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Biomedical subjects

Alexandre Mebazaa

Publications and source records attributed to Alexandre Mebazaa.

At least 19 recordsLinked to original sources
PubMed2006

Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: The EFICA study.

BACKGROUND: Little is known about the epidemiology of acute decompensated heart failure (ADHF) in patients admitted to intensive and coronary care units (ICU/CCU). Observational data may improve disease management and guide the design of clinical trials. AIMS: EFICA is an observational study of the clinical profile, management and survival of ADHF patients admitted to ICU/CCU. METHODS: The study included 599 patients admitted to 60 ICU/CCUs across France. Relevant data was recorded during hospitalisation. Survival was assessed at 4 weeks and 1 year. RESULTS: The main cause of ADHF was ischaemic heart disease (61%); 29% of patients had cardiogenic shock. Mortality was 27.4% at 4 weeks and 46.5% at 1 year, increasing to 43.2% and 62.5%, respectively, when including pre-admission deaths. Shock patients had the highest [57.8% vs. 15.2% without shock (p < 0.001)] and patients with hypertension and pulmonary oedema had the lowest 4-week mortality: (7%). Pre-admission NYHA class III-IV heart failure, not initial clinical presentation, influenced 1-year mortality. CONCLUSION: ADHF is a heterogeneous syndrome. Based on initial clinical presentation, three entities with distinct features and outcome may be described: cardiogenic shock, pulmonary oedema with hypertension, and 'decompensated' chronic heart failure. This should be taken into account in future observational studies, guidelines and clinical trials.

Aged↗
PubMed2006

The challenge of acute decompensated heart failure.

Acute heart failure syndromes (AHFS) is a broad spectrum of heterogeneous conditions including pulmonary oedema, hypertensive crisis, worsening exacerbated CHF and cardiogenic shock. HF hospitalizations have steadily risen with more than one million in 2004 in the United States and a similar number has been reported in Europe. Each year heart failure accounts for 6.5 million days spent in hospital in the USA and 1.4 million days in France. Mortality data are derived from registries or clinical trials. Registry data in patients admitted to general or cardiology wards such as in Euroheart Failure Survey and ADHERE provide a far more optimistic picture compared with data from consecutive unselected patients in the most acute situation. such as in EFICA. Four-week mortality was higher than 25% in this case. A great pathophysiologic understanding of the different features of the various AHFS is needed in order to identify targets for therapy and research. This includes hemodynamics, the role of myocardial injury, neurohormonal and cytokine abnormalities and the cardiorenal syndromes. So far, very little progress has been made in developing new, effective therapies and implementing management guidelines in this patient population. Future clinical trial endpoints should be better designed and tailored to the various pathophysiological conditions of this complex syndrome. The goal of AHFS therapy is not only to prevent disease progression but also to have a beneficial effect on an acute event that exacerbates disease progression. A combined endpoint assessing survival and rehospitalisation rates is becoming increasingly popular for acute therapies. Specific trials may also need to be designed according to the time of access to the patient.

Acute Disease↗
PubMed2006

Contemporary issues in the pharmacologic management of acute heart failure.

Acute heart failure is an evolving syndrome that continues to be defined by ongoing studies and registries. It is associated with significant morbidity and mortality and places a huge economic burden on health care systems. Improved understanding of the underlying pathophysiologic processes has prompted interest into understanding the implications of current and future pharmacologic management strategies beyond hemodynamics. Diuretics, vasodilators, and inotropes remain the mainstays of therapy with several new classes of agents on the horizon. Clinicians should understand the rationale for use and limitations of each therapy to maximize benefit and cost-effectiveness, while minimizing the potential for adverse outcomes.

Aged↗
PubMed2006

Endotoxin-induced myocardial dysfunction in senescent rats.

INTRODUCTION: Aging is associated with a decline in cardiac contractility and altered immune function. The aim of this study was to determine whether aging alters endotoxin-induced myocardial dysfunction. METHODS: Senescent (24 month) and young adult (3 month) male Wistar rats were treated with intravenous lipopolysaccharide (LPS) (0.5 mg/kg (senescent and young rats) or 5 mg/kg (young rats only)), or saline (senescent and young control groups). Twelve hours after injection, cardiac contractility (isolated perfused hearts), myofilament Ca2+ sensitivity (skinned fibers), left ventricular nitric oxide end-oxidation products (NOx and NO2) and markers of oxidative stress (thiobarbituric acid reactive species (TBARS) and antioxidant enzymes) were investigated. RESULTS: LPS (0.5 mg/kg) administration resulted in decreased contractility in senescent rats (left ventricular developed pressure (LVDP), 25 +/- 4 vs 53 +/- 4 mmHg/g heart weight in control; P < 0.05) of amplitude similar to that in young rats with LPS 5 mg/kg (LVDP, 48 +/- 7 vs 100 +/- 7 mmHg/g heart weight in control; P < 0.05). In contrast to young LPS rats (0.5 and 5 mg/kg LPS), myofilament Ca2+ sensitivity was unaltered in senescent LPS hearts. Myocardial NOx and NO2 were increased in a similar fashion by LPS in young (both LPS doses) and senescent rats. TBARS and antioxidant enzyme activities were unaltered by sepsis whatever the age of animals. CONCLUSION: Low dose of LPS induced a severe myocardial dysfunction in senescent rats. Ca2+ myofilament responsiveness, which is typically reduced in myocardium of young adult septic rats, however, was unaltered in senescent rats. If these results are confirmed in in vivo conditions, they may provide a cellular explanation for the divergent reports on ventricular diastolic function in septic shock. In addition, Ca2+-sensitizing agents may not be as effective in aged subjects as in younger subjects.

Aging↗
PubMed2005

Pharmacology of new agents for acute heart failure syndromes.

Current therapies for acute heart failure syndromes (AHFS) target hemodynamics by decreasing congestion or increasing myocardial contraction. Several new agents for AHFS use novel mechanisms of action that focus on new treatment targets, such as those providing anti-ischemic and anti-stunning effects, blocking vasopressin receptors, or blocking endothelin-1 receptors. For example, levosimendan acts as a calcium sensitizer and adenosine triphosphate-dependent potassium (K(ATP)) channel opener that increases contraction, causes vasodilation, and provides cardioprotective effects. This is accomplished by its dual mechanism of action. Levosimendan binds to cardiac troponin C, thereby enhancing calcium myofilament responsiveness and increasing myocardial contraction without increasing intracellular calcium levels. Thus, contraction is increased with no significant increase in myocardial oxygen consumption. The opening of K(ATP) channels by levosimendan causes vasodilation and exerts anti-ischemic and anti-stunning effects on the myocardium. Other new agents target neurohormonal pathways. Tezosentan is an antagonist of endothelin-1 receptors A and B. By inhibiting endothelin-1 receptors, tezosentan may counteract the activities of endothelin-1, which include vasoconstriction, proarrhythmic activities, potentiation of other neurohormones, and mediation of increased vascular permeability. Tolvaptan is a vasopressin V2-receptor antagonist that functions as an aquaretic (ie, it increases urine volume and serum sodium with little or no sodium loss). Therefore, by using novel mechanisms of action, these agents may provide new opportunities for helping patients with AHFS.

Acute Disease↗
PubMed2005

Randomized clinical trials with levosimendan.

There are important unmet needs in the treatment of acute heart failure syndromes (AHFS). The unique dual mechanism of action of levosimendan suggests that this new agent may help fill some of these unmet needs. A review of randomized, controlled clinical trials with levosimendan demonstrated that it is well tolerated, and its use results in significantly reduced pulmonary capillary wedge pressure (PCWP) and increased cardiac output. Effects of levosimendan on PCWP and cardiac output are more pronounced than those observed with dobutamine. Levosimendan treatment is also associated with significantly improved clinical symptoms. Moreover, data from 3 trials indicate that levosimendan treatment was associated with improved 6-month survival compared with dobutamine treatment or placebo. Emerging data suggest that levosimendan is beneficial for patients with acute myocardial ischemia. Thus, early clinical indicators suggest that levosimendan may help prevent myocardial injury during hospitalization for AHFS and may be well suited for first-line therapy for AHFS.

Acute Disease↗
PubMed2005

Edge-to-edge technique to treat post-mitral valve repair systolic anterior motion and left ventricular outflow tract obstruction.

BACKGROUND: Systolic anterior motion of the mitral valve causing left ventricular outflow tract obstruction is an uncommon complication of mitral valve repair that may necessitate immediate additional surgical action. We prospectively evaluated the technique of the edge-to-edge suture on post-mitral repair systolic anterior motion, which persisted despite conservative treatment. METHODS: From March 2002 to March 2004, 4 of 112 patients requiring mitral valve repair surgery for chronic degenerative mitral regurgitation had systolic anterior motion with severe left ventricular outflow tract obstruction and mitral regurgitation. All 4 patients (mean age, 50 years) had posterior leaflet prolapse with chordal rupture with a billowing anterior leaflet, but without chordal rupture. Repair was achieved through a quadrangular resection of the posterior leaflet, completed by plication of the annulus in 2 patients and leaflet sliding in the other 2. All patients had mitral annuloplasty; two patients had a complete CE Physio ring (Edwards Lifesciences, Irvine, CA) inserted, whereas the other 2 patients had an open CG Future band (Medtronic, Minneapolis, MN). Routine perioperative transesophageal echocardiography showed systolic anterior motion, severe left ventricular outflow tract obstruction (> 50 mm Hg), and mitral regurgitation. After resuming cardiopulmonary bypass, all patients had an edge-to-edge suture at the middle part of the free edge of the anterior and posterior leaflets. RESULTS: The control transesophageal echocardiography showed in all cases disappearance of the systolic anterior motion, of the left ventricular outflow tract obstruction and of mitral regurgitation. Mean follow-up was 14 months (range, 6 to 28 months). All patients were in New York Heart Association's functional class I. CONCLUSIONS: With the edge-to-edge repair, the early and 2-year results were satisfactory with total disappearance of the systolic anterior motion, of the left ventricular outflow tract obstruction and of the recurrent mitral regurgitation.

Cardiopulmonary Bypass↗
PubMed2005

Cardiac and renal effects of levosimendan, arginine vasopressin, and norepinephrine in lipopolysaccharide-treated rabbits.

BACKGROUND: Because sepsis-induced myocardial dysfunction related to sepsis is at least partially related to a decrease in cardiac myofilament response to calcium, the use of the new myofilament-calcium sensitizer, levosimendan, has been proposed. In addition, arginine vasopressin is increasingly proposed as a vasopressor in septic patients, although data on its effects on cardiac function are still scarce. The aim of the current study was to assess, invasively and noninvasively, whether levosimendan, arginine vasopressin, and norepinephrine, either alone or combined, may modify sepsis-induced myocardial dysfunction and renal hemodynamics. METHODS: Thirty-six hours after lipopolysaccharide or saline administration, rabbits were studied either after slight sedation for echocardiography or after general anesthesia with sodium pentobarbital for the following measurements: aortic flow velocity and maximum acceleration of blood flow in the ascending aorta and renal macrocirculation and microcirculation. RESULTS: Levosimendan improved, within 30 min of administration, both maximum acceleration of blood flow by 20 +/- 12% (n = 8; P < 0.05) and left ventricular shortening fraction by a similar extent. Furthermore, low doses of arginine vasopressin markedly deteriorated cardiac function via an afterload-independent mechanism, even when animals were pretreated with levosimendan, whereas norepinephrine showed no detrimental effects on cardiac function. The study also showed that norepinephrine often improved renal medullary blood flow, whereas arginine vasopressin consistently decreased it. CONCLUSION: Levosimendan and norepinephrine both exert beneficial effects in endotoxemic animals and should be further explored in human sepsis trials.

Animals↗
PubMed2005

Lack of alteration of endogenous nitric oxide pathway during prolonged nitric oxide inhalation in intensive care unit patients.

OBJECTIVE: To compare hemodynamic and gasometric variables and the plasma concentrations of nitric oxide metabolites (cyclic guanosine monophosphate and nitrate and nitrite), endothelin-1, and renin-angiotensin metabolites before and after the start of nitric oxide inhalation, after prolonged nitric oxide inhalation, and before and after nitric oxide withdrawal. DESIGN: Prospective study. SETTING: Surgical intensive care unit, university hospital. SUBJECTS: Patients with acute lung injury and right ventricular failure. INTERVENTIONS: Nitric oxide inhalation (10-12 ppm) during a median of 2.9 days (12 hrs to 6.5 days). MEASUREMENTS AND MAIN RESULTS: The pulmonary vasodilator effects of inhaled nitric oxide improved arterial oxygenation in patients with acute lung injury (p < .05) and reduced right atrial pressure in patients with right ventricular dysfunction (p < .01). These beneficial effects lasted the whole period of prolonged inhaled nitric oxide therapy up to 6.5 days. However, when inhaled nitric oxide was withdrawn, pulmonary vasodilator effects rapidly disappeared, and Pao2/Fio2 ratio markedly deteriorated in all studied patients to return to pre-inhaled nitric oxide levels. Changes in plasma cyclic guanosine monophosphate and nitrate and nitrite paralleled those of pulmonary vasodilatory effects. An immediate increase in plasma cyclic guanosine monophosphate with a slightly delayed increase in plasma nitrate and nitrite was observed at inhaled nitric oxide start with no attenuation during the prolonged inhaled nitric oxide therapy. A marked decrease toward pre-inhaled nitric oxide levels was seen within hours of inhaled nitric oxide withdrawal. In addition, no alteration of plasma endothelin-1 or renin-angiotensin mediators was observed during or after inhaled nitric oxide therapy. CONCLUSIONS: Our study showed a lack of attenuation in the beneficial effects of inhaled nitric oxide and a lack of alteration of endogenous nitric oxide, endothelin-1, and renin-angiotensin pathways during prolonged nitric oxide inhalation.

Administration, Inhalation↗
PubMed2004

Case report: greater meningeal inflammation in lumbar than in ventricular region in human bacterial meningitis.

Differences in the composition of ventricular and lumbar cerebrospinal fluid (CSF) based on single pairs of samples have previously been described. We describe a patient that developed post-surgical recurrent meningitis monitored by daily biochemical and bacteriological CSF analysis, simultaneously withdrawn from lumbar space and ventricles. A 20-year-old Caucasian man was admitted to the ICU after a resection of a chordoma that extended from the sphenoidal sinus to the anterior face of C2. CSF was continuously leaking into the pharyngeal cavity after surgery, and three episodes of recurrent meningitis, all due to Pseudomonas aeruginosa O12, occurred. Our case showed permanent ventricular-to-lumbar CSF gradients of leukocytes, protein and glucose that were increased during the acute phase of meningitis, with the greatest amplitude being observed when bacteria were present in both ventricular and lumbar CSF. This might suggest a greater extent of meningeal inflammation in the lumbar than in the ventricular region. Our case also showed that the increase in intravenous antibiotics (cefepim from 8 to 12 g/day and ciprofloxacine from 1.2 to 2.4 g/day) led to an increase in concentration in plasma but not in CSF.

Adult↗