Faculty Bibliography

OBJECTIVES: The aim of this study was to characterize the association between decongestion therapy and 30-day outcomes in patients hospitalized for heart failure (HF). BACKGROUND: Loop diuretic agents are commonly prescribed for the treatment of symptomatic congestion in patients hospitalized for HF, but the association between loop diuretic agent dose response and post-discharge outcomes has not been well characterized. METHODS: Cox proportional hazards models were used to estimate the association among average loop diuretic agent dose, congestion status at discharge, and 30-day post-discharge all-cause mortality and HF rehospitalization in 3,037 subjects hospitalized with worsening HF enrolled in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study With Tolvaptan) study. RESULTS: In univariate analysis, subjects exposed to high-dose diuretic agents (>/=160 mg/day) had greater risk for the combined outcome than subjects exposed to low-dose diuretic agents (18.9% vs. 10.0%; hazard ratio: 2.00; 95% confidence interval: 1.64 to 2.46; p < 0.0001). After adjustment for pre-specified covariates of disease severity, the association between diuretic agent dose and outcomes was not significant (hazard ratio: 1.11; 95% confidence interval: 0.89 to 1.38; p = 0.35). Of the 3,011 subjects with clinical assessments of volume status, 2,063 (69%) had little or no congestion at hospital discharge. Congestion status at hospital discharge did not modify the association between diuretic agent exposure and the combined endpoint (p for interaction = 0.84). CONCLUSIONS: Short-term diuretic agent exposure during hospital treatment for worsening HF was not an independent predictor of 30-day all-cause mortality and HF rehospitalization in multivariate analysis. Congestion status at discharge did not modify the association between diuretic agent dose and clinical outcomes.

STUDY OBJECTIVE: Observation unit admissions have been increasing, a trend that will likely continue because of recent changes in reimbursement policies. The purpose of this study is to determine the effect of the availability of observation units on hospitalizations and discharges to home for emergency department (ED) patients. METHODS: We studied ED visits with a final diagnosis of chest pain in the National Hospital Ambulatory Medical Care Survey from 2007 to 2010. ED visits that resulted in an observation unit admission were propensity-score matched to visits at hospitals without an observation unit. We used logistic regression to develop a prediction model for hospitalization versus discharge home for matched patients treated at nonobservation hospitals. The model was applied to matched observation unit patients to determine the likely alternative disposition had the observation unit not been available. RESULTS: There were 1,325 eligible visits that represented 5,079,154 visits in the United States. Two hundred twenty-seven visits resulted in an observation unit admission. The predictive model for hospitalization had a c statistic of 0.91; variables significantly associated with subsequent hospitalization included age, history of coronary atherosclerosis, systolic blood pressure less than 115 beats/min, and administration of antianginal medications. When the model was applied to matched observation unit patients, 49.9% of them were categorized as discharge home likely. CONCLUSION: In this study, we estimated that half of ED visits for chest pain that resulted in an observation unit admission were made by patients who may have been discharged home had the observation unit not been available. Increased availability of observation units may result in both decreased hospitalizations and decreased discharges to home.

BACKGROUND: Comorbid diabetes is common in heart failure and associated with increased hospitalization and mortality. Nonetheless, the association between glycemic control and outcomes among patients with heart failure and diabetes remains poorly characterized, particularly among low income and minority patients. METHODS: We performed a retrospective cohort study of outpatients with heart failure and diabetes in the New York City Health and Hospitals Corporation, the largest municipal health care system in the United States. Cox proportional hazard models were used to measure the association between HbA1c levels and outcomes of all-cause hospitalization, heart failure hospitalization, and mortality. RESULTS: Of 4723 patients with heart failure and diabetes, 42.6 % were black, 30.5 % were Hispanic/Latino, 31.4 % were Medicaid beneficiaries and 22.9 % were uninsured. As compared to patients with an HbA1c of 8.0-8.9 %, patients with an HbA1c of <6.5, 6.5-6.9, 7.0-7.9, and >/=9.0 % had an adjusted hazard ratio (aHR) (95 % CI) for all-cause hospitalization of 1.03 (0.90-1.17), 1.05 (0.91-1.22), 1.03 (0.90-1.17), and 1.13 (1.00-1.28), respectively. An HbA1c >/= 9.0 % was also associated with an increased risk of heart failure hospitalization (aHR 1.33; 95 % CI 1.11-1.59) and a non-significant increased risk in mortality (aHR 1.20; 95 % CI 0.99-1.45) when compared to HbA1c of 8.0-8.9 %. CONCLUSIONS: Among a cohort of primarily minority and low income patients with heart failure and diabetes, an increased risk of hospitalization was observed only for an HbA1c greater than 9 %.

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22-57] to 22 % [19-31], p = 0.05) and NPA (19 % [16-59] to 15 % [11-30], p = 0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328-555] to 333 MFI [232-407], p = 0.02) and P-selectin (351 MFI [269-492] to 279 [226-364], p = 0.03), and platelet adhesion to collagen (10.2 % [2.5-32.6] to 2.0 % [0.2-9.5], p = 0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.

PURPOSE: The purpose of this pilot study was to test the impact of language-free, low literacy self-care management patient education materials in an ethnically diverse multilingual heart failure (HF) population. METHODS: A one group pre-test-post-test design measured changes in self-care, knowledge and health-related quality of life (HRQL) after a 1month intervention using language-free, low literacy self-care management patient education materials and delivered by a health educator. RESULTS: The ethnically diverse sample (n=21) was predominately male (72%), 48% Black, 42% Hispanic, and 28% marginal/inadequate literacy. There were significant improvements in self-care and knowledge but not HRQL. CONCLUSIONS: Language-free, low literacy self-care patient education may facilitate improved self-care and knowledge in diverse populations who are at risk for poor HF outcomes.

PURPOSE: Chest pain is a common emergency department (ED) presentation that is often unexplained. Recent evidence suggests that disease of the microvessels (arterioles) as opposed to the coronary artery (conduit artery) could explain one third of these cases, particularly in women. Brachial artery reactivity (BAR) is a validated surrogate measure of coronary artery vasomotion. OBJECTIVES: The goal of this study was to compare brachial artery conduit vessel function (BAR) and microvascular function (postischemic peak reactive hyperemia [RH]) in subjects with and without chest pain and grouped according to sex. METHODS: This prospective cohort study was conducted from January through March 2010. Cases were patients admitted to an ED chest pain center with low to moderate risk of acute coronary syndrome; they were eligible for study if their creatinine level was <2.0 mg/dL and systolic blood pressure was >100 mm Hg or <180 mm Hg. Asymptomatic healthy volunteers on no medications were recruited as control subjects. BAR as a change in brachial artery diameter in response to transient forearm ischemia (endothelium-dependent vasodilation) and RH as a change in flow velocities were measured with a high-resolution ultrasound. Telephone follow-up visits were made at 1 month for recurrence of chest pain and recidivism. FINDINGS: A total of 57 patients and 21 control subjects were enrolled; there was 100% follow-up at 1 month. Most patients (86%) had at least 1 cardiac risk factor. Neither BAR nor RH varied significantly between patients and control subjects (P > 0.05). Symptomatic men had lower mean BAR than women (2.67% vs 6.22%; P < 0.01), even when normalized for shear stress (P = 0.01). Conversely, women with chest pain had lower RH compared with men (2.85 vs 4.61; P = 0.01). The sex-specific differences adjusted for age and Framingham risk scores persisted for BAR (P = 0.003) and RH (P = 0.002). Of 57 patients, 53% had recurrent pain, and 4 returned to the hospital within 1 month. IMPLICATIONS: Differences in BAR and RH in patients ruled out for myocardial infarction suggest that the pathophysiology of acute chest pain might be sex-specific. Men with chest pain exhibited lower BAR, indicating peripheral conduit artery dysfunction. Conversely, women with chest pain exhibited lower postischemic peak hyperemia, indicative of peripheral microvascular dysfunction. Sex differences in pathophysiology of chest pain and vascular dysfunction could inform development of effective therapeutics for patients with recurrent or persistent chest pain in the absence of obstructive coronary artery disease.

Takotsubo cardiomyopathy (TC) often occurs after emotional or physical stress. Norepinephrine levels are unusually high in the acute phase, suggesting a hyperadrenergic mechanism. Comparatively little is known about parasympathetic function in patients with TC. We sought to characterize autonomic function at rest and in response to physical and emotional stimuli in 10 women with a confirmed history of TC and 10 age-matched healthy women. Sympathetic and parasympathetic activity was assessed at rest and during baroreflex stimulation (Valsalva maneuver and tilt testing), cognitive stimulation (Stroop test), and emotional stimulation (event recall, patients). Ambulatory blood pressure monitoring and measurement of brachial artery flow-mediated vasodilation were also performed. TC women (tested an average of 37 months after the event) had excessive pressor responses to cognitive stress (Stroop test: p <0.001 vs baseline and p = 0.03 vs controls) and emotional arousal (recall of TC event: p = 0.03 vs baseline). Pressor responses to hemodynamic stimuli were also amplified (Valsalva overshoot: p <0.05) and prolonged (duration: p <0.01) in the TC women compared with controls. Plasma catecholamine levels did not differ between TC women and controls. Indexes of parasympathetic (vagal) modulation of heart rate induced by respiration and cardiovagal baroreflex gain were significantly decreased in the TC women versus controls. In conclusion, even long after the initial episode, women with previous episode of TC have excessive sympathetic responsiveness and reduced parasympathetic modulation of heart rate. Impaired baroreflex control may therefore play a role in TC.