Search PubMed⌕ Search

Biomedical subjects

J Morganroth

Publications and source records attributed to J Morganroth.

At least 37 records · Page 2Linked to original sources
PubMed1993

Variability of the QTc interval: impact on defining drug effect and low-frequency cardiac event.

Prolongation of the QT interval corrected for heart rate (QTc) can lead to the development of torsades de pointes, a life-threatening form of polymorphic ventricular tachycardia. However, the QTc interval duration exhibits a high degree of spontaneous variability and is not necessarily a direct predictor of the risk of torsades. This observation holds implications for the assessment of the potential proarrhythmic effects of noncardiac pharmacologic agents. To date, the antihistamine terfenadine is the only noncardiac drug that has undergone a comprehensive and systematic evaluation related to the consequences of its causing QTc prolongation. The results suggest that QTc prolongation resulting solely from terfenadine at clinical doses does not have an important impact on clinically relevant endpoints. The risk of serious ventricular arrhythmias with terfenadine using epidemiologic data is the same or less than that associated with traditional first-generation antihistamines. The risk of a clinical cardiac event (QTc prolongation, ventricular arrhythmias, syncope, or sudden death) with terfenadine is similar to that of other antihistamines. Factors associated with increased risk in patients taking terfenadine include significant liver disease, hypokalemia, overdose, and concomitant administration of ketoconazole-like agents or erythromycin; use of terfenadine is relatively contraindicated in these settings. No increased risk of serious arrhythmias has been confirmed in conjunction with the use of terfenadine in patients with cardiac disease.

Adult↗
PubMed1993

Indications for antiarrhythmic suppression of ventricular arrhythmias: a definition of life-threatening ventricular arrhythmias.

A surprising finding of the Cardiac Arrhythmia Suppression Trial (CAST), reported in 1989, is that well-tolerated and effective antiarrhythmic drugs may also be associated with an increase in mortality due to arrhythmia. Consequently, attention has been focused on the importance of the benefit-versus-risk assessment of such therapy. The benefits of antiarrhythmic therapy are reduction or elimination of arrhythmia-caused symptoms (both hemodynamic and nonhemodynamic) and of the associated risk of death. The risks of such treatment include not only noncardiac adverse effects and organ toxicity, but also early cardiac effects (proarrhythmia, heart failure, and conduction defects), as well as the newly recognized potential for late proarrhythmia or late arrhythmic death. Unfortunately, as the potential benefits of antiarrhythmic therapy increase in patients with poorer left ventricular function (owing to their being at greater risk for sudden death), the effectiveness of suppression decreases and the incidence of life-threatening complications increases. The impact of this benefit-risk profile is that the indication for most currently approved antiarrhythmic drugs needs to be limited to those patients with definite life-threatening ventricular arrhythmias that take the form of sustained ventricular tachyarrhythmias with associated hemodynamic symptoms. Broadening this indication to include patients with probable life-threatening or even possible life-threatening arrhythmias must await the availability of drugs with better benefit-risk profiles.

Anti-Arrhythmia Agents↗
PubMed1993

Diagnostic accuracy of seismocardiography compared with electrocardiography for the anatomic and physiologic diagnosis of coronary artery disease during exercise testing.

A multicenter study was performed to compare the diagnostic accuracy of a new technique, seismocardiography, with that of electrocardiography for physiologically and anatomically significant ischemic coronary artery disease (CAD) during exercise stress testing. Five participating centers enrolled 129 patients who had simultaneous seismocardiograms and 12-lead electrocardiograms at the time of their exercise treadmill stress tests. Two different definitions of CAD were used: anatomic and physiologically significant disease. The presence of anatomically significant CAD (> or = 50% diameter stenosis) was documented by coronary angiography. Physiologically significant CAD was defined as present in the same 129 patients when coronary arteriography (> or = 50% diameter stenosis) and thallium-201 scintigraphy (defect on initial postexercise images) were both abnormal. Seismocardiography had a significantly better sensitivity for detecting anatomic CAD than did electrocardiography (73 vs 48%; p < 0.001), without loss of specificity (78 vs 80%; p = NS). Exercise seismocardiography added significant incremental diagnostic information beyond that provided by exercise electrocardiography. Seismocardiography was more sensitive (without less specificity) in women and in patients who did not achieve maximal predicted heart rate. In patients with physiologically significant CAD, the seismocardiogram was also significantly more sensitive (78%) than was the electrocardiogram (55%) (p < 0.02), without loss of specificity (84 vs 74%). Seismocardiography significantly improved sensitivity for the detection of anatomic and physiologic CAD. It is easy to perform and may be a clinically useful adjunct in exercise stress testing.

Coronary Angiography↗
PubMed1992

Early and late proarrhythmia from antiarrhythmic drug therapy.

Antiarrhythmic drug therapy is used with the hope of suppressing arrhythmias and therefore decreasing their associated symptoms or prolonging life. Unfortunately, many antiarrhythmic drugs have the opposite effect of exacerbating or provoking arrhythmias, a phenomenon that is termed proarrhythmia when such an event is specifically due to the drug in use. Early proarrhythmic events (within 30 days of initiation of drug use) have been reasonably well characterized and are predicted by either type of drug employed or the nature of the patient's cardiac disease and arrhythmia type. Late proarrhythmic events, as defined by placebo-controlled trials, have now been recognized as an increased risk of arrhythmic death in patients on antiarrhythmic drugs after many months of therapy. Initially, this late proarrhythmic event was identified with encainide and flecainide, but now several new studies have demonstrated that the risk of late proarrhythmia of comparable magnitude may be present in patients subjected to commonly used drugs, such as quinidine, mexelitine, etc. At present, only moricizine and the class II drugs (beta-adrenergic blockers) appear not to have this potential late proarrhythmic response. Therefore, before instituting antiarrhythmic drug therapy, the physician must be able to quantitate the degree of proarrhythmia and other risks of such therapy, as compared to their potential benefit, to define the proper indications for these agents.

Anti-Arrhythmia Agents↗
PubMed1992

The relationship of anticoagulation level and complications after successful percutaneous transluminal coronary angioplasty.

The degree of anticoagulation and its effect on the frequency of abrupt coronary artery closure, coronary ischemia, bleeding complications requiring transfusion, and death were examined in 336 patients after elective percutaneous transluminal coronary angioplasty (PTCA). All patients received a bolus of 10,000 U of heparin at the beginning of the procedure followed by a continuous infusion of 2000 U/hr. At the conclusion of the procedure the infusion was reduced to 1000 U/hr and continued for 18 to 24 hours at which time the heparin infusion was suspended to allow removal of arterial and venous access sheaths. Partial thromboplastin time (PTT) was examined while patients continued to receive the heparin infusion. There was a variable degree of PTT prolongation in response to a standard dose of heparin with a range of 34 seconds to "greater than 150 seconds." Patients were divided into two groups according to the degree of heparin-induced PTT prolongation: group A included 271 patients with PTT greater than or equal to 3 times the control value, and group B comprised 65 patients with PTT less than 3 times the control value. Ischemic complications were analyzed on day 1 after PTCA and at hospital discharge. Bleeding complications and mortality were examined only at hospital discharge. There was a significant reduction in the incidence of abrupt coronary artery closure in group A on day 1 (1.5% vs 10.7%, p less than 0.001) and at hospital discharge (2.6% vs 10.7%, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1992

Proarrhythmic effects of antiarrhythmic drugs: evolving concepts.

Although antiarrhythmic drugs are prescribed to reduce an arrhythmia, they may have the paradoxic effect of actually exacerbating that arrhythmia or causing new or more serious forms. This effect is known as "proarrhythmia." Proarrhythmic events may be segregated into those that occur "early" after therapy (within 30 days) and those that occur "late," after many months of therapy and manifesting as a fatal event (an increased risk of sudden cardiac death). The ability of the physician to predict drug proarrhythmia and its severity depends on the class of antiarrhythmic drug chosen, the type of ventricular arrhythmia to be treated, and the severity of the patient's underlying left ventricular dysfunction. Before the start of antiarrhythmic therapy, the physician must be able to quantitate the degree of proarrhythmic risk so that the benefit/risk ratio of such drug use can be determined.

Anti-Arrhythmia Agents↗
PubMed1992

Drug-induced early and late proarrhythmia.

Proarrhythmia is the provocation of a new arrhythmia or the exacerbation of a spontaneously occurring arrhythmia due to drug therapy. A drug's toxic effect may occur early after its initiation, and specific definitions have been offered to detect its presence. Primary and secondary forms of proarrhythmia as well as the type of early proarrhythmic events (fatal, serious, and nonserious) have been recognized. More recently, the concept of a late proarrhythmic event (enhanced arrhythmic death) has been defined using placebo-controlled trials. This late proarrhythmic response is extremely important in defining the benefit versus risk ratio that is the key to proper use of drug therapy.

Arrhythmias, Cardiac↗
PubMed1991

Events in the cardiac arrhythmia suppression trial: baseline predictors of mortality in placebo-treated patients.

Patients randomized to placebo in the encainide and flecainide arms of the Cardiac Arrhythmia Suppression Trial (CAST) have been found to have a relatively low 1-year mortality rate of 3.9% in comparison with previous studies of patients in the postmyocardial infarction period. To determine the comparability of CAST with previous studies, baseline variables were examined in the 743 patients randomized to placebo in the flecainide and encainide arms of CAST. Twenty-three baseline characteristics were correlated with major outcome events: arrhythmic death (16 events), total mortality (26 events) and congestive heart failure (51 events). On multivariate analysis the risk of new or worsening congestive heart failure was significantly associated with diuretic use, diabetes, high New York Heart Association functional class, age, prolonged QRS duration and low ejection fraction. The risk of arrhythmic death or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, history of heart failure, use of digitalis, diabetes and prolonged QRS duration. Total mortality or resuscitated cardiac arrest was significantly associated with an index Q wave myocardial infarction, diabetes, ST segment depression, high functional class, prolonged QRS duration and low ejection fraction. The variables at baseline associated with mortality from all causes or arrhythmic death or resuscitated cardiac arrest and heart failure in the CAST placebo-treated patients are similar to those identified in previous postmyocardial infarction studies. Thus, the observation of increased mortality in CAST associated with the administration of encainide and flecainide for suppression of ventricular premature depolarizations is probably applicable to any comparably defined group of patients in the postmyocardial infarction period.

Aged↗
PubMed1991

Effect of angiotensin converting enzyme inhibition on the incidence of restenosis after percutaneous transluminal coronary angioplasty.

To determine whether angiotensin converting enzyme (ACE) inhibition may reduce the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we retrospectively identified 322 consecutive patients who underwent a successful procedure from June 1988 to December 1989. No patients developed chest pain, ST segment elevation, positive cardiac enzymes, or other evidence of abrupt vessel closure following the PTCA. All patients received intravenous heparin after PTCA and aspirin was begun on the day prior to PTCA. Patients were separated into two groups: those at hospital discharge incidentally treated for hypertension or heart failure with ACE inhibitors (n = 36), and those treated with a drug regimen which did not include ACE inhibitors (n = 286). The two groups were similar with respect to age (61 +/- 13.5 vs. 60 +/- 12.5, p = NS) and other demographic characteristics. Restenosis, defined as the presentation to a physician with symptoms of angina within 6 months of the PTCA and the finding on repeat catheterization of a significant restenosis at the site of the PTCA, occurred in 30% of the patients who were discharged on a drug regimen which did not include ACE inhibitors vs. 3% (p less than .05) in those treated with an ACE inhibitor. Thus, it appears that the use of ACE inhibitors may significantly reduce the incidence of restenosis after successful PTCA.

Aged↗
PubMed1991

A multicenter evaluation of the A&D TM-2420 ambulatory blood pressure recorder.

The A&D TM-2420 (A&D Engineering, Milpitas, CA) is an automatic, portable, noninvasive blood pressure (BP) recorder which uses a dual microphone system for the detection of Korotkoff sounds. Its accuracy and clinical performance were assessed in a multicenter study that also addressed issues such as observer agreement and the effects of age, arm circumference, heart rate, posture, and blood pressure level on the observer-device differences. We compared 906 simultaneous, same-arm BP measurements in 151 subjects using the TM-2420 versus two skilled clinicians per site using a teaching stethoscope. The agreement between the TM-2420 and mercury column determinations were within 10 mm Hg for 86 to 91% of systolic readings and 91 to 94% of diastolic readings, depending on the posture; a level of agreement which would receive a 'B+' grade from the recent British Hypertension Society guidelines. The limits of agreement (2 standard deviations about the mean difference) for systolic BP between observers and the TM-2420 tended to be greater for the standing position (-20 to 15 mm Hg) compared to supine (-14 to 12 mm Hg) and seated (-13 to 8 mm Hg) positions. Limits of agreement between the observers and device were not dependent upon age, heart rate, arm size, or blood pressure level. Twenty-four-hour blood pressure monitoring in two of the four centers demonstrated an error code rate of 3.4%, excluding 'retries' that are one of the device's features. These data demonstrate an acceptable level of accuracy and performance of the sixth generation of the TM-2420 for use in clinical practice and research.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis.

BACKGROUND: The interim results of the Cardiac Arrhythmia Suppression Trial requires physicians to use a higher threshold for employing antiarrhythmic agents in the treatment of benign or potentially lethal ventricular arrhythmias. Many have managed patients by switching to the traditional class I quinidine despite its known proarrhythmic tendency. METHODS AND RESULTS: To evaluate the relation between quinidine therapy and mortality in patients with benign or potentially lethal ventricular arrhythmias, we performed a meta-analysis on four randomized double-blind active controlled parallel trials evaluating 1,009 patients in which quinidine (n = 502) was compared to flecainide (n = 141), mexiletine (n = 246), tocainide (n = 67), and propafenone (n = 53). All four trials had similar patient selection, protocols, and methodology (e.g., placebo lead-in and Holter monitoring) but varying lengths of drug exposure. A total of 12 deaths were reported on quinidine and four deaths on the other drugs: two on mexiletine, one on flecainide, and one on tocainide. The statistical analysis of the mortality rates was based on techniques for combining data across separate strata. Based on maximum likelihood estimation, the combined risk of dying on quinidine was statistically significantly higher compared to the other four drugs with a risk difference of 1.6%. The 95% confidence interval was 0-3.1% (p = 0.05). The likelihood ratio test for uniformity of the risk difference across strata showed the trials to be homogeneous (p = 0.88). There was one death recorded for the placebo lead-in period (2 weeks' exposure for 624 patients and 1 week for 385 patients), and seven deaths were reported within 2 weeks on active drug treatment--six on quinidine and one on mexiletine. Furthermore, proarrhythmia was reported in 20 patients on quinidine versus 11 patients on the four other drugs (p = 0.09). CONCLUSIONS: These data suggest that quinidine may have an adverse effect on mortality as compared to other class I antiarrhythmic agents and that individualized patient selection for the use of this agent be carefully weighed relative to its potential for harm and benefit.

Anti-Arrhythmia Agents↗
PubMed1990

Dose effect of moricizine on suppression of ventricular arrhythmias.

To define the pharmacologic properties of moricizine in patients with benign or potentially lethal ventricular arrhythmias, 1,072 patients in the moricizine data base through February 1987 were evaluated. In dose-ranging and titration trials as well as in a cross-study analysis of th entire data base, the minimally effective dose for moricizine was found to be 600 mg/day and the optimal dose range from 600 to 900 mg/day. The dose efficacy relation plateaued beyond 900 mg/day. With use of a 75% reduction in ventricular premature complex frequency as the definition of a drug responder, 391 of 583 patients (67%) with paired Holter monitors demonstrated overall efficacy. The dose onset of moricizine was between 16 and 20 hours and the dose offset was at approximately 24 hours at the point when 50% of the ventricular arrhythmia frequency returned to baseline. Although moricizine was primarily given on a 3-times-a-day regimen during clinical trials, dose interval evaluation suggested that a twice-a-day regimen may produce the same degree of efficacy although there are limited data regarding comparable safety.

Anti-Arrhythmia Agents↗