Faculty Bibliography

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.

Reduced parasympathetic modulation of heart rate is an independent predictor of mortality in heart failure. It is not known whether enhancing parasympathetic outflow to the heart impacts survival in these patients. Our aim was to evaluate whether the neck collar technique, a noninvasive method of stimulating the carotid baroreceptors, was a reliable and reproducible means to evaluate baroreflex control of heart rate in patients with heart failure. Twenty-five patients (20 males, mean age 54 +/-10-years) with symptomatic heart failure (NYHA class II-III) were studied on two separate days, one week apart. All were free of cholesterol plaques in the carotid arteries. Blood pressure and RR intervals were measured continuously in the seated position. Graded pressure (-70 to +70 mmHg) was administered to the neck during a held expiration using a custom-designed collar. Maximum change in RR intervals was determined during the onset of neck pressure. Stimulus response curves were plotted for changes in RR intervals against estimated-carotid sinus pressure. The technique was well tolerated and there were no adverse events. The maximal differential, used to estimate baroreflex gain, was tightly correlated between visits 1 and 2 (R2= 0.8063, p < 0.0001). The corresponding "set point" of the reflex was also significantly correlated between visits (R2=0.3324 p=0.049). To our knowledge, this is the first time the neck collar technique has been validated in a medically fragile population. The technique is safe and reproducible and maybe useful to help understand whether strategies that enhance parasympathetic activity change outcomes in heart failure

Physical activity and cardiac rehabilitation (CR) are components of heart failure (HF) self-care. The aims of this study were to describe patterns of physical activity in African Americans (n = 30) with HF and to explore experience in CR. This was a mixed method, concurrent nested, predominantly qualitative study. Qualitative data were collected via interviews exploring typical physical activity, and CR experience. It was augmented by quantitative data measuring HF severity, self-care, functional capacity and depressive symptoms. Mean age was 60 +/- 15 years; 65% were New York Heart Association (NYHA) class III HF. Forty-three percent reported that they did less than 30 min of exercise in the past week; 23% were told "nothing" about exercise by their provider, and 53% were told to do "minimal exercise". A measure of functional capacity indicated the ability to do moderate activity. Two related themes stemmed from the narratives describing current physical activity: "given up" and "still trying". Six participants recalled referral to CR with one person participating. There was high concordance between qualitative and quantitative data, and evidence that depression may play a role in low levels of physical activity. Findings highlight the need for strategies to increase adherence to current physical activity guidelines in this older minority population with HF.

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: Comorbid diabetes is common in heart failure and associated with increased hospitalization and mortality. Nonetheless, the optimal treatment strategy for diabetes in heart failure patients remains poorly characterized, particularly among low income and minority populations. The purpose of this study was to evaluate the association between glycemic control and outcomes among patients with heart failure and diabetes who were seen in a safety net health care system. 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. Subjects with diagnoses of heart failure and diabetes mellitus were included if they had an outpatient visit in 2007-2010 with an HbA1c performed in the prior 90 days. HbA1c and covariates, including demographics, comorbidities, vital signs, labs, and prior utilization, were obtained from the HHC data warehouse, which was linked to the New York State Inpatient Database and to New York State Vital Statistics to ascertain hospitalization and mortality events, respectively. 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 4,723 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%

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.

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.

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.