Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients.

AIM: To determine the clinical reasons for conversion to everolimus (EVL) and long-term outcomes in heart transplant (HT) recipients. METHODS: A retrospective 12-mo study has been carried out in 14 Spanish centres to assess the efficacy and safety of conversion to EVL in maintenance HT recipients. RESULTS: Two hundred and twenty-two patients were included (mean age: 53 ± 10.5 years; mean time from HT: 8.1 ± 4.5 years). The most common reasons for conversion were nephrotoxicity (30%), chronic allograft vasculopathy (20%) and neoplasms (17%). The doses and mean levels of EVL at baseline (conversion to EVL) and after one year were 1.3 ± 0.3 and 1.2 ± 0.6 mg/d and 6.4 ± 3.4 and 5.6 ± 2.5 ng/mL, respectively. The percentage of patients receiving calcineurin inhibitors (CNIs) at baseline and on the final visit was 95% and 65%, respectively. The doses and mean levels of CNIs decreased between baseline and month 12 from 142.2 ± 51.6 to 98.0 ± 39.4 mg/d (P < 0.001) and from 126.1 ± 50.9 to 89.2 ± 47.7 ng/mL (P < 0.001), respectively, for cyclosporine, and from 2.9 ± 1.8 to 2.6 ± 1.9 mg/d and from 8.3 ± 4.0 to 6.5 ± 2.7 ng/mL (P = 0.011) for tacrolimus. In the subgroup of patients converted because of nephrotoxicity, creatinine clearance increased from 34.9 ± 10.1 to 40.4 ± 14.4 mL/min (P < 0.001). There were 37 episodes of acute rejection in 24 patients (11%). The most frequent adverse events were oedemas (12%), infections (9%) and gastrointestinal problems (6%). EVL was suspended in 44 patients (20%). Since the database was closed at the end of the study, no further follow-up data is available. CONCLUSION: Conversion to EVL in maintenance HT recipients allowed minimisation or suspension of the CNIs, with improved kidney function in the patients with nephrotoxicity, after 12 mo.

Impact of asymptomatic acute cellular rejection on left ventricle myocardial function evaluated by means of two-dimensional speckle tracking echocardiography in heart transplant recipients.

BACKGROUND: Our objective was to evaluate the impact of asymptomatic acute cellular rejection (ACR) in left ventricular myocardial strain in heart transplant (HT) recipients by means of two-dimensional speckle tracking echocardiography (2DSTE). METHODS: From September 1, 2009 to December 15, 2010 a conventional echocardiography and 2DSTE exam was performed on all consecutive HT recipients in their first year posttransplantation within 3 hours of the surveillance endomyocardial biopsies, as well as on 14 healthy controls. The association of strain echocardiographic variables with different grades of ACR was investigated. RESULTS: Of the 78 studies performed 4 ± 3 months after HT in 20 patients, 32 studies were coincident with grade 0R rejection, 41 with grade 1R, and 5 with grade 2R. Significantly lower values of average radial strain were found with higher grades of ACR (29.1 ± 7.7%, 23.2 ± 8.5%, and 14.3 ± 8.8% for grades 0R, 1R, and 2R of ACR, P = 0.001). Average deformation was similar for controls versus transplanted patients, in the absence of acute rejection: radial 29.1 ± 10.0% versus 29.1 ± 7.7%, P = 0.98; circumferential -19.3 ± 3.2% versus -20.2 ± 5.9%, P = 0.62; and longitudinal -20.7 ± 4.1% versus -18.5 ± 5.4%, P = 0.19. An average radial strain <25% presented 100% sensitivity, 48% specificity, 6% positive predictive value, and 100% negative predictive value for the presence of 2R rejection (area under the curve 0.80, IC 95% 0.60-0.99, P = 0.048). CONCLUSION: In this study, HT recipients showed significantly lower values of average radial left ventricle strain, evaluated by means of 2DSTE, with the presence of ACR.

Prognostic value of resting heart rate in a broad population of patients with stable coronary artery disease: prospective single-center cohort study.

INTRODUCTION AND OBJECTIVES: Our aim was to investigate the prognostic value of the resting heart rate (RHR) in a broad unselected population of patients with stable coronary artery disease (sCAD). METHOD: Between February 1, 2000 and January 31, 2004, 1264 ambulatory patients with sCAD were recruited into the prospective study. Patients were followed up for major events (i.e. death, acute coronary syndrome, coronary revascularization, stroke, and hospitalization for heart failure). Associations between these events and the RHR (i.e. ≥ 70 beats per minute [bpm] versus < 70 bpm) were evaluated. RESULTS: The patients' median age was 68 years (interquartile range [IQR] 60-74 years) and 926 (73%) were male. The RHR was ≥ 70 bpm in 645 patients (51%) and < 70 bpm in 619 (49%). After a median follow-up period of 25 months (IQR 12-39 months), with only seven patients lost to follow-up, the probability of an event was 17.48% in patients with an RHR ≥ 70 bpm and 17.67% in those with an RHR < 70 bpm (P =. 32) and total mortality was 2.32% and 2.5%, respectively (P = .56). After adjustment for age, sex, cardiovascular risk factors, blood pressure, baseline cardiac rhythm, ejection fraction and treatment at first visit, no significant association was found between the RHR and major events (hazard ratio [HR] = 1.04; 95% confidence interval [CI], 0.76-1.43; P = .79) or mortality (HR = 1.24; 95% CI, 0.55-2.81; P=.61). CONCLUSIONS: The RHR was not an adverse prognostic factor in this group of unselected patients with sCAD. The prognostic value of the RHR in daily clinical practice could be low in this population.

Valor pronóstico de la frecuencia cardiaca en reposo en una población general de pacientes con cardiopatía isquémica crónica: un estudio prospectivo, monocéntrico de cohortes / Prognostic value of resting heart rate in a broad population of patients with stable coronary artery disease: prospective single- center cohort study

Introducción y objetivos. Nuestro objetivo es evaluar el valor pronóstico de la frecuencia cardiaca en reposo (FCr) en una población general no seleccionada de pacientes con cardiopatía isquémica crónica (CIC). Métodos. Del 1 de febrero de 2000 al 31 de enero de 2004, se incluyó prospectivamente a 1.264 pacientes ambulatorios con CIC, y se los siguió para eventos mayores (mortalidad, síndrome coronario agudo, revascularización coronaria, ictus e ingreso por insuficiencia cardiaca) para evaluar la asociación de éstos con la FCr (≥ 70 frente a < 70 lat/min). Resultados. La mediana [p25-p75] de edad fue 68 [60- 74] años, y 926 pacientes eran varones (73%); 645 pacientes (51%) presentaron una FCr ≥ 70 lat/min y 619 (49%), FCr < 70 lat/min. Tras una mediana de seguimiento de 25 [12-39] meses, con sólo 7 pacientes perdidos, la probabilidad de eventos fue del 17,48% en pacientes con FCr ≥ 70 lat/min y del 17,67% en pacientes con FCr < 70 lat/min (p = 0,32) y la mortalidad total, del 2,32 y el 2,5% respectivamente (p = 0,56). Tras ajustar por edad, sexo, factores de riesgo cardiovascular, presión arterial, ritmo basal, fracción de eyección y tratamiento en la primera visita, no encontramos asociación entre la FCr y la tasa de eventos mayores (hazard ratio [HR] = 1,04; intervalo de confianza [IC] del 95%, 0,76-1,43; p = 0,79) o la mortalidad total (HR = 1,24; IC del 95%, 0,55-2,81; p = 0,61). Conclusiones. La FCr no ha sido un factor pronóstico adverso en esta muestra no seleccionada de pacientes con CIC. La importancia pronóstica de la FCr en la práctica clínica habitual podría ser baja en esta población (AU)

Introductions and objectives. Our aim was to investigate the prognostic value of the resting heart rate (RHR) in a broad unselected population of patients with stable coronary artery disease (sCAD). Method. Between February 1, 2000 and January 31, 2004, 1264 ambulatory patients with sCAD were recruited into the prospective study. Patients were followed up for major events (i.e. death, acute coronary syndrome, coronary revascularization, stroke, and hospitalization for heart failure). Associations between these events and the RHR (i.e. ≥70 beats per minute [bpm] versus <70 bpm) were evaluated. Results. The patients’ median age was 68 years (interquartile range [IQR] 60-74 years) and 926 (73%) were male. The RHR was ≥70 bpm in 645 patients (51%) and <70 bpm in 619 (49%). After a median follow-up period of 25 months (IQR 12-39 months), with only seven patients lost to follow-up, the probability of an event was 17.48% in patients with an RHR ≥70 bpm and 17.67% in those with an RHR <70 bpm (P=.32) and total mortality was 2.32% and 2.5%, respectively (P=.56). After adjustment for age, sex, cardiovascular risk factors, blood pressure, baseline cardiac rhythm, ejection fraction and treatment at first visit, no significant association was found between the RHR and major events (hazard ratio [HR]=1.04; 95% confidence interval [CI], 0.76-1.43; P=.79) or mortality (HR=1.24; 95% CI, 0.55-2.81; P=.61). Conclusions. The RHR was not an adverse prognostic factor in this group of unselected patients with sCAD. The prognostic value of the RHR in daily clinical practice could be low in this population (AU)

Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.