Trends and Outcomes During Rollout Phase of Non-Primary PCI at Sites Without Surgery On-Site: The Michigan Experience

Objectives: This study sought to compare outcomes of patients undergoing non-primary percutaneous coronary intervention (non-PPCI) at centers with and without surgery on-site (SoS) in Michigan during the introductory phase.Background: Non-PPCI recently received certificate of need approval in the state of Michigan to be performed at sites without SoS. This requires mandatory participation in the BMC2 registry, which involves rigorous quality oversight. Methods: Consecutive patients who underwent non-PPCI at 47 hospitals in Michigan from April 2016 to March 2018 were included. From this cohort, 4,643 propensity matched patients, in a 1:1 fashion, were used to compare baseline characteristics, procedural details, and in-hospital outcomes. Additionally, trends in non-PPCI distribution among sites were assessed.Results: Of the 61,864 PCI’s performed during the study period, 50,817 were non-PPCI’s, with 46,096 (90.7%) performed at sites with SoS and 4,721 (9.3%) at sites without SoS. While overall PCI volume remained relatively steady, there was a near three-fold rise in performance of non-PPCI at sites without SoS. In propensity matched cohorts, overall rate of major adverse cardiac events (2.6% vs. 2.8%; p = 0.443), in-hospital mortality (0.6% vs. 0.5%; p = 0.465), and other secondary clinical and quality outcomes, showed no clinically significant differences. Conclusion: In the two years since state approval, non-primary PCI at centers without cardiac SoS was associated with similar in-hospital outcomes and quality compared with centers with SoS. The mandatory rigorous quality oversight process that was put in place by state regulations can serve as a model for similar programs elsewhere.https://scholarlycommons.henryford.com/merf2019clinres/1002/thumbnail.jp

An Exome-Wide Sequencing Study of Lipid Response to High-Fat Meal and Fenofibrate in Caucasians from the GOLDN Cohort

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P \u3c 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.publishedVersio

Identification of Post-cardiac Arrest Blood Pressure Thresholds Associated With Outcomes in Children: An ICU-Resuscitation Study

INTRODUCTION: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge. METHODS: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled in the ICU-RESUScitation trial (NCT02837497). The lowest documented systolic BP (SBP) and diastolic BP (DBP) were percentile-adjusted for age, height and sex. Receiver operator characteristic curves and cubic spline analyses controlling for illness category and presence of pre-arrest hypotension were generated exploring the association of lowest post-arrest SBP and DBP with survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category of 1-3 or no change from baseline). Optimal cutoffs for post-arrest BP thresholds were based on analysis of receiver operator characteristic curves and spline curves. Logistic regression models accounting for illness category and pre-arrest hypotension examined the associations of these thresholds with outcomes. RESULTS: Among 693 index events with 0-6 h post-arrest BP data, identified thresholds were: SBP \u3e 10th percentile and DBP \u3e 50th percentile for age, sex and height. Fifty-one percent (n = 352) of subjects had lowest SBP above threshold and 50% (n = 346) had lowest DBP above threshold. SBP and DBP above thresholds were each associated with survival to hospital discharge (SBP: aRR 1.21 [95% CI 1.10, 1.33]; DBP: aRR 1.23 [1.12, 1.34]) and survival to hospital discharge with favorable neurologic outcome (SBP: aRR 1.22 [1.10, 1.35]; DBP: aRR 1.27 [1.15, 1.40]) (all p \u3c 0.001). CONCLUSIONS: Following pediatric IHCA, subjects had higher rates of survival to hospital discharge and survival to hospital discharge with favorable neurologic outcome when BP targets above a threshold of SBP \u3e 10th percentile for age and DBP \u3e 50th percentile for age during the first 6 h post-arrest

Brief Report: Incidence and Outcomes of Pediatric Tracheal Intubation-Associated Cardiac Arrests in the ICU-RESUS Clinical Trial

BACKGROUND: Tracheal intubation (TI)-associated cardiac arrest (TI-CA) occurs in 1.7% of pediatric ICU TIs. Our objective was to evaluate resuscitation characteristics and outcomes between cardiac arrest patients with and without TI-CA. METHODS: Secondary analysis of cardiac arrest patients in both ICU-RESUS trial and ancillary CPR-NOVA study. The primary exposure was TI-CA, defined as cardiac arrest occurred during TI procedure or within 20 min after endotracheal tube placement. The primary outcome was survival to hospital discharge with favorable neurological outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged). RESULTS: Among 315 children with cardiac arrests, 48 (15.2%) met criteria for TI-CA. Pre-existing medical conditions were similar between groups. Pre-arrest non-invasive mechanical ventilation was more common among TI-CA patients (18/48, 37.5%) compared to non-TI-CA patients (35/267, 13.1%). In 48% (23/48), the TI-CA occurred within 20 min after intubation (i.e., not during intubation). Duration of CPR was longer in TI-CA patients (median 11.0 min, interquartile range [IQR]: 2.5, 35.5) than non-TI-CA patients (median 5.0 min, IQR 2.0, 21.0), p = 0.03. Return of spontaneous circulation occurred in 32/48 (66.7%) TI-CA versus 186/267 (69.7%) non-TI-CA, p = 0.73. Survival to hospital discharge with favorable neurological outcome occurred in 29/48 (60.4%) TI-CA versus 146/267 (54.7%) non-TI-CA, p = 0.53. CONCLUSIONS: Fifteen percent of these pediatric ICU cardiac arrests were associated with TI. Half of TI-CA occurred after endotracheal tube placement. While duration of CPR was longer in TI-CA patients, there were no differences in unadjusted outcomes following TI-CA versus non-TI-CA. TRIAL REGISTRATION: The ICU-RESUS (ClinicalTrials.gov Identifier: NCT02837497)

Early Bolus Epinephrine Administration During Pediatric Cardiopulmonary Resuscitation for Bradycardia with Poor Perfusion: An ICU-Resuscitation Study

BACKGROUND: Half of pediatric in-hospital cardiopulmonary resuscitation (CPR) events have an initial rhythm of non-pulseless bradycardia with poor perfusion. Our study objectives were to leverage granular data from the ICU-RESUScitation (ICU-RESUS) trial to: (1) determine the association of early epinephrine administration with survival outcomes in children receiving CPR for bradycardia with poor perfusion; and (2) describe the incidence and time course of the development of pulselessness. METHODS: Prespecified secondary analysis of ICU-RESUS, a multicenter cluster randomized trial of children (\u3c 19 years) receiving CPR in 18 intensive care units in the United States. Index events (October 2016-March 2021) lasting ≥ 2 min with a documented initial rhythm of bradycardia with poor perfusion were included. Associations between early epinephrine (first 2 min of CPR) and outcomes were evaluated with Poisson multivariable regression controlling for a priori pre-arrest characteristics. Among patients with arterial lines, intra-arrest blood pressure waveforms were reviewed to determine presence of a pulse during CPR interruptions. The temporal nature of progression to pulselessness was described and outcomes were compared between patients according to subsequent pulselessness status. RESULTS: Of 452 eligible subjects, 322 (71%) received early epinephrine. The early epinephrine group had higher pre-arrest severity of illness and vasoactive-inotrope scores. Early epinephrine was not associated with survival to discharge (aRR 0.97, 95%CI 0.82, 1.14) or survival with favorable neurologic outcome (aRR 0.99, 95%CI 0.82, 1.18). Among 186 patients with invasive blood pressure waveforms, 118 (63%) had at least 1 period of pulselessness during the first 10 min of CPR; 86 (46%) by 2 min and 100 (54%) by 3 min. Sustained return of spontaneous circulation was highest after bradycardia with poor perfusion (84%) compared to bradycardia with poor perfusion progressing to pulselessness (43%) and bradycardia with poor perfusion progressing to pulselessness followed by return to bradycardia with poor perfusion (62%) (p \u3c 0.001). CONCLUSIONS: In this cohort of pediatric CPR events with an initial rhythm of bradycardia with poor perfusion, we failed to identify an association between early bolus epinephrine and outcomes when controlling for illness severity. Most children receiving CPR for bradycardia with poor perfusion developed subsequent pulselessness, 46% within 2 min of CPR onset

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease

The recommendations listed in this document are, whenever possible, evidence based. An extensive evidence review was conducted as the document was compiled through December 2008. Repeated literature searches were performed by the guideline development staff and writing committee members as new issues were considered. New clinical trials published in peer-reviewed journals and articles through December 2011 were also reviewed and incorporated when relevant. Furthermore, because of the extended development time period for this guideline, peer review comments indicated that the sections focused on imaging technologies required additional updating, which occurred during 2011. Therefore, the evidence review for the imaging sections includes published literature through December 2011

Primary percutaneous coronary intervention at centers with and without on-site surgical support: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2)

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is being increasingly performed nationally at sites without on-site cardiac surgery; however, recent guidelines only provide a Class IIa recommendation for this practice. The state of Michigan has permitted PPCI without on-site surgery under a closely monitored system that mandates auditing of all procedures and quarterly feedback on quality and outcomes. This study sought to compare outcomes of patients undergoing PPCI at centers with and without on-site surgery in the state of Michigan. METHODS: Consecutive patients who underwent PPCI at 47 hospitals in Michigan from January 2010 to December 2015 were included. From this cohort, 4,091 patients from sites with and without on-site cardiac surgery were propensity matched in a 1:1 fashion to compare baseline characteristics, procedural details, and in-hospital outcomes. RESULTS: Of the 25,886 PPCIs performed at 47 hospitals in Michigan from 2010 to 2015, 21,610 (83.5%) were performed at sites with on-site surgery and 4,276 (16.5%) at sites without on-site surgery. Using propensity score matched cohorts (4,091 patients for each site type), we found no significant differences in baseline characteristics. Overall mortality (5.4% vs 5.8%; P=.442); composite outcome of in-hospital mortality, contrast-induced nephropathy, bleeding, and stroke (13.8% vs 12.8%; P=.152); and individual outcomes within the composite group showed no significant differences. Additionally, there were no clinically meaningful differences in rates of urgent/emergent coronary artery bypass graft or length of stay. Significant differences, however, were found in procedural access site, antiplatelet therapy, contrast volume, and anticoagulant strategy. CONCLUSIONS: Primary PCI performed at centers with and without cardiac surgery have comparable outcomes and complication rates when performed with close monitoring of quality and outcomes