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Biomedical subjects

P F Nestico

Publications and source records attributed to P F Nestico.

At least 19 recordsLinked to original sources

New antiarrhythmic drugs.

While controversy still exists as to the precise indications for the treatment of all forms of ventricular arrhythmia, advances in the number and, more importantly, type of antiarrhythmic drugs can provide the clinician with a rational basis for selecting antiarrhythmic drug therapy. A host of new agents with different pharmacokinetic and electrophysiological actions are now available, and can be compared or contrasted to conventional antiarrhythmic agents such as quinidine, procainamide, disopyramide, lignocaine (lidocaine) and bretylium. This review summarises the electrophysiological, haemodynamic, pharmacokinetic, and efficacy and safety data of mexiletine, tocainide, flecainide, encainide, propafenone, amiodarone, sotalol, pirmenol, cibenzoline (cifenline) and ethmozine (moracizine, moricizine), and aims to provide a basis on which clinicians can compare and contrast these agents and form an algorithm for selection of antiarrhythmic drug therapy in the treatment of patients with ventricular arrhythmias.

Anti-Arrhythmia Agents↗

Efficacy of oral and intravenous indecainide in ventricular arrhythmias.

To evaluate the efficacy of oral and intravenous indecainide, a new class IC antiarrhythmic agent, 3 separate protocols were performed in patients with benign or potentially lethal ventricular arrhythmias. An open-label intravenous trail in 10 patients was conducted using a dose of 1.7 mg/kg/min under constant monitoring. An oral short-term in-hospital trial in 20 patients (8 patients entered directly from the intravenous short-term trial) was conducted using a single-blind placebo dose titration protocol in which 50 mg of indecainide every 8 hours was increased at 3-day intervals to 75 mg, and then 100 mg every 8 hours depending on the observed change in ventricular arrhythmia frequency by Holter monitoring. Finally, an outpatient long-term oral trial was conducted in 17 of the 20 patients who completed the inpatient oral short-term trail. Two of the 10 patients from the inpatient intravenous trail did not enter the oral trial, because a proarrhythmic response developed in 1 and because of a lack of efficacy in the other. During the inpatient oral trial, 17 of 20 patients (85%) responded to indecainide and entered the long-term phase. Two of these patients were removed from the trial because of lack of efficacy at 3 and 10 months, respectively. In the oral therapy protocols, minor side effects of the central nervous system occurred in 4 of 17 patients (24%). Six of 20 patients (30%) each had more than a 25% increase in PR and QRS duration that was not associated with higher degrees of block.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of beta blockade on systolic and diastolic left ventricular function at rest and during exercise in patients with chronic stable angina pectoris.

This study examined the effects of beta blockade with betaxolol, a cardioselective, lipid-soluble, beta-adrenergic-blocking agent, on rest and exercise systolic and diastolic left ventricular function in 15 patients, aged 40 to 70 years (mean = 52), with chronic stable angina pectoris. Each patient underwent three upright exercise studies at identical workloads; the first was a baseline study, the second was done 3 hours after a single oral dose, and the third was obtained after chronic therapy for 2 weeks. Beta blockade was evident by significant decreases in heart rate, systolic blood pressure, and diastolic blood pressure at rest and during exercise (p less than 0.04). Although there were no significant changes (at rest or during exercise) in mean left ventricular ejection fraction and peak filling rate, individual variations were seen after 3 hours and 2 weeks of therapy. During chronic therapy, the peak filling rate increased in three patients, decreased in five, and remained unchanged in seven. Also, discordant changes in systolic and diastolic functions were seen at rest and during exercise during both acute and chronic therapy. Thus, although acute and chronic beta blockade produces no significant changes in mean measurements of diastolic and systolic left ventricular performance, individual variations and discordant results are seen in many patients. The acute effects are generally consistent with the chronic effects, but exceptions are present.

Adrenergic beta-Antagonists↗

Relative prognostic value of rest thallium-201 imaging, radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring after acute myocardial infarction.

Rest thallium-201 scintigraphy, radionuclide ventriculography and 24 hour Holter monitoring are acceptable methods to assess myocardial necrosis, performance and electrical instability. This study examined the relative value of the three tests, when obtained a mean of 7 days after acute myocardial infarction, in predicting 1 year mortality in 93 patients. Planar thallium-201 images were obtained in three projections and were scored on a scale of 0 to 4 in 15 segments (normal score = 60). Patients were classified as having high risk test results as follows: thallium score less than or equal to 45 (33 patients), left ventricular ejection fraction less than or equal to 40% (51 patients) and complex ventricular arrhythmias on Holter monitoring (36 patients). During the follow-up of 6.4 +/- 3.4 months (mean +/- SD), 15 patients died of cardiac causes. All three tests were important predictors of survival by univariate Cox survival analysis; the thallium score, however, was the only important predictor by multivariate analysis. The predictive power of the thallium score was comparable with that of combined ejection fraction and Holter monitoring (chi-square = 21 versus chi-square = 22). Thus, rest thallium-201 imaging performed before hospital discharge provides important prognostic information in survivors of acute myocardial infarction which is comparable with that provided by left ventricular ejection fraction and Holter monitoring. Patients with a lower thallium score (large perfusion defects) are at high risk of cardiac death during the first year after infarction.

Adult↗

Antiarrhythmic agents for chronic ventricular arrhythmias.

A vast array of new antiarrhythmic agents have joined the old agents among the clinician's available resources. While treatment of ventricular arrhythmias is completely justifiable for patients with symptoms, their use to prevent sudden cardiac death has not yet been established. Because of their potential risks, the benefit/risk ratio must always be kept in mind. If we elect to treat patients who have benign or potentially lethal ventricular arrhythmias (usually to eliminate refractory symptoms) we typically begin with either a beta blocker or one of the new potent class IC antiarrhythmic agents such as flecainide or encainide. These drugs cause few side effects, no organ toxicity, and in the case of encainide or flecainide, have marked potency. Few important proarrhythmic effects are seen with these potent drugs in this group of patients. If these fail, one can try either a class IA or IB agent or a combination of a IA and IB agent. We always avoid amiodarone. In patients with lethal ventricular arrhythmias, one should choose a drug without negative inotropic potential such as quinidine or encainide as initial therapy. The combination of IA and IB agents should also be considered early in therapy. In patients with overt congestive heart failure with markedly depressed left ventricular function in the setting of lethal arrhythmias, disopyramide, beta blockers, and flecainide should be avoided. Amiodarone is used in this population only when the other available agents have proven to be ineffective or badly tolerated.

Amiodarone↗

Bepridil hydrochloride for treatment of benign or potentially lethal ventricular arrhythmias.

To define the efficacy and safety of a new once-a-day calcium antagonist, bepridil, 21 patients with frequent ventricular premature complexes (VPCs) underwent a 14-day inpatient monitored trial. After Holter monitoring during placebo administration, patients underwent 2 days of a loading dose of bepridil followed by 12 days of bepridil, 400 mg/day. Holter monitoring during therapy showed that 10 patients (48%) had more than a 70% reduction in VPC frequency and 8 of 16 patients (50%) at least a 95% reduction in frequency of nonsustained ventricular tachycardia. Gastrointestinal and central nervous system side effects considered to be mild occurred in 13 patients (62%). One patient had an asymptomatic increase in VPC frequency and another had sustained ventricular tachycardia associated with a loading dose of 900 mg of bepridil. Thus, bepridil has moderate antiarrhythmic efficacy in patients with ventricular arrhythmias, but further definition of its potential for causing proarrhythmia must be determined.

Bepridil↗

Implications of abnormal right ventricular thallium uptake in acute myocardial infarction.

The correlates of abnormal right ventricular (RV) thallium uptake were examined in 116 patients with documented acute myocardial infarction (AMI) who underwent predischarge thallium-201 scintigraphy at rest, radionuclide angiography and 24-hour ambulatory electrocardiography. The patients were separated into 2 groups: patients group 1 (n = 31) had increased RV thallium uptake and those in group 2 (n = 85) had no such uptake. The 2 groups were comparable in age, type and site of AMI, peak creatine kinase level, systolic blood pressure and heart rate. However, compared with group 2, group 1 had a lower mean left ventricular (LV) ejection fraction (33 +/- 15% vs 39 +/- 14%, p less than 0.05), higher prevalence of increased lung thallium uptake (45% vs 22%, p less than 0.02), more extensive LV perfusion defects (4.4 +/- 2.9 vs 3.0 +/- 3.0 segments, p less than 0.03) and more complex ventricular arrhythmias (55% vs 35%, p less than 0.05). At a mean follow-up of 6 months, 17 patients (8 in group 1 and 9 in group 2) died from cardiac causes. Actuarial life-table analysis showed that the survival rate was better in group 2 than in group 1 (Mantel-Cox statistics = 4.62, p = 0.03). Thus, patients with AMI and abnormal RV thallium uptake have worse LV function, more complex ventricular arrhythmias and worse prognosis.

Adult↗

Electrocardiographic diagnosis of posterior myocardial infarction revisited: a new approach using a multivariate discriminant analysis and thallium-201 myocardial scintigraphy.

This study examined the feasibility of using a multivariate discriminant analysis to design a useful electrocardiographic (ECG) model to diagnose posterior myocardial infarction (MI). Thallium-20) scintigraphy was used as a reference standard to identify posterior scar (fixed perfusion defects). The model was derived from 111 patients of whom 37 had fixed posterior defects and 74 had normal images, and its validity was subsequently tested in a separate group of 180 patients. In the initial group of patients, the fixed perfusion defects involved the posterior left ventricular wall alone in 15 patients, and the posterior and inferior walls in 22 patients. Stepwise multivariate discriminant analysis of 26 ECG variables produced a model of two variables (Q-wave duration in a VF and T-wave amplitude in V1) which provided a sensitivity of 78%, a specificity of 89%, and a predictive accuracy of 86% for the diagnosis of posterior MI. This model, when tested in the second group of 180 patients, yielded an overall prediction accuracy of 82% (sensitivity 65%, specificity 85%). Thus, the combination of Q-wave in a VF and upright T wave in V1 is the best ECG predictor of posterior MI. These two variables reflect the frequent association of posterior MI with inferior MI, and the reciprocal repolarization changes in the right precordial leads.

Adult↗

Coronary artery cardiomyopathy. Hemodynamic and prognostic implications.

To assess the prevalence and significance of left ventricular dilatation in patients with severe left ventricular dysfunction secondary to coronary artery disease (or coronary artery cardiomyopathy), we studied 70 patients with an ejection fraction of 35 percent or less and one-vessel coronary artery disease (n = 14) or with multivessel coronary artery disease (n = 56). None had had a recent myocardial infarction or valvular heart disease. Patients who underwent myocardial revascularization during follow-up were excluded. The left ventricular end-diastolic volume (measured by contrast ventriculography) was less than 110 ml/sq m in 14 patients (20 percent) (group 1), and was 110 ml/sq m or more in 56 patients (80 percent) (group 2). There were no differences between the two groups in age, sex, diabetes mellitus, hypertension, extent of coronary artery disease, or left ventricular asynergy. Patients in group 1 had lower pulmonary arterial wedge pressure (13 +/- 6 vs 22 +/- 10 mm Hg; p = 0.0008), lower left ventricular end-diastolic pressure (21 +/- 6 vs 27 +/- 9 mm Hg; p = 0.007), and higher left ventricular ejection fraction (31 +/- 2 vs 25 +/- 7 percent; p = 0.001) than patients in group 2. At a mean follow-up of 27 months, 24 patients had died of cardiac causes, all of whom were in group 2. Survival was significantly better in group 1 than in group 2 (Mantel-Cox, p = 0.009). Survival analysis (Cox models) of 20 clinical, hemodynamic, and angiographic variables showed that ejection fraction (chi2 = 13.6; p less than 0.001) and end-diastolic volume chi2 = 4.7; p = 0.03) were the most significant predictors of death. Thus, minimally dilated coronary artery cardiomyopathy is a distinct entity with favorable hemodynamics. Prognostically, the end-diastolic volume adds significant predictive information to the ejection fraction among conservatively treated patients.

Adult↗

Cardiac arrhythmias in the elderly: antiarrhythmic drug treatment.

The frequency of ventricular arrhythmias increases with age. Several factors make elderly people more prone to antiarrhythmic drug toxicity. Familiarity with the changes in the pharmacokinetics and pharmacodynamics of antiarrhythmic agents may reduce or prevent adverse response in this patient population.

Aged↗

Oral antiarrhythmic agents for ventricular arrhythmias.

Ventricular tachyarrhythmia is the most common terminal event causing sudden cardiac death. Risk stratification using 24-hour Holter monitoring to identify ventricular ectopy and noninvasive techniques to detect abnormal left ventricular function is becoming routine. Many cardiologists treat patients with potentially lethal ventricular arrhythmias even though it is unknown as yet whether sudden cardiac death can be prevented. Patients with lethal ventricular arrhythmias are always treated. A number of new oral antiarrhythmic agents have become available to the clinician. The modified Vaughan-Williams classification system categorizes the drugs according to their electrophysiologic and clinical characteristics. The class IC antiarrhythmic agents are emerging as the potential drugs of first choice for patients with benign or potentially lethal ventricular arrhythmias. The betablockers (class II) are used as antiarrhythmic agents, particularly in the presence of active myocardial ischemia or high catecholamine levels and in the postmyocardial infarction patient. Amiodarone (class III) may cause serious side effects and is reserved for patients with lethal ventricular arrhythmias when all other available agents have failed.

Administration, Oral↗

Forward ejection fraction: a new index of left ventricular function in mitral regurgitation.

Previous studies have shown that a normal LVEF is not a reliable index of LV function in MR. We hypothesized that the forward EF, which is the forward stroke volume (measured by Fick or thermodilution) divided by end-diastolic volume (measured by contrast ventriculography) may be a useful index of LV function, since it represents LV emptying into the aorta. This index was examined in 54 patients with chronic MR who had normal EF (greater than or equal to 50%). There were significant correlations between the forward EF and the end-diastolic volume index (r = -0.69, p less than 0.001), end-systolic volume index (r = -0.64, p less than 0.001), cardiac index (r = 0.43, p less than 0.01), and the ratio of systolic pressure-to-end-systolic volume (r = 0.65, p less than 0.001). Patients were divided into two groups according to the forward EF: group I (n = 34) had forward EF less than or equal to 35%; and group II (n = 20) had forward EF greater than 35%. Of the 32 patients who subsequently underwent mitral valve replacement, 24 patients were in group I and eight patients were in group II. At a mean follow-up of 35 months, four patients died; all of them were in group I. Improvement in functional class occurred in 75% of surgical survivors (80% in group I and 63% in group II, p = NS). These preliminary data suggest that forward EF may be a useful index of LV performance in patients with MR who have normal EF.

Adolescent↗