Late Failing Heart Allografts: Pathology of Cardiac Allograft Vasculopathy and Association With Antibody-Mediated Rejection.

In heart transplantation, there is a lack of robust evidence of the specific causes of late allograft failure. We hypothesized that a substantial fraction of failing heart allografts may be associated with antibody-mediated injury and immune-mediated coronary arteriosclerosis. We included all patients undergoing a retransplantation for late terminal heart allograft failure in three referral centers. We performed an integrative strategy of heart allograft phenotyping by assessing the heart vascular tree including histopathology and immunohistochemistry together with circulating donor-specific antibodies. The main analysis included 40 explanted heart allografts patients and 402 endomyocardial biopsies performed before allograft loss. Overall, antibody-mediated rejection was observed in 19 (47.5%) failing heart allografts including 16 patients (40%) in whom unrecognized previous episodes of subclinical antibody-mediated rejection occurred 4.5 ± 3.5 years before allograft loss. Explanted allografts with evidence of antibody-mediated rejection demonstrated higher endothelitis and microvascular inflammation scores (0.89 ± 0.26 and 2.25 ± 0.28, respectively) compared with explanted allografts without antibody-mediated rejection (0.42 ± 0.11 and 0.36 ± 0.09, p = 0.046 and p < 0.0001, respectively). Antibody-mediated injury was observed in 62.1% of failing allografts with pure coronary arteriosclerosis and mixed (arteriosclerosis and atherosclerosis) pattern, while it was not observed in patients with pure coronary atherosclerosis (p = 0.0076). We demonstrate that antibody-mediated rejection is operating in a substantial fraction of failing heart allografts and is associated with severe coronary arteriosclerosis. Unrecognized subclinical antibody-mediated rejection episodes may be observed years before allograft failure.

Generation and confinement of microwave gas-plasma in photonic dielectric microstructure.

We report on a self-guided microwave surface-wave induced generation of ~60 µm diameter and 6 cm-long column of argon-plasma confined in the core of a hollow-core photonic crystal fiber. At gas pressure of 1 mbar, the micro-confined plasma exhibits a stable transverse profile with a maximum gas-temperature as high as 1300 ± 200 K, and a wall-temperature as low as 500 K, and an electron density level of 10¹4 cm⁻³. The fiber guided fluorescence emission presents strong Ar⁺ spectral lines in the visible and near UV. Theory shows that the observed combination of relatively low wall-temperature and high ionisation rate in this strongly confined configuration is due to an unprecedentedly wide electrostatic space-charge field and the subsequent ion acceleration dominance in the plasma-to-gas power transfer.

Muscle fatigue experienced during maximal eccentric exercise is predictive of the plasma creatine kinase (CK) response.

Unaccustomed eccentric exercise may cause skeletal muscle damage with an increase in plasma creatine kinase (CK) activity. Although the wide variability among individuals in CK response to standardized lengthening contractions has been well described, the reasons underlying this phenomenon have not yet been understood. Therefore, this study investigated a possible correlation of the changes in muscle damage indirect markers after an eccentric exercise with the decline in muscle performance during the exercise. Twenty-seven healthy untrained male subjects performed three sets of 30 maximal isokinetic eccentric contractions of the knee extensors. The muscular work was recorded using an isokinetic dynamometer to assess muscle fatigue by means of various fatigue indices. Plasma CK activity, muscle soreness, and stiffness were measured before (pre) and one day after (post) exercise. The eccentric exercise bout induced significant changes of the three muscle damage indirect markers. Large inter-subject variability was observed for all criteria measured. More interestingly, the log (CK(post) /CK(pre)) and muscle stiffness appeared to be closely correlated with the relative work decrease (r = 0.84, r(2) = 0.70 and r = 0.75, r(2) = 0.56, respectively). This is the first study to propose that the muscle fatigue profile during maximal eccentric protocol could predict the magnitude of the symptoms associated with muscle damage in humans.

Wnt1 and BMP2: two factors recruiting multipotent neural crest progenitors isolated from adult bone marrow.

Recent studies have shown that neural crest-derived progenitor cells can be found in diverse mammalian tissues including tissues that were not previously shown to contain neural crest derivatives, such as bone marrow. The identification of those "new" neural crest-derived progenitor cells opens new strategies for developing autologous cell replacement therapies in regenerative medicine. However, their potential use is still a challenge as only few neural crest-derived progenitor cells were found in those new accessible locations. In this study, we developed a protocol, based on wnt1 and BMP2 effects, to enrich neural crest-derived cells from adult bone marrow. Those two factors are known to maintain and stimulate the proliferation of embryonic neural crest stem cells, however, their effects have never been characterized on neural crest cells isolated from adult tissues. Using multiple strategies from microarray to 2D-DIGE proteomic analyses, we characterized those recruited neural crest-derived cells, defining their identity and their differentiating abilities.

Heart transplantation as rescue treatment of left main stem occlusion by a recurrent aortic pseudoaneurysm.

A 58 year-old man was admitted in our ICU for cardiogenic shock and electrical storm. His medical history was marked by a triple redo valvular surgery complicated by a recurrent aortic pseudoaneurysm of the ascending aorta. Coronary angiogram and heart CT scan diagnosed an extensive anterior myocardial infarction related to an extrinsic compression of the left main stem by this massive and calcified pseudoaneurysm. Angioplasty or new cardiac surgery options were rejected by the heart team. Despite an unusual indication, the patient was registered on the heart transplant list, and underwent it successfully.

Tei index to assess perioperative left ventricular systolic function in patients undergoing mitral valve repair.

BACKGROUND: Using echocardiography, perioperative assessment of systolic function by fractional area change (FAC) is questionable in patients suffering from mitral regurgitation (MR). Tei index, an index expressing global cardiac function, has been reported to be unchanged after mitral valve surgery. We tested the hypothesis where the Tei index could be useful in assessing the perioperative cardiac function in patients undergoing mitral valve repair (MVR). METHODS: Twenty-five patients were enrolled. Transoesophageal echocardiography was performed perioperatively before and after the correction of MR. We compared the impact of the MVR on the left ventricular FAC and the Tei index. FAC was calculated from the transgastric short-axis view and Tei index was determined from the four chambers and deep transgastric views. RESULTS: Two patients were excluded because of poor acoustic windows. FAC significantly decreased after MVR from 53 (9)% to 42 (10)% (P<0.001), while Tei index was unaffected [0.46 (0.16) vs 0.47 (0.17), NS]. A significant relationship was found between the preoperative Tei index and the postoperative FAC (R=-0.64, P<0.001). Moreover, a significant and clinically relevant relationship was determined between the predicted (using preoperative Tei index) and the measured postoperative FAC (R=0.64, P<0.001). CONCLUSIONS: FAC but not the Tei index is influenced by MVR. The preoperative determination of the Tei index allows predicting postoperative FAC and offers the opportunity to identify patients in whom a severe unsuspected systolic dysfunction could render difficult the weaning from cardiopulmonary bypass.

Results after orthotopic heart transplantation accepting donor hearts >50 years: experience at La Pitie Salpetriere, Paris.

INTRODUCTION: We sought to examine the results of orthotopic heart transplantation accepting hearts from donors >50 years of age with special regard to the usefulness of peripheral extracorporeal membrane oxygenation for posttransplant graft dysfunction. PATIENTS: Between January 2000 and December 2004, a total of 247 patients underwent orthotopic heart transplantation. In 143 patients (58%) the heart donor was <50 years (group I, mean age of donor hearts 36 +/- 11 years; range, 8-49 years). In 104 recipients (42%) the heart donor was >50 years (group II, mean age of donor hearts 56 +/- 15 years; range, 50-67 years). Pretransplant characteristics of the two groups showed no significant differences. RESULTS: The in-hospital mortality was slightly increased in group II (24% vs 20% in group I, NS) and the 5-year survival rate significantly increased in group I (75% vs 63% in group II). Freedom from transplant vasculopathy after 3 years was similar in both groups (86% in group I vs 87% in group II). A total of 25 patients (17%) in group I and 27 patients (26%) in group II developed graft dysfunction. Eleven patients in group I and 10 patients in group II were treated using peripheral extracorporeal membrane oxygenation, whereas 3 of the 11 patients in group I and 5 of the 10 patients in group II were discharged following a complete recovery. Two patients in group I and 4 patients in group II were survivors beyond year. CONCLUSION: In our experience it was possible to increase the cardiac donor pool by accepting allografts from donors >50 years of age in selected cases. The incidence of transplant vasculopathy was not increased, whereas in-hospital mortality was slightly higher. In our limited cohort, patients with older donor hearts was developed graft dysfunction profited from primary extracorporeal membrane oxygenation implantation, an indication that should be examined further without delay.

Left ventricular assist device-related infections: a multicentric study.

OBJECTIVES: The implantable left ventricular assist device (LVAD) is a major therapeutic development for end-stage heart failure in selected patients. As their use is expanding, infectious complications are emerging, with limited data available to guide their management. We aimed to better characterize LVAD-related infections. METHODS: We enrolled all consecutive patients diagnosed with LVAD-related infections in three referral centres in France, using a standardized definition of infections in patients with LVAD. Data were collected from medical charts using a standardized questionnaire. RESULTS: Between 2007 and 2012, 159 patients received LVAD for end-stage heart failure. Among them, 36 (22.6%; 5 women, 31 men) presented at least one infectious complication, after a median time of 2.9 months from LVAD implantation (interquartile range, 1.8-7.5), with a median follow up of 12 months (interquartile range 8-17). Main co-morbidities were alcoholism (33%), diabetes (11%) and immunosuppression (11%). Mean age at implantation was 51 (±11) years. LVAD were implanted as bridge-to-transplantation (n=22), bridge-to-recovery (n=8), destination therapy (n=4), or unspecified (n=2). LVAD-related infections were restricted to the driveline exit site (n=17), had loco-regional extension (n=13), or reached the internal pump (n=3). The main bacteria isolated were Staphylococcus aureus (n=20), coagulase-negative staphylococci (n=7), Enterobacteriaceae (n=14), Pseudomonas aeruginosa (n=10) and Corynebacterium sp. (n=7), with polymicrobial infections in 19 cases. LVAD could be retained in all patients, with the use of prolonged antibacterial treatment in 34 (94%), and debridement in 17 (47%). One patient died due to LVAD-associated infection. CONCLUSIONS: LVAD-related infections are common after LVAD implantation, and may be controlled by prolonged antibiotic treatment.

[What's new in mechanical circulatory assistance: from clinical indications to material]. / Quoi de neuf en assistance circulatoire mécanique? Des indications au matériel.

Over the years, mechanical circulatoryassistance has progressively improved with the evolution of the clinical indications and the introduction of new devices. The management of situations of extreme emergency, cardiac arrest, acute myocardial infarction with cardiogenic shock, drug overdose, acute myocarditis, postoperative cardiac failure and post-transplantation right ventricular failure, may be undertaken with relatively simple systems such as the ECMO, in the catheter laboratory or at the bedside in the intensive care unit. These systems enable stabilisation of the circulatory problems in order to pass a difficult situation and then withdraw the assistance when myocardial function has been restored. When this is not possible and there is no contra-indication to cardiac transplantation, patients may benefit from more complex assistance devices as a bridge to transplantation. Many continuous flow pumps have been introduced recently. These small mono, left ventricular, assist devices provide improved patient comfort and suggest wider indications of long duration assist devices.

Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro.

Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.

Low molecular weight heparin after mechanical heart valve replacement.

BACKGROUND: Patients with mechanical heart valves require life-long anticoagulation. We report here the first large and comparative series of consecutive patients anticoagulated with low molecular weight heparin (LMWH) after mechanical heart valve replacement. METHODS AND RESULTS: In this comparative, nonrandomized study, 208 consecutive patients who underwent a single or double heart valve replacement with mechanical prostheses were anticoagulated subcutaneously with unfractionated heparin (UH) in the first period (n=106) and LMWH in the second phase (n=102) of the study. Baseline characteristics were similar in the 2 groups. The mean durations of UH and LMWH treatments were 13.6+/-0.5 and 14.1+/-0.6 days, respectively (not significant). On the second day of treatment, 87% of patients treated with LMWH had an anti-Xa activity within the range of efficacy (0.5 to 1 IU/mL), but only 9% of UH-treated patients had an activated partial-thromboplastin time value within the therapeutic range (1.5 to 2.5 times control, P<0.0001 between the 2 groups). On the last day of prescription, all LMWH-treated patients had anti-Xa activity above 0.5 IU/mL, but 19% were above 1 IU/mL. In the UH group, 27% of patients had an activated partial-thromboplastin time above 1.5 times control, but 62% were overanticoagulated. Two major bleedings occurred in each group, and one stroke occurred in the UH group. CONCLUSIONS: In this first comparative study, anticoagulation with LMWHs after mechanical heart valve replacement appears feasible, provides adequate biological anticoagulation, and compares favorably with UH anticoagulation. Randomized studies are now needed to further evaluate this new therapeutic approach.

Diagnostic value of anti-F-actin antibodies in a French multicenter study.

According to international criteria, autoimmune hepatitis (AIH) type 1 is characterized by the presence of antinuclear or anti-smooth muscle antibodies (SMA) with F-actin specificity. SMA have been found in 85% of AIH patients, but are not specific to this disease, and anti-F-actin specificity is not always verified when SMA are detected. The objective of this study was to determine the diagnostic value of anti-F-actin antibodies in a large population. A multicenter study involving 12 clinical centers was performed. Patients were selected on the basis of the presence of F-actin SMA detected by indirect immunofluorescence (IIF) on rat liver-kidney-stomach sections and was confirmed by IIF on Hep2 cells treated with colchicine, or F-actin dot-blot. The clinical status of patients was determined from their medical records. One hundred sixty-eight patients were included: 76% women, 24% men; mean age of 45 years (range, 2-88 years), with a bimodal age distribution. Sixty percent had AIH type 1, and 40% had another disease. In the group of women younger than 25 years, 90% had AIH type 1. Other pathologies associated with antiactin were other liver diseases (19%), including viral hepatitis C (7%), and non-liver diseases (21%), including connective tissue diseases (12%). Antibody titers were higher in AIH than in other diseases. Antiactin antibodies are of major diagnostic value in AIH, especially in young women; they may be found in other disease settings, but mostly at low levels.

Peripheral extracorporeal membrane oxygenation (ECMO) in patients with posttransplant cardiac graft failure.

INTRODUCTION: We sought to report the usefulness of extracorporeal membrane oxygenation (ECMO) in heart transplant patients. PATIENTS: Between March 2002 and August 2004, 14 heart transplant patients (11 men and three women, 36 +/- 15 years old, range = 12 to 50) with primary graft failure underwent peripheral ECMO implantation. Three patients had pulmonary hypertension and three had been transplanted with hearts from marginal donors. At the time of implantation, all were in severe cardiogenic shock despite maximal inotropic support. In six patients, the ECMO was implanted in the operating room since cardiopulmonary bypass could not be weaned. In the eight remaining patients, ECMO was implanted in the intensive care unit, during the first 48 hours in seven cases. In one patient, implantation was performed during external resuscitation. In all cases, femoral vessels were canulated using the Seldinger technique after anterior wall exposure. Distal arterial perfusion of the lower limb was systematically used. RESULTS: Pump outflow was high enough in all the cases (mean: 2.6 +/- 0.2 L/min/m(2)). Three patients died on circulatory support. One patient was implanted with a total artificial heart after a few hours and another one underwent unsuccessful emergent retransplantation. Nine patients were weaned from ECMO after a mean duration of 5 +/- 2.5 days. Among them, one died of infection at 10 days after weaning and seven others were discharged to rehabilitation centers. CONCLUSION: Fast operating room or bedside implantation of a peripheral ECMO allows the physician to stabilize the hemodynamic status of patients with cardiac graft failure, potentially leading toward myocardial recovery.

[Post-myocardial infarction cardiogenic shock and circulatory assistance]. / Choc cardiogénique post-infarctus et assistance circulatoire.

Post-myocardial infarction cardiogenic shock still carries a very poor prognosis despite the rapid recourse to effective methods of myocardial revascularisation. Circulatory assistance devices allow restoration of adequate haemodynamics with limitation of myocardial work. In the most severe cases, implantation of intra-thoracic devices is associated with a 70% survival rate in the latest series, providing they are used early. However, in many cases, the essential problem is to stabilise the patient's haemodynamic status, sometimes even before myocardial revascularisation. In these situations, implantation of a peripheral femoro-femoral extra corporeal circulation (ECMO: extra corporeal membrane oxygenation) re-establishes an appropriate cardiac output andprovides time to transfer the patient, to perform coronary revascularisation or to assess neurological status, before deciding on the indications for more complicated assist systems. This "bridge to bridge" concept avoids the risk of implanting complicated assist devices in cerebrally dead patients or in those with multi-organ failure beyond treatment. Conversely, it gives some patients with apparent contraindications to complicated assist systems or who are unable to benefit from these systems for geographical reasons, a chance to survive. In early cardiogenic shock, the ECMO which has a low rate of complications, could safely promote myocardial recovery.

[Pseudo-aneurysms of the ascending aorta in patients previously operated for acute aortic dissection]. / Pseudo-anévrismes de l'aorte ascendante chez les patients déjà opérés d'une dissection aortique aiguë. Diagnostic, traitement.

Pseudo-aneurysms of the ascending aorta are a rare but serious complication of surgery for acute dissection of the aorta. The diagnostic methods and surgical technique have changed in recent years. The authors report their experience over a period of 20 years. From January 1981 to December 2001, 21 patients underwent reoperation for pseudo-aneurysms of the ascending aorta. The average age was 54.2 +/- 3 years. Diagnosis is no longer based on aortography but on transthoracic or oesophageal multiplane echocardiography, thoracic spiral computed tomography or magnetic resonance imaging. Four patients presented with a recent history of severe pulmonary oedema. The risk associated with reopening the sternum is avoided by current operative techniques. The authors have chosen anterograde perfusion of the cervical arteries by direct canulation for cerebral protection. The operative mortality at one month is high (30%). All patients who had pulmonary oedema or cardiogenic shock in the immediate preoperative period died. There were no neurological complications. Twelve patients survived and one has to undergo a further operation for recurrence of the pseudo-aneurysm. The authors conclude that patients operated for dissection of the aorta must be followed up. It is important to resect as much as possible of the pathological aorta during the initial operation to avoid the risk of pseudo-aneurysm formation, at least in the proximal segment of the ascending aorta.

Bridge to transplantation using paracorporeal biventricular assist devices or the syncardia temporary total artificial heart: is there a difference?

AIM: Biventricular support can be achieved using paracorporeal ventricular assist devices (p-BiVAD) or the Syncardia temporary total artificial heart (t-TAH). The purpose of the present study was to compare survival and morbidity between these devices. METHODS: Data from 2 French neighboring hospitals were reviewed. Between 1996 and 2009, 148 patients (67 p-BiVADs and 81 t-TAH) underwent primary, planned biventricular support. There were 128 (86%) males aged 44±13 years. RESULTS: Preoperatively, p-BiVAD recipients had significantly lower systolic and diastolic blood pressures, more severe hepatic cytolysis and higher white blood cell counts than t-TAH recipients. In contrast, t-TAH patients had significantly higher rates of pre-implant ECLS and hemofiltration. Mean support duration was 79±100 days for the p-BiVAD group and 71±92 for t-TAH group (P=0.6). Forty two (63%) p-BiVAD recipients were bridged to transplantation (39, 58%) or recovery (3, 5%), whereas 51 (63%) patients underwent transplantation in the t-TAH group. Death on support was similar between groups (p-BiVAD, 26 (39%); t-TAH, 30 (37%); P=0.87). Survival while on device was not significantly different between patient groups and multivariate analysis showed that only preimplant diastolic blood pressure and alanine amino-transferase levels were significant predictors of death. Post-transplant survival in the p-BiVAD group was 76±7%, 70±8%, and 58±9% at 1, 3, and 5 years after transplantation, respectively, and was similar to that of the t-TAH group (77±6%, 72±6%, and 70±7%, P=0.60). CONCLUSION: Survival while on support and up to 5 years after heart transplantation was not significantly different in patients supported by p-BiVADs or t-TAH. Multivariate analysis revealed that survival while on transplantation was not affected by the type of device implanted.

Neuronal localization of the 25-kDa specific thiamine triphosphatase in rodent brain.

Thiamine triphosphate (ThTP) is found in small amounts in most organisms from bacteria to mammals, but little is known about its physiological role. In vertebrate tissues, ThTP may act as a phosphate donor for the phosphorylation of certain proteins; this may be part of a new signal transduction pathway. We have recently characterized a highly specific 25-kDa thiamine triphosphatase (ThTPase) that is expressed in most mammalian tissues. The role of this enzyme may be the control of intracellular concentrations of ThTP. As the latter has been considered to be a neuroactive form of thiamine, we have studied the distribution of ThTPase mRNA and protein in rodent brain using in situ hybridization and immunohistochemistry. With both methods, we found the strongest staining in hippocampal pyramidal neurons, as well as cerebellar granule cells and Purkinje cells. Some interneurons were also labeled and many ThTPase mRNA-positive and immunoreactive cells were distributed throughout cerebral cortical gray matter and the thalamus. White matter was not significantly labeled. ThTPase immunoreactivity seems to be located mainly in the cytoplasm of neuronal perikarya. Immunocytochemical data using dissociated cultured cells from hippocampal and cerebellum showed that the staining was more intense in neurons than in astrocytes. The protein was rather uniformly located in the perikarya and dendrites, suggesting that ThTP and ThTPase may play a general role in neuronal metabolism rather than a specific role in excitability. There was no apparent correlation between ThTPase expression and selective vulnerability of certain brain regions to thiamine deficiency.

In vitro and in vivo modulation of 5-hydroxytryptamine-, thyrotropin-releasing hormone- and calcitonin-gene related peptide-like immunoreactivities in adult rat sensory neurons.

In a previous work we have shown that culturing adult rat dorsal root ganglia neurons modifies their neurotransmitter phenotype in such a way that cultured neurons synthesize transmitters that are not found in situ, while several other transmitters are expressed in a much higher percentage of neurons in culture than in situ [Schoenen J. et al. (1989) J. Neurosci. Res. 22, 473-487]. The aim of the present study was to investigate the origin and the nature of the relevant environmental signals that allow this plasticity to be expressed, focusing on three neurotransmitters: 5-hydroxytryptamine, thyrotropin-releasing hormone and calcitonin-gene related peptide. The main results can be summarized as follows: (1) culturing cells in fetal calf serum or on feeder layers of astrocytes, Schwann cells or fibroblasts partially inhibits the serotoninergic phenotype of dorsal root ganglia neurons; (2) in vivo disconnection of dorsal root ganglia from their spinal targets but not from their peripheral or supraspinal targets induces a significant increase of the percentage of 5-hydroxytryptamine- and thyrotropin-releasing hormone-positive neurons in disconnected ganglia; (3) growth factors such as ciliary neuronotrophic factor or basic fibroblast growth factor but not nerve growth factor repress 5-hydroxytryptamine and calcitonin gene-related peptide immunoreactivity in cultured sensory neurons. In conclusion, neurotransmitter gene expression of adult dorsal root ganglia neurons is controlled by complex influences. Our data suggest that thyrotropin-releasing hormone and 5-hydroxytryptamine gene expression are tonically repressed in vivo by factors originating from the spinal segmental level and that growth factors such as ciliary neurotrophic factor or basic fibroblast growth factor could be potential vectors of this repressing effect.

Pacemaker infective endocarditis.

We identified 33 patients with definite pacemaker endocarditis--that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were > or = 60 years of age (mean 66 +/- 3; range 21 to 86). Pouch hematoma or inflammation was common (58%), but other predisposing factors for endocarditis were rare. At the time that pacemaker endocarditis was found, the mean number of leads was 2.4 +/- 1.1 (range 1 to 7). The interval from the last procedure to diagnosis of endocarditis was 20 +/- 4 months (range 1 to 72). Endocarditis appeared after pacemaker implantation, early (< 3 months) in 10 patients and late (> or = 3 months) in 23 patients. Fever was the most common symptom, being isolated in 36%, associated with a poor general condition in 24%, and associated with septic shock in 9%. Transthoracic echocardiography showed vegetations in only 2 of 9 patients. Transesophageal echocardiography demonstrated the presence of lead vegetations (n = 20) or tricuspid vegetations (n = 3) in 23 of 24 patients (96%; p <0.0001 compared with transthoracic echocardiography). Pulmonary scintigraphy showed a typical pulmonary embolization in 7 of 17 patients (41%). Pathogens were mainly isolated from blood (82%) and lead (91%) cultures. The major pathogens causing pacemaker endocarditis were Staphylococcus epidermidis (n = 17) and S. aureus (n = 7). S. epidermidis was found more often in early than in late endocarditis (90% vs 50%; p = 0.05). All patients were treated with prolonged antibiotic regimens before and after electrode removal. Electrode removal was achieved by surgery (n = 29) or traction (n = 4). Associated procedures were performed in 9 patients. After the intensive care period, only 17 patients needed a new permanent pacemaker. Overall mortality was 24% after a mean follow-up period of 22 +/- 4 months (range 1 to 88). Eight patients who were significantly older (74 +/- 3 vs 63 +/- 3 years; p = 0.05) died < or = 2 months after electrode removal, whereas 25 were alive and asymptomatic.