Composite Outcome Of All-cause Mortality Research Articles

Risk Reclassification With Coronary Computed Tomography Angiography-Visualized Nonobstructive Coronary Artery Disease According to 2018 American College of Cardiology/American Heart Association Cholesterol Guidelines (from the Coronary Computed Tomography Angiography Evaluation for Clinical Outcomes : An International Multicenter Registry [CONFIRM

The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends risk enhancers in the borderline-risk and statin recommended/intermediate-risk groups. We determined the risk reclassification by the presence and severity of coronary computed tomography angiography (CCTA)-visualized coronary artery disease (CAD) according to statin eligibility groups. Of 35,281 individuals who underwent CCTA, 1,303 asymptomatic patients (age 59, 65% male) were identified. Patients were categorized as low risk, borderline risk, statin recommended/intermediate risk or statin recommended/high risk according to the guideline. CCTA-visualized CAD was categorized as no CAD, nonobstructive, or obstructive. Major adverse cardiovascular events (MACE) were defined as a composite outcome of all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization (>90 days). We tested a reclassification wherein no CAD reclassifies downward, and the presence of any CAD reclassifies upward. During a median follow-up of 2.9 years, 93 MACE events (7.1%) were observed. Among the borderline-risk and statin-recommended/intermediate-risk groups eligible for risk enhancers, the presence or absence of any CCTA-visualized CAD led to a net increase of 2.3% of cases and 22.4% of controls correctly classified (net reclassification index [NRI] 0.27, 95% CI 0.13 to 0.41, p = 0.0002). The NRI was not significant among low- or statin-recommended/high-risk patients (all p >0.05). The presence or absence of CCTA-visualized CAD, including both obstructive and nonobstructive CAD, significantly improves reclassification in patients eligible for risk enhancers in 2018 ACC/AHA guidelines. Patients in low- and high-risk groups derive no significant improvement in risk reclassification from CCTA.

Predictive Prognostic Value of Ventilatory Inefficiency across the Spectrum of Heart Failure

Background Minute ventilation-carbon dioxide production relationship (VE/VCO2 slope), as assessed by cardiopulmonary exercise testing (CPET), strongly predicts outcomes in heart failure (HF). High VE/VCO2 slope can indicate ventilatory inefficiency. A single VE/VCO2 slope threshold defining abnormal of ≥ 34 to 36 is used clinically across HF categories; however, this threshold has been validated largely in patients with reduced left ventricular ejection fraction (LVEF). Objectives To examine the associations between VE/VCO2 slope categories and a composite outcome of all-cause mortality and HF hospitalization across the spectrum of HF patients defined by LVEF. Methods Single-center retrospective cohort study of 1347 patients with heart failure (60.5% male, age 58.0±14.6 years, LVEF 42 ± 17%) clinically referred for CPET between 2010 and 2016. LVEF was obtained from echocardiogram (n=1309) or cardiac MRI (n=38). All-cause mortality was determined using Partners Research Patient Data Registry, which is linked to National Death Index. HF hospitalization data were adjudicated by review of electronic medical record. Patients with HF were categorized based on LVEF into heart failure with reduced (HFrEF, LVEF Results At two-year follow-up post CPET, there were 197 composite events (64 deaths and 133 HF hospitalizations). Across the entire cohort, increases in VC category were associated with increasing risk of two-year composite outcome in unadjusted and adjusted models. Compared to patients in VC-I, patients in VC-II were at increased risk of having two-year composite outcome in both HFrEF and HFpEF cohorts. Patients in VC III and IV had incremental increases in the likelihood of two-year composite outcome across all three HF cohorts (Table). Conclusions Higher VE/VCO2 slope categories are associated with increased risk of the two-year composite outcome of all-cause mortality and HF hospitalization across the spectrum of HF defined by LVEF. A VE/VCO2 slope between 29 and 36, often considered borderline in clinical practice, is associated with increased risk of this composite outcome in patients with HFrEF and HFpEF. Identifying a wider VE/VCO2 slope associated with increased risk in HF may have important implications on risk stratification clinically.

Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response.

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P<0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61-13.36, P<0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97-6.59, P=0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.

SUN-176 THE LONG-TERM OUTCOMES OF ACUTE KIDNEY INJURY SURVIVORS FROM ICU IN RESOURCE-LIMITED AREA: RESULT FROM SEA-AKI STUDY

Acute kidney injury (AKI) is a common condition that leading to high morbidity and mortality during intensive care unit (ICU) admission. However, long-term patient outcomes with AKI in limited-resource countries remains poorly understood. This prospective multicenter observational study was conducted at 5 participating hospitals across Thailand during February 2013 to August 2017. All adult patients (age >15) without prior end-stage renal disease (ESRD) who survived until ICU discharge were included. Clinical data were collected using web-based case record form. For long-term outcomes, we searched the government administration database and Thailand Dialysis Registry using Thai 13-digit identification number to identify survival and dialysis status. The primary outcome was the composite outcome of all-cause mortality and dialysis dependence rate within 2-years after ICU admission, and the secondary outcomes were all-cause mortality and the dialysis dependence rate at 2 years. Survival data was visualized using the Kaplan-Meier plot, and multivariate Cox regression analysis was used to estimate adjusted hazard ratio (AHR) with 95% confidence interval (95% CI) of survival for the other clinical parameters. Of the 1,730 patients who survived until ICU discharge, 617 (35.7%) had AKI, with stages 1, 2, and 3 of 6.4%, 12.3% and 17.0%, respectively. With a median follow up time of 28.5 months, incidence of the primary composite outcome in AKI group was significantly higher than the non-AKI group (51.7% vs. 34.9%, p < 0.01.) In the multivariable cox regression adjusted for potentially confounding clinical parameters, diagnosis, and comorbidities, patients with AKI had a higher risk for 2-year composite outcome of death and dialysis dependence relative to patients without AKI (AHR 1.27; 95%CI: 1.07-1.52, p<0.01). Importantly, the mortality risk increased by AKI stages with AHRs (95% CI) were 1.31 (95%CI: 1.04-1.65) and 1.44 (95%CI: 1.13-1.84) for AKI stage 2 and 3, P = 0.02 and <0.01, respectively. Despite survival to ICU discharge, patients who had AKI still had a higher risk of long-term mortality and dialysis dependence relative to patients who did not have AKI, particularly, those with more severe stage of AKI. Therefore, follow up of patients with severe AKI after hospital discharge is essential.

Osmoregulation Performance and Kidney Transplant Outcome.

Kidney transplant recipients have an impaired ability to dilute urine but seldom develop baseline hyponatremia before ESRD. Although hyponatremia is a risk factor for adverse events in CKD and in kidney transplant recipients, it remains unclear whether subtler alterations in osmoregulation performance are associated with outcome. We studied a single-center prospective cohort of 1258 kidney transplant recipients who underwent a water-loading test 3 months after transplant to determine osmoregulation performance. Measured GFR (mGFR) was performed at the same visit. A group of 164 healthy candidates for kidney donation served as controls. We further evaluated the association of osmoregulation performance with transplantation outcomes and subsequent kidney function. Unlike controls, most kidney transplant recipients failed to maintain plasma sodium during water loading (plasma sodium slope of -0.6±0.4 mmol/L per hour in transplant recipients versus -0.12±0.3 mmol/L per hour in controls; P<0.001). Steeper plasma sodium reduction during the test independently associated with the composite outcome of all-cause mortality and allograft loss (hazard ratio [HR], 1.73 per 1 mmol/L per hour decrease in plasma sodium; 95% confidence interval [95% CI], 1.23 to 2.45; P=0.002) and allograft loss alone (HR, 2.04 per 1 mmol/L per hour decrease in plasma sodium; 95% CI, 1.19 to 3.51; P=0.01). The association remained significant in a prespecified sensitivity analysis excluding patients with hyperglycemia. In addition, a steeper plasma sodium slope 3 months after transplantation independently correlated with lower mGFR at 12 months (β=1.93; 95% CI, 0.46 to 3.41; P=0.01). Reduced osmoregulation performance occurs frequently in kidney transplant recipients and is an independent predictor of renal outcome.

Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229-0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131). What is Known: • Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects. • Limited studies on oral vitamin A supplementation did not document substantial benefits. What is New: • Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000IU/dose for 28days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress • No major adverse effects were documented.

Discrepancy between patient-reported quality of life and the prognostic assessment of Japanese patients hospitalized with acute heart failure.

Patient-reported quality of life (PRQL) is a primary therapeutic target for patients with chronic heart failure (HF) and is associated with long-term prognosis. However, its utility in hospitalized HF (HHF) patients in the acute setting remains unclear. We aimed to assess the utility of PRQL (the Kansas City Cardiomyopathy Questionnaire [KCCQ]) in HHF patients and its association with long-term prognosis as well as with the clinical risk score (Get With The Guidelines-Heart Failure [GWTG-HF] risk score). PRQL was evaluated using the KCCQ in consecutive 114 HHF patients. Its association with the composite outcome of all-cause mortality or HF readmission within the first year after discharge was analyzed. Furthermore, its distribution by the clinical risk score (GWTG-HF) was evaluated using Pearson's correlation coefficient. The median KCCQ was 34.9, but was widely distributed (interquartile range 23.7-56.8). After adjustment for known prognostic indicators, the KCCQ was not an independent predictor of the composite outcome within the first year (group with high vs. low KCCQ scores: hazard ratio, 0.67; 95% confidence interval 0.26-1.71). There was no significant correlation between the KCCQ and the GWTG-HF risk score. In conclusion, PRQL during the acute phase of HF was significantly impaired and also varied widely, irrespective of patient characteristics or severity. PRQL assessment and risk prediction for HHF patients in the acute setting seemed to provide two distinct types of information for health care providers.

Effectiveness and Safety of Off-Label Dose-Reduced Direct Oral Anticoagulants in Atrial Fibrillation

BackgroundDirect oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation but may result in serious bleeding complications. Off-label dose-reduced use of DOACs to mitigate bleeding is common in routine clinical practice although data about its consequences on patient outcomes are limited. Therefore, our objective was to evaluate the effectiveness and safety of off-label dose-reduced vs per-label standard-dose DOAC treatment. MethodsThe study cohort included newly diagnosed patients with nonvalvular atrial fibrillation that had initiated DOAC therapy between 2011 and 2017 in Clalit Health Services (Tel Aviv, Israel). Effectiveness was defined as the composite outcome of all-cause mortality, stroke, or myocardial infarction. The safety outcome was defined as bleeding events requiring hospitalization. Patients were followed until March 30, 2018 or until occurrence of an outcome event. Hazard ratios (HR) were adjusted for 21 variables, including comorbidities, concomitant medications, and socioeconomic factors, using multivariate regression. ResultsA total of 8425 patients met the study criteria; 5140 (61%) patients were treated with DOACs at per-label dosing and 3285 (39%) patients were treated with off-label dose-reduced DOAC. Off-label dose-reduced treatment was associated with a higher rate of the composite effectiveness outcome: adjusted HR 1.57 (95% confidence interval, 1.34-1.83; P < .001) and a higher rate of bleeding: adjusted HR 1.63 (95% confidence interval, 1.14-2.34; P = .008). ConclusionsAlmost 4 of 10 patients were treated with off-label dose-reduced DOAC, which was associated with reduced effectiveness without a safety benefit. Compliance with per-label dosage may significantly improve outcomes of this population.

Outcomes After Transcatheter Mitral Valve Repair in Patients With Renal Disease

Renal disease is associated with poor prognosis despite guideline-directed cardiovascular therapy, and outcomes by sex in this population remain uncertain. Patients (n=5213) who underwent a MitraClip procedure in the National Cardiovascular Data Registry Transcatheter Valve Therapy registry were evaluated for the primary composite outcome of all-cause mortality, stroke, and new requirement for dialysis by creatinine clearance (CrCl). Centers for Medicare and Medicaid Services-linked data were available in 63% of patients (n=3300). CrCl was <60 mL/min in 77% (n=4010) and <30 mL/min in 23% (n=1183) of the cohort. Rates of primary outcome were higher with lower CrCl (>60 mL/min, 1.4%; 30-<60 mL/min, 2.7%; <30 mL/min, 5.2%; dialysis, 7.8%; P<0.001), and all low CrCl groups were independently associated with the primary outcome (30-<60 mL/min: adjusted odds ratio, 2.32; 95% CI, 1.38-3.91; <30 mL/min: adjusted odds ratio, 4.44; 95% CI, 2.63-7.49; dialysis: adjusted hazards ratio, 4.52; 95% CI, 2.08-9.82) when compared with CrCl >60 mL/min. Rates of 1-year mortality were higher with lower CrCl (>60 mL/min, 13.2%; 30-<60 mL/min, 18.8%; <30 mL/min, 29.9%; dialysis, 32.3%; P<0.001), and all low CrCl groups were independently associated with 1-year mortality (30-<60 mL/min: adjusted hazards ratio, 1.50; 95% CI, 1.13-1.99; <30 mL/min: adjusted hazards ratio, 2.38; 95% CI, 1.78-3.20; adjusted hazards ratio: dialysis, 2.44; 95% CI, 1.66-3.57) when compared with CrCl >60 mL/min. The majority of patients who undergo MitraClip have renal disease. Preprocedural renal disease is associated with poor outcomes, particularly in stage 4 or 5 renal disease where 1-year mortality is observed in nearly one-third. Studies to determine how to further optimize outcomes in this population are warranted.

Abstract 16938: Late Gadolinium Enhancement on Cardiac Magnetic Resonance as Predictor of Overall Mortality in Patients With Non-Ischemic Cardiomyopathy

Background: Patients with heart failure due to non-ischemic cardiomyopathy (NICM) constitute a heterogenous group of patients with diverse prognosis. The presence of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging represents a measure of myocardial damage and can provide prognostic information. Objective: This study aimed to evaluate the prognostic role of the presence and pattern of LGE in patients with NICM . Methods: Using the NICM registry, we conducted a retrospective cohort study of adult patients with NICM, undergoing CMRI between 1999–2016. Using multivariable Cox regression model and Fine and Gray’s competing risk regression model, we evaluated the association between LGE presence and patterns with all-cause mortality, heart transplant, and ventricular assist device (VAD). We adjusted the model for clinically important covariates. Results: Our cohort of 1842 patients showed a mean age of 56 ± 14, 73% male sex, 30% NYHA class III-IV, 15% diabetic and 89% had idiopathic dilated cardiomyopathy. During a median follow-up of 2.3 years, we observed 215 composite outcome of all-cause mortality, transplant, or VAD. LGE was present in 56% of our cohort: 18% subendocardial, 18% mid-wall, 17% diffuse pattern, and 3% subepicardial. LGE was significantly associated with a 2-fold increased risk of events (HR 2.0, 95%CI 1.4-3.0) (figure). Of all LGE patterns, subendocardial, midwall, and diffuse LGE patterns were associated with the worst prognosis. (table). Conclusions: In patients with NICM, LGE in significantly associated with increased risk of death or need for advanced heart failure therapies. The use of CMR in patients with NICM provides both diagnostic and prognostic information.

Improve hip fracture outcome in the elderly patient (iHOPE): a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia

IntroductionHip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on...

Left atrial hemodynamics and left ventricular remodeling –predictors of outcomes after Transcatheter mitral valve repair with the MitraClip device

Increased afterload and reduced left ventricular (LV) performance are sequela of mitral valve repair. However, hemodynamic left atrial and ventricular parameters that can predict outcome following mitral valve repair remain elusive. One hundred and two consecutive patients undergoing MitraClip procedure from 2014 to 2017 at Banner University Medical Center were enrolled in this study. All patients underwent pre-procedure echocardiograms and intra-procedure invasive left atrial (LA) pressure monitoring. Clinical, laboratory, and procedural parameters were collected. The primary end-point was the composite outcome of all-cause mortality and repeat hospitalization within 90 days. The mean age was 77 ±10 years, the majority were Caucasians (93, 91.2%) and 47 (46.1%) were males. Thirty-two patients (31.4%) had diabetes, 39 (38.2%) had renal insufficiency, and 38 (37.3%) had a history of congestive heart failure. The median society of thoracic surgeons score was 6.7% (Interquartile range [IQR]: 3.9, 10.2). Immediately post-procedure there was a significant reduction in the LA pressure (Mean 12.0 vs. 18.6 mmHg, P < 0.001) and pulmonary artery systolic pressure (43.5 vs. 53.2 mmHg, P = 0.001) compared to baseline. LA pressure was an independent predictor of the composite outcome in an unadjusted (OR = 1.07, 95% CI: 1.00-1.13, P = 0.03) and adjusted (OR = 1.07, 95% CI: 1.00-1.14, P = 0.03) analysis respectively. LA pressure drop is an independent predictor of outcome after the MitraClip procedure. This finding has implications for early identification of patients at risk of poor outcomes and instituting aggressive medical therapy and close follow-up for avoiding hospitalizations for heart failure decompensation.

Association of Mortality and Acute Aortic Events With Ascending Aortic Aneurysm: A Systematic Review and Meta-analysis.

The natural history of ascending aortic aneurysm (AsAA) is currently not well characterized. To summarize and analyze existing literature on the natural history of AsAA. A search of Ovid MEDLINE (January 1, 1946, to May 31, 2017) and Embase (January 1, 1974, to May 31, 2017) was conducted. Studies including patients with AsAA were considered for inclusion; studies were excluded if they considered AsAA, arch, and descending thoracic aneurysm as 1 entity or only included descending aneurysms, patients with heritable or genetic-related aneurysms, patients with replaced bicuspid aortic valves, patients with acute aortic syndrome, or those with mean age less than 16 years. Two independent reviewers identified 20 studies from 7198 unique studies screened. Data extraction was performed according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline; 2 reviewers independently extracted the relevant data. Summary effect measures of the primary outcomes were obtained by logarithmically pooling the data with an inverse variance-weighted random-effects model. Metaregression was performed to assess the relationship between initial aneurysm size, etiology, and the primary outcomes. The primary composite outcome was incidence of all-cause mortality, aortic dissection, and aortic rupture. Secondary outcomes were growth rate, incidence of proximal aortic dissection or rupture, elective ascending aortic repair, and all-cause mortality. Twenty studies consisting of 8800 patients (mean [SD] age, 57.75 [9.47] years; 6653 [75.6%] male) with a total follow-up time of 31 823 patient-years were included. The mean AsAA size at enrollment was 42.6 mm (range, 35.5-56.0 mm). The combined effect estimate of annual aneurysm growth rate was 0.61 mm/y (95% CI, 0.23-0.99 mm/y). The pooled incidence of elective aortic surgery was 13.82% (95% CI, 6.45%-21.41%) over a median (interquartile range) follow-up of 4.2 (2.9-15.0) years. The linearized mortality rate was 1.99% per patient-year (95% CI, 0.83%-3.15% per patient-year), and the linearized rate of the composite outcome of all-cause mortality, aortic dissection, and aortic rupture was 2.16% per patient-year (95% CI, 0.79%-3.55% per patient year). There was no significant relationship between year of study completion and the initial aneurysm size and primary outcomes. The growth rate of AsAA is slow and has implications for the interval of imaging follow-up. The data on the risk of dissection, rupture, and death of ascending aortic aneurysm are limited. A randomized clinical trial may be required to understand the benefit of surgical intervention compared with surveillance for patients with moderately dilated ascending aorta.

Uric Acid as a Predictor of Immunoglobulin A Nephropathy Progression: A Cohort Study of 1965 Cases

Background: The role of serum uric acid (SUA) level in the progression of Immunoglobulin A nephropathy (IgAN) remains controversial. Methods: In a cohort of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA concentration with the primary outcome of a composite of all-cause mortality or kidney failure (defined as a reduction of estimated glomerular filtration rate [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or the outcome of kidney failure alone, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. Results: At baseline, the mean age was 33.37 ± 11.07 years, eGFR was 101.30 ± 30.49 mL/min/1.73 m², and mean uric acid level was 5.32 ± 1.76 mg/dL. During a median of 7-year follow-up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271 cases with reduction of eGFR by 40% from baseline). After adjustment for demographic and IgAN specific covariates and treatments, a higher quartile of uric acid was linearly associated with an increased risk of the primary outcome (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52–3.75) and kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62–4.01) in the Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL greater uric acid level was associated with 16% increased risk of primary outcome (HR 1.16, 95% CI 1.07–1.25) and 17% increased risk of kidney failure (HR 1.17, 95% CI 1.08–1.27), respectively, in the fully adjusted model. The multivariate ­logistic regression analyses for the sensitive analyses drew consistent results. In the subgroup analyses, significant interactions were detected that patients with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a higher association of SUA with the incidence of the primary outcome than those with MAP ≥90 mm Hg or those without mesangial hypercellularity respectively. Hyperuricemia was not significantly associated with the risk of developing the primary outcome in elder patients (≥32 years old), patients with eGFR < 90 mL/min or with tubular atrophy/interstitial fibrosis. Conclusions: SUA level may be positively associated with the progression of IgAN. It was noticeable that the association of hyperuricemia with IgAN progression was less significant in patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis, which may be due to some more confounders in association with the IgA progression in these patients. Future prospective studies are warranted to confirm these findings and to investigate the underlying mechanisms.

2034 Effect of balanced crystalloids on renal outcomes among critically ill adults does not differ from 0.9% saline across baseline risk of renal outcomes

OBJECTIVES/SPECIFIC AIMS: Traditional clinical trials typically enroll a homogenous population to test the efficacy of an intervention. Pragmatic trials deliberately enroll a more diverse population to enhance generalizability, but doing so may increase heterogeneity of treatment effect among subpopulations. For example, the effect of a treatment on an outcome may vary based on patients’ sex, comorbidities, or baseline risk of experiencing the outcome. We hypothesized that heterogeneity of treatment effect by baseline risk for the outcome could be demonstrated in a large pragmatic clinical trial. METHODS/STUDY POPULATION: We performed a prespecified secondary analysis of a recent pragmatic trial comparing balanced crystalloids Versus 0.9% saline among critically ill adults. The primary endpoint of the trial was major adverse kidney events within 30 days of ICU admission, censored at hospital discharge (MAKE30). MAKE30 is a composite outcome of all-cause mortality, new renal replacement therapy, or persistent renal dysfunction. Using a previously published model with high predictive accuracy for MAKE30 (area under the curve=0.903), we calculated the baseline risk of MAKE30 for all trial participants. We then developed a logistic regression model for MAKE30 with independent covariates of fluid group assignment, baseline risk of MAKE30 as a nonlinear continuous variable, and the interaction between group assignment and MAKE30 baseline risk. RESULTS/ANTICIPATED RESULTS: Among 15,802 patients from 5 intensive care units enrolled in the original trial, 126 had missing variables for predicted risk of MAKE30. Mean predicted risk of MAKE30 among all patients was 15.4%; median was 4.4% (interquartile range 2.2%–17.1%). Predicted risk of MAKE30 did not significantly differ between groups (p=0.61 by Mann-Whitney U-test). The incidence of MAKE30 in the trial was 14.9%, and the prediction model was well-calibrated overall (AUC=0.891). In a logistic regression model examining the interaction between group assignment and predicted risk of MAKE30, group assignment significantly affected MAKE30 (odds ratio saline:balanced 1.13, 95% CI: 1.02–1.27, p=0.02), but we observed no interaction between the effect of group assignment on MAKE30 and patients’ predicted risk of MAKE30 at baseline (p=0.66 for interaction term). DISCUSSION/SIGNIFICANCE OF IMPACT: In a large pragmatic trial demonstrating a significant difference in the primary outcome of MAKE30 between balanced crystalloids and saline, a previously published model accurately predicted MAKE30 using baseline factors. However, contrary to our hypothesis, the baseline risk of MAKE30 did not modify the effect of fluid group on the observed incidence of MAKE30. Our analysis could not account for unmeasured confounders and may be underpowered to detect a significant interaction. Our findings suggest that the impact of balanced crystalloids versus normal saline on renal outcomes in critically patients is consistent across all levels of risk.

High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial

BackgroundInfluenza leads to significant cardiopulmonary morbidity and mortality—particularly in patients with cardiovascular disease—that may be prevented with a standard influenza vaccine. However, patients with cardiovascular conditions have a reduced immune response to influenza vaccine, potentially resulting in reduced effectiveness for preventing clinical events. High-dose vaccine augments immune response in cardiac patients, suggesting that a high-dose influenza vaccination strategy may further reduce morbidity and mortality. Alternatively, broader coverage with an influenza vaccine containing an increased number of viral strains is an alternative strategy without direct evaluation. Research design and methodsINfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) is a pragmatic, randomized, double-blind, parallel-group, active-controlled trial comparing the effectiveness of an annual vaccination strategy of high-dose trivalent versus standard-dose quadrivalent influenza vaccine in patients with a history of recent heart failure or myocardial infarction hospitalization. The trial will enroll approximately 9,300 patients over 4 influenza seasons. The primary hypothesis is that high-dose influenza vaccine will reduce the composite outcome of all-cause mortality and hospitalization from a cardiovascular or pulmonary cause compared with standard-dose influenza vaccine within each enrolling season. Approximately 1,300 primary outcome events will provide >90% power to detect an 18% relative risk reduction at a 2-sided α level of .05. ConclusionINVESTED is the largest and longest study to assess whether high-dose influenza vaccine is superior to standard-dose influenza vaccine in reducing cardiopulmonary events in a high-risk cardiovascular population (ClinicalTrials.gov Identifier: NCT02787044).

The balance between short-term and long-term outcomes of bilateral internal thoracic artery skeletonization in coronary artery bypass surgery: a propensity-matched cohort study.

There is growing interest in the use of bilateral internal thoracic arteries (BITAs) for myocardial revascularization. This study sought to compare the balance between early benefits and long-term outcomes of skeletonized or non-skeletonized conduits and to determine whether differences in outcomes are affected by other patient risk factors. BITAs were used in 1504 cases with either SK or NSK conduits. Propensity matching was completed using 22 covariates identifying 441 pairs of patients. The primary outcomes are the sternal wound infection in the short term and the composite outcome of all-cause mortality, myocardial infarction, revascularization and congestive heart failure. Outcomes were assessed using paired analysis techniques and Cox proportional hazards regression models stratified using the matched pairs. Incidences of in-hospital mortality and perioperative myocardial infarction were similar in both groups. There were fewer sternal wound infections in the SK group (5.4 vs 9.1%, P = 0.033). Homogeneity testing of the relative risk estimates confirmed that there was a protective effect of skeletonization in men that was not demonstrated in women (P = 0.020). SK had a protective effect in diabetics not seen in non-diabetics (P = 0.048). The composite outcome of all-cause mortality, myocardial infarction, revascularization and congestive heart failure at a median of 5.6 years was comparable in both groups (hazard ratio 0.81, 95% confidence interval 0.57-1.15). Skeletonization results in better perioperative outcomes and comparable cardiac outcomes in patients undergoing BITA with the greatest benefit in men and patients with chronic obstructive pulmonary disease.

Low-Dose Aspirin in Heart Failure Not Complicated by Atrial Fibrillation: A Nationwide Propensity-Matched Study

ObjectivesThis study sought to assess safety and effectiveness of low-dose aspirin in heart failure (HF) not complicated by atrial fibrillation. BackgroundDespite lack of evidence, low-dose aspirin is widely used in patients with HF and sinus rhythm with and without prior ischemic heart disease. MethodsThe study included 12,277 patients with new-onset HF during 2007 to 2012 who had no history of atrial fibrillation. Of 5,450 patients using low-dose aspirin at baseline, 3,840 were propensity matched to non-aspirin users in a 1:1 ratio. Propensity-matched Cox models were calculated with respect to the primary composite outcome of all-cause mortality, myocardial infarction, and stroke and the secondary outcomes of bleeding and HF readmission. ResultsThe composite outcome occurred in 1,554 (40.5%) patients in the aspirin group and 1,604 (41.8%) patients in the non-aspirin group. Aspirin use was not associated with an altered risk of composite outcome (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.91 to 1.05), but it was associated with an increased risk of myocardial infarction (HR: 1.34; 95% CI: 1.08 to 1.67), whereas no differences were observed in all-cause mortality and stroke. An increased risk of HF readmission was observed in the aspirin group (HR: 1.25; 95% CI: 1.17 to 1.33). No difference in bleeding was observed. In subgroup analyses on the basis of a history of ischemic heart disease, the results were similar to the main result. ConclusionsNo association was detected between low-dose aspirin use and the composite outcome of all-cause mortality, admission for myocardial infarction, and admission for stroke in patients with HF with no history of atrial fibrillation. Aspirin use was associated with an increased risk of readmission for HF.

Does Statin Benefits Patients with Heart Failure Undergoing Percutaneous Coronary Intervention? Findings from the Melbourne Interventional Group Registry.

The effectiveness of statins in improving clinical outcomes among patients with heart failure (HF) undergoing percutaneous coronary intervention (PCI) is unclear. We examined the association between use of statins and clinical outcomes in patients with HF included in the Melbourne Interventional Group registry. Patients were followed from 30days to 1year post-PCI for a primary composite outcome of all-cause mortality and hospitalisation for cardiovascular (CV) causes. Secondary outcomes included major adverse cardiac events (MACE, a composite of all-cause mortality, myocardial infarction and target vessel revascularisation) and hospitalisation for CV causes. Outcomes were compared between statin-treated and non-statin-treated patients (at 30days post-PCI) using propensity scores to balance for risk factors. Among 991 patients included in the inverse probability-weighted Cox model, statin use had no significant effect on the primary composite outcome [adjusted hazard ratio (aHR), 1.03; 95% confidence interval (CI), 0.68 to 1.56; p = 0.89], nor MACE (aHR, 0.99; 95% CI, 0.54 to 1.84; p = 0.99) or hospitalisation for CV causes (HR, 1.13; 95% CI, 0.74 to 1.72; p = 0.57). Our results suggest that statin therapy may confer no significant benefits in patients with HF undergoing PCI. However, prospective randomised controlled trials are needed to provide more definitive answers.

Dementia is a risk factor for major adverse cardiac and cerebrovascular events in elderly Korean patients initiating hemodialysis: a Korean national population-based study

BackgroundDementia is common in end-stage renal disease (ESRD) patients on hemodialysis (HD) and is associated with worse outcomes. This study aimed to investigate the risk of major adverse cardiac and cerebrovascular event (MACCE) in elderly patients with dementia initiating HD.MethodsUsing the database from the Health Insurance Review & Assessment Service, we analyzed 10,171 patients aged 65 years or older who had initiated dialysis from 2005 to 2008. MACCE was defined as a composite outcome of all-cause mortality, nonfatal acute myocardial infarction, target vessel revascularization, and nonfatal ischemic and hemorrhagic stroke. The Kaplan-Meier method and Cox proportional hazards model were used, and further comparisons using propensity-score matching at 1:2 ratio were also performed.ResultsA total of 303 elderly patients (3.0%) had dementia at initiating HD. During follow-up, dementia was a significant predictor of MACCE after adjustment for confounding variables. In addition, further analyzed in the propensity-score matched groups, dementia was an independent predictor of both nonfatal ischemic stroke and all-cause mortality.ConclusionsDementia is an independent risk factor for mortality and ischemic stroke in elderly ESRD patients initiating HD. Patients with dementia who start dialysis should be closely monitored to reduce the risk of mortality and ischemic stroke.