John W. Fitzgerald

Arrhythmias in patients with mitral valve prolapse.

Resting ECGs, exercise treadmill tests and 24-hour ambulatory ECGs were recorded and analyzed in 24 unselected patients with mitral valve prolapse. Arrhythmias were frequent. There were three distinct groups of patients, defined on the basis of total number of premature ventricular contractions (PVCs) during the 24 hours: there were no PVCs in 25%, infrequent PVCs in 25%, and frequent PVCs in 50%. Complex ventricular arrhythmias, including ventricular tachycardia in five patients, were found almost exclusively in the group with frequent PVCs. Fifteen of the 24 patients demonstrated atrial premature contractions (APCs) during the 24 hours. Complex atrial arrhythmias were found among patients with infrequent, as well as those with frequent, APCs. Supraventricular tachycardia was detected in seven of these patients. The incidence of PVCs decreased during sleep in 58% of the patients, increased in 17%, and showed no change in 25%. The incidence of APCs decreased during sleep in 67% of the patients and showed no change during sleep in 33%. A poor correlation was found between symptoms recorded in patient diaries and changes noted on 24-hour ECG recordings. The peak PVCs/15 min and peak APCs/15 min during a 24-hour period of monitoring was found to be an excellent guide to the total number of PVCs and APCs occurring during that period. This permits an accurate prediction of the total number of PVCs in 24 hours after performing an exact PVC count on only 15 minutes of ECG data. Finally, the 24-hour ambulatory ECG was more sensitive than the treadmill test and both were superior to the 12-lead ECG for detecting arrhythmias in these patients.

Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide.

SUMMARY Tocainide, a new oral antiarrhythmic agent, was studied in man in a short-term protocol designed to evaluate the efficacy, kinetics, and toxicity of this compound. Premature ventricular contractions (PVCs) were suppressed by > 70% in 11 of 15 patients compared with pre-drug placebo controls. For these 11 responders, there was an average PVC reduction of 91% ± 10 (range 70 to 100%) at tocainide doses not associated with side effects. Mild transient central nervous system toxicity was observed in some patients near the time of peak concentrations during the highest dose administered. The drug was found to have linear kinetics over the dose range studied and a plasma half-life of 13.5 ± 2 hours. Plasma concentration-response curves indicate antiarrhythmic activity over all plasma concentrations, with 70% PVC reduction above 6.0 μg/ml. This study suggests that tocainide is a safe and effective antiarrhythmic agent during short-term administration and is worthy of further clinical trials.

Antiarrhythmic drug effect assessed from ventricular arrhythmia reduction in the ambulatory electrocardiogram and treadmill test: Comparison of propranolol, procainamide and quinidine☆

A 5 week study was performed in 17 patients with frequent ventricular ectopic complexes. The study design comprised an initial control period, 1 week each of treatment with propranolol (240 mg daily), procainamide (3.0 g daily) and quinidine (1.8 g daily) and a final control period. Twenty-four hour ambulatory electrocardiograms and maximal exercise tests were performed each week. For the group, the total number and qualitative types of ventricular ectopic complexes were similar during the two control periods; however, there were large variations among individual patients. Each drug reduced the total number of ventricular ectopic impulses and the percent of patients with each qualitative type. There was agreement between the ambulatory electrocardiogram and treadmill test in three quarters of the drug evaluations. Although it is possible to determine antiarrhythmic drug effects for a group, spontaneous variability in the occurrence of ventricular arrhythmias makes it difficult to evaluate the effects in individual patients.

Treatment of Recurrent Symptomatic Ventricular Tachycardia

Eleven consecutive patients with recurrent ventricular arrhythmias were treated by an aggressive protocol and followed up prospectively. Arrhythmias, symptoms, and cardiac lesions were defined. Antiarrhythmic drugs were given on schedule, with blood levels determining dose; success or failure was defined by elimination or recurrence of symptomatic arrhythmias. When drug therapy failed, left ventricular aneurysmectomy was done when appropriate. Recurrent ventricular tachycardia was most frequently responsible for symptoms; coronary artery disease was the most frequent underlying disease. Symptomatic arrhythmias were eliminated in 8 of 11 patients (5 with drugs and 3 with aneurysmectomies), with a 16.5-month symptom-free average follow-up. An average of 2.9 therapeutic trials per patient was needed to control symptomatic arrhythmias. The average time from entry into the study until the start of ultimately effective therapy was 18 days. Therapy that eliminated symptoms did not eliminate all premature ventricular contractions, and occasionally even brief asymptomatic episodes of ventricular tachycardia persisted. Recurrent symptomatic ventricular arrhythmias can be controlled in many patients by rigorous application of current therapies.

Propranolol for patients with mitral valve prolapse

This study evaluates propranolols effect on symptoms, arrhythmias, and exercise tolerance in 16 patients with mitral valve prolapse. Three patients (19 per cent) experienced symptomatic deterioration with propranolol therapy, seven (44 per cent) were unchanged, and six (37 per cent) noted an over-all symptomatic improvement, primarily due to a reduction in palpitation. Symptomatic improvement continues in these six patients an average of 12.5 months after beginning propranolol therapy. Treatment with propranolol alleviated chest pain in only two of eight patients and it did not improve the ability to perform treadmill exercise. Fatigue did not improve, and in three patients appeared for the first time during propranolol therapy. Premature ventricular contractions were reduced by at least 75 per cent in five of nin patients (56 per cent), and paroxysmal ventricular tachycardia was eliminated in three of four patients. We conclude that propranolol is not uniformly effective in patients with mitral vale prolapse. A trial of propranolol may be instituted fro patients with mitral valve prolapse who have severe symptoms and/or arrhythmias, but the drug should only be continued in those who demonstrate clinical and/or antiarrhythmic response.

Serial ambulatory electrocardiography and treadmill exercise testing after uncomplicated myocardial infarction

To compare the diagnostic and prognostic utility of ambulatory electrocardiography and treadmill exercise testing after clinically uncomplicated myocardial infarction, 90 men (mean age 52 years) were evaluated 3 weeks after the acute event and a variable number were evaluated 11, 26 and 52 weeks after the acute event. The prevalence of “any” premature ventricular complex and of “complex” ventricular ectopic activity was greater with ambulatory electrocardiography than with treadmill testing (78 versus 49 percent; p

The posterior aortic wall echocardiogram. Its relationship to left atrial volume change.

SUMMARY The normal posterior aortic wall echocardiogram shows anterior motion during left ventricular systole and predominantly posterior motion in three phases during left ventricular diastole. In six patients undergoing simultaneous left atrial angiograms and posterior aortic wall echocardiograms, there was excellent correlation between the posterior aortic wall motion and the change in the left atrial angiographic area showing the value of the posterior aortic wall echocardiogram in describing the left atrial volume curve. Left atrial and left ventricular pressures were measured with manometer tip catheters and correlated with simultaneous posterior aortic wall and mitral valve echocardiograms in four patients with atrial septal defects. These echocardiographic, angiographic, and hemodynamic correlations, as well as other evidence reported in this paper suggest that a major portion of posterior aortic wall motion is related to left atrial events and describes the left atrial volume curve.

The assessment of mitral stenosis and prosthetic mitral valve obstruction, using the posterior aortic wall echocardiogram.

The echocardiographic motion of the aortic root reflects, in part, left atrial filling and emptying. Patients with mitral valve obstruction were studied to determine whether clinically important alterations in patterns of left atrial emptying would alter motion of the posterior aortic wall. Patients with mitral stenosis had a characteristic pattern of slowing of left atrial emptying in early diastole, with loss of the conduit phase in mid-diastole. The atrial empty- Staning index, defined as the fraction of passive posterior aortic wall motion occurring in the first third of diastole, was significantly related to the mitral valve area index (r = 0.86), and thus provides a noninvasive quantitation of the degree of mitral stenosis. Determination of the atrial emptying index also proved useful in the evaluation of patients with prosthetic mitral valve obstruction and in documenting improvement in left atrial emptying after mitral valve surgery.

Contribution of ambulatory electrocardiographic monitoring to antiarrhythmic management

Abstract To date, ambulatory electrocardiographic monitoring has contributed to our understanding of the occurrence and significance of arrhythmias. Our appreciation of the spontaneous variability of ventricular arrhythmias, the relations between symptoms and the occurrence of arrhythmias, and the use of ambulatory monitoring in documenting drug effect for new antiarrhythmic drugs and for defining relations among drug dose, plasma concentration and antiarrhythmic effect have contributed to our ability to make more rational recommendations for prescribing and monitoring drug therapy. Further work is necessary to define the occurrence of arrhythmias in normal persons and to determine the prognostic importance of arrhythmias in normal subjects and patients with heart disease other than coronary artery disease. Studies assessing the role of spontaneous variation have indicated the problems that can occur in attempting to evaluate antiarrhythmic drug therapy in individual patients. These variations are so great that it may not be practical to monitor antiarrhythmic drug therapy in certain patients. For patients with coronary artery disease, ambulatory electrocardiographic monitoring can identify those with frequent complex arrhythmias who are at high risk of subsequent sudden cardiac death. Such monitoring can document the effectiveness of antiarrhythmic drug therapy for ventricular irritability and define the dosing regimens or plasma concentrations that are effective for most patients. Ultimately, multicenter intervention trials must document whether or not such antiarrhythmic drug therapy can influence the outcome in the high risk patients identified with ambulatory electrocardiographic recordings. It will be important to determine whether any observed reduction in sudden death in these trials can be related to suppression of asymptomatic ventricular ectopy as determined with ambulatory electrocardiographic recordings.

Response optimization of drug dosage: Antiarrhythmie studies with tocainide

The benefits of using antiarrhythmic response to optimize dosage regimens of antiarrhythmic drugs in individual patients have been examined. Graded antiarrhythmic response and simultaneously measured plasma drug concentrations have been obtained in 15 patients receiving multiple oral doses of a new antiarrhythmic, tocainide. Plasma drug concentration‐antiarrhythmic response data from each of 11 subjects responding to the drug have been fitted by a generalized concentration effect function which is valid over the entire range of response. With the use of experimentally determined pharmacokinetic parameters to define the dose‐plasma concentration relations hip and plasma drug concentration‐response parameters estimated for individual patients, simulations were carried out to show the effect of various dosage regimens on antiarrhythmic response in individual patients. Such simulations provide a means of assessing antiarrhythmic effect in the range of clinical interest (80% to 100% of maximum effect), where the antiarrhythmic effect is a non linear function of dose, plasma drug concentration, or their logarithms. The simulations also demonstrate that for identical daily doses and dosing intervals patients show marked variability in antiarrhythmic response.