Faculty Bibliography

BACKGROUND: Familial dysautonomia (FD) is a rare hereditary disease characterized by loss of afferent autonomic neural fiber signaling and consequent profound impairment of arterial baroreflex function and blood pressure regulation. Whether vascular endothelial dysfunction contributes to defective vasomotor control in this form of afferent autonomic failure is not known. METHODS: We assessed blood pressure response to orthostatic stress and vascular endothelial function with brachial artery reactivity testing in 34 FD subjects with afferent autonomic failure and 34 healthy control subjects. RESULTS: Forty-four percent of the afferent autonomic failure subjects had uncontrolled hypertension at supine rest (median systolic blood pressure = 148mm Hg, interquartile range (IQR) = 144-155mm Hg; median diastolic blood pressure = 83mm Hg, IQR = 78-105mm Hg), and 88% had abnormal response to orthostatic stress (median decrease in systolic blood pressure after upright tilt = 48mm Hg, IQR = 29-61mm Hg). Flow-mediated brachial artery reactivity did not differ in subjects with afferent autonomic failure vs. healthy control subjects (median = 6.00%, IQR = 1.86-11.77%; vs. median = 6.27%, IQR = 4.65-9.34%; P = 0.75). In afferent autonomic failure subjects, brachial artery reactivity was not associated with resting blood pressure or the magnitude of orthostatic hypotension but was decreased in association with reduced glomerular filtration rate (r = 0.62; P < 0.001). CONCLUSIONS: Brachial artery reactivity was preserved in subjects with afferent autonomic failure despite the presence of marked blood pressure dysregulation. Comorbid renal dysfunction was associated with reduced brachial artery reactivity.

BACKGROUND: Treatment of acute heart failure in the emergency department (ED) or observation unit is an alternative to hospitalization. Both ED management and observation unit management have been associated with reduced costs and may be used to avoid penalties related to rehospitalizations. The purpose of this study was to examine trends in ED visits for heart failure and disposition following such visits. METHODS: We used the National Hospital Ambulatory Medical Care Survey, a representative sample of ED visits in the United States, to estimate rates and characteristics of ED visits for heart failure between 2002 and 2010. The primary outcome was the discharge disposition from the ED. Regression models were fit to estimate trends and predictors of hospitalization and admission to an observation unit. RESULTS: The number of ED visits for heart failure remained stable over the period, from 914,739 in 2002 to 848,634 in 2010 (annual change -0.7%, 95% CI -3.7% to +2.5%). Of these visits, 74.2% led to hospitalization, wheras 3.1% led to observation unit admission. The likelihood of hospitalization did not change during the period (adjusted prevalence ratio 1.00, 95% CI 0.99-1.01 for each additional year), whereas admission to the observation unit increased annually (adjusted prevalence ratio 1.12, 95% CI 1.01-1.25). We observed significant regional differences in likelihood of hospitalization and observation admission. CONCLUSIONS: The number of ED visits for heart failure and the high proportion of ED visits with subsequent inpatient hospitalization have not changed in the last decade. Opportunities may exist to reduce hospitalizations by increasing short-term management of heart failure in the ED or observation unit.

BACKGROUND: Debate exists regarding the efficacy of a-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating a-blockers in myocardial infarction enrolling at least 100 patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion era (>50% undergoing reperfusion and/or receiving aspirin/statin) or pre-reperfusion era trials. RESULTS: Sixty trials with 102003 patients satisfied the inclusion criteria. In the acute myocardial infarction trials, a significant interaction (Pinteraction=0.02) was noted such that a-blockers reduced mortality in the pre-reperfusion[Incident Rate Ratio (IRR)=0.86, 95% CI 0.79-0.94] but not in the reperfusion era(IRR=0.98, 95% CI 0.92-1.05). In the pre-reperfusion era, a-blockers reduced cardiovascular mortality(IRR=0.87, 95% CI 0.78-0.98), myocardial infarction(IRR=0.78, 95% CI 0.62-0.97), and angina(IRR=0.88, 95% CI 0.82-0.95) with no difference for other outcomes. In the reperfusion era, a-blockers reduced myocardial infarction(IRR=0.72, 95% CI 0.62-0.83) (NNTB=209) and angina(IRR=0.80, 95% CI 0.65-0.98) (NNTB=26) at the expense of increase in heart failure(IRR=1.10, 95% CI 1.05-1.16) (NNTH=79), cardiogenic shock(IRR=1.29, 95% CI 1.18-1.41) (NNTH=90) and drug discontinuation(IRR=1.64, 95% CI 1.55-1.73) with no benefit for other outcomes. Benefits for recurrent myocardial infarction and angina in the reperfusion era appeared to be short-term (30-days). CONCLUSIONS: In contemporary practice of treatment of myocardial infarction, a-blockers have no mortality benefit but reduce recurrent myocardial infarction and angina (short-term) at the expense of increase in heart failure, cardiogenic shock and drug discontinuation. The guidelines should reconsider the strength of recommendations for a-blockers post myocardial infarction.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) have been investigated in small studies in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Erythropoiesis-stimulating agents did not show a clear effect on left ventricular function or clinical outcome, but some studies suggested an increased risk of thromboembolic events. METHODS: A systematic literature search in MEDLINE was performed, until December 2012. We included randomized clinical trials investigating the effect of ESAs in STEMI patients undergoing primary PCI, with >/=30 days of follow-up. The primary end point was a composite of all-cause mortality, myocardial infarction, and stent thrombosis after PCI. Secondary end point was all-cause mortality. RESULTS: Individual patient data were obtained from 10 of 11 trials, including 97.3% (1,242/1,277) of all patients randomized to control (n = 600) or to ESAs (n = 642). Baseline characteristics were well balanced between the treatment allocations. Mean follow-up time was 248 (+/-131) days. The primary end point occurred in 3.5% (20/577) in the control group and in 2.1% (13/610) in the ESA group (hazard ratio for ESAs, 0.63; 95% CI [0.31-1.27]; P = .20). Mortality occurred in 13 (2.3%) in the control group and 5 (0.8%) in the ESA group (hazard ratio for ESAs, 0.38; 95% CI [0.13-1.06]; P = .06). CONCLUSIONS: Erythropoiesis-stimulating agent administration does not result in an increased risk of adverse cardiac events in STEMI patients undergoing primary PCI. Results of ongoing studies may provide further insight to the potential beneficial clinical effects of ESAs in STEMI patients.

OBJECTIVE: Most of the day-to-day care for heart failure (HF) is done by the patient at home and requires skill in self-care. In this randomized controlled trial (RCT) we tested the efficacy of a community-based skill-building intervention on HF self-care, knowledge and health-related quality of life (HRQL) at 1- and 3-months. METHODS: An ethnically diverse sample (n=75) of patients with HF (53% female; 32% Hispanic, 27% Black; mean age 69.9+/-10 years) was randomized to the intervention group (IG) or a wait-list control group (CG). The protocol intervention focused on tactical and situational HF self-care skill development delivered by lay health educators in community senior centers. Data were analyzed using mixed (between-within subjects) ANOVA. RESULTS: There was a significant improvement in self-care maintenance [F(2,47)=3.42, p=.04, (Cohen's f=.38)], self-care management [F(2,41)=4.10, p=.02, (Cohen's f=.45) and HF knowledge [F(2,53)=8.00, p=.001 (Cohen's f=.54)] in the IG compared to the CG. CONCLUSIONS: The skill-building intervention improved self-care and knowledge but not HRQL in this community-dwelling sample. PRACTICE IMPLICATIONS: Delivering an intervention in a community setting using lay health educators provides an alternative to clinic- or home-based teaching that may be useful across diverse populations and geographically varied settings.

BACKGROUND: We have developed a novel and practical cardiovascular magnetic resonance (CMR) technique to evaluate left ventricular (LV) mitral annular motion by tracking the atrioventricular junction (AVJ). To test AVJ motion analysis as a metric for LV function, we compared AVJ motion variables between patients with hypertrophic cardiomyopathy (HCM), a group with recognized systolic and diastolic dysfunction, and healthy volunteers. METHODS: We retrospectively evaluated 24 HCM patients with normal ejection fractions (EF) and 14 healthy volunteers. Using the 4-chamber view cine images, we tracked the longitudinal motion of the lateral and septal AVJ at 25 time points during the cardiac cycle. Based on AVJ displacement versus time, we calculated maximum AVJ displacement (MD) and velocity in early diastole (MVED), velocity in diastasis (VDS) and the composite index VDS/MVED. RESULTS: Patients with HCM showed significantly slower median lateral and septal AVJ recoil velocities during early diastole, but faster velocities in diastasis. We observed a 16-fold difference in VDS/MVED at the lateral AVJ [median 0.141, interquartile range (IQR) 0.073, 0.166 versus 0.009 IQR -0.006, 0.037, P < 0.001]. Patients with HCM also demonstrated significantly less mitral annular excursion at both the septal and lateral AVJ. Performed offline, AVJ motion analysis took approximately 10 minutes per subject. CONCLUSIONS: Atrioventricular junction motion analysis provides a practical and novel CMR method to assess mitral annular motion. In this proof of concept study we found highly statistically significant differences in mitral annular excursion and recoil between HCM patients and healthy volunteers.