Charlson Comorbidity Index is Associated With Longer-Term Mortality and Re-Admissions Following Coronary Artery Bypass Grafting.

INTRODUCTION: The Charlson Comorbidity Index (CCI) is widely utilized for risk stratification by providers, payors, and administrative database researchers for non-cardiac surgical patients. CCI scores have not been validated in cardiac surgical patients. We hypothesize that the CCI will predict mid-term mortality and re-admissions, but performance may be different than purpose-built cardiac surgery risk calculators. METHODS: Patients undergoing isolated CABG between 2011 and 2017 were reviewed. Age-adjusted CCI scores were calculated based on clinical status at a time of index operation using prospectively captured data from institutional databases. Primary endpoint was 5-year mortality and 1-year re-admissions. The CCI, STS predicted mortality, and ASCERT 5-year mortality scores were compared in a sub-cohort of 500 patients. Patients underwent analysis using Cox Proportional Hazard ratios, Kaplan-Meier analysis, and ROC comparisons. RESULTS: Average CCI score for the overall population (n = 6064) was 3.40 ± 1.75. Kaplan-Meier analysis revealed significant difference in mortality stratified by CCI. Hazard ratio for 5-year mortality increased with each interval increase in CCI score value (HR 1.38 [1.33-1.43], P < 0.001), as did the risk of 1-year re-admission (HR 1.19 [1.15-1.22], P < 0.001). ROC curves for CCI, STS mortality, and ASCERT 5-year mortality risk demonstrate that all three scores are predictive at 5 y, but the ASCERT score performs best (ROC 0.76 versus 0.69, P = 0.004). CONCLUSIONS: The CCI can serve as a useful mid-term risk stratification tool in patients undergoing CABG when variables for the purpose-built STS and ASCERT scores are unavailable. However, the ASCERT score performs better at 5-year mortality calculation.

Trends and outcomes following total artificial heart as bridge to transplant from the UNOS database.

INTRODUCTION: Bridge to transplantation (BTT) with a SynCardia Total Artificial Heart (TAH) has been gaining momentum as a therapy for patients with biventricular heart failure. Recent transplant waitlist and posttransplant outcomes with this strategy have not been comprehensively characterized. We reviewed the United Network for Organ Sharing (UNOS) database to examine BTT outcomes for the TAH system since approval. METHODS: Adult patients listed for heart transplantation in the UNOS system between 2004 and 2020 who underwent BTT therapy with a TAH were included in the study. Trends in utilization of TAH compared with other durable mechanical support strategies were examined. The primary outcome was 1-year survival following heart transplantation following BTT with TAH. Secondary outcomes included waitlist deterioration and risk factors for waitlist or posttransplant mortality. RESULTS: During the study 433 total patients underwent TAH implant as BTT therapy; 236 (54.4%) were listed with the TAH, while the remaining patients were upgraded to TAH support while on the waitlist. Waitlist mortality was 7.4%, with 375 patients (86.6%) ultimately being transplanted. Age, cerebrovascular disease, functional status, and ventilator dependence were risk factors for waitlist mortality. One-year survival following successful BTT was 80%. Risk factors for mortality following BTT included age, body mass index, and underlying diagnosis. CONCLUSIONS: Patients undergoing BTT with TAH demonstrate acceptable waitlist survival and good 1-year survival. While utilization initially increased as a BTT therapy, there has been a plateau in relative utilization. Individual patient and transplantation center factors deserve further investigation to determine the ideal population for this therapy.

Circadian-Dependent and Sex-Dependent Increases in Intravenous Cocaine Self-Administration in Npas2 Mutant Mice.

Substance use disorder (SUD) is associated with disruptions in circadian rhythms. The circadian transcription factor neuronal PAS domain protein 2 (NPAS2) is enriched in reward-related brain regions and regulates reward, but its role in SU is unclear. To examine the role of NPAS2 in drug taking, we measured intravenous cocaine self-administration (acquisition, dose-response, progressive ratio, extinction, cue-induced reinstatement) in wild-type (WT) and Npas2 mutant mice at different times of day. In the light (inactive) phase, cocaine self-administration, reinforcement, motivation and extinction responding were increased in all Npas2 mutants. Sex differences emerged during the dark (active) phase with Npas2 mutation increasing self-administration, extinction responding, and reinstatement only in females as well as reinforcement and motivation in males and females. To determine whether circulating hormones are driving these sex differences, we ovariectomized WT and Npas2 mutant females and confirmed that unlike sham controls, ovariectomized mutant mice showed no increase in self-administration. To identify whether striatal brain regions are activated in Npas2 mutant females, we measured cocaine-induced ΔFosB expression. Relative to WT, ΔFosB expression was increased in D1+ neurons in the nucleus accumbens (NAc) core and dorsolateral (DLS) striatum in Npas2 mutant females after dark phase self-administration. We also identified potential target genes that may underlie the behavioral responses to cocaine in Npas2 mutant females. These results suggest NPAS2 regulates reward and activity in specific striatal regions in a sex and time of day (TOD)-specific manner. Striatal activation could be augmented by circulating sex hormones, leading to an increased effect of Npas2 mutation in females.SIGNIFICANCE STATEMENT Circadian disruptions are a common symptom of substance use disorders (SUDs) and chronic exposure to drugs of abuse alters circadian rhythms, which may contribute to subsequent SU. Diurnal rhythms are commonly found in behavioral responses to drugs of abuse with drug sensitivity and motivation peaking during the dark (active) phase in nocturnal rodents. Emerging evidence links disrupted circadian genes to SU vulnerability and drug-induced alterations to these genes may augment drug-seeking. The circadian transcription factor neuronal PAS domain protein 2 (NPAS2) is enriched in reward-related brain regions and regulates reward, but its role in SU is unclear. To examine the role of NPAS2 in drug taking, we measured intravenous cocaine self-administration in wild-type (WT) and Npas2 mutant mice at different times of day.