Management of anticancer treatment in patients under chronic dialysis: results of the multicentric CANDY (CANcer and DialYsis) study.

BACKGROUND: One million people worldwide benefit from chronic dialysis, with an increased rate in Western countries of 5% yearly. Owing to increased incidence of cancer in dialyzed patients, the management of these patients is challenging for oncologists/nephrologists. PATIENTS AND METHODS: The CANcer and DialYsis (CANDY) retrospective multicenter study included patients under chronic dialysis who subsequently had a cancer (T0). Patients were followed up for 2 years after T0. Prescriptions of anticancer drugs were studied with regard to their renal dosage adjustment/dialysability. RESULTS: A total of 178 patients from 12 institutions were included. The mean time between initiation of dialysis and T0 was 30.8 months. Fifty patients had received anticancer drug treatment. Among them, 72% and 82% received at least one drug needing dosage and one drug to be administered after dialysis sessions, respectively. Chemotherapy was omitted or prematurely stopped in many cases where systemic treatment was indicated or was often not adequately prescribed. CONCLUSIONS: Survival in dialysis patients with incident cancer was poor. It is crucial to consider anticancer drug treatment in these patients as for non-dialysis patients and to use current available specific drug management recommendations in order to (i) adjust the dose and (ii) avoid premature elimination of the drug during dialysis sessions.

Hypertension in renal transplantation: donor and recipient risk factors.

AIMS: To determine the respective roles of donor and recipient factors in the subsequent development of hypertension after renal transplantation. PATIENTS AND METHODS: All the patients transplanted between January 1990 and December 1999 who still had a functioning graft 1 year post-transplant (n = 321) were retrospectively studied. Blood pressure was assessed at 1 year post-transplant. Hypertension was defined as a systolic BP > or equal 140 mmHg or diastolic BP > or equal 90 mmHg, or use of antihypertensive medication. Relevant donor and recipient characteristics were recorded. RESULTS: Two-hundred-and-sixty-three patients (82%) were hypertensive. In multivariate analysis, pretransplant hypertension (RR, 1.74, 95% CI, 1.07 to 2.87), anticalcineurin use (RR, 2.59, 95% CI, 1.13 to 5.92), urinary protein excretion (RR, 1.84, 95% CI, 1.06 to 3.18), BMI (RR, 1.08, 95% CI, 1.01 to 1.16), donor age (RR, 1.28,95% CI, 1.05 to 1.59, for each 10-year increase in donor age) and donor aortorenal atheroma (OR, 2.34; 95% CI, 1.24 to 4.46) were associated with hypertension. Among patients under calcineurin inhibitors, those receiving cyclosporine were more prone to have hypertension than those receiving tacrolimus (88.7% vs 78%; p = 0.04). CONCLUSION: Both recipient and donor factors contribute to hypertension in RTR.

Determinants of mean arterial pressure and pulse pressure in chronic haemodialysis patients.

Hypertension is highly prevalent in the dialysis population, and has been implicated in the pathogenesis of the observed excess of cardiovascular morbidity and mortality in these patients. Nevertheless, there are no reports on the clinical and biochemical determinants of both pulse pressure (PP) and mean arterial pressure (MAP) in dialysis populations. A total of 541 haemodialysed patients from 11 dialysis centres were included in the study. The demographic, clinical, and biological characteristics were recorded. Both pre- and post- dialytic blood pressures (systolic and diastolic) were measured. PP and MAP were calculated. Mean predialytic PP was 67 +/- 17 mm Hg and significantly decreased after dialysis (60 +/- 18 mm Hg; P < 0.0001). In multivariate analysis, a 10 mm Hg increase in PP was positively associated with age (RR, 2.01; 95% CI, 1.35-5.01, for a 10-year increase in age), diabetes mellitus (RR, 1.08; 95% CI, 1.04-1.14), interdialytic weight gain (IWG) (RR, 1.84; 95% CI, 1.07-3.18, for 1% increase in IWG), and current smoking (RR, 2.59; 95% CI, 1.13-5.92) and negatively with Hb concentration (RR, 0.92; 95% CI, 0.84-0.99, for a 1 g/100 ml in Hb). Mean predialytic MAP was 98 +/- 15 mm Hg and significantly decreased after dialysis (91 +/- 16 mm Hg; P < 0.0001). In multivariate analysis, a 10 mm Hg increase in MAP was positively associated with parathyroid hormone (PTH) (RR, 1.32; 95% CI, 1.15-1.6, for 50 ng/ml in PTH), erythropoietin (EPO) treatment (RR, 1.09; 95% CI, 1.03-1.16), and current smoking (RR, 1.87; 95% CI, 1.39-2.41). PP and MAP are associated with different clinical parameters. Most of these factors are potentially reversible. Smoking cessation, correction of anaemia and limitation of IWG should be important challenges for physicians in care of dialysis patients.

Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients.

The high incidence of cardiovascular disease in hemodialyzed (HD) patients is well established and oxidative stress has been involved in this phenomenon. The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress. Sixteen HD patients were successively assessed for one month (i) on a high biocompatible synthetic dialyzer (AN) and (ii) on a vitamin E-coated dialyzer (VE). Blood samples were taken before and after the dialysis session at the end of each treatment period. HD session conducted with the AN dialyzer was responsible for acute oxidative stress, significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress. Plasma elastase activity, reflecting neutrophil activation, was also increased; soluble P-selectin, reflecting platelet activation, did not show any variation. The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane: basal vitamin C level was higher, and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased. Plasma vitamin E levels were not affected. Our study demonstrates that HD is associated with oxidative stress, which can be partially prevented by the use of a vitamin E-coated dialyzer. Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils.

Hyperhomocyst(e)inemia as a risk factor after renal transplantation.

Cardiovascular disease (CVD) is one of the leading cause of mortality in renal transplant recipients. Authors review accepted CVD risk factors. The role of additional factors like increased homocysteine level is discussed.

Polycystic kidney disease as a risk factor for post-transplant diabetes mellitus.

BACKGROUND: Insulin resistance with compensatory hyperinsulinaemia has been reported in adult polycystic kidney disease (APKD) patients. Diabetes mellitus is a common complication following transplantation and previous studies have demonstrated that inadequate insulin secretion was a prerequisite for the development of post-transplant diabetes mellitus (PTDM). We conducted a retrospective study to determine whether APKD is a risk factor for PTDM. METHODS: Twenty-six consecutive patients transplanted because of end-stage renal disease due to APKD were studied. A control patient matched for age, gender, immunosuppressive therapy and transplant year was selected for each APKD patient. PTDM was defined by fasting glycaemia exceeding 7.8 mmol/l and the need for insulin or oral antidiabetic therapy. RESULTS: Age, renal function, immunosuppressive regimen, number of acute rejection, cumulative dose of steroids and haemodialysis duration before transplantation were similar in both groups. PTDM occured in 10 APKD patients and four controls (34.6% vs 15.3%; P < 0.005). Among diabetic patients, six APKD patients and two controls required insulin therapy (60% vs 50%; P = n.s.). Diabetic patients were significantly older (55.8 +/- 7 years vs 50.2 +/- 11 years; P < 0.05). CONCLUSION: Although retrospective, this study suggests that APKD confers an increased risk of PTDM.

[Diagnostic criteria of ventricular tachycardia]. / Critères de diagnostic des tachycardies ventriculaires.

When ventricular tachycardia is very rapid or complicates cardiac disease it must be diagnosed as rapidly as possible so as not to delay treatment. A careful analysis of the surface electrocardiogramme is usually sufficient to distinguish ventricular tachycardia from other-wide QRS complex tachycardias when the widening is due to ventricular aberration. The diagnosis is easier when the start of the tachycardia is recorded or when the sinus rhythm is interspersed with ventricular extrasystoles of the same morphology as that of the tachycardia. Similarly, atrioventricular dissociation is diagnostic of ventricular tachycardia but its negative predictive value is weak. Extreme axial deviation of the QRS complexes, concording morphology in leads V1 or V2 and V6 and the analysis of the QRS complexes in the precordial leads nearly always enables identification of supraventricular tachycardia with aberration. On the other hand, the distinction between other causes of wide QRS complexes (supraventricular tachycardia with preexcitation or intraventricular conduction defects) remains difficult in the absence of a reference electrocardiogramme and the clinical context.

Hemodynamic correlates of effective arterial elastance in mitral stenosis before and after balloon valvotomy.

This study had the purpose of documenting the hemodynamic correlates of effective arterial elastance (Ea; i.e., an accurate estimate of hydraulic load) in mitral stenosis (MS) patients. The main hypothesis tested was that Ea relates to the total vascular resistance (R)-to-pulse interval duration (T) ratio (R/T) in MS patients both before and after successful balloon mitral valvotomy (BMV). High-fidelity aortic pressure recordings were obtained in 10 patients (40 +/- 12 yr) before and 15 min after BMV. Ea value was calculated as the ratio of the steady-state end-systolic aortic pressure (ESAP) to stroke volume (thermodilution). Ea increased after BMV (from 1.55 +/- 0.63 to 1.83 +/- 0.71 mmHg/ml; P < 0.05). Throughout the procedure, there was a strong linear relationship between Ea and R/T: Ea = 1.09R/T - 0.01 mmHg/ml, r = 0.99, P = 0.0001. This ultimately depended on the powerful link between ESAP and mean aortic pressure [MAP; r = 0.99, 95% confidence interval for the difference (MAP - ESAP) from -18.5 to +4.5 mmHg]. Ea was also related to total arterial compliance (area method) and to wave reflections (augmentation index), although to a lesser extent. After BMV, enhanced and anticipated wave reflections were observed, and this was likely to be explained by decreased arterial compliance. The present study indicated that Ea depended mainly on the steady component of hydraulic load (i.e., R) and on heart period (i.e., T) in MS patients.

[Radiofrequency ablation of accessory atrioventricular pathways]. / Ablation des voies accessoires par radiofréquence.

Since its introduction at the beginning of the 1980s, radiofrequency ablation of accessory atrioventricular pathways has become method because of its excellent results and the indications have increased to cases in which only symptomatic improvement is the objective. These advances have been made possible by technical innovations to the generators of the radiofrequency current and, above all, to the ablation catheters which enable mapping nearly all the perimeter of the atrioventricular rings and reach all the accessory pathways irrespective of their site. The approach depends on the localisation of the accessory pathway but the criteria of mapping are the same: detection of a specific accessory pathway potential, precession or concordance (depending on the topography) of the initial peak of the endocavitary ventriculogramme and the onset of the delta wave on the surface ECG, QS morphology of the ventriculogramme on monopolar recording, shortest VA' interval in orthodromic reciprocating tachycardia for latent kent bundles. In specialised centres, the global success rate is 90 to 98% but certain sites, especially the right lateral pathways, are more difficult to attain. The complication rate is about 4% but it tends to decrease with the experience of the operating teams and close monitoring of the patients. However, there persists an uncertainty concerning potentially arrhythmogenic effects of the lesions induced which justifies restricting the indications in young children.

[Classification and pitfalls of atrioventricular blocks]. / Classification et pièges des blocs auriculoventriculaires.

Atrioventricular blocks may be classified according to their degree, their site and their aetiology. Assessing the degree of block is not always easy when the P waves are poorly visible and/or masked by the ventricular complexes. Affirmation that a 2nd degree block is a Mobitz II block requires examination of the ECG to differentiate it from "false" Mobitz II due to variable PP intervals or concealed hisian extrasystoles. Complete atrioventricular block is easy to define on the ECG but not always synonymous with totally blocked conduction and should be interpreted taking into account the frequency of escape beats. Determining the site of block is important as it has therapeutic implications; the type of block evaluated from the surface ECG also provides useful but not always decisive information. The investigation of the aetiology of the block is valuable for differentiating acute, transient blocks from chronic (permanent or paroxysmal) blocks, the former sometimes requiring temporary but rarely permanent cardiac pacing.

Initial and long-term evaluation of escape rhythm after radiofrequency ablation of the AV junction in 50 patients.

Between 1986 and 1994, 50 patients (mean age 63 +/- 13 years), 25 of whom had organic heart disease and presenting with atrial arrhythmias refractory to 5.6 +/- 1.6 antiarrhythmic drugs, underwent radiofrequency ablation (5 +/- 3 pulses by procedure; duration of pulses 50.5 +/- 32 s) of the proximal AV junction to create complete and permanent AV block. The escape rhythm was studied immediately after the procedure and during long-term follow-up. Immediately after the procedure, an escape rhythm was observed in 80% of the patients (junctional in 92%). Over a mean follow-up of 36 +/- 16 months in 47 patients (2 patients died before assessment of escape rhythm and 1 was lost to follow-up), an escape rhythm was present in 39 patients (83%) and absent in the remaining 8 (17%). The only significant difference between the two groups was the initial presence of an escape rhythm (P = 0.008). However, three patients with an initial escape rhythm had none during long-term follow-up. The initial presence of an escape rhythm as a predictive factor of its presence during follow-up had a sensitivity of 87%, specificity of 63%, positive predictive value of 92%, and negative predictive value of 50%. Thus, the absence of an escape rhythm during long-term follow-up causing pacemaker dependency was noted in 1 of 6 patients. This represents a limitation to this palliative treatment, which should be reserved for patients suffering from supraventricular tachycardias refractory to other treatments.

[Double responses]. / Les doubles réponses.

Double response is a rare electrocardiographic phenomenon requiring two atrioventricular conduction pathways with very different electrophysiological properties. Double ventricular responses are the usual manifestation: an atrial depolarisation (spontaneous or provoked, anticipated or not) is followed by a first ventricular response dependent on an accessory pathway or a rapid nodal pathway and then a second response resulting from sufficiently delayed transmission through a nodal pathway for the ventricles to have recovered their excitability when the second wave of activation reaches them. A simple curiosity when isolated and occurring under unusual conditions, particularly during electrophysiological investigation of the Wolff-Parkinson-White syndrome, the double response may initiate symptomatic non-reentrant junctional tachycardia when associated with nodal duality and repeating from atria in sinus rhythm. The functional incapacity and resistance to antiarrhythmic therapy may require referral for ablation of the slow pathway.

Evaluation of radionuclide angiography in diagnosis of arrhythmogenic right ventricular cardiomyopathy.

OBJECTIVES: The accuracy of Fourier analysis of radionuclide angiography for the diagnosis of arrhythmogenic right ventricular cardiomyopathy was assessed versus X-ray right ventricular angiography. BACKGROUND: In patients with recurrent right ventricular tachycardia, the diagnosis of arrhythmogenic right ventricular cardiomyopathy is based on the presence of right ventricular wall motion abnormalities on conventional X-ray angiography without evidence of other heart disease. METHODS: X-ray and radionuclide angiography were prospectively compared in 73 patients with ventricular tachycardia. We analyzed the presence of a right ventricular enlargement, global hypokinesia and segmental wall motion abnormalities, using visual analysis for both techniques and Fourier analysis for radionuclide angiography. Disease was noted as absent or present and as diffuse or localized. The interobserver reproducibility of both techniques for the diagnosis of right ventricular wall motion abnormalities was tested in 27 randomly selected patients. RESULTS: According to X-ray angiography, 53 patients were considered to have arrhythmogenic right ventricular cardiomyopathy (22 diffuse, 31 localized forms) and 20 patients a normal right ventricle. The sensitivity of radionuclide angiography was 94.3%, specificity 90% and positive and negative predictive values 96% and 85.7%, respectively. Agreement for the location of the wall motion abnormalities was 60% for the apex, 76% for the outflow tract, 82% for the inferior wall and 74% for the free wall. The diagnostic interobserver reproducibility of X-ray and radionuclide angiography was 74% and 96.2%, respectively. CONCLUSIONS: In a selected cohort, Fourier analysis of radionuclide angiography is an accurate and reproducible tool for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

[Electrocardiographic aspects of atrial fibrillations]. / Aspects électrocardiographiques des fibrillations auriculaires.

The electrocardiographic analysis of atrial fibrillation is usually easy. However, some cases may be difficult to interpret: the organisation and voltage of the fibrillation waves can be very variable leading to appearances of atypical flutter in cases with large "f" waves or, conversely, in cases with low voltage fibrillation, to those of sinus mode dysfunction. The ventricular response may be slow: the conduction is usually delayed in the atrioventricular node where concealed conduction plays an important role in determining the ventricular response. Regular ventriculogrammes correspond to a junctional or ventricular escape rhythms. Aberrant conduction in the His-Purkinje system may sometimes be observed after long diastoles (phase 4 block) but often terminates short, preceded by long cycles (phase 3 block). It is usually easy to differentiate them from ventricular ectopics or preexcitation by careful examination and application of classical diagnostic criteria.

[Mivazerol and other benzylimidazoles with alpha-2 adrenergic properties]. / Mivazerol et autres benzylimidazoles á properiétés alpha-2 adrénergiques.

4-Benzyl-imidazole compounds derived from Salbutanol are evaluated for potential adrenergic activities. The prevalent property of a series of new bioisosteres of catecholamines either of the saligenol-(ucb LO61) or benzamide-(Mivazerol) type is a selective alpha-adrenergic agonism, at the presynaptic level. The present study stresses the structural features responsible for the alpha-2-agonistic property.

[Electrophysiological mechanisms of ventricular arrhythmia in myocardial infarction]. / Mécanismes électrophysiologiques des arythmies ventriculaires de l'infarctus du myocarde.

In experimental models of coronary occlusion, the physiopathology of ventricular arrhythmias varies with its timing, there being three main phases: early, late and chronic. The early phase covers the first 30 minutes and is dominated by tachycardias and fibrillations resulting from multiple micro-reentry circuits which are the consequence of major changes in conduction and excitability created by acute ischaemia. These arrhythmias may be triggered by extrasystoles which have a different mechanism related to the injury current generated in the border zone between ischaemic and healthy cells. The late phase lasts about 72 hours: it is characterised by polymorphic ventricular extrasystoles and bursts of relatively slow ventricular tachycardia. Much more rapid tachycardia can be induced by stimulation. The origin of these arrhythmias is usually in the surviving Purkinje fibres of the subendocardium. The mechanisms are variable: abnormal automaticity, reentry or activity triggered by delayed after depolarisations. During the chronic phase, reentrant tachycardia is possible but only when induced by stimulation. Delayed conduction is the consequence of non-uniform antisotropism related to the disorientation of the myocardial fibres caused by fibrosis. In the clinical situation, most research has been centered on sustained monomorphic ventricular tachycardias of the chronic phase. Their mechanism is almost exclusively reentry (the circuits usually being located in the subendocardium) as suggested by the triggering and interruption of clinical tachycardias by stimulation, the recording of fragmented activation or prepotentials at the site of emergence of the tachycardia and the phenomena of pacing.