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Biomedical subjects

E G Giardina

Publications and source records attributed to E G Giardina.

At least 19 recordsLinked to original sources
PubMed1995

Increased early mortality in women undergoing cardiac transplantation.

BACKGROUND: To evaluate factors that explain sex differences affecting mortality after cardiac transplantation, a retrospective analysis of adult patients undergoing orthotopic cardiac transplantation was undertaken at the Columbia-Presbyterian Medical Center. METHODS AND RESULTS: The study population consisted of 379 patients (75 women, 304 men) > or = 18 years of age who survived for > or = 48 hours after undergoing orthotopic cardiac transplantation between March 1985 and March 1992. The following were analyzed: incidence of death and treated rejection episodes, donor and recipient cytomegalovirus (CMV) matches, use of OKT3 induction therapy, and donor and recipient HLA mismatches. Women 49 +/- 12 years old and men 47 +/- 12 years old were characterized by differences in race and diagnosis. Women were more likely to be nonwhite (P < .01) and have idiopathic cardiomyopathy than were men (P < .01). A trend toward an increase in first-year rejection frequency was seen in women compared with men (P = .08). Overall actuarial survival was significantly reduced in women after transplantation (P < .05). At 36 months, female actuarial survival was 64 +/- 7% versus 76 +/- 3% for men (P < .05). The majority of patients in this study did not receive CMV prophylaxis. Univariate analysis revealed that only CMV(+) donor status and the use of OKT3 induction therapy affected survival in women. Multivariate analysis revealed a marked reduction in survival in female recipients of CMV(+) donors given OKT3 induction therapy. At 36 months, only 25% of women were still alive compared with 86% of women with neither risk factor (P < .001). Even without OKT3 induction there was markedly reduced survival in women with mismatched CMV status, ie, CMV(-) recipients of CMV(+) donors; 17% survival after 36 months versus 86% in women who were CMV(+) recipients (P < .05). Although at this institution during the study time period, CMV prophylaxis was not routinely employed and OKT3 induction was selectively used in higher-risk patients, conclusions regarding differences in outcome that are sex dependent are valid. CONCLUSIONS: (1) Women are at risk for reduced actuarial survival up to 3 years after cardiac transplantation. (2) Univariate analysis shows that women are selectively at risk for death when receiving hearts from CMV(+) donors and after receiving OKT3 induction therapy. (3) Multivariate analysis reveals that women are at even greater risk for death when receiving hearts from CMV(+) donors in conjunction with OKT3 induction therapy. (4) In the absence of OKT3 use, the greatest risk of death occurs in CMV(-) women transplanted with CMV(+) donor hearts. (5) When female to male survival curves are compared, factors that influenced survival in women did not appear to be problematic in men.

Actuarial Analysis↗
PubMed1994

Moricizine concentration to guide arrhythmia treatment: with attention to elderly patients.

To test the relationship between plasma moricizine concentration and the electrocardiogram (ECG) and arrhythmia suppression, 17 symptomatic cardiac patients with 30 or more ventricular premature complexes per hour were studied. Seven patients were mature adults, less than 60 years of age; and ten were elderly adults, more than 60 years of age. During steady-state moricizine therapy, patients had plasma moricizine concentration determined over a dosing interval, and had standard 12-lead ECG and a 24-hour ambulatory ECG recorded. The mean moricizine dose was 215 +/- 29 mg every 8 hours; mean maximal moricizine concentration was 1.4 +/- 0.84 micrograms/ml; and mean t1/2 beta was 1.5 +/- 0.7 hours. Baseline age-related differences were found, including prolonged electrocardiographic intervals (PR and QRS) (P < .05), increased ventricular arrhythmias (P < .05), and reduction in creatinine clearance (P < .05) in the elderly. Compared with pretreatment values, PR (P < .05) and QRS (P < .05) prolongation was observed, and was more marked in elderly patients. Over a dosing interval, there were dynamic changes on the ECG that paralleled plasma moricizine concentration; that is, peak and nadir intact moricizine concentration occurred simultaneously with ECG changes: QRS and JTc prolonged (P < .05), and PR prolongation approached significance (P = 0.09). Suppression of ventricular premature complexes of 80% or more occurred in 15 patients, and ventricular tachycardia was abolished in 10 of 12 patients. Probit analysis revealed that the therapeutic antiarrhythmic concentration ranged from 0.20 to 3.6 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effects of desipramine on autonomic control of the heart.

OBJECTIVE: To assess the effects of desipramine (DMI) on autonomic control of the heart. METHODS: Blood pressure, RR interval (the time between successive heart beats), and RR interval variability, a noninvasive measure of autonomic control of the heart, were assessed in 13 subjects younger than 30 years old. RESULTS: DMI treatment was associated with an increase in blood pressure, a decrease in RR interval, and a decline in low and high frequency RR interval variability. CONCLUSIONS: These preliminary data suggest that, in young people, DMI treatment produces a substantial decrease in parasympathetic input to the heart and an increase in the ratio of sympathetic to parasympathetic input, changes that in certain circumstances have been associated with an increased risk of arrhythmia. In exploring the cardiac effects of the tricyclic antidepressants (TCAs) in young people, the impact of TCAs on autonomic input to the heart should be examined.

Adolescent↗
PubMed1991

Time course of moricizine's effect on signal-averaged and 12 lead electrocardiograms: insights into mechanism of action.

The mechanism of action of moricizine, a new antiarrhythmic agent used in the Cardiac Arrhythmia Suppression Trial, is incompletely characterized. In addition, because moricizine is extensively metabolized, plasma moricizine concentration has an unknown relation to myocardial drug effect. Signal-averaged and standard electrocardiograms (ECGs) were used to monitor moricizine's myocardial effects in 16 patients with frequent ventricular premature complexes taking 600 to 900 mg daily. Three signal-averaged ECG variables were measured: total filtered QRS duration (fQRS), root-mean-square voltage in the terminal 40 ms of the QRS complex (V40) and the terminal low amplitude duration less than 40 microV (LAS). At steady state, plasma samples were collected and serial recordings of signal-averaged and standard ECGs were taken at 0, 1, 2, 4, 6 and 8 h after moricizine administration. A 24 h ambulatory ECG was recorded throughout the test period. Moricizine prolonged the fQRS (p less than 0.05) and decreased the V40 (p less than 0.05) of the signal-averaged ECG and prolonged the QRS (p less than 0.05) and corrected JT (JTc) intervals (p less than 0.05) of the standard ECG. The time course of the signal-averaged and standard ECG variables paralleled plasma moricizine concentration; that is, the maximal changes occurred at 1 to 2 h and declined to time 0 values at 8 h. The maximal changes were: fQRS (+8%), V40 (-33%), QRS (+8%) and JTc (+4%). Thus, dynamic changes were observed for intraventricular conduction (fQRS, QRS) and ventricular repolarization (JTc) over the dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Complexes, Premature↗
PubMed1991

Cardiovascular effects of bupropion in depressed patients with heart disease.

OBJECTIVE: The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients. METHOD: The subjects were 36 inpatients with DSM-III major depression and preexisting left ventricular impairment (N = 15), ventricular arrhythmias (N = 15), and/or conduction disease (N = 21). The patients continued their cardiac drug regimens and received bupropion for 3 weeks (mean +/- SD dose = 442 +/- 47 mg/day). Cardiovascular functioning was measured by pulse, blood pressure, high-speed ECG, 24-hour portable ECG, and radionuclide angiography. RESULTS: Although bupropion caused a rise in supine blood pressure, it did not cause significant conduction complications, did not exacerbate ventricular arrhythmias, had a low rate of orthostatic hypotension, and had no effect on pulse rate. However, bupropion treatment was discontinued for 14% of the patients because of adverse effects, including exacerbation of baseline hypertension in two patients. CONCLUSIONS: The cardiovascular profile of bupropion may make this drug a useful agent in the treatment of the depressed patient with preexisting cardiovascular disease. Further studies, with longer durations of bupropion treatment and more subjects, are needed to confirm these findings.

Aged↗
PubMed1991

Is doxepin a safer tricyclic for the heart?

BACKGROUND: Many clinicians believe that doxepin is the safest tricyclic with respect to cardiovascular effects. This belief has persisted for two decades despite the absence of rigorous prospective evaluation. METHOD: To address this issue, the authors studied the cardiovascular effects of doxepin in 32 depressed patients with preexisting left ventricular impairment, ventricular arrhythmias, and/or conduction disease. RESULTS: Doxepin (1) did not have a robust effect on heart rate, (2) did not adversely affect left ventricular function, (3) did have a significant antiarrhythmic effect, (4) slowed cardiac conduction, and (5) caused a significant increase in orthostatic hypotension. Five (16%) of the 32 patients dropped out due to cardiovascular side effects. The overall dropout rate was 41%. CONCLUSIONS: The cardiovascular effects of doxepin in depressed patients with heart disease are comparable to those documented for imipramine and nortriptyline. Doxepin afforded no greater margin of cardiovascular safety; in fact, the drug was poorly tolerated by this patient population.

Aged↗
PubMed1990

Low dose quinidine-mexiletine combination therapy versus quinidine monotherapy for treatment of ventricular arrhythmias.

Low dose quinidine-mexiletine combination therapy was compared with quinidine monotherapy in 15 patients with frequent ventricular premature complexes and nonsustained ventricular tachycardia in a dose escalation cross-over study. Oral combination therapy was initiated with quinidine gluconate (165 mg) plus mexiletine (150 mg) every 8 h. If ventricular premature complexes were not suppressed greater than or equal to 80% and nonsustained ventricular tachycardia greater than or equal to 90%, the dose was increased to a maximum of 330 mg of quinidine plus 200 mg of mexiletine. Quinidine monotherapy was initiated with 330 mg and escalated to a maximum of 660 mg every 8 h if criteria for effectiveness were not met. Combination quinidine-mexiletine therapy suppressed 80% of ventricular premature complexes in 13 of 14 patients and suppressed 100% of episodes of ventricular tachycardia in 6 of 8 patients (mean quinidine dose 200 +/- 70 mg; mean mexiletine dose 146 +/- 24 mg every 8 h). The mean effective trough quinidine and mexiletine concentration was 1.0 +/- 0.7 and 0.9 +/- 0.4 microgram/ml, respectively. Monotherapy was less effective; that is, greater than or equal to 80% suppression of ventricular premature complexes was observed in 5 of 15 patients and 100% suppression of ventricular tachycardia in 2 of 9 patients. The mean quinidine monotherapy dose was 462 +/- 155 mg every 8 h; the mean quinidine concentration was 1.8 +/- 0.8 microgram/ml. Adverse systemic effects occurred in 3 patients on quinidine-mexiletine therapy and in 11 on quinidine monotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1990

Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation.

Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability.

Amiodarone↗
PubMed1987

Indecainide compared with quinidine for chronic stable ventricular arrhythmias secondary to coronary artery disease or to cardiomyopathy.

Indecainide, a new type Ic antiarrhythmic agent, and quinidine sulfate were compared in a randomized double-blind parallel study. Cardiac patients with greater than or equal to 30 ventricular premature complexes per hour hour received indecainide, 50 mg, or quinidine, 200 mg every 6 hours, and the doses were increased until more than 80% suppression was noted, adverse effects occurred or a maximal dose of 100 mg of indecainide or 400 mg of quinidine given every 6 hours. Efficacy was achieved in 8 of 10 taking indecainide (p less than 0.05) and 7 of 9 taking quinidine (p less than 0.05). At least 90% of episodes of ventricular tachycardia were suppressed in 4 of 7 patients taking indecainide and 1 of 4 taking quinidine. No adverse effects were observed in the 7 patients who responded to indecainide and the 4 who responded quinidine, resulting in short-term efficacy without adverse effects in 7 patients (70%) taking indecainide and 4 (44%) taking quinidine. The effective or maximal mean daily indecainide and quinidine doses were 190 +/- 32 mg and 1,022 +/- 291 mg, respectively; mean trough indecainide and quinidine concentrations were 617 +/- 247 ng/ml and 3.3 +/- 1.4 micrograms/ml, respectively. Indecainide prolonged mean PR and QRS intervals (p less than 0.05), but not QT and QTc intervals. Quinidine did not change PR or QRS intervals but prolonged QTc interval (p less than 0.05). During dosing, 1 patient discontinued indecainide treatment because of nausea; 3 discontinued quinidine because of gastrointestinal complaints.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1987

Tricyclic antidepressants in depressed patients with cardiac conduction disease.

The observation that fatalities from tricyclic antidepressant (TCA) overdose are associated with heart block and/or arrhythmias has led to concern about the cardiovascular effects of TCAs. Contrary to expectations, studies have shown TCAs to be relatively safe in patients without heart disease. However, it is unclear whether these drugs are also safe in patients with heart disease. This prospective study compared the risk of cardiovascular complication at therapeutic plasma concentrations of TCAs in 196 depressed patients, 155 with normal electrocardiograms and 41 with either prolonged PR interval and/or bundle-branch block. The prevalence of second-degree atrioventricular block was significantly greater in patients with preexisting bundle-branch block (9%) than in patients with normal electrocardiograms (0.7%). Orthostatic hypotension occurred significantly more frequently with imipramine than with nortriptyline, and in patients with heart disease.

Antidepressive Agents, Tricyclic↗
PubMed1987

Cardiovascular effects of doxepin in cardiac patients with ventricular arrhythmias.

The effect of doxepin on ventricular arrhythmias, the ECG, and left ventricular function was evaluated in 10 cardiac patients with symptoms with frequent ventricular premature depolarizations in a dose-ranging protocol. Four patients (40%) had greater than or equal to 80% ventricular premature depolarization suppression; four of eight with pairs and four of six with ventricular tachycardia had greater than or equal to 90% suppression. The mean maximal doxepin dose was 115 +/- 41 mg/day; mean nadir total doxepin concentration was 61 +/- 48 ng/ml and mean nadir total desmethyldoxepin concentration was 51 +/- 42 ng/ml. Doxepin increased the heart rate and the PR, QRS, and QTc intervals of the surface ECG (P not significant). There was no significant change in resting mean left ventricular ejection fraction with doxepin: 41% +/- 15% vs. 43% +/- 19% (P not significant). Complaints of sedation (eight patients) limited dose ranging and tolerance to the drug. Although doxepin suppressed ventricular premature depolarizations in four patients, marked sedation limits its usefulness for primary treatment of arrhythmias in this population.

Adult↗
PubMed1987

Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure.

There has been a long-standing concern over the cardiovascular effects of tricyclic antidepressants, particularly in patients with preexisiting cardiac disease. Recent studies have demonstrated that imipramine causes no deleterious effect on ejection fraction as determined by radionuclide angiography in patients with impaired left ventricular function (LVF). However, the high rate of severe orthostatic hypotension induced by imipramine makes use of the drug problematic in these patients. Bupropion is a new antidepressant of the aminoketone class which is structurally unrelated to the tricyclics and which is relatively free of cardiac side effects in healthy depressed patients. We compared imipramine and bupropion in 10 depressed patients with impaired LVF in a random, double-blind crossover study. Neither imipramine nor bupropion adversely affected ejection fraction or other indices of LVF. However, as previously reported, severe orthostatic hypotension requiring discontinuation of drug developed in 50% of patients on imipramine. This difficulty did not occur with bupropion. From a cardiac perspective, bupropion may offer a safe alternative to imipramine in depressed patients with congestive heart failure.

Aged↗
PubMed1986

Nortriptyline in depressed patients with left ventricular impairment.

Previous studies of the effect of tricyclic antidepressants on left ventricular function in depressed patients with moderate to severe ventricular impairment have focused primarily on imipramine hydrochloride. In a prior study, we found that although imipramine had no effect on ejection fraction as measured by first-pass radionuclide angiography, the treatment could not be tolerated by 50% of the patients because of intolerable drug-induced orthostatic hypotension. Nortriptyline hydrochloride is an effective antidepressant that, in depressed patients without heart disease, causes significantly less orthostatic hypotension than imipramine. To see if this advantage could be safely extended to patients with congestive failure, we measured the effect of nortriptyline on ejection fraction and blood pressure in 21 depressed patients with left ventricular impairment. Ejection fraction was unchanged by nortriptyline treatment, and orthostatic hypotension developed in only one (5%) of 21 patients. Nortriptyline emerges as a relatively safe treatment for depression in patients with left ventricular impairment.

Aged↗
PubMed1986

The antiarrhythmic effect of nortriptyline in cardiac patients with ventricular premature depolarizations.

The effect of nortriptyline against ventricular arrhythmias was determined in 16 cardiac patients with 30 or more ventricular premature depolarizations per hour. Nortriptyline was administered orally, 0.5 mg/kg body weight per day, and increased by 0.5 mg/kg per day every third day until ventricular premature depolarizations were suppressed (greater than or equal to 80%), adverse effects occurred or a total daily dose of 3.5 mg/kg per day was given. Each patient had daily 24 hour continuous electrocardiograms, 12 lead standard electrocardiograms and physical examination; blood pressure was measured in the supine and standing position four times a day. Each patient also had radionuclide angiography at rest to measure ejection fraction before and at the effective or maximal dose. Thirteen patients (81%) had an antiarrhythmic response and 11 met the study criterion of at least 80% improvement. Doses ranged from 50 to 200 mg/day (mean 111 +/- 45), steady state plasma concentration ranged from 46 to 410 ng/ml (mean 153 +/- 96) and half-life of elimination of nortriptyline was 4 to 22 hours (mean 13 +/- 4). Administration of nortriptyline did not depress mean ejection fraction (before 42 +/- 12%, after 41 +/- 12%); it was associated with an orthostatic decrease in systolic blood pressure (mean -13 +/- 13 mm Hg). Nortriptyline is an effective antiarrhythmic agent which may be given twice a day even in patients with impaired ventricular function.

Adult↗
PubMed1985

Time course of alpha-1-acid glycoprotein and its relation to myocardial enzymes after acute myocardial infarction.

The acute phase reactant, alpha-1-acid glycoprotein, binds to a number of basic antiarrhythmic drugs, including lidocaine, quinidine, propranolol, imipramine and disopyramide. Binding to alpha-1-acid glycoprotein accounts for a decrease in free drug fraction and may alter the expected concentration: response relation of drugs particularly when there are unpredictably large or rapid changes in alpha-1-acid glycoprotein. To determine the time course and magnitude of alpha-1-acid glycoprotein for 1 month after acute myocardial infarction (AMI), blood samples were collected from 27 patients, 14 with AMI and 13 with a chest pain syndrome but no AMI. Patients with AMI had a significant increase in alpha-1-acid glycoprotein after 72 hours (mean 153 +/- 35 mg/dl) (p less than 0.05), and the maximum was observed on day 7 (mean 165 +/- 53 mg/dl) (p less than 0.05), returning to baseline by 28 days. There was no significant change in alpha-1-acid glycoprotein in patients with chest pain but no AMI. Regression analysis showed a significant relation between creatine kinase (p less than 0.005) and lactic dehydrogenase (p less than 0.001) vs alpha-1-acid glycoprotein indicating alpha-1-acid glycoprotein concentration is high in patients with large AMI. Changes in binding resulting from alpha-1-acid glycoprotein during AMI could account for misinterpretation of total drug concentration and response to antiarrhythmic drugs acutely, during convalescence and at discharge.

Adult↗
PubMed1985

Effect of imipramine and nortriptyline on left ventricular function and blood pressure in patients treated for arrhythmias.

The effect of imipramine or nortriptyline on left ventricular function and orthostatic blood pressure was evaluated in 20 nondepressed cardiac patients treated for ventricular premature depolarizations (VPDs). Drug was administered by mouth and dose ranging used, 1 mg/kg/day (imipramine) or 0.5 mg/kg/day (nortriptyline), was increased after four doses (imipramine) or six doses (nortriptyline) until greater than 80% suppression of VPDs or adverse effects occurred or until a maximum dose of 5 mg/kg/day (imipramine) or 3.5 mg/kg/day (nortriptyline) was given. Fourteen (70%) had greater than 80% VPD suppression, five had less than 80% improvement (range 25% to 77%), and one had a VPD frequency increase of 6%. Mean daily imipramine dose was 210 +/- 103 mg and mean nortriptyline dose was 100 +/- 29 mg. Neither drug significantly changed mean ejection fraction or peak systolic pressure end-systolic volume ratio by radionuclide angiogram. Both reduced standing systolic blood pressure: mean change after imipramine was 26 mm Hg (NS), and after nortriptyline, 14 mm Hg (p less than 0.05). Drug was discontinued in two patients because of symptomatic orthostatic blood pressure change greater than 30 mm Hg. There was not a significant relationship between dose, drug concentration, or functional class and orthostatic change in systolic blood pressure but there was for age (p less than 0.05). These observations suggest that even cardiac patients with impaired systolic function may take imipramine or nortriptyline for VPDs; however, frequent blood pressure measurement is advised, particularly in older patients.

Adult↗