Biomedical subjects

C Funck-Brentano

Publications and source records attributed to C Funck-Brentano.

At least 19 recordsLinked to original sources

PubMed1992

[Mishaps with anti-arrhythmic agents used to reduce mortality after infarction].

The presence of isolated and/or repetitive ventricular arrhythmias following myocardial infarction identifies a group of patients at increased risk of death. The availability of anti-arrhythmic drugs, noticeably drugs with class I activity, efficient at suppressing arrhythmias has led to the hope that their administration could reduce post-myocardial infarction mortality. However, this hypothesis has not been confirmed. The Cardiac Arrhythmia Suppression Trial, which was designed to have the power to test the hypothesis that suppression of ventricular arrhythmias is associated with a decrease in mortality following myocardial infarction, even showed an increase in mortality with two drugs with class I activity. Several meta-analyses have confirmed that administration of class I antiarrhythmic drugs is of no clinical benefit in patients with non sustained ventricular arrhythmias following myocardial infarction. Ongoings studies are testing the hypothesis that such benefit could exist with amiodarone. The clinical benefit of beta-blockers, in terms of reduction of both total and sudden death post-myocardial infarction, has been clearly documented and mandates their administration in this setting. Futures studies of anti-arrhythmic drugs will have to focus on groups of patients at increased risk of arrhythmic death.

Amiodarone↗

PubMed1992

Pharmacokinetic and pharmacodynamic interaction between toloxatone, a new reversible monoamine oxidase-A inhibitor, and oral tyramine in healthy subjects.

We examined the influence of toloxatone, a new reversible monoamine oxidase-A inhibitor used in the treatment of depression, on tyramine-induced pressor effect in healthy volunteers. The maximum increase in systolic blood pressure produced by four single oral doses of tyramine administered during a meal and ranging from 100 mg to 800 mg was compared during repeated (3 to 5 days) administration of placebo, 200 mg toloxatone three times a day and 400 mg toloxatone three times a day in a single-blind, three-period crossover study. Toloxatone by itself had no significant influence on blood pressure. During administration of toloxatone, no significant increase in tyramine-induced increase in systolic blood pressure was observed for tyramine doses of 200 mg or less that are consistently higher than those associated with normal food intake. However, toloxatone increased the tyramine-induced increase in blood pressure after 400 mg tyramine (400 mg toloxatone three times a day) and 800 mg tyramine (200 mg toloxatone three times a day and 400 mg toloxatone three times a day). This pharmacodynamic interaction could be explained by an increase in tyramine systemic bioavailability in the presence of toloxatone. It is concluded that interaction between tyramine in meals and toloxatone is unlikely to occur in patients after long-term administration of the drug at therapeutic dosages.

Administration, Oral↗

PubMed1992

Prediction of sotalol-induced maximum steady-state QTc prolongation from single-dose administration in healthy volunteers.

The relationship between racemic sotalol plasma concentrations and QTc interval prolongation after both single-dose and repeated administration of three sotalol oral doses was studied in a randomized crossover protocol performed in 10 healthy volunteers. QTc interval increase was significant after the three single-dose sotalol administrations and was significantly related to the administered dose (p < 0.0001). In 21 of 30 analyses, QTc interval was linearly correlated with sotalol plasma concentrations. After the 320 mg dose, the linear model was a best fit for 90% of the cases, and no hysteresis was observed. After repeated sotalol administration, 69 of 87 QTc interval measurements at steady state could be predicted from the plasma concentration versus effect relationship established after single-dose 320 mg administration. Seventeen of 18 errors (94%) corresponded to QTc intervals that were significantly lower than predicted. These findings suggest that a short-term individual linear model determined after a 320 mg test dose of sotalol allows a good prediction of expected maximal increase in QTc duration in healthy subjects.

Administration, Oral↗

PubMed1992

Relation between chloroguanide bioactivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans.

It has been suggested recently that the bioactivation of chloroguanide hydrochloride (proguanil) to its active antimalarial metabolite cycloguanil cosegregates with the genetically determined polymorphism of mephenytoin hydroxylation. We determined the chloroguanide to cycloguanil ratio in urine after oral administration of a single dose of 200 mg proguanil either alone or together with 100 mg racemic mephenytoin or 40 mg dextromethorphan in a randomized crossover study performed in 24 healthy subjects. The mephenytoin hydroxylation index was also determined after administration of 100 mg racemic mephenytoin either alone or together with 200 mg proguanil. Two subjects were poor metabolizers and one subject was an intermediate metabolizer of mephenytoin. These three subjects had chloroguanide to cycloguanil ratios of more than 50. The 21 subjects with the extensive metabolizer phenotype for mephenytoin hydroxylation had chloroguanide to cycloguanil ratios of less than 10. The chloroguanide to cycloguanil ratio was not significantly altered by mephenytoin or dextromethorphan coadministration. The trend toward a correlation between chloroguanide/cycloguanil ratio and log mephenytoin hydroxylation index did not reach statistical significance. Inclusion of the dextromethorphan metabolic ratio into the model did not improve the relationship. These findings confirm that the bioactivation of chloroguanide to cycloguanil cosegregates with the genetically determined activity of the CYP2C family. However, the chloroguanide to cycloguanil ratio and the mephenytoin hydroxylation index do not similarly reflect the variable activity of CYP2C.

Adult↗

PubMed1992

The pharmacokinetics of perindopril in patients with liver cirrhosis.

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.

Adult↗

PubMed1992

[Potassium channels and arrhythmia].

Cardiac repolarisation depends mainly on the cellular extrusion of positive electrical charge related to the potassium ion through different channels. There are many potassium channels which are responsible for repolarisation in different cardiac tissues. Prolongation or shortening of the repolarisation period may be both antiarrhythmic and proarrhythmic depending on the given experimental conditions. Different potassium channels may be opened or blocked by clinically prescribed drugs. Activators of the iK(ATP) channels may exert antiarrhythmic effects by inhibiting activity induced by prolonged repolarisation. Experimentally, they may exert a proarrhythmic effect by predisposing to arrhythmias during myocardial ischemia. However, these effects have not been clearly demonstrated clinically. Potassium channel blockers may have an antiarrhythmic effect by reducing the variability of repolarisation, by prolonging the atrial and ventricular refractory periods and by their antifibrillatory actions. Nevertheless, they may have proarrhythmic effects resulting in triggered activation under particular conditions of bradycardia and/or ischemia. Examples of these effects have been reported in man. The understanding of the relationship between potassium channels and arrhythmias is particularly complex because of the multiple factors regulating the duration of repolarisation and the effects of drugs on this duration. These factors include the activity of the autonomic nervous system, the heart rate, ischemia and acidosis and the differences in response to endocardial and epicardial tissues.

Anti-Arrhythmia Agents↗

PubMed1992

Polymorphism of dextromethorphan metabolism: relationships between phenotype, genotype and response to the administration of encainide in humans.

The polymorphism of dextromethorphan and encainide metabolism is genetically determined and is related to the activity of hepatic CYP2D6. In order to examine the relations between CYP2D6 phenotype, genotype and the electrocardiographic response to the oral administration of encainide, 110 healthy subjects were studied. Metabolic ratios were calculated in urine after oral administration of 40 mg of dextromethorphan and in plasma obtained 2.5 h after oral administration of 50 mg of encainide. Encainide-induced electrocardiographic changes were measured 2.5 h after oral administration of the drug. Genotype was determined in 52 subjects. Results showed that phenotype, either extensive or poor metabolizer, for CYP2D6-dependent metabolism could be identified from the dextromethorphan metabolic ratio calculated in urine, from the encainide metabolic ratio calculated in plasma and from the genotype. However, despite the fact that the changes in atrioventricular (PR) and intraventricular (QRS) conduction times produced by encainide were different in extensive and poor metabolizer subjects and correlated with CYP2D6 activity, the electrocardiographic response was never 100% specific and sensitive for the identification of either phenotype. Moreover, genotypic identification of heterozygous and homozygous extensive metabolizer subjects did not predict CYP2D6 activity, as determined by dextromethorphan and encainide metabolic ratios, or encainide response, as determined by intraventricular and atrioventricular changes. Thus, CYP2D6 activity does not fully predict the electrocardiographic effects of encainide, and genotype, as determined in our study, cannot replace the determination of metabolic ratio in predicting CYP2D6 activity and encainide response in extensive metabolizer subjects.

Adult↗

PubMed1992

[Ventricular repolarization].

Ventricular repolarisation is the period that depolarised cells require to become polarised, that is to say excitable. In general cardiological practice, the duration of repolarisation is assessed by measuring the QT interval on the surface electrocardiogram. This measurement may be difficult because of the lack of precision in defining the end of the T wave. Automatic systems are becoming available and should circumvent these difficulties of manual measurements. Interpretation of a change in the QT interval during drug administration or related to cardiac pathology should take the many sources of physiological variation of ventricular repolarisation into account. One of the main causes of this variation is the heart rate which influences the duration of repolarisation in a complex manner. Analysis of the duration of repolarisation has many implications in pathology and pharmacology. Prolongation of the QT interval and its failure to adapt to the heart rate are trigger factors for torsades de pointe. Many drugs prolonging the duration of repolarisation and of the ventricular refractory period are being developed. Their effects are partially dependent on the heart rate. Finally, prolongation of the QT interval is associated with a poor prognosis after myocardial infarction.

Action Potentials↗

PubMed1991

Influence of amiodarone on genetically determined drug metabolism in humans.

Amiodarone has been shown to interact with the nongenetically determined hepatic elimination of several drugs, including phenytoin and digoxin. Its influence on genetically determined metabolic pathways has not been studied in humans. We examined the effects of oral amiodarone therapy on the genetically determined metabolism of isoniazid (N-acetyltransferase), mephenytoin (cytochrome P450MEPH), and dextromethorphan (CYP2D6). Eight patients with arrhythmias were studied before and 76 +/- 16 days after amiodarone (loading dose of 1000 mg/day for 10 days followed by a maintenance dose of 200 to 400 mg/day). Genetically determined enzyme activity was assessed indirectly by calculating the metabolic ratio (parent drug/metabolite in 8-hour urine for CYP2D6 and P450MEPH and N-acetylisoniazid/isoniazid in plasma for N-acetyltransferase) after oral administration of the parent compounds. At the time of phenotyping, plasma concentrations of amiodarone and N-desethylamiodarone were 0.66 +/- 0.35 micrograms/ml and 0.65 +/- 0.26 micrograms/ml, respectively. Amiodarone increased the log(metabolic ratio) of dextromethorphan from a median of -2.5 (range, -2.9 to -2.0) to a median of -1.9 (range, -2.5 to -1.5; p less than 0.02) but did not alter the metabolic ratio of mephenytoin or isoniazid. The amount of dextromethorphan excreted in urine increased from a median of 0.084 mumol/8 hours (range, 0.041 to 0.161 mumol/8 hours) to a median of 0.205 mumol/8 hours (range, 0.064 to 0.288 mumol/8 hours; p less than 0.02) and the amount of its metabolite (dextrorphan) tended to decrease from a median of 26 mumol/8 hours (range, 15 to 37 mumol/8 hours) to a median of 20 mumol/8 hours (range, 7 to 27 mumol/8 hours; p less than 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Prospective pharmacokinetically based development of effective infusion regimens for ACC-9358, a new antiarrhythmic drug.

In this study we evaluated the clinical pharmacology of intravenous ACC-9358, a new antiarrhythmic drug derived from a Chinese herbal remedy. In a first-study phase, 0.125 to 1.0 mg/kg during 10 minutes was administered to six patients with chronic nonsustained ventricular arrhythmias. These data were then used to design 3-hour infusions to maintain stable plasma concentrations: these infusions suppressed arrhythmias by 90% or greater for 2 1/2 hours or more at plasma concentrations of 114 to 1010 ng/ml (mean, 400 +/- 421 ng/ml [SD]), and with QRS interval increases of 2.5% to 8.8% (5.1% +/- 2.9%). Mean clearance was 478 +/- 151 ml/min, and elimination half-life was 19.1 +/- 6.1 hours. ACC-9358 did not produce adverse effects in this study. ACC-9358 shows antiarrhythmic activity in humans at concentrations that prolong QRS only slightly and do not alter rate-corrected QT; further studies in other patient populations, at dosages and plasma concentrations defined here, are required to establish a clinical role for ACC-9358. The pharmacokinetically based dose-ranging approach allowed the safe initial evaluation of ACC-9358 in patients.

Aged↗

PubMed1991

Genetically determined stereoselective excretion of encainide in humans and electrophysiologic effects of its enantiomers in canine cardiac Purkinje fibers.

Encainide metabolism is mediated by the polymorphically distributed cytochrome P450IID6, which displays stereoselectivity for some substrates. In this study we found that urinary recovery during steady-state encainide in three poor metabolizers was high (49% to 80%), consisted mainly of unchanged encainide, was nonstereoselective (+/- ratio, 0.985 to 1.049), and was unchanged by quinidine, a potent inhibitor of P450IID6. In contrast, in seven extensive metabolizers the +/- urinary ratios were 1.20 +/- 0.06 for encainide and 0.81 +/- 0.06 (both p less than 0.01) for the cytochrome P450IID6 products O-desmethylencainide plus 3-methoxy-O-desmethylencainide; with quinidine the total percentage recovery rose from 4% +/- 4% to 37% +/- 9% because of increased recovery of unchanged encainide and became non-stereoselective (+/- ratio, 0.84 +/- 0.08 [encainide alone] versus 0.97 +/- 0.05 [encainide plus quinidine]). In vitro, encainide enantiomers depressed the maximum rate of metabolism with similar frequency and concentration dependence. We conclude that (-)-encainide undergoes preferential metabolism by cytochrome P450IID6; however, this genetically determined stereoselective disposition is unlikely to play a major role in mediating the clinical actions of encainide.

Action Potentials↗

PubMed1991

Rate dependence of sotalol-induced prolongation of ventricular repolarization during exercise in humans.

Studies in animals have shown that drug-induced action potential prolongation with class III antiarrhythmic agents increases with slow pacing rates. We studied the physiological rate dependence of sotalol effects on ventricular repolarization, measured as QT interval duration on the surface electrocardiogram at rest and during a maximal exercise test, in 10 normal volunteers. In a randomized, crossover study, three dosages of sotalol (160 mg/24 hr, 320 mg/24 hr, and 640 mg/24 hr) were administered during 4 days to each subject. In a control period, no drug was administered. During each period, 50-100 QT intervals were measured over a wide range of RR intervals recorded at rest and during the course of a maximal exercise test. Plasma sotalol concentration and beta-adrenoceptor blockade (percent reduction in peak exercise heart rate from control) were also measured. The QT-versus-RR relation was fitted to several formulas, and the overall best fit was used to calculate QT interval duration normalized for a heart rate of 60 beats/min (QTc) and to analyze the rate dependence of QT prolongation with sotalol. Sotalol-induced beta-adrenoceptor blockade and QTc prolongation were dose and concentration dependent. Sotalol reduced peak exercise heart rate by 13.8 +/- 7% at the dosage of 320 mg/24 hr and by 25.4 +/- 8% at the dosage of 640 mg/24 hr (both p less than 0.01). Sotalol prolonged QTc interval by 5.8 +/- 3.7% and 11.8 +/- 3% at these respective dosages (both p less than 0.01). The concentration of sotalol required to produce minimal (mean QTc prolongation, 5.6%; confidence interval, 0-11.2%) QTc prolongation (680 ng/ml) tended to be lower than that required for minimal (mean percent reduction in maximal exercise heart rate, 13.9%; confidence interval, 0-27.8%) beta-blockade (840 ng/ml). QT prolongation with sotalol increased with increasing RR intervals (i.e., decreasing heart rate) at all dosages. QT prolongation became statistically significant for RR of 800 msec or more at all dosages and for RR intervals of 600 msec or more at the dosage of 640 mg/24 hr. This rate dependence altered the relation between QT interval duration and sotalol plasma concentrations. These results suggest that sotalol prolongs QTc interval in humans at dosages and concentrations similar to those required to produce beta-adrenoceptor blockade, QT prolongation with sotalol is more pronounced when heart rate decreases and is not apparent during exercise-induced tachycardia, and the relation between QT prolongation with sotalol and plasma concentrations of the drug depends on the heart rate at which measurements are made.

Adult↗

PubMed1991

[Genetic polymorphism of the metabolism of drugs used in cardiac diseases].

The genetic determinants of the metabolism of certain drugs used in cardiology is one predictable cause of variability in their pharmacokinetics and effects. Genetic polymorphism of the metabolism of drugs is characterised by the existence of several metabolic phenotypes, usually 2, which allow distinction between fast and slow metabolisers. Clinical identification of these phenotypes is relatively simple. The enzymatic deficiency in slow metabolisers concerns a specific metabolic pathway responsible for the biotransformation of the drug but it respects other eventual metabolic pathways. For a given drug and a given metabolic pathway, slow metabolisers are unable to eliminate the parent product by hepatic metabolism. When the drug is given orally, the plasma concentrations of the parent product in slow metabolisers are 5 to 25 times higher than those observed in fast metabolisers. Depending on the given drug, doses usually well tolerated by fast metabolisers may cause excessive effects in slow metabolisers. The pharmacodynamic consequences of genetic polymorphism on the metabolism of drugs depend essentially on the therapeutic index of the drug concerned and on the activity of the metabolites formed by the genetically determined pathway of the parent product. The pharmacokinetic and pharmacodynamic consequences of the two main genetic polymorphisms concerning drugs used in cardiology are discussed: the polymorphism of N acetylation and that of cytochrome P-450 IID6.

Acetyltransferases↗

PubMed1991

[Pertinence of animal and human models in the evaluation of ventricular anti-arrhythmia agents].

The development of antiarrhythmic agents for the treatment of ventricular arrhythmias depends to a large extent on their effects in different animal and human models. The clinical relevance of the data so obtained is debatable. Firstly, in vitro animal models of arrhythmias are not very predictive of the multiple clinical forms of ventricular arrhythmias. Secondly, the intermediary criteria of evaluation of the effects of antiarrhythmic drugs in humans are generally not valid in terms of criteria of substitution for the evaluation of therapeutic effects. Nevertheless, cellular and hemodynamic studies of the electrophysiological properties of drugs are essential for correct clinical usage of antiarrhythmics. They help predict the principal clinical electrocardiographic changes and their modulation with respect to parameters such as ischemia or heart rate, their hemodynamic tolerance and certain undesirable, especially proarrhythmic, effects. However, the clinical pertinence of these studies remains limited for a number of reasons. In particular, most antiarrhythmic agents have multiple electrophysiological effects, the resultant of which is difficult to predict in the clinical situation. In addition, many of these drugs have active metabolites, the formation of which varies from person to person, which also reduces the clinical relevance of studies of the parent molecule alone. Clinical trials in appropriate patient populations should therefore be preferred to the multiplication of studies on experimental models of uncertain relevance.

Animals↗

PubMed1990

Effects of bepridil and diltiazem on ventricular repolarization in angina pectoris.

To examine the time-course and potential predictors of prolongation of ventricular repolarization with the calcium antagonist bepridil, the effects of bepridil (300 to 500 mg/day; n = 45) and diltiazem (180 to 300 mg/day; n = 42) on QT and QTc interval duration were analyzed in a randomized double-blind study in patients with angina pectoris. Electrocardiograms were recorded before and 14, 28, 70 and 112 days after treatment was begun. After 14 days, bepridil prolonged QT interval by 26 +/- 35 ms (range, -60 to 120 ms) and QTc (Bazett's formula) by 17 +/- 33 ms (range, -73 to 107 ms) compared to baseline (both p less than 0.05). QT or QTc did not significantly increase thereafter. However, among the 30 patients who had less than 40 ms QTc prolongation at day 14 compared with baseline, 13 (43%) exceeded this limit on at least 1 of the following visits. Diltiazem did not significantly alter QT or QTc intervals. The absolute change in QTc interval from baseline observed after 14 days of bepridil therapy was inversely proportional to the baseline QTc interval (r = -0.68; n = 42; p less than 0.001). The degree of bepridil-induced QTc prolongation on day 14 correlated with pretreatment RR interval (r = 0.36; n = 42; p less than 0.02). In conclusion, chronic administration of bepridil but not of diltiazem prolongs ventricular repolarization in patients with angina pectoris. The overall effects of bepridil therapy on QT and QTc intervals can be assessed by an electrocardiogram recorded after 14 days of treatment but subsequent measurements may be required in individual patients. A short baseline QTc interval and a slow initial heart rate may be potentially useful predictors of a greater QTc prolongation with bepridil.

Angina Pectoris↗

PubMed1990

The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone.

Propranolol and the sodium-channel-blocking antiarrhythmic agent propafenone share structural features. Although propafenone's beta-blocking actions are readily demonstrable in vitro, clinically significant beta-blockade occurs inconsistently in vivo. In this study, we tested the hypothesis that genetically determined variations in the biotransformation of propafenone to its 5-hydroxy metabolite account for variations in the drug's beta-blocking action. We assessed beta-blockade by measuring the reduction in tachycardia produced by boluses of isoproterenol and treadmill exercise in 14 normal subjects during treatment with placebo and with 150, 225, and 300 mg of propafenone every eight hours for five days each. Nine subjects (with the extensive-metabolizer phenotype) metabolized most of the propafenone to 5-hydroxy propafenone, and five (with the poor-metabolizer phenotype) did not produce this metabolite. At the lower dosages, beta-blockade was present in both groups but was significantly greater in the subjects with poor metabolism, in whom deficient 5-hydroxylation was associated with higher plasma propafenone levels. At the highest dose, a similar degree of beta-blockade was observed in the two groups. Propafenone also had a higher affinity for beta 2 receptors in vitro than either of its major metabolites. We conclude that the degree of beta-blockade during propafenone therapy reflects genetically determined variations in the metabolism of the parent drug, which is necessary for beta-blockade, and that this action of propafenone is considerably enhanced in patients with deficient 5-hydroxylation of propafenone.

Adrenergic beta-Antagonists↗

PubMed1990

Propafenone.

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Arrhythmias, Cardiac↗

PubMed1990

Concentration/response relations for the multiple antiarrhythmic actions of sotalol.

Sotalol, one of the first beta-receptor antagonists synthesized, is a promising investigational agent with remarkable efficacy for treatment of patients with ventricular and supraventricular arrhythmias. Unlike other beta blockers, sotalol also possesses class III antiarrhythmic action, evidenced by prolongation of the myocardial action potential duration. This additional action probably accounts for the greater antiarrhythmic efficacy of sotalol compared with other beta blockers. Sotalol's class III antiarrhythmic action becomes apparent at concentrations higher than those necessary for significant beta-receptor antagonism, both in vitro and in human subjects. In a study correlating dosage and antiarrhythmic response with prolongation of rate-corrected QT (QTc) (a measure of class III action) and the degree of beta-receptor blockade (assessed by the reduction of the maximal exercise-induced heart rate), 11 of 17 patients had an antiarrhythmic response. Eight of these 11 responders had been unresponsive to conventional beta-receptor antagonists. The plasma concentration associated with significant QTc prolongation (2.55 micrograms/ml) was found to be much greater than that associated with 50% reduction in maximal slowing of heart rate (0.8 micrograms/ml). As with other beta-receptor antagonists, the activities of sotalol's 2 stereoisomers differ, with the I-isomer having far more beta-blocking activity. However, both isomers have equal class III antiarrhythmic activity. When increasing doses of the d-isomer of sotalol (50 to 400 mg every 12 hours) were evaluated in patients with chronic ventricular arrhythmias, arrhythmia frequency was suppressed greater than 80% in 3 patients and 50% in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗