QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Importance of aetiology.

AIMS: Identification of patients with congestive heart failure at risk of sudden death remains problematic and few data are available on the prognostic implications of QT dispersion. We sought to assess the predictive value of QT dispersion for arrhythmic events in heart failure secondary to dilated cardiomyopathy or ischaemic heart disease. METHODS AND RESULTS: Twelve-lead ECGs calculated for QT dispersion, 24 h Holter ECGs and signal-averaged ECGs were prospectively recorded in 205 heart failure patients in sinus rhythm. The 86 patients with ischaemic heart disease and the 119 with dilated cardiomyopathy were not significantly different as regards NYHA grades (51 vs 49% in grades III-i.v.), cardiothoracic ratio (57 +/- 7 vs 57 +/- 6%) and ejection fraction (28 +/- 8 vs 29 +/- 9%). The mean QT dispersion (66 +/- 29 vs 65 +/- 27 ms), the frequency of non-sustained ventricular tachycardia (37 vs 38%) and ventricular late potentials (41 vs 40%) were not significantly different in patients with ischaemic or dilated cardiomyopathy. QT dispersion was significantly related to other arrhythmogenic markers. During follow-up (24 +/- 16 months), 66 patients died, 22 of them died suddenly and seven presented a spontaneous sustained ventricular tachycardia. In patients with dilated cardiomyopathy, in multivariate analysis, only a QT dispersion > 80 ms was an independent predictor of sudden death (RR: 4.9, 95% CI 1.4-16.8, P < 0.02) and arrhythmic events (RR: 4.5, 95% CI 1.5-13.5, P < 0.01). In patients with ischaemic heart disease, no studied parameter was found significantly related to sudden death or arrhythmic events. CONCLUSIONS: In congestive heart failure, abnormal QT dispersion can identify patients with dilated cardiomyopathy who are at high risk of arrhythmic events.

Lack of haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension induced by acute sino-aortic denervation.

1. The aims of the present experiments were to define a new experimental model of pulmonary hypertension induced by a post-capillary mechanism and to assess the haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension. 2. Cardiopulmonary variables of 28 male beagle dogs, anaesthetized with chloralose, 16 spontaneous breathing and 12 with assisted ventilation, were studied before and after sino-aortic denervation (SAD). The haemodynamic effects of inhaled nitric oxide (25 p.p.m., 10 min). N(omega)-nitro-L-arginine methyl ester (20 mg kg-1, i.v.), urapidil (0.5 mg kg-1-, i.v.) and propranolol (300 micrograms kg-1, i.v.) were studied after SAD. 3. SAD induced an acute and transient pulmonary hypertension, more marked in spontaneous breathing dogs. This pulmonary hypertension involved a post-capillary mechanism, secondary to the left ventricular haemodynamic effects of the acute increase of left ventricular after-load induced by systemic hypertension. In fact, the increase of mean pulmonary arterial pressure after SAD and the decrease of this parameter after urapidil or propranolol were strongly correlated with the variations of pulmonary capillary wedge pressure. Furthermore, no significant change in pulmonary vascular resistance was found after SAD or administration of alpha or beta-adrenoceptor antagonists. 4. Inhaled nitric oxide did not reverse pulmonary hypertension induced by SAD. N(omega)-nitro-L-arginine methyl ester had no significant haemodynamic effect of pulmonary circulation. 5. In conclusion, the lack of effect of inhaled nitric oxide and nitric synthase inhibitor on pulmonary circulation parameters SAD suggest that endothelium-derived oxide is not involved in the mechanisms leading to post-capillary pulmonary hypertension.

Prognostic value of arrhythmogenic markers in systemic hypertension.

OBJECTIVE: To evaluate the prognostic value of arrhythmogenic markers in hypertensive patients. DESIGN: Two hundred and fourteen hypertensive patients without symptomatic coronary disease, systolic dysfunction, electrolyte disturbances or anti-arrhythmic therapy were included. Recordings were made of 12-lead standard ECGs with calculations of QT interval dispersion, 24 h Holter ECGs (204 patients), echocardiography (187 patients) and signal-averaged ECGs (125 patients). BASELINE DATA: echocardiographic left ventricular hypertrophy was found in 63 patients (33.7%), non-sustained ventricular tachycardia (Lown class IV b) in 33 patients (16.2%), ventricular late potentials in 27 patients (21.6%). Mortality: after a mean follow-up of 42.4 +/- 26.8 months, global mortality was 11.2% (24 patients), cardiac mortality 7.9% (17 patients), sudden death 4.2% (nine patients). Univariate analysis: predictors of global, cardiac and sudden death were age > or = 65 years, ECG strain pattern, Lown class IV b and QT interval dispersion > 80 ms (P < or = 0.01). Left ventricular mass index was closely related to cardiac mortality (P = 0.002). Multivariate analysis: only Lown class IV b was an independent predictor of global (RR 2.6, 95% CI 1.2-6.0) and cardiac mortality (RR 3.5, 95% CI 1.2-9.7). CONCLUSION: In hypertensive patients, non-sustained ventricular tachycardia has a prognostic value.

Prognostic value of late potentials in patients with congestive heart failure.

To investigate whether detection of ventricular late potentials could provide prognostic information in patients with congestive heart failure with or without bundle branch block, we prospectively obtained a signal-averaged ECG from 151 patients with congestive heart failure, using specific criteria in 57 patients with bundle branch block. Late potentials were detected in 49 patients (32.5%); their incidence was not significantly different in patients without (31%; 29 patients) or with bundle branch block (35%; 20 patients). Late potentials were present in 25 of 73 patients (34%) with idiopathic dilated cardiomyopathy, in 20 of 57 patients (35%) with ischaemic cardiomyopathy and in four of 21 patients (19%) with hypertensive heart disease (ns). Age, NYHA class, ejection fraction and use of amiodarone were not statistically different among patients with or without late potentials. In contrast, patients with late potentials had more past episodes of sustained ventricular tachycardia (8.2%; four patients) than those without late potentials (1.9%; two patients). Twenty four hour ambulatory ECGs were obtained in 135 patients (89%). Non-sustained ventricular tachycardia was not correlated with the presence of late potentials found in 45 of 88 patients (51%) without late potentials and in 29 of 47 patients (62%) with late potentials (ns). The mean follow-up was 27 +/- 12 months; 51 patients died, 31 from progressive congestive heart failure and 13 suddenly; seven prospectively had sustained ventricular tachycardia. The total mortality rate, the cardiac mortality rate and sudden death risk were not significantly related to the presence of late potentials; their incidence were respectively 35% (36 patients), 32% (33 patients) and 10% (10 patients) in patients without late potentials and 31% (15 patients), 23% (11 patients) and 6% (three patients) in those without late potentials. The incidence of sustained ventricular tachycardia during follow-up was 2% (two patients) in patients without late potentials and 10% (five patients) in those with late potentials. The incidence of sustained ventricular tachycardia experienced by the patients before the study or seen during follow-up was significantly increased in the presence of late potentials: 18% (nine patients) vs 2% (two patients) in the absence of late potentials (P < 0.001). Removal from the study of data from patients with bundle branch block, patients with severe congestive heart failure (NYHA 3 or 4) or patients taking amiodarone did not alter these results. Thus, signal-averaged ECG results only improved risk stratification for sustained ventricular tachycardia in patients with congestive heart failure and failed to identify patients at high risk for sudden death.

Relationship between arterial blood pressure disturbances and alpha adrenoceptor density.

To investigate the influence of blood pressure disturbances on human platelet alpha 2-adrenoceptor density, we studied 7 normotensive Parkinsonians with orthostatic hypotension and 23 mild essential hypertensive patients. Plasma catecholamine levels were measured by HPLC and alpha 2-adrenoceptor number and affinity determined by [3H]-yohimbine binding. Alpha-adrenergic reactivity was investigated by blood pressure response to noradrenaline infusion in Parkinsonians and by adrenaline-induced platelet aggregation in hypertensive patients. In Parkinsonians with orthostatic hypotension, in comparison with Parkinsonians without orthostatic hypotension and normotensive control subjects age and sex matched, noradrenaline plasma levels were significantly lower (62 +/- 11, 195 +/- 14 and 219 +/- 13 pg. ml-1 respectively, p < 0.05), platelet alpha 2-adrenoceptor number was significantly higher (313 +/- 52, 168 +/- 9 and 174 +/- 4 fmol.mg-1 protein respectively, p < 0.05) and the noradrenaline dose required for a 25 mm Hg increase of systolic blood pressure significantly lower (0.19 +/- 0.03, 0.86 +/- 0.11 and 0.68 +/- 0.10 microgram.Kg-1 respectively, p < 0.05). In hypertensive patients, in comparison with normotensive control subjects age and sex matched, plasma noradrenaline levels remained unchanged (306 +/- 68 vs 246 +/- 28 pg.ml-1) whereas both platelet alpha 2-adrenoceptor number (137 +/- 15 vs 177 +/- 15 fmol.mg-1 protein, p < 0.05) and velocity of adrenaline-induced platelet aggregation were significantly decreased. These results indicate that platelet alpha 2-adrenoceptor density is related to blood pressure values. In Parkinsonians with orthostatic hypotension, the up-regulation of alpha 2-adrenoceptors was induced by the decrease of endogenous catecholamines. In contrast, in essential hypertension a down-regulation of alpha 2-adrenoceptors was observed in spite of no significant increase of catecholamine levels. These results suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptor regulatory mechanisms.

[Inferior wall myocardial infarction and atrioventricular block; angiography and prognosis]. / Infarctus inférieurs et blocs auriculo-ventriculaires; données angiographiques et pronostic.

This study was based on 42 cases of 2nd or 3rd degree atrioventricular block out of 292 cases of inferior wall myocardial infarction. The criteria of selection were monitoring in the intensive care unit during the acute phase, selective coronary angiography in the first 48 hours to 5 days, and regular clinical follow-up during the first year after infarction. The conduction defect was either immediately recorded on the first ECG, delayed (between the 12th and 24th hour) or late (after the 3rd day). These 42 inferior wall infarcts with atrioventricular block (incomplete in 14 and complete in 28 cases) differed from inferior infarction without block by: - the severity of the clinical signs during the acute phase (35% with cardiac failure, 19% with cardiogenic shock); - the severity of the coronary lesions (71.4% with triple vessel disease in infarction with atrioventricular block compared with 32% in those without block, p < 0.02); - the prevalence of the association of > 70% stenosis of the right coronary and left anterior descending arteries; - the alteration of left ventricular function (53% patients with atrioventricular block had ejection fraction of under 30%); - the severity of these infarcts was not related to the atrioventricular block which regressed in 95% of cases but to the severity of the coronary disease, the left ventricular dysfunction and the advanced age of the patients (72.3 +/- 8 years).

[Hypertensive cardiopathy and ventricular late potentials]. / Cardiopathie hypertensive et potentiels tardifs ventriculaires.

Ventricular arrhythmias occur with increased frequency in hypertensive patients with left ventricular hypertrophy (LVH). The aim of this work is to study the incidence of ventricular late potentials (LP) and their relation to ventricular arrhythmias in 148 hypertensive patients, 87 men and 55 women, without evidence of a coronaropathy. For each patient we carried out a signal-averaged electrocardiography, an echocardiogram to determine the LV mass index (LVMI) and the LV end-diastolic dimension (EDD), and 24 hours Holter monitoring to record ventricular arrhythmias filed according to Lown's classification. LP were considered present if the root-mean-square voltage during the last 40 ms of the QRS was: < 20 uV in absence of bundle branch block, or < or = 17 uV in presence of bundle branch block. [table: see text] The frequency of LP appears exceptional in hypertensive patients without LVH (5%) and remains uncommon in patients with concentric LVH (13%). The incidence of LP is only frequent at the end stage of hypertensive cardiopathy with eccentric LVH (48%). The severity of ventricular arrhythmias is only correlated to the presence of LP in patients with concentric LVH (p < 0.02).

[In which type of hypertension should ventricular hyperexcitability be suspected?]. / Chez quels hypertendus faut-il rechercher une hyperexcitabilité ventriculaire?

The aim of the present study was to determine when a search for ventricular arrhythmias, by ambulatory electrocardiographic monitoring, is necessary in hypertensive patients. An electrocardiogram, an echocardiogram and a 24 hour Holter monitoring were recorded in 88 patients with essential hypertension. According to the results of electrocardiogram patients were subdivided into 4 groups: normal electrocardiogram, isolated left auricular hypertrophy (LAH), isolated left ventricular hypertrophy (LVH) and major ST-T wave changes. According to the degree of septal thickness (ST), patients were classed in 4 groups. [table; see text] For hypertensive patients with normal electrocardiogram, Holter monitoring is not necessary; in fact practically no complex arrhythmias is found in this group. On the contrary, for hypertensive subjects with ST-T waves changes, this investigation seems very interesting, nearly 75% of them present high-grade ventricular arrhythmias. For the patients with electrocardiographic isolated LAH or LVH, the realisation of an echocardiography permits to separate the subjects with mild LVH (ST less than 12 mm) where Holter monitoring is not necessary (81% Lown O-I) and the patients with mean or severe LVH (ST greater than or equal to 12 mm) where this investigation seems very interesting, nearly 65% of them present high-grade ventricular arrhythmias.

[Complete bundle branch block during exercise test. Clinical and coronary angiographic data]. / Les blocs de branche complets au cours des épreuves d'effort. Données cliniques et coronarographiques.

Thirty-two complete bundle branch blocks were observed during 16,500 exercise stress tests between 1973 and 1988: there were 7 right bundle branch blocks and 25 left bundle branch blocks. Exercise stress testing was indicated in 15 cases for stable angina, in 15 cases for different functional disturbances and in 2 cases as a systematic investigation. All patients underwent coronary angiography and selective left ventriculography. Right bundle branch block occurring at a heart rate of 105 +/- 25/mn were associated with typical anginal pain at the time of apparition in 5 patients. Coronary angiography showed triple vessel disease in 3 cases, double vessel disease in 2 cases and an isolated proximal lesion of the left anterior descending artery in 2 cases. Left bundle branch block occurring at a heart rate of 125 +/- 12/mn was associated with normal coronary angiography in 7 cases. Eighteen patients had pathological coronary angiogrammes with severe lesions of the left anterior descending artery. Two women suffered from chest pain when the block developed and coronary angiography was normal in one of them. During follow-up (average 62 months), 16 coronary events were observed including 2 infarcts, and 6 patients developed cardiac failure. In conclusion, complete right bundle branch block appearing during exercise stress testing was constantly associated with atherosclerotic coronary artery disease. The predictive value of complete left bundle branch block on effort was 72%. Complete left bundle branch block occurring at heart rates of less than 120/mn was frequently associated with a proximal stenosis of the left anterior descending artery.

[Neurogenic arterial hypertension in humans]. / Hypertension artérielle neurogène de l'homme.

The purpose of this study was to investigate baroreflex activity in hypertensive patients with orthostatic hypotension (OH) due to sinoaortic baroreceptor denervation. The study concerned 3 patients (pts), 58-63 years, mean age 60.6 +/- 2 with both arterial hypertension (paroxysms recorded at 250/130 mmHg) and OH. They received radiation therapy to the entire cervical area for neoplasm, 9.6 +/- 2.8 years ago and had a carotid murmur without significant stenosis. Every pt had a severe and symptomatic OH: blood pressure (BP) and heart rate (HR) were respectively 163 +/- 17/105 +/- 7, 82 +/- 5 b/mn in lying position and 82 +/- 16/53 +/- 9 mmHg, 99 +/- 1 b/mm in standing position. The standing-induced increase in HR was lower (delta HR = + 17.3 b/mn) than expected; atropine (0.02 mg/kg) infusion and cold pressor test were ineffective; the massage of sinocarotid receptors induced a slight decrease in HR (delta HR = - 8 b/mn) and BP was not modified by Valsalva's maneuver. Infusion of norepinephrine (0.016 mg/mn) performed in one pt, increased BP without effect on HR. Platelet alpha 2-adrenoreceptors (alpha 2AR) evaluated by (3H) Yohimbine binding showed a significant increase in alpha 2AR number (Bmax), without any significant change in affinity (KD) when compared with normotensive and essential hypertensive pts: (table; see text) This study described an unusual etiology of a paroxysmal hypertension with orthostatic hypotension, demonstrated the impairment of baroreflex activity and suggested the potential interest of platelet alpha 2 adrenoceptors measurement to evaluate sympathetic tone in these patients.