Hepatic mitochondrial function in ketogenic states. Diabetes, starvation, and after growth hormone administration.

The study was designed to evaluate hepatic mitochondrial function during ketotic states. The ketogenic models studied were streptozotocin-induced diabetic ketoacidosis, 48 h of starvation, and after growth hormone administration. In the last-mentioned model we observed increased free fatty acids but not ketonemia. Oxidative phosphorylation was measured using the citric acid cycle substrates pyruvate and succinate, the amino acid glutamate, a ketone body beta-hydroxybutyrate, and a long-chain fatty acid palmitoyl-l-carnitine. State 3 (ADP stimulated) and state 4 (ADP limited) respiration, respiratory control ratio (state 3/state 4), and the ADP/O ratios were normal in the controls and the experimental groups. Uncoupled respiration produced by dinitrophenol with a variety of substrates was unchanged in the experimental groups compared to the controls. Fatty acid oxidation was studied in detail. The rate of utilization of palmitoyl-l-carnitine by controls or experimental groups did not depend on the product formed (citrate, acetoacetate). No significant changes were observed in the oxidation of palmitoyl-CoA (+ carnitine) or with an intermediate-chain fatty acid hexanoate. The specific activity of hepatic mitochondria carnitine palmitoyltransferase did not change in any of the three experimental groups. It is concluded that during diabetic ketoacidosis, starvation, and growth hormone administration, there is (a) no alteration in hepatic mitochondrial function; (b) no change in the intrinsic capacity of hepatic mitochondria to oxidize fatty acids; and (c) no change in the specific activity of mitochondrial carnitine palmitoyltransferase. The mechanism by which the body restrains flux through the mitochondrial oxidative machinery remains to be fully determined.

Antiadrenergic effects of adenosine on His-Purkinje automaticity. Evidence for accentuated antagonism.

The effects of adenosine on the human His-Purkinje system (HPS) were studied in nine patients with complete atrioventricular (AV) block. Adenosine had minimal effect on the control HPS cycle length, but in the presence of isoproterenol increased it from 906 +/- 183 to 1,449 +/- 350 ms, P less than 0.001. Aminophylline, a competitive adenosine antagonist, completely abolished this antiadrenergic effect of adenosine. In isolated guinea pig hearts with surgically induced AV block, isoproterenol decreased the HPS rate by 36%, whereas in the presence of 1,3-dipropyl-8-phenyl-xanthine, a potent adenosine antagonist, the HPS rate decreased by 48% and was associated with an increased release of adenosine. Therefore, by blocking the effects of adenosine at the receptor level, the physiologic negative feedback mechanism by which adenosine antagonizes the effects of catecholamines was uncoupled. The results of this study indicate that adenosine's effects on the human HPS are primarily antiadrenergic and are thus consistent with the concept of accentuated antagonism. These effects of adenosine may serve as a counterregulatory metabolic response that improves the O2 supply-demand ratio perturbed by enhanced sympathetic tone. Some catecholamine-mediated ventricular arrhythmias that occur during ischemia or enhanced adrenergic stress may be due to an imbalance in this negative feedback system.

Effect of prostacyclin on vascular capacity in the dog.

Since the discovery of prostacyclin (PGI2) in 1976, there has been great interest in its vascular effects and potential clinical applications. High infusion rates of PGI2 markedly depress arterial blood pressure both in animal studies and in clinical trials. This fall in pressure may result entirely from a decrease in arterial resistance. However, it is possible that the administration of PGI2 may decrease ventricular filling due to an increase in vascular capacity. To investigate whether or not PGI2 affects vascular capacity, we infused PGI2 intraarterially at both 10 and 25 micrograms/min into 15 dogs on total cardiopulmonary bypass. These infusions were associated with a 25 +/- 3 mmHg decrease in arterial pressure and an increase in vascular capacity of 155 +/- 29 ml (SE, P less than 0.005). This increase in capacity was greater (P less than 0.02) than the increase of 23 +/- 42 ml resulting from infusions of nitroglycerin into eight dogs at 2 mg/min, which produced a decrease in arterial pressure of 23 +/- 4 mmHg, which was the maximal effect that could be achieved. Neither bilateral cervical vagotomy nor beta adrenergic blockade with propranolol significantly diminished the increase in vascular capacity associated with infusions of PGI2. The results from studies in four eviscerated dogs indicated that PGI2 acts on both splanchnic and extrasplanchnic capacity vasculature. To compare the direct effects of PGI2 with those of nitroglycerin and nitroprusside on venous tone, we used an isolated canine spleen preparation. Infusions of PGI2 (100 mcg/min) increased spleen weight in this preparation by 9.0 +/- 2.4% (n = 10, P less than 0.001); this increase was significantly greater than increases of 3.6 +/- 2.2% (P less than 0.001) and 3.5 +/- 2.3% (P less than 0.001) caused by high dose infusions of nitroglycerin (1 mg/min) and nitroprusside (400 micrograms/min), respectively. Thus, PGI2 substantially increases vascular capacity by a mechanism that appears to involve a direct action on vascular smooth muscle. Furthermore, these results suggest that PGI2 might be useful in clinical conditions in which an increase in vascular capacity is indicated.

A comparison of rate control and rhythm control in patients with atrial fibrillation.

BACKGROUND: There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. METHODS: We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. RESULTS: A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. CONCLUSIONS: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.

Sustained intraatrial reentrant tachycardia: clinical, electrocardiographic and electrophysiologic characteristics and long-term follow-up.

Although intraatrial reentry has been traditionally listed as a mechanism for supraventricular tachycardia, few reports describing the clinical features of this arrhythmia exist. Nineteen patients with a clinical history of sustained supraventricular tachycardia were diagnosed as having intraatrial reentrant tachycardia. Seventeen (89%) patients of the 19 had underlying structural heart disease and 17 had echocardiographic evidence of atrial enlargement; the mean left ventricular ejection fraction was 51 +/- 16%. A history of concomitant atrial fibrillation or flutter was present in 13 patients (68%). The mean atrial cycle length during tachycardia was 326 +/- 57 ms (range 260 to 460). Fourteen patients had 1:1 atrioventricular (AV) conduction during tachycardia, of whom 50% had an RP'/RR' ratio greater than 0.5. Intravenous adenosine (dose range 37.5 to 150 micrograms/kg) and verapamil (dose range 5 to 10 mg) had no effect on atrial tachycardia cycle length in 13 of 14 and 9 of 9 patients, respectively, despite induction of second degree AV block. Type 1a antiarrhythmic drugs achieved long-term suppression of intraatrial reentrant tachycardia in only 6 patients, whereas amiodarone (326 +/- 145 mg/day) was successful in 11 patients during a 32 +/- 20 month follow-up period. The remaining two patients and one patient who later developed amiodarone toxicity either progressed to (n = 1) or had (n = 2) catheter-induced high grade AV block and were treated with long-term ventricular pacing. It is concluded that intraatrial reentrant tachycardia is often associated with structural heart disease, particularly of types that cause atrial abnormalities, but left ventricular dysfunction is not a requisite finding. Other arrhythmias are frequently observed in these patients. This arrhythmia responds poorly to type 1a antiarrhythmic drugs, but is effectively treated with amiodarone. Catheter ablation of the AV junction offers a therapeutic option for patients who are refractory to medical therapy.

Paroxysmal supraventricular tachycardia with Wenckebach block: evidence for reentry within the upper portion of the atrioventricular node.

Paroxysmal supraventricular tachycardia with Wenckebach block is an uncommon electrocardiographic finding. Electrophysiologic studies performed in a patient who exhibited this phenomenon indicated that the tachycardia was not caused by either sinus node or intraatrial reentry or abnormal automaticity. The tachycardia cycle length decreased after atropine administration and increased in response to propranolol. Administration of either adenosine (75 to 112.5 micrograms/kg) or verapamil (10 mg) terminated individual episodes of tachycardia. After verapamil and when atrial extrastimuli were introduced, dissociation of atrial activity from His-ventricular activity could be observed even though atrioventricular (AV) nodal block with a clear Wenckebach periodicity could also occur. These findings suggest that paroxysmal supraventricular tachycardia may be produced by reentry located solely within the upper portion of the AV node.

Current-based versus energy-based ventricular defibrillation: a prospective study.

Defibrillation is thought to be mediated by a depolarizing current; however, the present method of defibrillation is based on delivering an empiric dose of energy to all patients. The hypothesis of this study was that for equivalent efficacy rates, a current-based defibrillation method would result in delivering less energy and peak current than would the standard energy-based method. In a group of 86 consecutive patients with ventricular fibrillation, every other patient was prospectively assigned to receive shocks according to method 1 or method 2. Method 1 was current based and delivered successive shocks of 25, 25 and a maximum of 40 A; method 2 was energy based and delivered shocks of 200, 200 and 360 joules. Patients in both groups were similar with respect to age, gender, weight, cardiac diagnosis, ejection fraction, antiarrhythmic therapy, chest circumference, chest depth and transthoracic impedance. Each method had statistically equivalent first shock (79% current-based versus 81% energy-based) and cumulative shock success rates. The mean first shock energy was 120 +/- 30 joules for patients receiving the current-based method and 200 joules for patients receiving energy-based shocks (p = 0.0001). The mean peak current was 24 +/- 2.3 and 33 +/- 5.0 A, respectively (p = 0.0001). Therefore, for equivalent first shock success rates, the energy-based method delivered 67% more energy and 38% more current than the current-based method. High transthoracic impedance (greater than or equal to 90 omega) predicted first shock failure only in patients undergoing defibrillation by the energy-based method (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained ventricular tachyarrhythmias within 2 months of acute myocardial infarction: results of medical and surgical therapy in patients resuscitated from the initial episode.

Sustained ventricular tachycardia or fibrillation that develops during the early recovery period after acute myocardial infarction is a common clinical problem whose management remains controversial. Fifty-three patients who survived an initial episode of sustained ventricular tachycardia or fibrillation occurring between 3 and 60 days (mean +/- SD 21 +/- 16) after myocardial infarction were evaluated. Most of these patients had had a large (peak creatine kinase = 1,729 +/- 882 IU) complicated infarction. Forty-two (79%) of the 53 patients had had repetitive sustained ventricular arrhythmias and the condition of 19 of these could not be stabilized with drug therapy. Twenty-eight patients received medical therapy only. Twenty-four survived and were discharged from the hospital. Twenty-five patients underwent infarctectomy or aneurysmectomy either on an emergency basis (16 patients) or electively because of coexistent heart failure or angina (9 patients). Intraoperative mapping was attempted in these patients but was completely successful in only 13 (52%). Operative mortality was 16% with all deaths occurring in patients who were in shock before surgery. Five of 21 surgically treated survivors required long-term antiarrhythmic therapy. Twenty-one of 24 patients medically treated remain alive and well after 15 +/- 10 months of follow-up. Nineteen of 21 surgically treated patients remain alive and well after 17.9 +/- 11 months. One of these patients required reoperation for severe mitral regurgitation. These results confirm the poor medical prognosis of sustained ventricular tachyarrhythmias that present during the first 2 months after myocardial infarction but demonstrate that an acceptable rate of survival can be achieved with a combined medical and surgical approach to therapy.

Relation between amiodarone and desethylamiodarone plasma concentrations and electrophysiologic effects, efficacy and toxicity.

Because the value of monitoring amiodarone plasma concentrations remains undefined, this study was performed to evaluate its role during the management of patients receiving amiodarone. The early electrophysiologic effects of amiodarone were assessed in 40 consecutive patients with coronary artery disease and sustained ventricular tachycardia or fibrillation who underwent electrophysiologic studies and measurement of amiodarone plasma concentration before and 29 +/- 15 (mean +/- SD) days after initiation of therapy. Amiodarone and desethylamiodarone plasma levels did not correlate with changes in either sinus cycle length, QTc interval, ventricular effective refractory period, AH and HV intervals or ventricular tachycardia cycle length. Amiodarone and desethylamiodarone plasma concentrations and the effects of the drug on conduction intervals or right ventricular effective refractory periods were not related to suppression of arrhythmia induction by ventricular stimulation after 1 month of therapy. The relation between amiodarone plasma concentrations and both toxicity and efficacy during long-term therapy were prospectively assessed in a larger series of 114 consecutive patients with either symptomatic supraventricular or ventricular arrhythmias who were followed up on long-term amiodarone therapy for 26 +/- 15 months. Sixty-three patients (55%) had one or more adverse effects attributed to amiodarone. By life-table analysis, 40, 69 and 80% of patients had experienced an adverse reaction after 1, 2 and 3 years of therapy, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias.

Adenosine has been shown to affect both sinus node automaticity and atrioventricular (AV) nodal conduction. The effects of increasing doses of intravenous adenosine were assessed in 46 patients with supraventricular tachyarrhythmias. Adenosine reliably terminated episodes of supraventricular tachycardia in all 16 patients with AV reciprocating tachycardia, in 13 of 13 patients with AV nodal reentrant tachycardia and in 1 of 2 patients with junctional tachycardia with long RP intervals. Adenosine produced transient high grade AV block without any effect on atrial activity in six patients with intraatrial reentrant tachycardia, four patients with atrial flutter, three patients with atrial fibrillation and in single patients with either sinus node reentry or an automatic atrial tachycardia. The dose of adenosine required to terminate episodes of supraventricular tachycardia was variable (range 2 to 23 mg). Side effects were minor and of short duration. These results demonstrate that adenosine is useful for the acute therapy of supraventricular tachycardia whenever reentry through the AV node is involved. When arrhythmia termination is not affected, atrial activity may be more readily analyzed during adenosine-induced transient AV block.

Mechanism of atropine-resistant atrioventricular block during inferior myocardial infarction: possible role of adenosine.

Mechanisms responsible for atrioventricular (AV) block during acute inferior myocardial infarction are only partially understood. Increased parasympathetic tone is the factor usually postulated; however, persistence of AV block after atropine administration is frequently observed. Adenosine, an endogenous ischemic metabolite, has well established depressant effects on AV node conduction. In this report, an episode of atropine-resistant AV block was reversed by aminophylline, a competitive adenosine antagonist, in a patient with an acute inferior myocardial infarction. This observation suggests a role for adenosine in the mediation of ischemia-induced AV node block.

Coexistence of type I atrial flutter and intra-atrial re-entrant tachycardia in patients with surgically corrected congenital heart disease.

OBJECTIVES: This study assessed the coexistence of intra-atrial re-entrant tachycardia (IART) and isthmus-dependent atrial flutter (IDAF) in patients presenting with supraventricular tachyarrhythmias after surgical correction of congenital heart disease (CHD). BACKGROUND: In patients with CHD, atrial tachyarrhythmias may result from IART or IDAF. The frequency with which IART and IDAF coexist is not well defined. METHODS: Both IDAF and IART were diagnosed in 16 consecutive patients using standard criteria and entrainment mapping. Seven patients had classic atrial flutter morphology on surface electrocardiogram (ECG), whereas nine had atypical morphology. RESULTS: A total of 24 circuits were identified. Three patients had IDAF only, five had IART only, seven had both, and one had a low right atrial wall tachycardia that could not be entrained. Twenty-two different reentry circuits were ablated. Successful ablation was accomplished in 13 of 14 (93%) IART and 9 of 10 (90%) IDAF circuits. There was one IART recurrence. The slow conduction zone involved the region of the right atriotomy scar in 12 of 14 (86%) IART circuits. No procedural complications and no further recurrences were seen after a mean follow-up of 24 months. CONCLUSIONS: Both IDAF and IART are the most common mechanisms of atrial re-entrant tachyarrhythmias in patients with surgically corrected CHD, and they frequently coexist. The surface ECG is a poor tool for identifying patients with coexistent arrhythmias. The majority of IART circuits involve the lateral right atrium and may be successfully ablated by creating a lesion extending to the inferior vena cava.

Use of a regional wall motion score to enhance risk stratification of patients receiving an implantable cardioverter-defibrillator.

OBJECTIVES: We postulated that preoperative assessment of both regional wall motion and left ventricular ejection fraction would serve as an accurate prognostic indicator of long-term cardiac mortality and functional outcome in patients treated with an implantable cardioverter-defibrillator. BACKGROUND: Long-term cardiac mortality has remained high in patients receiving an implantable cardioverter-defibrillator. The ability to risk stratify patients before defibrillator implantation is becoming increasingly important from a medical and economic standpoint. METHODS: The hypothesis was retrospectively tested in 74 patients who had received an implantable cardioverter-defibrillator. Left ventricular ejection fraction and regional wall motion score, derived from centerline chord motion analysis, were calculated for each patient from the preoperative right anterior oblique contrast ventriculogram. Wall motion score was the only significant independent predictor of long-term cardiac mortality and functional status by multivariate analysis because of its enhanced prognostic capability in patients with an ejection fraction in the critical range of 30% to 40%. RESULTS: Patients with an ejection fraction > 40% had a 3-year cardiac mortality rate of 0% compared with 25% for those with an ejection fraction of 30% to 40% and 48% for those with an ejection fraction < 30% (p < 0.05). Similarly, 75% of patients with an ejection fraction > 40% were in New York Heart Association functional class I or II during long-term follow-up compared with 59% of those with an ejection fraction 30% to 40% and 29% of those with an ejection fraction < 30%. Among patients with an ejection fraction of 30% to 40%, those with a wall motion score > 16% had a 3-year cardiac mortality rate of 0% compared with 71% of those with a wall motion score < or = 16% (p = 0.002). In addition, 86% of patients with a wall motion score > 16% were in functional class I or II during long-term follow-up compared with 13% of those with a wall motion score < or = 16% (p = 0.001). CONCLUSIONS: Long-term cardiac mortality and functional outcome in patients receiving an implantable cardioverter-defibrillator can be predicted if the left ventricular ejection fraction and regional wall motion score are measured preoperatively.

Treatment strategies for atrial fibrillation.

Atrial fibrillation is the most common arrhythmia observed in clinical practice, occurring in 0.4% of the general population and in up to 4% of people greater than 60 years old. It is often associated with other cardiovascular disorders, such as hypertension, coronary artery disease, or cardiomyopathy. Critical evaluation and management of patients with atrial fibrillation requires knowledge of etiology, prognosis, and treatment options of this arrhythmia. On initial presentation, emergency electrical cardioversion should be performed if the patient is hemodynamically unstable. If the patient is stable, initial rate control is recommended, using atrioventricular nodal blocking agents. Further treatment mainly depends upon the duration of the episode. Patients who are in atrial fibrillation <48 hours can be safely cardioverted. Patients who are in atrial fibrillation for >48 hours are commonly anticoagulated for 3 to 4 weeks before and after cardioversion because of the risk of thromboembolism formation in the left atrial appendage. An alternate strategy, which is especially attractive when immediate cardioversion is desired, is transesophageal echocardiography to exclude left atrial thrombus followed by prompt cardioversion. After cardioversion, sinus rhythm can be maintained with class I and III drugs, such as flecainide and propafenone or amiodarone and sotalol. New treatment options, such as atrial defibrillation, atrioventricular junctional ablation, or modification of atrial pacing to prevent atrial fibrillation, are currently under investigation. Although atrial fibrillation is so common in clinical practice, it still remains difficult to treat. Conversion and maintenance to sinus rhythm with antiarrhythmic drug therapy has not shown any improvement in mortality, and some patients may benefit more from ventricular rate control. This review article discusses different treatment strategies for patients with atrial fibrillation.

Relation of therapeutic response to nifedipine to coronary anatomy and motion of S-T segment during unstable angina pectoris.

Of 77 patients hospitalized for unstable angina pectoris and failure of oral, dermal, or intravenous nitrates and/or beta blockade, 81 percent with negligible or single-vessel disease and 55 percent with two- or three-vessel disease showed response (p less than 0.05) to nifedipine therapy. Patients with either S-T elevation or no change during pain responded better (31 of 45) than those with any S-T depression (16 of 32; p less than 0.05). Patients with negligible or single-vessel disease had a higher prevalence of S-T elevation (13 of 16) than patients with two- or three-vessel disease (15 of 31; p = 0.004). S-T motion did not predict response in patients with two- or three-vessel disease, but did predict response in patients with negligible or single-vessel disease. On follow-up study at 9 +/- 8 (range one to 33) months, 39 of 42 who had shown response were free from pain. Three died from infarction without unstable angina. (range one to 33) months, 39 of 42 who had shown response were free from pain. Three died from infarction without unstable angina. Five who showed response had elective bypass surgery. The addition of nifedipine abolished or reduced pain episodes by more than 50 percent in 61 percent of patients with refractory unstable angina pectoris. Patients with negligible or single-vessel disease with S-T elevation benefit most. In patients with two- or three-vessel disease, the type of S-T motion did not predict response. Follow-up of all those with response indicated sustained amelioration by nifedipine therapy. Failure of nifedipine therapy should not be accepted until a dose of 120 mg per day has been achieved, or until intolerable side effects appear.

Mexiletine for refractory-ventricular arrhythmias: results using serial electrophysiologic testing.

Mexiletine was administered during serial drug testing to 35 patients with electrically inducible ventricular arrhythmias and to 6 with recurrent ventricular tachycardia that could not be induced or terminated by programmed cardiac stimulation. All patients had arrhythmias resistant to all conventionally available agents. Electrically induced arrhythmias were completely suppressed during mexiletine therapy in 13 patients. In 12 patients no antiarrhythmic regimen was completely suppressive and in 7 of these mexiletine favorably modified the response to programmed stimulation. In four of six patients with frequent episodes of spontaneous ventricular tachycardia that were not inducible by programmed cardiac stimulation, arrhythmia was controlled by mexiletine. The presence of complete arrhythmia suppression with mexiletine during acute testing accurately predicted long-term freedom from recurrent arrhythmia in 16 of 17 patients over a mean follow-up period of 12.6 +/- 6 months. Severe adverse neurologic effects were noted early during mexiletine therapy in three patients, but no patient discharged on such therapy experienced major adverse effects. The study demonstrates that mexiletine can provide well tolerated effective prophylaxis against recurrent ventricular arrhythmias in a significant proportion of patients resistant to conventional drugs.

Quinidine for ventricular arrhythmias: value of electrophysiologic testing.

Quinidine was evaluated during serial electrophysiologic testing with programmed ventricular stimulation in 89 patients with life-threatening ventricular arrhythmias. In 30 of the 89 patients, quinidine therapy prevented the initiation of ventricular tachycardia (VT) during programmed ventricular stimulation. In 8 additional patients no single drug tested was effective, and quinidine in combination with either mexiletine (7 patients) or propranolol (1 patient) prevented the initiation of VT during electrophysiologic testing. The mean serum concentrations of quinidine in the patients who responded and those who failed to respond were 2.9 +/- 0.8 and 2.8 +/- 1.1 micrograms/ml, respectively; however, but nonresponders were characterized by more severe congestive heart failure and an increased incidence of digitalis use. During chronic therapy (24 +/- 3 months) with quinidine either alone or in combination with a second antiarrhythmic drug in the 38 patients whose arrhythmia had been suppressed during electrophysiologic testing, 32 (84%) remain symptom-free while 3 have had recurrent arrhythmia and 3 discontinued quinidine because of adverse effects. These data demonstrate that quinidine, when selected on the basis of electrophysiologic testing, provides effective long-term prophylaxis against recurrent ventricular arrhythmia and that approximately 40% of patients tested are likely to respond either to quinidine alone or quinidine in combination with another antiarrhythmic agent.

Entrainment mapping in patients with sustained atrioventricular nodal reentrant tachycardia: insights into the sites of conduction slowing in the slow atrioventricular nodal pathway.

The inferoposterior region of the triangle of Koch is hypothesized to be the location of the atrial insertion of the slow atrioventricular (AV) nodal pathway. However, the actual site of conduction slowing in the slow AV nodal pathway is unknown. Entrainment mapping during AV nodal reentry can localize the reentrant pathway as follows: the AH interval measured from the mapping catheter = A'H (where A' is the exit site of the reentrant circuit) minus A'A (the conduction time from A' to the site of mapping); the SH interval during entrainment = SA' (the conduction time from stimulus into the reentry circuit) plus A'H. Thus, in all cases, the SH interval should be greater than or equal to the AH interval, and the deltaAH-SH should increase as distance and conduction time (SA' and A'A) from the reentry circuit increases. Fourteen patients with typical AV nodal reentry (cycle length 346 +/- 62 ms) and 1 with fast-slow (cycle length 430 ms) underwent activation and entrainment mapping from 8 to 12 sites in the triangle of Koch and coronary sinus. Pacing was performed at 2 to 3 mA above threshold, at a cycle length 10 ms shorter than tachycardia. A mapping site was defined as being in close proximity to the circuit if the deltaAH-SH was within 120% of the shortest 20th percentile deltaAH-SH value from all measured sites. In the 14 typical cases, 45 of 83 sites (54%) in the anatomic slow pathway region fulfilled criteria for close proximity to the reentry circuit compared with 13 of 50 sites (26%) outside of this region (p = 0.005). For these patients, the shortest SH interval measured from any entrainment site was 294 +/- 58 ms (89 +/- 10% of tachycardia cycle length, range 70% to 119%), indicating that the site of slow conduction in the slow pathway during AV nodal reentrant tachycardia was distal to all mapped sites. Thus, during typical AV nodal reentry, the "slow" pathway does not conduct slowly, and its insertion is located at or within the inferoposterior or midseptal regions in most cases.

Predictors of acute and long-term success after radiofrequency catheter ablation of type 1 atrial flutter.

A history of atrial fibrillation and right atrial size are both determinants of procedural and long-term outcome after RF catheter ablation of type 1 atrial flutter. The results of this study suggest that patients with no history of atrial fibrillation and a normal right atrial size have the best short- and long-term results from this procedure.

Electrocardiographic abnormalities after radiofrequency catheter ablation of accessory bypass tracts in the Wolff-Parkinson-White syndrome.

Repolarization abnormalities on surface electrocardiograms have been described after loss of ventricular preexcitation in some patients with the Wolff-Parkinson-White syndrome. Radiofrequency catheter ablation of overt accessory pathways provides a unique opportunity to study this phenomenon. In this study, serial electrocardiograms were obtained before and after radiofrequency ablation of manifest accessory pathways in 19 patients, of concealed accessory pathways in 6 and after radiofrequency atrioventricular nodal modification in 12. Seven patients undergoing manifest right-sided accessory pathway ablation had left superior frontal plane T-wave axis deviations after ablation (-42 +/- 13 degrees). No patient with a manifest left-sided or concealed accessory pathway, or atrioventricular nodal modification had T-wave abnormalities after ablation; however, left anterior fascicular block and incomplete right bundle branch block each occurred in 1 patient with left accessory pathway ablation. Repolarization abnormalities observed after ablation were similar to T-wave abnormalities during the absence of preexcitation before ablation and persisted up to 5 weeks after the procedure. Patients with repolarization abnormalities after ablation had significantly longer preexcited QRS durations than those without such changes, suggesting that the initial contribution of the pathway to ventricular activation is an important determinant of T-wave changes after ablation. The proposed mechanism for repolarization abnormalities after ablation is the phenomenon of T-wave "memory."