Richard P. Shannon

Potential Effects of Aggressive Decongestion During the Treatment of Decompensated Heart Failure on Renal Function and Survival

Background— Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function during the treatment of decompensated heart failure. If diuresis occurs at a rate greater than extravascular fluid can refill the intravascular space, the concentration of such intravascular substances as hemoglobin and plasma proteins increases. We hypothesized that hemoconcentration would be associated with worsening renal function and possibly would provide insight into the relationship between aggressive decongestion and outcomes. Methods and Results— Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited data set with a baseline/discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline-to-discharge increases in these parameters were evaluated, and patients with ≥2 in the top tertile were considered to have evidence of hemoconcentration. The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (P<0.05 for all). Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3; P<0.001), whereas changes in right atrial pressure (P=0.36) and pulmonary capillary wedge pressure (P=0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31; P=0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16; P=0.001). Conclusion— Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question of whether aggressive decongestion, even in the setting of worsening renal function, can positively affect survival.

Translating novel strategies for cardioprotection: the Hatter Workshop Recommendations

Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number of novel cardioprotective strategies have been discovered in the research laboratory, their translation to the clinical setting has been largely disappointing. The reason for this failure can be attributed to a number of factors including the inadequacy of the animal ischemia–reperfusion injury models used in the preclinical cardioprotection studies and the inappropriate design and execution of the clinical cardioprotection studies. This important issue was the main topic of discussion of the UCL-Hatter Cardiovascular Institute 6th International Cardioprotection Workshop, the outcome of which has been published in this article as the “Hatter Workshop Recommendations”. These have been proposed to provide guidance on the design and execution of both preclinical and clinical cardioprotection studies in order to facilitate the translation of future novel cardioprotective strategies for patient benefit.

The Extrapancreatic Effects of Glucagon-Like Peptide-1 and Related Peptides

CONTEXTnGlucagon-like peptide-1 (GLP-1) 7-36 amide, an insulinotropic hormone released from the intestinal L cells in response to nutrient ingestion, has been extensively reviewed with respect to beta-cell function. However GLP-1 receptors are abundant in many other tissues. Thus, the function of GLP-1 is not limited to the islet cells, and it has regulatory actions on many other organs.nnnEVIDENCE ACQUISITIONnA review of published, peer-reviewed medical literature (1987 to September 2008) on the extrapancreatic actions of GLP-1 was performed.nnnEVIDENCE SYNTHESISnThe extrapancreatic actions of GLP-1 include inhibition of gastric emptying and gastric acid secretion, thereby fulfilling the definition of GLP-1 as an enterogastrone. Other important extrapancreatic actions of GLP-1 include a regulatory role in hepatic glucose production, the inhibition of pancreatic exocrine secretion, cardioprotective and cardiotropic effects, the regulation of appetite and satiety, and stimulation of afferent sensory nerves. The primary metabolite of GLP-1, GLP-1 (9-36) amide, or GLP-1m, is the truncated product of degradation by dipeptidyl peptidase-4. GLP-1m has insulinomimetic effects on hepatic glucose production and cardiac function. Exendin-4 present in the salivary gland of the reptile, Gila monster (Heloderma suspectum), is a high-affinity agonist for the mammalian GLP-1 receptor. It is resistant to degradation by dipeptidyl peptidase-4, and therefore has a prolonged half-life.nnnCONCLUSIONnGLP-1 and its metabolite have important extrapancreatic effects particularly with regard to the cardiovascular system and insulinomimetic effects with respect to glucose homeostasis. These effects may be particularly important in the obese state. GLP-1, GLP-1m, and exendin-4 therefore have potential therapeutic roles because of their diffuse extrapancreatic actions.

Trials, tribulations and speculation! Report from the 7th Biennial Hatter Cardiovascular Institute Workshop

The 7th biennial Hatter Cardiovascular Institute Workshop, comprising 21 leading basic science and clinical experts, was held in South Africa in August 2012 to discuss the current cutting edge status of cardioprotection and the application of cardioprotective modalities in the clinical management of myocardial ischaemia/reperfusion injury in the context of acute coronary syndromes and cardiac surgery. The meeting, chaired by Professor Derek Yellon and Professor Lionel Opie, was run to a format of previous Hatter Cardiovascular workshops with data presented by proponents followed by discussion and debate by the faculty.

Understanding Why Patients Of Low Socioeconomic Status Prefer Hospitals Over Ambulatory Care

Patients with low socioeconomic status (SES) use more acute hospital care and less primary care than patients with high socioeconomic status. This low-value pattern of care use is harmful to these patients health and costly to the health care system. Many current policy initiatives, such as the creation of accountable care organizations, aim to improve both health outcomes and the cost-effectiveness of health services. Achieving those goals requires understanding what drives low-value health care use. We conducted qualitative interviews with forty urban low-SES patients to explore why they prefer to use hospital care. They perceive it as less expensive, more accessible, and of higher quality than ambulatory care. Efforts that focus solely on improving the quality of hospital care to reduce readmissions could, paradoxically, increase hospital use. Two different profile types emerged from our research. Patients in Profile A (five or more acute care episodes in six months) reported social dysfunction and disability. Those in Profile B (fewer than five acute care episodes in six months) reported social stability but found accessing ambulatory care to be difficult. Interventions to improve outcomes and values need to take these differences into account.

Use of benchmarking and public reporting for infection control in four high-income countries.

Benchmarking of surveillance data for health-care-associated infection (HCAI) has been used for more than three decades to inform prevention strategies and improve patients safety. In recent years, public reporting of HCAI indicators has been mandated in several countries because of an increasing demand for transparency, although many methodological issues surrounding benchmarking remain unresolved and are highly debated. In this Review, we describe developments in benchmarking and public reporting of HCAI indicators in England, France, Germany, and the USA. Although benchmarking networks in these countries are derived from a common model and use similar methods, approaches to public reporting have been more diverse. The USA and England have predominantly focused on reporting of infection rates, whereas France has put emphasis on process and structure indicators. In Germany, HCAI indicators of individual institutions are treated confidentially and are not disseminated publicly. Although evidence for a direct effect of public reporting of indicators alone on incidence of HCAIs is weak at present, it has been associated with substantial organisational change. An opportunity now exists to learn from the different strategies that have been adopted.

Patient-Centered Community Health Worker Intervention to Improve Posthospital Outcomes: A Randomized Clinical Trial

IMPORTANCE Socioeconomic and behavioral factors can negatively influence posthospital outcomes among patients of low socioeconomic status (SES). Traditional hospital personnel often lack the time, skills, and community linkages required to address these factors. OBJECTIVE To determine whether a tailored community health worker (CHW) intervention would improve posthospital outcomes among low-SES patients. DESIGN, SETTING, AND PARTICIPANTS A 2-armed, single-blind, randomized clinical trial was conducted between April 10, 2011, and October 30, 2012, at 2 urban, academically affiliated hospitals. Of 683 eligible general medical inpatients (ie, low-income, uninsured, or Medicaid) that we screened, 237 individuals (34.7%) declined to participate. The remaining 446 patients (65.3%) were enrolled and randomly assigned to study arms. Nearly equal percentages of control and intervention group patients completed the follow-up interview (86.6% vs 86.9%). INTERVENTIONS During hospital admission, CHWs worked with patients to create individualized action plans for achieving patients stated goals for recovery. The CHWs provided support tailored to patient goals for a minimum of 2 weeks. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was completion of primary care follow-up within 14 days of discharge. Prespecified secondary outcomes were quality of discharge communication, self-rated health, satisfaction, patient activation, medication adherence, and 30-day readmission rates. RESULTS Using intention-to-treat analysis, we found that intervention patients were more likely to obtain timely posthospital primary care (60.0% vs 47.9%; Pu2009=u2009.02; adjusted odds ratio [OR], 1.52; 95% CI, 1.03-2.23), to report high-quality discharge communication (91.3% vs 78.7%; Pu2009=u2009.002; adjusted OR, 2.94; 95% CI, 1.5-5.8), and to show greater improvements in mental health (6.7 vs 4.5; Pu2009=u2009.02) and patient activation (3.4 vs 1.6; Pu2009=u2009.05). There were no significant differences between groups in physical health, satisfaction with medical care, or medication adherence. Similar proportions of patients in both arms experienced at least one 30-day readmission; however, intervention patients were less likely to have multiple 30-day readmissions (2.3% vs 5.5%; Pu2009=u2009.08; adjusted OR, 0.40; 95% CI, 0.14-1.06). Among the subgroup of 63 readmitted patients, recurrent readmission was reduced from 40.0% vs 15.2% (Pu2009=u2009.03; adjusted OR, 0.27; 95% CI, 0.08-0.89). CONCLUSIONS AND RELEVANCE Patient-centered CHW intervention improves access to primary care and quality of discharge while controlling recurrent readmissions in a high-risk population. Health systems may leverage the CHW workforce to improve posthospital outcomes by addressing behavioral and socioeconomic drivers of disease. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01346462.

Interaction between loop diuretic-associated mortality and blood urea nitrogen concentration in chronic heart failure.

OBJECTIVESnThe purpose of this study was to investigate whether a surrogate for renal neurohormonal activation, blood urea nitrogen (BUN), could identify patients destined to experience adverse outcomes associated with the use of high-dose loop diuretics (HDLD).nnnBACKGROUNDnLoop diuretics are commonly used to control congestive symptoms in heart failure; however, these agents cause neurohormonal activation and have been associated with worsened survival.nnnMETHODSnSubjects in the BEST (Beta-Blocker Evaluation of Survival Trial) receiving loop diuretics at baseline were analyzed (N = 2,456). The primary outcome was the interaction between BUN- and HDLD-associated mortality.nnnRESULTSnIn the overall cohort, HDLD use (≥160 mg/day) was associated with increased mortality (hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.35 to 1.80). However, after extensively controlling for baseline characteristics, this association did not persist (HR: 1.06; 95% CI: 0.89 to 1.25). In subjects with BUN levels above the median (21.0 mg/dl), both the unadjusted (HR: 1.59; 95% CI: 1.34 to 1.88) and adjusted (HR: 1.29; 95% CI: 1.07 to 1.60) risk of death was higher in the HDLD group. In patients with BUN levels below the median, there was no associated risk with HDLD (HR: 0.99; 95% CI: 0.75 to 1.34) and after controlling for baseline characteristics, the HDLD group had significantly improved survival (HR: 0.71; 95% CI: 0.49 to 0.96) (p interaction = 0.018).nnnCONCLUSIONSnThe risk associated with HDLD use is strongly dependent on BUN concentrations with reduced survival in patients with an elevated BUN level and improved survival in patients with a normal BUN level. These data suggest a role for neurohormonal activation in loop diuretic-associated mortality.

Effect of Right Ventricular Function and Venous Congestion on Cardiorenal Interactions During the Treatment of Decompensated Heart Failure

Recent reports have demonstrated the adverse effects of venous congestion on renal function (RF) and challenged the assumption that worsening RF is driven by decreased cardiac output (CO). We hypothesized that diuresis in patients with right ventricular (RV) dysfunction, despite decreased CO, would lead to a decrease in venous congestion and resultant improvement in RF. We reviewed consecutive admissions with a discharge diagnosis of heart failure. RV function was assessed by multiple echocardiographic methods and those with >or=2 measurements of RV dysfunction were considered to have significant RV dysfunction. Worsening RF was defined as an increase in creatinine of >or=0.3 mg/dl and improved RF as improvement in glomerular filtration rate >or=25%. A total of 141 admissions met eligibility criteria; 34% developed worsening RF. Venous congestion was more common in those with RV dysfunction (odds ratio [OR] 3.3, p = 0.009). All measurements of RV dysfunction excluding RV dilation correlated with CO (p <0.05). Significant RV dysfunction predicted a lower incidence of worsening RF (OR 0.21, p <0.001) and a higher incidence of improved RF (OR 6.4, p <0.001). CO emerged as a significant predictor of change in glomerular filtration rate during hospitalization in those without significant RV dysfunction (r = 0.38, p <0.001). In conclusion, RV dysfunction is a strong predictor of improved renal outcomes in patients with acute decompensated heart failure, an effect likely mediated by relief of venous congestion.

GLP-1 (9–36) Amide, Cleavage Product of GLP-1 (7–36) Amide, Is a Glucoregulatory Peptide

Objective: Glucagon‐like peptide‐1 (GLP‐1) (7–36) amide is a glucoregulatory hormone with insulinotropic and insulinomimetic actions. We determined whether the insulinomimetic effects of GLP‐1 are mediated through its principal metabolite, GLP‐1 (9–36) amide (GLP‐1m).