Faculty Bibliography

Cardiogenic shock occurs in up to 5% to 10% of acute myocardial infarctions(MI) and is associated with high short- and long-term mortality risk. Since its introduction into clinical practice >50 years ago, intra-aortic balloon counterpulsion has been used empirically to provide hemodynamic support in patients undergoing coronary revascularization in the setting of MI and cardiogenic shock. In the landmark SHOCK (Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock) trial, conducted between 1993 and 1998, intra-aortic balloon pumps (IABP) were placed in 86% of participants, irrespective of the assigned management strategy.¹ Although expert opinion supported clinical benefit of IABP use in cardiogenic shock, the first large randomized, multi-center trial of IABP, published in 2012, upended this conventional wisdom. The IABP-SHOCK II(Intra-aortic Balloon Pump in Cardiogenic Shock II) trial randomly assigned 600 participants planned for early revascularization of acute MI complicated by cardiogenic shock to either IABP placement or no IABP placement.² The primary end point was 30-day all-cause mortality. At 30 days, all-cause mortality was 40%, with no difference between patients randomized to receive an IABP versus those who were not. There were no differences between treatment groups in secondary outcomes, including bleeding, ischemic complications, stroke, time to hemodynamic stabilization, intensive care unit length of stay, and the dose and duration of catecholamine therapy. A previous intermediate-term report of IABP-SHOCK II trial outcomes demonstrated no difference between treatment groups for allcause mortality at 12 months.³ In this issue of Circulation, Thiele et al⁴ report the 6-year results of the IABPSHOCK II randomized trial. At 6 years of follow-up, all-cause mortality was high and did not differ between the IABP and control groups (66.3% versus 67.0%) in intention-to-treat, per-protocol, and as-treated analyses. No signal for benefit associated with IABP use was observed in any prespecified or post hoc subgroups. There were no differences in the frequency of recurrent MI, repeat revascularization, stroke, or cardiovascular rehospitalization between the 2 groups. Quality of life, measured by the EuroQol 5D questionnaire and New York Heart Association classification, was favorable in survivors of cardiogenic shock. Four of 5 survivors had New York Heart Association Class I or II symptoms, with no difference between patients randomly assigned to IABP and no IABP therapy.

INTRODUCTION/BACKGROUND:Blood donation has been proposed as a potential therapy to reduce risk of cardiovascular disease, but the effects of phlebotomy on vascular function in human subjects have not been well characterized. AIMS/OBJECTIVE:We conducted a prospective randomized double-blind study to determine the effects of serial phlebotomy on vascular endothelial function in the brachial artery. 84 iron-replete, non-anemic subjects were randomly assigned to one of three study treatment groups: 1) four serial phlebotomy procedures each followed by intravenous infusion of placebo normal saline; 2) four serial phlebotomy procedures each followed by intravenous infusion to replete lost iron; and 3) four serial sham phlebotomy procedures each followed by intravenous infusion of placebo normal saline. Assigned phlebotomy procedures were conducted at 56-day intervals. We measured brachial artery reactivity (BAR, %) in response to transient oxidative stress induced by oral methionine with high-resolution duplex ultrasound imaging before and one week after the fourth study phlebotomy. RESULTS:Before phlebotomy, oral methionine decreased BAR by -2.04% (95% CI -2.58, -1.50%), p<0.001) with no significant difference between groups (p=0.42). After phlebotomy, the BAR response to oral methionine did not significantly change between groups (p=0.53). Brachial artery nitroglycerin-mediated dilation did not change in response to phlebotomy. CONCLUSIONS:Four serial phlebotomy procedures over six months with or without intravenous iron supplementation did not alter vascular endothelial function in the brachial artery when compared with sham phlebotomy.

The Principal INvestigator Development and Resources (PINDAR) program was developed at the NYU-H+H Clinical and Translational Science Award (CTSA) hub in response to a perceived need for focused good clinical practice (GCP) training designed specifically for principal investigators (PIs) performing human subject research. PINDAR is a novel 6-hour, instructor lead, participatory, in-person course for PIs developed de novo, piloted, and implemented. One hundred and seventeen faculty PIs participated in PINDAR from November 2016 through September 2018. All obtained mutual recognition for ICH E6 GCP training from TransCelerate Biopharma. PINDAR was well received by participant PIs, and feedback surveys have revealed a high degree of satisfaction with the program. Other CTSA hubs and research-intensive health systems should consider adopting a similar course focused on GCP for PIs.

OBJECTIVES/OBJECTIVE:The aim of this study was to determine whether frailty is associated with increased bleeding risk in the setting of acute myocardial infarction (AMI). BACKGROUND:Frailty is a common syndrome in older adults. METHODS:Frailty was examined among AMI patients ≥65 years of age treated at 775 U.S. hospitals participating in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry from January 2015 to December 2016. Frailty was classified on the basis of impairments in 3 domains: walking (unassisted, assisted, wheelchair/nonambulatory), cognition (normal, mildly impaired, moderately/severely impaired), and activities of daily living. Impairment in each domain was scored as 0, 1, or 2, and a summary variable consisting of 3 categories was then created: 0 (fit/well), 1 to 2 (vulnerable/mild frailty), and 3 to 6 (moderate-to-severe frailty). Multivariable logistic regression was used to examine the independent association between frailty and bleeding. RESULTS:Among 129,330 AMI patients, 16.4% had any frailty. Frail patients were older, more often female, and were less likely to undergo cardiac catheterization. Major bleeding increased across categories of frailty (fit/well 6.5%; vulnerable/mild frailty 9.4%; moderate-to-severe frailty 9.9%; p < 0.001). Among patients who underwent catheterization, both frailty categories were independently associated with bleeding risk compared with the non-frail group (vulnerable/mild frailty adjusted odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.23 to 1.44; moderate-to-severe frailty adjusted OR: 1.40, 95% CI: 1.24 to 1.58). Among patients managed conservatively, there was no association of frailty with bleeding (vulnerable/mild frailty adjusted OR: 1.01, 95% CI: 0.86 to 1.19; moderate-to-severe frailty adjusted OR: 0.96, 95% CI: 0.81 to 1.14). CONCLUSIONS:Frail patients had lower use of cardiac catheterization and higher risk of major bleeding (when catheterization was performed) than nonfrail patients, making attention to clinical strategies to avoid bleeding imperative in this population.

To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n = 34) and non-gout healthy controls (n = 64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20 ± 0.53 vs 3.56 ± 0.31, p = 0.021) and NMD (16.69 ± 1.54 vs 24.51 ± 0.90, p = 0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta = - 1.36 (SE 0.58), p = 0.02; adjusted beta = - 1.16 (SE 0.78), p = 0.14 and NMD unadjusted beta = - 7.68 (SE 1.78), p < 0.0001; adjusted beta = - 5.33 (SE 2.46), p = 0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R = - 0.5, p = 0.003), and between FMD and hsCRP (R = - 0.42, p = 0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.

BACKGROUND: Interventions to reduce readmissions following acute heart failure hospitalization require early identification of patients. The purpose of this study was to develop and test accuracies of various approaches to identify patients with acute decompensated heart failure (ADHF) using data derived from the electronic health record. METHODS AND RESULTS: We included 37,229 hospitalizations of adult patients at a single hospital in 2013-2015. We developed four algorithms to identify hospitalization with a principal discharge diagnosis of ADHF: 1) presence of one of three clinical characteristics; 2) logistic regression of 31 structured data elements; 3) machine learning with unstructured data; 4) machine learning with both structured and unstructured data. In data validation, Algorithm 1 had a sensitivity of 0.98 and positive predictive value (PPV) of 0.14 for ADHF. Algorithm 2 had an area under the receiver operating characteristic curve (AUC) of 0.96, while both machine learning algorithms had AUCs of 0.99. Based on a brief survey of three providers who perform chart review for ADHF, we estimated providers spent 8.6 minutes per chart review; using this this parameter, we estimated providers would spend 61.4, 57.3, 28.7, and 25.3 minutes on secondary chart review for each case of ADHF if initial screening was done with algorithms 1, 2, 3, and 4, respectively. CONCLUSION: Machine learning algorithms with unstructured notes had best performance for identification of ADHF and can improve provider efficiency for delivery of quality improvement interventions.