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Biomedical subjects

P E Fenster

Publications and source records attributed to P E Fenster.

At least 19 recordsLinked to original sources
PubMed1999

Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation: II. Dense spontaneous echocardiographic contrast (The Stroke Prevention in Atrial Fibrillation [SPAF-III] study).

We analyzed transesophageal echocardiograms from 772 participants in the Stroke Prevention in Atrial Fibrillation (SPAF-III) study, characterizing spontaneous echocardiographic contrast (SEC) in the left atrium or appendage as faint or dense. The association of dense SEC with stroke risk factors and anatomic, hemodynamic, and hemostatic parameters related to specific thromboembolic mechanisms was evaluated by multivariate analysis. Spontaneous echocardiographic contrast was present in 55% of patients and was dense in 13%. Age (odds ratio [OR] 2.4/decade, P <.001), constant atrial fibrillation (OR 6.9, P <.001), history of hypertension (OR 3. 2, P <.001), and current tobacco smoking (OR 2.6, P =.04) were independent clinical predictors of dense SEC. Multivariate analysis of clinical, echocardiographic, and hemostatic parameters yielded age as the sole independent clinical predictor of dense SEC (OR 2. 4/decade, P <.001). Other independent predictors were measures of left atrial/appendage flow dynamics, left atrial size (OR 2.4/cm diameter, M-mode, P <.001), atherosclerotic aortic plaque (OR 2.8, P =.002), and plasma fibrinogen >350 mg/dL (P <.001). Results were similar when SEC of any density was analyzed. In conclusion, SEC occurred in more than half of these patients with prospectively defined nonvalvular atrial fibrillation but was usually faint. Dense SEC was strongly associated with previously reported clinical predictors of stroke, linking them to thromboembolism through atrial stasis. Diverse pathophysiologic factors including atrial stasis, fibrinogen level, and aortic plaque influence SEC.

Aged↗
PubMed1997

Additional antianginal and anti-ischemic efficacy of mibefradil in patients pretreated with a beta blocker for chronic stable angina pectoris.

This study assessed the safety, tolerability, and efficacy of mibefradil when added to beta-blocker monotherapy in patients with chronic stable angina pectoris. Two hundred five patients were randomized to receive double-blind treatment with either placebo (n = 70), mibefradil 25 mg (n = 67), or mibefradil 50 mg (n = 68) for 2 weeks. Exercise tolerance tests (ETTs) were performed at the end of the run-in (baseline) and double-blind treatment periods, and patients maintained an anginal diary. Compared with placebo, treatment with mibefradil 50 mg resulted in significant increases in exercise duration (36 +/- 51 seconds; p = 0.036), time to onset of angina (48 +/- 65 seconds; p = 0.002), and time to persistent 1-mm ST-segment depression (47 +/- 77 seconds; p = 0.004). Greater reductions in heart rate, blood pressure, and the rate-pressure product were more apparent at each stage of the ETT in the 50-mg mibefradil group than in the placebo group. Daily treatment with mibefradil 50 mg was associated with a significant decrease in the number of weekly anginal attacks (-2.1 +/- 4.0, p = 0.020) compared with placebo. The addition of mibefradil to existing beta-blocker therapy was well tolerated. Dizziness was the most frequently reported adverse event in the mibefradil 50-mg dose, and occurred with an incidence of 4.4%. The addition of mibefradil 50 mg, administered once daily, to patients on stable beta-blocker therapy produced additive antianginal and anti-ischemic effects and was well tolerated.

Adrenergic beta-Antagonists↗
PubMed1995

Cardiovascular effects of sevoflurane compared with those of isoflurane in volunteers.

BACKGROUND: Sevoflurane is a new inhalational anesthetic with desirable clinical properties. In some clinical situations, an understanding of the detailed cardiovascular properties of an anesthetic is important, so the authors evaluated the hemodynamic effects of sevoflurane in healthy volunteers not undergoing surgery. METHODS: Twenty-one subjects were randomized to receive sevoflurane, isoflurane, or sevoflurane: 60% N2O. Anesthesia was induced and maintained by inhalation of the designated anesthetic. Hemodynamic measurements were performed before anesthesia, during controlled ventilation, during spontaneous ventilation, and again during controlled ventilation after 5.5 h of anesthesia. RESULTS: A few subjects became excessively hypotensive at high anesthetic concentrations (2.0 minimum alveolar concentration [MAC] sevoflurane, 1.5 and 2.0 MAC isoflurane), preventing data collection. Sevoflurane did not alter heart rate, but decreased mean arterial pressure and mean pulmonary artery pressure. Cardiac index decreased at 1.0 and 1.5 MAC, but in subjects with mean arterial pressure > or = 50 mmHg returned to baseline values at 2.0 MAC when systemic vascular resistance decreased. Sevoflurane did not alter echocardiographic indices of ventricular function, but did decrease an index of afterload. Sevoflurane caused a greater decrease in mean pulmonary artery pressure than did isoflurane, but the cardiovascular effects were otherwise similar. Administration of sevoflurane with 60% N2O, prolonged administration or spontaneous ventilation resulted in diminished cardiovascular depression. CONCLUSIONS: At 1.0 and 1.5 MAC, sevoflurane was well tolerated by healthy volunteers. At 2.0 MAC, in subjects with mean arterial pressure > or = 50 mmHg, no adverse cardiovascular properties were noted. Similar to other contemporary anesthetics, sevoflurane caused evidence of myocardial depression. Hemodynamic instability was noted in some subjects at high anesthetic concentrations in the absence of surgical stimulation. The incidence was similar to that with isoflurane. The cardiovascular effects of sevoflurane were similar to those of isoflurane, an anesthetic commonly used in clinical practice since 1981.

Adult↗
PubMed1993

Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure: the PROMISE Study.

OBJECTIVES: The aim of this study was to determine the prognostic significance of alterations in serum magnesium in patients with moderate to severe congestive heart failure. BACKGROUND: Reductions in serum magnesium have been postulated to play a role in promoting arrhythmias and to have an adverse impact on survival in congestive heart failure, although support for this postulate is lacking. METHODS: Serum magnesium levels were measured in 1,068 patients enrolled in a survival study of class III or IV heart failure at the time of double-blind randomization to milrinone, a phosphodiesterase inhibitor, or placebo. All patients received conventional therapy with digoxin, diuretic drugs and a converting enzyme inhibitor throughout the trial. The median follow-up period was 6.1 months (range 1 day to 20 months). RESULTS: Patients with high serum magnesium (defined as > or = 1.9 mEq/liter, n = 242) were less likely to survive than were patients with a normal magnesium level (n = 627) (p < 0.05, risk ratio = 1.41). Patients with a low magnesium level (defined as < or = 1.5 mEq/liter, n = 199) had no difference in survival compared with the group with a normal magnesium level (p = NS, risk ratio = 0.89). At baseline, the patients in the high magnesium group were older and had more severe functional and renal impairment. An analysis after adjustment for these variables demonstrated no difference in survival comparing the low, normal and high magnesium groups. Although the three groups had no difference in frequency of ventricular tachycardia, length of longest run or frequency of ventricular premature beats on baseline Holter monitoring, the group with hypomagnesemia had more frequent ventricular couplets. CONCLUSIONS: Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure. Hypomagnesemia is associated with an increase in the frequency of certain forms of ventricular ectopic activity, but this is not associated with an increase in clinical events. The higher mortality rate among the patients with hypermagnesemia is attributable to older age, more advanced heart failure and renal insufficiency.

Aged↗
PubMed1989

Antiarrhythmic efficacy of desipramine.

The effect of desipramine on chronic ventricular ectopic depolarizations (VEDs) was studied in 10 patients with at least 30 VEDs per hour. A single-blind, placebo-controlled, dose-ranging protocol was followed. Efficacy was defined as a decrease in VED frequency of at least 75%, base on three 24 hour ambulatory ECGs obtained on each dose. Among seven patients with analyzable data, one responded to 75 mg daily, and three others responded to 150 mg daily. Six of the seven patients demonstrated decreases in VED frequency with increases in desipramine serum concentration. Among five patients with episodes of nonsustained ventricular tachycardia, desipramine completely abolished the episodes in two, and reduced the frequency of episodes by at least 90% in two others. Adverse reactions were common, and necessitated drug discontinuation or dose reduction in five patients. Desipramine has an antiarrhythmic effect in patients with chronic ventricular ectopy, but its clinical utility is limited by adverse effects.

Adult↗
PubMed1989

Cibenzoline for symptomatic ventricular arrhythmias: a prospective, randomized, double-blind, placebo controlled trial and a long term open label study.

To assess the efficacy and safety of cibenzoline, 18 patients with symptomatic premature ventricular complexes (30/h or more) on baseline 48 h Holter monitors were randomized to oral cibenzoline versus placebo. The cibenzoline and placebo doses were increased from 130 to 160 mg bid after one week if premature ventricular complex (PVC) suppression was less than 75%. The double-blind placebo controlled phase (phase 1) lasted for two weeks prior to the open label long term study (phase 2). Efficacy was defined as suppression of at least 75% PVCs, 85% couplets and 90% ventricular tachycardia on follow-up 48 h Holter monitoring. At the six month mark of phase 2, patients were placed on placebo for seven days to evaluate for spontaneous resolution of PVCs. Of the seven patients on cibenzoline in phase 1, four had a positive response, one had partial control (73% suppression of PVCs) and two noted dizziness and withdrew. Of the 11 patients randomized to placebo, nine noted no change, two had a significant decrease in PVCs and one noted dizziness and withdrew. Fifteen patients were enrolled in phase 2 on open label cibenzoline at 130 to 160 mg bid. At a mean follow-up of 17 +/- 4 months (range 12 to 25), eight patients had control of symptomatic ventricular arrhythmias without adverse effects, three patients did not respond to cibenzoline, one had PVC recurrence after initial control on cibenzoline, one died of myocardial infarction without arrhythmias, one had spontaneous resolution of PVCs and one was withdrawn because of poor compliance. In conclusion, cibenzoline is effective in controlling symptomatic PVCs and is moderately well tolerated.

Aged↗
PubMed1988

Transient heart block associated with head trauma.

Atrioventricular nodal block is a rare consequence of head trauma. We report a case of a 63-year-old male with coronary artery disease who sustained a skull fracture. Twelve hours later the cardiac monitor recorded an episode of high-grade atrioventricular block with a ventricular escape rhythm. Subsequent electrophysiologic evaluation revealed no abnormality of atrioventricular nodal conduction nor of intraventricular conduction. Atrioventricular block after head trauma may be caused by enhanced vagal tone.

Creatine Kinase↗
PubMed1987

Enhanced antiarrhythmic efficacy of propafenone when used in combination with procainamide or quinidine.

This study evaluated the efficacy and safety of combining propafenone with procainamide or quinidine for treating ventricular arrhythmias in patients in whom procainamide or quinidine therapy alone failed to suppress arrhythmias. In 30 patients, the addition of propafenone resulted in a significant reduction of premature ventricular contraction (PVC) frequency compared to drug-free baseline (406 PVC/hr vs 33, p less than 0.001) and to procainamide or quinidine monotherapy (211 PVC/hr vs 27, p less than 0.01). Propafenone alone was also more effective than either procainamide or quinidine and resulted in significant suppression of PVC compared to the drug-free state (406 PVC/hr vs 38, p less than 0.001). However, higher propafenone doses were necessary during monotherapy as compared to propafenone therapy combined with procainamide or quinidine (730 mg/day vs 480 mg/day, p less than 0.001). Of the 30 patients, 22 required an increase in propafenone dose during monotherapy as compared to combination therapy. Thus, propafenone is an effective antiarrhythmic agent when used in combination with type IA antiarrhythmic drugs. With these combinations, lower doses of propafenone can be utilized effectively than with propafenone alone.

Adult↗
PubMed1987

Atenolol for ventricular ectopy: a dose-response study.

The antiarrhythmic efficacy, safety, and tolerance of atenolol was evaluated in 32 patients with an average of at least 60 ventricular ectopic depolarizations/hr. Patients received, single-blind, the following treatments for 2 weeks each: placebo and atenolol, 50, 100, and 200 mg daily. A 24-hour ambulatory ECG recording was obtained each week. Reduction in ventricular ectopic frequency by at least 75% occurred in six of 32 patients receiving 50 mg daily, five of 30 patients receiving 100 mg daily, and three of 21 patients receiving 200 mg daily (P = not significant for any paired dose comparison). No patient who failed to respond to a lower dose responded to 200 mg daily. The frequency of ventricular tachycardia was reduced by at least 75% in eight of 17 patients receiving 50 mg daily, seven of 16 patients receiving 100 mg daily, and eight of 11 receiving 200 mg daily (P = not significant for any paired dose comparison). Atenolol was discontinued because of adverse effects in 12 patients. The results indicate that atenolol is more effective in suppressing ventricular tachycardia than in suppressing overall ventricular ectopy.

Adult↗
PubMed1987

Antiplatelet effects of oral diltiazem, propranolol, and their combination.

1. The antiplatelet effects of a single oral dose of the calcium entry blocker diltiazem (60 mg), the beta-adrenoceptor blocker propranolol (40 mg), and their combination were studied in five healthy subjects. 2. Platelet aggregation and ATP release induced by adrenaline and ADP and ADP induced platelet thromboxane A2 generation were significantly inhibited (P less than 0.05) by either diltiazem or propranolol, although propranolol tended to have greater inhibitory effects on platelet function than diltiazem that did not reach statistical significance. 3. Combination therapy resulted in additive antiplatelet effects that were significantly (P less than 0.05) greater than either drug alone. 4. These data indicate that combined administration of a calcium entry blocker and a beta-adrenoceptor blocker results in additive inhibitory effects on platelet function. These effects may mediate part of the therapeutic efficacy of combination therapy in patients with coronary artery disease.

Adenosine Diphosphate↗
PubMed1986

Effects of oral diltiazem on platelet function: alone and in combination with "low dose" aspirin.

The effects of 3 days of oral diltiazem, "low dose" aspirin (40 mg/day), and their combination on platelet function was studied in 5 normal subjects. Both drugs inhibited platelet aggregation and ATP release induced by collagen, epinephrine and threshold concentrations of ADP. Aspirin and diltiazem decreased thromboxane A2 generation during ADP induced aggregation by 94 percent and 53 percent respectively, however both agents inhibited aggregation similarly, which suggests that diltiazem's anti-platelet effect was due to mechanisms other than inhibition of thromboxane metabolism alone. Combination therapy resulted in a partially additive inhibitory effect on ADP induced aggregation and thromboxane A2 generation. Two subjects had bleeding times over 15 minutes after receiving combination therapy.

Adenosine Diphosphate↗
PubMed1986

Ethmozine for ventricular premature complexes.

Twenty patients with an average of more than 30 ventricular premature complexes (VPCs) per hour were treated with ethmozine. Eighteen had either not responded or had adverse reactions to at least 1 other antiarrhythmic drug. Patients were treated with 200 to 300 mg 3 times daily (8.25 to 11.7 mg/kg) and were followed for up to 6 months. Three patients were withdrawn from ethmozine therapy because of unwanted effects before evaluation of efficacy. One of these patients had sustained ventricular tachycardia (VT) after a loading dose of ethmozine. Eleven of the remaining 17 patients (65%) experienced more than a 75% reduction in ventricular ectopic activity. Six patients had a smaller or no decrease in VPC frequency. Eleven of 16 patients (68%) with paired VPCs had a more than 90% reduction in paired VPC frequency. Eleven of 13 patients (84%) with VT events of 3 beats or more had more than a 90% reduction in VT events. Of the 11 patients in whom a more than 75% reduction in VPC frequency occurred, 1 patient died suddenly after 133 days of effective drug therapy. Three patients discontinued ethmozine therapy for reasons not related to the drug. Of the 6 patients in whom there was less than a 75% reduction in VPC frequency, 2 patients discontinued treatment, 1 patient because of hyperanxiety and 1 because of drug-related left anterior hemiblock. Ethmozine lengthened PR and QRS intervals but not the JT interval. Thus, ethmozine is effective and clinically useful for suppression of frequency VPCs in 50% (10 of 20 patients) of a selected population.

Aged↗
PubMed1985

Significance of the Q wave in acute myocardial infarction.

Acute myocardial infarction may be associated with the development of Q waves on the electrocardiogram (ECG), or with changes limited to the ST segment or T wave. The ECG changes do not accurately differentiate transmural from nontransmural infarction. However, the presence or absence of a Q wave does correlate with some aspects of the clinical course of patients after myocardial infarction, and is therefore of prognostic value. Q-wave infarctions are more likely to be complicated by congestive heart failure during hospitalization. The in-hospital mortality is also higher after a Q-wave infarction than after a non-Q infarction. Both of these findings are probably due to the association of a Q wave with a larger mass of infarcted myocardium. The long-term mortality, however, is the same for Q-wave and non-Q-wave infarctions. This is probably due to an increased late mortality after non-Q infarctions, related in part to a higher rate of reinfarction. The differences between Q-wave and non-Q-wave infarctions are not due to obvious differences in extent and location of coronary artery obstructions. However, there may be differences in the collateral circulation, with more extensive collaterals associated with non-Q infarcts. Appreciation of the prognostic significance of the ECG changes in acute myocardial infarction may help direct the evaluation and management of the patient after myocardial infarction.

Cardiac Catheterization↗
PubMed1985

Management of patients after thrombolytic therapy for acute myocardial infarction.

The coronary artery thrombus that causes acute myocardial infarction can be lysed, and reperfusion can be achieved, in the first few hours after infarction. However, the infarct vessel will reocclude in 15-30% of patients, and this event is frequently associated with pain, reinfarction, arrhythmias, or death. The risk of reocclusion is greatest in patients with high-grade residual stenosis after thrombolysis. Percutaneous coronary angioplasty may be performed safely after thrombolytic therapy. Angioplasty effectively decreases the degree of residual stenosis, and may thereby reduce the risk of reocclusion and consequent ischemic events. However, a substantial proportion of patients with acute infarction are not suitable candidates for angioplasty. Coronary artery bypass surgery has also been safely performed within several days after thrombolytic therapy. Further studies are needed to determine which patients will benefit most from this aggressive approach to acute myocardial infarction.

Angioplasty, Balloon↗
PubMed1985

Bioavailability of the bis- and monodigitoxosides of digitoxigenin.

The pharmacokinetic behavior of digitoxigenin is affected by the number of glycosides present. This study was conducted to compare the bioavailabilities of the bis- and monodigitoxosides of digitoxigenin in man. Intravenous and oral doses of the two drugs were administered to six normal volunteers. Blood samples were collected up to 28 days after each dose, and assayed for the specific drug administered and for total radioassayable drug. Both drugs were virtually completely absorbed, based on serum concentrations of administered drug plus metabolites. However, the mean bioavailability of unchanged bisdigitoxoside was only 56.3% indicating that substantial metabolism occurred prior to entry into the systemic circulation. Monodigitoxoside was virtually completely metabolized prior to entry into the systemic circulation.

Administration, Oral↗
PubMed1985

Pharmacokinetic evaluation of the digoxin-amiodarone interaction.

Amiodarone is known to raise serum digoxin levels. This study was designed to evaluate the pharmacokinetic basis of this interaction in 10 normal subjects. The pharmacokinetic variables for digoxin were determined after a 1.0 mg intravenous dose of digoxin in each subject, before and after oral amiodarone, 400 mg daily for 3 weeks. During amiodarone administration, systemic clearance of digoxin was reduced from 234 +/- 72 ml/min (mean +/- standard deviation) to 172 +/- 33 ml/min (p less than 0.01). This was due to reductions in both renal clearance (from 105 +/- 39 to 84 +/- 15 ml/min) (p less than 0.05) and nonrenal clearance (from 130 +/- 38 to 88 +/- 20 ml/min) (p less than 0.01). Digoxin half-life of elimination was prolonged from 34 +/- 13 to 40 +/- 16 hours (p less than 0.05). Digoxin volume of distribution was not significantly changed. Amiodarone caused a three- to fivefold increase in serum reverse triiodothyronine levels, but changes in thyroid function were not quantitatively related to the changes in digoxin pharmacokinetics. These alterations in digoxin pharmacokinetics produced by amiodarone explain the increase in serum digoxin level that has been observed when this drug combination has been used clinically.

Adult↗