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Paul Dorian

Publications and source records attributed to Paul Dorian.

72 records · Page 4Linked to original sources
PubMed2003

Quality of life variables in the selection of rate versus rhythm control in patients with atrial fibrillation: observations from the Canadian Trial of Atrial Fibrillation.

Many patients with atrial fibrillation develop symptoms attributable to the cardiac arrhythmia itself. These symptoms may be improved either by restoring sinus rhythm or by controlling the rapid and irregular ventricular response that often accompanies this arrhythmia. One of the principal goals of therapy of atrial fibrillation management is improvement of patient symptoms; it is important to quantify these symptoms by some form of quality of life analysis. The Canadian Trial of Atrial Fibrillation (CTAF) was a multi-centre randomized clinical trial of amiodarone compared with either propafenone or sotalol in patients with recent atrial fibrillation. The quality of life (QOL) substudy of CTAF was a prospective, comprehensive assessment of quality of life of patients enrolled in CTAF. Summary measures of physical and mental health on the generic QOL scale (SF-36) improved significantly with treatment from baseline to 3 months (41.9 +/- 9.6 to 43.7 +/- 9.2, p = 0.001 for the physical component and 47.5 +/- 10.4 to 49.0 +/- 9.8, p = 0.023 for the mental component). On an arrhythmia specific scale (SCL), a significant and larger improvement was noted from baseline to 3 months in both arrhythmia symptom frequency and severity (symptom frequency from 20.4 +/- 9.4 to 16.2 +/- 9.5, symptom severity from 16.7 +/- 8.2 to 12.9 +/- 7.6, both p < 0.001). The quality of life improvements were similar in the amiodarone group compared to the sotalol or propafenone groups, both for the SF-36 and the disease-specific symptom checklist (SCL) measures. In contrast, an atrial fibrillation severity scale (AFSS) did show differences between the assigned drug therapies, which were associated with different rates of arrhythmia recurrence in the parent study. By 3 months global well-being was significantly worse for patients who had recurrent atrial fibrillation compared to those who did not (6.9 +/- 1.8 versus 7.4 +/- 1.8, p = 0.04). Similarly, symptom severity at 3 months was 11.8 +/- 7.4 for patients without recurrence, compared to 14.8 +/- 7.4 for those with recurrence ( p = 0.001). Interestingly, none of the usual clinical variables that might be perceived to be associated with quality of life, e.g., male versus female sex, age, NYHA class, beta blocker use, and ejection fraction, had much impact on subjective quality of life measures. Quality of life improves with treatment atrial fibrillation and at least some of these improvements are related to the restoration and maintenance of sinus rhythm.

Amiodarone↗
PubMed2003

Role of amiodarone in the era of the implantable cardioverter defibrillator.

Amiodarone is one of the most frequently used antiarrhythmic drugs in clinical practice. In patients with atrial fibrillation, in whom rhythm control is judged desirable, amiodarone is the most effective therapy. Amiodarone effectively prevents atrial fibrillation and may improve quality of life, but there is no evidence that it decreases mortality or severe morbidity in atrial fibrillation. In patients at risk for life-threatening ventricular arrhythmias, amiodarone may decrease mortality to a small degree, but the evidence for this benefit is incomplete. Patients with implantable cardioverter defibrillators frequently require antiarrhythmic drug therapy, especially to treat electrical storm. Amiodarone is useful in these patients; however, it may increase defibrillation thresholds in some patients. In patients with out-of-hospital DC shock-resistant VF, amiodarone is the most effective antiarrhythmic drug available to assist in resuscitation. Amiodarone is a complicated drug, and its optimal use requires careful patient surveillance with respect to potential adverse effects.

Amiodarone↗
PubMed2003

Biphasic versus monophasic cardioversion in shock-resistant atrial fibrillation:.

UNLABELLED: Biphasic versus Monophasic Cardioversion. INTRODUCTION: Cardioversion of atrial fibrillation using monophasic transthoracic shocks occasionally is ineffective. Biphasic cardioversion requires less energy than monophasic cardioversion, but its efficacy in shock-resistant atrial fibrillation is unknown. Thus, we compared the efficacy of cardioversion using biphasic versus monophasic waveform shocks in patients with atrial fibrillation previously refractory to monophasic cardioversion. METHODS AND RESULTS: Fifty-six patients with prior failed monophasic cardioversion were randomized to either a 360-J monophasic damped sinusoidal shock or biphasic truncated exponential shocks at 150 J, followed by 200 J and then 360 J, if necessary. If either waveform failed, patients were crossed over to the other waveform. The primary endpoint was defined as the proportion of patients achieving sinus rhythm following initial randomized therapy. Stepwise multivariate logistic regression examined independent predictors of shock success, including patient age, sex, left atrial diameter, body mass index, drug therapy, and waveform. Twenty-eight patients were randomized to the biphasic shocks and 28 to the monophasic shocks. Sinus rhythm was restored in 61% of patients with biphasic versus 18% with monophasic shocks (P = 0.001). Seventy-eight percent success was achieved in patients who crossed over to the biphasic shock after failing monophasic cardioversion, whereas only 33% were successfully cardioverted with a monophasic shock after crossover from biphasic shock (P = 0.02). Overall, 69% of patients who received a biphasic shock at any point in the protocol were cardioverted successfully, compared to 21% with the monophasic shock (P < 0.0001). The type of shock was the strongest predictor of shock success (P = 0.0001) in multivariate logistic regression. CONCLUSION: An ascending sequence of 150-, 200-, and 360-J transthoracic biphasic cardioversion shocks are successful more often than a single 360-J monophasic shock. Thus, biphasic shocks should be the recommended configuration of choice for all cardioversions.

Atrial Fibrillation↗
PubMed2003

Effect of pacing mode on health-related quality of life in the Canadian Trial of Physiologic Pacing.

BACKGROUND: Both "physiologic" (dual-chamber or atrial only) or ventricular-pacing-only permanent pacemakers provide chronotropic competence, with unknown health-related quality of life (QOL) differences between these options. The QOL studies within the Canadian Trial of Physiologic Pacing were performed to assess whether QOL differences exist in patients randomized to these 2 pacing modes. METHODS: Two QOL protocols were performed: 1) a substudy of 269 patients with detailed QOL measures (The Medical Outcomes Study, Short-Form [SF-36], the Pacemaker Syndrome Scale, an activity scale, and a pacemaker-specific scale) at baseline and 6 months after implantation; and 2) a parent study assessment of QOL in 1721 patients with a 12-item QOL instrument package (SF-6, "ladder of life," and pacemaker syndrome scale) given 6 months after implantation only. RESULTS: In the substudy, pacing was associated with an average significant (P <.05) 0.36 SD unit improvement in QOL across all domains (SF-36: 38 +/- 9 to 41 +/- 11 for physical scores, 47 +/- 11 to 52 +/- 9 for mental health scores, both P <.001). Similar improvements were seen with the pacemaker-specific scales. There were no significant differences in the absolute or relative improvement in QOL between assigned pacing modes. The parent study similarly showed no differences in QOL between pacing modalities. Presyncope occurred in 31% of patients in the physiological pacing group, compared with 38% of the patients in the ventricular pacing group (P <.01). No other symptoms were different between the 2 groups. Pacemaker dependency, defined as an escape heart rate <50 beats per minute, did not influence the lack of difference in QOL scores between the 2 assigned pacing modes. CONCLUSION: In this largest randomized assessment of QOL in patients with pacemakers, with the instruments used, there was no significant health-related QOL difference seen between "physiologic" pacing and ventricular pacing.

Aged↗
PubMed2003

Long-term amiodarone therapy and the risk of complications after cardiac surgery: results from the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT).

OBJECTIVE: This study was undertaken to determine the association between amiodarone therapy and risk of complications of cardiac surgery in patients in the randomized placebo-controlled, double-blind Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. METHODS: Prospectively collected data regarding postoperative complications in 82 patients who underwent cardiac surgery during Canadian Amiodarone Myocardial Infarction Arrhythmia Trial participation were analyzed; 36 patients were randomly assigned to receive amiodarone and 46 were assigned to receive placebo. Of the patients randomly assigned to receive amiodarone, 24 patients continued amiodarone treatment to within 7 days of the operation (active amiodarone group) and 12 patients had the amiodarone discontinued at least 7 days before the operation (discontinued amiodarone group). RESULTS: The baseline characteristics of the three groups were similar. The risks of ventricular fibrillation, atrial fibrillation, and respiratory complications were similar. The risk of requiring an intra-aortic balloon pump was significantly increased by amiodarone (34.8% vs 16.7% vs 8.7% for active amiodarone, discontinued amiodarone, and placebo groups, respectively, P =.024). There was no significant difference in the use of temporary pacing. Neither the mean duration of stay in the intensive care unit nor the 7- and 30-days mortalities were affected by amiodarone. CONCLUSIONS: Patients receiving long-term amiodarone treatment after myocardial infarction had a higher rate of intra-aortic balloon use after cardiac surgery. There was no increased risk of pulmonary complications, need for pacing, or death.

Administration, Oral↗
PubMed2003

Strategies for reversing shock-resistant ventricular fibrillation.

PURPOSE OF REVIEW: Shock-resistant ventricular fibrillation is defined as ventricular fibrillation persisting after three defibrillation attempts. In approximately 10 to 25% of all cardiac arrests, shock-resistant ventricular fibrillation develops, and 87 to 98% of these patients die. RECENT FINDINGS: In the treatment of shock-resistant ventricular fibrillation, defibrillation using biphasic waveforms is considered as an intervention of choice. Intravenous amiodarone is also acceptable, safe, and useful, based on evidence from two randomized clinical trials. Intravenous vasopressin is acceptable and probably safe and useful, but the evidence supporting this recommendation is coming from a small, randomized clinical trial. Procainamide is acceptable but not recommended. In the presence of acute myocardial infarction and recurrent ventricular fibrillation, if all other therapies fail, beta-blockers can be considered. Magnesium, lidocaine, and bretylium are not recommended in the treatment of shock-resistant ventricular fibrillation. SUMMARY: Biphasic defibrillation and intravenous amiodarone are useful in shock-resistant ventricular fibrillation.

Adrenergic beta-Antagonists↗
PubMed2003

Correlates of therapeutic response in panic disorder presenting with palpitations: heart rate variability, sleep, and placebo effect.

OBJECTIVE: To examine the correlates of therapeutic response of patients with panic disorder presenting with palpitations, we hypothesized that therapeutic response would correlate with heart rate variability (HRV) and sleep measures. METHODS: After a 1-week placebo washout, 27 patients free of structural heart disease and not on cardioactive drugs were randomized in a double-blinded fashion to 4 weeks of treatment with clonazepam (a known antipanic agent) or placebo. We performed standard sleep measures and recorded HRV from 24-hour Holter acquisitions at baseline and end of study. We defined response to therapy as a 50% improvement in the Hamilton Anxiety Rating Scale (HARS) score, confirmed by questionnaires and reaction to sodium lactate infusion. RESULTS: There were 12 responders and 15 nonresponders. Normalization of sleep pattern (including less stage 1 and rapid eye movement [REM] sleep) was observed in both drug and placebo responders (P = 0.011 and P = 0.05, respectively) and in placebo responders alone, compared with nonresponders (P = 0.006 and P = 0.013, respectively). Placebo responders were more likely to show less depression, but even after we controlled for depression, main sleep effects remained. None of the HRV measures correlated with response, but compared with placebo, clonazepam led to a decrease in all the time and frequency domain measures of HRV (all P < 0.05). CONCLUSIONS: Central mechanisms are related to the therapeutic response of patients with panic disorder presenting with palpitations, but this does not directly correlate with HRV. Larger and longer studies may allow objective explanations of placebo response in panic disorder.

Adolescent↗
PubMed2003

Antiarrhythmic drug therapy of atrial fibrillation: focus on new agents.

The precise mechanisms of clinical effect of antiarrhythmic agents and the ideal "molecular targets" against arrhythmias, in particular atrial fibrillation, are poorly understood. Current antiarrhythmic drug development, particularly for drugs expected to be active against atrial fibrillation, has focused on drugs with multiple ionic mechanisms of action, in particular on those that block multiple potassium channels. Investigation of antiarrhythmic agents is complicated by the diversity of animal-disease models studied, by the potential multiple mechanisms of arrhythmias, and by the incompletely understood relationships between risks and benefits of antiarrhythmic drug therapy. Furthermore, rhythm control strategies in large groups of patients with atrial fibrillation have failed to show substantial clinical benefit. Nevertheless, drugs that block multiple potassium channels and appear to have relatively little organ toxicity, such as tedisamil, may represent an important new avenue in the therapeutic approach to highly symptomatic arrhythmias such as atrial fibrillation.

Action Potentials↗
PubMed2003

Left ventricular performance during acute rate control in atrial fibrillation: the importance of heart rate and agent used.

BACKGROUND: The relation between heart rate and left ventricular function during rate control in atrial fibrillation is incompletely understood. METHODS: Twenty-four patients (age 67 +/- 11 years) with symptomatic recent onset rapid atrial fibrillation and rapid ventricular rate (> 110 bpm) were randomly assigned to receive either intravenous digoxin (13 mcg/kg) or intravenous diltiazem (0.25 mg/kg bolus plus a maintenance infusion). A portable radionuclide detector was used to collect validated measures of relative left ventricular volumes, along with heart rate data, every 15 seconds for 6 hours. RESULTS: Heart rate decreased significantly at 15 minutes and 180 minutes in the diltiazem group (from 133 +/- 18 bpm to 111 +/- 26 bpm [P <.01] to 94 +/- 24 bpm [P <.001]) but not in the digoxin group (from 129 +/- 18 bpm to 126 +/- 17 bpm [P = NS] to 118 +/- 15 bpm [P = NS]). Left ventricular ejection fraction improved in both groups to a similar extent (from 39 +/- 10% to 50 +/- 8%, [P <.05] after diltiazem, and from 38 +/- 8% to 52 +/- 11% [P <.05] after digoxin at baseline vs 180 minutes, respectively). The ejection fraction vs heart rate slope was steeper in the digoxin group than in the diltiazem group (-0.34 +/- 0.18 vs -0.16 +/- 0.17, P =.048) indicating a more pronounced improvement in ejection fraction per unit decrease in heart rate. CONCLUSION: In patients with acute atrial fibrillation, digoxin led to similar improvements in ejection fraction compared to diltiazem despite a slower and less potent heart rate slowing.

Aged↗
PubMed2003

Guidelines for implantable cardioverter defibrillator follow-up in Canada: a consensus statement of the Canadian Working Group on Cardiac Pacing.

A survey on the follow-up practices of patients with implantable cardioverter defibrillators (ICDs) in Canada was conducted by the Canadian Working Group on Cardiac Pacing in 1999. The survey identified the need for national guidelines. The present guidelines for ICD follow-up represent a consensus statement of the Canadian Working Group on Cardiac Pacing. They recommend that patients be assessed before hospital discharge, at two to 12 weeks following implantation, six months after implantation, and at a minimum of every six months thereafter. More frequent assessments may be required for some patients depending on associated cardiovascular problems and specific ICD devices. A typical follow-up visit should include a targeted cardiovascular assessment, interrogation of the ICD, review of telemetered data, assessment of the underlying rhythm, pacing and sensing thresholds, lead impedance and appropriate reprogramming of ICD parameters to optimize device function and longevity.

Cardiac Pacing, Artificial↗
PubMed2003

Folie à deux: an old diagnosis with a new technology.

The implantable cardioverter defibrillator (ICD) is the treatment of choice for life-threatening ventricular tachyarrhythmias. Despite this, indications for explantation have been described. Psychiatric complications have been considered in the decision to not re-implant a previously explanted device but never as a primary indication for explantation. The case of a woman who requested ICD explantation amidst concerns that the titanium used in its construction was absorbing harmful negative electromagnetic field energy from the environment resulting in intermittent bouts of fatigue, diaphoresis and an overall sense of impending doom is presented. She and her husband had significant psychosocial impairment because of this belief system. The present case is the first known report of a psychiatric complication as the primary indication for ICD explantation. It is illustrative of diagnostic dilemmas, competency and the importance of quality of life.

Aged↗
PubMed2002

Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation.

BACKGROUND: Lidocaine has been the initial antiarrhythmic drug treatment recommended for patients with ventricular fibrillation that is resistant to conversion by defibrillator shocks. We performed a randomized trial comparing intravenous lidocaine with intravenous amiodarone as an adjunct to defibrillation in victims of out-of-hospital cardiac arrest. METHODS: Patients were enrolled if they had out-of-hospital ventricular fibrillation resistant to three shocks, intravenous epinephrine, and a further shock; or if they had recurrent ventricular fibrillation after initially successful defibrillation. They were randomly assigned in a double-blind manner to receive intravenous amiodarone plus lidocaine placebo or intravenous lidocaine plus amiodarone placebo. The primary end point was the proportion of patients who survived to be admitted to the hospital. RESULTS: In total, 347 patients (mean [+/-SD] age, 67+/-14 years) were enrolled. The mean interval between the time at which paramedics were dispatched to the scene of the cardiac arrest and the time of their arrival was 7+/-3 minutes, and the mean interval from dispatch to drug administration was 25+/-8 minutes. After treatment with amiodarone, 22.8 percent of 180 patients survived to hospital admission, as compared with 12.0 percent of 167 patients treated with lidocaine (P=0.009; odds ratio, 2.17; 95 percent confidence interval, 1.21 to 3.83). Among patients for whom the time from dispatch to the administration of the drug was equal to or less than the median time (24 minutes), 27.7 percent of those given amiodarone and 15.3 percent of those given lidocaine survived to hospital admission (P=0.05). CONCLUSIONS: As compared with lidocaine, amiodarone leads to substantially higher rates of survival to hospital admission in patients with shock-resistant out-of-hospital ventricular fibrillation.

Aged↗
PubMed2002

Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation.

BACKGROUND: The impact of atrial fibrillation (AF) and its treatment on health-related quality of life (QOL) is not well understood. We assessed QOL in patients with symptomatic AF participating in the Canadian Trial of Atrial Fibrillation. METHODS: Self-report QOL questionnaires including the Short-Form-36 (SF-36), symptom checklist (SCL) and AF Severity Scale (AFSS) were completed at baseline and 3, and 12 months after randomization. RESULTS: The study group was aged 65 +/- 10 years and 59% were male. By design, 50% of patients were randomized to amiodarone (n = 132), 25% to sotalol (n = 66), and 25% to propafenone (n = 66). Most patients had normal left ventricular function (89%). Physical (41.9 +/- 9.3 to 43.7 +/- 9.2, P =.001) and mental health (47.5 +/- 10.5 to 49.0 +/- 9.8, P =.023) summary measures from the SF-36 improved significantly from baseline to 3 months. Arrhythmia symptom frequency and severity (SCL) also improved markedly from baseline to 3 months (symptom frequency 20.4 +/- 9.4 to 16.2 +/- 9.5 and symptom severity 16.7 +/- 8.2 to 12.9 +/- 7.4, both P <.001). QOL improvements were not significantly different among the groups randomized to amiodarone, sotalol, or propafenone. However, patients with no symptomatic recurrences of AF had higher scores at 3 months on measures of global well-being than those with recurrences in the first 3 months (7.4 +/- 1.8 vs 6.9 +/- 1.8, P <.05). There were no significant QOL changes from the 3 to 12 month assessment. CONCLUSION: In patients with symptomatic AF, QOL improves after treatment, independent of the specific drug used for treatment. This is especially true for patients in whom treatment prevents AF recurrence.

Aged↗
PubMed2002

Quality of life in the Canadian Implantable Defibrillator Study (CIDS).

BACKGROUND: The primary aim of this study was to compare quality-of-life outcome between patients randomized to implantable cardioverter defibrillator (ICD) therapy and patients randomized to amiodarone treatment in the Canadian Implantable Defibrillator Study (CIDS). A secondary aim was to evaluate the effects on quality-of-life outcomes of receiving shocks from the device. METHODS: Quality of life was assessed in 317 English-speaking participants by use of the Rand Corporation's 38-item Mental Health Inventory (MHI) and the Nottingham Health Profile (NHP). Assessments were done in the hospital at baseline and with mailed questionnaires after 2, 6, and 12 months of follow-up. Sixty-two percent of patients completed the follow-up assessments at 6 and 12 months. RESULTS: Repeated measures analysis of variance revealed significant time by treatment group interaction effect on total MHI and the psychological distress and psychological well-being sub-scales, and on 5 of the 7 NHP scales (energy, physical mobility, emotional reactions, sleep disturbance, and lifestyle impairment) (P <.05). Emotional and physical health scores were shown to improve significantly in the ICD group and were either unchanged (emotional health) or deteriorated (energy and physical mobility) in the amiodarone-treated group by means of post-hoc comparisons. Quality of life did not improve in the subgroup of patients in the ICD-treated group who received > or =5 shocks from their device. CONCLUSION: Quality of life is better with ICD therapy than with amiodarone therapy. The beneficial quality-of-life effects from an ICD are not evident in patients who receive numerous shocks from their device.

Aged↗
PubMed2002

Terikalant and barium decrease the area of vulnerability to ventricular fibrillation induction by T-wave shocks.

The area of vulnerability (AOV) to ventricular fibrillation (VF) induction by high-voltage shocks has been proposed as a measure of vulnerability to VF. Biphasic shocks spanning the T wave and ranging between 50 V and the upper limit of vulnerability (ULV) to VF were delivered before and after terikalant (1 mg/kg) and barium (1.1 mg/kg load followed by 0.05-0.10 mg/kg/min maintenance) or vehicle in dogs. The AOV decreased by 34% and 28% (p < 0.01) after terikalant and barium (n = 8 dogs each), respectively. Mean ULV, defibrillation threshold (DFT), and ventricular vulnerability period (VVP) decreased by 16%, 23%, and 31% (p < 0.01), respectively, after terikalant, and by 25%, 17% (p < 0.01), and 13% (p = 0.08), respectively, after barium. Vehicle (n = 14) did not significantly alter any of these variables. The ULV was correlated with the DFT before and after terikalant (r = 0.78, p < 0.01) and barium (r = 0.83, p < 0.01). Potassium channel blockers of the current reduce the ability to induce VF; this effect may be related to the anti-fibrillatory action of class III anti-arrhythmic drugs and their ability to decrease DFT.

Action Potentials↗
PubMed2002

Combination IK1 and IKr channel blockade: no additive lowering of the defibrillation threshold.

Selective blockade of the inward rectifier potassium channel I(K1) by barium, or of the rapidly activating delayed rectifier potassium channel I(Kr) by D,L-sotalol, prolongs repolarization and reduces the defibrillation threshold (DFT). This study hypothesized that combination I(K1) and I(Kr) channel block would produce concentration-dependent additive effects on DFT and ventricular refractoriness. A range of barium and D,L-sotalol concentrations, alone and in combination, were examined with respect to DFT, ventricular effective refractory period (VERP), and ventricular fibrillation cycle length (VFCL) in 133 Langendorff-perfused rabbit hearts. Barium produced a concentration-dependent reduction of DFT (-49+/-4%), with concentration-dependent increases in VERP (26+/-6%) and VFCL (42+/-18%). D,L-Sotalol produced a concentration-dependent lowering of DFT (-53+/-6%) with a concentration-dependent increase in VFCL (34+/-8%) but not VERP. Low (1.6 microM), intermediate (3.1 microM), and high (12.5 microM) barium concentrations combined with varying D,L-sotalol concentrations produced equal or smaller decreases in DFT compared with corresponding doses of barium or D,L-sotalol alone. Except at the lowest concentrations of barium (1.6 and 3.1 microM) (p < 0.05), there was no significant additive interaction between barium and D,L-sotalol on VERP or VFCL. Combination I(K1) and I(Kr) channel block by barium and D,L-sotalol does not produce additive reduction of DFT.

Algorithms↗
PubMed2002

The effect of isoproterenol on the class III effect of azimilide in humans.

BACKGROUND: Many class III antiarrhythmic agents lose efficacy under beta-adrenergic stimulation and at high heart rates (reverse rate dependence). This effect is thought to be due to selective blockade of the rapidly (I(Kr)), but not the slowly (I(Ks)), activating component of the delayed inward rectifier potassium current. Azimilide is an investigational class III antiarrhythmic agent that blocks both IKr and IKs. METHODS: We investigated the electrophysiologic effect of azimilide with and without beta-adrenergic stimulation in humans. Right ventricular effective refractory period at cycle lengths of 600 and 400 milliseconds and monophasic right ventricular action potential duration at 90% repolarization at cycle lengths of 250, 300, 400, 500 and 600 milliseconds were measured in 13 patients at baseline. Isoproterenol was then infused to increase the heart rate to 125% of baseline, and the pacing protocol was repeated. Patients then received, in a single-blind randomized manner, azimilide dihydrochloride (4.5 mg/kg intravenous loading dose followed by 0.625 mg/kg/h) plus either isoproterenol at the previous dose, or saline. After measurements were taken, treatment groups were crossed over, the azimilide infusion was continued and the procedure repeated. RESULTS: Azimilide significantly (P < 0.05) prolonged monophasic action potential duration compared to baseline at all cycle lengths except for the 250 millisecond cycle length. In the presence of isoproterenol, azimilide maintained its class III effect, prolonging the action potential duration at 90% repolarization by a mean of 8.7 +/- 3.9 milliseconds, (3.7 +/- 1.7%), whereas isoproterenol alone shortened the action potential duration at 90% repolarization by -2.6 +/- 3.2 milliseconds (-1.2 +/- 1.4%) (P = 0.0051). Isoproterenol alone shortened the right ventricular effective refractory period by -13.6 +/- 3.4 milliseconds, whereas with isoproterenol in the presence of azimilide, the right ventricular effective refractory period was essentially unaffected (-1.4 +/- 3.4 milliseconds, P = 0.0085). CONCLUSIONS: Azimilide maintained its class III effect in the presence of isoproterenol and at increased heart rates, suggesting that IKs block may be of particular benefit in these circumstances.

Action Potentials↗