J. Segovia

Report from a consensus conference on primary graft dysfunction after cardiac transplantation

Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes.

Heart transplantation using allografts from older donors: Multicenter study results

BACKGROUND The lengthy waiting time for heart transplantation is associated with high mortality. To increase the number of donors, new strategies have emerged, including the use of hearts from donors ≥50 years old. However, this practice remains controversial. The aim of this study was to evaluate outcomes of patients receiving heart transplants from older donors. METHODS We retrospectively analyzed 2,102 consecutive heart transplants in 8 Spanish hospitals from 1998 to 2010. Acute and overall mortality were compared in patients with grafts from donors ≥50 years old versus grafts from younger donors. RESULTS There were 1,758 (84%) transplanted grafts from donors < 50 years old (Group I) and 344 (16%) from donors ≥50 years old (Group II). Group I had more male donors than Group II (71% vs. 57%, p = 0.0001). The incidence of cardiovascular risk factors was higher in older donors. There were no differences in acute mortality or acute rejection episodes between the 2 groups. Global mortality was higher in Group II (rate ratio, 1.40; 95% confidence interval, 1.18-1.67; p = 0.001) than in Group I. After adjusting for donor cause of death, donor smoking history, recipient age, induction therapy, and cyclosporine therapy, the differences lost significance. Group II had a higher incidence of coronary allograft vasculopathy at 5 years (rate ratio, 1.67; 95% confidence interval, 1.22-2.27; p = 0.001). CONCLUSIONS There were no differences in acute and overall mortality after adjusting for confounding factors. However, there was a midterm increased risk of coronary allograft vasculopathy with the use of older donors. Careful selection of recipients and close monitoring of coronary allograft vasculopathy are warranted in these patients.

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.

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.

Comentarios a la guía de práctica clínica de la ESC sobre diagnóstico y tratamiento de la insuficiencia cardiaca aguda y crónica 2012. Un informe del Grupo de Trabajo del Comité de Guías de Práctica Clínica de la Sociedad Española de Cardiología

El Comite de Guias de Practica Clinica de la SEC formo un grupo de trabajo integrado por cardiologos clinicos, electrofisiologos, cirujanos cardiacos y personal de enfermeria, expertos en los diversos aparta-dos de la IC que cubre la guia de la ESC, propuestos por la Seccion de Insuficiencia Cardiaca y Trasplante y el Grupo de Trabajo sobre Resin-cronizacion Cardiaca de la SEC y por la Asociacion Espanola de Enfer-meria Cardiovascular, con el objetivo general de revisar las evidencias y recomendaciones aportadas por la guia europea sobre IC antes citada

Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study

J.F. Delgado, N. Manito, L. Almenar, M. Crespo‐Leiro, E. Roig, J. Segovia, J.A. Vázquez de Prada, E. Lage, J. Palomo, M. Campreciós, J.M. Arizón, J.L. Rodríguez‐Lambert, T. Blasco, L. de la Fuente, D. Pascual, G. Rábago. Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study
Transpl Infect Dis 2011: 13: 136–144. All rights reserved

Risk factors associated with moderate- to-severe renal dysfunction among heart transplant patients: results from the CAPRI study

Delgado JF, Crespo‐Leiro MG, Gómez‐Sánchez MA, Paniagua MJ, González‐Vílchez F, Vázquez de Prada JA, Fernández‐Yáñez J, Pascual D, Almenar L, Martínez‐Dolz L, Díaz B, Roig E, Segovia J, Arizón JM, Garrido I, Blasco T, López J, Brossa V, Manito N, Muñiz J. Risk factors associated with moderate‐to‐severe renal dysfunction among heart transplant patients: results from the CAPRI study.
Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01249.x
© 2010 John Wiley & Sons A/S.

Chronic Renal Dysfunction in Maintenance Heart Transplant Patients: The ICEBERG Study

Chronic renal dysfunction (CRD) is a major complication after heart transplantation. We sought to describe the renal function over time, to assess the risk factors associated with CRD development, and to evaluate the clinical attitudes on diagnosis and treatment of CRD. A retrospective, cross-sectional, multicenter study was conducted in 13 outpatient clinics in Spain. A total of 244 heart recipients who survived more than 2 years after transplantation were included. Post-transplantation follow-up was 7.7 years (range: 2-22 years). CRD was diagnosed in 32.4% of patients at a mean of 3.3 years after transplantation. Serum creatinine increased 0.1 ± 0.2 mg/dL per year in CRD group compared with 0.0 ± 0.2 mg/dL per year in non-CRD group (P = .003) and glomerular filtration rate decreased -1.5 ± 4.3 mL/min/1.73 m(2) per year in CRD group versus -0.1 ± 4.8 mL/min/1.73 m(2) per year in non-CRD group (P = .027). After CRD diagnosis, major changes in immunosuppression based on calcineurin inhibitors reduction were instituted in 46.8% of patients. Multivariate model identified recipient age (P < .0001), female sex (P = .0398), and time since transplant (P < .0001) as predictors of CRD. In conclusion, the prevalence of CRD in long-term heart recipient survivors was quite high. CRD was associated with nonmodifiable factors (age, gender, and time since transplant).

Study of the safety and tolerability of Simulect® (basiliximab) versus OKT3 in heart transplantation

Purpose: The objective of this study was to assess safety of two types of induction in de novo heart transplantation: Simulect® (basiliximab) vs OKT3. Methods: 101 adult cardiac allograft receptors were randomized (1:1) to either basiliximab or OKT3, with cyclosporin, MMF and steroids, with 1 year of follow-up. Basiliximab, 40 mg, was administered as i.v. bolus in two doses (day 0 and 4 after transplantation), while OKT3, 5 mg/day, was administered as i.v. bolus from day 0 to 6. Results: Interim results at 3 months are presented. No differences in demographics were observed. The incidence of biopsy confirmed acute rejection grade ≥3A was similar in both groups (29.2% in basiliximab group and 25.0% in OKT3 group, p=ns). The incidence of specific adverse events during first month (i.e. fever, cephalea, acute pumonary edema, hypotension) was observed in more patients in OKT3 (14.69%) than basiliximab (2.17%) group; although this difference was only significant during first week postransplantation (43.75% vs 4.26%, p<0.0001). Regarding other reported adverse events, none of them were related to basiliximab compared to 12.8% related to OKT3. The most frequent infection was CMV, which was found in 22.92% of the OKT3 group vs 16.66% of the basiliximab group (p<ns). At 3 months, 7 deaths have been reported in OKT3 group vs 3 in basiliximab group (14.6% and 6.3%, respectively; p=ns). Conclusions: Preliminary results suggest that Simulect® (basiliximab) has a similar efficacy and shows a tendency toward a lower incidence of adverse events compared with OKT3. Therefore, it could be a valid alternative for immunosuppressive treatment in de novo heart transplant receptors.

Prognostic Implications of Donor Age in Outcomes of Heart Transplantation

Purpose The lengthy waiting list for heart transplantation (HTx) is associated with increased mortality. Left ventricular assist device implantation and the increase of donor’s age have been strategies to improve survival. However, the use of grafts from older donors is still controversial. Methods and Materials We retrospectively analyzed the outcome of 2247 transplanted patients in eight centers of Spain from 1998 until November 2009. Clinical data was obtained from the National Registry for HTx. From the total 2247 HTx, 1840 (84%) were performed with donors 2R) and presence of coronary allograft vasculopathy (CAV) were compared between patients with donors Results Man donor was more frequently found in younger than in older donors (71% vs. 57%, p=0.0001). The incidence of cardiovascular risk factors was significantly higher in older donors, especially hypertension (20% vs. 8%, p Conclusions Donors ≥50 years were more frequently implanted in older recipients. During follow-up there were no differences in acute rejection episodes or CAV diagnosis. However, they had increased risk of death. The increased mortality has to be balanced against the risk of death being in the waiting list.