Faculty Bibliography

Left ventricular (LV) remodeling is the most common term used to describe the functional, structural, myocellular, and interstitial changes that occur in response to myocardial injury and/or chronic changes in myocardial loading conditions. Progression of LV remodeling over time in response to neurohormonal activation, increased wall stress, and inflammatory signaling pathways is associated with an increased risk of major morbidity and mortality. LV reverse remodeling describes the process by which an injured LV with a dilated spherical phenotype may return toward a normalization of ventricular structure and function, either spontaneously or in response to therapeutic interventions. LV reverse remodeling can occur in response to interventions that mitigate the source of myocardial injury, or that reduce or eliminate the neurohormonal and/or hemodynamic factors that contribute to the progression of the LV remodeling process. In this article, we review selected studies that demonstrate the LV reverse remodeling process in response to pharmacological, pacemaker device, and mechanical circulatory support device interventions. Future therapies targeting the physiological, neurohormonal, and/or molecular signaling pathways to effect reverse remodeling may further improve clinical outcomes in heart failure patients.

BACKGROUND: Self-care is the cornerstone of heart failure (HF) management. Numerous approaches to improving HF self-care, which involves adherence to the treatment plan, routine symptom monitoring, and the response to symptoms when they occur, have been developed with little impact on HF outcomes. On the basis of HF practice recommendations that patients receive education and counseling that emphasizes self-care and targets skill building of critical target behaviors, we are conducting a clinical trial designed to improve self-care among community-dwelling older adults using an innovative group-based, skill-building approach led by a trained health educator. OBJECTIVE: This article describes the study design and research methods used to implement and evaluate the intervention. METHODS: The study uses a staggered randomized controlled design to assess feasibility of providing an HF self-care intervention in a community group setting to improve HF self-care, knowledge, and health-related quality of life at 1 and 3 months. A community engagement approach is used to partner with the community throughout all phases of the project. Seventy-five older adults with HF are randomly assigned to the intervention consisting of six to eight 60-minute sessions held in community senior centers or to the wait-list control group. Focus groups are used to elicit feedback on the participants' experience in the program. RESULTS: Preliminary study participation data (n=60; women, 48%; black, 27%; Hispanic, 32%; mean [SD] age, 70 [10] years) and focus group feedback suggest that the delivery approach is feasible and acceptable, and the participants are very satisfied with the program. CONCLUSIONS: Implementation of a community-based HF self-care intervention delivered in partnership with established community-based centers is an innovative approach to intervention. If efficacy is demonstrated, this intervention has far-reaching implications for helping the growing population of HF patients in ethnically diverse communities.

AIM: To describe the results of the process evaluation of an exercise counseling intervention using motivational interviewing (MI). BACKGROUND: Exercise can safely be incorporated into heart failure self-care, but many lack access to cardiac rehabilitation. One alternative is to provide exercise counseling in the clinical setting. METHODS: This process evaluation was conducted according to previously established guidelines for health promotion programs. This includes an assessment of recruitment and retention, implementation, and reach. RESULTS: Desired number of subjects were recruited, but 25% dropped out during study. Good fidelity to the intervention was achieved; the use of MI was evaluated with improvement in adherence over time. Dose included initial session plus 12 weekly phone calls. Subjects varied in participation of daily diary usage. Setting was conducive to recruitment and data collection. CONCLUSIONS: Evaluating the process of an intervention provides valuable feedback on content, delivery and fidelity.

OBJECTIVE: Congenital insensitivity to pain with anhidrosis (CIPA) is caused by mutations in the NKTR1 gene. This affects the development of nerve growth factor (NGF)-dependent neurons including sympathetic cholinergic neurons in the skin, causing anhidrosis. Cardiovascular and blood pressure regulation appears normal, but the integrity of sympathetic adrenergic neurons has not been tested. METHODS: We examined the effect of posture on blood pressure, heart rate, plasma concentration of catecholamines, vasopressin, endothelin, and renin activity in 14 patients with CIPA, 10 patients with chronically deficient sympathetic activity (pure autonomic failure), and 15 normal age-matched controls. RESULTS: In all 14 patients with CIPA, plasma norepinephrine levels were very low or undetectable and failed to increase when the patient was upright, yet upright blood pressure was well maintained. Plasma epinephrine levels were normal and increased when the patient was upright. Plasma renin activity also increased appropriately when the patient was upright and after furosemide-induced volume depletion. Nitric oxide-mediated endothelial function was intact. Patients with pure autonomic failure also had very low levels of plasma norepinephrine both supine and upright, but in contrast to patients with CIPA failed to maintain blood pressure upright. INTERPRETATION: The results indicate that postganglionic sympathetic neurons are severely depleted in CIPA, but chromaffin cells of the adrenal medulla are spared. This confirms the differential effect of NGF signaling for sympathetic neural and chromaffin cell development. The finding that patients with CIPA maintain blood pressure well on standing challenges current concepts of the role of norepinephrine in the regulation of arterial pressure. Ann Neurol 2015;77:743-752.

Introduction: Endothelial dysfunction is a precursor and plays a significant role in development of atherosclerosis. Retrograde flow and resulting retrograde shear stress has been shown to adversely affect the endothelial function but the results may be flawed due to experimental conditions. Change in the limb position might result in increase in retrograde flow and adversely affect endothelial function. We hypothesized that elevation of arm above the level of the heart will result in increased retrograde flow and reduced endothelial function as measured by flow mediated dilation (FMD). Methods: We enrolled 27 healthy subjects after obtaining informed consent. Endothelial function was measured by FMD in brachial artery before and after arm elevation with elbow support for 30 minutes in fasting state. Flow velocities were recorded and analyzed at baseline, 10 and 20 minutes after arm elevation and at the end of 30 minutes. Results: The mean retrograde flow velocity was 9.9 +/- 7.75 cm/sec at baseline, which increased to 15.8 +/- 6.56 cm/sec (p=0.0019) after arm elevation. Out of the 27 subjects 21 (78%) subjects had increase in retrograde flow (20% or more). The difference in FMD change between the groups with increased or no change in retrograde flow was statistically non-significant (p=0.4). Conclusion: In conclusion arm elevation for 30 minutes was associated with statistically significant increase in retrograde flow without significant change in endothelial function in normal healthy subjects. The change in endothelial function between subjects who had augmented retrograde shear and those who did not was statistically not significant

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.