Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro.

BACKGROUND: Transient receptor potential vanilloid 2 is a calcium channel activated by probenecid. Probenecid is a Food and Drug Administration-approved uricosuric drug that has recently been shown to induce positive lusitropic and inotropic effects in animal models through cardiomyocyte transient receptor potential vanilloid 2 activation. The aim of this study was to test the hypothesis that oral probenecid can improve cardiac function and symptomatology in patients with heart failure with reduced ejection fraction and to further elucidate its calcium-dependent effects on myocyte contractility. METHODS AND RESULTS: The clinical trial recruited stable outpatients with heart failure with reduced ejection fraction randomized in a single-center, double-blind, crossover design. Clinical data were collected including a dyspnea assessment, physical examination, ECG, echocardiogram to assess systolic and diastolic function, a 6-minute walk test, and laboratory studies. In vitro force generation studies were performed on cardiomyocytes isolated from murine tissue exposed to probenecid or control treatments. The clinical trial recruited 20 subjects (mean age 57 years, mean baseline fractional shortening of 13.6±1.0%). Probenecid therapy increased fractional shortening by 2.1±1.0% compared with placebo -1.7±1.0% (P=0.007). Additionally, probenecid improved diastolic function compared with placebo by decreasing the E/E' by -2.95±1.21 versus 1.32±1.21 in comparison to placebo (P=0.03). In vitro probenecid increased myofilament force generation (92.36 versus 80.82 mN/mm2, P<0.05) and calcium sensitivity (pCa 5.67 versus 5.60, P<0.01) compared with control. CONCLUSIONS: Probenecid improves cardiac function with minimal effects on symptomatology and no significant adverse effects after 1 week in patients with heart failure with reduced ejection fraction and increases force development and calcium sensitivity at the cardiomyocyte level. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01814319.

Improvement in health-related quality of life after hospitalization predicts event-free survival in patients with advanced heart failure.

BACKGROUND: Health-related quality of life (HRQOL) is a major clinical outcome for heart failure (HF) patients. We aimed to determine the frequency, durability, and prognostic significance of improved HRQOL after hospitalization for decompensated HF. METHODS AND RESULTS: We analyzed HRQOL, measured serially using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), for 425 patients who survived to discharge in a multicenter randomized clinical trial of pulmonary artery catheter versus clinical assessment to guide therapy for patients with advanced HF. All patients enrolled had 1 or more prior HF hospitalizations or chronic high diuretic doses and 1 or more symptom and 1 sign of fluid overload at admission. Improvement, defined as a decrease of more than 5 points in MLHFQ total score, occurred in 68% of patients by 1 month and stabilized. The degree of 1-month improvement differed (P < .0001 group x time interaction) between 6-month survivors and non-survivors. In a Cox regression model, after adjustment for traditional risk factors for HF morbidity and mortality, improvement in HRQOL by 1 month compared to worsening at 1 month or no change predicted time to subsequent event-free survival (P=.013). CONCLUSIONS: In patients hospitalized with severe HF decompensation, HRQOL is seriously impaired but improves substantially within 1 month for most patients and remains improved for 6 months. Patients for whom HRQOL does not improve by 1 month after hospital admission merit specific attention both to improve HRQOL and to address high risk for poor event-free survival.

Prediction of rehospitalization and death in severe heart failure by physicians and nurses of the ESCAPE trial.

BACKGROUND: The predictive accuracy of physician investigators and nurse coordinators in estimating the risk of rehospitalization and death was determined for 373 hospitalized patients with severe advanced heart failure enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial. METHODS AND RESULTS: Estimates were made at discharge, and patients were followed for 6 months after hospitalization. A statistical prognostic model was developed from clinical and laboratory data for the end points of rehospitalization and death. Both nurse and physician predictions of death were generally associated with the observed deaths (c-indices of 0.675 and 0.611), although the nurses' prediction was significantly better (chi-square = 4.75, P = .029). The prediction ability of the prognostic model was similar to the physicians' model (c-index = 0.603). The predictions of rehospitalization were much weaker for nurse, physician and prognostic models. CONCLUSIONS: Nurses' estimations of survival in discharged, advanced-stage heart failure patients were superior to either physicians' or model-based predictions. Not nurses, physicians, or the prognostic model provided useful predictions for rehospitalizations, but this may have resulted from the fact that the rehospitalization estimates did not include the death risk.

Case management for heart failure in the emergency department.

Heart failure affects approximately 5 million individuals in the United States and is the most common discharge diagnosis among the elderly. The number of individuals diagnosed with heart failure will continue to rise as the population of the United States ages. The natural course of the disease is characterized by periods of stability interrupted by periods of symptom exacerbation. These periods of exacerbation often require emergency intervention or hospitalization for management. Once an individual is hospitalized, they are at a greater risk for rehospitalization. The causes of rehospitalizations are multifactorial and many are preventable. Case managers are in a position to have a positive impact on the readmission rate. Interventions include adherence to medication guidelines, increasing patients' knowledge of self-care measures, assessing discharge readiness and needs, and increasing the frequency of symptom monitoring for early intervention. Case management begins in the emergency department and facilitates care throughout the patient's stay by fostering communication among all caregivers and the patient and family. Case managers also affect the quality of care patients receive by instituting processes that streamline care and ensure that quality care is provided to the patients. They also serve as mentors and resources for other members of the healthcare team. Most of the information about case management comes from inpatient and outpatient programs; however, the emergency department nurse can adapt these models to support their role. More research is needed as to what specific portions of the case manager's role are most appropriate for the emergency department.

Strongyloides hyperinfection syndrome after heart transplantation: case report and review of the literature.

Stronglyoides hyperinfection syndrome (SHS) is an augmentation of the infective life cycle of S stercoralis. Immunosuppressed patients, especially those taking corticosteroid therapy, are at risk. We present a case of fatal SHS with disseminated infection following orthotopic heart transplantation. The patient was treated with increased doses of immunosuppressive medications for graft rejection, including corticosteroids. A review of the literature describing the pathophysiology, host defenses and treatment of SHS is also presented. Diagnostic tests for S stercoralis are reviewed. SHS should be part of the differential diagnosis in immunosuppressed patients presenting with sepsis or gastrointestinal or pulmonary complaints. Pretransplant evaluation for parasitic infections, including strongyloidiasis, should occur in endemic areas or in patients at risk for occult infestation.