James B. Martins

Significance of inducible tachycardia in patients with syncope of unknown origin: A long-term follow-up

The frequency of inducible tachycardia was assessed in patients presenting with syncope whose noninvasive evaluation did not reveal a cause for syncope. It was also determined whether treatment of tachyarrhythmias during programmed electrical stimulation would prevent recurrence of syncope. One hundred five patients were studied and 97 were followed up for a mean period of 25.8 months. Sixty-eight patients (65%) did not have inducible tachycardia. Sixty of these 68 patients could be followed up; 12 (20%) had recurrent syncope. Ventricular or supraventricular tachycardia was inducible in 37 patients (35%). The frequency of organic heart disease was not higher in this group or in those with inducible ventricular tachycardia as compared with those with inducible supraventricular tachycardia. Three patients with inducible ventricular tachycardia died suddenly or were resuscitated from cardiac arrest, and an additional seven had recurrent syncope; thus, the total recurrence rate was 27%. Of 23 patients undergoing effective therapy as predicted by electrophysiologic testing, 3 (14%) had a recurrent event. Results were significantly different in patients receiving ineffective therapy as judged by electrophysiologic testing. Of 13 patients in this latter category, 7 patients (54%) had recurrence of syncope or cardiac arrest (p less than 0.05). In three patients, recurrence took place a mean of 5 months after cessation of therapy; on resumption of effective therapy, no syncope recurred for 15.6 months (p less than 0.025). Tachycardia is frequently induced in patients with syncope of unknown origin, whether or not organic heart disease is present. Treatment of inducible tachycardia may prevent recurrence of syncope.

Anomalous Origin of the Right Coronary Artery from the Left Sinus of Valsalva

ANOMALOUS origin of the right coronary artery from the left sinus of Valsalva is a rare congenital abnormality. For many years pathologists classified it as a minor anomaly of no clinical importance. Recently, manifestations of myocardial ischemia have been described in patients with this anomaly in the absence of additional atherosclerotic or other disease processes. These manifestations have included acute myocardial infarction, angina pectoris, syncope, nonfatal ventricular fibrillation, and sudden death.1 2 3 4 5 6 Although clinical, anatomic, and angiographic data suggest impaired physiologic function of an anomalous right coronary artery that originates from the left sinus of Valsalva, no actual physiologic measurements have .xa0.xa0.

Effect of direct-current countershocks on regional myocardial contractility and perfusion. Experimental studies.

Very high energy electrical countershocks can cause morphologic damage to the myocardium. In this study we searched for functional correlates of these shock-induced morphologic changes. We used ultrasonic sonomicrometers to measure myocardial contractility and radiolabeled microspheres to assess perfusion. Acute and chronic experiments were conducted in 45 dogs, assessing the effect of both direct (epicardial) and transthoracic shocks on beating and fibrillating hearts. High-energy or rapidly repeated epicardial shocks caused subepicardial contraction abnormalities. This indicates that electrical current delivered to the myocardium in sufficiently high amounts and concentration can cause functional damage. Thus, in open-chest defibrillation during cardiac surgery, low energies (10–20 J) should be used initially and higher energies resorted to only if lower-energy shocks fail. However, single and multiple transthoracic shocks up to 460 J delivered energy caused no detectable contraction abnormalities. Myocardial perfusion did not fall after shocks. Thus, high-energy transthoracic shocks may have no deleterious effects on the contraction and perfusion of normal myocardium.

Mitral valve prolapse in anxiety neurosis (panic disorder)

Our purpose was to determine the incidence of mitral valve prolapse in patients with anxiety neurosis or panic disorder, with symptoms including recurrent anxiety attacks, dyspnea, palpitations, chest pain, dizziness, and paresthesias. Twenty-one patients and 20 age- and sex-matched normal controls were studied. Objective cardiac abnormalities were significantly (p < 0.05) more frequent in the patient group as compared to the control group; these comprised echocardiographic prolapse, ST-T abnormalities on resting ECG, premature ventricular contractions on exercise ECG, and the combination of echo prolapse with clicks/murmurs of exercise-induced PVC. We conclude that patients with anxiety neurosis or panic disorder may also have evidence of an organic abnormality--the mitral prolapse syndrome.

Usefulness of isoproterenol facilitation of ventricular tachycardia induction during extrastimulus testing in predicting effective chronic therapy with beta-adrenergic blockade

Previous studies indicate that programmed extrastimulus testing (PES) during isoproterenol infusion facilitates induction of clinical ventricular tachycardia (VT) in some patients. This study attempts to determine if VT inducible only during isoproterenol infusion predicts suppression of VT with chronic oral beta-adrenergic blockade. Nine patients, aged 23 to 77 years, with symptomatic VT or syncope not necessarily provoked by exercise or stress were evaluated. Extrastimuli did not induce VT in any patient. However, during isoproterenol infusion (1 to 4 micrograms/min), all patients had reproducibly inducible VT corresponding to their spontaneously occurring VT (recordings available in 7 patients). Coupling intervals inducing tachycardia during isoproterenol were similar to intervals that did not induce VT without isoproterenol. No patient had VT with isoproterenol infusion alone (without extrastimuli). In only 4 of 8 patients who underwent exercise tests while not taking medications was VT provoked. With propranolol therapy (160 mg/day) or its equivalent, only 1 patient had recurrent symptoms during a mean follow-up of 39 months (range 23 to 52). VT inducible with extrastimuli only during isoproterenol infusion predicts that oral beta-adrenergic blockade will prevent spontaneous VT or syncope long term. These data suggest that occurrence of VT in some patients depends on premature depolarizations in the setting of beta-adrenergic influence.

Usefulness of isoproterenol in facilitating atrioventricular nodal reentry tachycardia during electrophysiologic testing

In some patients with documented atrioventricular (AV) nodal supraventricular tachycardia (SVT), the arrhythmia is not inducible during a standard stimulation protocol. In these patients the level of sympathetic activity may be an important factor. This study evaluates the influence of isoproterenol on anterograde and retrograde pathway properties in patients with AV nodal SVT and the mechanism by which this SVT is facilitated. Group 1 consisted of 8 consecutive patients, ages 23 to 85 years (mean +/- standard error, 57 +/- 8) who had no inducible AV nodal SVT during electrophysiologic testing until isoproterenol (0.5 to 3.0 micrograms/min) was infused. These patients were compared with 6 patients in the same age range (45 to 78 years, mean +/- standard error, 64 +/- 5) who had inducible AV nodal SVT without isoproterenol and who comprised group 2. In comparing group 1 (before isoproterenol) with group 2, there was no significant difference in the refractory periods of the anterograde slow and fast pathways, although the anterograde block cycle length was longer in group 1 patients (421 +/- 18 vs 362 +/- 14 ms, p less than 0.05). The retrograde block cycle length was also longer in 7 of the 8 group 1 (before isoproterenol) patients in whom it could be measured versus those in group 2 (411 +/- 14 vs 318 +/- 27 ms, p less than 0.05). During isoproterenol, the anterograde and retrograde block cycle lengths in group 1 were not different from group 2. Therefore, AV nodal SVT may not be inducible in some patients during routine electrophysiologic testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of β-adrenergic stimulation on the QRS duration of the signal-averaged electrocardiogram ☆ ☆☆ ★

Isoproterenol, a [3-adrenergic agonist, shortens ventricular effective refractory period and may facilitate the induction of ventricular tachyarrhythmias by programmed electrical stimulation. 1 Isoproterenol has also been shown to enhance the voltage-sensitive sodium current in rabbit cardiac myocytes. 2 In both dissociated rabbit cardiac myocytes and isolated rabbit hearts, isoproterenol reverses blockade of the sodium channel by lidocaine. 3 Because the sodium current is a major determinant of conduction Velocity, it stands to reason that [3-adrenergic stimulation could enhance conduction in the myocardium. This supposition may be important in helping to explain both the occurrence of ventricular arrhythmias and the variable effects of antiarrhythmic therapy in patients. The QRS duration may be used as an indicator of conduction in the ventricle. We used the signal-averaged electrocardiogram (SAECG) to measure QRS duration in this study to test the hypothesis that isoproterenol shortens QRS duration in human beings. Seven randomly selected patients who were undergoing an electrophysiology (EP) study for various clinical indications were included. The study was approved by the University of Iowa Committee on Human Subjects Research, and all patients gave written informed consent. At the time of the initial EP study, two quadripolar electrode catheters were percutaneously inserted into a femoral vein and advanced to the right ventricular apex and to the His bundle position under fluoroscopic guid-

Autonomic control of ventricular tachycardia: Direct effects of beta-adrenergic blockade in 24 hour old canine myocardial infarction

The purpose of this study was to determine whether alpha- or beta-adrenergic influences directly modulate the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 41) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Neither intracoronary saline solution nor phenylephrine (0.3 to 12 micrograms) changed the rate of ventricular tachycardia; however, isoproterenol (0.01 to 10 micrograms) produced dose-dependent increases in the rate. In six dogs, metoprolol, 5 mg given intravenously, slowed ventricular tachycardia from 174 +/- 10 (mean +/- SE) to 140 +/- 17 beats/min (p less than 0.05). This was accompanied by decreases in mean arterial pressure from 106 +/- 7 to 95 +/- 8 mm Hg, cardiac output from 2.6 +/- 0.3 to 1.6 +/- 0.3 liters/min and prolongation of atrioventricular conduction from 134 +/- 10 to 189 +/- 29 ms (all p less than 0.05) during atrial pacing at a cycle length of 300 ms. In 10 dogs, metoprolol (0.5 mg) given intracoronary, a dose that shifted the isoproterenol dose-response curve to the right, slowed ventricular tachycardia from 174 +/- 7.2 to 140 +/- 9.7 beats/min (p less than 0.05) without hemodynamic changes. Additional metoprolol (4.5 mg) given intravenously produced hemodynamic alterations, but ventricular tachycardia did not slow further. Therefore, beta- but not alpha-adrenergic influences control the rate of ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Furthermore, beta-adrenergic blockade slows ventricular tachycardia solely by a direct electrophysiologic effect on the tachycardia foci and not indirectly as a result of hemodynamic effects.

Hemodynamic and reflex sympathetic control of transmural activation and rate of ventricular tachycardia in ischemic and hypertrophic ventricular myocardium of the dog.

BackgroundA previous study found that the electrophysiological response to ischemia is altered in hypertrophic myocardium, resulting in prolonged transmural activation time (TAT) associated with induction of sustained monomorphic ventricular tachycardia. This study investigated the role of hemodynamics in modulating TAT and the cycle length of induced ventricular tachycardia (VT) in dogs with left ventricular hypertrophy (LVH). Methods and ResutsAnesthetized open-chest dogs underwent 3 hours of uninterrupted circumflex coronary occlusion. During atrial drive, TAT was recorded between endocardial and epicardial bipolar pairs on the same multipolar plunge needle placed in nonischemic and ischemic zones, documented by triphenyltetrazolium chloride staining. TAT and VT induced by up to three extrastimuli were studied during hypertension (control), during normotension produced most frequently by nitroprusside infusion (3–6 μg/kg/min), and during further hypertension most frequently produced by phenylephrine infusion (1–5 μg/kg/min). Twenty-five dogs with chronic hypertension and LVH (group 1) produced by a single-kidney renal clamp mechanism and 15 control dogs were studied. In the latter, neither intervention altered TAT, and no VT was inducible. In group 1, however, nitroprusside reversibly prolonged TAT within the ischemic zone (mean±SEM, 31±3 to 34±3 msec, p < 0.005) and cycle length of induced VT (204±19 to 240±17 msec, p < 0.01). Phenylephrine reversibly shortened both TAT in the ischemic zone (33±2 to 28±2 msec, p < 0.05) and cycle length ofVT (219±17 to 165±11 msec, p < 0.025). Cycle length of VT and TAT were dissociated from blood pressure elevation in two dogs with LVH; when blood pressure was elevated by sympathetic nerve stimulation, cycle length of VT and TAT were prolonged. In 11 dogs with LVH (group 2), prolongation of TAT with nitroprusside infusion was prevented by intravenous metoprolol (1.0 mg/kg). Of 12 dogs with LVH and inducible VT (group 3), seven still had VT inducible after metoprolol, but the cycle length of VT was still prolonged with nitroprusside infusion. ConclusionsThese results suggest that 1) TAT in acutely ischemic LVH was uniquely responsive to hemodynamic influences, an effect prevented by β-blockade with metoprolol, and 2) the cycle length ofVT was also uniquely regulated by hemodynamic influences but not blocked by metoprolol.

Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT2 receptor

Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT(2) blocker PD-123319 (PD), or AT(1) blocker losartan, will affect this VT. Anesthetized dogs (n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1-3 h after CAO received AGII, and those with VT received either PD or losartan. Focal endocardium excised from ischemic sites was studied in vitro with standard microelectrode. Of 33 dogs with no inducible VT, AGII infusion resulted in sustained VT of only focal Purkinje origin in 13 (39%) compared with 0 of 20 dogs with saline. Of 26 dogs with inducible VT at baseline, given PD, reinduction was blocked in 8 of 10 (P < 0.05) focal VT, but only 1 of 15 with reentry. In contrast, of 11 dogs given losartan, reinduction of either mechanism was not blocked. In vitro triggered activity in Purkinje was blocked by PD in 13 of 19 (P < 0.05), but not by losartan in 8. Also, triggered activity was promoted by AGII, losartan, or the combination in 9 of 12 tissues. AGII promotes only focal, mainly Purkinje ischemic VT. PD, but not losartan, preferentially blocked focal VT, which is likely due to triggered activity due to delayed afterdepolarizations in Purkinje.