José Luis R Lambert

Prevalence of heart failure in Asturias (a region in the north of Spain).

C disagreement exists on data published on the prevalence of heart failure.1–6 However, studies on both the prevalence and natural history of heart failure generally tend to be retrospective and to have been performed in patients referred to specialized centers (most of whom are in advanced stages of heart failure). Therefore, these patients are not representative of congestive heart failure in the community.6–8 Because of the lack of diagnostic criteria and data on the prevalence of heart failure, we conducted a field study in 1996 to establish its prevalence of this in our community. For these reasons we followed the Framingham clinical criteria of heart failure3 (Table 1). We also included 2 dimensional echo-Doppler examinations to stratify heart failure into systolic or diastolic failure.9–11 • • • In September 1995, the census of Asturias in Northen Spain, with a population of 1,098,725, contained 515,487 persons aged . 40 years. Assuming an epsilon of 6 1, a confidence interval of 95%, and a prevalence of heart failure .1% (1% to 5%), we selected a random sample of 380 subjects, a number statistically representative of this population. The total sample size for the study included 6% more subjects than what was originally estimated to adjust for the possible effect of dropouts; we decided not to replace those who failed to attend appointments. These subjects were stratified according to age and sex. Of the 400 randomized persons, 9 were excluded because of census errors. The remaining 391 persons (100%) underwent medical examination, 367 (93%) underwent electrocardiography, 356 (91%) chest xray examinations; 2 dimensional echo-Doppler studies estimated left ventricular ejection fraction in 351 patients (89%). Two dimensional echo-Doppler studies were recorded with a Hewlett-Packard (Andover, Massachusetts) ultrasound unit (model 1500) and 2.5MHz transducer. Those presenting with a left ventricular ejection fraction .50% (by the Teichholz method) were considered to have normal systolic function.9,12,13 Diastolic function10,11,14 was assessed by left ventricular filling patterns: mitral valve E (m/s)/mitral valve A (m/s) (E/A) ratio, deceleration time, and isovolumetric relaxation time (Table 2). For systolic and diastolic assessment, a mean of 3 measurements was obtained in each patient with sinus rhythm, and a mean of 5 measurements was obtained in those with atrial fibrillation. The echo study results were used for further stratification of heart failure (systolic and diastolic dysfunction). Stratification of the population according to age and sex, presence of heart failure, and echo data results are shown in Table 3. Table 3 shows the stratification according to the age of the population and of the sample aged .40 years. The mean age of the sample was 59.5 6 12.5 years. In terms of gender our sample contained 183 men From the Division of Cardiology, Hospital Central de Asturias, Oviedo University, Asturias, Spain. This work was supported by a Merck, Sharp & Dohme Grant. Dr. Cortina’s address is: Division of Cardiology, Hospital Central de Asturias, C/Julian Claveria s/n, 33006 Oviedo, Asturias, Spain. E mail: ROSARIOCORTINA@teleline.es. Manuscript received October 12, 2000; revised manuscript received and accepted January 17, 2001. TABLE 1 Criteria for Heart Failure

Conferencia de Consenso de los Grupos Españoles de Trasplante Cardiaco

La Seccion de Insuficiencia Cardiaca, Trasplante Cardiaco y otras Alternativas Terapeuticas de la Sociedad Espanola de Cardiologia desarrollo en Sevilla, en junio de 2005, una Conferencia de Consenso sobre trasplante cardiaco (TC) a la que fueron invitados a participar todos los grupos espanoles de TC. El objetivo fue determinar, discutir y consensuar los aspectos mas relevantes y/o controvertidos de diferentes areas del TC en la actualidad: organizacion, seleccion del receptor, donantes, rechazo, inmunosupresion, enfermedad vascular del injerto, complicaciones a largo plazo y TC pediatrico. Este documento reune las recomendaciones del grupo de trabajo incluyendo el grado de evidencia con que se respalda cada una.

Primary graft failure after heart transplantation: Characteristics in a contemporary cohort and performance of the RADIAL risk score

BACKGROUND Primary graft failure (PGF) is the leading cause of early heart transplantation (HT) mortality. Our aim was to analyze PGF currently and explore the ability of a dedicated score for PGF risk stratification. METHODS After applying a dedicated PGF definition, we analyzed its incidence, mortality, and associated factors in a multicenter cohort of 857 HTs performed in 2006 to 2009. We used the following criteria: recipient right (R) atrial pressure ≥ 10 mm Hg; age (A) ≥ 60 years; diabetes (D) mellitus, and inotrope (I) dependence; donor age (A) ≥ 30 years, and length (L) of ischemia ≥ 240 minutes to calculate the RADIAL score for PGF risk prediction. RESULTS PGF incidence was 22%. The right ventricle was almost always affected, alone (45%) or as part of biventricular failure (47%). Mechanical circulatory support was used in 55%. Mortality attributable to PGF was 53% and extended through the third month after HT, but thereafter, PGF had little influence in long-term outcome. The RADIAL score was higher in PGF patients (2.78 ± 1.1 vs. 2.42 ± 1.1, p = 0.001) and stratified 3 groups with incremental PGF incidence: low risk (12.1%), intermediate risk (19.4%), and high risk (27.5%, p = 0.001). CONCLUSIONS PGF had a strong impact, with an incidence of 22% and a mortality exceeding 50% that extends through the third post-HT month. The RADIAL score classified patients into 3 groups with incremental risk for PGF and may be useful for its prevention and early therapy.

Withdrawal of proliferation signal inhibitors due to adverse events in the maintenance phase of heart transplantation

BACKGROUND The increasing use of proliferation signal inhibitors (PSIs) has raised the issue of their risk profile. We sought to determine the causes, incidence, risk factors, and consequences of withdrawal due to adverse events of PSIs in maintenance heart transplantation. METHODS This was a retrospective study from 9 centers of the Spanish Registry for Heart Transplantation. Demographic, clinical, analytic, and evolution data were obtained for patients in whom a PSI (sirolimus or everolimus) was used between October 2001 and March 2009. RESULTS In the first year, 16% of 548 patients could not tolerate PSIs. This incidence rate stabilized to 3% to 4% per year thereafter. The most frequent causes for discontinuation were edema (4.7%), gastrointestinal toxicity (3.8%), pneumonitis (3.3%), and hematologic toxicity (2.0%). In multivariate analysis, withdrawal of PSI was related to the absence of statin therapy (p = 0.006), concomitant treatment with anti-metabolites (p = 0.006), a poor baseline renal function (p = 0.026), and multiple indications for PSI use (p = 0.04). Drug discontinuation was associated with a decline in renal function (p = 0.045) but not with an excess in mortality (p = 0.42). CONCLUSIONS In this large cohort of maintenance heart transplant recipients taking a PSI, 16% withdrew treatment in the first year, and 25% had stopped PSI due to severe adverse events by the fourth year. This high rate of toxicity-related PSI withdrawal could limit the clinical utility of this otherwise novel class of immunosuppressive agents.

Clinical recommendations for the use of everolimus in heart transplantation

Proliferation signal inhibitors (PSIs), everolimus (EVL), and sirolimus are a group of immunosuppressor agents indicated for the prevention of acute rejection in adult heart transplant recipients. Proliferation signal inhibitors have a mechanism of action with both immunosuppressive and antiproliferative effects, representing an especially interesting treatment option for the prevention and management of some specific conditions in heart transplant population, such as graft vasculopathy or malignancies. Proliferation signal inhibitors have been observed to work synergistically with calcineurin inhibitors (CNIs). Data from clinical trials and from the growing clinical experience show that when administered concomitantly with CNIs, PSIs allow significant dose reductions of the latter without loss of efficacy, a fact that has been associated with stabilization or significant improvement in renal function in patients with CNI-induced nephrotoxicity. The purpose of this article was to review the current knowledge of the role of PSIs in heart transplantation to provide recommendations for the proper use of EVL in cardiac transplant recipients, including indications, treatment regimens, monitoring, and management of the adverse events.

Use of mTOR inhibitors in chronic heart transplant recipients with renal failure: Calcineurin-inhibitors conversion or minimization?

BACKGROUND In the last decade, mTOR inhibitors (mTOR-is) have become the cornerstone of the calcineurin inhibitor (CNI)-reduced/free regimens aimed to the preservation of post-transplant renal function. We compared utility and safety of the total replacement of calcineurin inhibitors with a mTOR-i with a strategy based on calcineurin inhibitor minimization and concomitant use of m-TOR-i. METHODS In a retrospective multi-center cohort of 394 maintenance cardiac recipients with renal failure (GFR<60 mL/min/1.73 m(2)), we compared 235 patients in whom CNI was replaced with a mTOR-i (sirolimus or everolimus) with 159 patients in whom mTOR-is were used to minimize CNIs. A propensity score analysis was carried out to balance between group differences. RESULTS Overall, after a median time of 2 years from mTOR-i initiation, between group differences for the evolution of renal function were not observed. In a multivariate adjusted model, improvement of renal function was limited to patients with mTOR-i usage within 5years after transplantation, particularly with the conversion strategy, and in those patients who could maintain mTOR-i therapy. Significant differences between strategies were not found for mortality, infection and mTOR-i withdrawal due to drug-related adverse events. However, conversion group tended to have a higher acute rejection incidence than the minimization group (p=0.07). CONCLUSION In terms of renal benefits, our results support an earlier use of mTOR-is, irrespective of the strategy. The selection of either a conversion or a CNI minimization protocol should be based on the clinical characteristics of the patients, particularly their rejection risk.

Immunosenescence and inflammation characterize chronic heart failure patients with more advanced disease

BACKGROUND Chronic heart failure (CHF) is characterized by an inflammatory status with high levels of cytokines such as IL-6. We hypothesized that patients with CHF may develop immunosenescence due to inflammation and that this may be associated with a worse stage of the disease. METHODS AND RESULTS We compared the immunological features of 58 elderly CHF patients (ECHF), 40 young CHF patients (YCHF), 60 healthy elderly controls (HEC) and 40 healthy young controls (HYC). We characterized leukocyte and lymphocyte subpopulations by flow cytometry, and IL-6 concentration by ELISA. The extent of CHF was classified according to functional and/or morphological criteria: New York Heart Association functional class, AHA/ACC heart failure stages, left ventricular ejection fraction, and left ventricular hypertrophy. CHF patients showed an increased number of leukocytes, neutrophils and monocytes, but a decreased number of lymphocytes. CHF patients had significantly lower levels of B-cells and CD4+ T-cells, increased NK-cells in YCHF, and increased CD8+ T-cells only in ECHF. CHF was associated with high differentiation in CD4+ and CD8+ T-lymphocyte subsets. Aging of T-lymphocyte subpopulations and high IL-6 levels were associated with a worse clinical status. IL-6 also correlated positively with the number of highly differentiated T-lymphocytes and with their accelerated aging. CONCLUSIONS We conclude that CHF patients show a higher degree of immunosenescence than age-matched healthy controls. T-lymphocyte differentiation and IL-6 levels are increased in patients with an advanced clinical status and may contribute to disease impairment through a compromised adaptive immune response due to accelerated aging of their immune system.

Management and risk factors for mortality in very elderly patients with acute myocardial infarction

Aim:  Elderly patients often remain underrepresented in clinical trials. The aim of our study was to analyze the treatment, clinical outcome and risk factors for mortality in patients aged ≥85 years with ST‐segment elevation myocardial infarction (STEMI).

Update for 2014 on clinical cardiology, geriatric cardiology, and heart failure and transplantation.

In the present article, we review publications from the previous year in the following 3 areas: clinical cardiology, geriatric cardiology, and heart failure and transplantation. Among the new developments in clinical cardiology are several contributions from Spanish groups on tricuspid and aortic regurgitation, developments in atrial fibrillation, syncope, and the clinical characteristics of heart disease, as well as various studies on familial heart disease and chronic ischemic heart disease. In geriatric cardiology, the most relevant studies published in 2014 involve heart failure, degenerative aortic stenosis, and data on atrial fibrillation in the geriatric population. In heart failure and transplantation, the most noteworthy developments concern the importance of multidisciplinary units and patients with preserved systolic function. Other notable publications were those related to iron deficiency, new drugs, and new devices and biomarkers. Finally, we review studies on acute heart failure and transplantation, such as inotropic drugs and ventricular assist devices.

Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long‐term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient‐years) was significantly higher than that observed on CNI therapy in the pre‐conversion period (2.2 per 100 patient‐years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post‐conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow‐up. Conversion to a CNI‐free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post‐conversion rejection could help to refine the current PSI conversion strategies.