Safety of long-term flecainide and propafenone in the management of patients with symptomatic paroxysmal atrial fibrillation: report from the Flecainide and Propafenone Italian Study Investigators.

To compare the relative safety of flecainide acetate to propafenone HCl during long-term treatment (12 months), we conducted a randomized, open-label, comparative, parallel, multicenter trial in 200 patients with paroxysmal atrial fibrillation (AF) and no history of heart disease. Initial daily doses were flecainide 200 mg (n = 97) or propafenone 450 mg (n = 103). Dose escalations up to a maximum of flecainide 300 mg/day or propafenone 900 mg/day were permitted after > or = 2 attacks of paroxysmal AF. Patients were assessed for safety and drug tolerance at designated intervals over the 12-month study unless discontinued for adverse experience or inadequate response. Ten patients on flecainide reported 14 cardiac adverse experiences; 4 discontinued the drug. Seven propafenone patients reported 8 cardiac adverse experiences; 5 discontinued the drug. Three proarrhythmic events occurred: 1 propafenone patient developed ventricular tachycardia and 2 flecainide patients experienced AF with a rapid ventricular response. An intention-to-treat analysis showed that the probability of safe and effective treatment after 12 months was 77% for flecainide-treated patients and 75% for the propafenone-treated patients. There was an acceptable risk-benefit profile in patients with paroxysmal AF and no evidence of clinically significant heart disease who were treated with flecainide or propafenone for 12 months. Further, there was no statistically significant difference in safety or efficacy between flecainide and propafenone in this study.

Safety of flecainide versus propafenone for the long-term management of symptomatic paroxysmal supraventricular tachyarrhythmias. Report from the Flecainide and Propafenone Italian Study (FAPIS) Group.

In order to compare the long-term safety of flecainide and propafenone, an open label, randomized, parallel group study was performed in 335 patients with paroxysmal atrial fibrillation (n = 200) or paroxysmal supraventricular tachycardia (n = 135), and no history of heart disease. Patients were treated with an initial daily dose of flecainide 100 mg (n = 72) or propafenone 450 mg (n = 63) for paroxysmal supraventricular tachycardia and flecainide 200 mg (n = 97) or propafenone 450 mg (n = 103) for paroxysmal atrial fibrillation. Dose escalations were permitted after > or = 2 attacks, up to a maximum of flecainide 300 mg or propafenone 900 mg.day-1.Follow-up duration was 12 months, or when patients stopped the treatment as a result of inadequate efficacy or adverse experiences. Twelve patients on flecainide reported 16 cardiac adverse experiences, of whom six discontinued the treatment. Seven propafenone patients had eight cardiac adverse experiences, of whom five discontinued the treatment. Serious proarrhythmic events were infrequent: one case of ventricular tachycardia on propafenone: two cases of atrial fibrillation with rapid ventricular response on flecainide, associated in one patient with pulmonary oedema. An intention-to-treat analysis showed that the probability of 12 months' safe and effective treatment of paroxysmal supraventricular tachycardia was 93% for flecainide and 86% for propafenone (P = 0.24), whereas in paroxysmal atrial fibrillation it was 77% for flecainide and 75% for propafenone (P = 0.72). In conclusion, flecainide and propafenone were safe in the long-term treatment of patients with paroxysmal supraventricular tachyarrhythmias and without evidence of clinically significant heart disease.

Once daily felodipine in preventing ergonovine-induced myocardial ischaemia in Prinzmetal's variant angina.

The efficacy of extended-release felodipine in preventing ergonovine-induced myocardial ischaemia was assessed in 14 patients (12 male, two female, aged 56 +/- 7 years) with Prinzmetal's variant angina. Four of the patients had normal coronary arteries, eight had one-vessel and two had two-vessel disease. The ergonovine test was performed once in basal conditions and twice 5 days after beginning the oral administration of felodipine 20 mg o.d., 4 and 24 h after the last administration. During a continuous 6-lead ECG recording, ergonovine was injected at doses of 25, 50, 100, 200, and 400 micrograms at 5 min intervals. Blood samples for felodipine plasma concentrations were drawn at the time of the tests. The basal ergonovine test was positive in all 14 patients (seven with anterior and seven with inferior ST segment elevation > 0.1 mV) at a mean ergonovine dose of 162 +/- 138 micrograms. The test was repeated 4 h after the last felodipine administration and was negative in 13 patients (93%), but 24 h after the last drug administration, eight patients (57%) had a positive test response (five with anterior, three with inferior ST segment elevation) at a higher ergonovine dose than at baseline (150 vs 97 micrograms, P = 0.042). The only differences between patients with a negative and a positive test were the mean values of the left ventricular end-diastolic pressure (9.3 vs 14.9 mmHg, P = 0.002) and the ergonovine doses used in the baseline tests (250 vs 97 micrograms, P = 0.034).(ABSTRACT TRUNCATED AT 250 WORDS)

Factors that predict spontaneous remission of ectopic atrial tachycardia.

Ectopic atrial tachycardia (EAT) is usually considered as benign and easy to treat. The natural history of the disease, however, has not yet been clarified. The purpose of the study was to analyse its spontaneous evolution in a cohort of EAT patients and to define a predictive model of remission based on several factors. Between 1973 to 1989, 46 patients (25 male, 21 female), aged 38 +/- 18 years, entered the study. Clinically EAT was paroxysmal in 23 patients, permanent in 12 and repetitive in 11; six patients were asymptomatic. Thirty-five complained of palpitations; dyspnoea, dizziness and syncope were also reported less frequently. All patients underwent an electrophysiological study to clarify the mechanism of the arrhythmia and to localize its site of origin. In 15 patients no heart disease was documented. Five patients underwent surgery and were excluded from subsequent analysis. Seven patients were discharged without antiarrhythmic treatment. We defined remission as the absence of recurrence of EAT within 6 months from withdrawal of therapy. Logistic regression was applied to identify potential predictors of remission. Seven clinical and electrophysiological covariates were entered in the model; univariate and multivariate tests were performed, using the GLIM3 statistical package. During a follow-up period of 5.1 +/- 4.5 years, 14 instances of remission (34%) were observed in 5/22 patients with paroxysmal EAT, 4/8 patients with permanent EAT and 5/11 patients with repetitive EAT. Mean age of patients with remission was 25 +/- 14 years vs 45 +/- 15 years in the group without remission. No covariate had an independent predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)

[The behavior of late potentials in myocardial infarct patients undergoing myocardial revascularization]. / Comportamento dei potenziali tardivi in pazienti con infarto miocardico sottoposti a rivascolarizzazione miocardica.

Ventricular late potentials recorded on the body surface in patients with old myocardial infarction (MI) are considered to reflect slow conduction, due to the presence in the infarct border zone of viable myocardium within scarred tissue. To assess the prevalence of late potentials in a population with old MI and no malignant arrhythmias and to verify whether myocardial revascularization may influence the substrate responsible for the occurrence of late potentials, 80 patients with old MI (75 males, 5 females), aged 55 +/- 9 years, undergoing coronary surgery, were studied. A Marquette MAC15 HiRes electrocardiogram recorder was used to identify late potentials before and after surgery. Late potentials were defined following the most accepted criteria reported in the literature. Statistical analysis was performed using logistic regression to determine the association of several clinical, hemodynamic and surgical variables with the presence of late potentials. Late potentials were present in 28 patients (35%) before surgery and disappeared in 11 (39%) after surgery. Inferior MI and female sex were the only independent predictors of the presence of preoperative late potentials. On the other hand, persistence of late potentials after surgery was related to the presence of inferior MI and left ventricle aneurysm. These data suggest that revascularization is capable of abolishing late potentials, probably due to functional recovery of perinecrotic hibernated myocardium. With particular anatomic conditions (inferior MI, aneurysm), this functional recovery seems not to be sufficient for the disappearance of late potentials.

Comparison of isoproterenol and exercise tests in asymptomatic subjects with Wolff-Parkinson-White syndrome.

In order to evaluate the effects of increases of sympathetic tone in ventricular response during atrial fibrillation and in the relationship between the accessory pathway effective refractory period (ERP) and ventricular rate during atrial fibrillation, 20 male subjects, aged 19 +/- 6 years, were studied electrophysiologically in basal conditions, after isoproterenol infusion (2-4 micrograms/min) and during submaximal bicycle exercise test, at a constant workload equal to that which increases the sinus rate to the same extent (140 beats/min) induced by isoproterenol infusion. Accessory pathway ERP was evaluated at the same driven rate (150 beats/min) in both instances. In the control study as during both tests atrial fibrillation paroxysms were induced by burst stimulation. In control conditions the rate increase from 100 to 150 beats/min induced a reduction of accessory pathway ERP from 266 +/- 27 msec to 244 +/- 22 msec (P less than 0.005). At the same driven rate of 150 beats/min, isoproterenol infusion and exercise test induced a more marked shortening of accessory pathway ERP to 211 +/- 28 msec (P less than 0.005) and to 214 +/- 29 msec (P less than 0.005), respectively. Atrial fibrillation paroxysms lasting more than 10 seconds were induced in 20/20 cases in the control study, in 15/20 during isoproterenol infusion and in 13/19 cases during exercise test. The shortest cycle length during atrial fibrillation was reduced from a basal value of 253 +/- 72 msec to 204 +/- 27 msec (P less than 0.05) during isoproterenol infusion and to 236 +/- 32 msec (NS) during exercise test.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic and clinical effects of oral encainide in paroxysmal atrioventricular node reentrant tachycardia.

The electrophysiologic effects of oral encainide (75 to 150 mg daily) were evaluated in 14 patients (6 male and 8 female, aged 49 +/- 9 years) with atrioventricular (AV) node reentrant tachycardia of the slow-fast type. The patients were studied in control conditions and after 2 to 12 days of treatment. Encainide increased the AH interval from 67 +/- 10 to 82 +/- 23 ms (p less than 0.02). Anterograde Wenckebach cycle length was increased in three patients, reduced in four, unchanged in one; it was not measurable in the remaining patients because tachycardia was induced. Retrograde Wenckebach periodicity increased from 307 +/- 71 to 401 +/- 92 ms (p less than 0.005) in all nine patients in whom it was measurable; complete retrograde block was observed in one patient. At the control study, tachycardia was induced in all patients, with a mean cycle length of 341 +/- 50 ms; after encainide, tachycardia was inducible in only 1 patient, with an increase in cycle length from 270 to 320 ms; in the other patients, tachycardia was not inducible because of a lack of retrograde (11 patients) or anterograde (2 patients) conduction. The mean plasma concentrations of encainide and its metabolites O-demethyl-encainide and 3-methoxy-O-demethyl-encainide measured in 13 patients during the repeat study were 161 +/- 304, 128 +/- 100 and 95 +/- 85 ng/ml, respectively; three poor metabolizers who presented a high concentration of the parent compound were observed in this series. All patients were discharged on encainide at a mean daily dose of 112 +/- 39 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

[An electrophysiologic and electropharmacological study of functional properties of the bundle of Kent in Wolff-Parkinson-White syndrome]. / Studio elettrofisiologico ed elettrofarmacologico delle proprietà funzionali del fascio di Kent nella sindrome di Wolff-Parkinson-White.

The aim of this report is to attempt a definition of functional properties of Kent bundle on the basis of electrophysiologic and electropharmacologic data obtained from 89 cases of Wolff-Parkinson-White syndrome selected among a total number of 114 consecutive cases of WPW syndrome that underwent electrophysiologic intracavitary study. In 36 cases anterograde (ant) and retrograde (retr) effective refractory period (ERP) of accessory pathway were evaluated with premature (atrial and ventricular) stimulation at the same driven cycle length. The ant-ERP was longer than retr-ERP in 28/36 patients, shorter in 5 and equal in 2. This strong discrepancy between ant- and retr- ERP suggests an important role of "impedance mismatch" in the activation of ventricular (or atrial) muscle through an anomalous muscular bundle. In 11 cases an intermittent pattern of ventricular preexcitation was observed; in all these patients an anterograde supernormal conduction through the accessory pathway was observed. This aspect could be related to the activation of ventricular muscle, beyond Kent bundle, in its supernormal phase of excitability, suggesting the critical role played by ventricular activation for the appearance of preexcitation. Isoproterenol, injected in 11 cases (1 among them with intermittent ventricular preexcitation in basal conditions), produced a reduction of ant-ERP in all these cases, in spite of its well known poor effect on refractoriness of myocardial fibers. Ajmaline, injected in 32 patients, was able to block ventricular preexcitation in 81% of the cases, in spite of its poor effect on refractoriness of normal tissues. It is very likely that the disappearance of ventricular preexcitation is in this instance expression of lack of ventricular excitation (distal to Kent bundle) consequent to a drug-induced reduction of membrane responsiveness of ventricular cells. In conclusion, all these aspects strongly suggest that the appearance of ventricular (or atrial) preexcitation could be related to the activation of ventricular (or atrial) muscle distal to Kent bundle, rather than to conduction through the Kent bundle itself.

Time-related decrease in sensitivity to ergonovine in patients with variant angina.

Eighteen patients with variant angina, a positive ergonovine test, and a favorable response to calcium antagonists were studied by serial ergonovine tests and Holter monitoring to assess the long-term changes in response to ergonovine and the relationship with the spontaneous activity of the disease. The number of patients with a positive test decreased from 18 of 18 in the acute phase to 12 of 18 (66%) at 3 months, 10 of 17 (59%) at 6 months, and five of 17 (29%) at 12 months. The mean dose level of ergonovine associated with a positive response and the percentage of positive tests with ST segment depression increased progressively during follow-up. The results of the ergonovine test were well correlated with the spontaneous activity of the disease in 94%, 83%, 76%, and 71% of the patients at initial observation and at 3, 6 and 12 months, respectively. Thus in patients with variant angina and a favorable response to calcium antagonists, a time-related decrease in sensitivity to ergonovine develops during follow-up. In most patients the response to ergonovine is well correlated with the spontaneous activity of the disease; thus the ergonovine test may be a useful tool in the assessment of the natural evolution of vasospastic angina.

Hyperventilation and ergonovine tests in Prinzmetal's variant angina pectoris in men.

Hyperventilation and ergonovine tests were carried out in a group of 30 patients with variant angina to assess the sensitivity of the 2 tests and to correlate the response with spontaneous disease activity. Hyperventilation produced a positive response in 83% (25 of 30) and ergonovine in 93% (28 of 30) of the patients. After hyperventilation 22 of 25 showed ST-segment elevation, 2 ST depression and 1 T-wave pseudonormalization; after ergonovine ST-segment elevation developed in 23 patients, ST depression in 4 and T-wave pseudonormalization in 1. In all cases the electrocardiographic changes occurred in the same leads as during the spontaneous attacks. The incidence of chest pain and ventricular arrhythmias was similar during both tests; spontaneous remission of ischemia, however, was more frequent (48 vs 14%) after hyperventilation than after ergonovine. Acute ischemia developed at a mean of 218 +/- 112 seconds after the end of hyperventilation in 19 of 25 positive tests; at that time double product was not significantly different from basal values. The sensitivity of hyperventilation was similar (95 vs 100%) to ergonovine in the patients with greater than or equal to 1 daily attack, while in those with less than 1 daily attack the sensitivity of hyperventilation decreased to 55% compared to 77% with ergonovine. Thus, in variant angina the sensitivity of both tests correlates with disease activity. Hyperventilation is a safe provocative test with a sensitivity similar to ergonovine in patients with active disease; however, in patients with sporadic attacks hyperventilation has a lower sensitivity than ergonovine and therefore a limited diagnostic value.

Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration.

The aim of this study was to compare the pharmacokinetics and antiarrhythmic activity of dihydroquinidine and quinidine in 14 patients (11 men, 3 women, aged 28 to 67 years) with heart disease and chronic, stable, high-frequency premature ventricular beats (PVB) (greater than 100/hr). A randomized, double-blind, crossover, placebo-controlled protocol was utilized. During Holter monitoring the patients were given either dihydroquinidine or quinidine as the gluconates in an oral solution (600 mg); blood samples were taken 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours later. The patients were then assigned to three successive treatment periods of 7 days each: dihydroquinidine HCl (900 mg/day), quinidine polygalacturonate (1,650 mg/day), or placebo. At the end of each period 24-hour Holter monitoring was carried out and a blood sample was taken for determination of drug concentration. By comparing the area under the curves dihydroquinidine was 59% as available as quinidine; rates of absorption and elimination were similar. Mean peak blood levels of dihydroquinidine and quinidine were 1.06 +/- 0.34 and 2.15 +/- 0.96 micrograms/ml, respectively. After dihydroquinidine, eight patients had a positive response (greater than 50% reduction in PVB frequency), while seven patients responded to quinidine. During maintenance treatment both dihydroquinidine (233 +/- 330) and quinidine (234 +/- 311) reduced the mean PVB frequency per hour compared to placebo (690 +/- 569). Nine patients (64%) on dihydroquinidine and eight (57%) on quinidine had greater than 70% decrease in mean PVB frequency per hour. Steady-state peak plasma concentrations of dihydroquinidine and quinidine were 1.10 +/- 0.41 and 2.24 +/- 1.13 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of surgery in the treatment of post-infarction ventricular tachycardia. A 5 year experience.

The purpose of this report is to present a 5 year experience in electrophysiologically guided surgical treatment of post-infarction ventricular tachycardia (VT) in a consecutive series of 39 patients. In every case the arrhythmia was not responsive to pluripharmacological therapy. The diagnostic steps included preoperative endocardial, intraoperative epi- and endocardial mapping, automatically carried out when possible. Surgical techniques were: classic Guiraudon's encircling endocardial ventriculotomy (EEV), partial EEV, endocardial resection (ER), cryoablation or combined procedures. The hospital mortality was of 4 patients (10%). During the follow-up period (1-68 mo), 4 patients (11%) died of cardiac non-VT related causes. Among the survivors, 90% are in sinus rhythm. The authors consider electrophysiologically guided surgery a safe and reliable method for the treatment of post-infarction VT and suggest more extensive indications. They stress the importance of automatic mapping in pleomorphic and non-sustained VT, and the necessity of tailoring the surgical technique to the characteristics of each case.

Electrophysiologic and clinical effects of intravenous and oral encainide in patients with Wolff-Parkinson-White syndrome and paroxysmal atrial fibrillation.

The electrophysiologic effects of encainide were studied in 10 patients with Wolff-Parkinson-White syndrome after intravenous (1 mg kg-1 in 60 minutes) and oral administration of two dose regimens (75 and 150 mg daily). Under control conditions atrial fibrillation (AF) with a rapid ventricular response was induced in all patients and atrioventricular reciprocating tachycardia (AVRT) in 9 patients. After intravenous encainide AF was no longer induced in 3/9 patients; in 3 of the remaining the accessory pathway (AP) was totally blocked and in the others the shortest RR interval increased from 213 +/- 6 to 297 +/- 91 ms and the mean RR interval from 293 +/- 39 to 362 +/- 79 ms. The lower dose of oral encainide prolonged the shortest RR interval from 206 +/- 24 to 273 +/- 64 ms and the mean RR interval from 280 +/- 48 to 368 +/- 52 ms in 6 patients; in 2 cases no preexcited beats were recorded and in 1 AF was not inducible. After the higher dose of oral encainide AF was still inducible in 7/8 cases; in 3 the AP was blocked and in the others the shortest and mean RR intervals increased from 202 +/- 30 to 280 +/- 24 ms and from 276 +/- 59 to 436 +/- 80 ms, respectively. After intravenous encainide antegrade conduction over the AP was blocked in 4/9 patients and the antegrade effective refractory period (ERP) was prolonged in another 4. Oral encainide blocked AP conduction in 4 cases and prolonged ERP considerably in the others.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous remission of variant angina documented by Holter monitoring and ergonovine testing in patients treated with calcium antagonists.

Twenty-four patients with Prinzmetal's variant angina showing a favorable initial response to calcium antagonist treatment were studied to assess the evolution of the disease and the frequency and time course of spontaneous remission. At 3, 6 and 12 months from the acute phase, patients underwent in-hospital control studies, with 48-hour Holter monitoring and ergonovine testing carried out during treatment and after its interruption. During calcium antagonist therapy complete protection from spontaneous attacks was documented in 22 of 24 patients at 3 months, in 19 of 21 at 6 months and in all 21 at 12 months; ergonovine test results were negative in 16 of 23 patients at 3 months, in 16 of 20 at 6 months and in all 20 studied at 12 months. After stopping treatment spontaneous attacks did not reappear in 7 of 24 patients (29%), 14 of 21 (66%) and 16 of 21 (76%) at 3, 6 and 12 months respectively, while the ergonovine test response remained negative in 6 of 21 (28%), 7 of 18 (39%) and 13 of 20 (65%) of the patients controlled at 3, 6 and 12 months. Thus, complete remission of angina documented by both Holter recording and ergonovine testing occurred in 5 of 24 patients (21%) at 3 months, in 7 of 21 (33%) at 6 months and in 12 of 21 (57%) at 12 months. Patients with remission of angina had a shorter duration of symptoms and more often showed normal or not critically diseased coronary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)