Prognostic impact of diabetes mellitus in patients with heart failure and preserved ejection fraction: a prospective five-year study.

OBJECTIVE: To evaluate the prognostic impact of diabetes mellitus (DM) in patients with heart failure and preserved ejection fraction (HFPEF) DESIGN: A five-year prospective observational study SETTING: Population of 368 consecutive patients from 11 healthcare establishments PATIENTS: All patients hospitalised for a first episode of HFPEF in 2000 in the Somme department, France. INTERVENTIONS: Diagnosis of heart failure (HF) was validated during the index hospitalisation by two independent cardiologists. Diabetic and non-diabetic groups were compared. After discharge, patients were managed by the general practitioner or referring cardiologist. MAIN OUTCOME MEASURES: Overall and cardiovascular mortality. RESULTS: The 96 diabetic patients (26%) were younger and had a higher prevalence of clinical coronary artery disease (CAD) than non-diabetic patients. Patients with DM had higher discharge prescription rates of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, nitrates and statins. During the five-year follow-up, 208 patients died (43.5%). DM was a potent independent predictor of five-year overall mortality (HR 1.77, 95% CI 1.27 to 2.48, p = 0.001). Compared to the expected survival of the age-matched and gender-matched general population, the five-year survival of patients with DM was dramatically lower (32% vs 79%). The five-year relative survival (observed/expected survival) of diabetic patients was lower than that of the non-diabetic group (41% vs 68%). Cardiovascular causes were responsible for >60% of deaths in the DM group. DM was associated with an increased risk of death in patients with clinical CAD (HR 1.82, 95% CI 1.02 to 3.25, p = 0.04), as well as in patients without clinical CAD (HR 1.85, 95% CI 1.22 to 2.82, p = 0.004). CONCLUSION: In patients with HFPEF, DM is a strong predictor of poorer long-term survival.

Interaction between pulse wave velocity, augmentation index, pulse pressure and left ventricular function in chronic heart failure.

Pulse wave velocity (PWV), the carotid augmentation index (AIx), and pulse pressure (PP) may be prognostic factors in heart failure, but the possible influence of the ejection fraction (EF) and other simple haemodynamic variables on them has not been investigated in this setting. Noninvasive methods were used to measure carotid-radial (CR), carotid-femoral (CF) PWV and AIx, and brachial PP, in 135 consecutive patients with stable symptomatic chronic heart failure. The patients were divided into two groups, with preserved (>or=40%) or reduced (<40%) EF. CF-PWV, AIx and PP were lower in the decreased EF group (8.85+/-2.77 versus 10.60+/-2.75 m/s, P<0.001; 121+/-21 versus 132+/-24, P=0.009 and 41+/-19 versus 67+/-17 mmHg, P<0.001), but CR-PWV values were similar regardless of the EF status. These results were not modified after adjustment for age and sex. Multiple regression analysis showed that AIx and PP were systematically related to time domain parameters (heart rate or ejection duration) and EF, whatever the group. CF-PWV was weakly related to time domain values and unrelated to mean blood pressure (BP) or EF in the preserved EF group, whereas it was related to both mean BP and EF in the low EF group. In conclusion, whatever the EF level, PP and AIx were strongly modulated in the time domain, by pressure and by the EF level. The same relationships were found with CF-PWV, but only in the reduced EF group. Whether CF-PWV is the best prognostic factor in patients with 'diastolic' heart failure must be confirmed in a prospective study.

[Heart failure and cachexia]. / Insuffisance cardiaque et cachexie.

Cachexia is related to a malnutrition state related to hypercatabolism. Initially described in cancer, it is also related to several chronic diseases including heart failure. Defined by an unintentional weight loss exceeding 7.5% of body mass during more than 6 months, it is presented by the association of nutritional deficiencies, digestive and/or urinary losses as well as metabolic abnormalities causing fat and lean mass loss and is associated to a poor prognosis. The pathophysiology of cachexia and heart failure presented some similarities associating especially neuro-hormonal activation, a cortisol/DHEA ratio imbalance, as well as pro-inflammatory cytokines activation. Currently the treatment of cachexia is mainly preventive, based on ACE-inhibitors and beta-blockers therapy and physical reconditioning. The benefits of hormonal and nutritional substitutes remains to be evidenced.

[Medical treatment of acute heart failure]. / Traitement médical de l'insuffisance cardiaque aiguë décompensée.

Medical treatment of acute decompensated heart failure has little changed in the last years, except with the advent of non-invasive ventilation. Doppler-echocardiography and BNP dosing have simplified the diagnostic approach and limited the need for invasion evaluation. Vasodilators remain probably underused whereas some doubts have emergency regarding the safety of positive inotropes. Analysis of the hemodynamic profile is mandatory for an optimal management of these patients. The next decade will be that of morbimortality trials in this common form of heart failure with severe prognosis.

Association between pulse pressure, carotid intima-media thickness and carotid and/or iliofemoral plaque in hypertensive patients.

Increased common carotid artery intima-media thickness (CCA-IMT) and carotid and/or iliofemoral (C/IF) plaque are frequent in subjects treated for hypertension, but their association with pulse pressure (PP) has rarely been studied. Using ultrasound techniques, CCA-IMT and C/IF plaques were studied in 323 hypertensive subjects, who were classified into four groups according to the adequacy of blood pressure (BP) control (systolic BP (SBP) <140 mmHg and diastolic BP (DBP) <90 mmHg) and PP (high or low). After adjustment for confounding variables, an increase in CCA-IMT was the only factor significantly and independently associated with high PP, irrespective of the effectiveness of blood pressure control and of antihypertensive drug treatment. CCA-IMT correlated with age, PP, waist-to-hip ratio, tobacco consumption, and heart rate. C/IF plaques correlated with age, tobacco consumption, diabetes mellitus, and dyslipidaemia. To conclude, even with SBP<140 mmHg and DBP<90 mmHg on treatment, hypertensive subjects may have increased CCA-IMT values and C/IF plaque. Four cardiovascular risk factors seem to be involved in these alterations, namely tobacco consumption, dyslipidaemia, diabetes and increased PP. Only the latter factor does not have a standardized effective treatment.

[Primary aldosteronism. A risk factor for aortic dissection?]. / Hyperaldostéronisme primaire. Un facteur de risque de dissection aortique?

Aortic dissection is a rare but severe disease. Numerous risk factors have been reported, all leading to an alteration of arterial structures, particularly extracellular matrix. Aortic dissection is a complication of arterial hypertension, whatever its origin. Primary aldosteronism, frequent cause of secondary arterial hypertension, is associated with arterial structural alterations, indirectly by a pressure factor, and directly by aldosterone, which modifies collagen contents and elastin/collagen ratios. In addition to the three previously reported cases, the three cases reported in the present paper lead to the hypothesis of a causal relationship between aldosteronism and aortic dissection. The need for hypertension screening and diagnosis of its potential causes, namely primary aldosteronism, is highlighted.

[Arterial hypertension, non-drug treatment and cardiovascular risk]. / Hypertension artérielle, traitement non médicamenteux et risque cardiovasculaire.

Four non-drug measures have been shown to be effective on reduction of blood pressure: low-salt diet, weight loss, reduction of alcohol consumption and sports activity. Other measures, mainly dietary (increased potassium intake, DASH diet), may also be effective. The two limits to non-drug treatment of HT are the absence of demonstrated benefit in terms of cardiovascular morbidity-mortality, and the difficulty to ensure good patient compliance with this type of often constraining measure. However, these non-drug measures could probably decrease the overall level of cardiovascular risk. The main drawback, related to the required modification of the patient's lifestyle, is poor compliance with these measures. Compliance can be improved by various methods which share in common their time-consuming nature.

Bile and blood ratios of cyclosporin and its metabolites in patients on continuous infusion during the first three weeks after liver transplantation.

Ten patients with orthotopic liver transplants were investigated during routine therapeutic monitoring to study the relationship between the concentrations of cyclosporin and its metabolites in blood, bile and urine, and whether this information can provide early signs of severe hepatic disorders post-transplantation. Cyclosporin (Sandimmun®) was administered by continuous infusion at a constant rate of 5 mg/kg/day, modified to keep the blood cyclosporin concentration within the target range (400 to 500 µg/L). The concentrations of cyclosporin and combined cyclosporin-metabolites in blood, bile and urine were assayed daily during the 3 post-transplantation weeks that the patients spent in intensive care.All patients developed cholestatis and cytolysis during the first week. The severity of these liver transplant disorders increased in 5 patients and decreased in the other 5 in the second week. The pharmacokinetics of cyclosporin differed in the 2 groups: in patients without severe hepatic disorders, the blood metabolites/cyclosporin ratio (M/C) stabilised at 1.2 ± 0.4 in week 2 and at 0.8 ± 0.2 in week 3, bile cyclosporin/blood cyclosporin (bile C/blood C) fluctuated around 13.5 (13.5 ± 9.5 in week 2 and 13.5 ± 9.0 in week 3) and the bile metabolite/blood metabolite (bile M/blood M) ratio was very high and variable (131 ± 86 in week 2 and 159 ± 116 in week 3). Metabolites significantly accumulated in the blood of patients with severe hepatic disorders (M/C = 2.8 ± 0.6 in week 2 and 3.5 ± 1.0 in week 3); bile C/blood C (2.6 ± 2.1 in week 2 and 3.4 ± 1.1 in week 3) and bile M/blood M (11.9 ± 7.8 in week 2 and 12.5 ± 7.9 in week 3) significantly decreased and showed less interindividual variability.Blood cyclosporin is usually monitored to help optimise the dosage. However, if this was extended to include the monitoring of metabolites in the blood, and cyclosporin and metabolites in the bile, it could provide an early indication of severe hepatic disorders in patients with transplanted livers.

[Major liver injury. Role of preoperative transcutaneous endoluminal aortic clamping]. / Traumatisme hépatique majeur. Intérêt du clampage aortique endoluminal transcutané pré-opératoire.

Severe contusion of the liver (type V in the Moore and Flint classification) still has a very poor prognosis. Exsanguination may lead to cardiac arrest when the abdomen is opened. Three patients with major liver injury were treated after percutaneous intra-aortic balloon occlusion and complete vascular exclusion of the liver. Two patients survived and one died due to complications resulting from lung trauma. The aorta was occluded with a balloon catheter inserted via the femoral route. The hepatic vascular exclusion was performed surgically after resuscitation had reestablished a satisfactory haemodynamic situation. Liver resection could then be performed under safe conditions. Aortic occlusion is a simple procedure with minimal disadvantages which could improve prognosis of major liver contusion by reducing the rate of intra-operative death.

Intrapleural bupivacaine analgesia after thoraco-abdominal incision for oesophagectomy.

Intrapleural bupivacaine administration is said to produce good analgesia for the pain induced by a subcostal incision. However, reports of its efficacy after thoracotomy are conflicting. The goal of this study was to compare the analgesia produced by intrapleural administration of bupivacaine after oesophagectomy using a thoraco-abdominal incision with that obtained from intrapleural saline. After informed consent and institutional approval were obtained, 20 patients were randomly assigned to two groups of 10 patients each. Subjects received intrapleurally 10 ml of either 0.25% bupivacaine with 1:200,000 adrenaline or normal saline, every 8 h, beginning on the first post-operative day and lasting for 4 days. Pain was evaluated using a visual-analogue scale 2 h after the first daily treatment at rest and during physiotherapy. Pain scores were significantly lower in the bupivacaine group than in the saline group. Additionally, PaO2 was significantly higher in the bupivacaine group than in the saline group on Day 1 (P less than 0.05). The plasma bupivacaine concentration never reached the level of toxicity. Plasma bupivacaine concentrations on Day 1 after the first intrapleural bupivacaine injection were less than 350 ng ml-1; on Day 4 after the last injection they were less than 1300 ng ml-1. In conclusion, intrapleural administration of bupivacaine produces effective analgesia after oesophagectomy performed with a thoracoabdominal incision. The technique is easy to perform and is safe.

Clinical pharmacokinetics after repeated intrapleural bupivacaine administration.

Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first-order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.

[Multiple-organ procurement for transplantation]. / Les prélèvements multiples d'organes en vue de transplantation.

In the last few years, the tremendous growth of clinical transplantations has greatly increased the need for grafts. Combined heart, liver and kidney harvesting in a same donor could provide an answer. The results are presented of multiple organ retrieval (MOR) carried out in an University hospital located in an area with 1,350,000 inhabitants. In addition to the usual problems of donor maintenance and legal aspects, it was necessary to carry out a specific work-up for each organ to be harvested. The job of the local coordinator was extremely important in the search for potential recipients and the organization of the procedure (time-table, air transport) in order to give optimal conditions. The priority given to retrieving the heart and in situ cooling of the liver and kidneys guaranteed the good quality of the harvested organs. Over a period of three years, 28 MOR have been carried out. Of the 94 organs harvested, 88 were transplanted in France or another European country (49 kidneys, 23 hearts, 16 livers); 75 are still functioning (47 kidneys, 19 hearts, 9 livers). As a result of this experience, and taking into account the need for organs, all brain dead patients should be considered as potential multiple organ donors, and not just as kidney donors. The intervention of several teams, often quite distant from the site of retrieval, requires careful planning. The surgical procedure, even when performed by a trained team, is often complex, perfect synchronization of the surgical steps of the operation being the most important point.(ABSTRACT TRUNCATED AT 250 WORDS)

Prilocaine in arthroscopy: clinical pharmacokinetics and rational use.

Prilocaine pharmacokinetics were determined in 60 patients receiving the drug by two different routes of administration (intra-articular and subcutaneous) during arthroscopy under local anesthesia with controlled pressure irrigation. Resorption of prilocaine by subcutaneous tissues was slow and did not lead to high serum levels. On the contrary, prilocaine resorption by the synovium was fast and induced a sharp serum peak (265.8 +/- 163.5 ng/ml) in the hour after the end of the examination. The drug was completely eliminated from the blood after 24 hours, as the prilocaine t1/2 is about 5 hours. The first procedure was perfected to reduce the risk of methemoglobinemia, which occurred in four of 105 patients. Applied pressure was lowered to 100 mm Hg to prevent the escape of anesthetic solution into the soft tissue of the leg, the prilocaine concentration was reduced to 1 gm/L, and the arthroscope was only set up after a delay to allow the intra-articular anesthetic effect of prilocaine to become established. So far, 200 arthroscopies have been performed with this improved protocol without any problem.