[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.

Sleep apnoea in ischaemic heart disease: differences between acute and chronic coronary syndromes.

OBJECTIVE: To evaluate the incidence of sleep apnoea in acute and chronic coronary syndromes. DESIGN: Analysis of sleep and breathing characteristics in a polysomnographic study. SETTING: Cardiology department in tertiary referral centre. PATIENTS: 23 patients were studied soon after acute myocardial infarction (group 1), 22 after clinical stabilisation of unstable angina (group 2), and 22 who had stable angina (group 3). Conditions liable to cause sleep apnoea, such as obesity, chronic obstructive pulmonary disease, neurological disorders, or the use of benzodiazepines, were exclusion criteria. MAIN OUTCOME MEASURES: Sleep apnoea and hypopnoea, oxygen saturation, and sleep indices evaluated soon after clinical stabilisation in groups 1 and 2 and also in group 3. RESULTS: Sleep apnoea, mainly of the central type, was equally present in groups 1 and 2 (mean (SD) apnoea-hypopnoea index: 11.10 (19.42) and 14.79 (20.52), respectively) and more severe than in group 3 (2.82 (6.43), p < 0. 01). Total time spent at SaO(2) < 90%, although significantly greater in group 1 and 2 (0.89 (2.4), 1.42 (3.23) min) than in group 3 (0.01 (0.05) min, p < 0.05), was clinically irrelevant. More arousals per hour of sleep (p < 0.05) were detected in group 1 (5.15 (3.71)) and group 2 (5.31 (2.14)) than in group 3 (2.83 (1.51)). CONCLUSIONS: Sleep apnoea, chiefly of the central type, not only characterises acute myocardial infarction, as found by others, but also unstable angina studied after recent stabilisation. Patient selection by exclusion of other causes of breathing disorders shows that coronary disease related apnoea is absent in the chronic coronary syndrome. In acute syndromes the lack of clinically significant apnoea related oxygen desaturation, together with the low associated incidence of major ischaemic and arrhythmic events, suggests that sleep apnoea is benign in these circumstances, despite a worsening of sleep quality.

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.

Influence of transdermal scopolamine on cardiac sympathovagal interaction after acute myocardial infarction.

In 41 survivors of acute myocardial infarction (AMI) a prospective study was performed in 2 sequential phases. In phase 1, the role of baroreflex sensitivity and heart rate variability as predictors of inducible and spontaneous sustained ventricular tachyarrhythmias was evaluated. In phase 2, the effects of transdermal scopolamine on baroreflex sensitivity, spectral and nonspectral measures of heart rate variability were investigated. At a mean follow-up of 10 +/- 3 months after AMI, 5 of 41 patients (12%) developed a late arrhythmic event. Of these, all (100%) had inducibility of sustained monomorphic ventricular tachycardia at programmed stimulation compared with 3 of 36 patients (8%) without events (p < 0.0001). At multivariate analysis, baroreflex sensitivity had the strongest relation to both inducibility of sustained monomorphic ventricular tachycardia (p < 0.0001) and occurrence of arrhythmic events (p < 0.0001). Of 41 patients, 28 (68%) consented to undergo phase 2 of the investigation. Baroreflex sensitivity significantly (p < 0.00001) increased after transdermal scopolamine as well as heart rate variability indexes. Of these, the mean of SDs of normal RR intervals for 5-minute segments (p < 0.0001) and the total power (p < 0.0001) had the most significant improvement after scopolamine. The present investigation confirms that assessment of autonomic function is an essential part of arrhythmic risk evaluation after AMI. Transdermal scopolamine, administered to survivors of a recent AMI, reverses the autonomic indexes that independently predict arrhythmic event occurrence. On the basis of these data, transdermal scopolamine could be a potential useful tool in the prophylaxis of life-threatening ventricular arrhythmias after AMI.

Prediction of late arrhythmic events after acute myocardial infarction from combined use of noninvasive prognostic variables and inducibility of sustained monomorphic ventricular tachycardia.

A combined use of noninvasive techniques and electrophysiologic study in the prediction of arrhythmic events was prospectively evaluated in 303 surviving patients of acute myocardial infarction (AMI). The most powerful combination of noninvasive prognostic variables in identifying patients suitable for invasive strategies was also assessed. Patients who had > or = 2 variables among left ventricular ejection fraction < 0.4, ventricular late potentials and repetitive ventricular premature complexes (VPCs) were considered eligible for programmed ventricular stimulation. After 15 +/- 7 months of follow-up, 19 patients (6%) had an arrhythmic event. Left ventricular dyskinesia (p < 0.00001) and ejection fraction < 0.4 (p < 0.000001), late potentials (p < 0.001), filtered QRS duration > or = 106 ms (p < 0.00001), VPCs/hour > 6 (p < 0.05), paired VPCs (p < 0.01), > or = 2 runs of unsustained ventricular tachycardia (VT) per monitoring (p < 0.001), heart rate variability index < or = 29 (p < 0.00001) and mean RR interval < or = 750 ms (p < 0.01) were found to be significant univariate predictors of events. At multivariate analysis, only low left ventricular ejection fraction, prolonged filtered QRS duration, reduced heart rate variability index and detection of > or = 2 runs of unsustained VT per monitoring had an independent relation to late arrhythmic events. Of 67 eligible patients, 47 (70%) consented to undergo programmed stimulation. A positive electrophysiologic study was found to be the strongest independent predictor of events among patients preselected by noninvasive techniques. With a good sensitivity (81%), a combined use of noninvasive tests and electrophysiologic study selected a group of post-AMI patients at sufficiently high risk (event rate 65%) to be considered candidates for interventional therapy. The combination of > or = 2 variables among left ventricular ejection fraction < 0.4, filtered QRS duration > or = 106 ms and > or = 2 runs of unsustained VT was superior to the other ones in identifying high-risk subjects (positive and negative predictive values for arrhythmic events of 44 and 99%, respectively). On the basis of the data, this scheme appears to be the most appropriate for selecting patients suitable for electrophysiologic testing and invasive strategies after AMI.