Global right atrial mapping of human atrial flutter: the presence of posteromedial (sinus venosa region) functional block and double potentials : a study in biplane fluoroscopy and intracardiac echocardiography.

BACKGROUND: Previous studies of atrial flutter have found linear block at the crista terminalis; this was thought to predispose the patient to the arrhythmia. More recent observations, however, have demonstrated crista conduction. We sought to characterize the posterior boundary of atrial flutter. METHODS AND RESULTS: Patients with counterclockwise flutter (n=20), clockwise flutter (n=3), or both (n=5) were studied using two 20-pole catheters. Biplane fluoroscopy determined catheter positions. During counterclockwise flutter, craniocaudal activation occurred along the entire lateral and posterior right atrial walls. Septal activation proceeded caudocranially. In all patients, a line of block was seen in the posteromedial (sinus venosa) right atrium; this was manifested by the presence of double potentials where the upward and downward activations collided. Anatomic location was confirmed by intracardiac echocardiography in 9 patients. In patients with clockwise flutter, the line of block and double potentials were seen in the same location during counterclockwise flutter, but the activation sequence around the line of block was reversed. Pacing near the site of double potentials during sinus rhythm excluded a fixed line of block, and premature atrial complexes demonstrated functional block with manifest double potentials. In 2 patients, posterior ectopy organized to subsequently initiate isthmus-dependent atrial flutter. CONCLUSIONS: (1) A functional line of block is seen at the posteromedial (sinus venosa region) right atrium during counterclockwise and clockwise atrial flutter. (2) All lateral wall right atrial activation can be uniform during flutter, without linear block or double potentials in the region of the crista terminalis. (3) Activation at the site of posteromedial right atrial functional block can organize to subsequently initiate isthmus-dependent atrial flutter.

Adenosine: potential modulator for vasovagal syncope.

OBJECTIVES: This study examined the hypothesis that adenosine could provoke a vasovagal response in susceptible patients. Mechanisms of the vasovagal response were further explored by studying the adenosine-mediated reactions. BACKGROUND: Increased sympathetic activity is frequently observed before vasovagal syncope. Recent studies have demonstrated that adenosine, in addition to its direct bradycardiac and vasodilatory effects, can increase sympathetic discharge by activating cardiovascular afferent nerves. METHODS: The effects of adenosine and head-up tilt-table testing with or without isoproterenol were prospectively evaluated in 85 patients examined for syncope after negative results of electrophysiologic testing (51 men and 34 women, mean [+/- SD] age 61 +/- 17 years). Adenosine bolus injections of 6 mg and 12 mg were sequentially administered to patients in the upright position. The same protocol was implemented in 14 normal control subjects (7 men and 7 women, mean [+/- SD] age 38 +/- 10 years). RESULTS: Transient hypertension or tachycardia was observed in 57 (67%) and 20 (24%) patients after administration of 6 mg and 12 mg of adenosine, respectively, during the immediate phase (first 15 s), suggesting direct sympathetic activation. Hypotension and reflex tachycardia were observed in all patients during the delayed phase (15 to 60 s after adenosine injection), suggesting baroreceptor unloading. A vasovagal response was induced in 22 (26%) and 29 (34%) patients after adenosine administration and during tilt-table testing. Inducibility of a vasovagal response by these two methods was comparable (p = 0.12). Of the control subjects, one (7%) had a vasovagal response after adenosine administration and one (7%) had a positive response during tilt-table testing. CONCLUSIONS: These observations support the idea that adenosine is an endogenous modulator of the cardiac excitatory afferent nerves. Sympathetic activation by adenosine can be direct (i.e., cardiac excitatory afferent nerves) and indirect (i.e., vasodilation and reflex sympathetic activation). Adenosine could be an important modulator in triggering a vasovagal response in susceptible patients during examination for syncope.

Electrophysiologic characteristics of diverse accessory pathway locations of antidromic reciprocating tachycardia.

This study assessed antidromic reciprocating tachycardia (ART) in patients with paraseptal accessory pathways (APs). Previous clinical experience suggests that paraseptal APs are unable to serve as the anterograde limb during ART. Based on the reentry wavelength concept, we hypothesized that anatomic location of a paraseptal AP may not preclude occurrence of ART. If wavelength criteria were met due to prolonged conduction time retrogradely in the atrioventricular node or anterogradely in the AP, ART may be sustained. All patients who had ART in the electrophysiologic laboratory at our institution (1991 to 1998) were studied. Based on fluoroscopically guided electrophysiologic mapping and radiofrequency ablation, AP location was classified as paraseptal, posterior, or lateral. Conduction time and refractoriness measurements were made for all components of the ART circuit. Of 24 patients with ART, 5 (21%) had ART utilizing a paraseptal AP. Anterograde conduction time through the AP and retrograde atrioventricular nodal conduction time were significantly longer in patients with paraseptal versus lateral pathways. Isoproterenol was required for ART induction in 38% of patients with a posterior AP, 36% with lateral AP location, but not in patients with a paraseptal AP. There were no significant differences in tachycardia cycle length or refractoriness of anterograde and/or retrograde components of the macroreentry circuit between the 3 pathway locations. Thus, ART can occur in patients with a paraseptal AP. Slower anterograde pathway conduction, or retrograde atrioventricular nodal conduction renders the wavelength critical for completion of the antidromic re-entrant circuit.

Unstable angina.

Unstable angina can manifest as an array of symptom complexes. In some patients, medical therapy will stabilize the episodes of angina, and only predismissal exercise testing or angiography (or both) will be necessary. At the other end of the spectrum are patients with rest angina or multiple episodes of silent ischemia who are refractory to medical therapy and experience undetected microinfarction. Most of these patients require immediate catheterization and subsequent intervention with intra-aortic balloon pulsation, percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. An entire spectrum of manifestations exists between these two extremes. One challenge during the 1990s will be better stratification of patients with unstable angina so that safe, efficient, cost-effective treatment strategies can be appropriately applied to all patients.

Constrictive pericarditis and pleuropulmonary disease linked to ergot dopamine agonist therapy (cabergoline) for Parkinson's disease.

Cabergoline is one of several ergoline dopamine agonist medications used in the treatment of Parkinson's disease (PD). We diagnosed constrictive pericarditis (CP) in a patient with PD receiving cabergoline therapy (10 mg daily), who had symptoms and signs of congestive heart failure (CHF). In the absence of previous reported cases of this condition linked to ergoline drugs, cabergoline was not initially identified as the cause. Shortly thereafter, however, the patient developed of a severe pleuropulmonary inflammatory-fibrotic syndrome, a recognized complication of ergoline medications, thus suggesting a common pathogenesis due to cabergoline therapy. To our knowledge, this is the first case in the English literature, although we speculate that CP may be more common than reported among patients with PD who are treated with an ergoline drug (cabergoline, bromocriptine, pergolide, or lisuride). The diagnosis of CP is difficult and requires a high level of suspicion; symptoms may masquerade as CHF due to common mechanisms such as coronary artery disease. In patients with PD who are taking not only cabergoline but also one of the other ergoline drugs, CP should be suspected if symptoms of CHF develop.

Consistent subcutaneous prepectoral implantation of a new implantable cardioverter defibrillator.

OBJECTIVE: To describe the use of a new implantable cardioverter defibrillator (ICD) that can be placed in the prepectoral region rather than implanted in the abdominal wall. DESIGN: We report the experience of placement of this new ICD in the prepectoral region in 13 patients from Sept. 28, 1993, through Jan. 10, 1994, at the Mayo Clinic. MATERIAL AND METHODS: Thirteen consecutive patients offered this new ICD underwent placement of transvenous defibrillation leads, and the pulse generator was placed in a pocket formed in the subcutaneous, prepectoral space. Testing ensured a defibrillation threshold of 24 J or less. RESULTS: In all 13 patients, the pulse generator could be placed in the subcutaneous, prepectoral space. In all except one patient, acceptable defibrillation thresholds were achieved by using lead systems placed totally transvenously. Only one patient required placement of a subcutaneous patch. All but two patients were dismissed from the hospital within 3 days after the ICD implantation. CONCLUSION: Consistent subcutaneous, prepectoral placement of this new ICD pulse generator is possible. Because the entire procedure can be performed in the pacemaker implantation room, the potential exists for decreasing the duration of the hospitalization and associated costs.

Reversible catecholamine-induced cardiomyopathy in a heart transplant candidate without persistent or paroxysmal hypertension.

BACKGROUND: Both dilated and hypertrophic cardiomyopathy have been reported in patients with pheochromocytoma, who were almost always hypertensive. The outcome frequently has been fatal, yet cardiac dysfunction can be reversible after medical or surgical therapy for the pheochromocytoma. METHODS: We report the case of a patient with dilated cardiomyopathy without persistent or paroxysmal hypertension, who was found to have a pheochromocytoma during initial medical evaluation. RESULTS: The identification and treatment of the pheochromocytoma led to significant improvement in cardiac function and cardiac transplantation was avoided. CONCLUSIONS: This case illustrates some unusual features in pheochromocytoma-induced cardiomyopathy: (1) absence of persistent or paroxysmal hypertension, (2) initial presentation with acute myocardial infarction and normal coronary arteries, and (3) recurrent episodes of nonsustained ventricular tachycardia.

The effect of intravenous procainamide on the HV interval at electrophysiologic study.

The His bundle electrogram recorded at electrophysiologic study clearly differentiates atrioventricular (AV) node disease from distal conduction system disease. The distal conduction system may be tested further by infusing procainamide (10-15 mg/kg) intravenously. High-grade distal AV block or prolongation of the HV interval <80 ms was defined as an abnormal response to this test. We retrospectively reviewed the medical records of 79 patients who underwent electrophysiologic study with intravenous procainamide. An abnormal response to procainamide was observed in only 3% of 37 patients with a normal baseline HV (

Voltage dependence of beta-adrenergic modulation of conduction in the canine Purkinje fiber.

Although recent voltage-clamp and microelectrode studies have demonstrated beta-adrenergic modulation of Na+ current (INa) the modulation of conduction by catecholamines and the voltage dependence of that process have not been elucidated. To determine whether voltage-dependent modulation of conduction occurs in the presence of a beta-adrenergic agonist, the effect of 1 mumol/L isoproterenol on impulse propagation in canine Purkinje fibers was examined by using a dual-microelectrode technique. At physiological membrane potentials ([K+]o 5.4 mmol/L), isoproterenol increased squared conduction velocity [theta 2, 0.39 +/- 0.25 (m/s)2 (mean +/- SD)] from 3.46 +/- 0.86 to 3.85 +/- 0.98 (m/s)2 (P < .011), an 11% change, without altering the maximum first derivative of the upslope of phase 0 of the action potential (Vmax, 641 +/- 50 versus 657 +/- 47 V/s, P = NS). At transmembrane potential of -65 mV, produced by 12 mmol/L [K+]o titration, theta 2 declined 79% to 0.73 +/- 0.44 (m/s)2 as Vmax decreased 85% to 95 +/- 43 V/s (P < .02). The addition of isoproterenol further decreased theta 2 to 0.49 +/- 0.33 (m/s)2 (P = .02) in parallel with a further decline in Vmax to 51 +/- 25 V/s (P < .05). Isoproterenol produced a 3-mV hyperpolarizing shift of apparent Na+ channel availability curves generated from both theta 2 and Vmax, used as indexes of the fast inward INa, without changing the slopes of the relation. The relation between normalized theta 2 and Vmax over a range of depolarized potentials was linear and was not appreciably altered by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of lethal proarrhythmia observed in the Cardiac Arrhythmia Suppression Trial: role of adrenergic modulation of drug binding.

A variety of recent in vivo studies have sought to clarify the mechanism underlying the proarrhythmic response of flecainide in the Cardiac Arrhythmia Suppression Trial (CAST). Increased inducibility of relatively stable ventricular arrhythmias in subacute and chronic postinfarction models has been universally observed. The arrhythmogenesis has been explained in part by drug induced modulation of anisotropic conduction in persistently ischemic tissue, increased durations of vulnerable windows, enhanced generation of unidirectional block with the introduction of extrastimuli, variability of repolarization within the ventricular wall, and the creation of stable reentrant circuits with narrow central zones of propagation. While these data explain arrhythmogenesis in general, malignant ventricular arrhythmia capable of producing the excess sudden or arrhythmic death mortality in the CAST trial have not been universally observed, nor have the proported beneficial effects of beta-blockade seen in the CAST trial and other studies been explained. Additional studies examining the adrenergic modulation of flecainide binding have shown reversal of flecainide effects in normal tissue, but paradoxical amplification of flecainide induced conduction slowing in depolarized tissue. This variable effect in normal versus abnormal tissue produces significant dispersions of conduction with an expected increased propensity for conduction failure in response to ectopy, increased liminal length for impulse propagation, enhanced vulnerability to premature extrastimuli, and completed reentrant circuits in regions of depressed membrane potentials. This, along with the decrease in action potential duration and accompanying refractoriness in the setting of adrenergic modulation may favor more malignant double wavelet or unstable ventricular arrhythmias.

Effects of slow pathway ablation on fast pathway function in patients with atrioventricular nodal reentrant tachycardia.

INTRODUCTION: This study investigated whether fast pathway conduction properties are altered by slow pathway ablation in patients with AV nodal reentrant tachycardia. METHODS AND RESULTS: Forty consecutive patients who underwent successful ablation of the slow pathway were prospective subjects for the study. Isoproterenol was used to enhance conduction and to differentiate interactive mechanisms. Potential electrotonic interactions were assessed by comparing patients with and those without residual dual AV node physiology after slow pathway ablation. Paired and unpaired t-tests were used when appropriate P < 0.05 was considered statistically significant. In the entire study population, heart rates were not significantly different before and after slow pathway ablation (RR = 770 +/- 114 msec before and 745 +/- 99 msec after, P = 0.07). Anterograde fast pathway conduction properties were unchanged after slow pathway ablation (effective refractory period, 348 +/- 84 msec before and 336 +/- 86 msec after, P = 0.13; shortest 1:1 conduction, 410 +/- 93 msec before and 400 +/- 82 msec after, P = 0.39). Retrograde fast pathway characteristics also were similar before and after ablation. Neither anterograde nor retrograde fast pathway conduction properties during isoproterenol infusion were changed by slow pathway ablation. When the study population was further divided into patients with (n = 13) or without (n = 27) residual dual AV node physiology, no significant change was detected in fast pathway function in either group after slow pathway ablation. CONCLUSIONS: Fast pathway conduction characteristics were not affected by slow pathway ablation. In patients with AV nodal reentrant tachycardia, observations suggest that fast and slow pathways are functionally distinct.

A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989.

BACKGROUND: Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS: We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS: The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.

Is sinus node modification appropriate for inappropriate sinus tachycardia with features of postural orthostatic tachycardia syndrome?

Inappropriate sinus tachycardia and postural orthostatic tachycardia are ill-defined syndromes with overlapping features. Although sinus node modification has been reported to effectively slow the sinus rate, long-term clinical response has not been adequately assessed. Furthermore, whether patients with postural orthostatic tachycardia would benefit from sinus node modification is unknown. The study prospectively assessed the short- and long-term clinical outcomes of seven consecutive female patients with postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia who were treated with sinus node modification. The study was conducted in a tertiary care center. The electrophysiological and clinical responses were prospectively assessed as defined by autonomic function testing, including Valsalva maneuver, deep breathing, tilt table testing, and quantitative sudomotor axonal reflex testing. Among the study population (mean age was 41+/-6 years), 5 (71%) patients had successful sinus node modification. At baseline, heart rates were 101+/-12 beats/min before modification and 77+/-9 beats/min after modification (P = 0.001). With isoproterenol, heart rates were 136+/-9 and 105+/-12 beats/min (P = 0.002) before and after modification, respectively. The mean heart rate during 24-hour Holter monitoring was also significantly reduced: 96+/-9 and 72+/-6 beats/min (P = 0.005) before and after modification, respectively. Despite the significant reduction in heart rate, autonomic symptom score index (based on ten categories of clinical symptoms) was unchanged before (15.6+/-4.1) and after (14.6+/-3.6) sinus node modification (P = 0.38). Sinus rate can be effectively slowed by sinus node modification. Clinical symptoms are not significantly improved after sinus node modification in patients with inappropriate sinus tachycardia and postural orthostatic tachycardia. A primary subtle autonomic disregulation is frequently present in this population. Sinus node modification is not recommended in this patient population.

Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation that is refractory to drug therapy, radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemaker are an alternative therapeutic approach. The effect of this procedure on long-term survival is unknown. METHOD: We studied all patients who underwent ablation of the atrioventricular node and implantation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival was compared with the survival rates in two control populations: age- and sex-matched members of the Minnesota population between 1970 and 1990 and consecutive patients with atrial fibrillation who received drug therapy in 1993. RESULTS: A total of 350 patients (mean [+/-SD] age, 68+/-11 years) were studied. During a mean of 36+/-26 months of follow-up, 78 patients died. The observed survival rate was significantly lower than the expected survival rate based on the general Minnesota population (P<0.001). Previous myocardial infarction (P<0.001), a history of congestive heart failure (P=0.02), and treatment with cardiac drugs after ablation (P=0.03) were independent predictors of death. Observed survival among patients without these three risk factors was similar to expected survival (P=0.43). None of the 26 patients with lone atrial fibrillation died during follow-up (37+/-27 months). The observed survival rate among patients who underwent ablation was similar to that among 229 controls with atrial fibrillation (mean age, 67+/-12 years) who received drug therapy (P=0.44). CONCLUSIONS: In the absence of underlying heart disease, survival among patients with atrial fibrillation after ablation of the atrioventricular node is similar to expected survival in the general population. Long-term survival is similar for patients with atrial fibrillation, whether they receive ablation or drug therapy. Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adversely affect long-term survival.

Intra-atrial conduction block along the mitral valve annulus during accessory pathway ablation: evidence for a left atrial "isthmus".

INTRODUCTION: We observed a change in the atrial activation sequence during radiofrequency (RF) energy application in patients undergoing left accessory pathway (AP) ablation. This occurred without damage to the AP and in the absence of a second AP or alternative arrhythmia mechanism. We hypothesized that block in a left atrial "isthmus" of tissue between the mitral annulus and a left inferior pulmonary vein was responsible for these findings. METHODS AND RESULTS: Electrophysiologic studies of 159 patients who underwent RF ablation of a left free-wall AP from 1995 to 1999 were reviewed. All studies with intra-atrial conduction block resulting from RF energy delivery were identified. Fluoroscopic catheter positions were reviewed. Intra-atrial conduction block was observed following RF delivery in 11 cases (6.9%). This was evidenced by a sudden change in retrograde left atrial activation sequence despite persistent and unaffected pathway conduction. In six patients, reversal of eccentric atrial excitation during orthodromic reciprocating tachycardia falsely suggested the presence of a second (septal) AP. A multipolar coronary sinus catheter in two patients directly demonstrated conduction block along the mitral annulus during tachycardia. CONCLUSION: An isthmus of conductive tissue is present in the low lateral left atrium of some individuals. Awareness of this structure may avoid misinterpretation of the electrogram during left AP ablation and may be useful in future therapies of atypical atrial flutter and fibrillation.