Biomedical subjects
Publications and source records attributed to R Cappato.
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Sodium channel blockers and class III antiarrhythmic compounds, as well as beta blockers, have been used in preventing recurrences of sudden cardiac death. In recent years, implantable cardioverter-defibrillators (ICDs) have been used increasingly, but no data from randomized trials comparing antiarrhythmic drug and ICD therapy have been reported in this setting. In 1987, the Cardiac Arrest Study Hamburg (CASH), a prospective, randomized trial, was initiated to compare metoprolol, amiodarone, propafenone, and ICD implantation in patients surviving sudden cardiac death due to documented ventricular tachycardia and/or ventricular fibrillation. The details of the study design and preliminary results are presented herein. The primary endpoint of the study is total mortality. The data reviewed in March 1992, representing a mean follow-up period of 11 months, indicated no significant differences among patients randomized to metoprolol, amiodarone, and ICDs. However, there was a significantly higher total mortality and cardiac arrest recurrence in patients randomized to propafenone compared with those randomized to the ICD treatment limb. The study continues with the deletion of the propafenone treatment limb.
In 17 patients (aged 78 +/- 9 years) with symptomatic atrial fibrillation and a slow ventricular response not related to drugs, a resting electrocardiogram and 24-hour Holter recording were obtained before and 5 to 6 days after administration of slow-release theophylline (700 mg/day), and successively every 3 months during the long-term phase. Fourteen patients had organic heart disease, and 13 complained of syncope or presyncope, and 4 of asthenia and easy fatigability. At the steady-state evaluation, theophylline significantly increased resting heart rate (HR) by 42%, mean 24-hour HR by 31% and minimal 24-hour HR by 34%. Cardiac pauses > 2,500 ms disappeared or markedly decreased. The daily number of wide QRS complexes increased. Serum theophylline level was 13 +/- 5 ng/ml. During the follow-up period (20 +/- 18 months), the mean daily theophylline dosage was 450 mg and the mean serum theophylline level 9 ng/ml. Seven patients died: 1 because of heart failure, and 6 because of noncardiac death. One patient complained of a syncopal episode during 1 visit. The drug markedly reduced asthenia and easy fatigability. During the long-term phase, HR increased spontaneously in 3 patients, and the treatment was interrupted. In 2 patients, theophylline had to be discontinued because of gastric intolerance. During long-term therapy, HR was similar to that observed at the steady-state evaluation, despite the reduction in daily dosage. The data suggest that theophylline is an effective therapy in most patients with symptomatic atrial fibrillation and a slow ventricular response.
OBJECTIVES: This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. BACKGROUND: Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. The relative role of the two components, if present, might improve our understanding of the therapeutic and proarrhythmic mechanisms of quinidine on the ventricular tissue. METHODS: Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 15 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intravenous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); oral quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same method in a second study. RESULTS: During the control study, the mean slope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0.05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulation (from 0.14 +/- 0.05 to 0.19 +/- 0.05, p < 0.05), thus annulling the differences observed between the two states in the control study. CONCLUSIONS: A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ventricular repolarization. This effect is not evident in the basal state owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventricular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidine.
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The aim of this study was to determine whether the time of occurrence of sudden death exhibits a circadian rhythm depending on its different anatomoclinical causes. A longitudinal prospective investigation of 610 nonhospitalized subjects who died suddenly in the Emergency Room of Ferrara Hospital between January 1983 and December 1990 was conducted. All subjects underwent autopsy. Sudden death was classified on the basis of the following pathological causes; acute myocardial infarction, acute myocardial failure, intracerebral hemorrhage, rupture of aortic aneurysm, pulmonary embolism, and clinical causes, i.e., arrhythmia and circulatory failure. The investigated cases were stratified into 2 groups according to age; Group A = age < 70 years (n = 301, 49.3%), and Group B = age > or = to 70 (n = 309, 51.7%). The assessment of circadian rhythmicity was performed utilizing the single cosinor method. The results by cosinor analysis found a circadian rhythmicity for cases of sudden death (peak at 14.04, n = 610, p = 0.036), and in particular for females (peak at 13.12, n = 200, p = 0.004). Spectral analysis detected a statistical ultradian cycle in males having an 8-hour period (p = 0.015). A statistically significant circadian rhythm was found for cases of sudden death due to acute myocardial infarction (peak at 15.28, n = 330, p = 0.013), pulmonary embolism (peak at 11.46, n = 56, p = 0.003) and arrhythmia (peak at 13.08, n = 291, p = 0.04). In Group A no significant circadian rhythm was found, whereas in Group B a significant rhythmicity was found for sudden death from cardiac causes at 13.32 (n = 249, p = 0.015), from myocardial infarction at 15.02 (n = 154, p = 0.018) and from arrhythmia at 13.07 (n = 122, p = 0.014). Different circadian patterns of onset of sudden death may be shown in various subgroups of patients, due not only to different pathophysiologic mechanisms but also to anatomo-clinical aspects.
BACKGROUND: The influences of the sympathetic tone on the conduction in the Kent bundle have been widely investigated; on the contrary, very little is known about the effects of the vagal tone on such a bypass. Vagal influences on Kent bundle can be adequately investigated only after sympathetic blockade. METHODS: An electrophysiological study was performed in 12 subjects with Wolff-Parkinson-White syndrome (7 F and 5 M, age: 30 +/- 17 years) during basal state, after beta-blockade (propranolol 0.2 mg/Kg iv) and after atropine (0.04 mg/Kg iv). RESULTS: In no subject were signs of organic heart disease present. The anterograde effective refractory period of the bypass significantly lengthened after propranolol (291 +/- 65 ms vs 313 +/- 52 ms, p < .01), and shortened after atropine (313 +/- 52 ms vs 290 +/- 46 ms, p < .01). This parameter showed no significant differences in the basal state nor after complete autonomic blockade. The longest pacing atrial cycle length for a second degree atrio-ventricular block in the bypass significantly lengthened after propranolol (322 +/- 55 ms vs 383 +/- 44 ms, p < .01) and shortened after atropine, even if the variation was not statistically significant (383 +/- 44 ms vs 368 +/- 39 ms, p: NS); such a parameter was significantly more prolonged after complete autonomic blockade than in the basal state (p < .05). The retrograde conduction in the bypass showed a similar behaviour: the retrograde effective refractory period and the longest ventricular pacing cycle length for a second degree ventriculo-atrial block significantly lengthened after propranolol (434 +/- 133 ms vs 532 +/- 188 ms, p < .01 and 398 +/- 150 ms vs 492 +/- 179 ms, p < .01, respectively) and shortened after atropine (532 +/- 188 ms vs 464 +/- 157 ms, p < .01, and 492 +/- 179 ms vs 431 +/- 158 ms, p < .05, respectively). These parameters were more prolonged after complete autonomic blockade than in the basal state (p < .05). CONCLUSIONS: These data evidence a vagal influence on the conduction in the resting Kent bundle; the vagal effect appears, however, less marked than the sympathetic one.
The aim of this study was to determine whether sudden cardiac death from pulmonary embolism exhibits any chronobiological rhythm. Five hundred and seven consecutive subjects dying suddenly outside of hospital and brought into our Emergency Department from January 1983 to December 1989 were studied. The time and date of event were accurately recorded. All subjects underwent autopsy and 48 of them were found to have died of pulmonary embolism (23 males, mean age 73.9 +/- 8 years and 25 females, mean age 76 +/- 12 years). All data were analysed by means of single cosinor[19,20]. In the subjects with pulmonary emboli both a circadian and a circannual rhythmicity were found, with a significant acrophase respectively in the morning (h.min. 11.46, P = 0.003) and in winter (-19.3, P = 0.009).
Dependence of QT interval duration on cardiac heart rate has been well established and is considered to be an intrinsic property of ventricular myocardium. Conclusive results of autonomic influences on such phenomena are lacking. To evaluate whether rate-dependent changes of QT interval are conditioned by the autonomic nervous system, 28 normal subjects with no heart disease and a normal QT interval were electrophysiologically assessed. The QT interval was calculated at 6 paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) during the basal state, and after beta blockade (propranolol 0.2 mg/kg) and autonomic blockade (propranolol plus atropine 0.04 mg/kg). Because of atrioventricular nodal conduction limits, intrapatient cross-comparisons were performed in 10 subjects (aged 42 +/- 15 years). Single regression lines, evaluated in each subject, showing correlation between pacing cycle length and QT duration at each of the 3 states were analyzed. The mean slope observed after autonomic blockade (b = 0.10 +/- 0.04) was significantly lower than that seen during the basal state (b = 0.22 +/- 0.12, p less than 0.05) and after beta blockade (b = 0.23 +/- 0.08, p less than 0.05); nonsignificant differences were found between slopes during the basal state and after beta blockade. Results showed that vagal tone increased intrinsic dependence of QT at increasing cycle length, whereas sympathetic tone did not seem to interfere significantly. Since (in each subject) beta blockade was performed--or achieved--before atropine administration, the vagal influences are likely to be directly exerted on the ventricular electrophysiologic substrate.
This study was undertaken to evaluate a possible role of sinus node (SN) artery disease in the pathogenesis of sick sinus syndrome (SSS) in patients with an inferior wall acute myocardial infarction (AMI). Coronary angiography and electrophysiologic studies of the SN, both in the basal state and after pharmacologic autonomic blockade, were performed in 23 study patients (mean age 60 years) with SSS and a previous inferior wall AMI and in another 23 control patients (mean age 57 years) with normal sinus rate and a previous inferior AMI. Stenosis of the SN artery (or that proximal to its origin) greater than 50% was present in 13 study patients (56%) and in 8 control patients (34%) (p less than 0.05). In the study group, the intrinsic heart rate was abnormal in 5 of the 6 patients (83%) with severe SN artery stenosis (greater than or equal to 75% narrowing), in 3 of the 7 (43%) with moderate stenosis (50 to 75% narrowing) and in 3 of the 10 (30%) with insignificant stenosis (less than 50% narrowing). In the study group, the correlation between the SN measures (heart rate, corrected SN recovery time and sinoatrial conduction time) and the severity of SN artery stenosis was good after autonomic blockade (r between 0.59 and 0.64) and poor in the basal state. These data provide evidence for a role of SN artery disease in the pathogenesis of SSS in patients with an inferior wall AMI.
In 17 patients with symptomatic sinus bradycardia (age: 66 +/- 11 years), a resting electrocardiogram, a 24-hour Holter recording, and a treadmill test were performed both before and after administration of slow-release theophylline (700 mg daily). The drug increased resting heart rate (46 +/- 7 versus 62 +/- 18 beats/min, p less than 0.01), mean 24-hour rate (51 +/- 6 versus 64 +/- 16 beats/min, p less than 0.01), and minimal 24-hour heart rate (36 +/- 6 versus 43 +/- 10 beats/min, p less than 0.05). Cardiac pauses greater than 2.5 seconds were present in four patients during control recording, and disappeared after theophylline. The daily number of premature supraventricular and ventricular beats increased slightly after the drug. Exercise heart rate was higher after theophylline than during the control test (p less than 0.01). Thirteen patients were followed for a period of 17 +/- 3 months. Suppression of symptoms was achieved in 12 patients. Asthenia and easy fatigue were reduced markedly by the drug. During long-term therapy, the sinus rate was similar to that observed at the steady-state evaluation. In 3 of the 17 patients theophylline had to be discontinued because of gastric intolerance (in two at the end of the steady-state evaluation and in one during long-term therapy). These data suggest that oral theophylline can represent an effective therapy in some patients with symptomatic sinus bradycardia.
Theophylline increases sinus rate, but as yet its use has not been investigated in patients with chronic atrioventricular conduction disturbances. Resting electrocardiogram, 24-h Holter recording and treadmill test were performed in 17 patients with chronic atrial fibrillation and a slow ventricular response not related to drugs (age: 75 +/- 8 years). Then slow-release theophylline was administered (700 mg daily) and after 5 days these investigations were repeated with the same methods. Theophylline increased mean resting heart rate (51 +/- 6 versus 67 +/- 13 beats.min-1, P less than 0.01), mean 24-h heart rate (51 +/- 6 versus 68 +/- 14 beats.min-1, P less than 0.01) and minimal 24-h heart rate (32 +/- 6 versus 42 +/- 11 beats.min-1, P less than 0.01). Cardiac pauses greater than 2.5 s were present in 13 patients during control recording; after theophylline they disappeared in 11 and markedly decreased in the remaining two. The longest R-R interval decreased in all patients (3218 +/- 943 versus 2121 +/- 518 ms, P less than 0.01). The daily number of wide QRS complexes increased in 16 out of 17 patients (428 +/- 752 versus 1146 +/- 1464 ms, P less than 0.01). Exercise heart rate, evaluated at the end of first and second stage, was higher after theophylline than during control test (P less than 0.01). These data suggest that oral theophylline can represent a valid therapy in most patients with atrial fibrillation and a slow ventricular response.
A total of 4401 subjects admitted to the Medical Division of St Camillo Hospital in Comacchio (Ferrara, Italy) over a period of 7 years were prospectively evaluated in order to determine whether the heterozygous beta-thalassaemic (HBT) could be considered as a protective factor against the occurrence of acute myocardial infarction (AMI). Of the total patient sample, 3954 subjects were non beta-thalasaemics (NBTs), and 447 subjects were heterozygous beta-thalassaemics (HBTs). AMI was diagnosed in 384 patients, of whom 17 individuals were HBTs and 367 subjects were NBTs. The prevalence of HBTs in this group was significantly lower than expected (4.43%, P less than 0.0001). Furthermore, an analysis by sex showed that this lower prevalence could be attributed to male patients. Moreover, only in male subjects was a significant negative correlation observed between AMI and HBT. The mean age at which AMI occurred in male HBTs was significantly higher than in male NBTs (72 +/- 2.69 vs. 63 +/- 0.7 years, P less than 0.05), while no differences were found in the mean age at which AMI occurred between HBT and NBT female subjects. This study demonstrates that the thalassaemic trait may afford some protection against the occurrence of AMI in men.
A precise localization of the most proximal His bundle (HB) is useful both for diagnostic and for therapeutic purposes, allowing the modification of atrioventricular (AV) nodal conduction. For selective diagnosis a bipolar lead is utilized; for therapy, a unipolar lead. The aim of the present study was to determine the relationship between the most proximal HB and the morphology of intracavitary pressure curves. In 15 patients (aged 64 +/- 10 years), both bipolar and unipolar H-V intervals were continuously recorded while gradually withdrawing the catheter, which detected the pressure at its tip, from the right ventricle to the atrium. The longest bipolar H-V was 55.5 +/- 13 ms and the shortest 44.5 +/- 11 ms (P less than 0.001); the longest unipolar H-V was 56.5 +/- 14 ms and the shortest 46.2 +/- 11 ms (P less than 0.001). During unipolar recording, H deflection was present in all patients at the same time as ventricular, transvalvular and atrial pressure curves; during bipolar recording, the H electrogram was not present in only one patient concomitantly with the atrial curve. During bipolar recording, the atrial H-V interval was greater than transvalvular H-V in nine patients (mean differences: 6 +/- 2 ms) and they were equal in five; with unipolar recording the atrial H-V interval was greater than transvalvular H-V in 13 patients (mean difference: 8 +/- 6 ms) and they were equal in two. In all patients, the H wave amplitude diminished from the transvalvular area to the atrial one.(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of this study was to find out whether transesophageal pacing could be utilized for assessment of sinus node function in patients with sick sinus syndrome (SSS). In 17 patients with SSS (study group) we compared the results of sinus node tests obtained both in the basal state and after pharmacological autonomic blockade by endocavitary stimulation and, 24 hours later, by transesophageal pacing. In another group of 17 patients with SSS (control group), we compared the results obtained by two endocavitary studies. In "study group", sinus cycle length (SCL) and corrected sinus node recovery time (CSRT) did not show significant differences between the two studies both in the basal state and after autonomic blockade, whereas sinoatrial conduction time (SACT) was more prolonged during esophageal pacing (P less than 0.01). In "control group", sinus node measures did not show significant differences between the two studies. In the "study group," the following coefficients of correlation were obtained in the basal state; SCL, r = 0.65, CSRT, r = 0.57, SACT, r = 0.52 and after autonomic blockade: SCL, r = 0.95, CSRT, r = 0.62 and SACT, r = 0.53. In the basal state, the correlation for SCL and CSRT between the two studies was lower in the "study group" than in the "control group" (P less than 0.05), whereas after autonomic blockade the correlation for sinus node measures did not show significant differences between the two groups of patients. These data suggest that transesophageal study influences the autonomic tone regulating the sinus node; however, it is not responsible for important variations in sinus node measures.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was undertaken to determine if oral flecainide exerts autonomically mediated actions in addition to its direct depressant effect. Electrophysiologic studies were performed twice in each of 15 patients (mean age 59 years) with normal resting and intrinsic heart rate and normal A-H interval. In the first study, the variables of sinus node and atrioventricular node were evaluated both in the basal state and after autonomic blockade (propranolol 0.2 and atropine 0.04 mg/kg). Oral flecainide was administered for 4 to 5 days (200 to 250 mg daily) and the study was then repeated using the same methods. From comparison of data obtained in the 2 studies in the basal state, the overall effect of flecainide was evaluated and by comparing those obtained after autonomic blockade, the direct action of the drug was assessed. The overall effect of flecainide on sinus node was slight; sinus cycle length, corrected sinus node recovery time and sinoatrial conduction time did not change significantly after the drug. In contrast, after autonomic blockade the variables of sinosal automaticity were increased significantly (p less than 0.01). Flecainide significantly prolonged the atrioventricular node variables both in the basal state and after autonomic blockade (p less than 0.01), but the degree of increase was more marked after autonomic blockade (p less than 0.05). These data show dual effects of oral flecainide: a direct depressant action and an autonomically mediated opposing action, likely of vagolytic type.
The purpose of this study was to find out whether transesophageal pacing could be utilized for assessment of sinus node function, besides Wenckebach point, in patients with sick sinus syndrome. In 17 patients with sino-atrial disease (group I) we compared the results of sinus node tests obtained both in the basal state and after pharmacological autonomic blockade by endocavitary stimulation and 24 hours later, by transesophageal pacing. In another group of 17 patients with sino-atrial disease (control group) we compared the results obtained from two endocavitary studies. In group I, sinus cycle length and corrected sinus recovery time did not show significant differences between the two studies either the basal state or after autonomic blockade, whereas sino-atrial conduction time was more prolonged during esophageal pacing (P less than 0.01). In the control group, sinus node measures did not show significant differences between the two studies. In group I, the following coefficients of correlation were obtained: A) in the basal state sinus cycle length, r = 0.65, corrected sinus recovery time, r = 0.57, sinoatrial conduction time, r = 0.52; B) after autonomic blockade sinus cycle length, r = 0.95, corrected sinus recovery time, r = 0.62 and sino-atrial conduction time, r = 0.53. In the basal state, the correlation for sinus cycle length and corrected sinus recovery time between the two studies was lower in the "study group" than in the "control group" (P less than 0.05). However, after autonomic blockade the correlation for sinus node measures did not show any significant differences between the two groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
In 55 patients with persistent sinus bradycardia who underwent an electrophysiologic study of sinus node, both in the basal state and after autonomic blockade (propranolol, 0.2 mg/kg, and atropine, 0.04 mg/kg), an atropine test (0.02 mg/kg) was performed the following day. The 49 patients in whom sinus rate could be evaluated after atropine were subdivided into two groups--group I, 24 patients (age: 54 +/- 13 years) with normal intrinsic sinus automaticity (normal intrinsic heart rate and intrinsic corrected sinus node recovery time) and group II, 25 patients (age: 62 +/- 9 years) with abnormal intrinsic sinus automaticity. In group I, atropine increased sinus rate from 53.7 +/- 4 to 87.9 +/- 17 bpm (delta %: 65.5 +/- 33) and in group II from 51.6 +/- 5 to 73.9 +/- 14 bpm (delta %: 43.1 +/- 26). The discriminant threshold of sinus rate after atropine and its percent increase, obtained by discriminant analysis, was 80 bpm and +52%, respectively, with a misleading classification of 32% and 36%, respectively. The overall predictive accuracy of sinus rate after atropine was higher than the percent change in sinus rate (73% and 65%, respectively). These data evidence that the atropine test is not very helpful in discriminating between an organic and an autonomic involvement of sinus automaticity in patients with sinus bradycardia.