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.

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.

Evaluation of the elasticity and characteristic impedance of the ascending aorta in man.

In 30 patients, simultaneous measurements of ascending aortic pressure and diameter were performed, allowing one to evaluate: (1) the influence of age, the aortic diastolic pressure, and the radius on the aortic elasticity; (2) the correlations between characteristics impedance of the aorta (Zo), systemic arterial resistance, age and diastolic aortic pressure; and (3) the importance of Zo when comparing two indices of left ventricle performance; one during isovolumic phase ([dP/dt]/Pt)max and the other during the outflow phase (maximum acceleration of aortic blood flow).

Post-extrasystolic left ventricular peak pressure with and without left ventricular failure.

18 patients without valvular pathology, coronary artery disease, or idiopathic hypertrophic subaortic stenosis were haemodynamically and angiographically investigated in order to analyse the effects of a ventricular extrasystolic beat upon the post-extrasystolic left ventricular peak pressure. In eight normal patients (group I), the post-extrasystolic peak pressure (P.ES.P.P.) was lower than that of the pre-extrasystolic beat; in 10 patients with symptoms of left ventricular failure (group II) the P.ES.P.P. significantly increased. The reasons are: 1) cardiac origin: stroke volume increased more in group II; 2) arterial origin. a) aortic compliance was lower in group II (this is probably related to the older age of patients in group II), and by decrease in end-diastolic aortic pressure was smaller in group II. Part of this arterial effect (2b) may probably be explained from the fact that post-extrasystolic compensatory pauses are equal in both groups, but the decay time of arterial pressure during diastole (assuming an exponential decay) is larger in group II. At the same age and with the identical aortic compliance only the two factors 1 and 2b play a part in the changes in P.ES.P.P.

Aortic input impedance in normal man and arterial hypertension: its modification during changes in aortic pressure.

The purpose of this work was to study the factors determining aortic input impedance in hypertensive patients. Aortic input impedance (simultaneous measurements of aortic pressure and blood flow), mean (Wm) and pulsatile (Wp) powers and the Wp/Wm ratio were compared in normal subjects (n = 13) and hypertensive patients (n = 12) under basal conditions and during blood pressure manipulation--angiotensin infusion in five normal patients and nitroprusside infusion in six hypertensive patients. Pulse wave velocity (Möens-Korteweg equation; simultaneous measurement of aortic pressure and radius) was determined under basal conditions in normal subjects and in 11 hypertensive patients. The results show that: 1) the changes in impedance curves in hypertensive patients are related to increased peripheral resistance, pulse wave velocity, wave reflection and aortic radius; 2) in most hypertensive patients impedance curves are normalised when blood pressure is reduced, whereas the Wp/Wm ratio remains higher. This latter result demonstrates that pulsatile energy losses are greater in hypertensive patients and suggests either that the aortic wall remains stiffer, despite the reduction in aortic pressure, or that the flow wave becomes more pulsatile since impedance curves of hypertensive patients seen after lowering blood pressure are similar to those of normal subjects.

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.

Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris.

To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil.

Danger of vasodilator therapy for pulmonary hypertension in patent foramen ovale.

A 23-year-old woman with systemic lupus erythematosus was found to have severe pulmonary hypertension with secondary patency of the foramen ovale. Infusion of hydralazine increased the basal right-to-left shunt and resulted in a dramatic fall in arterial oxygen pressure, with subsequent irreversible cardiovascular collapse. Vasodilator therapy appears to be hazardous in patients with severe pulmonary hypertension and patent foramen ovale.

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.

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.

Non-invasive measurement of pulmonary arterial pressure: II. A radionuclide method.

Pulmonary artery pulse pressure (PP) and diastolic pressure (Pd) may be obtained by applying a haemodynamic model of blood flow kinetics and wall mechanics to the pulmonary artery: Pp = rho(ws/(Ss/Sd-1))2log(Ss/Sd)-1/2 rho w2s Pd = (Sd/Ss)1/2Pp where rho is blood density, ws is peak ejection velocity, and Ss and Sd are peak maximal and end diastolic cross-sectional areas of the main pulmonary artery. The different parameters of the equations were measured from radionuclide first pass and equilibrium studies. Radionuclide first pass studies were performed in 24 patients with intravenous injection of 20 mCi of 99Tcm red blood cells with a gamma camera in a 20 degrees right anterior oblique position: data were collected in list mode, i.e. a continuous sequence of spatial and temporal coordinates of each photon. Pulmonary arterial pressure was recorded simultaneously with a microtip catheter during the first pass study. Gated first pass images of the right side of the heart were reconstructed, regions of interest drawn over the right ventricle and the main pulmonary artery (MPA) and time-activity curves generated. Peak systolic (Cs) and end diastolic (Cd) counts obtained from the MPA curve were proportional to the cross sections Ss and Sd of the MPA and Ss/Sd = Cs/Cd. The diameter (D) of the pulmonary artery was calculated as the distance between the two zeros of the second derivative of a cross-sectional profile. The averaged cross-sectional area was S = pi D2/4. ECG gated blood pool studies were performed in a LAO 40 degrees position when the tracer was at equilibrium; they were processed automatically and the right ventricular end diastolic counts (EDC) converted into volume (EDV) using an aortic volume/count ratio. Right ventricular peak ejection rate (PER) was obtained from the RV time-activity curve and the instantaneous peak ejection velocity was calculated, ws = PER X EDV/S X EDC. PP and Pd were calculated in mmHg and the radionuclide method yielded pressure values that correlated reasonably with catheterisation values: PP(rad) = 0.99 PP(cath)-0.55, r = 0.84 and Pd(rad) = 0.67 Pd(cath) + 4.91, r = 0.74. We conclude that radionuclide techniques can provide a non-invasive method based on a haemodynamic model for measuring pulmonary arterial pressure.

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.

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.

[Arrhythmia caused by potassium deficiency]. / Troubles du rythme par déficit potassique.

Although experimental hypokalaemia leads to a wide range of arrhythmias and conduction defects, the only significant clinical result of potassium depletion (with or without hypokalaemia) is observed at ventricular level: ventricular extrasystoles, typical forms of ventricular tachycardia or, more commonly, the form suggesting torsades de pointe . The mechanism of these ventricular arrhythmias is obscure and may involve either reentry phenomena favored by the heterogenicity of the refractory periods at the Purkinje-ventricular junction or automaticity related to the increase in the slope of diastolic depolarisation or with the appearance of early post-potentials in series. Although arrhythmias are rare in isolated hypokalaemia and a healthy heart, they are common and serious if hypokalaemia complicates organic cardiac disease, especially when associated with another factor of cellular desynchronisation such as bradycardia or myocardial impregnation by certain antiarrhythmic drugs. The increased toxicity of digitalis in hypokalaemia is a well known example. Treatment is based essentially on compensating the potassium depletion, bearing in mind the risks of massive supplements administered too rapidly, and on the administration of potassium-sparing drugs (spironolactone and others). Rapid cardiac pacing is often useful in preventing recurrence of torsades de pointe while waiting for adequate potassium repletion.

[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.

[Intranodal reciprocal dual rhythm]. / Double rythme réciproque intranodal.

In a patient with spells of paroxysmal supraventricular tachycardia of two types, the stimulation tests demonstrated a dual intranodal conduction responsible sometimes for "usual" reciprocal rhythms (slow anterograde pathway and rapid retrograde pathway), sometimes for "reversed" reciprocal rhythms (rapid anterograde pathway and slow retrograde pathway). The latter contrasted with the lack of discontinuity of the retrograde nodal function curve (V1-V2 versus A1-A2).

[Treatment of arrhythmias in chronic cardiac insufficiency]. / Traitement des troubles du rythme de l'insuffisance cardiaque chronique.

Arrhythmias are frequent and associated with a poor prognosis, especially when they arise from the ventricle. Although the correction of predisposing factors and improvement of hemodynamic conditions are essential, the use of antiarrhythmic drugs in this context poses problems. The treatment of even complex ventricular extrasystoles has not been shown to effectively prevent the serious arrhythmias responsible for sudden death. Depression of left ventricular function and: Or proarrhythmic effects of antiarrhythmic therapy in some patients, probably offset the benefits observed in others. The treatment of atrial arrhythmias remains traditional: reduction by drugs or electrotherapy and prevention of recurrences, or simply slowing the ventricular response. Sustained ventricular tachycardia and resuscitated ventricular fibrillation should be managed more aggressively, not by empirical antiarrhythmic treatment but by medical therapy guided by the results of electrophysiological studies, and, when this fails, by non-medical treatment: fulguration, implantable defibrillator, antiarrhythmic surgery, or even cardiac transplantation.

[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.

[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.

[Obvious or inapparent Wolff-Parkinson-White syndrome associated with duality of nodal conduction. Apropos of 4 cases]. / Syndrome de Wolff-Parkinson-White patent ou inapparent associé à une dualité de conduction nodale. A propos de 4 observations.

In a series of 48 patients undergoing electrophysiological investigation for attacks of reciprocating tachycardia related to concealed or overt Wolff-Parkinson-White syndrome in sinus rhythm, 4 patients were found to have duality of nodal conduction. This association was responsible for several tachycardia circuits: in 2 patients the activation passed constantly retrogradely through the accessory pathway and then either through the slow nodal pathway or the rapid nodal pathway in the anterograde direction. In the other two patients, in addition to classical orthodromic tachycardia, purely intranodal reciprocating rhythms giving rise to sustained tachycardia in one case and to simple echos in the other, were observed.