Livia Adams Goldraich

Cost-effectiveness of heart failure therapies

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Management of HF involves accurate diagnosis and implementation of evidence-based treatment strategies. Costs related to the care of patients with HF have increased substantially over the past 2 decades, partly owing to new medications and diagnostic tests, increased rates of hospitalization, implantation of costly novel devices and, as the disease progresses, consideration for heart transplantation, mechanical circulatory support, and end-of-life care. Not surprisingly, HF places a huge burden on health-care systems, and widespread implementation of all potentially beneficial therapies for HF could prove unrealistic for many, if not all, nations. Cost-effectiveness analyses can help to quantify the relationship between clinical outcomes and the economic implications of available therapies. This Review is a critical overview of cost-effectiveness studies on key areas of HF management, involving pharmacological and nonpharmacological clinical therapies, including device-based and surgical therapeutic strategies.

Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression

Abstract Context: Elevated plasmatic microRNAs (miRs) are observed in heart failure (HF). However, the cardiac origin of these miRs remains unclear. Objective: We calculated transcoronary gradients of miR-29b, miR-133a and miR-423-5p in 17 outpatients with stable systolic HF and in controls without structural cardiac disease. Materials and methods: MicroRNAs were measured by quantitative real-time polymerase chain reaction. Results: Positive transcoronary miR gradients were observed in patients with HF but not in controls (p = 0.03). B-type natriuretic peptide (BNP) moderately correlated with the transcoronary gradients of miR-133a and miR-423-5p. Discussion and conclusions: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.

Manejo não-farmacológico de pacientes hospitalizados com insuficiência cardíaca em hospital universitário

OBJETIVO: Descrever o manejo nao-farmacologico de pacientes internados com insuficiencia cardiaca (IC) em um hospital universitario. METODOS: Estudo de coorte longitudinal de pacientes com IC diagnosticados pelo escore de Boston. Durante as 72 horas iniciais de internacao, enfermeiras da clinica de IC realizaram entrevistas padronizadas e revisoes de prontuarios. RESULTADOS: Foram avaliadas 283 internacoes de 239 pacientes (idade = 64 ± 15 anos), aproximadamente 50% sexo masculino e 37% de etiologia isquemica. O padrao de prescricao dos diferentes cuidados nao-farmacologicos foi restricao de sal em 97%, controle de diurese em 85%, balanco hidrico em 75%, controle de peso em 61% e restricao hidrica em apenas 25% das internacoes. Embora os cuidados referidos estivessem nas prescricoes, frequentemente nao eram realizados pela equipe responsavel (p < 0,01 para todas as comparacoes). O uso irregular dos farmacos prescritos na semana anterior a hospitalizacao ocorreu em 22% e 21% dos pacientes sem e com re-internacoes, respectivamente (p = 1,00). Os pacientes com reinternacoes (n = 38) apresentaram disfuncao sistolica grave, mais hospitalizacoes previas e tempo prolongado de sintomas de IC, quando comparados aos nao-reinternados, alem de terem conhecimento mais adequado de aspectos relacionados com autocuidado (todos valores de p < 0,05). Na analise multivariada, apenas tempo de doenca sintomatica permaneceu como preditor independente de reinternacoes. CONCLUSAO: Nossos dados indicam que mesmo em hospital universitario ha importantes lacunas relativas a prescricao e realizacao de medidas nao-farmacologicas de autocuidado na IC. Demonstramos que pacientes que reinternam aparentam bom conhecimento da doenca; esse achado, entretanto, esta relacionado de forma importante com a gravidade e o tempo de evolucao da IC.

Genetic polymorphisms of the adrenergic system and implantable cardioverter-defibrillator therapies in patients with heart failure

AIMS We investigated whether the combination of beta(1)-Gly389Arg and GNB3 C825T, two genetic polymorphisms strictly related to adrenergic system modulation, could act as predictors of appropriate therapies in patients with heart failure (HF) using implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS Patients with HF and ICD implantation for primary and secondary prevention were studied. All ICD therapies were registered and classified as appropriate (secondary to ventricular tachycardia) or inappropriate (others). Genetic analysis was performed by polymerase chain reaction and restriction fragment length polymorphism methods. Seventy-three patients with mean left ventricular ejection fraction of 35 +/- 11% were evaluated. Overall, 35 ICD therapies occurred during follow-up in 31 (42.5%) patients. Twenty-four therapies (33%) were appropriate, and 11 (15%) were inappropriate. Individual analysis of each polymorphism only identified T825 carriers of GNB3 C825T as predictor of appropriate shocks. The combined presence of risk genotypes (Arg389 of the beta(1)-Gly389Arg and T825 of the GNB3 C825T) identified patients with higher risk of appropriate shocks. Patients with two at-risk genotypes had a survival rate free of appropriate shocks lower than those with none or only one of these markers (87 vs. 54%, respectively; log-rank statistic = 0.006). Using a Cox regression model, each at-risk genotype was associated with an increment of risk of appropriate ICD shocks (odds ratio = 3.9, 95% confidence interval of 1.3-12.0; P = 0.02). CONCLUSION Genetic polymorphisms of the adrenergic system may help to identify HF patients who are more likely to receive appropriate ICD therapies. Further studies are necessary to determine the clinical applicability of these polymorphisms as predictors of arrhythmias.

Are scores useful in advanced heart failure

Advanced heart failure (HF) is becoming an increasingly challenging problem as more patients with this disease are living longer, yet experiencing its inexorable progression. Adding to this complex matter, there are different views on how to define advanced HF, whereby an acute decompensation episode does not necessarily indicate advanced disease. Several scores have been described aiming at a better prognostic performance across the HF spectrum. These include the Heart Failure Survival Score, the Seattle Heart Failure Model, the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure predictive schemes, the Acute Decompensated Heart Failure National Registry regression tree discrimination, among others. Most scoring systems have been built based on outpatient populations or recently hospitalized HF subjects. The setting of advanced HF has not gained much attention as far as prognostication is concerned, and yet there lies potentially challenging decision-making situations where issues, such as heart transplantation, use of costly devices and end-of-life questions, are raised.

Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis

Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at ≥2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long‐term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow‐up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2‐year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV.

Anemia in Heart Failure: Association of Hepcidin Levels to Iron Deficiency in Stable Outpatients

Background: Anemia is a prevalent condition in heart failure with multiple potential causes. The complex interaction between iron stores, hepcidin, inflammation and anemia is poorly comprehended. We tested the hypothesis that, in stable heart failure patients with anemia, hepcidin is associated with iron deficiency status irrespective of inflammation. Methods and Results: Stable systolic heart failure outpatients with and without anemia underwent a complete iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-α assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean hemoglobin 11.4 ± 1 g/dl) were older (69.6 ± 9.6 vs. 58 ± 10.8 years old, p < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 ± 1.1 g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-α and hepcidin were 29 and 21% higher in patients with anemia, respectively, compared to nonanemic patients; however, no correlations were found between hepcidin and TNF-α levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were strongly associated with iron deficiency (OR 16.5, 95% CI 2.2–121.2; p < 0.01). Conclusion: In stable heart failure patients with anemia, hepcidin levels may be more importantly regulated by patients’ iron stores than by inflammation.

Triceps skinfold as a prognostic predictor in outpatient heart failure

Background Most reports regarding the obesity paradox have focused on body mass index (BMI) to classify obesity and the prognostic values of other indirect measurements of body composition remain poorly examined in heart failure (HF). Objective To evaluate the association between BMI and other indirect, but easily accessible, body composition measurements associated with the risk of all-cause mortality in HF. Methods Anthropometric parameters of body composition were assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of ≤50% from a prospective HF cohort that was followed-up for 30 ± 8.2 months. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. Results HF patients were predominantly male, of non-ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 ± 9%). Triceps skinfold (TSF) was the only anthropometric index that was associated with HF prognosis and had significantly lower values in patients who died (p = 0.047). A TSF ≥ 20 mm was present in 9% of patients that died and 22% of those who survived (p = 0.027). Univariate analysis showed that serum creatinine level, LVEF, and NYHA class were associated with the risk of death, while Cox proportional hazard regression analysis showed that TSF ≥ 20 was a strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95% CI = 0.13-0.97, p = 0.03). Conclusion Although BMI is the most widely used anthropometric parameter in clinical practice, our results suggested that TSF is a better predictive marker of mortality in HF outpatients.

Serum procollagen type III is associated with elevated right-sided filling pressures in stable outpatients with congestive heart failure

Elevated filling pressures are associated with heart failure deterioration, but mechanisms underlying this association remain poorly understood. We sought to investigate whether or not elevated filling pressures are associated with increased collagen turnover, evaluated by procollagen type III aminoterminal peptide (PIIINP) levels, in stable systolic heart failure. Eighty patients with heart failure with severe systolic dysfunction (ejection fraction 26 ± 7%) were included. Patients underwent simultaneous echocardiogram with evaluation of haemodynamic parameters and blood sampling for PIIINP measurement. Mean PIIINP level was 6.11 ± 2.62 μg l−1. PIIINP was positively associated with estimated right atrial pressure (RAP) (r = 0.36; p = 0.001). Mean PIIINP values were 5.04 ± 2.42 μg l−1 in patients with estimated RAP ≤ 5 mmHg, and 7.59 ± 2.54 μg l−1 in those with RAP > 15 mmHg (p < 0.01). In conclusion, elevated right-side filling pressures are associated with evidence of active extracellular matrix turnover, as indicated by elevated PIIINP levels, in stable systolic heart failure. Activation of extracellular matrix turnover may be implicated in the accelerated progression of heart failure syndromes seen in patients with persistent congestion.

Association between Spirituality and Adherence to Management in Outpatients with Heart Failure

Background Spirituality may influence how patients cope with their illness. Objectives We assessed whether spirituality may influence adherence to management of outpatients with heart failure. Methods Cross sectional study enrolling consecutive ambulatory heart failure patients in whom adherence to multidisciplinary treatment was evaluated. Patients were assessed for quality of life, depression, religiosity and spirituality utilizing validated questionnaires. Correlations between adherence and psychosocial variables of interest were obtained. Logistic regression models explored independent predictors of adherence. Results One hundred and thirty patients (age 60 ± 13 years; 67% male) were interviewed. Adequate adherence score was observed in 38.5% of the patients. Neither depression nor religiosity was correlated to adherence, when assessed separately. Interestingly, spirituality, when assessed by both total score sum (r = 0.26; p = 0.003) and by all specific domains, was positively correlated to adherence. Finally, the combination of spirituality, religiosity and personal beliefs was an independent predictor of adherence when adjusted for demographics, clinical characteristics and psychosocial instruments. Conclusion Spirituality, religiosity and personal beliefs were the only variables consistently associated with compliance to medication in a cohort of outpatients with heart failure. Our data suggest that adequately addressing these aspects on patient’s care may lead to an improvement in adherence patterns in the complex heart failure management.