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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.

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 μg 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 m V) at a mean ergonovine dose of 162±138 μg. 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 μg, P =0⋅042). The only dtfferences 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 μg, P =0⋅034). The mean felodipine plasma level 4 h after dosing was 18⋅0±12⋅2 nmol. l−1; 24 h post-dosing plasma concentrations were generally very low (

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 atria] fibrillation, 20 male subjects, aged 19 ± 6 years, were studied electrophysiologically in basal conditions, after isoproterenol infusion (2–4 μ/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 < 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 < 0.005) and to 214 ± 29 msec (P < 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 < 0.05) during isoproterenol infusion and to 236 ± 32 msec (NS) during exercise test. Similar behavior was observed in the mean cycle length during atrial fibrillation (from 372 ± 67 to 291 ± 36 and to 329 ± 70 msec, respectively). In conclusion, isoproterenol and exercise test, when exerting the same effect on sinus rate, induce the same accessory pathway ERP decrease, mainly due to a direct electrophysiological effect, which overcomes that secondary to increase in heart rate. Isoproterenol reduces the shortest and mean RR intervals during atrial fibrillation more than exercise test, probably because other determinants in addition to the accessory pathway ERP may influence heart rate during atrial fibrillation. The increase of sympathetic tone seems to reduce atrial fibrillation electrical inducibility.

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).

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)

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.

Acute intoxication with verapamil (2400 mg) induced A-V dissociation and circulatory failure in a 38-year-old woman with no previous cardiac disease. Resumption of A-V conduction was observed after administration of orciprenalin, calcium gluconate, and dopamine, with no effect on blood pressure. Epinephrine infusion finally restored satisfactory blood pressure level and allowed a favorable outcome.

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)

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.

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, highfrequency premature ventricular beats (PVB) (>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 μg/ml, respectively. After dihydroquinidine, eight patients had a positive response (>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 >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 μg/ml, respectively. Dihydroquinidine thus has stronger antiarrhythmic activity than quinidine and so may be used in lower doses; it is effective with plasma concentrations lower than those of quinidine.

Two patients with vasospastic angina at rest developed ST segment elevation both in the anterior and inferior leads during spontaneous and ergonovine-induced attacks. In both cases the acute myocardial ischemia secondary to multivessel coronary spasm led to reversible electromechanical dissociation. Coronary arteriography showed normal coronary arteries in one case and severe three-vessel disease in the other; spasm of the right coronary artery was demonstrated in both patients. These cases show that in patients with vasospastic angina coronary spasm may simultaneously involve different arteries and lead to ischemic electromechanical dissociation. Ergonovine testing is contraindicated in those patients with suspected or proved multivessel coronary spasm.

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 progresively 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.

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 andatrioventricular reciprocating tachycardia (A VRT) 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 preexcitedbeats were recorded and in 1 AF was not inducible. After the higher dose of oral encainide A F was still inducible in 7/8 cases; in 3 the A P 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 A P was blocked in 4/9 patients and the antegrade effective refractory period (ERP) was prolonged in another 4. Oral encainide blocked A P conduction in 4 cases and prolonged ERP considerably in the others. Induction of A V RT was prevented in 1/8 patients after intravenous and in 5/9 patients after oral encainide; in the 4 patients in whom AVRTremained inducible cycle length increasedfrom 306±31 to 3 54 ±49 ms after intravenous encainide and to 392 ±46 ms after oral administration. All patients were discharged on encainide (mean maintenance dose, 127 mg daily) and followed for 21 ±7 months; no recurrence of AF was observed; two patients complained of transient mild side effects. These data show that in patients with Wolff-Parkinson- White syndrome encainide prolongs refractoriness and slows conduction over the AP; it prevents induction of AVRT and markedly slows ventricular response during AF, thus protecting patients against life-threatening arrhythmias

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 < 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 < 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. One patient dropped out of the study 1 month later because of neurologic side effects (blurred vision and vertigo). During a mean follow-up period of 24 ± 11 months, nine patients are completely free of attacks, three patients had only one recurrence and one patient had a marked reduction of attacks; no one complained of side effects.Encainide appears to be highly effective in preventing AV node reentrant tachycardia, mainly by depressing conduction in the retrograde limb of the reentrant circuit. The drug demonstrates long-term clinical efficacy and does not induce any significant side effect at the doses used in this trial.

Alternative surgical solutions have been proposed for some years in the face of the difficulties presented by medical treatment of ventricular tachycardia (VT) following myocardial infarction. Deeper knowledge of the electrophysiological mechanisms [2–5] of this type of tachycardia and above all the improvement of endo- and epicardial mapping techniques [6] in man have recently permitted the introduction of rational surgical techniques directed to the interruption of the reentry mechanism implicated in the pathogenesis of postinfarction VT.

T-wave changes can be observed in many clinical situations and they are classically divided into primary and secondary T-wave changes. Secondary T- wave changes occur during anomalous ventricular activation while primary changes occur when the activation sequence is normal, thus appearing independent from the pattern of ventricular activation. However, at the resumption of normal intraventricular conduction, after a certain period of anomalous activation, a peculiar type of T-wave changes occurs, which mimics ischemic-type modifications. Such a change needs some time to appear and to reach the maximum level, till anomalous activation is present, and a longer time to disappear, after the disappearance of the abnormal ORS pattern. This phenomenon is suggestive of modulation of repolarization related to the entity and duration of the anomalous activation (1–3).

Patients with the Wolff-Parkinson-White syndrome in whom the atrioventricular accessory pathway has a short anterograde effective refractory period (ERP) are considered at risk of sudden death if atrial fibrillation occurs. 1 Administration of ajmaline during sinus rhythm (50-mg intravenous bolus over 3 minutes) has been suggested as a test for identifying patients with an accessory pathway ERP shorter than 270 ms; in such patients the drug usually does not block anterograde conduction over the accessory pathway. 2 This study evaluates (1) the relation between dose of ajmaline, injected at a constant rate of 10 mg/min, blocking conduction over the accessory pathway, and duration of the accessory pathway ERP; (2) the reproducibility of the test, so modified; and (3) the possibility of predicting accessory pathway ERP on the basis of the dose of ajmaline blocking conduction over the accessory pathway. Thirty-two consecutive patients (21 men, 11 women), mean age 34 4- 15 years, with Wolff-ParkinsonWhite syndrome were studied. During continuous 6lead (I, II, III, V1,V~ and V6) electrocardiographic recording, ajmaline was administered intravenously at a constant rate of 10 mg,/min up to conduction block of the accessory pathway or a maximum total dose of 100 mg. The next day, after the patient gave informed written consent, electrophysiologic study was performed; the anterograde accessory pathway ERP was determined as the longest atrial premature beat interval not followed by anterograde conduction over the accessory pathway, at a driven rate 10 beats/rain faster than sinus rate. In 15 patients the ajmaline test was repeated after 24 to 72 hours. In 6 of the first 22 patients treated, ajmaline did not block conduction aver the accessory pathway: in 2 of them the accessory pathway ERP could not be determined because it was less than atrial refractoriness (250 and 200 ms, respectively) and in 4 the mean acces

The effectiveness of nifedipine in treating angina pectoris at rest was evaluated in 14 patients with frequent ischemic episodes associated with S-T segment elevation or depression. The trial consisted of (1) a 48 hour control period; (2) a placebo period and a period of treatment with nifedipine of 48 hours each; and (3) a second placebo period and a second period of treatment with nifedipine of 24 hours each. The efficacy of treatment was evaluated by continuous electrocardiographic recording to detect painless ischemic episodes. During coronary angiography coronary spasm was demonstrated in five patients. The ergonovine maleate test was positive in seven of eight patients. No statistically significant difference was found in the mean daily number of ischemic episodes between the control period and the first placebo period, or between the control and the second placebo periods. Nifedipine produced a highly significant reduction in the mean daily number of episodes compared with the response to placebo during the first as well as the second period. Nifedipine is effective in angina at rest caused by coronary arterial spasm. The prevention of ischemia may be related to the ability of nifedipine to decrease calcium-dependent coronary muscle tone and to prevent coronary spasm.

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% polmonary 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 drug's 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.

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.

The effectiveness of nitroglycerin ointment in vasospastic angina pectoris at rest was evaluated in 10 patients selected for study. The study was performed after a 24 hour control period, and a randomized single-blind crossover experimental design was followed. Two percent nitroglycerin ointment (15 mg) or placebo ointment was administered every 6 hours for a period of 48 hours each; the first treatment period was followed by a second in which each preparation was used for a 24 hour period. All patients were hospitalized in the coronary care unit; an objective evaluation was carried out using a multichannel electrocardiographic recording to assure recognition of the painless ischemic episodes. Coronary angiography showed critical stenosis of one or two vessels in 9 of the 10 patients; spasm was demonstrated in 3. Results of the ergonovine test were positive in nine of nine patients. Nitroglycerin ointment produced a significant reduction in the mean daily number of episodes during the first (12.5 +/- 3.9 versus 0.5 +/- 0.4, p less than 0.02) as well as the second treatment period (10.6 +/- 3.8 versus 0.6 +/- 0.4, p less than 0.02). These results demonstrate that nitroglycerin ointment provides effective, long-lasting protection against angina due to coronary spasm.

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.

The site of atrioventricular block determines its clinical significance and, hence, the proper mode of treatment or implantation of an electronic pacemaker. For practical purposes, the site of block can be identified in most instances by the duration of the QRS complex.

Although coronary artery spasm is a well established cause of variant angina, its pathogenetic mechanism is not known. Autonomic nervous system imbalance or alterations in myocardial metabolism may play a role in the pathogenesis of coronary spasm, z,2 We describe a patient with variant angina in whom transient remission of ischemic attacks (IAs) was observed during atrial fibrillation (AF), suggesting that changes in autonomic nervous tone and myocardial metabolism associated with AF prevented coronary spasm.