[Evaluation of the benefit of early valve surgery in the treatment of infective endocarditis. Contribution of propensity analyses]. / Evaluation du bénéfice de la chirurgie valvulaire précoce dans le traitement de l'endocardite infectieuse. Apport des analyses de propension.

Early valve surgery for infective endocarditis, that is surgery performed during the course of antibiotic therapy, is widely used. However, this intervention has never been proven effective in any clinical trial. Five recently published observational studies, using propensity analysis, analyzed the relationship between surgery and mortality. But they gave conflicting results, mainly because of their methodological limitations. Thus, to date, there is no reliable estimation of early valvular surgery impact on mortality. In addition, this example allows for discussing the interest of propensity analyses and to emphasizing their limitations.

[Staphylococcus aureus bacteremia and endocarditis]. / Bactériémies et endocardites àStaphylococcus aureus.

The prevalence of Stapylococcus bacteriaemia is increasing worldwide, because of the increasing use of invasive procedures leading to nosocomial infections, but also of a changing way of life (increasing fashion for tattoos or piercing, use of intravenous drugs). Infective endocarditis develops in 10-30% of the cases of staphylococcus bacteriaemia. Staphylococcus aureus endocarditis must be suspected when it develops in the year following heart surgery or implantation of permanent devices. In drug users, it usually involves the tricuspid valve. According to the resistance of the germ to meticillin, antibiotic therapy uses a combination of intravenous penicillin or glycopeptide and an aminoside. Other antibiotics such as fosfomycin, rifampicin, fusidic acid, or clindamycin can be used when aminosides are contra-indicated. The role of newer antibiotic agents, such as daptomycin or linezolide, remains to be established.

[Non-valvular cardiac devices endocarditis]. / L'endocardite sur matériel de stimulation intracardiaque.

The risk of infective endocarditis on pacemaker or ICD is not negligible and has increased in recent years. Several host-related, procedure-related, or device-related risk factors have been recognized. Owing to its potential severity, the possibility of infective endocarditis should be envisaged in patients with repeated pulmonary infections or documented bacteremia and transesophageal echocardiography should then be used. The most common germs causing pacemaker endocarditis are staphylococci. Treatment requires prolonged antibiotic therapy and retrieval of the pacemaker and leads.

Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence.

OBJECTIVES: This study aimed to determine whether the myocardial T2 relaxation time, determined using a black-blood magnetic resonance imaging (MRI) sequence, could predict acute heart transplant rejection. BACKGROUND: The use of black-blood MRI sequences allows suppression of the confusing influence of blood signal when myocardial T2 is calculated to detect myocardial edema. METHODS: A total of 123 investigations, including cardiac MRI and myocardial biopsy, were performed 8 +/- 11 months after heart transplantation. Myocardial T2 was determined using an original inversion-recovery/spin-echo sequence. RESULTS: A higher than normal T2 (> or = 56 ms) allowed an accurate detection of the moderate acute rejections evidenced at baseline biopsy (> or = International Society for Heart and Lung Transplantation grade 2): sensitivity, 89% and specificity, 70% (p < 0.0001). T2 was increased in grade 2 (n = 11) compared with grade 0 (n = 49, p < 0.05), grade 1A (n = 34, p < 0.05) and grade 1B (n = 21, p < 0.05); T2 was further increased in grade 3 (n = 8) compared with grade 2 (p < 0.05). In addition, in patients without rejection equal to or greater than grade 2 at baseline, a T2 higher than normal (> or = 56 ms) was correlated with the subsequent occurrence of equal or greater than grade 2 rejection within the next three months: sensitivity 63% (12/19) and specificity 78% (64/82) (p = 0.001). CONCLUSIONS: Myocardial T2 determined using a black-blood MRI sequence, is sufficiently sensitive to identify most of the moderate acute rejections documented with biopsy at the same time, but is also a predictor of the subsequent occurrence of such biopsy-defined rejections.

[Use of ecarin clotting time in whole blood for monitoring recombinant hirudine treatment during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia]. / Utilisation du temps de coagulation par l'écarine en sang total pour la surveillance d'un traitement anticoagulant par lépirudine (Refludan au cours de circulation extracorporelle dans un contexte de thrombopénie induite par l'héparine.

Lepirudin (Refludan is a recombinant hirudin, approved for anticoagulation treatment of heparin-induced thrombocytopenia patients with thrombosis. We report here our method for laboratory monitoring with ecarin clotting time (ECT) of hirudin therapy as anticoagulation for cardiac surgery. Ecarin is extracted from the Echis carinatus snake venom and directly converts prothrombin to its intermediate, meizothrombin. This one binds in a stoechiometric way to hirudin to be proportioned in whole blood. The activation of coagulation starts up only when the totality of the hirudin is bound to the meizothrombin. To minimize the effect of dilution related to the CEC on the prothrombin and fibrinogen levels, thus lengthening the ECT, the specimen to be tested is diluted with normal whole blood. In 1997, when we have performed our first surgery with cardiopulmonary bypass, only one team (Pötzsch et al., 1997) had described the use of the ECT in whole blood. We describe in this work our assay to dose hirudin with ECT after dilution in whole blood. This assay was used during 8 CEC among 7 patients affected with HIT (n = 6) or potentially sensitized with heparin (n = 1). Experimental conditions and interpretation of the assay are reported here. This test is fast enough to provide useful information for adjusting the dose during cardiopulmonary bypass.

[Mortality prognostic factors of cardiogenic shock complicating an acute myocardial infarction and treated by percutaneous coronary intervention]. / Facteurs pronostiques de mortalité chez les patients en etat de choc cardiogénique primaire traités par angioplastie en phase aiguë d'infarctus.

OBJECTIVE: To determine the in-hospital prognosis and late outcome of cardiogenic shock complicating acute myocardial infarction treated by early (< 24 hours) percutaneous coronary intervention (PCI). METHODS: Retrospective monocentric study of a consecutive cohort of patients undergoing early PCI (< 24 heures) for cardiogenic shock complicating acute myocardial infarction from 1994 to 2004. RESULTS: The cohort included 175 patients (mean age = 65 +/- 14 years, 68% male). A successful PCI was obtained in 69% of patients. The in-hospital mortality was 43%. Independent risk factors associated with an increased mortality were: absence of TIMI three flow (P < 0.0001), absence of smoking (P < 0.009) and the need for mechanical ventilation (P < 0.002). Nor stent use or anti GP IIb/IIa infusions were predictors of a better outcome. At hospital discharge, mean left ventricular ejection fraction (LVEF) was 38 +/- 12%. Kaplan-Meier estimate of survival was 63% for in-hospital survivors (maximum follow-up = 9 years). Independent predictors of an impaired long-term outcome were: a LVEF < 0.3 (P < 0.028) and 3-vessel disease on coronary angiography (P < 0.004). CONCLUSION: In-hospital mortality of patients suffering cardiogenic shock complicating acute myocardial infarction and treated by PCI remains high despite PCI improvement. The long-term survival appears, however, to be better than that of patients with coronary artery disease and low LVEF.

Activation of metalloproteinase-2, loss of matrix scleroprotein content and coronary artery calcification.

Plaques from the coronary arteries of explanted hearts showed massive calcification (15-fold increase) with a loss of scleroproteins (-36%), an increase in the collagen to elastin ratio (twofold) and activation (+15%) of matrix metalloproteinase-2 (MMP-2). Plaque-free portions of the coronary artery gave results similar to those obtained with the internal mammary artery. There was a significant correlation between plaque calcification and MMP-2 activation, suggesting that the two processes may be linked.

Changes in hemodynamic and metabolic parameters following induced brain death in the pig.

Changes in hemodynamic and metabolic parameters (systemic oxygen delivery, [DO2], oxygen consumption [VO2], arterial lactate content) in brain-dead and control pigs in the absence of any inotropic or fluid support were studied. Brain death was induced by the inflation of a Foley catheter balloon placed into the subdural space of the animals. Serial atrial natriuretic peptide (ANP) determinations were performed to evaluate concomitant changes occurring in the endocrine function of the heart. Experiments were completed by a volume expansion protocol to provide a dynamic evaluation of these parameters. A significant increase in heart rate (from 113 +/- 5 to 176 +/- 11 beats/min), pulmonary capillary wedge pressure (from 7 +/- 1 to 12 +/- 3 mmHg), dP/dt (from 2040 +/- 340 to 4200 +/- 660 mmHg/sec-1), cardiac output (from 2.4 +/- 0.2 to 3.3 +/- 0.4 L/min), mean arterial pressure (from 66 +/- 8 to 93 +/- 14 mmHg), and systemic oxygen delivery (from 360 +/- 30 to 530 +/- 90 ml/min-1), was observed following brain death induction. These parameters returned below basal values within 60 min. On the contrary, serum lactate and VO2 remained unchanged. Following volume expansion, brain-dead pigs exhibited impaired hemodynamic response, with a significant decrease in dP/dt, MAP, and DO2. These changes were accompanied by a significant decrease in VO2 and a significant increase in lactate plasma levels. At the same time, a similar increase in ANP release was observed in both groups in response to volume expansion, suggesting that despite impaired myocardial contractility, endocrine function of the heart was preserved following brain death. We conclude that brain death leads to early impaired left ventricular contractility, which could be responsible for the changes observed in aerobic to anaerobic metabolism in response to rapid volume infusion. These results suggest that the use of fluid infusion to reduce the need in inotropic support in conventional therapeutic modalities should be used with care in the management of a brain-dead potential organ donor.

Estimation of myocardial interstitial norepinephrine release after brain death using cardiac microdialysis.

Brain death is a pathophysiological condition associated with major hemodynamic changes, temporary myocardial ischemia, and histological damage of the heart. These modifications could be related to a major local release of norepinephrine from myocardial sympathetic nerve endings leading to norepinephrine cardiotoxicity. This study was designed to evaluate the utility of cardiac microdialysis to measure interstitial myocardial norepinephrine release resulting from brain death. The dialysis probe consisted in a 10 x 0.20-mm dialysis fiber with a 18,000 mol wt cutoff. Dialysis probes were implanted into the right and left ventricular walls of the beating heart in anesthetized pigs and perfused with Ringer solution at 2 microliters/min. Dialysate norepinephrine concentration was measured using HPLC with electrochemical detection. The relative recovery rate of norepinephrine in vivo was 34 +/- 4%. Interstitial fluid concentrations were obtained using the following formula: [C]interstitium = [C]dialysate/Recovery in vivo. After brain death, a transient increase in interstitial norepinephrine concentration was observed (from 0.74 +/- 0.20 to 4.50 +/- 0.60 ng/ml and 0.76 +/- 0.20 to 6.2 +/- 0.9 ng/ml in left and right ventricle, respectively, P < 0.01) which far exceeded plasma level increase (from 0.50 +/- 0.10 ng/ml to 0.91 +/- 0.20 ng/ml, P < 0.05). This increase in myocardial norepinephrine was, moreover, biphasic, with a second peak occurring 40 min after brain death. The present study confirms the onset of a dramatic increase in cardiac norepinephrine release from myocardial nerve endings following brain death, and demonstrate the utility of the new cardiac microdialysis technique to assess changes in interstitial fluid content.

Ro 44-9883, a new non-peptidic GPIIb-GPIIIa antagonist prevents platelet loss in a guinea pig model of extracorporeal circulation.

Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 44-9883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 +/- 4% and 25 +/- 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 +/- 8% and 54 +/- 9%; p < 0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 +/- 8%) and only slightly decreased at 60 min (80 +/- 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.

Experimental carotid thrombosis in the guinea pig.

The aim of our study was to develop a new carotid thrombosis model with an arterial shear rate close to that prevailing in affected arteries of patients with transient ischemic attacks (TIAs) and moderate carotid stenosis and to test various antithrombotic principles. In anaesthetized guinea pigs, carotid blood flow was monitored by a Doppler flow probe and the vessel was damaged by 2 or 3 brief pinches by a surgical forceps. The intravenous effects of aspirin (20 mg/kg), heparin (200 U/kg) and hirudin (500 micrograms/kg) or Ro 44-9883 (0.2 to 1 mg/kg), a new selective non-peptidic GP IIb-IIIa inhibitor were tested. After the damage, blood flow progressively decreased to zero and could regularly and reproducibly be restored by a mechanical shaking of the artery. The occlusive thrombus consisted mainly of platelet aggregates. The estimated shear rate in the damaged carotid artery was in the range of 1500 to 2800 s-1. The resulting cyclic flow variations (CFVs) were obtained in all the guinea pigs and were abolished in 10%, 20% and 60% of the animals treated with heparin, hirudin and aspirin, respectively. Ro 44-9883 abolished dose dependently the CFVs with 100% abolition at 1 mg/kg. Thus reproducible thrombosis without additional stenosis can be generated in the carotid artery of the guinea pig at a lower shear rate than that prevailing in the classical thrombosis models. GPIIb-IIIa blockade showed a higher curative efficacy than inhibition of the cyclooxygenase pathway or that of thrombin generation either through an antithrombin III dependent or independent mechanism.

Ro 44-9883, a new nonpeptide glycoprotein IIb/IIIa antagonist, prevents platelet loss during experimental cardiopulmonary bypass.

Extensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the study was to test the efficacy of Ro 44-9883, a new nonpeptide, reversible, glycoprotein IIb/IIIa antagonist in preventing platelet count drop in dogs undergoing cardiopulmonary bypass during 2 hours. Twenty-two heparinized dogs were divided into three groups, one control group (n = 9) not treated, one group treated with a low dose of Ro 44-9883 (145 micrograms/kg intravenously, n = 6), and one group treated with a high dose of Ro 44-9883 (870 micrograms/kg intravenously, n = 7). In the control group, platelet counts declined to 53% +/- 15% of initial levels at the start of cardiopulmonary bypass and remained lower than 80% of initial levels during follow-up. Platelet count drop was completely prevented in the Ro 44-9883 high-dose group, whereas it was only partially prevented in the low-dose group. Blood loss was similar in the three groups despite the fact that bleeding times were longer in the Ro 44-9883 high-dose group than in the control group. We conclude that Ro 44-9883, together with heparin as a standard anticoagulant, is highly effective in preventing platelet count drop during cardiopulmonary bypass without causing excessive bleeding.

Endocrine response to plasma volume expansion during the early postoperative period in heart transplant recipients.

The purpose of this study was to investigate the changes in endocrine control of blood pressure and electrolyte homeostasis during the early postoperative period after heart transplantation. Dynamic testing using volume-expansion to increase cardiac filling pressures was performed to determine changes in alpha atrial natriuretic peptide, renin, aldosterone, and vasopressin secretion in response to a physiologic stimulus. Volume expansion was performed on five heart transplant patients each day from postoperative day 1 to postoperative day 5. Alpha atrial natriuretic peptide, renin, aldosterone, and vasopressin plasma levels were assessed by radioimmunoassay before and during the 6 hours after the beginning of infusion. No significant changes in the secretion of any of the various hormones studied were found after volume expansion. Moreover, we found that heart transplant recipients were unable to increase water and sodium renal excretion after volume expansion. The physiologic decrease in vasopressin release after volume expansion appears to be altered by graft denervation. Furthermore, persistently elevated alpha atrial natriuretic peptide plasma levels at rest despite improved patient hemodynamic status and the absence of enhanced hormone secretion after a physiologic stimulus are in favor of an intrinsic hypersecretion of this hormone. Moreover, the absence of an appropriate renal response could be a major consequence of both the lack of further increased alpha atrial natriuretic peptide secretion and the heart denervation resulting from transplantation. This blunted renal response should be taken into account when managing patients in the early period after transplantation.

Left ventricular contractility after hypothermic preservation: predictive value of phosphorus 31-nuclear magnetic resonance spectroscopy.

Early graft failure accounts for a substantial portion of the mortality after heart transplantation. This factor underscores the need for the development of reliable methods for predicting graft performance and thus ensuring optimal clinical outcome. The aim of this study was to describe the link between myocardial metabolism evaluated throughout preservation with the use of phosphorus 31-nuclear magnetic resonance spectroscopy and ventricular contractility after reperfusion. Thirteen pig hearts were excised and preserved from 3 to 12 hours with clinical techniques. During preservation the hearts underwent phosphorus 31-nuclear magnetic resonance spectroscopy. After reperfusion, left ventricular contractility was evaluated with an isolated heart model undergoing isovolumetric contraction. Throughout storage, beta-adenosine triphosphate remained stable and intracellular pH and phosphocreatine decreased exponentially, whereas inorganic phosphate increased exponentially. Intracellular pH, phosphocreatine, inorganic phosphates measured at the onset of preservation, and intracellular pH and phosphocreatine measured at the end of preservation correlated significantly with the left ventricular contractility after reperfusion. We conclude that the metabolic state of myocardium at excision is especially important and that phosphorus 31-nuclear magnetic resonance evaluation of the heart during preservation appears to provide reliable indexes for predicting subsequent ventricular contractility after reperfusion.

Microdialysis in the estimation of interstitial myocardial neuropeptide Y release.

The purpose of this study was to investigate the feasibility of cardiac microdialysis for the in vivo estimation of cardiac interstitial peptide concentrations, and, to determine the changes in neuropeptide Y release in myocardial tissue during experimental brain death in pigs. Using a specifically designed concentric flexible probe, perfused with Ringer solution containing 0.5% of bovine serum albumin at a flow rate of 2 microliters/min, allowed us to obtain a 23 +/- 2% relative recovery rate in vitro. Based on these in vitro recovery data, a regional study of the kinetics of interstitial NPY levels following brain death was obtained by monitoring the changes in NPY dialysate levels recorded from dialysis probes implanted into the right and left ventricular walls of the beating heart in vivo. Basal dialysate NPY levels determined by radioimmunoassay were of 95.2 +/- 7.0 and 93.2 +/- 9.1 pmol/l in left and right ventricle, respectively. Brain death was followed by a sustained 2 h increase in NPY dialysate levels in both ventricles (peak levels: 173.2 +/- 30.9 pmol/l in left ventricle, and 149.7 +/- 23.9 pmol/l in right ventricle), which then returned to control levels. We conclude that cardiac microdialysis is a simple and promising new tool for evaluating the role of peptides in cardiovascular regulation.

Myocardial effects of experimental acute brain death: evaluation by hemodynamic and biological studies.

BACKGROUND: Because of problems concerning the functional quality of heart transplants, more and more interest has been focused on the physiologic changes occurring during brain death, one of the major possible contributing factors to the myocardial alterations. METHODS: The aim of this study was to describe the link between acute experimental brain death and myocardial metabolism. This was achieved by in vivo 3-hour hemodynamic and biological (myocardial lactate production) studies and then in vitro 6-hour phosphorus-31 nuclear magnetic resonance spectroscopy. Two groups of pigs were involved in the study: group I (n = 10) as control and group II (n = 10) as brain-dead animals. RESULTS: Within the first hour, we observed a strong increase in myocardial activity associated with the onset of myocardial lactate production, lasting 2 hours and corresponding to a myocardial anaerobic metabolism period. Despite the apparent normalization before excision of the hearts, phosphorus-31 nuclear magnetic resonance spectroscopy revealed a significant decrease in adenosine triphosphate levels in group II when compared with group I. CONCLUSIONS: We conclude that, in our study, acute experimental brain death is associated with an early and transient period of myocardial anaerobic metabolism and adenosine triphosphate consumption. These myocardial consequences of brain death could partially explain some observations of heart graft dysfunction.

Inhaled nitric oxide as an adjunct to pulmonary thromboendarterectomy.

In chronic pulmonary vascular thrombotic disease, pulmonary thromboendarterectomy has proved to be effective in reducing pulmonary hypertension and improving gas exchange. However, persistent pulmonary hypertension and unrelenting reperfusion edema are the main causes of death. We report a case of pulmonary thromboendarterectomy followed by an immediate unfavorable postoperative course with acute and persistent pulmonary hypertension, gas exchange impairment, and heart dysfunction. In this particular case, inhaled nitric oxide was successfully administered.

Mitral valve tumor revealed by stroke.

Valvular tumors are uncommon and usually benign lesions, discovered accidentally or when neurological or cardiological complications occur. We report a case of mitral valve papillary fibroelastoma measuring less than 1 cm and revealed by stroke. Transesophageal echocardiography was the best method to establish the diagnosis as it provided higher discriminative power than the transthoracic echocardiography or nuclear magnetic resonance. The embolic risks justify the surgical treatment of these lesions while anticoagulation therapy can be suggested as a substitute to surgery for the high risk patients.

Aortic valve surgery in osteogenesis imperfecta: report of two cases and review of the literature.

Aortic insufficiency is a well known but uncommon valvular dysfunction in patients with osteogenesis imperfecta. In such cases, aortic valve surgery has rarely been performed, and carries a high risk of perioperative complications. We report two patients with osteogenesis imperfecta, who underwent elective successful aortic valve replacement. The surgical problems encountered in this connective tissue disorder are also reviewed.

Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin.

BACKGROUND: Acute pulmonary hypertension occurring after cardiopulmonary bypass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed endothelin antagonist affected the pulmonary hypertension induced by experimental cardiopulmonary bypass. METHODS: Pigs were anesthetized and instrumented to determine hemodynamic measurements. Pigs were randomized to receive either 3 mg/kg bolus + 7 mg/kg per h bosentan (n = 8) or saline (n = 7). All pigs underwent 90 min of cardiopulmonary bypass and were further observed for a 120-min period. RESULTS: In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and accompanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.005), whereas, in the treated group, bosentan completely prevented these deleterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.6%, P < 0.05). CONCLUSIONS: The present findings support the hypothesis that endogenous endothelin is a mediator of acute pulmonary hypertension occurring after cardiopulmonary bypass. Bosentan, a mixed endothelin antagonist completely prevented pulmonary hypertension after cardiopulmonary bypass and may, therefore, have therapeutic applications in the management of patients following cardiac surgery.