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Biomedical subjects

P Dorian

Publications and source records attributed to P Dorian.

At least 19 recordsLinked to original sources
PubMed2006

The impact of implantable cardiac defibrillators for primary prophylaxis in the community: baseline risk and clinically meaningful benefits.

OBJECTIVE: To estimate the baseline risk of arrhythmic death required for prophylactic implantable cardiac defibrillators (ICDs) to result in clinically meaningful survival benefits in the population. BACKGROUND: While proven efficacious, the absolute survival impact of ICDs for the primary prevention of sudden cardiac death among patients with left ventricular (LV) dysfunction is highly dependent upon patient's baseline risk of arrhythmic death. METHODS: Using echocardiographic data from a random sample of patients identified from community echocardiographic laboratories, patients with moderate or severe LV dysfunction (ejection fraction < 35%) were linked to administrative databases to characterize baseline mortality risk (median follow-up duration of 4.85 years). Relative efficacy was ascertained from meta-analysis and clinical trial data. The baseline annual risk of arrhythmic death required for prophylactic ICDs to result in clinically meaningful survival benefits in the population was estimated at different ranges of relative efficacy and numbers needed to treat (NNTs) thresholds. RESULTS: LV dysfunction was a significant independent predictor of adverse outcomes. In total, 35.4% of the patients with moderate to severe LV dysfunction died during the follow-up period. Assuming a base-case relative efficacy of 66%, we estimated that the baseline risk for arrhythmic death required to exert a clinically meaningful NNT threshold of 50 in order to prevent one death (from any cause) was 3% per year or higher. CONCLUSIONS: The survival impact and cost-effectiveness of prophylactic ICDs in the population will depend upon the ability to risk-stratify and identify patients whose baseline risk for sudden cardiac death exceed 3% per year.

Death, Sudden, Cardiac↗
PubMed2005

Improvement in Cheyne-Stokes respiration following cardiac resynchronisation therapy.

The effect of standard cardiac resynchronisation therapy (CRT) on the severity of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure was studied. It was hypothesised that CRT, through its known beneficial effects on cardiac function, would stabilise the control of breathing and reduce CSR. Twenty-eight patients who were eligible for CRT and receiving optimised medical treatment for congestive heart failure were referred for overnight polysomnography, including monitoring of thoracic and abdominal movements to identify CSR and obstructive sleep apnoea events. Patients underwent repeat polysomnography after 6 months of CRT to re-evaluate sleep quality and sleep-disordered breathing. Twelve of the 28 patients had significant CSR (43%); 10 patients had a successful implantation and underwent repeat polysomnography a mean+/-SD 27+/-7 weeks after continuous biventricular pacing. Six of the 10 patients experienced a significant decrease in CSR severity following CRT, associated with correction of congestive heart failure-related hyperventilation and hypocapnia. Circulation time, oxygen saturation, frequency of obstructive apnoeas and sleep quality did not change. In conclusion, cardiac resynchronisation therapy is associated with a reduction in Cheyne-Stokes respiration, which may contribute to improved clinical outcome in patients treated with cardiac resynchronisation therapy.

Aged↗
PubMed2005

Canadian Cardiovascular Society commentary on implantable cardioverter defibrillators in Canada: waiting times and access to care issues.

The Canadian Cardiovascular Society is the national professional society for cardiovascular specialists and researchers in Canada. In the spring of 2004, the Canadian Cardiovascular Society Council formed an Access to Care Working Group in an effort to use the best science and information to establish reasonable triage categories and safe wait times for access to common cardiovascular services and procedures. The Working Group has elected to publish a series of commentaries to initiate a structured national discussion on this very important issue. Access to treatment with implantable cardioverter defibrillators is the subject of the present commentary. The prevalence pool of potentially eligible patients is discussed, along with access barriers, regional disparities and waiting times. A maximum recommended waiting time is proposed and the framework for a solution-oriented approach is presented.

Canada↗
PubMed2001

Gap junction blockers decrease defibrillation thresholds without changes in ventricular refractoriness in isolated rabbit hearts.

BACKGROUND: The maintenance and termination of reentry arrhythmias are determined by tissue properties such as refractoriness and conduction velocity. Although the effects of Na(+) and K(+) channel block on electrophysiological properties and defibrillation threshold (DFT) have been studied, little is known about the effect of gap junction blockers on defibrillation and tissue electrophysiological properties. METHODS AND RESULTS: Triplicate DFTs (volts) were obtained before and 15 minutes after 4 micromol/L 16-doxyl-stearic acid (16-DSA, n=8), 1 mmol/L 1-heptanol (n=12) (both gap junction blockers), 3 microg/mL lidocaine (a sodium channel blocker) (n=8), and respective controls (n=27) in isolated perfused rabbit hearts. DFT decreased after 16-DSA (23+/-14%, P<0.01) and 1-heptanol (21+/-16%, P<0.01) but increased after lidocaine (26+/-28%, P<0.05). Ventricular fibrillation cycle length (VFCL) and QRS duration increased after all 3 agents, by 36+/-19% and 44+/-16% (16-DSA), 87+/-42% and 49+/-15% (heptanol), and 57+/-20% and 43+/-26% (lidocaine), respectively (all P<0.01). Spatially averaged temporal VFCL dispersion decreased significantly after all 3 agents, by 47+/-42% (16-DSA, P<0.05), 74+/-19% (1-heptanol, P<0.01), and 82+/-13% (lidocaine, P<0.01), respectively. Ventricular effective refractory period and monophasic action potential duration at 90% repolarization were unchanged after 16-DSA and 1-heptanol (P=NS) but increased after lidocaine (16+/-13%, P<0.01, and 6+/-5%, P=NS, respectively). There were no significant changes in DFT or any other electrophysiological variable in control hearts. CONCLUSIONS: Electrical uncoupling by 16-DSA and 1-heptanol significantly lowers DFT and dispersion of VFCL without altering refractoriness; lidocaine, at doses resulting in similar slowing of conduction, increases DFT.

Animals↗
PubMed2001

New-onset atrial fibrillation: sex differences in presentation, treatment, and outcome.

BACKGROUND: Although sex differences in coronary artery disease have received considerable attention, few studies have dealt with sex differences in the most common sustained cardiac arrhythmia, atrial fibrillation (AF). Differences in presentation and clinical course may dictate different approaches to detection and management. We sought to examine sex-related differences in presentation, treatment, and outcome in patients presenting with new-onset AF. METHODS AND RESULTS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF. Participants were followed at 3 months, at 1 year, and annually thereafter. Treatment was at the discretion of the patients' physicians and was not directed by CARAF investigators. Baseline and follow-up data collection included a detailed medical history, clinical, ECG, and echocardiographic measures, medication history, and therapeutic interventions. Three hundred thirty-nine women and 560 men were followed for 4.14+/-1.39 years. Compared with men, women were older at the time of presentation, more likely to seek medical advice because of symptoms, and experienced significantly higher heart rates during AF. Compared with older men, older women were half as likely to receive warfarin and twice as likely to receive acetylsalicylic acid. Compared with men on warfarin, women on warfarin were 3.35 times more likely to experience a major bleed. CONCLUSIONS: Anticoagulants are underused in older women with AF relative to older men with AF, despite comparable risk profiles. Women receiving warfarin have a significantly higher risk of major bleeding, suggesting the need for careful monitoring of anticoagulant intensity in women.

Anticoagulants↗
PubMed2001

Thrombogenicity of radiofrequency ablation procedures: what factors influence thrombin generation?

AIMS: Thromboembolic complications have been reported after radiofrequency ablation but the low incidence of overt clinical events has been a limitation to the study of factors affecting thrombogenic risk. The aim of this study was to determine whether radiofrequency ablation has a procoagulant effect and to examine variables that affect thrombio generation. METHODS AND RESULTS: Thirty-seven consecutive patients who underwent radiofrequency ablation were studied prospectively. Blood samples were assayed for thrombin-antithrombin III (TAT) and d-dimer (DD) at five different time points: (1) baseline; (2) after sheath insertion; (3) after electrophysiological study but before radiofrequency ablation; (4) at completion of the procedure; and (5) 24 h post-procedure. TAT levels were within the normal range at baseline and increased significantly after sheath insertion from 2.1 +/- 1.2 microg l(-1) to 13.3 +/- 16.0 microg l(-1) (P<0.01). Levels increased further to 24.0 +/- 19.9 microg l(-1) (P<0.01) after electrophysiological study but did not increase after radiofrequency ablation. TAT normalized at 24 h. DD increased significantly from baseline values (230.2 +/- 176.8 ng ml(-1)) to 285.4 +/- 237.4 ng ml(-1) (P=0.019) after sheath insertion. There was a further significant increase after electrophysiological study to 423.4 +/- 324.3 ng ml(-1) (P<0.01), and a slight but non-significant increase to 464.4 +/- 307.4 ng ml(-1) after radiofrequency ablation (P=0.159). DD remained elevated at 24 h. Procedure duration was the only variable that correlated with the relative increase in TAT and DD. The patients with the longest procedure durations had more catheters inserted, more radiofrequency applications and largely consisted of accessory bypass tract-mediated tachycardias. Heparin administration significantly blunted the relative increase in TAT after radiofrequency ablation (P=0.005). CONCLUSION: Radiofrequency ablation procedures confer an increased risk of thrombosis. Catheterization and diagnostic study contribute largely to the thrombogenic stimulus. Thrombogenicity is increased in prolonged, complex procedures and is decreased in patients who have been administered heparin during the procedure.

Adult↗
PubMed2001

Intravenous antiarrhythmic agents.

Intravenous antiarrhythmic drugs can be used as diagnostic tools; for example, adenosine can be used to reveal the underlying rhythm in narrow QRS tachycardia. Newer class III antiarrhythmic agents, like ibutilide and dofetilide, are effective at the conversion of acute atrial fibrillation; however, electrical cardioversion is still the most effective method for restoration of sinus rhythm in persistent atrial fibrillation. Lidocaine and bretylium in the treatment and prevention of ventricular tachyarrhythmia are de-emphasized because of inefficacy, safety concerns (lidocaine), or shortage of drug (bretylium). Procainamide is effective for stable ventricular tachycardia, and amiodarone is effective in the treatment of shock-refractory ventricular fibrillation. Adrenergic blockade is likely important in the management of tachyarrhythmias, particularly in electrical storm, but more data will be necessary to establish its role.

Amiodarone↗
PubMed2001

Effects of rhythm regularization and rate control in improving left ventricular function in atrial fibrillation patients undergoing atrioventricular nodal ablation.

OBJECTIVES: To assess the relative contributions of rate control and rhythm regularization to left ventricular function in atrial fibrillation (AF) patients undergoing atrioventricular nodal ablation. This was performed by assessing the effect of ventricular rhythm regularization on left ventricular function during AF, and the effect of varying heart rate on left ventricular function after ablation. PATIENTS AND METHODS: Eleven patients with continuous AF and V/VI-R pacemakers undergoing therapeutic atrioventricular nodal ablation were studied. Preablation patients underwent two 30 min observation periods in a randomized, blinded fashion during which they were either in baseline AF (pacer set to default V/VI 50/min) or being paced using a rhythm stabilizing algorithm (RSA) designed to regularize rhythm without changing baseline ventricular rate. Six weeks after ablation, patients were again observed during the two following 30 min periods: pacing at a low clinically indicated rate (69+/-9 beats/min), and pacing at the rapid, mean preablation rate. During all observation periods, left ventricular function was measured continuously using a nuclear vest that provided validated measures of heart rate, ejection fraction, and normalized end-systolic volume (ESV) and end-diastolic (EDV) volume. RESULTS: Before ablation, RSA successfully regularized rhythm, decreasing the coefficient of variation of interbeat intervals 20+/-5% to 10+/-4% (P<0.001). The heart rate with RSA (105+/-19 beats/min) was not significantly different from the baseline AF rate (102+/-21 beats/min). Increased rhythm regularity achieved by RSA significantly improved left ventricular function, decreasing ESV from 62+/-12 units to 57+/-11 units (P=0.03), and increasing the ejection fraction from 31+/-11% to 36+/-11% (P=0.03). After ablation, at the clinically indicated low pacing rate of 69+/-9 beats/min, a much greater improvement in ejection fraction was observed, increasing to 44+/-13% (P=0.005 compared with preablation). However, rapid regular pacing at the mean preablation rate of 110+/-18 beats/min eradicated this improvement, decreasing the ejection fraction to 31+/-8% (P=0.003), and increasing ESV from 53+/-13 units to 62+/-8 units (P=0.006). CONCLUSIONS: Rhythm regularity achieved by a regularizing pacing algorithm can significantly, albeit modestly, improve left ventricular function in AF. However, more marked improvements in left ventricular function seen after ablation are primarily due to rate reduction alone.

Aged↗
PubMed2000

Role of gender and personality on quality-of-life impairment in intermittent atrial fibrillation.

Patients with atrial fibrillation (AF) report impaired health-related quality of life (QOL). Differences between men and women with AF have not been described and personality attributes such as somatization (tendency to amplify benign bodily sensations) may mediate potential gender differences in QOL. Patients with AF (n = 264, 59% men) who participated in the Canadian Trial of Atrial Fibrillation (n = 403) completed validated QOL questionnaires at baseline, 3 months, and 12 months after antiarrhythmic drug treatment. Women were significantly older than men and a greater proportion had hypertension, but other cardiac variables did not differ between women and men. At baseline, after controlling for significant clinical and demographic factors, women reported worse physical health (p = 0.002) and functional capacity (p < 0.001), but not mental health or general well-being. Women also had more frequent and severe cardiac symptoms than men (both p < 0.001). Physical health improved significantly from baseline to 3 months for women (p = 0.002), but not for men (p = 0.066). Conversely, mental health improved for men (p = 0.007), but not for women. Cardiac symptom frequency and severity improved over time for women and men (all p < 0.001). Tendency to somatize predicted poor QOL, and women had higher scores than men (p = 0.023). However, after controlling for somatization, women still had worse physical function, functional capacity, and symptom burden than men. Independent of cardiac disease severity and age, women with AF had significantly more impaired QOL than men, specifically on domains related to physical rather than emotional functioning. Personality attributes may have a role in influencing QOL outcomes.

Age Factors↗
PubMed2000

Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.

Aged↗
PubMed2000

Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone.

BACKGROUND: Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone. METHODS AND RESULTS: A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, -7.7% to 40%; P=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, -7.2% to 57.8%; P=0.094). CONCLUSIONS: A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.

Aged↗
PubMed2000

Effect of physiological mechanical perturbations on intact human myocardial repolarization.

OBJECTIVE: The objective of this study was to investigate the relationship between acute decreases in right ventricular volume during Valsalva strain (with resultant changes in autonomic neural tone) and measures of local endocardial repolarization time independent of heart rate and autonomic neural tone. METHODS: Patients implanted with a stimulus to T wave (Stim-T) sensing pacemaker specially adapted to output a validate measure of beat to beat local repolarization (n = 9) performed Valsalva manoeuvers (40 mmHg for 15 s) while paced at a cycle length of 500 ms. Stim-T intervals were measured before and after autonomic blockade (Block: 0.03 mg/kg i.v. atropine +/- 0.15 mg/kg propranolol). Right ventricular end diastolic volume was estimated by simultaneous 2D-echocardiography. RESULTS: Without autonomic blockade, compared to baseline, repolarization significantly prolonged during Valsalva strain (1.1 +/- 0.7%) and shortened during release (-1.4 +/- 1.0%). After block, strain related repolarization prolongation was also observed (1.0 +/- 0.6%), with significantly less release related repolarization shortening (-0.8 +/- 0.8%) compared to pre-block (P < 0.05). Right ventricular end diastolic volume decreased during strain by 11 +/- 10 and 9 +/- 16% from baseline, pre- and post-block respectively (P < 0.05). CONCLUSION: In a chronically instrumented human model, an acute physiologic volume reduction modestly prolongs right ventricular repolarization independent of changes in rate or autonomic tone.

Action Potentials↗
PubMed2000

Inappropriate therapy from atrial fibrillation and sinus tachycardia in automated implantable cardioverter defibrillators.

BACKGROUND: Inappropriate therapy from supraventricular tachyarrhythmias (atrial fibrillation [AF] and sinus tachycardia [ST]) in patients with implanted cardioverter defibrillators is a major challenge. We tested the performance of stability algorithms from 3 manufacturers for episodes of inappropriate therapy delivered because of AF and an onset algorithm for all episodes of inappropriate therapy caused by ST. METHODS: Therapy was classified as caused by ventricular tachycardia (VT), ST, or AF from review of stored intracardiac electrograms, history, clinical information, and R-R data before study inception. By using 30 to 60 R-R intervals before therapy, sensitivity and specificity for a family of stability values and percentage of onset values were calculated for each manufacturer and receiver operating characteristic curves generated. RESULTS: Of the 217 patients monitored, 62 (29%) received inappropriate therapy, and 40 had complete R-R information available. Of the 40 patients, 21 patients received therapy for AF, 19 for ST, and 1 patient for noise; 15 (38%) also received appropriate therapy for VT. We analyzed 83 episodes of VT from 18 patients, 94 episodes of AF from 21 patients, and 56 episodes of ST from 19 patients. Specificity, in the clinically relevant sensitivity range of >/=95%, was comparable across manufacturers at about 40%. An onset value of 80% was associated with 91% sensitivity and 95% specificity for the specific algorithm tested. CONCLUSIONS: Inappropriate therapy is a common problem in implantable cardiac defibrillators. The performance of the stability algorithms used to differentiate AF from VT was less than ideal, though comparable across manufacturers. The onset algorithm accurately differentiates ST from VT.

Aged↗
PubMed2000

The impairment of health-related quality of life in patients with intermittent atrial fibrillation: implications for the assessment of investigational therapy.

OBJECTIVES: We sought to assess the impact of intermittent atrial fibrillation (AF) on health-related quality of life (QoL). BACKGROUND: Intermittent AF is a common condition with little data on health-related QoL questionnaires to guide investigational therapies. METHODS: Outpatients from four centers, with documented AF (n = 152), completed validated QoL questionnaires (Medical Outcomes Study Short Form 36 [SF-36], Specific Activity, Symptom Checklist, Illness Intrusiveness and University of Toronto AF Severity Scales). Comparison groups were made up of healthy individuals (n = 47) and four cardiac control groups: published (n = 78) and created for study (n = 69) percutaneous transluminal coronary angioplasty (PTCA); published heart failure (n = 216) and published postmyocardial infarction (MI) (n = 107). RESULTS: Across all domains of the SF-36, AF patients reported substantially worse QoL than healthy controls (1.3 to 2.0 standard deviation units), with scores of 24%, 23%, 16% and 30% lower than healthy individuals on measures of physical and social functioning, mental and general health, respectively (all p < 0.001). Patients with AF were either significantly worse (p < 0.05, published controls) or as impaired (study controls) as either PTCA or post-MI patients on all domains of the SF-36 and the same as heart failure controls on SF-36 psychological subscales. Patients with AF were as impaired or worse than study PTCA controls on measures of illness intrusiveness, activity limitations and symptoms. Associations between objective disease indexes and subjective QoL measures had poor correlations and accounted for <6% of the total variability in QoL scores. CONCLUSIONS: Quality of life is as impaired in patients with intermittent AF as in patients with significant structural heart disease. Patients' perception of QoL is not dependent on the objective measures of disease severity that are usually employed.

Anti-Arrhythmia Agents↗