Effects of intravenous amiodarone in patients with inducible repetitive ventricular responses and ventricular tachycardia

We studied the effects of intravenous amiodarone administration (5 mg/kg) on reproducible repetitive ventricular responses and ventricular tachycardia (VT) induced by programmed electrical stimulation of the heart in 32 patients. Intravenous amiodarone prevented induction of bundle branch reentry in only 2 of 11 patients (18.2%) and did not change His-Purkinje conduction and refractoriness in the remaining 9 of 11 (81.8%) patients. In contrast to the small effect of intravenous amiodarone on bundle branch reentry, the drug completely abolished intraventricular reentry in three of nine (33.3%) patients and in the remaining six of nine (66.7%) patients decreased the number of intraventricular reentrant beats from up to five beats in control to one to two beats after the drug. The drug also prevented induction of VT (greater than or equal to 5 ventricular ectopic beats in a row) in three of five (60%) patients with nonsustained VT and in three of seven (42.9%) patients with sustained VT. In two of seven (28.6%) patients with sustained VT, only nonsustained tachycardia could be induced after drug administration. In another two of seven (28.6%) patients, sustained VT with slower rates was induced after the drug. In 11 of 12 (91.7%) patients with VT the coupling interval between the last stimulus and the first ventricular beat increased after drug administration. These effects of intravenous amiodarone occurred in the absence of effect on ventricular effective refractory period. These findings suggest that intravenous amiodarone might have greater effect on diseased ventricular tissue, the site of reentry in VT, than on healthy ventricular tissue.     

Simultaneous anterograde fast-slow atrioventricular nodal pathway conduction after procainamide

Three patients with paroxysmal supraventricular tachycardia underwent electrophysiologic studies that included His bundle recordings, incremental atrial and ventricular pacing and extrastimulation before and after intravenous infusion of 500 mg of procainamide. In all three patients the tachycardia was induced during atrial pacing or premature atrial stimulation, or both. Two of the three patients had discontinuous atrioventricular (A-V) nodal curves with induction of a slow-fast tachycardia during failure in anterograde fast pathway conduction and one patient had a smooth A-V nodal curve with induction of a slow-fast tachycardia at critical A-H interval delays. After procainamide: (1) in all three patients atrial pacing induced A-V nodal Wenckebach periodicity (cycle length 300 to 400 ms) resulting in simultaneous anterograde fast and slow pathway conduction (one atrial beat resulting in two QRS complexes) and retrograde fast pathway conduction initiating an echo response or a slow-fast tachycardia, or both; (2) in all three patients there was enhanced conduction and shortening of refractoriness of the anterograde fast pathway and depressed conduction and lengthening of refractoriness of the retrograde fast pathway; and (3) in two patients there was inability to sustain tachycardia because of selective block within the retrograde fast pathway. In conclusion: (1) procainamide altered conduction and refractoriness of the anterograde fast and slow pathways so that simultaneous conduction could occur during atrial pacing, resulting in a double ventricular response and a slow-fast echo or tachycardia, or both; and (2) the differential effects of procainamide on anterograde fast and retrograde fast pathways suggests two functional A-V nodal fast pathways, one for anterograde and the other for retrograde conduction.     

Electrophysiologic effects of propafenone on canine ischemic cardiac cells

The electrophysiologic effects of propafenone were studied by conventional microelectrode techniques in ischemic myocardial and Purkinje fibers from 1-day-old myocardial infarction in the dog. Propafenone reduced the amplitude and rate of rise of normal myocardial and Purkinje action potentials and had little effect on the resting potential. In the control state, both ischemic myocardial and Purkinje fibers had reduced resting potential, action potential amplitude and upstroke velocity. These fibers were more susceptible to the depressant effects of propafenone than normal fibers. Ischemic myocardial fibers were particularly sensitive to the actions of propafenone that resulted in marked depression of action potential characteristics, with little effect on resting potential. These changes resulted in cycle length-dependent conduction disorders in ischemic epicardial preparations. However, in ischemic endocardial preparations in which triggered activity could be initiated, propafenone reversibly suppressed the triggered activity. Termination of the triggered activity was preceded by slowing of the rate, which was attributed to a decrease in the rate of rise of the delayed afterdepolarizations. This activity terminated when the delayed afterdepolarization failed to attain threshold potential. This study suggests that propafenone has a membraneanesthetic effect, with the abnormal fast channel in ischemic cells being more sensitive; propafenone depresses delayed afterdepolarizations in ischemic Purkinje fibers; and the actions of propafenone could result in an antiarrhythmic effect in vivo on both reentrant ventricular rhythms in ischemic myocardium and triggered rhythms in ischemic Purkinje fibers.     

Differential effects of functional autonomic blockade on the variables of sinus nodal automaticity in sick sinus syndrome

To study the pathophysiologic mechanism of sick sinus syndrome and to establish the relation of intrinsic heart rate, corrected sinus nodal recovery time and sinoatrial conduction time in this syndrome, electrophysiologic studies were conducted in 22 men (mean age 60 ± 12 years) with the clinical diagnosis of sick sinus syndrome. Measurements were determined before and after autonomic blockade with propranolol (0.2 mg/kg body weight) and atropine sulfate (0.04 mg/kg). Fifty-nine percent of patients (Group I) had an abnormal intrinsic heart rate, suggesting intrinsic abnormality of sinus nodal automaticity; 41 percent (Group II) had a normal intrinsic heart rate after autonomic blockade, suggesting disturbed autonomic regulation. One patient with an observed intrinsic heart rate higher than the upper limit of predicted intrinsic heart rate was also included in Group II. The mean corrected sinus nodal recovery time before autonomic blockade was 751 ± 502.8 ms and was abnormal (more than 450 ms) in 10 of the 13 patients in Group I and 2 of the 9 patients in Group II. After autonomic blockade this interval was 694 ± 638.7 ms and was abnormal in 12 of the 13 patients in Group I and in 2 of the 9 patients in Group II. The patients in each group could be further classified into three groups on the basis of normal or abnormal corrected sinus nodal recovery time before or after autonomic blockade. Not all patients with abnormal intrinsic heart rate (Group I) had abnormal corrected sinus nodal recovery time and vice versa. Patients in Group II were younger in age, had a lesser incidence of organic heart disease and were more severely symptomatic.Mean sinoatrial conduction time during control studies was 210.4 ±96.3 ms and decreased significantly (143.2 ± 59.6 ms, p < 0.005) after autonomic blockade. This interval was abnormal in 3 of the 13 patients in Group I and in 6 of the 9 patients in Group II during control studies; after autonomic blockade it remained abnormal in 3 patients in Group I and in 1 patient in Group II.It is concluded that determination of heart rate and corrected sinus nodal recovery time after autonomic blockade increases the sensitivity of electrophysiologic testing and offers some insight into the pathophysiology of sick sinus syndrome. Patients with sick sinus syndrome who have a normal intrinsic heart rate have a greater incidence of abnormal sinoatrial conduction time than do those with an abnormal intrinsic heart rate. Thus, abnormal sinoatrial conduction time is usually due to extrinsic autonomic influences.     

Effects of digitalis on the human sick sinus node after pharmacologic autonomic blockade

To study the effects of digitalis on the sinus node and the mechanisms involved, 16 patients with the sick sinus syndrome had electrophysiologic assessment of sinus nodal function during (1) control study, (2) after pharmacologic autonomic blockade with propranolol (0.2 mg/kg body weight and atropine sulfate 0.04 mg/kg intravenously), and (3) 10 minutes after 0.01 mg/kg of intravenous ouabain. The study was completed within 30 minutes of pharmacologic autonomic blockade. During the control study 50 percent of patients had an abnormal corrected sinus nodal recovery time or abnormal sinoatrial conduction time, or both. The effects of ouabain on sinus nodal function were compared with those after pharmacologic autonomic blockade. Ouabain significantly increased both intrinsic sinus cycle length (ouabain 975 ± 194 ms [mean ± standard deviation]; autonomic blockade 1,025 ± 218 ms, probability [p] < 0.001) and corrected sinus nodal recovery time (ouabain 615 ± 503 ms; autonomic blockade 575 ± 536 ms, p < 0.05). In contrast there was no significant change in sinoatrial conduction time after ouabain (ouabain 141 ± 56 ms; autonomic blockade 132 ± 45 ms; difference not significant). The effects of ouabain were similar in patients with both normal and abnormal sinus nodal function.These findings suggest that (1) digitalis in therapeutic doses has a depressant effect on intrinsic sinus nodal automaticity in patients with normal as well as abnormal sinus nodal function; (2) digitalis has no significant effects on sinoatrial conduction; and (3) the effects of digitalis on sinus nodal automaticity are primary and independent of its vagal and antiadrenergic effects.     

Clinical significance of slow paroxysmal atrial tachycardia

This study examines the clinical setting, characteristics, and follow-up of 173 patients who had slow paroxysmal atrial tachycardia (SPAT) (> 4 beats, rate < 150 bpm) during 24-hour Holter monitoring. These episodes were classified by probable mechanism according to recognized ECG criteria and included AV nodal reentry (AVNR), sinoatrial nodal reentry (SANR), and automatic (A). There were 76 males (44%) with a mean age of 72 years and 97 females (56%) with a mean age of 73 years. The indications for Holter recording revealed that the SANR and A subgroups had a higher frequency of cerebral symptoms compared to AVNR (p < 0.01). Chest pain was more common in the SANR group as compared to the other two groups (p < 0.01). There was no difference in the frequency of palpitation in the three subgroups. The mean rate of SPAT for the entire groups was 115.2 ± 14 and these episodes had a mean duration of 5.58 ± 3.07 seconds. The SANR subgroup had a significantly slower rate (107.1 ± 9.2) as compared to the AVNR subgroup (p < 0.01). One hundred fourteen patients were available for follow-up. The average period of follow-up was similar for all three groups. At follow-up the frequency of sick sinus syndrome as determined clinically and permanent pacemaker insertion was significantly greater in the SANR subgroup (p < 0.01) as compared to the other subgroups which did not differ from each other.     

Refractory paroxysmal supraventricular tachycardia incited by multiple mechanisms

A patient with refractory paroxysmal supraventricular tachycardia post acute myocardial infarction is presented. His bundle recordings and atrial stimulation studies suggest atrioventricular nodal reentry precipitated by three different mechanisms. Therapy required permanent coronary vein pacing and drugs.     

Noninvasive His bundle electrogram: Value of three vector lead recordings

Studies were conducted in 45 patients to determine whether the reliability of the measurement of the His bundle potential from the body surface was increased by signal averaging of three simultaneously recorded electrocardiographic potentials from horizontal (X), frontal (Y) and sagittal (Z) axes as opposed to recording of any of these. Potentials from the X, Y and Z leads were amplified by 250,000, filtered between 80 hertz (12 dB/octave) and 200 hertz (24 dB/octave) and signal averaging of 1,000 beats was performed. The His bundle potential could be clearly defined in 25 of the 45 patients in the X, Y or Z lead. His bundle potentials were evident in the X lead in 17 (68 percent) of these 25 patients, in the Y lead in 19 (77 percent) and in the Z lead in 11 (44 percent). No single lead gave satisfactory His bundle electrographic potentials in all patients. In 20 patients the His bundle electrogram could not be recorded because terminal atrial activity overlapped activity of the His bundle potential. The three lead system defined the His bundle potential in a significantly greater number of patients than did the best single lead because it (1) displayed the vectorial lead with the largest His bundle potential, (2) permitted validation of the His bundle potential in more than one lead, and (3) displayed the vectorial lead with the most isoelectric terminal P wave. It is concluded that reliable His bundle potential measurements are obtained in a significantly greater number of patients with use of the simultaneous three lead system than with use of any single lead.     

Effects of vasodilators on pulmonary hemodynamics and gas exchange in left ventricular failure

Nitroprusside (NP) has been shown to improve left ventricular function in patients with congestive heart failure, but despite an increased cardiac output and decreased pulmonary capillary pressure, arterial oxygen tension (P_aO₂) may fall. In order to determine the mechanism of this hypoxemia, and to determine if similar effects occur with non-parenteral vasodilators, hemodynamic, respiratory, and blood gas responses to NP, hydralazine (H), and hydralazine combined with isiosorbide dinitrate (H+N) were studied in 10 patients with left ventricular failure. At the dosages used, all three drug regimens increased cardiac output equivalently, but pulmonary vascular responses differed. NP and H+N decreased mean pulmonary artery pressure, pulmonary wedge pressure, and pulmonary arteriolar resistance, while H did not. NP decreased P_aO₂ by 10.4 mm. Hg (p < .01) and H+N decreased it by 5.3 mm. Hg (p < .06) while H did not alter P_aO₂. Arteriolar-alveolar oxygen gradient increased with NP (150 ± 39 per cent, p < .01) and with H+N (73 ± 23 per cent, p < .01) but not H alone (51 ± 16 per cent). Similarly, per cent change in venous admixture increased on NP (28.7 ± 3.3 to 38.5 ± 3.1 per cent, p < .01) and H+N (28.1 ± 3.3 to 36.8 ± 3.5 per cent, p < .01) but not H alone (28.1 ± 3.3 to 31.5 ± 4.1 per cent). There was no increase in arterial carbon dioxide tension or change in pulmonary function studies with any of the drugs. Due to the increase in cardiac output, oxygen delivery index (cardiac output times arterial oxygen content) increased with each regimen despite the changes in P_aO₂. Changes in arteriolar-alveolar oxygen gradient correlate with the changes in pulmonary arteriolar resistance. Thus vasodilators which have prominent pulmonary vascular effects can decrease P_aO₂ in patients with congestive heart failure, and this effect is most likely due to increasing ventilation-perfusion inequities.     

Nonrandom occurrence of single-vessel coronary artery disease

The location of obstructive coronary artery lesions in single-vessel disease is nonrandom. The circumflex coronary artery is protected relative to the right coronary artery. This may have important implications regarding the causation of coronary obstructive lesions.     

Chronic effects of amiodarone in patients with refractory ventricular tachycardia

We examined the chronic electrophysiologic, systemic, and pharmacologic effects of chronic oral amiodarone therapy in 24 patients with refractory ventricular tachycardia and organic heart disease. Chronic amiodarone therapy resulted in significant increases in R-R interval (from 798 +/- 182 msec to 912 +/- 100 msec; P less than 0.01), P-R interval (from 205 +/- 66 msec to 221 +/- 87 msec; P less than 0.02), QRS duration (from 103 +/- 24 msec to 115 +/- 28 msec; P less than 0.001), and Q-Tc interval (from 413 +/- 48 msec to 470 +/- 46 msec; P less than 0.001). Significant increases were also noted in P-A interval (from 36 +/- 14 msec to 45 +/- 13 msec; P less than 0.05), A-H interval (from 119 +/- 61 msec to 141 +/- 87 msec; P less than 0.02), and H-V interval (from 52 +/- 12 msec to 64 +/- 11 msec; P less than 0.001). Electrophysiologic parameters showing changes included corrected sinus node recovery time (from 271 +/- 140 msec to 425 +/- 122 msec; P less than 0.01), the effective refractory period of the atrium (from 263 +/- 32 msec to 321 +/- 47 msec; P less than 0.01), the effective refractory period of the atrioventricular node (from 348 +/- 109 msec to 478 +/- 157 msec; P less than 0.001), the effective refractory period of the ventricle (from 253 +/- 21 msec to 291 +/- 28 msec; P less than 0.001), the atrial pacing cycle length producing A-V nodal Wenckebach (from 436 +/- 109 msec to 531 +/- 95 msec; P less than 0.001), and the functional refractory period of the A-V node (from 422 +/- 68 msec to 499 +/- 95 msec; P less than 0.001). Programmed electrical stimulation performed after 21-88 (mean 31) days of treatment was highly predictive of long-term results if suppression of arrhythmia induction was demonstrated (12 patients) or if the spontaneous arrhythmia was reinduced (5 patients). Induction of morphologically new ventricular tachyarrhythmias was frequent (42%) but had a low spontaneous recurrence rate (10%) during follow-up. Systemic parameters on chronic amiodarone therapy showed significant increases in total T4 and reverse T3, with no change in pulmonary function tests or left ventricular ejection fraction. Serum amiodarone levels at chronic electrophysiologic study ranged from 0.44-4.10 (mean 1.3) micrograms/ml. Long-term follow-up (2.5 to 20 months) demonstrated a marked improvement in clinical symptoms and mortality, but a significant recurrence rate of a well-tolerated slower arrhythmia persisted. Adverse effects on chronic amiodarone therapy were frequent (10 patients) and often disabling but required drug discontinuation in only 1 patient.     

Atrioventricular conduction patterns in patients with paroxysmal supraventricular tachycardia.

Atrioventricular conduction patterns suggestive of dual A-V nodal pathways have been reported in patients with and without a history of paroxysmal A-V nodal re-entrant tachycardia (PSVT). The purpose of this study was to determine whether significant association exists between this conduction pattern and the occurrence of PSVT in man. The pattern of A-V conduction was evaluated at similar pacing rates in 13 patients with documented PSVT and 135 patients with PSVT. Patients without PSVT were divided into groups with normal PR intervals (106 patients), PR intervals of 120 msec. or less (12 patients), and PR intervals of 200 msec. or greater (17 patients). Evidence of dual A-V nodal pathways was found in seven of 13 patients with PSVT and nine of 135 patients without PSVT, including eight of 106 patients with normal PR intervals, none of 12 patients with short PR intervals, and one of 17 patients with PR intervals of 200 msec. or greater. The incidence of dual A-V nodal pathways was significantly greater (P less than 0.01) in patients with PSVT when compared with all other groups. In two of four patients with PSVT, propranolol was found to unmask evidence of dual pathways; no evidence of dual pathways was produced by propranolol in 23 patients without PSVT. The data show that the pattern of dual A-V nodal pathways is common only in patients with PSVT and is significantly less frequent in patients without PSVT regardless of the presence of short or long PR intervals. The results of this study establish a strong association between this conduction pattern and the occurrence of PSVT in man.     

Beta-thromboglobulin levels in the nephrotic syndrome

Beta-thromboglobulin (BTG), a platelet-specific protein released on platelet aggregation, was measured in 13 patients with clinical and biochemical evidence of the nephrotic syndrome. All 13 patients had increased concentrations of BTG compared to both 10 normal controls and to 12 non-nephrotic azotemic patients (p < 0.001). In five patients with the nephrotic syndrome in remission, the BTG levels returned to normal. These results support the contention that the nephrotic syndrome is associated with a state of hypercoagulability and suggest that increased platelet aggregation may be the primary underlying mechanism.     

Paroxysmal ventricular tachycardia in Wolff-Parkinson-White syndrome: Case report and review of the literature

A case with Type A Wolf f-Parkinson-White pattern and recurrent sustained ventricular tachycardia is presented. Because of ventricular pre-excitation, electrocardiographic clues suggestive of ventricular tachycardia were ignored and the diagnosis of supraventricular tachycardia with conduction to the ventricles over the accessory pathway was made during reach admission to the hospital. Ventricular tachycardia was suspected only when programmed stimulation studies performed twelve years after initial presentation and many hospitalizations failed to induce a tachycardia with a QRS pattern similar to that of spontaneously occurring tachycardia. The diagnosis of ventricular tachycardia was later confirmed by intracardiac recordings made during a spontaneous episode of tachycardia. Tachycardia was unresponsive to all conventional antiarrhythmic agents but was controlled with amiodarone.The differential diagnosis of wide QRS complex tachycardia in patients with Wolff-Parkinson-White syndrome, the implications of correctly diagnosing the tachycardia, and the usefulness of intracardiac electrophysiologic studies in differentiating supraventricular tachycardia with aberrant conduction from ventricular tachycardia are discussed.     

Electrocardiographic observations on the termination of supraventricular tachycardia by verapamil.

The effect of intravenous verapamil on the termination of supraventricular tachycardia (SVT) was studied by continuous electrocardiographic monitoring of 27 episodes of SVT. Progressive increase of the cycle length heralded conversion in eight episodes while cycle-length alternation preceded cessation of the arrhythmia in 13 episodes. In five patients the arrhythmia was either stopped or closely followed by a ventricular premature beat (VPB), followed by further VPBs in three. Runs of bizarre ventricular tachycardia followed initial sinus-beats in two patients. Sinus standstill, lasting 30 seconds, was observed in one patient. The first post SVT beats had an aberrant QRS configuration with a normal P-R interval in four cases and an aberrant QRS complex with a short P-R interval, resembling Wolff-Parkinson-White complexes, in a further seven patients. The possible mechanisms causing this variability of pre- and post-conversion period are discussed. It is suggested that some aspects of verapamil action may be explained by a parasympaticomimetic effect on the myocardium.     

Silent mitral stenosis masquerading as pulmonary neoplasm

We report the findings in a patient with severe silent mitral stenosis whose chest X-ray was interpreted to show post obstructive pneumonia due to a subcarinal mass.