Components of arterial systolic pressure and RR-interval oscillation spectra in a case of baroreflex failure, a human open-loop model of vascular control.

The baroreflex control of circulation is always operating and modulates blood pressure and heart rate oscillations. Thus, the study of cardiovascular variability in humans is performed in a closed-loop model and the physiology of post-sinoaortic denervation is completely unknown in humans. We dissected for the first time the different components of systolic arterial pressure (SAP) and RR-interval spectra in a patient with 'baroreflex failure' (due to mixed cranial nerve neuroma) who represents a human model to investigate the cardiovascular regulation in an open-loop condition. Interactions among cardiovascular variability signals and respiratory influences were described using the multivariate parametric ARXAR model with the following findings: (1) rhythms unrelated to respiration were detected only at frequencies lower than classical low frequency (LF; Slow-LF, around 0.02 Hz) both in SAP an RR spectra, (2) small high-frequency (HF) modulation is present and related with respiration at rest and in tilt (but for SAP only) and (3) the Slow-LF fluctuations detected both in SAP and RR oscillate independently as the multivariate model shows no relationships between SAP and RR, and these oscillations are not phase related. Thus, we showed that in a patient with impaired baroreflex arc integrity the Slow-LF rhythms for RR have a central origin that dictates fluctuations on RR at the same rhythm but unrelated to the oscillation of SAP (which may be related with both peripheral activity and central rhythms). The synchronization in LF band is a hallmark of integrity of baroreflex arc whose impairment unmasks lower frequency rhythms in SAP and RR whose fluctuations oscillate independently.

Metabolic syndrome in patients with intermittent claudication referred to vascular rehabilitation.

AIM: The prevalence of the metabolic syndrome, a clustering of cardiovascular risk factors whose underlying pathophysiology is related to insulin resistance, was estimated in patients with intermittent claudication referred to a short-course intensive rehabilitation program focused on physical training. Improvements in walking distance at the end of the program were also compared among patients with and without the syndrome. METHODS: The metabolic syndrome was documented among 34 (39%) out of 87 enrolled patients, without significant differences between those with and without the syndrome concerning sex (males 91% vs 92% respectively, P=0.816), age (64+/-8 vs 65+/-7 years, P=0.54), coronary heart disease (44% vs 32%, P=0.365), localization of peripheral arterial disease, and impairment of walking capacity as evaluated by constant treadmill test (initial claudication distance (ICD) 156+/-93 vs 176+/-126 m, P=0.428; absolute claudication distance (ACD) 429+/-324 vs 409+/-269 m, P=0.756). RESULTS: At the end of the program, both ICD and ACD significantly improved without any of significant differences between the two groups (ICD +152% vs +174% respectively, P=0.518; ACD +112% vs +177%, P=0.053). CONCLUSIONS: Metabolic syndrome is frequent among patients with intermittent claudication and is not associated with poor response to physical training. Our data highlight the need for considering vascular rehabilitation in these patients in order to both improve walking capacity and minimize cardiovascular morbidity and mortality.

Economic evaluation of a short-course intensive rehabilitation program in patients with intermittent claudication.

AIM: The aim of this study was to provide cost-description and cost-effectiveness of a short-course intensive in-hospital rehabilitation program in patients with intermittent claudication. METHODS: Costs per case treated were calculated according to a local standard protocol including diagnostic evaluation of peripheral arterial disease and other related cardiovascular conditions, physical training, and secondary prevention. Three additional less structured scenarios were also evaluated. RESULTS: All 107 enrolled patients (males 91%, mean age 65+/-8 years) completed the program (4-week duration; twice a day walking exercise) and showed significant increases in walking performance, as evaluated by constant treadmill-test. At admission, the mean values of initial claudication distance (ICD) and absolute claudication distance (ACD) were 150+/-111 and 432+/-327 m, respectively. At the end of the program, 12 (11%) patients completed the treadmill test without pain, while 31 (29%) completed the test without stopping due to maximal pain. Among the remaining 64 (60%) patients, the ICD and ACD increased by 137% and 112%, respectively. The cost per case treated ranged from Euro 1733.2 (standard protocol) to Euro 918.9 (physical training only). By adding the cost of hospitalization and indirect costs, the same costs ranged from Euro 4626.2 to Euro 3811.9. The average cost to walk one additional meter without pain as a result of the rehabilitation program was Euro 57.5, while the cost to walk one additional meter before stopping was Euro 27. As showed by sensitivity analysis, the maintenance of the expected level of treatment success was crucial for program's cost-effectiveness. CONCLUSION: From the societal viewpoint, short-course intensive rehabilitation may be cost-effective in patients with stable intermittent claudication and could be considered in decision models evaluating different therapeutic options.

Clinical validation of an anxiety and depression screening test for intensive in-hospital rehabilitation.

Routine hospital psychological care must necessarily make use of a clinically reliable screening instrument for the identification of the patients to be referred for a clinical interview with a psychologist. This study compared two tests for the evaluation of anxiety and depression that are widely used in the hospital setting: the Hospital Anxiety and Depression Scale (HADS) and Form A-D, consisting of the State-Trait Anxiety Inventory (STAI-X1) for the evaluation of anxiety, and the Depression Questionnaire (DQ) for measuring depression. The aim of the study was to identify which of these instruments is the most suitable for screening a population admitted at in-hospital intensive rehabilitation using the clinical interview-based psychological evaluation as the gold standard. Both of the tests showed a concordance with the clinical opinion expressed by the psychologist, whose judgement was guided by the use of the validation study evaluation form. The analyses confirmed the good correlation of the two instruments in measuring anxiety and depression. The sensitivity of the STAI-X1 (52%) was less than that of HADS section A (72%), but its specificity (99%) was greater than that observed with the application of the HADS Anxiety subscale (84%). Analysis of the ROC curves showed that the STAI-X1 percentages of sensitivity and specificity tended to balance at higher level with a cut-off point equal to the 80th percentile. The results of the analysis of the DQ demonstrated equivalence with the results obtained using HADS section D, with a cut-off point of the 90th percentile. On the basis of these results, and given that both the STAI-X1 and the DQ have a broadly based Italian normative population, we feel that they can be recommended for psychological screening of patients in an in-hospital intensive rehabilitation.

[Stratification of arrhythmia risk in infarction: reflexions in the light of large trials]. / Stratificazione del rischio aritmico nell'infartuato: riflessioni alla luce dei grandi trial.

The identification of patients at higher risk of life-threatening ventricular arrhythmias after myocardial infarction still represents a clinically relevant problem, particularly after results of recent studies which support the efficacy of implantable cardioverter defibrillator (ICD) in reducing total mortality in patients with a previous myocardial infarction and left ventricular dysfunction, with and without additional risk markers. However, owing to the high cost of ICD therapy, an effective arrhythmic risk stratification may be desirable. The low diagnostic accuracy reported by various studies using single risk stratifiers (either invasive and non invasive) suggested a combined use of multiple parameters in order to improve the predictive power of the risk stratification algorithms. This approach, that takes into account the multifactorial genesis of malignant ventricular arrhythmias, has been demonstrated to be able to identify subgroups of patients at very high arrhythmic risk. In particular, a two-level algorithm based upon the selection of candidates to electrophysiologic study among patients with abnormal non-invasive testing, showed itself as a particularly effective tool for identification of such patients. In this paper the Authors summarize most recent results on the risk stratification protocols and the use of ICDs and provide an operative algorithm that keeps into account either aggressive and moderate approaches to patients surviving a myocardial infarction.

[Stratification of the arrhythmia risk after acute myocardial infarct]. / La stratificazione del rischio aritmico dopo infarto miocardico acuto.

Recent studies clearly support the role of the cardioverter implantable defibrillator in reducing arrhythmic and all-cause mortality in patients with a previous myocardial infarction. However, the use of the cardioverter implantable defibrillator cannot be extended to all myocardial infarction patients despite its effectiveness because implantation is an invasive procedure and the cost of the device is high. Thus, the correct and effective identification of patients at high risk of life-threatening ventricular arrhythmias represents a clinically relevant problem owing to the availability of an effective but expensive therapeutic tool. Many non-invasive tests have been studied in past years to assess the risk of ventricular arrhythmias after myocardial infarction; moreover, also programmed ventricular stimulation has been used to evaluate inducibility of ventricular tachycardia. Nevertheless, the positive predictive value of both non-invasive and invasive testing is low and not adequate to make a clinical decision. This finding is probably related to the multifactorial genesis of malignant ventricular arrhythmias which need several concomitant factors to trigger arrhythmias. For this reason the combined use of multiple risk markers is needed in order to improve diagnostic accuracy and identify subgroups of patients at high enough risk to define specific prophylactic options. In this scenario, according to available data, patients with two or more non-invasive risk markers should undergo electrophysiologic testing. In fact, patients with a recent myocardial infarction who have positive non-invasive tests and also show inducibility of sustained monomorphic ventricular tachycardia at programmed ventricular stimulation have a high incidence of arrhythmic events during the subsequent follow-up period and, in the author's opinion, should undergo a cardioverter defibrillator implantation. In the present review, an analysis of the main diagnostic tests for risk stratification of postinfarction patients will be performed and operative suggestions will be provided.

Despite good compliance, very low fat diet alone does not achieve recommended cholesterol goals in outpatients with coronary heart disease.

AIM: A low-saturated, low-cholesterol diet is important in the treatment of hypercholesterolaemia in patients with coronary heart disease. The aim of this study was to investigate the efficacy of a very low fat diet to achieve a targeted serum low density lipoprotein (LDL) cholesterol level (3.37mmol x l-1 were investigated 12-14 weeks after an acute coronary event. After overnight fasting each patient had (a) his resting energy expenditure measured (indirect calorimetry using standard protocol) and (b) venous blood sampled from a forearm vein to determine lipid profile. All the patients were randomly allocated to four groups of treatment: Group A on a very low fat diet (resting energy expenditure-fat diet, where fat intake was

Which strategy is "best" after myocardial infarction? The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator Trial: rationale and study design.

The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator (BEST-ICD) Trial is a multicenter prospective randomized trial that started in June 1998, in 95 centers in Italy and Germany. The trial will test the hypothesis whether, in high-risk post myocardial infarction (MI) patients already treated with beta blockers, electrophysiologic study (EPS)-guided therapy (including the prophylactic implantation of implantable cardioverter defibrillator [ICD] in inducible patients) will improve survival compared with conventional therapy. Patients eligible for the study are survivors of recent MI (> or = 5 and < or = 21 days), aged < or = 80 years, with left ventricular ejection fraction < or = 35% and > or = 1 of the following additional risk factors: (1) ventricular premature beats > or = 10/hour; (2) decreased heart rate variability (standard deviation of unusual RR intervals < 70 msec); and (3) presence of ventricular late potentials. Furthermore, all enrolled patients must be able to tolerate at least 25 mg of metoprolol per day. These patients constitute about 9% of all patients with recent MI and are expected to have a 2-year all-cause mortality > 25% of which 50% is anticipated to be from sudden death. The main criteria of exclusion from the study are (1) a history of sustained ventricular arrhythmia; (2) documentation of nonsustained ventricular tachycardia during the screening phase; and (3) the need for myocardial revascularization and contraindications or intolerance to beta-blocker therapy. Eligible patients will be randomized to 2 different therapeutic strategies: conventional strategy or EPS/ICD strategy. Patients allocated to the EPS/ICD strategy will undergo further risk stratification, and electrophysiologically inducible patients (approximately 35%) will receive prophylactic ICDs, in addition to the conventional therapy, whereas noninducible patients will be only conventionally treated. The primary endpoint of the study will be death from all causes. By hypothesizing a 30% reduction in the 2-year mortality (from 20% to 14%) in the EPS/ICD group compared with conventionally treated patients, 1,200 patients will have to be included. A triangular, 2-sided sequential design with preset boundaries, for a 5% significance level and 90% power to detect a reduction in 2-year mortality from 20% to 14%, will be used to permit early termination of the trial if the strategy is found to be efficacious, no difference, or inefficacious.

Prognosis in myocardial infarction survivors with left ventricular dysfunction is predicted by electrocardiographic RR interval but not QT dispersion.

OBJECTIVES: The aim of the study was to assess if QT dispersion and RR interval on the standard 12-lead electrocardiogram (ECG) predict cardiac death and late arrhythmic events in postinfarction patients with low left ventricular ejection fraction (LVEF). QT dispersion on a standard electrocardiogram (ECG) is a measure of repolarization inhomogeneity, but its prognostic meaning in myocardial infarction (MI) survivors is unclear, especially in patients with left ventricular dysfunction. RR interval has been shown to predict mortality in post-MI patients, but its prognostic power has not been compared with other noninvasive risk factors. METHODS: Retrospective cohort study. Ninety patients were identified, from a series of 547 consecutive postinfarction patients admitted to our institution for phase II cardiac rehabilitation, as having a LVEF of <0.40 at two-dimensional echocardiography (mean LVEF 0.35+/-0.04; range 0.20-0.39). QT dispersion and RR interval were analyzed on the admission 12-lead electrocardiogram, 20+/-10 (range 8-45) days after MI, using specially designed software. Additional risk markers were collected from clinical variables, signal-averaged ECG and Holter recording. RESULTS: During 24+/-18 (range 1-63) months of follow-up, 10 of 90 patients (11%) died, all from cardiac causes, and there were 18 late arrhythmic events, defined as sudden death or the occurrence of a sustained ventricular arrhythmia > or =5 days after the index MI. QT interval and dispersion were not significantly prolonged in patients who died compared to survivors and not significantly different between patients with and without arrhythmic events. Mean RR interval from standard ECG was significantly shorter in patients with both cardiac death (682+/-99 vs. 811+/-134 ms; P=0.004) and arrhythmic events (720+/-100 vs. 818+/-139 ms; P=0.006). A Cox proportional hazards model identified RR interval from standard ECG (P<0.001) and a history of more than one MI (P=0.002) as significant predictors of cardiac death independent of thrombolytic therapy, LVEF, filtered QRS complex duration at signal-averaged ECG, mean RR and its standard deviation at 24-h Holter monitoring. CONCLUSIONS: Measurement of QT interval and dispersion 3 weeks after MI has no prognostic power in patients with LV dysfunction after a recent MI. RR interval on standard 12-lead ECG is as good a prognostic indicator as other, more expensive, noninvasive markers. These findings may be relevant in this era of limited health care resources.

[The use of bilateral mammary artery in myocardial revascularization. The risk factors emergent from a multivariate analysis conducted on 474 patients]. / L'uso della arteria mammaria bilaterale nella rivascolarizzazione miocardica. Fattori di rischio emersi da un'analisi multivariata condotta su 474 pazienti.

BACKGROUND: The internal mammary artery is used as coronary artery graft conduit because of its superior patency. According to some authors, the bilateral IMA can increase perioperative morbidity. The aim of this study was to determine the risk factors increasing perioperative mortality and morbidity in the use of bilateral IMA. METHODS: We analyzed the data of 474 patients operated consecutively with the use of bilateral IMA between January 1987 and December 1995 at the Department of Cardiac Surgery of the Varese Hospital. The univariate analysis was done on 17 ordinal variables using a "Fisher exact test" and on 4 continuous variables by "pooled-variance t-test" to investigate risk factors for mortality, mediastinitis, superficial wound infection and aseptic dehiscence of the sternum; a p-value lower than 0.1 was used as cut-off point to introduce the variables into a stepwise multiple logistic regression analysis. RESULTS: From the univariate analysis are: postoperative low-output syndrome (p = 0.01), LVEF (p = 0.02) and number of grafts (p = 0.04) are correlated to hospital mortality (1.5%); obesity (p < 0.001) and peripheral arteriopathy (p = 0.009) are correlated to postoperative mediastinitis (5%); obesity (p < 0.001), peripheral arteriopathy (p = 0.009), surgeon (p = 0.001), year of operation (p < 0.001), reoperation for bleeding (p = 0.004) and length of extracorporeal circulation (p = 0.02) are correlated to superficial wound infection (7%); obesity (p = 0.002) and COPD (p = 0.05) are correlated to aseptic dehiscence of the sternum (2%). The multivariate analysis identified low LVEF as the only independent risk factor for hospital mortality (p = 0.03), whereas obesity (p = 0.01) and peripheral vasculopathy (p = 0.03) proved to be correlated to postoperative mediastinitis; obesity (p < 0.001), year of the operation (p < 0.001), low LVEF (p = 0.007) and reoperation for bleeding (p = 0.01) were correlated to superficial infection of the wound and obesity turned out to be the only risk factor for aseptic dehiscence for the sternum (p = 0.003). The infection of the wound did not increase mortality, but it did increase the mean postoperative length of hospital stay (6 days for patients free of any complications of the wound versus 29.7 days for patients with complications of the wound). CONCLUSIONS: In patients with bilateral mammary grafts, obesity is the main risk factor for complications of the wound and this event greatly increases the length of the patient's hospital stay. Consequently, we suggest that bilateral mammary artery grafts be used carefully in this subset of patients.

Autonomic control of heart rate: pharmacological and nonpharmacological modulation.

The evidence of the predictive value of autonomic markers has generated a growing interest for interventions able to influence autonomic control of heart rate. The hypothesis is that an increase in cardiac vagal activity as detected by an increase in heart rate variability (HRV) or baroreflex sensitivity (BRS) may be beneficial in the ischemic heart. Numerous experimental data support the hypothesis that augmenting vagal activity might be protective against lethal ischemic arrhythmias. Among them is the evidence that ventricular fibrillation during acute myocardial ischemia may be largely prevented by electrical stimulation of the right cervical vagus or by pharmacological stimulation of cholinergic receptors with oxotremorine. There is an inherent danger in the so far unwarranted assumption that modification of HRV or BRS translates directly in cardiac protection. This may or may not be the case. It should be remembered that the true target is the improvement in cardiac electrical stability and that BRS or HRV are just markers of autonomic activity. Low dose scopolamine increases HRV in patients with a prior myocardial infarction. This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective after MI. We tested low dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective and found that this intervention does indeed increase cardiac vagal markers but has minimal antifibrillatory effects. This is in contrast to exercise training that in the same experimental model had a marked effect on both BRS and HRV and at the same time provided strong protection from ischemic ventricular fibrillation. Thus, based on the current knowledge it seems appropriate to call for caution before attributing excessive importance to changes in "markers" of vagal activity in the absence of clearcut evidence for a causal relation with an antifibrillatory effect.

Evaluation of regional left ventricular wall motion with color kinesis: comparison with two-dimensional echocardiography in patients after acute myocardial infarction.

BACKGROUND: Color kinesis (CK) is a new echocardiographic technique for the assessment of left ventricular (LV) wall motion based on acoustic quantification. Using integrated backscatter data, this technique identifies the pixel value transitions from blood to myocardial tissue throughout systole and tracks endocardial motion in real time. The color-encoded images, built on a frame-by-frame basis by adding one color at a time, provide an integrated display of the timing and amplitude of endocardial motion in a single end-systolic frame. Recent studies have shown that CK is a promising clinical tool for quantitative assessment of regional LV function. OBJECTIVES: The aim of this study was to evaluate the feasibility and accuracy of CK in identifying the regional wall-motion abnormalities diagnosed by conventional two-dimensional (2-D) echocardiography in patients after acute myocardial infarction (AMI). METHODS: The end-systolic color overlays were analyzed using a method to quantify the regional timing and amplitude of endocardial systolic excursion (ESE) based on the count of the numbers of colors. At this point, the total duration (ESE timing) and distance (ESE amplitude) of endocardial excursion from end-diastolic to end-systolic color-frame was calculated in each segment. In 54 patients after AMI, we compared the feasibility and ability of CK superimposed on 2-D superimposed on 2-D superimposed on 2-D echocardiographic images and visual 2-D echo analysis to evaluate the endocardial border excursion in parasternal short-axis (SAX) and apical four-(AP4CH) and two-(AP2CH) chamber views. In 20 normal subjects, the end-systolic color overlays were used to evaluate the variability of the measurements of ESE timing (msec) and amplitude (cm) and to define the reference values. Image quality was considered adequate if at least 12 of 16 segments could be evaluated for systolic function by conventional visual 2-D echo. Among 54 patients, 35 with adequate studies were selected to determine the accuracy of quantitative analysis of CK images in identifying regional wall-motion abnormalities. RESULTS: The SAX view was obtained in 36 of 54 patients; of the possible 216 segments, 210 (97%) were adequately visualized by 2-D echocardiography and 207 (96%) by CK. Apical views were obtained in 50 patients (93%); of the possible 300 segments, 93% were visualized by 2-D echocardiography and 90% by CK in the AP4CH view and 94% and 92%, respectively, were visualized by the two methods in the AP2CH view. In normal subjects, measurements of ESE timing and amplitude were found to be consistent and the mean values were 346 msec (range 280-360) and 0.99 cm (range 0.72-1.26) respectively. In the 35 selected patients, 2-D echocardiography identified 355 normokinetic segments in which ESE timing and amplitude were similar to the reference values. In 83 hypokinetic segments and 108 akinetic segments, ESE timing and amplitude were significantly inferior to values of normokinetic segments (p < 0.001). An ESE timing below the reference values of 280 msec identified all of the 191 asynergic segments (sensitivity and specificity = 100%) and an ESE amplitude of less than 0.70 cm identified 188 asynergic segments (sensitivity = 98% and specificity = 99%). CONCLUSIONS: CK showed good feasibility and diagnostic accuracy in identifying regional wall motion abnormalities in patients with acute myocardial infarction. The model used in our study for the quantitative analysis of color kinesis images, which provided easy and feasible indices of timing and amplitude of endocardial excursion, enabled fast and objective evaluation of LV regional wall motion.

Cost-effectiveness analysis of invasive and noninvasive tests in high risk patients treated with amiodarone after acute myocardial infarction.

OBJECTIVES: We sought to evaluate 1) the cost-effectiveness of amiodarone therapy in postinfarction patients; and 2) the influence of alternative diagnostic strategies (noninvasive only vs. noninvasive and electrophysiologic testing) on survival benefit and cost-effectiveness ratio of amiodarone therapy. BACKGROUND: The cost-effectiveness of amiodarone therapy in postinfarction patients is still unknown, and no study has determined which diagnostic strategy should be used to maximize amiodarone survival benefit while improving its cost-effectiveness ratio. METHODS: We designed a postinfarction scenario wherein heart rate variability analysis on 24-h Holter monitoring was used as a screening test for 2-year amiodarone therapy in a cohort of survivors (mean age 57 years) of a recent myocardial infarction. Three different therapeutic strategies were compared: 1) no amiodarone; 2) amiodarone in patients with depressed heart rate variability; 3) amiodarone in patients with depressed heart rate variability and a positive programmed ventricular stimulation. Total variable costs and quality-adjusted life expectancy during a 20-year period were predicted with use of a Markov simulation model. Costs and charges were calculated with reference to an Italian and American hospital. RESULTS: Amiodarone therapy in patients with depressed heart rate variability and a positive programmed ventricular stimulation was dominated by a blend of the two alternatives. Compared with the no-treatment strategy, the incremental cost-effectiveness ratio of amiodarone therapy in patients with depressed heart rate variability was $10,633 and $39,422 per gained quality-adjusted life-year using Italian costs and American charges, respectively. CONCLUSIONS: Compared with a noninterventional option, amiodarone prescription in all patients with depressed heart rate variability seems to be a more appropriate approach than the alternative based on the combined use of heart rate variability and electrophysiologic study.

AIDS and tuberculosis control programmes: an integrated approach at educational level.

In developing countries with a high prevalence of individuals co-infected by human immunodeficiency virus (HIV) and tuberculosis (TB), urgent public health measures should be implemented to prevent the spread of both diseases. This study was performed by a combined acquired immune deficiency syndrome (AIDS)-TB health team with the following aims: 1) to assess knowledge, attitudes and practice towards AIDS; 2) to identify target groups for health education (HE); 3) to evaluate HE impact; 4) to circulate correct information on AIDS and TB through target groups; and 5) to evaluate integration of AIDS and control TB activities. Secondary school students of Arua District, Uganda, participated in a standardized HE session (covering the key-points of AIDS and TB control) preceded by a pretest (multiple choice) questionnaire and followed 3 months later by the same questionnaire (post-test). The impact of HE on AIDS control was evaluated by comparing answers to pre- and post-test questionnaires and its influence on the TB programme by evaluating case-finding performances in the period preceding and following the survey. We analysed 1,478 questionnaires. The results of our study gave information on knowledge about AIDS, identified females and students < 16 yrs of age as good targets for HE, revealed that the impact of HE was significantly associated with improved knowledge, contributed to improved TB case-finding and offered suggestions for the integration of programmes. The survey represented an opportunity to create a stable AIDS/TB health team at district level.

Effects of oral pirenzepine on heart rate variability and baroreceptor reflex sensitivity after acute myocardial infarction.

OBJECTIVES: Our aims were 1) to assess whether oral pirenzepine could increase indexes of cardiac vagal activity in postinfarction patients, and 2) to compare the effects of this agent with those of transdermal scopolamine. BACKGROUND: Depression of vagal tone and reflexes predicts a poor arrhythmic outcome after myocardial infarction. Interventions for shifting the sympathovagal balance toward vagal dominance are now of increased clinical interest. Intravenous pirenzepine increases RR interval variability in normal volunteers, a finding that could have therapeutic implications if confirmed in postinfarction patients after oral administration of the drug. METHODS: In a single-blind placebo-controlled crossover trial, short-term RR interval variability and baroreceptor reflex sensitivity were evaluated in 20 patients an average of 19 +/- 6 days after infarction. Analysis was performed during control conditions and during administration of placebo, oral pirenzepine and transdermal scopolamine. RESULTS: Compared with placebo, at a dose of 25 mg twice daily, pirenzepine significantly increased all time and frequency domain measures of RR interval variability and augmented baroreceptor reflex sensitivity by 60% (mean +/- 1 SD 10.4 +/- 5.9 vs. 6.5 +/- 3.2 ms/mm Hg, p = 0.0007). Pirenzepine and scopolamine showed a similar vagomimetic effect, but the overall incidence of adverse effects was lower with pirenzepine (1 [5%] of 20 vs. 10 [50%] of 20). CONCLUSIONS: In patients with a recent myocardial infarction, oral pirenzepine proved equal to transdermal scopolamine in significantly increasing indexes of cardiac vagal activity. These data suggest that oral pirenzepine may have a therapeutic potential for preventing malignant ventricular arrhythmias after infarction.

Effect of thrombolysis on heart rate variability and life-threatening ventricular arrhythmias in survivors of acute myocardial infarction.

OBJECTIVES: The aim of the present study was to determine the influence of early thrombolysis on ventricular tachyarrhythmias (clinical and inducible) and heart rate variability in survivors of myocardial infarction at high risk for life-threatening ventricular arrhythmias. BACKGROUND: A greater electrical heart stability may be important in improving survival in patients treated with thrombolysis. Few data are available about the influence of fibrinolysis on postinfarction arrhythmic events and other prognostic variables, such as inducible ventricular tachycardia and heart rate variability. METHODS: The study group comprised 51 consecutive patients who underwent electrophysiologic study within 30 days of infarction, owing to the presence of two or more of the following criteria: left ventricular ejection fraction < 40%, late potentials and repetitive ventricular ectopic beats. Thirty patients underwent thrombolysis within 6 h of the onset of symptoms (Group A), and 21 received conventional treatment (Group B). Inducibility of sustained monomorphic ventricular tachycardia was tested in both groups, and the standard deviation of all normal RR intervals during 24-h Holter monitoring was calculated. All patients were prospectively evaluated for occurrence of arrhythmic events. RESULTS: The two groups were similar with regard to left ventricular ejection fraction (mean +/- 1 SD 38 +/- 6% [Group A] vs. 36 +/- 8% [Group B]). Ventricular tachycardia was induced in 6 (20%) of 30 Group A patients versus 14 (67%) of 21 Group B patients (p = 0.002). The standard deviation of normal RR intervals was higher in Group A than in Group B (113 +/- 36 vs. 90 +/- 39 ms, p = 0.05). In patients with anterior infarction, the standard deviation of normal RR intervals was higher in 19 patients with thrombolysis than in 16 patients with conventional treatment (118 +/- 41 vs. 74 +/- 24 ms, p = 0.0002). During a mean follow-up period of 23 +/- 11 months, 4 (13%) of 30 Group A patients had an arrhythmic event versus 9 (43%) of 21 Group B patients (p = 0.04). CONCLUSIONS: After myocardial infarction, in high risk patients, thrombolysis significantly reduced the occurrence of arrhythmic events independently of left ventricular function. This effect may be related to both an improvement in electrical heart stability, as elucidated by electrophysiologic study, and a favorable action on the cardiac sympathovagal balance.