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)

[Usefulness and limitations of the ergonovine maleate test in the evaluation of calcium-antagonist therapy in Prinzmetal variant angina]. / Utilità e limiti del test con ergonovina maleato nella valutazione della terapia calcio-antagonista nell'angina variante di Prinzmetal.

Ergonovine testing was carried out in a selected group of 25 patients with Prinzmetal's variant angina treated with calcium-antagonists in order to: define its usefulness in the evaluation of the short-term effectiveness of calcium-antagonist treatment; compare the results of the test with those of Holter monitoring; verify if the results of the test during the acute phase are correlated with the long-term response to treatment. In all patients a control period lasting 2-6 days was carried out, after which a treatment period with calcium-antagonists (nifedipine, diltiazem, verapamil), lasting 2-8 days, was instituted. In 20 patients only 1 calcium-antagonist was evaluated, in 1 patient 2 calcium-antagonists and in 4 all of them. Scalar ergonovine test was carried out in control conditions and repeated during each calcium-antagonist treatment period. During both control and treatment periods all patients underwent Holter monitoring for evaluation of frequency of the spontaneous attacks. After the acute phase 21 of the 25 patients were discharged on calcium-antagonist treatment and followed-up for a mean period of 11 +/- 7 months. In control conditions ergonovine test was positive in 24 patients at a mean dose of 0.11 +/- 0.09 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

When are arrhythmias and conduction disturbances markers of myocardial ischemia at rest?

Myocardial ischemia, particularly when transmural as in variant angina pectoris, may be associated with ventricular tachycardia, ventricular fibrillation and paroxysmal atrioventricular block (15%). Syncope (7%) and sudden death (3%) due to these malignant arrhythmias are sometimes a unique marker of myocardial ischemia. Two-hundred fifty-four patients (220 males and 34 females), aged 5 +/- 9 years with transmural myocardial ischemia related to coronary artery spasm, were studied. Particular attention was paid to the role of syncopal attacks as unique clinical manifestation of silent ischemia. Patients examined were divided into 3 Groups. Group 1 includes 5/254 (2%) patients with atrial fibrillation during acute ischemia. Group 2 was divided into four subgroups: subgroup A includes 17/254 (7%) patients with syncopal attacks due to malignant arrhythmias (ventricular tachycardia and advanced A-V block); subgroup B, 15/254 (6%) patients with documented malignant arrhythmias, without syncopal attacks; subgroup C, 7/254 (3%) with ventricular fibrillation during acute ischemia and subgroup D, 18/254 (7%) patients with history of syncopal attacks without documented arrhythmias during hospital observation. Group 3 includes 17/254 (7%) patients with left anterior hemiblock in basal condition, 7/254 (3%) patients with left anterior hemiblock and one left posterior hemiblock during acute ischemia and one patient with right bundle branch block during acute ischemia. Syncopal symptoms are present in many of these cases of angina pectoris; paroxysmal A-V block is documented in nearly half of the cases with syncope (65%); ventricular tachycardia is frequently demonstrated during ischemia but leads to syncope in only a few cases; patients with syncope do not present specific clinical features.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular tachycardia in post-myocardial infarction patients. Preoperative and intraoperative mapping.

Ventricular tachycardia has become a relatively common complication of myocardial infarction and often is an important therapeutic problem, as it is recurrent and life-threatening. Here we report a group of 36 patients with ventricular tachycardia occurring 13 days to 30 years after a myocardial infarction. All patients were resistant to medical treatment and 34 of the 36 patients had had at least one cardiac arrest. All were candidates for surgery for their arrhythmia. The study protocol included prolonged ECG monitoring, a preoperative electrophysiological study with catheter mapping and intraoperative epicardial and endocardial mapping. A total of 52 different tachycardias were mapped in 36 patients. The procedure was facilitated by an automatic mapping device, that allowed the acquisition of 35 simultaneous signals, so that even pleomorphic ventricular tachycardias could be mapped. The information obtained from both preoperative and intraoperative maps guided surgery and restricted the extent of the surgical damage.

Medical and surgical treatment of sustained and recurrent post-infarction ventricular tachycardia.

Over a five-year period 57 patients (pts) with sustained, recurrent, post-infarction ventricular tachycardia (VT) refractory to conventional antiarrhythmic treatment were evaluated. In 28 (49%) pts VT was controlled by amiodarone (A) in a dose of 3000 mg week-1. During long-term follow-up 5/28 (18%) pts died; no severe side-effects were observed with this dosage. In 17 of the 29 pts not controlled by this regimen, the dosage of A was increased to 6000-8000 mg week-1; short-term control of VT was achieved in 9/17 (53%) pts, but over a long-term follow-up 5/9 (56%) died and severe side-effects (11% pulmonary fibrosis and 11% hepatitis) occurred in 22%. Twenty pts, resistant to a low (12 pts) or high (8 pts) doses of A, underwent map-guided surgical treatment. In conclusion A is superior to conventional drugs in the treatment of sustained, recurrent, post-infarction VT, but when high doses are necessary to prevent VT, long-term results are poor and severe side-effects frequent. In pts refractory to standard doses of A, map-guided surgery is the treatment of choice.

Occlusion and reperfusion as possible different mechanisms of ventricular tachyarrhythmias in Prinzmetal's variant angina.

A case of a patient with variant angina associated with severe ventricular tachyarrhythmias studied by continuous electrocardiographic and haemodynamic monitoring is reported. Severe ventricular arrhythmias developed both during maximal ST-segment elevation, in association with haemodynamic signs of acute ischaemic cardiac dysfunction and after nitroglycerin-induced reversion of ischaemia and return of the haemodynamic variables to the basal state. Thus, in this patient, ventricular arrhythmias during acute ischaemia could be related not only to acute vasospastic coronary occlusion but probably also to reperfusion after relief of coronary spasm.

[Intravenous and oral encainide: electrophysiological effects in patients with paroxysmal reciprocating supraventricular tachycardia]. / Encainide endovenosa ed orale: effetti elettrofisiologici in pazienti con tachicardia parossistica sopraventricolare reciprocante.

The electrophysiologic effects of encainide (E) after acute i.v. (1 mg/kg in 60') and oral administration (75 to 150 mg/die for 48-72 h) were evaluated in 10 pts with PSVT (5 men and 5 women, mean age 48 +/- 15 years). The mechanism of PSVT was related to a reentry through an accessory A-V pathway in 6 cases while in the other 4 the reentry was confined in the A-V node. PA, AH and HV intervals lengthened from 42.8 +/- 5.1, 77.8 +/- 19.7 and 38.3 +/- 6.6 msec to 50 +/- 13.5, 91.7 +/- 22.9 and 49.4 +/- 12.9 and to 48.3 +/- 7.1, 94.4 +/- 33.9 and 44.4 +/- 9.2 msec, after i.v. and oral E respectively. Atrial and ventricular refractory periods showed slight not significant variations. Wenckebach point lengthened from 316 +/- 28 msec to 354 +/- 32 and to 359 +/- 45 msec, after i.v. and oral E respectively. Tachycardia cycle length was 358 +/- 32 msec in basal conditions. After i.v. E tachycardia was inducible only in 6 cases, with a mean cycle length of 403 +/- 48 msec. After oral E tachycardia was reproduced only in 3 patients with a mean cycle length of 433 +/- 85 msec. Nine patients were treated chronically with E, at a mean dose of 89 +/- 36 mg/day. After a follow-up of 18 +/- 8 months, tachycardia recurred but with a marked reduction of the attacks, in 3 patients; only 3 patients complained of side effects (blurred vision). Thus E is highly effective in the prevention of PSVT; the drug seems well tolerated thanks to the low dosage required for the control of PSVT.

Dihydroquinidine versus disopyramide: efficacy in patients with chronic stable ventricular ectopy.

Dihydroquinidine (DQ) is contained in substantial amounts in quinidine salts, but its direct antiarrhythmic action has not been studied. The efficacy of oral DQ (300 mg t. i. d.) compared to disopyramide (D) (200 mg t.i.d.) was thus investigated using a double-blind crossover placebo-controlled protocol in 12 patients, aged 13 to 67 years, with chronic stable high frequency premature ventricular beats (PVB), defined as greater than 100 PVB/h during 48-72-h control Holter monitoring. The protocol included three 72-h treatment periods: DQ, D, and placebo at random. On days 2 and 3 of each period a 24-h Holter recording was carried out; drug blood levels were determined at peak (days 2 and 3) and trough time (day 3). No significant difference in the mean PVB/h was found between control (735 +/- 400) and placebo periods (564 +/- 388), or between the two Holter recordings of each period. Compared to placebo both DQ (106 +/- 113, p less than 0.005) and D (240 +/- 263, p less than 0.05) reduced the mean PVB/h, but the decrease was significantly higher with DQ (78 versus 53%, p less than 0.02). Nine patients (75%) on DQ and 5 (42%) on D had a greater than 70% decrease in mean PVB/h; complex PVBs were abolished in 3 of 6 patients on both treatments. On day 3, DQ plasma levels were 1.31 +/- 0.44 (peak) and 0.92 +/- 0.45 (trough) mg/l; D plasma levels were 2.88 +/- 0.64 (peak) and 2.02 +/- 0.31 (trough) mg/l; no significant difference was found between day 2 and day 3 samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy, duration and mechanism of action of nifedipine in stable exercise-induced angina pectoris.

The duration of effect of single oral doses of 10 and 20 mg of nifedipine was studied in 10 patients with angiographically proven coronary artery disease and with stable exercise-induced angina pectoris. In a randomized double-blind manner exercise tests were carried out 1 hour before and 1, 2, 4 and 6 h after the administration of placebo, nifedipine 10 mg(N10) and nifedipine 20 mg(N20). Compared with the placebo both N10 and N20 produced a statistically significant increase in exercise tolerance at 1(P less than 0.05), 2(P less than 0.01), 4(P less than 0.01) and 6(P less than 0.05) hours after N10 and at 1(P less than 0.01), 2(P less than 0.01), 4(P less than 0.01) and 6(P less than 0.05) hours after N20. At peak exercise the product of heart rate X systolic blood pressure (RPP) was significantly increased compared with placebo at 2, 4 and 6 h after N10 and at 2, 4 and 6 h after N20 with maximal ST-segment depression unchanged. At the same duration of exercise at which angina had occurred during control studies the RPP was unaffected by nifedipine while a statistically significant reduction of ST-segment depression was seen at 1, 2 and 4 h after N10 and at 1, 2 and 4 h after N20. Direct measurements of great cardiac vein flow during exercise in two patients showed that nifedipine is effective in preventing the abnormal increase of exercise-induced coronary tone in the area supplied by stenotic vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular tachyarrhythmias in Prinzmetal's variant angina: clinical significance and relation to the degree and time course of S-T segment elevation.

Fifty-six patients with active Prinzmetal's variant angina were studied to determine the incidence and clinical significance of ventricular tachyarrhythmias and the correlation between arrhythmias and degree and time course of S-T segment changes during the ischemic attacks. Twenty-nine patients (Group I) had no ventricular arrhythmias in any of the 1,083 recorded episodes, while 27 patients (Group II) developed arrhythmias in 18% of the attacks. No significant differences in clinical, electrocardiographic, angiographic, or hemodynamic findings could be found between the 2 groups. In 23 of the 27 Group II patients, ventricular arrhythmias developed during maximal S-T segment elevation (occlusion arrhythmias), while in 10 they occurred during resolution of S-T segment changes (reperfusion arrhythmias); 6 of the latter patients also had occlusion arrhythmias. Eight of the 23 patients with occlusion arrhythmias and 6 of the 10 with reperfusion arrhythmias had ventricular fibrillation or ventricular tachycardia. Maximal S-T segment elevation was significantly greater (p less than 0.001) in patients with occlusion arrhythmias than in those without arrhythmias. The episodes with reperfusion arrhythmias were significantly longer (p less than 0.001) and showed a significantly greater S-T segment elevation (p less than 0.001) than those without arrhythmias in Group I patients. This study shows that significant ventricular tachyarrhythmias develop during ischemic attacks in about 50% of patients with active variant angina; clinical and angiographic features are not useful in distinguishing patients with arrhythmias from the others. Our findings suggest that in variant angina ventricular arrhythmias may be due to the effects of both coronary artery occlusion and reperfusion; both types of arrhythmias are correlated with the severity of ischemia, as measured by the degree of S-T segment elevation. Reperfusion arrhythmias also appear to be correlated with the duration of ischemia.

Variable threshold exertional angina in patients with transient vasospastic myocardial ischemia. Repeat exercise test results and therapeutic implications.

Thirty-five of 70 patients with vasospastic angina at rest complained of chest pain during exercise or during usual daily activity. In 22, the angina threshold was described as variable during exercise: that is, the amount of exertion that induced angina was not always the same. In 12 patients with variable threshold exertional angina, 3 exercise tests performed in the morning on different days yielded different results, because chest pain and ischemic electrocardiographic changes occurred at different work loads with a wide range in heart rate-systolic pressure product. Two patients, in whom great cardiac vein flow was measured during exercise before and after taking nifedipine, tolerated heavier work loads after receiving the drug, with a more marked increase in flow during exercise. It is concluded that variable threshold exertional angina can be objectively demonstrated by repeat exercise tests in patients with vasospastic angina. Variability of the angina threshold may be due to a functional mechanism that causes myocardial ischemia in addition to the increased myocardial metabolic requirements provoked by exercise. Because in such patients fluctuations in coronary arterial tone play an important role in determining the response to exercise, calcium antagonistic drugs, which lower coronary tone and prevent the occurrence of coronary spasm, are effective in increasing exercise capacity.

Dipyridamole test in angina pectoris: diagnostic value and pathophysiological implications.

The value of the dipyridamole test (0.75 mg/kg i.v.) in the diagnosis of angina pectoris was studied in 54 patients with angina pectoris (35 with angina on effort associated or not associated with rest angina and 19 with angina only at rest) and in 12 control subjects. The test induced electrocardiographic signs of ischemia (positive test) in 74% of patients with angina on effort, while it was negative in all cases with angina only at rest and in control subjects. All anginal patients with normal coronary arteries or less than 50% stenosis had a negative test; a positive response was observed in 36, 79 and 60% of cases with one-, two-or three-vessel disease, respectively. Hemodynamic changes with a marked arteriolar vasodilatation were observed both in the negative and in the positive tests. In the positive tests no significant change of double product, blood pressure and left ventricular end-diastolic pressure occurred before ischemia appeared. The results of the study show that dipyridamole as a diagnostic test in angina pectoris has a high specificity but a lower sensitivity than exercise test. The hemodynamic and eletrocardiographic findings in the positive tests suggest that dipyridamole-induced ischemia is due to a flow maldistribution with selective subendocardial ischemia secondary to the coronary arteriolar dilatation caused by the drug.