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Novel therapeutic and diagnostic management of heart transplant patients.

ABSTRACT: Heart transplantation was performed for the first time 40 years ago and it is now universally considered the "gold standard" treatment for individuals suffering from end-stage heart failure. The increased understanding of the molecular mechanisms and of the role of the immune system in allograft rejection led to an overall improvement of graft survival, which is now around 10 years. The introduction of novel immunosuppressive drugs reduced the rate of acute allograft rejection but did not improve significantly the long-term graft survival. In addition, adverse effects (e.g. infections, cancer and renal failure) associated with immunosuppressive drugs are increasing over time and may affect post-transplantation outcomes. An immunosuppression-free protocol based on tolerance induction is the Holy Grail for heart transplant recipients, but it is still far beyond our reach. In this review, we discuss the landscape of immunological challenges that heart transplanted individuals face and we critically review the novel immunological approaches available to overcome these remaining issues. Some of the novel approaches, successfully tested in preclinical and clinical models, may lead to a prolongation of patient's and heart allograft survival.

SUBMITTER: D'Addio F

PROVIDER: S-EPMC4593017 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Novel therapeutic and diagnostic management of heart transplant patients.

D'Addio Francesca F Margonato Davide D Pensato Umberto U Borgese Laura L Potena Luciano L Fiorina Paolo P

Heart, lung and vessels 20150101 3

Heart transplantation was performed for the first time 40 years ago and it is now universally considered the "gold standard" treatment for individuals suffering from end-stage heart failure. The increased understanding of the molecular mechanisms and of the role of the immune system in allograft rejection led to an overall improvement of graft survival, which is now around 10 years. The introduction of novel immunosuppressive drugs reduced the rate of acute allograft rejection but did not improv ...[more]

PMID: 26495265

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Project description:Aims:Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results:We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P < 0.01) and a trend to decreased thromboembolic complications (TA = 1/66 (2%) vs. no-TA = 7/71 (10%); P = 0.06). Controlling treatment crossovers provided an incidence rate-ratio [hazard ratio (HR) 10.31, 95% confidence interval (CI) 3.67-35.70; P < 0.01] in disadvantage of TA for haemorrhagic complications. Analyses of TA-timing displayed significant harm until Day 13 after ICH (HR 7.06, 95% CI 2.33-21.37; P < 0.01). The hazard for the composite-balancing both complications, was increased for restarted TA until Day 6 (HR 2.51, 95% CI 1.10-5.70; P = 0.03). Conclusion:Restarting TA within less than 2 weeks after ICH in patients with MHV was associated with increased haemorrhagic complications. Optimal weighing-between least risks for thromboembolic and haemorrhagic complications-provided an earliest starting point of TA at Day 6, reserved only for patients at high thromboembolic risk.

Dataset Information

Novel therapeutic and diagnostic management of heart transplant patients.

Publications

Novel therapeutic and diagnostic management of heart transplant patients.

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