Incidence of stent thrombosis and adverse cardiac events 5 years after sirolimus stent implantation in clinical practice.

BACKGROUND: The long-term incidence of stent thrombosis (ST) and complications after sirolimus-eluting stents (SES) implantation is still a matter of debate. METHOD: We conducted a systematic follow-up on the day of their 5-year SES implantation anniversary, in a series of consecutive real-world patients treated with a SES. The use of SES implantation was not restricted to "on-label" indications, and target lesions included in-stent restenosis, vein graft, left main stem locations, bifurcations, and long lesions. The Academic Research Consortium criteria were used for ST classification. RESULTS: Three hundred fifty consecutive patients were treated with SES between April and December 2002 in 3 Swiss hospitals. Mean age was 63 +/- 6 years, 78% were men, 20% presented with acute coronary syndrome, and 19% were patients with diabetes. Five-year follow-up was obtained in 98% of eligible patients. Stent thrombosis had occurred in 12 patients (3.6%) [definite 6 (1.8%), probable 1 (0.3%) and possible 5 (1.5%)]. Eighty-one percent of the population was free of complications. Major adverse cardiac events occurred in 74 (21%) patients and were as follows: cardiac death 3%, noncardiac death 4%, myocardial infarction 2%, target lesion revascularization 8%, non-target lesion revascularization target vessel revascularization 3%, coronary artery bypass graft 2%. Non-TVR was performed in 8%. CONCLUSION: Our data confirm the good long-term outcome of patients treated with SES. The incidence of complications and sub acute thrombosis at 5 years in routine clinical practice reproduces the results of prospective randomized trials.

[The pivotal role of the pathologist in transplantation]. / Rôle du pathologiste en transplantation.

The management of rejection has recently become more complex, in particular since the identification of antibody-mediated rejection in addition to the full-established pictures of cellular rejection. The pathologist who reads graft biopsies must solve these problems in order to arrive at a clear histopathological diagnosis. The diagnosis will then have to be discussed in a multidisciplinary approach with the clinical persons, in order to decide upon the optimal treatment approach. Protocol biopsies may detect subclinical rejection and, hence help adjust the immunosuppressive treatment for an extended allograft survival. Finally, allograft biopsies performed with the purpose of "staging" may yield helpful informations concerning the condition of the organ, and may thus help to anticipate a possible future re-transplantation.

A prospective randomized comparison between paclitaxel and sirolimus stents in the real world of interventional cardiology: the TAXi trial.

OBJECTIVES: We conducted this trial to assess whether a sirolimus-eluting stent (SES) produces similar results to a paclitaxel-eluting stent (PES) when used in the real world of interventional cardiology. BACKGROUND: Several drug-eluting stents have been shown to exert a beneficial effect on restenosis when used in the treatment of coronary artery disease. Any potential superiority of one drug over the others, however, is still unknown. METHODS: To evaluate whether a PES or an SES is superior in daily practice, we randomized all patients suitable to receive a drug-eluting stent in our institution. Clinical follow-up was obtained after at least six months. RESULTS: A total of 202 patients were included in this trial. One hundred patients received a PES and 102 received an SES. Procedural success was 99% in both groups. Incidence of major adverse cardiac events at follow-up (mean 7 +/- 2 months) was 4% with the PES and 6% with the SES (p = 0.8). The need for target lesion revascularization was very low in both groups (1% with the PES and 3% with the SES). CONCLUSIONS: Our results confirm that the high success rate obtained with both stents in randomized trials can be replicated in routine clinical practice. In this small group of patients we were unable to show any advantage of one stent over the other.

CCR5, RANTES and CX3CR1 polymorphisms: possible genetic links with acute heart rejection.

BACKGROUND: The inflammation response is modulated by the elaborated chemokine-chemokine receptor system, which also plays an important role in the development of acute rejection (AR). In this study, we hypothesized that functional genetic variants of some of these modulatory proteins might influence the outcome of AR. METHODS: In a retrospective analysis of a cohort of heart transplanted patients (n=158), we examined eight polymorphisms in four genes implicated in this inflammatory process: RANTES, CCR5, CCR2 and CX3CR1. On the basis of timing occurrence, AR episodes (grade>or= 3A) were classified in "early" (0-3 months posttransplantation; EAR) or "late" outcomes (4-12 months posttransplantation; LAR). RESULTS: The incidences of EAR and LAR were 57.6% and 41%, respectively. Number of LAR episodes was significantly higher in subjects that have already experienced one or more EAR episodes, as compared to subjects that had no EAR (median [25%-75%]: 4 () vs. 1 [1-2.5] respectively; P<0.0001). Statistical univariate analysis showed that none of the mentioned polymorphisms were correlated with EAR or LAR. However, allele-allele association analysis showed that subjects carrying both the CX3CR1 249I allele and CCR5 No-E haplotypes were significantly at lower risk of experiencing EAR (OR=0.2 [95%-CI=0.1-0.5], P=0.001). In contrast subjects carrying both the CCR5 E haplotype and the RANTES -403A allele were significantly at higher risk to develop LAR (OR=8.1 [95%-CI=2.3-28.7], P=0.002). CONCLUSIONS: This exploratory study in heart transplantation suggests that the outcomes of EAR and LAR episodes may be influenced by genetic variant interactions such as "CX3CR1 249I*CCR5 No-E" and "CCR5 E*RANTES -403A."

Determinants of protracted cytomegalovirus infection in solid-organ transplant patients.

BACKGROUND: Recurrent infection frequently follows the response to the initial treatment of cytomegalovirus (CMV) infection in solid-organ transplant (SOT) recipients. The objective of this study was to describe the course of CMV infection in SOT patients and to identify factors that would predict protracted CMV infection with recurrences. METHODS: Quantitative polymerase chain reaction (PCR) assay for CMV DNA in leukocytes and in plasma were used to assess viral load changes retrospectively in consecutive SOT patients, whose CMV infection episodes had been attended therapeutically or preemptively using quantitative blood culture. RESULTS: Among 101 SOT patients, CMV infection occurred in 63, of whom 32 developed recurrent infection after the initial episode. In patients with recurrent infection, PCR indicated that a majority (27) of recipients had high level of CMV DNA in peripheral blood leukocytes and plasma throughout a protracted (>/=1 month) period including after preemptive or therapeutic ganciclovir courses. Predictors of protracted high-level infection were increasing age, CMV donor seropositivity, and all measures of viral load during the initial episode. CMV recipient seropositivity protected strongly against protracted infection. End of treatment plasma CMV DNA best discriminated between patients who did or did not develop protracted infection. CONCLUSIONS: In SOT patients, protracted CMV infection is associated with increasing age, donor seropositivity, recipient seronegativity, and high viral load during the first episode. End of therapy plasma CMV DNA level best predicts the occurrence of protracted infection. In patients with a high risk of protracted infection, prophylaxis is likely to be particularly cost effective.

Three-year follow-up of the first prospective randomized comparison between paclitaxel and sirolimus stents: the TAXi-LATE trial.

GOAL: Analysis of the 3-year outcome of the original population of the TAXi trial which compared the efficacy of the paclitaxel (PES) and the sirolimus (SES) stents in a randomized "real world" investigation. HISTORY: The widespread use of drug-eluting stents strongly modified the world of interventional cardiology. The TAXi trial was a randomized comparison between PES and SES and showed similar efficacy between the two prostheses. Recently, emerging discussions raised questions about potential long-term risk with the use of DES. The present work attempts to describe the long-term outcome of the patients compared during the TAXi trial. METHOD: During April 2003 and January 2004, 202 patients were prospectively randomly assigned to the PES group (102 patients) and to the SES group (100 patients). The primary aim of the present investigation was the comparison of combined incidence of cardiac death, myocardial infarction, and target lesion revascularization within 36-months. RESULTS: No difference in mortality of all causes was noted in the PES and the SES groups (3% vs. 7%, P=0.98) or in major adverse cardiac event free survival (89% vs. 83%, P=0.28). Four stent thromboses were observed, two in the PES group (205 and 788 days) and two in the SES group (210 and 772 days). CONCLUSION: The long-term outcome analysis of the TAXi trial confirms available published data showing the equivalence of PES and SES on clinical basis.

Use of sirolimus-eluting coronary stents in routine clinical practice.

Restenosis has long remained the major limitation of intracoronary stenting, but several randomized trials have recently shown that the use of drug-eluting stents appear to reduce markedly the risk of recurrence following treatment of de novo lesions. To evaluate whether the results of randomized trials can be generalized to routine clinical practice, all patients receiving at least one sirolimus-eluting stent (SES) in two Swiss hospitals were entered into a prospective registry. Only target vessels with a reference diameter > 3.5 mm were excluded. Clinical follow-up was obtained after 6 months. A total of 183 patients were included. The procedural success was 97.8% and the incidence of in-hospital MACE was 2.2%. At 7 +/- 2 months, 95.6% of the patients were event-free, and target lesion revascularization was required in only three patients (1.6%). The excellent medium-term results obtained with the SES in randomized trials can be replicated in routine clinical practice.

Repeated intracoronary beta radiation for recurrent in-stent restenosis.

More than 70% of percutaneous coronary interventions are followed by a stent implantation. In-stent restenosis still occurs in 20-30% of patients and remains a therapeutic challenge. At present only vascular brachytherapy has been shown to be an effective treatment option. We report here one case of recurrent in-stent restenosis after vascular brachytherapy that was successfully treated by a second beta radiation treatment.