Prognostic value of plasma B-type natriuretic peptide in patients with severe cardiotoxic drug poisoning.

BACKGROUND/OBJECTIVES: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. METHODS: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. RESULTS: While BNP values on admission were poorly informative, subsequent BNP measurements (11 ± 6 h after admission) were significantly increased in patients with CS compared to those with non-CS (756; [364-1130] versus 24; [15-65] pg/ml respectively; P = 0.008). This second BNP level was also significantly increased in non-survivor patients compared to survivor patients (784; [654-1028] versus 29; [15-104] pg/ml respectively; P = 0.05): BNP levels above 360 pg/ml predicted in-hospital mortality (sensitivity = 100%, specificity = 92%). In a multivariate analysis, BNP, SAPS II score and lactate blood level were associated with death. CONCLUSIONS: Serial BNP measurements after admission for cardiotoxic drug poisoning are useful to identify patients at the highest risk of CS as well as in-hospital death.

Evidence of cardiac myolysis in severe nonischemic heart failure and the potential role of increased wall strain.

BACKGROUND: Myocyte death could play a role in heart failure (HF) irrespective of the presence of coronary artery disease. The study aimed to assess this hypothesis by use of the cardiac troponin I (cTnI) assay. METHODS AND RESULTS: Seventy-one patients with nonischemic HF, New York Heart Association (NYHA) class II-IV, with a normal coronary angiogram and after exclusion of myocardiopathies were evaluated in the study. The control group included 9 healthy subjects and 15 patients hospitalized for severe noncardiac dyspnea. Cardiac TnI concentrations were determined at admission with a research reagent (cTnIus) characterized by a detection limit of 0.026 ng/mL and a high analytic sensitivity of 0.002 ng/mL. cTnIus levels were more than 0.026 ng/mL in 19 HF patients, ranging between 0.027 and 0.463 ng/mL, whereas no cTnIus level was detectable in the control group. With use of a reference assay, only 2 HF patients had abnormal cTnI values. Severe HF was observed in 17 of these 19 patients, assessed by NYHA class IV or by the presence of pulmonary edema. Patients with an increased cTnIus level had a more restrictive mitral Doppler pattern (P <.001) and a more distinctive left ventricular (LV) concentric remodeling (P <.0001), whereas LV ejection fraction was similar in both HF groups. The increased cTnIus level was also associated with a LV wall strain biologic marker (ie, an increased brain natriuretic peptide plasma level) (P <.001). CONCLUSIONS: cTnI assay is a promising biochemical method for detecting cardiac myolysis in HF, independent of the presence of coronary artery disease. This subtle myolysis could be in part related to the severely increased LV wall strain.

Assessment of exercise tolerance in chronic congestive heart failure.

In patients with chronic heart failure, exercise capacity is poorly related to cardiac hemodynamics, and peripheral circulation is an important determinant of exercise tolerance. The ability of the muscle vasculature to dilate is markedly impaired, in part, because of exaggerated neurohumoral activity increasing vascular wall stiffness. For this reason, increasing cardiac output is not sufficient to increase exercise capacity if not accompanied by improving vascular reactivity. The poor reliability and reproducibility of exercise tolerance assessed by maximal exercise duration or maximal attained work load (particularly on a treadmill) has led to widespread measurement of respiratory gas during exercise. Peak oxygen consumption (peak VO2), even if it is symptom-limited, has been shown to be a very reproducible criterion of exercise tolerance; moreover, because VO2 is the product of cardiac output and arteriovenous oxygen difference, it also has a qualitative hemodynamic significance. Ventilatory threshold can be determined before maximal exercise; however, problems of determination limit the practical value of this criterion. Unfortunately, peak VO2 lacks sensitivity to detect minor improvement or impairment of symptoms during daily life, although these are significant to the patient. Submaximal exercises have been proposed for this purpose and are currently being evaluated.

Comparison of oxygen uptake during bicycle exercise in patients with chronic heart failure and in normal subjects.

Prediction of oxygen uptake (VO2) during exercise from relations established in normal subjects between VO2 and work load in watts (W) may be inaccurate in patients with chronic heart failure because these patients could manifest delayed VO2 kinetics at final stages of exercise. To test the hypothesis that even at low levels of work, patients exhibit a lower VO2 than do normal subjects, 77 patients with heart failure and 27 control subjects with a normal heart or with disease other than heart failure underwent bicycle exercise with respiratory gas analysis. Work load was increased by 10 W/min from an initial 20 W. VO2 (ml/min per kg) was measured every 15 s. The delta VO2/delta W ratio was significantly reduced only in the most severely impaired patients in heart failure class C-D (8.75 +/- 2.14 versus 11.05 +/- 0.38, p less than 0.05). Class B patients showed a lower ratio at a work load of greater than or equal to 80 W, whereas class C-D patients manifested a lower ratio at greater than or equal to 20 W. Even with a low incremental work rate protocol, compared with sedentary normal subjects or patients without heart failure, patients with heart failure demonstrate impaired oxygen uptake. This observation suggests the presence of anaerobic metabolism or delayed VO2 uptake, or both; accordingly, indirect estimates of VO2 requirements derived from intensity or duration of exercise in such patients are overestimated.

[Primary hyperparathyroidism disclosed by heart arrhythmia]. / Hyperparathyroïdie primitive révélée par des troubles du rythme cardiaque.

The authors report a case of primary hyperparathyroidism in a 47 year old woman presenting with cardiac arrhythmias. She had paraoxystic supraventricular tachycardias and rate-dependent ventricular hyperexcitability suggestive of a catecholamine-induced phenomenon which were resistant to antiarrhythmic therapy over a 3 year period; the plasma calcium concentration was 3.30 mmol/l. An ectopic parathyroid adenoma was removed surgically, normalising the biological changes, and no further arrhythmias were detected by Holter monitoring during the 2 year follow-up period. The association of atrial and ventricular arrhythmias seems to be relatively rate in hyperparathyroidism; patients usually present with atrioventricular block and ventricular hyperexcitability. The other cardiovascular abnormalities observed in hyperparathyroidism are hypertension and myocardial hypertrophy. The electrophysiological mechanisms underlying the clinical manifestations remain obscure.

Prevalence and significance of left ventricular filling abnormalities determined by Doppler echocardiography in young type I (insulin-dependent) diabetic patients.

In 16 insulin-dependent diabetic patients, 36 +/- 8 years old with no microangiopathy, hypertension or coronary artery disease, and 16 healthy control subjects matched for sex, age and body surface area, the following parameters were obtained by Doppler-echocardiography: (1) end-diastolic left ventricular thickness and radius; (2) aortic pulse wave velocity; (3) mitral flow with measurement of early and late (atrial) peak velocities (E and A), pressure half-time and the velocity time integrals of the entire mitral curve and of the atrial wave; and (4) isovolumic relaxation time (i.e., the time between aortic closure and the mitral opening signals recorded simultaneously by continuous-wave Doppler). Heart rate and systolic blood pressure were not different in the 2 groups. Aortic pulse wave velocity and the wall thickness to radius ratio were significantly increased in the diabetic patients compared to the controls. E was significantly reduced whereas A/E, pressure half-time, the atrial contribution to the left ventricular filling (i.e., the ratio of the atrial velocity time integral to the mitral velocity time integral) and the isovolumic relaxation time were significantly increased in the diabetic group versus the control subjects. Lastly, 11 of 16 diabetic patients (69%) had at least 2 of the following abnormalities: A/E greater than 0.71, an atrial contribution to the left ventricular filling greater than 0.25, a pressure half-time greater than 50 ms and an isovolumic relaxation time greater than 88 ms. No correlations were found between the wall thickness to radius ratio, aortic pulse wave velocity and the filling indexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic action of nicorandil in chronic congestive heart failure.

Nicorandil is a new compound that has shown potent vasodilator activities on venous and arterial beds in experimental pharmacology. This study was designed to evaluate the magnitude and the time course of hemodynamic effects of different doses of nicorandil in congestive heart failure. Eleven patients with severe congestive heart failure (New York Heart Association class III or IV), with a cardiac index less than 3 liters/min/m2 and a pulmonary wedge pressure greater than 15 mm Hg were enrolled in the study. Three patients had ischemic dilated cardiomyopathy and 8 had idiopathic dilated cardiomyopathy. Hemodynamic assessments were performed by right-sided cardiac catheterization (Swan-Ganz catheter) with cardiac output determination (thermodilution) at baseline and from 30 minutes to 12 hours after single oral administration of nicorandil; 3 patients were given 40 mg, 6 patients 60 mg, and 2 patients 80 mg. Maximal hemodynamic changes were observed 30 minutes after dosing and remained statistically significant at 3 hours. Thirty minutes after drug administration, pulmonary wedge pressure decreased 34 +/- 6%, cardiac index increased by 55 +/- 13% and diastolic and mean arterial pressures decreased by 15 +/- 3% and 9 +/- 2%, respectively, from baseline values. The decrease in systolic blood pressure was slight (5 +/- 2%) and not statistically significant. Calculated systemic vascular resistances decreased by 36 +/- 6% and heart rate did not significantly change. Nicorandil was well tolerated. Thus, the results of this first study of nicorandil in congestive heart failure demonstrated the unloading action of this compound on the failing heart, leading to an improvement in cardiac function; further investigation of nicorandil in this therapeutic area is needed.

[Physical properties of the aorta and left ventricular geometry evaluated by Doppler echocardiography in normal subjects]. / Propriétés physiques de l'aorte et géométrie ventriculaire gauche évaluées par échocardiographie-Doppler chez des sujets normaux. Relations avec l'âge.

UNLABELLED: In 45 normotensive subjects (21-84 years) we simultaneously measured: 1) arterial pressure (AP) according to guidelines of the World-health-organization; 2) left ventricular (LV) wall thickness (WT) and antero-posterior radius (r), aortic diameter (AD) by M-mode echo with 2D echo control; 3) isthmus--diaphragm pulse wave delay (PWD) by measurement of time, between the foot of aortic velocity curves, respectively in the isthmus and near the diaphragm; 4) sternal length (L). We derived WT/r ratio, pulse wave velocity (PWV) as the ratio L/PWD, the product AD X PWD and the PWD/AD. RESULTS: AP, WT/r, PWD, PWV, AD, AD X CFD, PWD/AD are significantly correlated with age (respective r = 0.30, p = 0.05; r = 0.61, p less than 0.001; r = -0.67, p less than 0.001; r = 0.73, p less than 0.001; r = 0.61, p less than 0.001; r = -0.49, p less than 0.001; r = 0.52, p less than 0.001. WT/r is significantly correlated with PWD (r = -0.52, p less than 0.001); PWV (r = 0.50, p less than 0.001); AD (r = 0.44, p less than 0.03); AD X PWD (r = -0.38, p = 0.01) and PWD/AD (r = 0.35, p less than 0.02) but not systolic AP.(ABSTRACT TRUNCATED AT 250 WORDS)

[Coronary and renal circulation in patients with cardiac failure after converting enzyme inhibitors]. / Circulations coronaire et rénale chez des malades en insuffisance cardiaque après inhibiteurs de l'enzyme de conversion.

The cardiac output and its peripheral distribution must fulfill the metabolic and/or functional requirements of the different organs. The various techniques used to measure blood flow rates in the coronary and renal arteries provide much information on this point, but they do not tell us all we would like to know about the distribution and "utilization" of these flows in tissues. In normal subjects the myocardial oxygen consumption is not markedly different from the renal oxygen consumption, but the mechanisms that regulate the coronary and renal circulations are not the same. The flow rate in the coronary vessels is about 10% of the cardiac output, the arteriovenous oxygen gradient is superior to 10 vol % and regulation is metabolic. In the renal vessels, which are primarily "functional", the flow rate is about 25% of the cardiac output and the arteriovenous oxygen gradient is inferior to 2 vol %. In heart failure patients, despite reduced cardiac output the blood pressure is kept normal for a long time by vasoconstriction of the arterioles, a process which involves, at least partly, the renin-angiotensin system. The vasoconstriction predominates in some circuits (the renal flow rate is less than 15% of the cardiac output) and spares the "privileged" circuits (the coronary flow rate is more than 15% of the cardiac output). Under the influence of angiotensin converting enzyme inhibitors, the cardiac output increases and its distribution is modified. The coronary flow rate remains stable or is reduced in proportion to the decrease in myocardial oxygen consumption, the metabolic regulation is preserved and there is no "coronary steal". The percent increase in renal flow rate is usually superior to that of the cardiac output. This peripheral redistribution of coronary and renal blood flow rates in heart failure patients after treatment with converting enzyme inhibitors seems to correspond to the physiological purposes of the two regional blood flows.