Toby R. Engel

Effect of whiskey on atrial vulnerability and “holiday heart”

Vulnerability to atrial fibrillation and flutter was examined in 11 alcohol abusers who did not have cardiomyopathy or manifest heart failure. Atrial extrastimulation was done with rapid pacing (drive cycle length 500 ms) to facilitate induction of atrial vulnerability, seen in four alcohol abusers. The remaining seven were retested 30 minutes after drinking 60 to 120 ml of 86 proof whiskey (ethanol blood levels were 49 to 101 mg/100 ml but pulmonary capillary wedge pressure remained normal in all) and atrial fibrillation or flutter was induced in three of the drinkers. Three nondrinkers, symptomatic with sinus bradycardia but not in heart failure, were found not to be vulnerable to atrial fibrillation or flutter, but flutter was induced in two of the three after drinking whiskey. Whiskey did not alter atrial functional refractory periods (mean +/- standard error of the mean 297 +/- 14 to 290 +/- 12 ms) or widen the dispersion among three disparate right atrial sites (57 +/- 13 to 47 +/- 12 ms). Thus, whiskey enhanced vulnerability to atrial fibrillation and flutter in patients without heart failure or cardiomyopathy, substantiating the holiday heart syndrome.

Effects of Digitalis on Atrial Vulnerability

The effects of digitalis on vulnerability to atrial fibrillation and flutter were assessed in man, using the model of repetitive atrial firing initiated by post-drive atrial extrastimulation. Nine patients without heart failure or significant mitral valve disease were tested before and 30 minutes after the administration of 0.01 mg/kg ouabain. When repetitive firing was manifested by flutter, neither the flutter cycle length nor the interval from the initiating beat to the first flutter beat was consistently altered by ouabain. Repetitive firing was found at the atrial site with the shortest functional refractory period. The vulnerable zone bordered this refractory period. The functional refractory period was lengthened after ouabain, from 231 +/- 13 to 246 +/- 15 msec (mean +/- standard error of the mean) (P less than 0.025). Partly because of prolonged refractoriness, the vulnerable zone was curtailed by ouabain, from 32.2 +/- 5.7 to 9.4 +/- 4.6 msec (P less than 0.001). This result suggests a protective effect of digitalis against atrial fibrillation and flutter independent of its hemodynamic actions.

Diagnostic Implications of Atrial Vulnerability

Extrastim‐ulution in the atrial vulnerable zone may result in atrial fibrillation or flutter (AFF), especially with stimulation of multiple atrial sites. However, the clinical relevance of such vulnerability to AFF is unknown. Therefore, single twice‐threshold extru‐stimuli were applied at three disparate right atrial sites in 45 consecutive unmrdi‐cated patients without overt heart failure. Group I consisted of 12 patients with documented spontaneous paroxysms of AFF. AFF was duplicated in 9 of 12 patients using extraslimulation in the vulnerable zone (5 in sinus rhythm, 4 requiring atrial pacing at 120 beats/min/. Croup II consisted of 33 patients without documented AFF despite monitoring. Vulnerability to AFF was found in 12 of 33 patients (4 in sinus rhythm, 8 requiring atrial pacing). The duration of induced AFF did not discriminate between the two groups. Among the 12 Group II patients vulnerable to AFF, 3 had rapid palpitations, 2 had undiagnosed rapid tachycardias, 1 had atrial tachycardias and 1 junctional tachycardias. In vulnerable patients, the pause after AFF correlated with the pause after atrial pacing, but only 1 of 11 Group II patients with sick sinus syndrome was vulnerable. Thus, paroxysmal AFF may be duplicated with the extruslimulus technique if sufficient arial sites are stimulated, providing a model for evaluation of these arrhythmias. But atrial vulnerability, even to extra‐stimulation at normal heart rates, may be seen in patients suspected of atrial tachy‐arrhythmic in the absence of documented AFF, and does not contribute to the diagnosis of sinoatriul dysfunction.

Modification of ventricular tachycardia by procainamide in patients with coronary artery disease

Fifteen consecutive patients with coronary artery disease had rapid (158 to 272 beats/min) and sustained ventricular tachycardia induced by the extrastimulus technique, and received procainamide infusion. Before the study, all but one patient had severe symptoms with tachycardia, and six had survived apparent sudden death. Procainamide consistently slowed ventricular tachycardia. However, in traditional doses (1 g infusion, plasma concentration greater than 4 micrograms/ml), it prevented induction of ventricular tachycardia in only 2 of the 15 patients. Induction of ventricular tachycardia was facilitated by procainamide in 10 patients. Larger doses of procainamide (plasma concentration 20.2 micrograms/ml +/- 9.7 [mean +/- standard deviation]) prevented induction of ventricular tachycardia in one of eight patients. Rapid ventricular rates (more than 210 beats/min) that were not slowed (by 50 percent or more) after a 1 g infusion of the drug predicted failure of procainamide to prevent ventricular tachycardia. Therefore, procainamide slowed but did not prevent induced ventricular tachycardia in most of these patients with coronary artery disease at risk of sudden death.

Electrophysiologic effects of hydralazine on sinoatrial function in patients with sick sinus node syndrome.

The electrophysiologic effects of hydralazine were evaluated in nine hypertensive patients with sinoatrial dysfunction. Intravenous hydralazine, 0.15 mg/kg, caused no significant reduction in arterial blood pressure. Yet this dose of hydralazine increased heart rate from 61.9 +/- 4.1 beats/min (mean +/- standard error of the mean) to 68.6 +/- 4.9 (P less than 0.001). Sinus nodal recovery time upon termination of atrial pacing shortened from 3,207 +/- 1,098 to 2,064 +/- 573 msec (P less than 0.05) and second escape cycles shortened as well (P less than 0.025). Acceleration of heart rate and abbreviation of recovery time did not closely correlate with change in blood pressure (r = 0.41 and 0.18, respectively). Junctional escape beats became more frequent and junctional escape time shortened from 2,525 +/- 692 to 1,705 +/- 382 msec (P less than 0.05). Sinoatrial conduction time tended to shorten, but a significant change was not observed. Atrial tachyarrhythmias did not occur and atrial refractoriness was unchanged. Thus, a minimal blood pressure response to hydralazine was associated with enhanced automaticity. Hydralazine merits clinical trial for treatment of sick sinus syndrome with concomitant hypertension.

Effect of procainamide on induced ventricular tachycardia.

Ventricular extrastimulation was performed in 11 patients evaluated for chronic recurrent ventricular tachycardia, before and after a 1‐gm procainamide infusion. Extrastimulation caused only nonsustained extra beats (<4) in 3 patients. Sustained tachycardia was induced in 7 patients in the basal state, of which 6 continued to have inducible tachycardia after procainamide was given (5.2 to 9.8 mg/L). The zone of coupling intervals that initiated tachycardia was unchanged or widened in these 6 patients because ventricular refractoriness was unchanged or because the tachycardia zone shifted to later diastole by an interval at least equivalent to the prolongation of ventricular refractoriness. Post‐procainamide tachycardia cycle length was prolonged in all patients, by an average 51 msec. The one patient who responded to procainamide had a shartened ventricular refractory period, but the greatest slowing of tachycardia. Finally, sustained ventricular tachycardia could be induced in the eleventh patient only following procainamide administration, consistent with his clinical history. These results suggest that procainamide often may be ineffective in preventing sustained ventricular tachycardia, and that slowed conduction, rather than prolonged refractoriness, is the basis for the procainamide antiarrhythmie effect. Our data emphasize that antiarrhythmie drug effectiveness be evaluated in terms of effect on sustained arrhythmia rather than suppression of isolated ectopic beats.

Late induction of tachycardia in patients with ventricular fibrillation associated with acute myocardial infarction

A prospective study was made of 57 asymptomatic patients, 1 to 24 months after acute myocardial infarction, 17 with (Group I) and 40 without (Group II) ventricular fibrillation during the acute event. None of the 57 patients had symptomatic arrhythmias, uncontrolled heart failure or unstable angina. There was no significant difference between the two patient groups in time from acute myocardial infarction, medication used or left ventricular ejection fraction. Repetitive forms of arrhythmia (Lown grade 4) were more prevalent (29 versus 16%, not significant) during 24 hour ambulatory monitoring in patients in Group I (ventricular fibrillation group). Programmed extrastimulation was performed using 1 to 3 twice-threshold, 2 ms decremental extrastimuli delivered during right ventricular drive. Of the 17 patients in Group I, 8 had no induced arrhythmia (less than or equal to 4 extra responses), 4 had nonsustained ventricular tachycardia and 5 had sustained ventricular tachycardia (degenerating into ventricular fibrillation requiring electrical reversion in 4). None of the 40 patients in Group II had induced sustained ventricular tachycardia (p less than 0.005), although 9 had nonsustained ventricular tachycardia. Patients with ventricular fibrillation during acute myocardial infarction may have an increased risk for ventricular tachycardia or ventricular fibrillation that may be exposed by programmed electrical stimulation even when not yet clinically manifest.

Relationship of delayed depolarization to the QT interval after acute myocardial infarction

The relationship between conduction delay, as manifested by a prolonged QRS or late potentials (LP) detected by signal averaging, and QT prolongation was analyzed in six patients who had QTc greater than or equal to 0.42 second within 48 hours of acute myocardial infarction (AMI). Total QRS, LP, QT, and QTc durations were measured on days 2 to 3, 4 to 5, 6 to 7, and 8-9. In each recording period, the QT interval and QTc interval did not correlate with the QRS duration and LP duration (r less than or equal to 0.52 for each comparison). In 19 out of 27 instances, a sequential change in QT or QTc intervals was discordant with changes in QRS duration and/or LP, i.e., temporal changes in QT intervals were not determined by conduction. Thus, QT prolongation after AMI is not primarily due to regional slowing of conduction that results in regional delays in termination of some action potentials. Global prolongation of repolarization would seem to result from dispersion of action potential duration, not onset.

Effect of procainamide on dispersion of ventricular refractoriness

Ventricular arrhythmias after Q-T prolongation by drugs could result from a nonhomogeneous increase in refractoriness (dispersion). Dispersion of effective refractory periods (ERP) was measured before and after infusion of 1 g of procainamide using twice-threshold extrastimuli applied in sinus rhythm and with 500 ms ventricular drive cycle length at 3 right ventricular sites (2 patients) or 2 right and 1 left ventricular site (10 patients). Procainamide prolonged ERP. In drive, average ERP was 247 +/- 5 ms (standard error of the mean) before and 277 +/- 7 ms after procainamide (p less than 0.001). The Q-T interval was prolonged by 50 ms in drive (p less than 0.001), but Q-T prolongation did not reflect the increased ERP (r =-0.05). However, procainamide did not alter measured dispersion (54 +/- 16 to 44 +/- 14 ms in sinus, 48 +/- 14 to 47 +/- 13 ms in drive). Polymorphic ventricular tachycardia (VT) was induced in 6 patients in whom drive itself generally failed to reduce dispersion, and failure to induce tachycardia or shorter runs after procainamide was associated with narrowed dispersion. Polymorphic VT was not induced after procainamide in 2 patients with clinical episodes of torsades de pointes caused by type I agents. The mechanism of torsades de pointes was not explained by dispersion of refractoriness or by polymorphic VT initiated by premature beats after a type I drug.

Arrhythmias and Social Drinking

Excerpt The holiday heart syndrome was described a few years ago by Ettinger and associates (1), who noted paroxysms of arrhythmias in alcoholic patients without overt cardiomyopathy more often a...