the Seattle Heart Failure Model (SHFM) differentiates patients with adult congenital heart disease (ACHD) at high versus low risk for cardiovascular outcomes and poor exercise capacity. The ACHD population is growing and presents increasingly for care in the community and at tertiary centers. Few strategies exist to identify the patients with ACHD at high risk for heart failure and mortality.We studied 153 adults with transposition of the great arteries, Ebstein anomaly, tetralogy of Fallot, double outlet right ventricle, and single ventricle from 2 ACHD centers. The primary outcome was cardiovascular death, with a secondary composite outcome of death, transplant, ventricular assist device, cardiovascular admission, and treatment for arrhythmia. We defined risk groups based on SHFM 5-year predicted survival: high (predicted survival <70%), intermediate (70% to 85%), and low risk (>85%). Ten patients had the primary outcome of death, and 46 the combined end point. The hazard of death in the SHFM high- versus the intermediate-risk group was 7.09 (95% confidence interval 1.5 to 33.4, p = 0.01; no deaths in the low-risk group) and the hazard of the composite outcome between the high- versus low-risk group was 6.64 (95% confidence interval 2.5 to 17.6, p = 0.0001). Kaplan-Meier survival analysis showed greater probability of all-cause mortality (p = 0.003) in the high-risk group. In conclusion, the SHFM can help identify subjects with ACHD at risk for adverse outcome and poor cardiopulmonary efficiency. This may add to the care of patients with ACHD in the community and streamline care at tertiary centers.

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus

ObjectiveFailure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes...

Procedural Volume and Outcomes With Radial or Femoral Access for Coronary Angiography and Intervention

The study sought to evaluate the relationship between procedural volume and outcomes with radial and femoral approach. RIVAL (RadIal Vs. femorAL) was a randomized trial of radial versus femoral access for coronary angiography/intervention (N = 7,021), which overall did not show a difference in primary outcome of death, myocardial infarction, stroke, or non-coronary artery bypass graft major bleeding. In pre-specified subgroup analyses, the hazard ratios for the primary outcome were compared among centers divided by tertiles and among individual operators. A multivariable Cox proportional hazards model was used to determine the independent effect of center and operator volumes after adjusting for other variables. In high-volume radial centers, the primary outcome was reduced with radial versus femoral access (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.28 to 0.87) but not in intermediate- (HR: 1.23; 95% CI: 0.88 to 1.72) or low-volume centers (HR: 0.83; 95% CI: 0.52 to 1.31; interaction p = 0.021). High-volume centers enrolled a higher proportion of ST-segment elevation myocardial infarction (STEMI). After adjustment for STEMI, the benefit of radial access persisted at high-volume radial centers. There was no difference in the primary outcome between radial and femoral access by operator volume: high-volume operators (HR: 0.79; 95% CI: 0.48 to 1.28), intermediate (HR: 0.87; 95% CI: 0.60 to 1.27), and low (HR: 1.10; 95% CI: 0.74 to 1.65; interaction p = 0.536). However, in a multivariable model, overall center volume and radial center volume were independently associated with the primary outcome but not femoral center volume (overall percutaneous coronary intervention volume HR: 0.92, 95% CI: 0.88 to 0.96; radial volume HR: 0.88, 95% CI: 0.80 to 0.97; and femoral volume HR: 1.00, 95% CI: 0.94 to 1.07; p = 0.98). Procedural volume and expertise are important, particularly for radial percutaneous coronary intervention. (A Trial of Trans-radial Versus Trans-femoral Percutaneous Coronary Intervention [PCI] Access Site Approach in Patients With Unstable Angina or Myocardial Infarction Managed With an Invasive Strategy [RIVAL]; NCT01014273).

Elevated troponin I levels but not low grade chronic inflammation is associated with cardiac-specific mortality in stable hemodialysis patients

BackgroundElevated cardiac troponin I (TnI) levels are associated with all-cause mortality in stable hemodialysis patients. Their relationship to cardiac-specific death has been inconsistent, and the reason for their elevation is not well understood. We hypothesized that elevated TnI levels in chronic stable hemodialysis patients more specifically track with cardiac mortality, and this mechanism is independent of other contributors of cardiac mortality, such as inflammation.MethodsWe conducted a single-centre, cohort study of prevalent hemodialysis patients at a tertiary care hospital. Plasma TnI levels were measured with routine monthly blood tests in clinically stable patients for two consecutive months. Plasma TnI was measured by immunoassay and a value above the laboratory reference range (0.06 μg/L) was considered elevated. The primary outcome of death was adjudicated separately for this study, and classified as cardiac, non-cardiac, or unknown. Cox proportional hazard models were used to examine the association of TnI with the all-cause and cardiac-specific mortality, adjusting for potential confounders, including C-reactive protein (CRP) as a marker of inflammation.ResultsOf 133 patients followed for a median of 1.7 years, there were 38 deaths (58% non-cardiac, 39% cardiac, 3% unknown). Elevated TnI was associated with adjusted HR for all-cause mortality of 2.57 (95% CI 1.30-5.09) and an adjusted HR for cardiac death of 3.14 (95% CI 1.07-9.2), after accounting for age, time on dialysis, diabetes status, prior coronary artery disease history, and C-reactive protein. Although CRP was also independently associated with all-cause mortality, it did not add prognostic information to TnI for cardiac-specific death.ConclusionElevated TnI levels are independently associated with cardiac and all-cause mortality in asymptomatic hemodialysis patients. The mechanism for this risk is likely independent of inflammation, but may reflect chronic subclinical myocardial injury or unmask those with subclinical atherosclerotic heart disease. Whether those with elevated TnI levels may benefit from additional investigations or more aggressive therapies to treat cardiovascular disease remains to be determined.

Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old.

The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ≤ 750 cells/mm(3) or per cent CD4 ≤ 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children. To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012. Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART. Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity. Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16). This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations.

Comparison of Predictors of Heart Failure–Related Hospitalization or Death in Patients With Versus Without Preserved Left Ventricular Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is recognized as a major cause of cardiovascular morbidity and mortality. An ability to identify patients with HFpEF who are at increased risk for adverse outcomes can facilitate their more careful management. We studied the patients having heart failure (HF) using data from the Heart Failure Adherence and Retention Trial (HART). HART enrolled 902 patients in the New York Heart Association (NYHA) class II or III who had been recently hospitalized for HF to study the impact of self-management counseling on the primary outcome of death or HF hospitalization. In HART, 208 patients had HFpEF and 692 had HF with reduced ejection fraction (HFrEF) and were followed for a median of 1,080days. Two final multivariate models were developed. In patients having HFpEF, predictors of primary outcome were male gender (odds ratio [OR] 3.45, p= 0.004), NYHA class III (OR 3.05, p= 0.008), distance covered on a 6-minute walk test (6-MWT) of <620 feet (OR 2.81, p= 0.013), and <80% adherence to prescribed medications (OR 2.61, p= 0.018). In patients having HFrEF, the predictors were being on diuretics (OR 3.06, p= 0.001), having ≥3 co-morbidities (OR 2.11, p= 0.0001), distance covered on a 6-MWT of <620 feet (OR 1.94, p= 0.001), NYHA class III (OR 1.90, p= 0.001), and age >65years (OR 1.63, p= 0.01). In conclusion, indicators of functional status (6-MWT and NYHA class) were common to both patients with HFpEF and those with HFrEF, whereas gender and adherence to prescribed therapy were unique to patients having HFpEF in predicting death or HF hospitalization.

Impact of physician continuity on death or urgent readmission after discharge among patients with heart failure

Early physician follow-up after discharge is associated with lower rates of death and readmission among patients with heart failure. We explored whether physician continuity further influences outcomes after discharge. We used data from linked administrative databases for all adults aged 20 years or more in the province of Alberta who were discharged alive from hospital between January 1999 and June 2009 with a first-time diagnosis of heart failure. We used Cox proportional hazard models with time-dependent covariates to analyze the effect of follow-up with a familiar physician within the first month after discharge on the primary outcome of death or urgent all-cause readmission over 6 months. A familiar physician was defined as one who had seen the patient at least twice in the year before the index admission or once during the index admission. In the first month after discharge, 5336 (21.9%) of the 24 373 identified patients had no follow-up visits, 16 855 (69.2%) saw a familiar physician, and 2182 (9.0%) saw unfamiliar physician(s) exclusively. The risk of death or unplanned readmission during the 6-month observation period was lower among patients who saw a familiar physician (43.6%; adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.83-0.91) or an unfamiliar physician (43.6%; adjusted HR 0.90, 95% CI 0.83-0.97) for early follow-up visits, as compared with patients who had no follow-up visits (62.9%). Taking into account all follow-up visits over the 6-month period, we found that the risk of death or urgent readmission was lower among patients who had all of their visits with a familiar physician than among those followed by unfamiliar physicians (adjusted HR 0.91, 95% CI 0.85-0.98). Early physician follow-up after discharge and physician continuity were both associated with better outcomes among patients with heart failure. Research is needed to explore whether physician continuity is important for other conditions and in settings other than recent hospital discharge.

Outcome of Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention During On- Versus Off-hours (A Harmonizing Outcomes With RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI] Trial Substudy)

Patients with ST-segment elevation myocardial infarction (STEMI) admitted during nonregular working hours (off-hours) have been reported to have greater mortality than those admitted during regular working hours (on-hours), perhaps because of the lower availability of catheterization laboratory services and longer door-to-balloon times. This might not be the case, however, for hospital centers in which primary percutaneous coronary intervention (PCI) is invariably performed. We conducted a substudy using the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction study data to determine whether the STEMI arrival time was associated with differing clinical outcomes. We identified all patients with STEMI admitted to a PCI-capable hospital who underwent primary PCI. Patients presenting during on-hours were compared to those presenting during off-hours. The primary outcome of death, major adverse cardiovascular events, and net adverse clinical events was examined. We identified 2,440 patients (1,205 [49%] on-hours and 1,235 [51%] off-hours). Similar baseline characteristics were observed. The off-hour patients had a significantly longer door-to-balloon time (92 vs 75 minutes; p <0.0001) and total ischemic time (209 vs 194 minutes; p <0.0001). Despite these differences, the risk-adjusted all-cause mortality, major adverse cardiovascular events, and net adverse clinical events rates were similar for both groups during the in-hospital, 1-year, and 3-year follow-up. In conclusion, patients with STEMI presenting to primary PCI hospitals during off-hours might have slightly longer delays to revascularization; however, they experienced similar short- and long-term survival and clinical outcomes as those arriving during on-hours.

Cardiac Resynchronization Therapy in Patients With Permanent Atrial Fibrillation

Background— Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation. Methods and Results— The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65–1.41; P =0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55–1.71; P =0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38–1.01; P =0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m; P =0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20; P =0.057). Conclusions— Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00251251.

Ischemia Change in Stable Coronary Artery Disease Is an Independent Predictor of Death and Myocardial Infarction

The aim of this study was to evaluate the independent prognostic significance of ischemia change in stable coronary artery disease (CAD). Recent randomized trials in stable CAD have suggested that revascularization does not improve outcomes compared with optimal medical therapy (MT). In contrast, the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found that revascularization led to greater ischemia reduction and suggested that this may be associated with improved unadjusted outcomes. Thus, the effects of MT versus revascularization on ischemia change and its independent prognostic significance requires further investigation. From the Duke Cardiovascular Disease and Nuclear Cardiology Databanks, 1,425 consecutive patients with angiographically documented CAD who underwent 2 serial myocardial perfusion single-photon emission computed tomography scans were identified. Ischemia change was calculated for patients undergoing MT alone, percutaneous coronary intervention, or coronary artery bypass grafting. Patients were followed for a median of 5.8 years after the second myocardial perfusion scan. Cox proportional hazards regression modeling was used to identify factors independently associated with the primary outcome of death or myocardial infarction (MI). Formal risk reclassification analyses were conducted to assess whether the addition of ischemia change to traditional predictors resulted in improved risk classification for death or MI. More MT patients (15.6%) developed ≥5% ischemia worsening compared with those undergoing percutaneous coronary intervention (6.2%) or coronary artery bypass grafting (6.7%) (p < 0.001). After adjustment for established predictors, ≥5% ischemia worsening remained a significant independent predictor of death or MI (hazard ratio: 1.634; p = 0.0019) irrespective of treatment arm. Inclusion of ≥5% ischemia worsening in this model resulted in significant improvement in risk classification (net reclassification improvement: 4.6%, p = 0.0056) and model discrimination (integrated discrimination improvement: 0.0062, p = 0.0057). In stable CAD, ischemia worsening is an independent predictor of death or MI, resulting in significantly improved risk reclassification when added to previously known predictors.

A Pilot Study of Darbepoetin Alfa for Prophylactic Neuroprotection in Aortic Surgery

Descending aortic (DA) surgery poses a high risk for spinal and cerebral infarction and routine use of lumbar drains allows for measurement of CSF markers of neurologic injury. Erythropoiesis medications have extensive preclinical data demonstrating neuroprotection. We hypothesized that prophylactic darbepoetin alfa (DARB) given before surgery reduces neurologic injury in patients undergoing DA repair. We performed a prospective adaptive dose-finding trial of prophylactic DARB ( www.clinicaltrials.gov NCT00647998) that terminated prematurely following publication of an erythropoietin stroke study showing possible harm. Enrollment halted before dose adjustments; nine patients each received 1 mg/kg IV DARB immediately before surgery. A prospective cohort of nine untreated patients was subsequently obtained for comparison. The primary outcome of death or neurologic impairment at discharge occurred in 1/9 (11 %) DARB patients and 3/9 (33 %) controls (p = 0.58). There were no statistical differences in changes of CSF biomarkers from baseline to 48 h comparing DARB patients to controls: S100β, median 214 versus 260 ng/ml (p = 0.69); glial fibrillary acidic protein (GFAP), median 0.022 versus 0.58 ng/ml (p = 0.45). In patients with early perioperative neurologic ischemia, there were greater changes in CSF biomarkers, compared to those without ischemia: S100β, median 2301 versus 124 ng/ml (p = 0.04); GFAP, median 31.78 versus 0.31 ng/ml (p = 0.34). There were no significant effects of prophylactic DARB on clinical outcome or CSF markers of neurologic injury in this pilot study, although all point estimates favored treatment. DA repair is a promising model of prophylactic neuroprotection.

New insights in prevention, diagnosis and treatment of stroke: its relation with atrial fibrillation

New insights in prevention, diagnosis and treatment of stroke: its relation with atrial fibrillation

Abstract 1: Did Carotid Stenting and Endarterectomy Outcomes Change Over Time in the Carotid Revascularization Endarterectomy versus Stenting Trial?

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) enrolled 2502 patients between December of 2000 and mid-July of 2008. We analyzed temporal changes in outcomes for both CEA and CAS over the course of this study. Methods Enrollment was divided into 3 consecutive epochs (5 years, 14 months, and 16 months), each with approximately 834 patients ( Table ). Rates for the primary outcome of death, stroke, and myocardial infarction (DSMI) and for death and stroke (DS) during the periprocedural period were calculated. Poisson regression was used to adjust rates for age, sex, dyslipidemia, and symptomatic status, all of which were found to influence outcomes. Results For CAS, there was a 26% decline in DSMI (6.2% → 4.6%) and a 35% decline in DS (5.5% → 3.6%). For both composite endpoints in CEA there was no consistent pattern ( Table ). As CREST progressed, it enrolled younger patients, more men, patients more likely to be dyslipidemic and enrolled more asymptomatic patients (all p &lt; 0.05). Adjustment for these changes mediated the improvement in event rates for the CAS patients, and had no consistent effect on CEA event rates ( Table ). Conclusion Periprocedural safety for CAS improved over time in CREST. Changes were inconsistent for CEA. Improvements for CAS in part appear to reflect changes in patient selection related to age, sex, and risk factors, as adjustment for those variables attenuated the decline in rates. Linking rates to operator experience was not feasible because of the large number of new interventionalists and surgeons entering CREST over time.

Temperature profile and outcomes of neonates undergoing whole body hypothermia for neonatal hypoxic-ischemic encephalopathy

Decreases below the target temperature were noted among neonates undergoing cooling in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. To examine the temperature profile and impact on outcome among ≥ 36 wk gestation neonates randomized at ≤ 6 hrs of age targeting an esophageal temperature of 33.5°C for 72 hrs. Infants with intermittent temperatures recorded of <32.0°C during induction and maintenance of cooling were compared to all other cooled infants, and the relationship with outcome at 18 months was evaluated. None. There were no differences in the stage of encephalopathy, acidosis, or 10 min Apgar scores between infants with temperatures of <32.0°C during induction (n = 33) or maintenance (n = 10) and all other infants who were cooled (n = 58); however, birth weight was lower and the need for blood pressure support higher among infants with temperatures of <32.0°C compared to all other cooled infants. No increase in acute adverse events was noted among infants with temperatures of <32.0°C, and hours spent at <32°C was not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months. Term infants with a lower birth weight are at risk for decreasing temperatures of <32.0°C while undergoing body cooling using a servo-controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy.

504 Does cardiac resynchronization therapy improve outcomes in patients with chronic atrial tachyarrhythmias? results from the resynchronization for ambulatory heart failure trial (raft)

Cardiac resynchronization (CRT) improves survival, prevents heart failure hospitalizations and improves quality of life in patients with systolic heart failure and QRS prolongation. However; the role of CRT in patients with chronic atrial arrhythmias is unclear, as most trials excluded these patients. The RAFT trial randomized patients with NYHA II and III heart failure, a left ventricular ejection fraction of ≤30% and a QRS width of ≥ 120 msec to an implantable defibrillator (ICD) or ICD + CRT. Randomization was stratified based on the presence or absence or chronic atrial tachyarrhythmias. At baseline, 229 patients were identified as having chronic atrial tachyarrhythmias and randomized to ICD (n = 115) or CRT-ICD (n = 114). Patients receiving a CRT-ICD were similar to those receiving an ICD in terms of: age (71.6 ± 7.3 vs. 70.4 ± 7.7 years), left ventricular ejection fraction (22.9 ± 5.3% vs. 22.3 ± 5.1%) and QRS duration (151.0 ± 23.6 vs. 153.4 ± 24.7 msec). Only 1 patient had an AV junction ablation within 6 months of randomization. There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD vs. ICD (HR = 0.96; 95% CI, 0.65-1.41, P = 0.82). This result was similar among patients with a baseline resting heart rate above (HR = 0.75; 95% CI, 0.42-1.33, P = 0.33) and below (HR = 1.16, 95% CI, 0.67-1.99, P = 0.60) the median value of 68 beats per minute. Cardiovascular death was similar between treatment arms (HR = 0.97; 95% CI, 0.55-1.71, P = 0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (HR = 0.58; 95% CI, 0.38-1.01, P = 0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (ICD: 16 ± 76 metres vs. CRT-ICD: 19 ± 84 metres, P = 0.88). Patients treated with CRT showed a trend (P = 0.057) for a greater improvement in Minnesota Living with Heart Failure Score between baseline and 6 months (ICD: 33 ± 20 to 28 ± 20; CRT-ICD: 41 ± 21 to 31 ± 21); however, there were important differences in baseline scores. RAFT is the largest randomized trial of CRT in patients with chronic atrial tachyarrhythmias and shows no clear reduction in clinical events or improvement in surrogate measures.