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Biomedical subjects

Robert Sheldon

Publications and source records attributed to Robert Sheldon.

At least 19 recordsLinked to original sources
PubMed2006

Prevention of Syncope Trial (POST): a randomized, placebo-controlled study of metoprolol in the prevention of vasovagal syncope.

BACKGROUND: Previous studies that assessed the effects of beta-blockers in preventing vasovagal syncope provided mixed results. Our goal was to determine whether treatment with metoprolol reduces the risk of syncope in patients with vasovagal syncope. METHODS AND RESULTS: The multicenter Prevention of Syncope Trial (POST) was a randomized, placebo-controlled, double-blind, trial designed to assess the effects of metoprolol in vasovagal syncope over a 1-year treatment period. Two prespecified analyses included the relationships of age and initial tilt-test results to any benefit from metoprolol. All patients had >2 syncopal spells and a positive tilt test. Randomization was stratified according to ages <42 and > or =42 years. Patients received either metoprolol or matching placebo at highest-tolerated doses from 25 to 200 mg daily. The main outcome measure was the first recurrence of syncope. A total of 208 patients (mean age 42+/-18 years) with a median of 9 syncopal spells over a median of 11 years were randomized, 108 to receive metoprolol and 100 to the placebo group. There were 75 patients with > or =1 recurrence of syncope. The likelihood of recurrent syncope was not significantly different between groups. Neither the age of the patient nor the need for isoproterenol to produce a positive tilt test predicted subsequent significant benefit from metoprolol. CONCLUSIONS: Metoprolol was not effective in preventing vasovagal syncope in the study population.

Adrenergic beta-Antagonists↗
PubMed2005

Diagnostic criteria for vasovagal syncope based on a quantitative history.

AIMS: Our goal was to develop historical criteria for the diagnosis of vasovagal syncope. METHODS AND RESULTS: We administered a 118-item historical questionnaire to 418 patients with syncope and no apparent structural heart disease. The prevalence of each item was compared between patients with positive tilt tests and those with syncope of other, known causes. The contributions of symptoms to diagnoses were estimated with logistic regression, point scores were developed, and the scores were tested using receiver operator characteristic analysis. The accuracy of the decision rule was assessed with bootstrapping. Data sets were complete for all subjects. The causes of syncope were known in 323 patients and included tilt-positive vasovagal syncope (235 patients) and other diagnoses such as complete heart block and supraventricular tachycardias (88 patients). The point score correctly classified 90% of patients, diagnosing vasovagal syncope with 89% sensitivity and 91% specificity. The decision rule suggested that 68% of an additional 95 patients with syncope of unknown cause and a negative tilt test have vasovagal syncope. CONCLUSION: A simple point score of historical features distinguishes vasovagal syncope from syncope of other causes with very high sensitivity and specificity.

Adult↗
PubMed2005

Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial Fibrillation.

BACKGROUND: After its initial diagnosis, atrial fibrillation (AF) may progress from paroxysmal to chronic AF (CAF). The rate of progression and risk factors for progression are not clearly defined. METHODS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 6 Canadian cities at the time of their first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, carefully documenting clinical outcomes, recurrence of paroxysmal AF, and progression to CAF. Baseline clinical, electrocardiographic, and echocardiographic variables were evaluated by univariate Cox proportionate hazards analysis. A stepwise approach was used to model the association between echocardiographic and clinical variables with progression to CAF. RESULTS: A total of 757 patients with a baseline diagnosis of paroxysmal AF were evaluated. Median follow-up was 8.0 years (range 2 days to 11.1 years). The probability of progression to CAF by 1 year was 8.6% and thereafter there was a slow but steady progression to 24.7% by 5 years. By 5 years, the probability of documented recurrence of any AF (chronic or paroxysmal) was 63.2%. Increasing age, significant aortic stenosis or mitral regurgitation, left atrial enlargement, and diagnosis of cardiomyopathy were independently associated with progression to CAF. A more rapid heart rate during AF was associated with decreased risk of progression. CONCLUSIONS: After the initial diagnosis of paroxysmal AF, there is a slow but steady progression to CAF. Baseline echocardiographic variables, age, cardiomyopathy, and heart rate were independently associated with progression to CAF.

Adolescent↗
PubMed2005

Tilt testing for syncope: a reappraisal.

PURPOSE OF REVIEW: Tilt-table tests have provided a diagnostic window on the most common cause of syncope, the common faint. The purpose of this review is to summarize the major contributions of tilt tests and provide a critical assessment of the true validity and usefulness of this diagnostic test. RECENT FINDINGS: Tilt-table tests have provided mixed benefits in the field of neurally mediated syncope. They have greatly improved informed care of syncope patients and have led to a revived interest in the field. They have provided study populations having at least one objective finding in common for diagnostic studies, long-term observational studies, and randomized clinical trials. Tilt tests have been used as platforms for physiologic studies and pilot treatment studies. However, more specific benefits have proven illusive. The main problem is that the neurally mediated syncope syndrome is defined by the test, rather than by evidence-based and widely accepted clinical criteria. Tilt tests have a complex mix of significant methodological variables, have not been validated against gold standard populations, are only moderately reproducible, do not provide prognostic predictive power, and have not been shown useful in selecting efficacious therapies. It may be difficult to achieve important advances in the field until a clinical reflex syncope syndrome is defined by evidence-based diagnostic criteria. SUMMARY: Tilt tests have made neurally mediated syncope amenable to clinical study, but their true usefulness will only be known when an evidence-based, widely accepted definition of this syndrome is developed.

Humans↗
PubMed2004

Dissection of long-range heart rate variability: controlled induction of prognostic measures by activity in the laboratory.

OBJECTIVES: We sought to determine whether the long-range measures of heart rate variability (HRV)--the standard deviation of sequential 5-min heart period mean values (SDANN) and the heart period spectral amplitude in the ultra-low frequency band <0.0033 Hz (ULF)--had their origins partly in physical activity. BACKGROUND: The SDANN and ULF are prognostic HRV factors whose physiologic origins are obscure. Their discontinuous presence throughout the day suggested that they arise from changes in heart period due to activity. METHODS: Heart period sequences were recorded from 14 patients with left ventricular dysfunction and 14 control subjects during an unrestricted 24-h day, 4-h supine rest, and 4-h epoch with scripted activities. RESULTS: The SDANN was higher during activity than during rest (74 +/- 23 ms vs. 43 +/- 17 ms, p < 0.0001), as were ULF magnitudes (p < 0.0001). The increase in SDANN was due to specific activities that contributed heavily (p < 0.0001 by analysis of variance); for example, a 10-min walk and 90-min rest each contributed 22% of total SDANN. Patients with heart disease had a lower SDANN and ULF and a higher mean heart rate than control subjects during all recordings. The proportional ranges in heart period were the same in the two groups during controlled, scripted activities but were wider in control subjects than in patients during ambulatory recordings, suggesting decreased activity by patients. CONCLUSIONS: Activity increases SDANN by increasing the range of heart periods. Patients with diminished ventricular function have a reduced SDANN on ambulatory electrocardiograms, possibly and partly because of a higher mean heart rate and reduced variations in physical activity.

Aged↗
PubMed2004

Prognostic differences between atrial fibrillation and atrial flutter.

This report presents the outcome of a cohort of 94 patients with atrial fibrillation from the Canadian Registry of Atrial Fibrillation, in which we paid particular attention to the probability of stroke and death. We also evaluated warfarin use over time and compared left atrial dimensions in patients with atrial flutter with those with atrial fibrillation.

Aged↗
PubMed2004

The association of left atrial size and occurrence of atrial fibrillation: a prospective cohort study from the Canadian Registry of Atrial Fibrillation.

BACKGROUND: The effect of left atrial (LA) dimension on the recurrence of atrial fibrillation (AF) has been examined in small studies. We evaluated the effect of LA dimension on the occurrence of AF using 2- and 4-year echocardiographic data in a large cohort of patients with new onset AF. METHODS: The Canadian Registry of AF (CARAF) enrolled subjects with AF at the first electrocardiographically confirmed diagnosis. Patients were classified at 2 and 4 years as no recurrent AF (No RAF), paroxysmal AF (PAF), or chronic AF (CAF) based on clinical symptoms and electrocardiographic documentation. The association between baseline, 2-, and 4-year LA dimensions with occurrence of AF as determined by echocardiography was evaluated using a multivariate analysis. RESULTS: The No RAF group (n = 176) had a significantly smaller LA dimension (36.9 +/- 6.8 mm) at baseline compared to the CAF group (n = 227) (42.8 +/- 7.5 mm, P <.0001). The No RAF and PAF (n = 153) groups did not have a significant change in LA dimension at 2 or 4 years. Only those with CAF had a significant increase in LA dimension at 2 and 4 years, +1.39 mm (95% CI 0.01-2.8) and +3.48 mm (95% CI 1.8-5.2), respectively. CONCLUSIONS: A larger baseline LA dimension is associated with progression to CAF. Patients with no or paroxysmal recurrence had no change in LA dimension over a 4-year period. These findings have implications in tailoring modes of therapy in patients with AF.

Aged↗
PubMed2004

Management of vasovagal syncope: 2004.

Vasovagal syncope is a common disorder that affects at least 20% of people at some time in their lives. Probably half of these patients faint recurrently; for many this causes physical trauma, a substantial reduction in quality of life, and difficulties with driving, employment and education. The last 15 years have seen striking advances in diagnostic approaches and prognostic understanding. A number of physiological, pharmacological and electrical therapies have been developed and tested to various degrees in patients. These include counterpressure manoeuvres, salt and fluid recommendations, and attempted treatment with fludrocortisone, midodrine, beta-blockers, serotonin reuptake inhibitors, and permanent pacemakers. This review highlights the most important of these advances and suggests strategies for managing this often difficult problem.

Adrenergic alpha-Agonists↗
PubMed2004

Innovative strategic Canadian research training from TomorrOw's Research Cardiovascular Health Care Professionals (TORCH).

Cardiovascular research training is experiential, and "skills" are traditionally acquired through a master-apprentice paradigm. The complexity of contemporary clinical research requires a new model for research training. Facilitated through a Strategic Training Program Initiative, the Canadian Institutes of Health Research (CIHR), with its partners the Alberta Heritage Foundation for Medical Research and the Heart and Stroke Foundation, supported the Universities of Alberta and Calgary to create a new and innovative training model. Tomorrow's Research Cardiovascular Health Professionals (TORCH) is an integrated 2-year program for health care professionals from diverse disciplines to be mentored toward careers as leaders in translational cardiovascular research, applying discovery to human health. This report describes the vision, mission, core values, objectives, design and curriculum of the program. Our vision is the development of a new generation of cardiovascular research clinician-scientists, with particular emphasis on thought, leadership and collaboration. The program incorporates 4 core values: innovation and discovery, a translational and transdisciplinary focus, an emphasis on collaboration and integration of research concepts, and the teaching of a core body of research knowledge coupled with real-world "survival" skills. The core curriculum, organized according to a cluster concept, traverses the 4 pillars of the CIHR. Through the medium of 1-hour weekly videoconferences, the curriculum cycles through case studies, seminars and a journal club in focused areas of cardiovascular research. Mentors in the TORCH program have diverse backgrounds that epitomize the transdisciplinary translational aspects of the program and are chosen for their proven record of research accomplishment and prior history of successful mentoring. The program has recruited 19 trainees from a broad cross-section of disciplines, integrating 2 University of Alberta campuses. The preliminary experience has been both favourable and gratifying.

Canada↗
PubMed2003

Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial.

CONTEXT: Three previous small randomized trials have reported that pacemaker therapy is beneficial for patients with severe recurrent vasovagal syncope. However, because these trials were not double blind, they may have been biased in their assessment of outcomes and had a placebo effect of surgery. OBJECTIVE: To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope. DESIGN, SETTING, AND PATIENTS: A randomized double-blind trial of pacemaker therapy in outpatients referred to syncope specialists at 15 centers from September 1998 to April 2002. In the year prior to randomization, patients had had a median of 4 episodes of syncope. Patients were followed up for up to 6 months. INTERVENTION: After implantation of a dual chamber pacemaker, 100 patients were randomly assigned to receive dual-chamber pacing (DDD) with rate drop response or to have only sensing without pacing (ODO). MAIN OUTCOME MEASURE: Time to first recurrence of syncope. RESULTS: No patients were lost to follow-up. Of the 52 patients randomized to ODO, 22 (42%) had recurrent syncope within 6 months compared with 16 (33%) of 48 patients in the DDD group. The cumulative risk of syncope at 6 months was 40% (95% confidence interval [CI], 25%-52%) for the ODO group and 31% (95% CI, 17%-43%) for the DDD group. The relative risk reduction in time to syncope with DDD pacing was 30% (95% CI, -33% to 63%; 1-sided P =.14). Lead dislodgement or repositioning occurred in 7 patients. One patient had vein thrombosis, another had pericardial tamponade leading to removal of the pacemaker system, and a third had infection involving the pacemaker generator. CONCLUSIONS: In this double-blind randomized trial, pacing therapy did not reduce the risk of recurrent syncope in patients with vasovagal syncope. Because of the weak evidence of efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first-line therapy for patients with recurrent vasovagal syncope.

Adult↗
PubMed2003

Second Vasovagal Pacemaker Study (VPS II): rationale, design, results, and implications for practice and future clinical trials.

Vasovagal syncope causes substantial morbidity. Various medications have been studied with goals of reducing event-rates and improving quality of life. Results have been mixed, with few drugs demonstrating benefit. Bradycardia usually accompanies vasovagal syncope during positive tilt table tests, and is recorded in up to 50% of clinical syncopal spells documented on electrocardiographic loop recorders. These findings form the rationale for studies of the effectiveness of pacing in preventing vasovagal syncope. Three historically controlled trials of permanent pacing showed that 80-90% of patients had a marked symptomatic improvement, with 90-95% reductions in the number of expected syncopal spells. Subsequently three open-label trials randomized a total of 189 patients evenly to medical therapy or pacemakers in trials that used the proportion of patients with recurrent syncope as the primary outcome. They showed relative risk reductions of 80-87% in the paced patients. However these early studies were not blinded, raising concern about the possible role of a significant placebo effect. This issue was addressed in the recent Second Vasovagal Pacemaker Study (VPS II), in which 100 patients received pacemakers. They then were randomized to pacing with rate drop sensing, or sensing without pacing. The cumulative risk of syncope at 6 months was 40% for the control group and 31% for the actively paced group. The relative risk reduction in time to syncope with pacing was 30% (1 p = 0.14). The AHA/ACC guidelines about pacing and vasovagal syncope should be reassessed. Future clinical trials of therapies for vasovagal syncope should be randomized and placebo-controlled.

Bradycardia↗
PubMed2003

Similarity of spontaneous and induced heart rate and blood pressure turbulence.

BACKGROUND: Heart rate turbulence (HRT) is a transient tachycardia-bradycardia that follows premature ventricular complexes (PVCs). The physiology of turbulence is studied in the electrophysiology lab using induced premature ventricular stimuli but the reliability of this model for HRT is unknown. OBJECTIVES: To compare heart rate and blood pressure signatures of induced and spontaneous HRT. METHODS: Each patient received 10 ventricular extrastimuli at 1-min intervals. Electrocardiogram and continuous blood pressure results were digitized for 34 electrophysiology patients. RESULTS: Fifteen patients yielded at least one induced and one spontaneous analyzable PVC. Per subject, 3.6+/-2.2 spontaneous and 6.1+/-3.3 induced HRT sequences were detected. Spontaneous and inducible HRT were indistinguishable according to turbulence onset (median -1.7% versus -2.3%, P=0.09), turbulence slope (median 7.1 ms/beat versus 10.0 ms/beat, P=0.73), turbulence tachycardia (median 29 ms versus 22 ms, P=0.97) and turbulence bradycardia (45 ms versus 72 ms, P=0.60). Accompanying blood pressure signatures were indistinguishable according to initial hypotension (-0.5+/-5.9 mmHg versus 12.1+/-5.5 mmHg, P=0.19), hypertension time (7.7+/-3.6 s versus 7.8+/-1.9 s, P=0.93) and turbulence hypertension (13.5+/-5.7 mmHg versus 16.1+/-9.2 mmHg, P=0.19). Baroreflex sensitivities estimated by the spontaneous sequence method were similar for spontaneous and induced turbulence (median 7.5 ms/mmHg versus 7.2 ms/mmHg, P=0.89) and correlated with each other (r2=0.81). Heart rate and blood pressure turbulence induced in the electrophysiology laboratory were similar to those following spontaneous PVCs and induced turbulence was a valid model for study under controlled conditions.

Aged↗
PubMed2002

Induction of heart rate and blood pressure turbulence in the electrophysiologic laboratory.

Heart rate turbulence (HRT) is a transient tachycardia and/or bradycardia that follows ventricular premature complexes (VPCs). Absent or blunted HRT is associated with a poor prognosis in patients with heart disease, but its physiology is unknown. We hypothesized that HRT might be mediated by baroreflexes following early depolarizations. We sought to induce and characterize HRT in the electrophysiologic laboratory by introducing 1 ventricular extrastimulus every 60 seconds in 23 patients who underwent invasive electrophysiologic studies. On average, HRT was characterized by an initial RR interval decrease of 38 ms occurring 3.4 seconds after early depolarization. This was followed by a transient RR interval increase of 88 ms occurring 5.4 seconds later. HRT was preceded by similar hypotensive and/or hypertensive blood pressure turbulence. Baroreflex sensitivity estimates from post-VPCs and sinus sequences were similar (12.3 +/- 10.3 vs 10.2 +/- 8.9 ms/mm Hg, p = 0.51). The failure to induce HRT was associated with a limited initial hypotensive phase of blood pressure turbulence (-7.9 vs -12.1 mm Hg, p = 0.037). Patients with structural heart disease had reduced turbulence onset and reduced turbulence slope relative to those with structurally normal hearts, although blood pressure response was similar in both groups. HRT is an inducible, transient tachycardia and/or bradycardia that likely arises from a baroreflex response to transient hypotension following VPCs. Patients with structural heart disease have blunted HRT.

Aged↗
PubMed2002

Effects of ventricular premature stimulus coupling interval on blood pressure and heart rate turbulence.

BACKGROUND: Heart rate turbulence (HRT) is a promising noninvasive risk stratifier for mortality after myocardial infarction. On the basis of a study of ventricular premature complex coupling interval and sympathetic nerve burst amplitude, we hypothesized that measures of HRT would increase with increased prematurity of the coupling interval. METHODS AND RESULTS: Twenty-eight patients undergoing programmed electrical stimulation were studied (12 with prior myocardial infarction, aged 60+/-18 years). An extrastimulus was delivered from the right ventricular apex after 20 sinus beats with a V-S(2) coupling interval decremented by 20 to 30 ms until refractoriness was reached. Turbulence slope (TS), turbulence timing (TT), and turbulence onset were calculated for each extrastimulus, and the linear regressions of these parameters on coupling interval and compensatory pause were calculated. Arterial blood pressure was measured with arterial catheter or a noninvasive continuous blood pressure transducer (Buffington cuff). TS and turbulence onset were abnormal in 4 and 13 patients, respectively. HRT parameters were significantly correlated with coupling interval or compensatory pause in only 2 or 3 patients for a given regression analysis. This absence of correlation was found likely to be due to lack of correlation between compensatory pause and systolic blood pressure after the compensatory pause. Heart rate and TS were correlated: Patients with high heart rate had low TS and late TT (TS=-2.7+0.01xsinus cycle length, P=0.018; TT=8.8 to 0.005xsinus cycle length, P=0.013). CONCLUSIONS: HRT can be induced by programmed stimulation. In this setting, heart rate affects HRT but not ventricular premature complex prematurity. Induced HRT seems to be a valid method for measuring HRT parameters in patients with few ventricular premature complexes.

Arrhythmias, Cardiac↗
PubMed2002

Historical criteria that distinguish syncope from seizures.

OBJECTIVES: We prospectively sought evidence-based criteria that distinguished between seizures and syncope. BACKGROUND: Loss of consciousness is usually due to either seizures or syncope. There are no evidence-based historical diagnostic criteria that distinguish them. METHODS: A total of 671 patients with loss of consciousness completed a 118-item historical questionnaire. Data sets were complete for all subjects. The data set was randomly divided into two equal groups. The contributions of symptoms to diagnoses in one group were estimated with logistic regression and point scores were developed. The accuracy of the decision rule was then assessed using split-half analysis. Analyses were performed with and without inclusion of measures of symptom burden, which were the number of losses of consciousness and the duration of the history. The scores were tested using receiver-operator characteristic analysis. RESULTS: The causes of loss of consciousness were known satisfactorily in 539 patients and included seizures (n = 102; complex partial epilepsy [50 patients] and primary generalized epilepsy [52 patients]) and syncope (n = 437; tilt-positive vasovagal syncope [267 patients], ventricular tachycardia [90 patients] and other diagnoses such as complete heart block and supraventricular tachycardias [80 patients]). The point score based on symptoms alone correctly classified 94% of patients, diagnosing seizures with 94% sensitivity and 94% specificity. Including symptom burden did not significantly improve accuracy, indicating that the symptoms surrounding the loss of consciousness accurately discriminate between seizures and syncope. CONCLUSIONS: A simple point score of historical features distinguishes syncope from seizures with very high sensitivity and specificity.

Case-Control Studies↗