Joel Morganroth

Relation between echocardiographically determined left atrial size and atrial fibrillation.

In an attempt to define quantitatively the relation between left atrial size and atrial fibrillation, echocardiography was used to study 85 patients with isolated mitral valve disease, 50 patients with isolated aortic valve disease, and 130 patients with asymmetric septal hypertrophy. In all three groups of patients, atrial fibrillation was rare when left atrial dimension was below 40 mm (3 of 117 or 3%) but common when this dimension exceeded 40 mm (80 of 148 or 54%). In addition, when left atrial dimension exceeds 45 mm, cardioversion, while initially successful, is unlikely to produce sinus rhythm that can be maintained at least six months. These data suggest that left atrial size is an important factor in the development of atrial fibrillation and in determining the long term result of cardioversion. The pathophysiologic mechanism most consistent with this is that a chronic hemodynamic burden initially produces left atrial enlargement which in turn predisposes to atrial fibrillation. Only prospective studies will determine definitively whether these observations will be useful in decisions concerning prophylactic anticoagulation and elective cardioversion.

Flecainide: Its proarrhythmic effect and expected changes on the surface electrocardiogram

The proarrhythmic potential and electrophysiologic effect of flecainide acetate, a potent class IC anti-arrhythmic agent, are considered in this report. Although the definition of a proarrhythmic effect is arbitrary, several such definitions are discussed and applied to data on flecainide. In patients with chronic ventricular arrhythmias, an increase in VPC frequency developed in 0 to 4% of patients, compared with 1 to 8% of patients who received quinidine and 2% who received encainide, another class IC agent. In patients with acute hemodynamically significant ventricular arrhythmias, the proarrhythmic effects were noted in 5 to 12%. Proarrhythmic effects appear to be more common in patients with left ventricular dysfunction and life-threatening ventricular arrhythmias. The depression of atrioventricular conduction produced by flecainide is similar to that seen with other class IC agents. Increases in PR and QRS intervals are related to dose and plasma concentration and are approximately 25% at therapeutic levels. These changes in the electrocardiographic intervals do not appear to carry important clinical implications and do not require discontinuation of flecainide. QT prolongation is absent or minimal with flecainide. Guidelines for management of patients with flecainide are suggested.

Immediate diagnosis of acute myocardial infarction by two-dimensional echocardiography

To define the role of portable two-dimensional echocardiography (2-D echo) in the immediate diagnosis of acute chest pain syndrome, 80 consecutive patients were studied. Adequate 2-D echo studies were obtained in 65 (81%). Thirty-three patients had clinical evidence of transmural or nontransmural acute myocardial infarction (AMI), 18 of whom had nondiagnostic initial ECGs. Thirty-two did not have a clinical AMI. Thirty-one of the 33 (94%) patients with clinical AMI had regional wall motion abnormalities on the initial 2-D echo; the other two had uncomplicated nontransmural AMIs, diagnosed only by ECG in one and by ECG and moderate elevation of CK-MB isoenzyme in the other. Twenty-seven of the 32 patients without clinical AMI had normal regional wall motion on the initial 2-D echo and none had a complication (severe arrhythmia, recurrent pain, heart failure or death) during the hospital course. Conversely, 10 of the 36 patients with initial 2-D echo regional wall motion abnormalities had a complication (p < 0.05). Thus, in patients with acute chest pain syndrome, an initial 2-D echo that shows no regional wall motion abnormality suggests that such patients will not develop an AMI or clinical complication during the hospital course. An initial 2-D echo with regional wall motion abnormality identifies a high-risk group of patients who are likely to have AMI and important cardiac complications and may, therefore, benefit from admission to an intensive care unit.

Electrocardiographic left atrial enlargement electrophysiologic, echocardiographic and hemodynamic correlates

The mechanism of the electrocardiographic pattern termed left atrial enlargement was evaluated in 21 patients. Left atrial size and pressure as well as interatrial conduction were correlated with electrocardiographic left atrial enlargement using echocardiography, mean pulmonary capillary wedge pressure and activation time from the P wave to the coronary sinus. In the group as a whole only prolongation of interatrial conduction time was consistently related to the electrocardiographic pattern of left atrial enlargement; left atrial size or pressure was not predictably abnormal in patients with this pattern. Five patients had neither elevation of pulmonary capillary wedge pressure nor echocardiographic evidence of an enlarged left atrium. When the etiologic type of heart disease was analyzed, an enlarged left atrium correlated with electrocardiographic left atrial enlargement only in patients with rheumatic mitral valve disease (eight of nine patients). Elevated pulmonary capillary wedge pressure correlated with electrocardiographic left atrial enlargement in all four patients with cardiomyopathy. In patients with coronary artery disease the electrocardiographic pattern was unrelated to either left atrial pressure or volume overload. Thus, the electrocardiographic pattern termed left atrial enlargement appears to represent an interatrial conduction defect that can be produced by a variety of factors.

Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy

The efficacy of amiodarone was assessed in 38 patients with atrial fibrillation resistant to quinidine and an effort made to identify factors correlated with amiodarone response. The study group included 29 patients with and 9 without organic heart disease and either persistent (n = 11) or paroxysmal (n = 27) atrial fibrillation. All patients were treated with amiodarone and followed up in a research clinic. Efficacy was classified as excellent (no recurrent symptomatic atrial fibrillation) in 15 (55%) of 27 patients with paroxysmal and 5 (45%) of 11 patients with persistent atrial fibrillation. Efficacy was poor (no effect on atrial fibrillation) in 5 (19%) of 27 patients with paroxysmal and 6 (55%) of 11 patients with persistent atrial fibrillation. Efficacy was good (amelioration but not total suppression) in 7 (26%) of 27 patients with paroxysmal atrial fibrillation. Efficacy was related to echocardiographic left atrial dimension, left ventricular ejection fraction and, in patients with persistent atrial fibrillation, the duration of the arrhythmia. During the follow-up period of 15 months (range 1 to 36), overall efficacy (considering response and toxicity) was 67% in the 27 patients with paroxysmal and 45% in the 11 patients with persistent atrial fibrillation. It is concluded that amiodarone offers an additional therapeutic alternative in quinidine-resistant atrial fibrillation and that certain clinical factors are correlated with amiodarone response.

Nonsustained ventricular tachycardia in ambulatory patients: characteristics and association with sudden cardiac death.

Thirty-seven patients with nonsustained ventricular tachycardia (greater than or equal to triplets) were identified retrospectively from a population of 518 consecutive patients referred for 24-hour Holter monitoring and studied to determine the prognostic significance of this finding. Ten of these 37 patients suffered sudden cardiac death during a mean follow-up of 19 +/- 5 months. Nine of 19 patients with a diagnosis of congestive cardiomyopathy or history of congestive heart failure died suddently compared to only one of the other 18 patients. No other patient data were predictive of sudden death. Remarkably, no characterisitc of the ventricular tachycardia including beats per episode, episodes per day, rate, prematurity index (RR1/QT) of the initiating beat, or the occurrence of associated arrhythmias was important prognostically. Thus, patients with congestive cardiomyopathy or congestive heart failure and nonsustained paroxysmal ventricular tachycardia are at a high risk for sudden death and are ideal candidates for prophylactic interventions.

Usefulness of electrophysiologic testing in evaluation of amiodarone therapy for sustained ventricular tachyarrhythmias associated with coronary heart disease

The prognostic importance of electrophysiologic studies in patients with sustained ventricular tachyarrhythmias treated with amiodarone was prospectively studied in 100 consecutive patients. Sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) was inducible in all patients before amiodarone therapy. After amiodarone administration 2 groups of patients were identified. In group 1 patients the ventricular tachyarrhythmia was no longer inducible and in group 2 patients the arrhythmia remained inducible. In group 1, no recurrent arrhythmia occurred during a follow-up of 18 +/- 10 months. In group 2, 38 of 80 patients (48%) had arrhythmia recurrence during a follow-up of 12 +/- 9 months. The difference between group 1 and 2 could not be explained by clinical variables, amiodarone doses or plasma concentrations, or electrocardiographic variables. In patients in whom cardiovascular collapse or other severe symptoms where noted during electrophysiologic study after amiodarone treatment, recurrences caused sudden death (n = 12). However, in patients in whom the induced arrhythmia produced moderate symptoms, the recurrent arrhythmia was nonfatal VT (n = 26). Electrophysiologic testing provides clinical guidance and predicts prognosis in patients treated with amiodarone as it does for the evaluation of other antiarrhythmic agents.

Dose-response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: Distinguishing a drug effect from spontaneous variability

The primary goal of this investigation was to describe the effect of terfenadine on the QT interval corrected for heart rate (QTc) of the scalar electrocardiogram (ECG). The design was double-blind, four-period crossover, dose escalation, which involved 28 normal healthy volunteers and 28 patients with stable cardiovascular disease. At baseline, the normal subjects had a mean QTc interval of 407 msec, whereas the patients with cardiovascular disease had a mean QTc interval of 417 msec (p<0.01). The largest increase in mean QTc on terfenadine was 24 msec in a normal subject and 28 msec in a patient with cardiovascular disease. The longest average QTc observed was 449 msec and 501 msec in any normal subject and patient with cardiovascular disease, respectively. Compared to baseline, terfenadine 60 mg twice daily is associated with a QTc increase of 6 msec in normal subjects and a 12 msec increase in patients with cardiovascular disease (p<0.01 vs baseline; p>0.05 when the two populations were compared). Although the QTc increase from baseline are statistically significant, the magnitude of the spontaneous variability in QTc in the same patients is much greater. Because 40 ECGs were obtained while taking placebo in each participant, the spontaneous variability in QTc interval with placebo was also described. Only one of the 28 normal subjects had a mean baseline QTc=440 msec, yet 14 of the 28 normal subjects had at lease one of the 40 placebo ECGs with a QTc=440 msec. The 28 patients with cardiovascular disease had a mean QTc at baseline of 417 msec; yet 20 of 28 had at lease one ECG on placebo with a QTc interval = 440 msec. On the average, the QTc fluctuated 56 msec in each patient during placebo administration. From the observed placebo variability, we calculated that an increase in QTc of=35 msec while receiving drug therapy is likely to represent a drug effect at the 95% confidence interval.

Classification by type of ventricular arrhythmia predicts frequency of adverse cardiac events from flecainide

Antiarrhythmic therapy is known to be associated with a significant risk of adverse cardiac reactions, including a proarrhythmic response. This study assessed in 1,330 patients followed up for 292 +/- 393 days the predictive value for cardiovascular safety of a system by which patients were classified according to ventricular arrhythmias on entry, presence or absence of organic heart disease and drug dose for flecainide acetate. Baseline arrhythmia subgroups included patients with premature ventricular complexes only, nonsustained ventricular tachycardia, and sustained ventricular tachycardia. Proarrhythmic events occurred in 6.8% of patients overall and were serious in 2.3% and lethal in 1.0%. However, proarrhythmia was highly dependent on arrhythmia class on entry: serious nonlethal proarrhythmic events occurred in 6.6% of patients with sustained ventricular tachycardia, only 0.9% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes (p less than 0.01). Proarrhythmic death occurred in 3.1% of patients with sustained ventricular tachycardia, 0.2% with nonsustained ventricular tachycardia and 0% with premature ventricular complexes only (p less than 0.01). Proarrhythmia was also influenced by the presence of structural heart disease: serious nonlethal proarrhythmia occurred in 2.6% of patients with versus 0.4% of those without organic heart disease, and death occurred in 1.2 versus 0%, respectively. These adverse events were also dependent on dosing regimen. Flecainide caused premature discontinuation due to new or worsened heart failure in 1.4% of patients, all with underlying organic heart disease; however, heart failure was not clearly related to dose or type of arrhythmia. Symptomatic conduction disturbances occurred in 2.2%, and were predicted by preexistent sinus node disease but not by other baseline features.(ABSTRACT TRUNCATED AT 250 WORDS)

Two dimensional echocardiography in mitral, aortic and tricuspid valve prolapse: The clinical problem, cardiac nuclear imaging considerations and a proposed standard for diagnosis

The mitral valve prolapse syndrome may present with a variety of clinical manifestations and has proved to be a common cause of nonspecific cardiac symptoms in clinical practice. Primary and secondary forms must be distinguished. Myxomatous degeneration appears to be the common denominator of the primary form. The diagnostic standard of this form has not previously been defined because the detection of mitral leaflet tissue in the left atrium (prolapse) on physical examination or angiography is nonspecific. M mode echocardiography has greatly enhanced the recognition of this syndrome but has not proved to be the best diagnostic standard because of its limited view of mitral valve motion. The advent of two dimensional echocardiography has provided the potential means for specific identification of the mitral leaflet motion in systole and can be considered the diagnostic standard for this syndrome. Primary myxomatous degeneration with leaflet prolapse is not localized to the mitral valve. Two dimensional echocardiography has detected in preliminary studies tricuspid valve prolapse in up to 50 percent and aortic valve prolapse in about 20 percent of patients with idiopathic mitral valve prolapse.