[Cardiac surgery in Cameroon. Results at one year of the pilot phase]. / Chirurgie cardiaque au Cameroun. Résultats à un an de la phase pilote.

In the framework of implementation of his national program for control and prevention of cardiovascular diseases, Cameroonian government has set up a cardiac surgery project. We report in this manuscript results of one year follow up of the patients operated during the pilot phase. From September 22 till 26, 2008, 11 patients have been operated in Cameroun. Surgical procedures were 5 mitral mechanic valve replacement, 2 aortic mechanic valve replacement, 1 atrial septal defect closure, 2 pace maker implantation. No intrahospital death was observed. One patient died at 11th month after the operation due to mitral valve thrombosis and attributed to lack of compliance. One patient presented low cardiac output, pneumonia and a pleural effusion. 2 patients presented 2 minor complications consisting of pericarditis and superficial wound infection. The results of the pilot phase of cardiac surgery in Cameroon are effective. However, the sustainability of the program require human, material capacity building, and funding mechanism as well.

The link between cardiac autonomic activity and sleep delta power is altered in men with sleep apnea-hypopnea syndrome.

We hypothesize that sleep apnea-hypopnea alters interaction between cardiac vagal modulation and sleep delta EEG. Sleep apnea-hypopnea syndrome (SAHS) is related to cardiovascular complications in men. SAHS patients show higher sympathetic activity than normal subjects. In healthy men, non-rapid eye movement (NREM) sleep is associated with cardiac vagal influence, whereas rapid eye movement (REM) sleep is linked to cardiac sympathetic activity. Interaction between cardiac autonomic modulation and delta sleep EEG is not altered across a life span nor is the delay between appearances of modifications in both signals. Healthy controls, moderate SAHS, and severe SAHS patients were compared across the first three NREM-REM cycles. Spectral analysis was applied to ECG and EEG signals. High frequency (HF) and low frequency (LF) of heart rate variability (HRV), ratio of LF/HF, and normalized (nu) delta power were obtained. A coherency analysis between HF(nu) and delta was performed, as well as a correlation analysis between obstructive apnea index (AI) or hypopnea index (HI) and gain, coherence, or phase shift. HRV components were similar between groups. In each group, HF(nu) was larger during NREM, while LF(nu) predominated across REM and wake stages. Coherence and gain between HF(nu) and delta decreased from controls to severe SAHS patients. In SAHS patients, the delay between modifications in HF(nu) and delta did not differ from zero. AI and HI correlated negatively with coherence, while HI correlated negatively with gain only. Apneas-hypopneas affect the link between cardiac sympathetic and vagal modulation and delta EEG demonstrated by the loss of cardiac autonomic activity fluctuations across shifts in sleep stages. Obstructive apneas and hypopneas alter the interaction between both signals differently.

Progressive aging does not alter the interaction between autonomic cardiac activity and delta EEG power.

OBJECTIVE: We tested the hypothesis that the reductions of the changes in the respective influence of the cardiac sympathetic and vagal activity control and delta EEG activity with aging alter the interactions between the heart rate variability (HRV) and the delta sleep EEG power band. METHODS: A polysomnography was performed on 16 healthy young men and 19 healthy middle-aged men across the first 3 NREM-REM cycles. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. High Frequency (HF(nu)) of HRV as well as the maximum of cross-spectrum, coherency, gain and phase shifts between HF(nu) and delta sleep EEG power band were compared between both groups. RESULTS: Young men experienced more deep sleep than middle-aged men (P<0.001). In middle-aged subjects, HF(nu) was lower than the HF(nu) of their younger counterparts (P<0.001), but they showed similar increases during NREM sleep and similar decreases during REM sleep as the young subjects. Cross-spectrum values, coherency, gain and phase shifts between HF(nu) and delta were identical between the two groups. Modifications in HF(nu) show parallel changes and precede changes in delta EEG band by a similar leads of 11+/-6min in young men and 9+/-7 min in middle-aged men (P=0.23). CONCLUSIONS: Reduced changes in the respective influence of the cardiac sympathetic and vagal activity and delta EEG activity with progressive aging do not alter the relationship and phase difference between changes in the relative predominant cardiac vagal activity and delta power in middle-aged men. SIGNIFICANCE: Interaction between the cardiac sympathetic and vagal activity with delta EEG activity is maintained in middle-aged men.

A study of the dynamic interactions between sleep EEG and heart rate variability in healthy young men.

OBJECTIVE: We investigated the interactions between heart rate variability and sleep electroencephalogram power spectra. METHODS: Heart rate and sleep electroencephalogram signals were recorded in 8 healthy young men. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. Spectral components of RR intervals were studied across sleep stages. The cross-spectrum maximum was determined as well as coherencies, gains and phase shifts between normalized high frequency of RR intervals and all electroencephalographic frequency bands, calculated over the first 3 NREM-REM cycles. RESULTS: RR intervals increased from awake to NREM and decreased during REM. Normalized low frequency decreased from awake to NREM and increased during REM while normalized high frequency evolved conversely. Low to high frequency ratio developed in opposition to RR intervals. Coherencies between normalized high frequency and power spectra were high for all bands. The gain was highest for delta band. Phase shift between normalized high frequency and delta differed from zero and modifications in normalized high frequency preceded changes in delta by 41+/-14 degrees. CONCLUSIONS: Our study demonstrates that: (1) all electroencephalographic power bands are linked to normalized high frequency; (2) modifications in cardiac vagal activity show predominantly parallel changes and precede changes in delta band by a phase shift corresponding to a lead of 12+/-5 min.

Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study rationale and design.

The PICXEL study is designed to evaluate the effects of long-term administration of very low-dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) vs enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. This multicentre, controlled, randomised, double-blind, parallel group study is carried-out to assess the variation of left ventricular mass index (LVMI) after treatment, using a centralised control of M-mode echocardiography determinations, and a dedicated software for semi-automatic measurement. Following a 4-week placebo run-in period, hypertensive outpatients aged >/=18 years, with LVH (LVMI >120 and 100 g/m(2) for men and women, respectively), are randomised to receive once daily, over 52 weeks, either Per/Ind or enalapril. According to blood pressure levels, the dose may be adjusted. In addition to clinical examinations, ECG, blood pressure, heart rate and laboratory assessments echocardiographic determinations are performed for selection, at baseline, after 24 weeks and at the end of the study. The main outcome criteria is the change from baseline in LVMI which is considered the primary efficacy criterion; changes in blood pressure and echo-Doppler parameters constitute secondary criteria. Two-sided Student's t-test for independent samples will be used to differentiate the effects of the treatment between groups with alpha = 5%, and the inter-group difference of LVMI variation will be analysed with a power of 90%. A sample size of 500 patients is required making it necessary to randomise at least 550 patients, based on a 10% proportion of potentially non-assessable patients. The results of this study, obtained after applying strict methodological procedures and requirements, are expected to provide valuable and reliable information on the effects of long-term administration of Per/Ind on LVH, and on its potential superiority over enalapril.

[The cardiology department]. / Le Service de Cardiologie.

Cardiology was present since the very beginning of the Erasme hospital. The Department of Cardiology was created in 1979. This department is made of a hospitalization unit (54 beds), a coronary care unit (12 beds) and a large technical unit. Clinical activity has increased tremendously and this had led to an important research activity in the fields of cardio-respiratory and metabolic adaptation to exercise, particularly after cardiac transplantation, of cardiovascular epidemiology, of clinical pharmacology and in pulmonary as well as systemic hypertension.

Differential characteristics of neural circulatory control: early versus late after cardiac transplantation.

BACKGROUND: Reappearance of low-frequency (LF) (+/-0.10 Hz) oscillations in RR interval (RR) after cardiac transplantation is indicative of sympathetic efferent reinnervation. We hypothesized that restored LF oscillations in RR in heart transplant recipients (HTRs) are linked to oscillations in muscle sympathetic nerve traffic (MSNA). METHODS AND RESULTS: RR, RR variability, and MSNA were recorded 5+/-2 months (n=7, short-term HTRs) and 138+/-8 months (n=7, long-term HTRs) after heart transplantation and compared with matched hypertensive patients (n=7). A coherence function determined the coupling between LF oscillations in MSNA and RR. RR variance did not differ between short-term and long-term HTRs. However, LF variability was only 1+/-0.5 ms(2) in the short-term HTRs but was 15+/-8 ms(2) in the long-term HTRs (P<0.05). Normalized LF variability was also higher in the long-term HTRs (40+/-14 normalized unites) versus the short-term HTRs (6+/-3 normalized united, P<0.05) but did not differ from the LF variability of the hypertensive patients. Long-term HTRs were taking less cyclosporine (P<0.01) but had higher MSNA than the short-term HTRs (62+/-7 versus 31+/-7 burst/min, respectively, P<0.05). Coherence between LF oscillations in MSNA and RR was similar in the long-term HTRs (0.59+/-0.11) and the hypertensive patients (0.60+/-0.07) and was 3-fold greater than in the short-term HTRs (0.20+/-0.06, P<0.05). CONCLUSIONS: Cardiac reinnervation after long-term heart transplantation is characterized by a restoration of the coherence between LF oscillations in RR and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time elapsed after cardiac transplantation may be a major determinant of sympathetic excitation in heart transplant recipients.

Contrasting effects of phentolamine and nitroprusside on neural and cardiovascular variability.

The relative contributions of a central neural oscillator and of the delay in alpha-adrenergic transmission within the baroreflex loop in the predominance of low-frequency (LF) cardiovascular variability during sympathetic activation in humans are unclear. We measured R-R interval (RR), muscle sympathetic nerve activity (MSNA), blood pressure (BP), and their variability in 10 normal subjects during sympathetic activation achieved by BP lowering with sodium nitroprusside (SNP) and alpha-adrenergic blockade using phentolamine. SNP and phentolamine induced comparable reductions in BP (P > 0.25). Despite tachycardia and sympathetic activation with both SNP and phentolamine, LF variability in RR, MSNA, and BP increased during SNP and decreased during phentolamine (SNP: RR +20 +/- 6%, MSNA +3 +/- 5%, systolic BP +9 +/- 6%, diastolic BP +7 +/- 5%; phentolamine: RR -2 +/- 7%, MSNA -34 +/- 6%, systolic BP -16 +/- 8%, diastolic BP -13 +/- 4%, P < 0.05 except systolic BP, where P = 0.09). Thus LF variability is reduced when sympathetic activation is induced by alpha-adrenergic blockade. This suggests that alpha-adrenergic transmission within the baroreflex loop may contribute importantly to the predominance of LF cardiovascular variability associated with sympathetic excitation in humans.

Importance of ventilation in modulating interaction between sympathetic drive and cardiovascular variability.

Chemoreflex stimulation elicits both hyperventilation and sympathetic activation, each of which may have different influences on oscillatory characteristics of cardiovascular variability. We examined the influence of hyperventilation on the interactions between changes in R-R interval (RR) and muscle sympathetic nerve activity (MSNA) and changes in neurocirculatory variability, in 14 healthy subjects. We performed spectral analysis of RR and MSNA variability during each of the following interventions: 1) controlled breathing, 2) maximal end-expiratory apnea, 3) isocapnic voluntary hyperventilation, and 4) hypercapnia-induced hyperventilation. MSNA increased from 100% during controlled breathing to 170 +/- 25% during apnea (P = 0.02). RR was unchanged, but normalized low-frequency (LF) variability of both RR and MSNA increased markedly (P < 0.001). During isocapnic hyperventilation, minute ventilation increased to 20.2 +/- 1.4 l/min (P < 0.0001). During hypercapnic hyperventilation, minute ventilation also increased (to 19.7 +/- 1.7 l/min) as did end-tidal CO(2) (both P < 0.0001). MSNA remained unchanged during isocapnic hyperventilation (104 +/- 7%) but increased to 241 +/- 49% during hypercapnic hyperventilation (P < 0.01). RR decreased during both isocapnic and hypercapnic hyperventilation (P < 0.05). However, normalized LF variability of RR and of MSNA decreased (P < 0.05) during both isocapnic and hypercapnic hyperventilation, despite the tachycardia and heightened sympathetic nerve traffic. In conclusion, marked respiratory oscillations in autonomic drive induced by hyperventilation may induce dissociation between RR, MSNA, and neurocirculatory variability, perhaps by suppressing central genesis and/or inhibiting transmission of LF cardiovascular rhythms.

Effects of aging and cardiac denervation on heart rate variability during sleep.

BACKGROUND: Cardiac vagal predominance increases the RR interval and RR high-frequency (HF) variability during non-rapid eye movement (non-REM) sleep (stages I through IV) in young subjects. Aging suppresses deep sleep, but effects of age-related changes in sleep architecture on RR are unknown. Whether mechanical effects of changes in the breathing pattern on the sinus node during sleep affect RR variability is unclear. METHODS AND RESULTS: Polygraphic sleep recordings and RR and RR spectral profiles were determined in 8 young (22.5+/-3.3 years) and 8 older (55.0+/-7.3 years) healthy volunteers. HF oscillations in RR of 8 cardiac-denervated heart transplant recipients determined mechanical effects of respiration on the sinoatrial node during sleep. Transition from wakefulness to non-REM sleep increased the RR interval in young and older subjects and increased the HF variability of RR in the young (P:<0.05) but not in the older subjects. Older subjects disclosed a faster RR (P:<0.01) and a lower HF variability (P:<0.05) during non-REM sleep than the young subjects. Aging did not affect light and REM sleep but decreased deep sleep (stage IV) from 39+/-23 to 6+/-6 minutes (P:<0.001). Reduction in sleep stage IV with aging blunted the increase in RR and in RR HF variability during non-REM sleep (r>0.55, P:<0.05). Transition from wakefulness to non-REM sleep doubled the markedly reduced HF variability of RR in the heart transplant recipients (P:<0.05). CONCLUSIONS: Disappearance of deep sleep with aging impairs nocturnal increase in cardiac vagal activity. Mechanical effects of changes in breathing pattern during sleep favor increases in HF oscillations of the RR interval during non-REM sleep.

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study.

OBJECTIVE: To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). DESIGN: The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. SETTING: European hospitals, general practitioners and cardiologists. PATIENTS: Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. INTERVENTIONS: Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. MAIN OUTCOME MEASURES: LVMI variation in the perprotocol population. RESULTS: Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. CONCLUSIONS: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

Power spectral analysis of cardiovascular variability in critically ill neurosurgical patients.

OBJECTIVE: Patients with brain damage exhibit a number of changes in heart rate and cardiovascular control. The aim of this study was to relate changes in autonomic cardiovascular control seen in critically ill neurosurgical patients to the quality of subsequent outcome and survival. DESIGN: Prospective, longitudinal, outcome study. SETTING: Intensive care department of a university teaching hospital. PATIENTS: A total of 29 consecutive neurosurgical patients admitted for > or =2 days to the intensive care department with a Glasgow Coma Scale score < 13 who needed electrocardiographic and invasive arterial monitoring. INTERVENTIONS: Sampling of the electrocardiogram, respiratory rate, and arterial pressure into a personal computer was carried out for > or =60 mins. Power spectral analysis was then applied to the data by using a fast Fourier transformation. Arterial baroreflex sensitivity was determined as the gain of the transfer function between systolic arterial blood pressure and electrocardiograph R-R interval (RRI) variability. All surviving patients were followed up at 3 months postadmission to measure quality of outcome. MEASUREMENTS AND MAIN RESULTS: There were reductions in the total power (p < .01) of RRI variability in those who subsequently died compared with those who survived. This was significant for very low frequency (p < .001) and low-frequency (LF) (p < .05) but not high-frequency (HF) bands (p = .11). Blood pressure variability, however, did not change between groups. Baroreflex sensitivity was 8.7+/-2.2 msecs/mm Hg for patients with a good later outcome and 4.4+/-1.5 msecs/mm Hg for patients who subsequently died (p = .03). Patients who recovered to a good quality outcome also had a raised LF/HF ratio in RRI (p = .05). CONCLUSION: A reduction in the total power variability of RRI and a lowered LF/HF ratio of the RRI are associated with a poor quality recovery or death after neurosurgical illness. A reduction in the baroreflex was specifically associated with death in this patient group.

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity.

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.

Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.

Ambulatory blood pressure and neuroendocrine control after diet-assisted gastric restrictive surgery.

BACKGROUND: Long-term weight control after conventional diet is disappointing but may be improved when diet is assisted by gastric restrictive surgery (GRS). OBJECTIVE: To determine the effects of GRS on ambulatory blood pressure (ABP) and neuroendocrine BP control in 28 morbidly obese subjects. METHODS: A BP and heart rate were recorded every 10 min for 25 h before and 4 months after GRS. Effects of marked reductions in body weight on the renin-angiotensinaldosterone system, on plasma insulin and on sympathetic activity were also determined. RESULTS: Body mass index decreased from 43 +/- 1 to 34 +/- 1 kg/m2 and systolic (S) BP decreased by 7 +/- 2 mmHg during daytime (P=0.01) and by 8 +/- 3 mmHg during the night (P=0.02). Pulse pressure, a marker of reduced arterial compliance, decreased by 5 +/- 1 mmHg throughout the 24 h period (P < 0.001). Diastolic BP remained unchanged. Heart rate decreased more during the night (-13 +/- 2 bpm, P<0.0001) than during daytime (-5 +/- 2 bpm, P=0.03). Reductions in SBP were largest in subjects with highest initial BP values (r = -0.63, P<0.001) but were unrelated to weight loss. GRS decreased fasting glycaemia, plasma insulin, plasma C peptide and 24 h urine sodium (n=20) and noradrenaline (n=19) excretion (P<0.01). CONCLUSIONS: Diet-assisted GRS favourably affects neuroendocrine BP control in obese patients. Reductions in sodium intake, insulin levels and sympathetic tone combined with possible improvements in arterial compliance induce persistent 24 h reductions in SBP and pulse BP. Reductions in BP are largest in subjects with highest initial BP values and are unrelated to the amount of weight loss, thereby emphasizing the importance of even moderate reductions in weight on BP control.

Study on COgnition and Prognosis in the Elderly (SCOPE).

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by <10 mmHg since the randomization visit, or DBP is >85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged.

Prolonged antihypertensive effect of amlodipine: a prospective double-blind randomized study.

Amlodipine is a calcium antagonist with a long elimination half-life (35 to 50 h) allowing a once daily dosing in the treatment of hypertension. This randomized, double-blind study was performed to assess the residual antihypertensive effect of amlodipine 5 mg O.D. 3 days after discontinuing therapy in previously well-controlled mild to moderate hypertensive patients. Blood pressure (BP) was evaluated by conventional (OBP) and by ambulatory blood pressure monitoring (ABPM). Amlodipine 5 mg OD administered during a 6-week period, significantly reduced both OBP and ABPM mean values (p < 0.05), whereas no change in heart rate was observed. At the end of the active treatment period, adequately controlled patients were randomized either to amlodipine 5 mg OD (group A) or amlodipine for 12 days followed by a 3-day period on placebo. After this double-blind treatment phase, group P exhibited no significant increase in BP (assessed by OBP or ABPM) when compared to group A. In conclusion, the duration of action of amlodipine extends largely beyond the 24-h span, and when patients omit their treatment for 3 days BP does not significantly increase.

Arterial baroreflex control of the sinus node during dobutamine exercise stress testing.

The contributions of increases in circulating catecholamines, changes in central command, and muscle afferents on baroreflex control of the sinus node during exercise are unclear. We used a dobutamine infusion to induce hemodynamic changes comparable to those of moderate physical exercise in the absence of changes in central command and muscle afferents in 13 healthy subjects. Dobutamine (up to 9 microg/kg body weight per minute) increased systolic blood pressure, shortened the RR interval, increased systolic blood pressure variability, but blunted RR interval variability (P<0.05 versus placebo). Consequently, dobutamine decreased the coherence between variations in systolic blood pressure and RR interval and decreased arterial baroreflex sensitivity from 12+/-2 to 3+/-1 ms/mm Hg (P<0.01). The largest increases in systolic blood pressure with dobutamine were paralleled by the greatest impairments in arterial baroreflex sensitivity (0. 50

Sympathetic rhythmicity in cardiac transplant recipients.

BACKGROUND: Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, +/-0.1 Hz) and a high frequency (HF, +/-0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. METHODS AND RESULTS: We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74+/-3) than either patients with heart failure (56+/-6) or normal subjects (40+/-4) (P<0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (P<0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (P<0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. CONCLUSIONS: Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.