Prevalence and Correlates of Cost-Related Medication Nonadherence to Immunosuppressive Drugs After Heart Transplantation: The International Multicenter Cross-sectional Bright Study

Cost-related medication nonadherence (CRMNA) refers to not taking medications as prescribed because of difficulties paying for them.; The aims of this study were (1) to assess the prevalence of CRMNA to immunosuppressants in heart transplant recipients internationally and (2) to determine multilevel correlates (patient, center, and healthcare system levels) of CRMNA.; Using data from the cross-sectional international BRIGHT study, applying multistaged sampling, CRMNA was assessed via 3 self-report items in 1365 patients from 36 heart transplant centers in 11 countries. Cost-related medication nonadherence was defined as any positive answer on any of the 3 items. Healthcare system-level (ie, insurance coverage, out-of-pocket expenditures) and patient-level (ie, intention, perceived financial burden, cost as a barrier, a health belief regarding medication benefits, cost-related self-efficacy, and demographic factors) CRMNA correlates were assessed. Correlates were examined using mixed logistic regression analysis.; Across all study countries, CRMNA had an average prevalence of 2.6% (range, 0% [Switzerland/Brazil] to 9.8% [Australia]) and was positively related to being single (odds ratio, 2.29; 95% confidence interval, 1.17-4.47), perceived financial burden (odds ratio, 2.15; 95% confidence interval, 1.55-2.99), and cost as a barrier (odds ratio, 2.60; 95% confidence interval, 1.66-4.07). Four protective factors were identified: white ethnicity (odds ratio, 0.37; 95% confidence interval, 0.19-0.74), intention to adhere (odds ratio, 0.44; 95% confidence interval, 0.31-0.63), self-efficacy (odds ratio, 0.54; 95% confidence interval, 0.43-0.67), and belief about medication benefit (odds ratio, 0.70; 95% confidence interval, 0.57-0.87). Regarding variability, 81.3% was explained at the patient level; 13.8%, at the center level; and 4.8%, at the country level.; In heart transplant recipients, the CRMNA prevalence varies across countries but is lower than in other chronically ill populations. Identified patient-level correlates are novel (ie, intention to adhere, cost-related barriers, and cost-related self-efficacy) and indicate patient-perceived medication cost burden

The influence of metformin and the presence of type 2 diabetes mellitus on mortality and hospitalisation in patients with heart failure

Background: Metformin is one of the antihyperglycaemic drugs, reducing the risk of major cardiovascular events, including fatal ones. Although it is formally contraindicated in moderate and severe functional stages of heart failure (HF), it is commonly used in patients with concomitant type 2 diabetes mellitus (T2DM).Aim: We sought to evaluate the effect of metformin and T2DM on total mortality and hospitalisation rates in patients with HF.Methods: This retrospective analysis included 1030 adult patients (> 18 years) with HF from the Polish section of the HF Long-Term Registry (enrolled between 2011 and 2014). Patients with T2DM (n = 350) were identified and divided into two groups: those receiving metformin and those not. Both groups were subjected to one-year follow-up.Results: Mean patient age was 65.3 ± 13.5 years, with the predominance of male sex (n = 726) and obesity (mean bodymass index 30.3 ± 5.5 kg/m2) and mean left ventricular ejection fraction was 34.3% ± 14.1%. Among patients with T2DM (n = 350) only 135 (38.6%) were treated with metformin. During one-year follow-up, 128 patients with HF died, of whom 53 had T2DM (15.1% vs. 10.9%, hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.87–0.91, p = 0.045). Metformin was associated with a lower mortality rate compared to other antihyperglycaemic agents (9.6% vs. 18.6%, HR 0.85; 95% CI 0.81–0.89, p = 0.023). There were no significant differences in the hospitalisation rate, including that due to HF decompensation, among patients treated with metformin and the remainder (53.5% vs. 40.0%, respectively HR 0.93, 95% CI 0.82–1.04, p = 0.433).Conclusions: Metformin treatment in patients with different degrees of HF and T2DM is associated with a reduction in mortality and does not affect the hospitalisation rate

Nosocomial pneumonia in the postoperative period after heart transplantation

Introduction Infections are a major complication during the postoperative period after heart transplantation (HT). In our hospital, nosocomial pneumonia is the most frequent infection in this period. The objective of this study is to determine the epidemiological and microbiological characteristics of this disease in our centre. Methods A descriptive retrospective study of all medical records of HT performed in a single institution from 1991 to 2009 followed until June 2010. Clinical and microbiological variables were considered. Centre for Diseases Control (CDC) criteria were used to define nosocomial infections. Invasive aspergillosis was considered if there were criteria for probable aspergillosis according to IDSA criteria. Results In 594 HTs there were 97 infectious episodes in 75 patients (12.6%). Eighty-f ve patients (14.3%) died during hospitalization. Infection is the second cause of mortality during the postoperative period (17.9% of dead patients). The most common locations of infections were pneumonia (n = 31, 31.9% of infection episodes), bloodstream (n = 24, 24.7%), urinary tract (n = 14, 14.4%), surgical site (n = 13, 13.4%) and intraabdominal infections (n = 13, 13.4%). Patients with pneumonia were treated according to knowledge in a specif c moment, thus different antibiotics were used. The duration of antibiotic therapy was 20 + 15.5 days. In nine episodes of pneumonia according to the CDC no germ was isolated in the cultures. Six of the episodes were polymicrobial infections. The most frequent microbes isolated were E. coli (n = 7, 22.5% of pneumonia cases), A. fumigatus (n = 7, 22.5%), S. aureus (n = 3, 9.68%), P. aeruginosa (n = 3, 9.68%), P. mirabilis, K. pneumoniae, E. cloacae, E. faecalis, C. glabrata, and S. marcescens (one case each, 3.22%). Pneumonia was suspected but not confirmed in 75 patients. Despite this, antibiotic treatment was maintained for a media of 17.35 + 7.01 days: 56 wide-spectrum treatments and 18 targeted therapy after k

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry

AIMS To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). METHODS AND RESULTS Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. CONCLUSIONS In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category

Long‐term safety of intravenous cardiovascular agents in acute heart failure: results from the European Society of Cardiology Heart Failure Long‐Term Registry

[Abstract] Aims. The aim of this study was to assess long‐term safety of intravenous cardiovascular agents—vasodilators, inotropes and/or vasopressors—in acute heart failure (AHF). Methods and results. The European Society of Cardiology Heart Failure Long‐Term (ESC‐HF‐LT) registry was a prospective, observational registry conducted in 21 countries. Patients with unscheduled hospitalizations for AHF (n = 6926) were included: 1304 (18.8%) patients received a combination of intravenous (i.v.) vasodilators and diuretics, 833 (12%) patients received i.v. inotropes and/or vasopressors. Primary endpoint was long‐term all‐cause mortality. Main secondary endpoints were in‐hospital and post‐discharge mortality. Adjusted hazard ratio (HR) showed no association between the use of i.v. vasodilator and diuretic and long‐term mortality [HR 0.784, 95% confidence interval (CI) 0.596–1.032] nor in‐hospital mortality (HR 1.049, 95% CI 0.592–1.857) in the matched cohort (n = 976 paired patients). By contrast, adjusted HR demonstrated a detrimental association between the use of i.v. inotrope and/or vasopressor and long‐term all‐cause mortality (HR 1.434, 95% CI 1.128–1.823), as well as in‐hospital mortality (HR 1.873, 95% CI 1.151–3.048) in the matched cohort (n = 606 paired patients). No association was found between the use of i.v. inotropes and/or vasopressors and long‐term mortality in patients discharged alive (HR 1.078, 95% CI 0.769–1.512). A detrimental association with inotropes and/or vasopressors was seen in all geographic regions and, among catecholamines, dopamine was associated with the highest risk of death (HR 1.628, 95% CI 1.031–2.572 vs. no inotropes). Conclusions. Vasodilators did not demonstrate any association with long‐term clinical outcomes, while inotropes and/or vasopressors were associated with increased risk of all‐cause death, mostly related to excess of in‐hospital mortality in AHF

Conversion from immediate-release tacrolimus to prolonged-release tacrolimus in stable heart transplant patients: a retrospective study

[Abstract] Background Lifelong adherence with post-transplant immunosuppression is challenging, with nonadherence associated with greater acute rejection (AR) risk. Methods This retrospective study evaluated conversion from immediate-release tacrolimus (IRT) to prolonged-release tacrolimus (PRT), between January 2008 and December 2012 in stable adult heart transplant recipients. Cumulative incidence rate (IR) of AR and infection pre- and postconversion, safety, tacrolimus dose and trough levels, concomitant immunosuppression, and PRT discontinuation were analyzed (intention-to-treat population). Results Overall, 467 patients (mean age, 59.3 [SD, 13.3] years) converted to PRT at 5.1 (SD, 4.9) years post transplant and were followed for 3.4 (SD, 1.5) years. During the 6 months post conversion, 5 patients (1.1%; 95% CI, 0.35%–2.48%) had an AR episode and IR was 2.2/100 patient-years (95% CI, 0.91–5.26). Incidence of rejection preconversion varied by time from transplant to conversion. Infection IR was similar post- and preconversion (9.2/100 patient-years [95% CI, 7.4–11.3] vs 10.6/100 patient-years [95% CI, 8.8–12.3], respectively; P = .20). Safety variables remained similar post conversion. The IR of mortality/graft loss was 2.3/100 patient-years (95% CI, 1.7–3.1). Conclusions Conversion from IRT to PRT in heart transplant recipients in Spain was associated with no new safety concerns and appropriate immunosuppressive effectiveness

Prognostic value of discharge heart rate in acute heart failure patients: More relevant in atrial fibrillation?

Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results: The mean age of the study population was 72+/-12years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR)=1.182, confidence interval (CI) 95% 1.024-1.366, p=0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR=1.276, CI 95% 1.115-1.459, p</=0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients

Health‐related quality of life, social support, and caregiver burden between six and 120 months after heart transplantation: a Spanish multicenter cross‐sectional study

[Abstract] A multicenter cross-sectional study was conducted to determine the current heart transplant (HTx) outcomes in Spain. Clinical and functional status, health-related quality of life (HRQoL), social support, and caregiver burden were analyzed in 303 adult transplant recipients (77.9% males) living with one functioning graft. Mean age at time of HTx (SD) was 56.4 (11.4) years, and the reason for transplantation in all patients was congestive heart failure. All patients had received a first heart transplant 6 (± 1), 12 (± 2), 36 (± 6), 60 (± 10), or 120 (± 20) months previously. Participants completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D, the Duke-UNC Functional Social Support Questionnaire, and the Zarit Caregiver Burden Scale. Reasonable HRQoL, social support, and caregiver burden levels were found at all time points, although a slight decrease in HRQoL was recorded at 120 months (p ≤ 0.033). Multivariate regression analyses showed that complications, comorbidities, and hospitalizations were associated with HRQoL (EQ-5D: 48.4% of explained variance, F4,164 = 38.46, p < 0.001; KCCQ overall summary score: 45.0%, F3,198 = 54.073, p < 0.001). Patient functional capabilities and complications affected caregiver burden (p < 0.05). In conclusion, HTx patients reported reasonable levels of HRQoL with low caregiver burden. Clinical variables related to these outcomes included functional status, complications, and number of admissions

Adecuación en España a las recomendaciones terapéuticas de la guía de la ESC sobre insuficiencia cardiaca: ESC Heart Failure Long-term Registry

[Abstract] Introduction and objectives. To estimate the percentage of heart failure patients in Spain that received the European Society of Cardiology recommended treatments, and in those that did not, to determine the reasons why. Methods. The study included 2834 consecutive ambulatory patients with heart failure from 27 Spanish hospitals. We recorded general information, the treatment indicated, and the reasons why it was not prescribed in some cases. In patients who met the criteria to receive a certain drug, true undertreatment was defined as the percentage of patients who, without justification, did not receive the drug. Results. In total, 92.6% of ambulatory patients with low ejection fraction received angiotensin converting enzyme inhibitors or angiotensin receptor blockers, 93.3% beta-blockers, and 74.5% mineralocorticoid receptor antagonists. The true undertreatment rates were 3.4%, 1.8%, and 19.0%, respectively. Target doses were reached in 16.2% of patients receiving angiotensin converting enzyme inhibitors, 23.3% of those with angiotensin receptor blockers, 13.2% of those prescribed beta-blockers, and 23.5% of those with mineralocorticoid receptor antagonists. Among patients who could benefit from ivabradine, 29.1% received this drug. In total, 36% of patients met the criteria for defibrillator implantation and 90% of them had received the device or were scheduled for implantation, whereas 19.6% fulfilled the criteria for resynchronization therapy and 88.0% already had or would soon have the device. In patients who met the criteria, but did not undergo device implantation, the reasons were not cost-related. Conclusions. When justified reasons for not administering heart failure drugs were taken into account, adherence to the guideline recommendations was excellent. Exclusive use of the percentage of treated patients is a poor indicator of the quality of healthcare in heart failure. Measures should be taken to improve the attainment of optimal dosing in each patient.[Resumen] Introducción y objetivos. Estimar la proporción de pacientes con insuficiencia cardiaca atendidos en España que reciben los tratamientos recomendados por la Sociedad Europea de Cardiología y razones de que no los reciban, en su caso. Métodos. Se incluyó a 2.834 pacientes ambulatorios consecutivos con insuficiencia cardiaca de 27 hospitales españoles. Se recogió información general, tratamiento indicado y causas de que no lo recibiera, en su caso. De los pacientes que cumplen criterios para recibir tratamiento, infratratamiento real es la proporción que, sin justificación, no lo recibe. Resultados. El 92,6% de los pacientes ambulatorios con fracción de eyección reducida recibieron inhibidores de la enzima de conversión de la angiotensina o antagonistas del receptor de la angiotensina II; el 93,3%, bloqueadores beta y el 74,5%, antagonistas del receptor mineralocorticoideo. El infratratamiento real es del 3,4, el 1,8 y el 19,0% respectivamente. Alcanzan dosis objetivo de inhibidores de la enzima de conversión de la angiotensina el 16,2% de los pacientes; de antagonistas de los receptores de la angiotensina II, el 23,3%; de bloqueadores beta, el 13,2% y de antagonistas del receptor mineralocorticoideo, el 23,5%. El 29,1% de los pacientes que podrían beneficiarse de ivabradina la reciben; el 36% cumple criterios para implantar desfibrilador; de ellos, el 90% lo tienen ya implantado o programado; las cifras correspondientes en resincronización son el 19,6 y el 88,0%; el porcentaje restante no se debe a causas económicas. Conclusiones. Considerando razones justificadas para no administrar fármacos a estos pacientes, el cumplimiento de las guías es excelente. Utilizar solo la proporción de pacientes tratados es un mal indicador de calidad de la asistencia en insuficiencia cardiaca. Es necesario introducir medidas que mejoren el logro de la dosis óptima para cada paciente

AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217