Faculty Bibliography

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.

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.

BACKGROUND: The prevalence and significance of right ventricular dysfunction (RVD) in patients with cardiogenic shock due to acute myocardial infarction (AMI-CS) has not been well characterized. We hypothesized that RVD is common in AMI-CS and associated with worse clinical outcomes. METHODS AND RESULTS: We retrospectively analyzed patients with available hemodynamics enrolled in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK (SHOCK) Trial (n=139) and Registry (n=258) to identify RVD in AMI-CS. RVD was defined by an elevated central venous pressure (CVP), elevated CVP/ pulmonary capillary wedge pressure (PCWP) ratio, decreased pulmonary artery pulsatility index (PAPi), and decreased right ventricular stroke work index (RVSWI). A p value of less than 0.01 was used to infer significance. In both the SHOCK trial and registry, 38% and 37% of patients had RVD, however RVD was not associated with 30-day or 6-month survival (HR 1.51 (0.92, 2.49) p=0.10). RV failure using inclusion criteria from the Recover Right Trial for RV failure (RR-RVF) requiring percutaneous mechanical circulatory support included an elevated CVP, CVP/PCWP ratio, and a low cardiac index despite >/=1 inotrope or vasopressor. In both the SHOCK trial and registry, 45% (n=63/139) and 38% (n=98/258) of patients met RR-RVF criteria respectively. The RR-RVF criteria were not significantly associated with 30-day mortality in the registry cohort (HR 1.44 (1.01,2.04), p=0.04), or in the trial cohort (HR 1.51(0.92,2.49), p=0.10). CONCLUSIONS: Hemodynamically defined RVD is common in AMI-CS. Routine assessment with PA catherization allows detection of RVD; however, further work is needed to identify interventions that will result in improved outcomes for these patients.

Heart failure is a common form of heart disease associated with progressive exercise intolerance and high risk of adverse clinical outcome events. The pathophysiology of chronic systolic heart failure is fundamentally determined by the failure of the circulatory system to deliver oxygen sufficient for metabolic needs, and it is best explained by a complex interplay between intrinsic abnormalities of ventricular pump function and extracardiac factors that limit oxygen use in metabolically active tissues. This brief review highlights the role of extracardiac factors (peripheral factors) that may impact exercise capacity in patients with chronic systolic heart failure. Reduced metabolic vasodilation limits delivery of available cardiac output reserve to skeletal muscle during exercise, and it is associated with reduced peak oxygen capacity. Abnormal substrate use in skeletal muscle due to reduced skeletal muscle mass, change in skeletal muscle fiber type, and mitochondrial dysfunction reduces work efficiency and submaximal exercise endurance capacity in patients with systolic heart failure. These extracardiac peripheral mechanisms of impaired exercise tolerance in chronic heart failure may be targets for novel therapeutic development in this patient population.