Association of Acute Kidney Injury and Cardiovascular Disease Following Percutaneous Coronary Intervention: Assessment of Interactions by Race, Diabetes, and Kidney Function.

RATIONALE & OBJECTIVE: Black patients and those with diabetes or reduced kidney function experience a disproportionate burden of acute kidney injury (AKI) and cardiovascular events. However, whether these factors modify the association between AKI and cardiovascular events after percutaneous coronary intervention (PCI) is unknown and was the focus of this study. STUDY DESIGN: Observational cohort. SETTING & PARTICIPANTS: Patients who underwent PCI at Duke between January 1, 2003, and December 31, 2013, with data available in the Duke Databank for Cardiovascular Disease. EXPOSURE: AKI, defined as ≥1.5-fold relative elevation in serum creatinine within 7 days from a reference value ascertained 30 days before PCI, or a 0.3 mg/dL increase from the reference value within 48 hours. OUTCOME: A composite of all-cause death, myocardial infarction, stroke, or revascularization during the first year after PCI. ANALYTICAL APPROACH: Cox regression models adjusted for potential confounders and with interaction terms between AKI and race, diabetes, or baseline estimated glomerular filtration rate (eGFR). RESULTS: Among 9,422 patients, 9% (n = 865) developed AKI, and the primary composite outcome occurred in 21% (n = 2,017). AKI was associated with a nearly 2-fold higher risk of the primary outcome (adjusted HR, 1.94 [95% CI, 1.71-2.20]). The association between AKI and cardiovascular risk did not significantly differ by race (P interaction, 0.4), diabetes, (P interaction, 0.06), or eGFR (P interaction, 0.2). However, Black race and severely reduced eGFR, but not diabetes, each had a cumulative impact with AKI on risk for the primary outcome. Compared with White patients with no AKI as the reference, the risk for the outcome was highest in Black patients with AKI (HR, 2.27 [95% CI, 1.83-2.82]), followed by White patients with AKI (HR, 1.87 [95% CI, 1.58-2.21]), and was least in patients of other races with AKI (HR, 1.48 [95% CI, 0.88-2.48]). LIMITATIONS: Residual confounding, including the impact of clinical care following PCI on cardiovascular outcomes of AKI. CONCLUSIONS: Neither race, diabetes, nor reduced eGFR potentiated the association of AKI with cardiovascular risk, but Black patients with AKI had a qualitatively greater risk than White patients with AKI or patients of other races with AKI. PLAIN-LANGUAGE SUMMARY: This study examined differences by race, diabetes, or kidney function in the well-known association of AKI with increased risk for cardiovascular outcomes among patients undergoing percutaneous coronary intervention. The authors found that AKI was associated with a greater risk for cardiovascular outcomes, but this risk did not differ by patients' race, diabetes status, or level of kidney function before the procedure. That said, the risk for cardiovascular outcomes was numerically highest among Black patients compared with White patients or those of other races. These study findings suggest that future efforts to prevent AKI among patients undergoing the procedure could reduce racial disparities in risk for unfavorable cardiovascular outcomes afterward.

OptiVol for Volume Assessment in Patients With Continuous Flow Left Ventricular Assist Device.

OptiVol (Medtronic PLC, Minneapolis, MN) is a diagnostic feature of some cardiac implantable electronic devices (CIEDs) based on changes in thoracic impedance (TI) over time. Changes in TI can predict heart failure (HF) hospitalizations and mortality in HF populations. However, the utility of this feature is unknown in patients with a left ventricular assist device (LVAD). To determine if OptiVol and TI correlate with clinical HF events in a population of LVAD patients, hospitalization outcomes were collected retrospectively from the electronic health records at a single academic medical center in 80 LVAD patients with an OptiVol-capable CIED. Demographics, medical history, and available clinical data were reviewed and reported. The primary outcomes of interest were TI and OptiVol trends before and after hospitalization, and association of trends before and after these events was evaluated. Most patients had a HeartMate II LVAD and most CIEDs were defibrillators, and 23 (29%) had at least one HF hospitalization during the study period. HF hospitalizations were preceded by signs of volume overload in Optivol (60%) and TI (78%) with recovery of these measures post hospitalization in 33% and 25% of patients, respectively. Monitoring of TI and OptiVol may be one effective component of HF management in LVAD patients as part of a comprehensive program.

Risk Factor Burden and Long-Term Prognosis of Patients With Premature Coronary Artery Disease.

Background Coronary artery disease (CAD) is increasing among young adults. We aimed to describe the cardiovascular risk factors and long-term prognosis of premature CAD. Methods and Results Using the Duke Databank for Cardiovascular Disease, we evaluated 3655 patients admitted between 1995 and 2013 with a first diagnosis of obstructive CAD before the age of 50 years. Major adverse cardiovascular events (MACEs), defined as the composite of death, myocardial infarction, stroke, or revascularization, were ascertained for up to 10 years. Cox proportional hazard regression models were used to assess associations with the rate of first recurrent event, and negative binomial log-linear regression was used for rate of multiple event recurrences. Past or current smoking was the most frequent cardiovascular factor (60.8%), followed by hypertension (52.8%) and family history of CAD (39.8%). Within a 10-year follow-up, 52.9% of patients had at least 1 MACE, 18.6% had at least 2 recurrent MACEs, and 7.9% had at least 3 recurrent MACEs, with death occurring in 20.9% of patients. Across follow-up, 31.7% to 37.2% of patients continued smoking, 81.7% to 89.3% had low-density lipoprotein cholesterol levels beyond the goal of 70 mg/dL, and 16% had new-onset diabetes mellitus. Female sex, diabetes mellitus, chronic kidney disease, multivessel disease, and chronic inflammatory disease were factors associated with recurrent MACEs. Conclusions Premature CAD is an aggressive disease with frequent ischemic recurrences and premature death. Individuals with premature CAD have a high proportion of modifiable cardiovascular risk factors, but failure to control them is frequently observed.

Claims-based cardiovascular outcome identification for clinical research: Results from 7 large randomized cardiovascular clinical trials.

BACKGROUND: Medicare insurance claims may provide an efficient means to ascertain follow-up of older participants in clinical research. We sought to determine the accuracy and completeness of claims- versus site-based follow-up with clinical event committee (+CEC) adjudication of cardiovascular outcomes. METHODS: We performed a retrospective study using linked Medicare and Duke Database of Clinical Trials data. Medicare claims were linked to clinical data from 7 randomized cardiovascular clinical trials. Of 52,476 trial participants, linking resulted in 5,839 (of 10,497 linkage-eligible) Medicare-linked trial participants with fee-for-service A and B coverage. Death, myocardial infarction (MI), stroke, and revascularization incidences were compared using Medicare inpatient claims only, site-reported events (+CEC) only, or a combination of the 2. Randomized treatment effects were compared as a function of whether claims-based, site-based (+CEC), or a combined system was used for event detection. RESULTS: Among the 5,839 study participants, the annual event rates were similar between claims- and site-based (+CEC) follow-up: death (overall rate 5.2% vs 5.2%; adjusted κ 0.99), MI (2.2% vs 2.3%; adjusted κ 0.96), stroke (0.7% vs 0.7%; adjusted κ 0.99), and any revascularization (7.4% vs 7.9%; adjusted κ 0.95). Of events detected by claims yet not reported by CEC, a minority were reported by sites but negatively adjudicated by CEC (39% of MIs and 18% of strokes). Differences in individual case concordance led to higher event rates when claims- and site-based (+CEC) systems were combined. Randomized treatment effects were similar among the 3 approaches for each outcome of interest. CONCLUSIONS: Claims- versus site-based (+CEC) follow-up identified similar overall cardiovascular event rates despite meaningful differences in the events detected. Randomized treatment effects were similar using the 2 methods, suggesting claims data could be used to support clinical research leveraging routinely collected data. This approach may lead to more effective evidence generation, synthesis, and appraisal of medical products and inform the strategic approaches toward the National Evaluation System for Health Technology.

Predictors of contemporary coronary artery bypass grafting outcomes.

OBJECTIVES: The study objective was to identify the predictors of outcomes in a contemporary cohort of patients from the Reduction in cardiovascular Events by acaDesine in patients undergoing CABG (RED-CABG) trial. Despite the increasing risk profile of patients who undergo coronary artery bypass grafting, morbidity and mortality have remained low, and identification of the current predictors of adverse outcomes may permit new treatments to further improve outcomes. METHODS: The RED-CABG trial was a multicenter, randomized, double-blind, placebo-controlled study that determined that acadesine did not reduce adverse events in moderately high-risk patients undergoing nonemergency coronary artery bypass grafting. The primary efficacy end point was a composite of all-cause death, nonfatal stroke, or the need for mechanical support for severe left ventricular dysfunction through postoperative day 28. Logistic regression modeling with stepwise variable selection identified which prespecified baseline characteristics were associated with the primary outcome. A second logistic model included intraoperative variables as potential covariates. RESULTS: The 4 independent preoperative risk factors predictive of the composite end point were (1) a history of heart failure (odds ratio, 2.9); (2) increasing age (odds ratio, 1.033 per decade); (3) a history of peripheral vascular disease (odds ratio, 1.6); and (4) receiving aspirin before coronary artery bypass grafting (odds ratio, 0.5), which was protective. The duration of the cardiopulmonary bypass (odds ratio, 1.8) was the only intraoperative variable that contributed to adverse outcomes. CONCLUSIONS: Patients who had heart failure and preserved systolic function had a similar high risk of adverse outcomes as those with low ejection fractions, and new approaches may mitigate this risk. Recognition of patients with excessive atherosclerotic burden may permit perioperative interventions to improve their outcomes. The contemporary risks of coronary artery bypass grafting have changed, and their identification may permit new methods to improve outcomes.

Risk-adjusted survival after tissue versus mechanical aortic valve replacement: a 23-year assessment.

BACKGROUND AND AIM OF THE STUDY: Detailed analyses of risk-adjusted outcomes after mitral valve surgery have documented significant survival decrements with tissue valves at any age. Several recent studies of prosthetic aortic valve replacement (AVR) also have suggested a poorer performance of tissue valves, although analyses have been limited to small matched series. The study aim was to test the hypothesis that AVR with tissue valves is associated with a lower risk-adjusted survival, as compared to mechanical valves. METHODS: Between 1986 and 2009, primary isolated AVR, with or without coronary artery bypass grafting (CABG), was performed with currently available valve types in 2148 patients (1108 tissue valves, 1040 mechanical). Patients were selected for tissue valves to be used primarily in the elderly. Baseline and operative characteristics were documented prospectively with a consistent variable set over the entire 23-year period. Follow up was obtained with mailed questionnaires, supplemented by National Death Index searches. The average time to death or follow up was seven years, and follow up for survival was 96.2% complete. Risk-adjusted survival characteristics for the two groups were evaluated using a Cox proportional hazards model with stepwise selection of candidate variables. RESULTS: Differences in baseline characteristics between groups were (tissue versus mechanical): median age 73 versus 61 years; non-elective surgery 32% versus 28%; CABG 45% versus 35%; median ejection fraction 55% versus 55%; renal failure 6% versus 1%; diabetes 18% versus 7% (p<0.01). Unadjusted Kaplan-Meier survival was significantly lower with tissue than mechanical valves; however, after risk adjustment for the adverse profiles of tissue valve patients, no significant difference was observed in survival after tissue or mechanical AVR. Thus, the hypothesis did not hold, and risk-adjusted survival was equivalent, of course qualified by the fact that selection bias was evident. CONCLUSION: With selection criteria that employed tissue AVR more frequently in elderly patients, tissue and mechanical valves achieved similar survival characteristics across the spectrum of patient risk. Further studies of the relative outcomes of mechanical versus tissue valves across the spectrum of patient age seem indicated.

Link between decisions regarding resuscitation and preferences for quality over length of life with heart failure.

AIMS: Survival preferences, ascertained from time-trade-off utilities, have not been studied in heart failure patients who designate a 'do not resuscitate' (DNR) status. Therefore, the aim of this study was to determine the association of heart failure patients' resuscitation preferences with survival preferences and mortality in the ESCAPE trial. METHODS AND RESULTS: We analysed the association of resuscitation orders at 1 month with time-trade-off utilities and 6-month mortality. There were 26 and 349 patients with a DNR order and Full Code order, respectively. DNR patients were older, had more coronary artery disease, hypertension, renal impairment, and poorer exercise capacity than Full Code patients. DNR patients also experienced longer hospitalization and higher 6-month mortality. In multivariate analysis, DNR preference was associated with 10-fold higher odds of willingness to trade survival time (lower time-trade-off utility) in favour of improved quality of life [odds ratio 10.33, 95% confidence interval (CI) 1.65-64.80]. DNR preference was the best predictor of mortality (χ(2) 26.12, P < 0.0001, hazard ratio 6.88, 95% CI 3.28-14.41), despite adjustment for known predictors including brain natriuretic peptide. CONCLUSIONS: Heart failure patients' requests to forego resuscitation may signify more than simply 'what-if' directives for emergency care. DNR decisions may reflect preferences for intervention to enhance quality rather than prolong survival, which is particularly important as these patients have high early mortality.

Safety of selective serotonin reuptake inhibitor use prior to coronary artery bypass grafting.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been shown to increase bleeding risks. This study examined the association of perioperative coronary artery bypass grafting (CABG) bleeding risks and SSRI use prior to CABG. HYPOTHESIS: SSRI may be associated with increased bleeding risks after CABG resulting in elevated reoperation rates due to bleeding complications. METHODS: Patients who underwent CABG between 1999 and 2003 (n = 4794) were identified in a tertiary medical center. SSRI use (n = 246) was determined using inpatient pharmacy records. Outcomes included primary end point of reoperation due to bleeding complications and other secondary measures. Multivariate regression models were constructed to adjust for baseline differences between SSRI and control groups. RESULTS: Reoperation due to bleeding complications among SSRI users was not significantly different (odds ratio [OR]: 1.14 (0.52-2.47); P = 0.75) compared to the control group. Other secondary outcomes and 30-day mortality (2.0% in SSRI vs 2.1% in control group; P = 0.92) between the 2 groups were similar. However, the adjusted total volume of postoperative red blood cell (RBC) units transfused was higher in the SSRI group. CONCLUSION: We conclude that there is no compelling evidence to limit the use of SSRIs among patients with coronary artery disease who undergo CABG given the current evidence. Further research may be needed on individual SSRI medications.