Biomedical subjects
N A Estes
Publications and source records attributed to N A Estes.
Evolving strategies for the management of atrial fibrillation. The role of amiodarone.
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Usefulness of clinical characteristics in predicting the outcome of electrophysiologic studies in unexplained syncope.
Guidelines for the use of electrophysiologic studies in syncope have not yet been formulated. To confirm the sensitivity and specificity of a previously derived model to predict the results of electrophysiologic testing in syncope, the importance of 6 clinical predictors was assessed in a new data set of 141 consecutive patients with unexplained syncope who were referred for electrophysiologic studies. The 6 predictors were: organic heart disease; premature ventricular beats, sinus bradycardia, first-degree heart block and bundle branch block by electrocardiogram; and nonsustained ventricular tachycardia by Holter monitor. Organic heart disease and nonsustained ventricular tachycardia by Holter monitoring were highly sensitive for serious ventricular tachyarrhythmias at electrophysiologic study (sensitivity 100%), whereas sinus bradycardia, first-degree heart block or bundle branch block by electrocardiogram were sensitive for bradyarrhythmic outcomes (sensitivity 79%). Because these variables are so sensitive for serious outcomes of electrophysiologic testing in syncope, invasive studies in patients without these clinical predictors are likely to be of very low diagnostic yield.
Medically unexplained syncope: relationship to psychiatric illness.
The purpose of this article is to review the literature and present new data concerning the relationship between psychiatric disorders and unexplained syncope. Several case series are presented of patients with syncope in whom psychiatric structured interviews were undertaken, tilt-table (physiologic) testing was performed, and health-related quality of life was measured. Patients seen in a syncope specialty clinic underwent structured psychiatric interviews in addition to in-depth medical evaluations. Tilt-table testing was performed on a separate series of patients to determine susceptibility to syncope during the orthostatic challenge of head-up tilt; in some cases, tilt studies included simultaneous electroencephalographic (EEG) monitoring and cerebral blood flow measurements. Formal functional status assessment was carried out using the Sickness Impact Profile, the Symptom Check List 90, and the Medical Outcomes Study Short-Form 36. Psychiatric disorders (in particular, panic disorders and major depression) were a common cause of syncope (24-31% of syncope patients). Tilt table studies showed several physiologic profiles in syncope: (a) a typical vasovagal (hypotension-bradycardia) response, (b) a "psychosomatic" response (fainting with normal vital signs), and (c) a gradual decline in blood pressure (dysautonomic response). EEG and cerebral blood flow measurements in three patients with the psychosomatic response to tilt were normal during fainting. Functional status measurements showed serious impairment in two series of syncope patients. Conclusions were as follows: (a) Psychiatric disorders are common in syncope. (b) Tilt-table methodology may elucidate underlying mechanisms of syncope in these subjects. (c) Syncope can seriously disrupt a patient's life and result in important psychosocial sequelae. (d) There is an intimate relationship between unexplained syncope and psychiatric illness, mandating a combined medical and psychiatric approach to such patients.
Limited clinical utility of endomyocardial biopsy in patients presenting with ventricular tachycardia without apparent structural heart disease.
To determine the cardiac pathology underlying ventricular tachyarrhythmias, endomyocardial biopsy was performed in 14 patients, 10 men and 4 women, with a mean age of 40 years (range 17-63) and no apparent structural heart disease, presenting with high-density symptomatic nonsustained ventricular tachycardia (VT) (n = 4), sustained VT (n = 6), and ventricular fibrillation (n = 4). The absence of coronary or valvular heart disease was documented by cardiac catheterization. The mean left ventricular ejection fraction was 56 +/- 10%. Noninvasive assessment of the ventricular arrhythmia was made in all patients with Holter monitoring and/or exercise testing, while invasive evaluation with programmed electrical stimulation was performed in 13 patients. Biopsy findings included subendocardial and interstitial fibrosis in 7 patients, and monocytes containing periodic acid Schiff (PAS) positive vacuoles in 1 patient; biopsy was normal in 6 patients. There was no relationship between the presence or absence of pathologic abnormalities on biopsy and left ventricular ejection fraction, presenting or induced arrhythmias, or prognosis. Pathologic evidence supporting a specific treatable diagnosis was not present in any biopsy. Drugs to suppress spontaneous (3 patients) or induced (8 patients) VT were instituted, while 2 patients were not treated. In 1 patient who was resuscitated from out-of-hospital cardiac arrest an automatic defibrillator was implanted. In 24.6 months of mean follow-up there was 1 nonfatal arrhythmia recurrence, 1 noncardiac death, and 1 sudden death in a patient with fibrosis on biopsy, an ejection fraction of 45%, and both inducible and spontaneous sustained VT suppressed with an antiarrhythmic agent.(ABSTRACT TRUNCATED AT 250 WORDS)
Cost-effectiveness of the implantable cardioverter-defibrillator: effect of improved battery life and comparison with amiodarone therapy.
The implantable cardioverter-defibrillator (ICD) greatly reduces the incidence of sudden cardiac death among patients with recurrent sustained ventricular tachycardia and fibrillation who do not respond to conventional antiarrhythmic therapy. A cost-effectiveness analysis was performed, comparing the ICD, amiodarone and conventional agents. Actual variable costs of hospitalization and follow-up care were used for 21 ICD- and 43 amiodarone-treated patients. Life expectancy and total variable costs were predicted with use of a Markov decision analytic model. Clinical event rates and probabilities were based on published reports or expert opinion. Life expectancy with an ICD (6.1 years) was 50% greater than that associated with treatment with amiodarone (3.9 years) and 2.5 times that associated with conventional treatment (2.5 years). Assuming replacement every 24 months, ICD lifetime treatment costs (in 1989 dollars) for a 55-year old patient are expected to be $89,600 compared with $24,800 for amiodarone and $16,100 for conventional therapy, yielding a marginal cost/effectiveness ratio for ICD versus amiodarone therapy of 1f429,200/year of life saved, which is comparable to that of other accepted medical treatments. If technologic improvements extend average battery life to 36 months, the marginal cost/effectiveness ratio would be $21,800/year of life saved, and at 96 months it would be $13,800/year of life saved. Patient age at implantation did not significantly affect these results. If quality of life on amiodarone therapy is 30% lower than that with the ICD, the marginal cost/effectiveness ratio decreases by 35%. If the quality of life for patients receiving drugs is 40% lower than that of patients treated with an ICD, use of the defibrillator becomes the dominant strategy.
Junctional tachycardias: anatomic substrate and its significance in ablative procedures.
The conduction system was studied by serial section in three patients with intractable supraventricular tachycardias originating from the atrioventricular (AV) junction who died suddenly. The three patients were a 6 month old girl (Case 1), a 5 month old boy (Case 2) and a 22 year old woman (Case 3). The latter had a pacemaker inserted after surgical ablation of the AV node. The heart was hypertrophied and enlarged in all. In Case 1, the AV node was partly within the central fibrous body and there was a left-sided AV bundle with acute necrosis in the summit of the ventricular septum, adjacent to the AV node and bundle. In Case 2, the coronary sinus was displaced cranially close to the central fibrous body, resulting in abnormality of the latter, with entrapment, distortion and division of the AV node and bundle into two distinct components within the central fibrous body. In Case 3, a left-sided AV node was connected to the atrial septum. The right AV node was completely interrupted by sutures and the penetrating and branching bundle and bundle branches were markedly fibrosed. In addition, the atrial septum and summit of the ventricular septum showed marked inflammatory reaction with fibrosis, which was more marked on the right ventricular side. Histologic examination of the conduction system in all three cases demonstrated congenital abnormalities of the AV junction that may be related to the tachycardia. These findings emphasize the need to carefully evaluate the atrial septum and AV junctional area, including the coronary sinus, before ablative procedures are undertaken.(ABSTRACT TRUNCATED AT 250 WORDS)
Accuracy of rhythm classification using a data log system in implantable cardioverter defibrillators.
Because the presence or absence of symptoms alone may be insufficient to correctly diagnose the rhythm for which implantable cardioverter defibrillator therapy is delivered, we hypothesized that the addition of data log information available in Telectronics ATP 4210 may improve the accuracy of rhythm classification. With this system the recorded ventricular electrogram cycle length is reported on a beat-to-beat basis immediately before, during, and after the tachyarrhythmia is detected. Using this information recorded from the data log in 32 separate tachyarrhythmia episodes in 20 patients, we compared the sensitivity, specificity, and predictive accuracy of rhythm classification on the basis of symptoms alone, data log alone, and data log combined with symptoms. While classification based on symptoms alone is highly specific (10/10 episodes), it is insensitive and has an overall predictive accuracy of 53%. By contrast, data log is sensitive (90%) and specific (91%) with better predictive accuracy (94%) than symptoms alone (P = 0.002). The addition of symptoms to information on beat-to-beat cycle length from data log resulted in a slight increase in predictive accuracy.
Inappropriate shocks and elevation of defibrillation thresholds in a patient with automatic defibrillator patch Silastic erosion and titanium mesh fraying.
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Electrophysiologic and electrocardiographic effects, efficacy and safety of encainide in malignant ventricular arrhythmias associated with coronary artery disease.
The electrophysiologic and electrocardiographic effects, efficacy and safety of encainide were evaluated in 48 patients with coronary artery disease undergoing programmed stimulation for ventricular tachyarrhythmias. The study group included 41 men and 7 women, aged 64 +/- 8 years (mean +/- standard deviation), who had presented with nonsustained ventricular tachycardia (VT) (4 patients), sustained VT (32), ventricular fibrillation (8) or unexplained syncope (4). The left ventricular ejection fraction averaged 34 +/- 13%. The arrhythmias induced at the baseline, drug-free electrophysiologic study included nonsustained VT in 8 patients, sustained VT in 35 and ventricular fibrillation in 5. All patients had failed greater than or equal to 1 class IA and a combination of class IA and IB agents (mean 2.2 +/- 1.1 drugs) before encainide. Oral encainide was given in a mean daily dose of 80 +/- 11 mg for greater than or equal to 3 days before repeat programmed stimulation. Encainide was discontinued before follow-up electrophysiologic testing in 5 patients due to spontaneous development of new sustained VT. Of the 43 patients undergoing electropharmacologic testing with encainide, 5 had no inducible arrhythmia. In 9 patients VT was inducible by fewer extrastimuli, in 2 patients a previously stable VT required cardioversion, whereas in 28 patients VT remained inducible by the same number of or more extrastimuli. Thus, encainide prevented the induction of VT or ventricular fibrillation in 5 of 48 patients (10%), while it had a possible proarrhythmic effect in 15 patients (31%). Of the 5 patients without inducible VT administered long-term encainide therapy, 1 returned within 4 weeks of hospital discharge with VT recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)
Syncope: current diagnostic evaluation and management.
OBJECTIVE: To provide a comprehensive review of the causes, current diagnostic evaluation, and treatment of syncope. DATA IDENTIFICATION: New data and knowledge in this evolving field were critically analyzed by doing a MEDLINE search on syncope supplemented by selective review of English language literature citations in the Index Medicus before 1980. STUDY SELECTION: We reviewed approximately 200 published articles on syncope and closely related topics as well as using our own clinical experience. We selected articles if they addressed the pathophysiology of syncope, classification and causes, differential diagnosis, noninvasive and invasive evaluation, and current therapy. RESULTS OF DATA SYNTHESIS: Syncope is a common clinical problem, occurring in 30% to 50% of the adult population. The prognosis for syncope depends on its cause. Cardiac syncope has the worst prognosis and therefore mandates thorough evaluation and prompt treatment. Diagnostic evaluation is made difficult by the transient nature of the episodes and the many causes. Noninvasive testing reveals the cause of syncope in approximately 50% of cases. More extensive evaluation, including invasive electrophysiologic studies, has assumed a larger role in defining the cause of syncope in selected patients with structural heart disease in whom a noninvasive evaluation has been nondiagnostic. Recently tilt-table studies have been proposed as a clinically useful noninvasive test for vagally mediated syncope. CONCLUSIONS: A rational stepwise diagnostic and therapeutic approach to patients with syncope can be developed by initially doing a careful history and physical examination followed by a noninvasive evaluation and selective use of additional, more specialized or invasive tests. Future research should focus on defining the validity and utility of current diagnostic testing in syncope and on exploring further the pathophysiology of patients with recurrent, unexplained syncope.
Value of programmed ventricular stimulation in the evaluation and management of patients with nonsustained ventricular tachycardia associated with coronary artery disease.
Programmed ventricular stimulation with up to 3 extrastimuli at the right ventricular apex was performed in 52 patients with spontaneous nonsustained ventricular tachycardia (VT) associated with coronary artery disease. There were 44 men and 8 women, aged 66 +/- 9 years (range 45 to 86). The mean left ventricular ejection fraction was 41 +/- 14%. Nonsustained VT was asymptomatic in 10 patients (19%), while the arrhythmia was detected during evaluation of palpitations in 5 patients (10%), presyncope in 11 (21%) and syncope in 26 patients (50%). All patients were tested in the drug-free state and were classified as having no inducible arrhythmia (31 patients, group I), or an inducible arrhythmia (21 patients, group II). The age, gender, type of heart disease, symptoms and left ventricular ejection fraction were similar in both groups. Group I patients had a higher overall incidence of syncope. Group I patients received no therapy, while group II patients received antiarrhythmic therapy guided by electropharmacologic testing. At 21 +/- 17 months there was no sustained VT in either group. There were 3 deaths in group I patients, including 1 sudden, 1 nonsudden cardiac and 1 noncardiac death. In group II patients 6 deaths occurred including 4 nonsudden cardiac and 2 noncardiac deaths. In patients with nonsustained VT and coronary artery disease undergoing programmed ventricular stimulation, the incidence of significant arrhythmic events is low in those without therapy with no inducible arrhythmia, and in those with an inducible arrhythmia with therapy guided by electrophysiologic testing.
Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery.
To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.
Mexiletine: pharmacology and therapeutic use.
Mexiletine is a Class IB antiarrhythmic which has basic and clinical electrophysiologic properties similar to lidocaine. Like other Class I antiarrhythmic agents, mexiletine blocks the rapid inward sodium current responsible for phase 0 of the action potential. It has been noted in the clinical electrophysiology laboratory to have minimal effect on sinus node function and AV nodal and His-Purkinje system conduction. Pharmacokinetic studies have shown that oral absorption is rapid with bioavailability of 80-90%. Mexiletine is predominantly metabolized by the liver with elimination half-life of 9 to 12 hours. The antiarrhythmic effects of the primary drug's metabolites remain to be defined. Hemodynamic studies have shown mexiletine to have a lesser negative inotropic effect than procainamide or disopyramide. Although mexiletine as a single agent successfully suppresses 60 to 80% of spontaneous ventricular arrhythmias, it has lower efficacy in suppression of induced ventricular arrhythmias. Multiple studies have shown that as monotherapy mexiletine is effective in preventing the induction of ventricular tachycardia in approximately 20% of patients. When used in combination with a Class IA antiarrhythmic drug for suppression of induced ventricular arrhythmias, multiple investigators have reported greater efficacy. Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients while gastrointestinal side effects (nausea, anorexia, gastric irritation) occur in up to 40% of patients. Proarrhythmia or other serious toxicity from the drug is uncommon.
Apical hypertrophic cardiomyopathy presenting with sustained monomorphic ventricular tachycardia and electrocardiographic changes simulating coronary artery disease and left ventricular aneurysm.
A 52-year-old male presented with sustained monomorphic ventricular tachycardia as the initial manifestation of apical hypertrophic cardiomyopathy. The electrocardiogram during normal sinus rhythm showed a pattern of an old anterior wall myocardial infarction with aneurysm formation. Cardiac catheterization documented angiographically normal coronary arteries. Apical hypertrophic cardiomyopathy was documented at cardiac catheterization and by echocardiogram and Doppler studies. Monomorphic ventricular tachycardia was reproducibly initiated and terminated during electrophysiological studies and antiarrhythmic drugs failed to control the tachycardia. At the time of implantation of a cardioverter defibrillator, left ventricular apical biopsy revealed pathologic findings characteristic of hypertrophic cardiomyopathy.
Automatic implantable cardioverter defibrillator. Current status.
The automatic implantable cardioverter defibrillator was conceived by Mirowski as an implantable device for detection and termination of ventricular fibrillation. Since the initial human implant of the defibrillator in 1980, there has been a dramatic expansion of the clinical experience with more than 5000 implants. The technology of the device, which is now capable of sensing and terminating both ventricular tachycardia and fibrillation, has evolved rapidly. Although still not an ideal antiarrhythmic device, it has already had a major impact on arrhythmic mortality with a marked reduction in the sudden death rates in a high-risk patient population.
Reversal of electrophysiologic effects of flecainide on the accessory pathway by isoproterenol in the Wolff-Parkinson-White syndrome.
To determine the reversibility of the effects of flecainide on accessory pathways, electrophysiologic studies were performed in the drug-free control state, after flecainide loading and with isoproterenol infusion during flecainide treatment in 12 patients with symptomatic preexcitation syndrome. After the baseline drug-free evaluation, oral flecainide was given in dosages of 50 to 200 mg twice daily (mean daily dose 282 +/- 75) for at least 4 days before the repeat electrophysiologic study. Isoproterenol infusion was given in dosages of 1 to 4 micrograms/min to increase the heart rate at rest by 50%. Anterograde block in the accessory pathway was observed in 3 patients with flecainide therapy, whereas in the other patients the anterograde refractory period increased from 243 +/- 20 to 315 +/- 23 ms (p less than 0.05). The shortest preexcited RR interval during atrial fibrillation lengthened from 234 +/- 27 ms before flecainide to 313 +/- 38 ms (p less than 0.05). Retrograde block occurred in 2 patients after flecainide, whereas the retrograde refractory period of the accessory pathway increased from 247 +/- 26 to 337 +/- 45 ms in the other patients. Orthodromic atrioventricular reciprocating tachycardia, inducible in 10 patients before therapy, became noninducible in 3 patients. Its rate was significantly slowed in the other 7 patients (from 346 +/- 50 to 471 +/- 81 ms). In 2 patients the tachycardia was nonsustained during flecainide treatment. Atrial fibrillation, inducible in all patients at baseline, was rendered nonsustained and more difficult to induce in 7 patients with flecainide. When isoproterenol was infused during flecainide treatment, complete anterograde (3 patients) or retrograde block (2 patients) persisted in the accessory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Prognostic value of early electrophysiologic studies for ventricular tachycardia recurrence in patients with coronary artery disease treated with amiodarone.
Amiodarone was used in 86 patients with ventricular tachycardia (VT) (67 patients) or ventricular fibrillation (19 patients) secondary to coronary artery disease. The mean +/- standard deviation left ventricular ejection fraction was 30 +/- 12% (range 8 to 65%). Prior trials with 4 +/- 1.2 alternate antiarrhythmic agents had been unsuccessful. Amiodarone was loaded at dosages of 1,200 to 1,800 mg/day, with maintenance dosages of 400 to 600 mg/day. Drug efficacy was evaluated by programmed stimulation at 10 to 14 days in 68 patients. In 38 patients sustained VT or ventricular fibrillation was inducible (group I), whereas 30 patients (group II) had either no inducible VT (8) or had nonsustained VT induced (22). Holter monitoring was used to assess drug efficacy in 18 patients (group III). All patients were evaluated at 3- to 6-month intervals with Holter monitors for efficacy and a standard protocol for toxicity. During a long-term follow-up of 18 +/- 16 months, sudden death occurred in 5 patients and nonfatal arrhythmia recurrences were detected in 16. The actuarial probability of freedom from fatal and nonfatal arrhythmia recurrences at 24 months was 0.52 for group I, 0.97 for group II and 0.68 for group III. The mode of induction, rate change or hemodynamic tolerance of the induced ventricular tachycardia did not predict arrhythmia recurrence. Among the clinical variables analyzed, only an ejection fraction of less than or equal to 30% was identified as a significant predictor of arrhythmia recurrence. Nonsudden cardiac death occurred in 21 patients, including 19 from heart failure and 2 from myocardial infarction. Noncardiac death occurred in 7 patients.(ABSTRACT TRUNCATED AT 250 WORDS)