Search

Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of the CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition. However, the predictive value of the CVS for the development of clinical MS in patients with suspected demyelinating disease is still unknown. Moreover, the lack of standardization for the definition and imaging of the CVS currently limits its clinical implementation and validation. On the basis of a thorough review of the existing literature on the CVS and the consensus opinion of the members of the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative, this article provides statements and recommendations aimed at helping radiologists and neurologists to better understand, refine, standardize and evaluate the CVS in the diagnosis of MS.

Objective: To characterize patients misdiagnosed with multiple sclerosis (MS)., Methods: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS., Results: Of 110 misdiagnosed patients, 51 (46%) were classified as "definite" and 59 (54%) "probable" misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms., Conclusions: Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis., (© 2016 American Academy of Neurology.)

Background: Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust., Objective: To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials., Methods: An anonymous online instrument was developed., Results: 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials., Conclusions: Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Randomized placebo-controlled clinical trials have been considered the most rigorous method of evaluating the efficacy of novel treatment interventions. The first effective disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) were approved in the 1990s after a number of pivotal placebo-controlled trials. Since then, the ethics of the continued use of placebo in clinical trials of new DMTs for RRMS has been the subject of repeated policy statements and recommendations by international committees. As further data have accumulated demonstrating a reduction in long-term morbidity and mortality with early initiation of DMT, a growing consensus has emerged that further inclusion of placebo arms in clinical trials of novel RRMS therapies is no longer ethical., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The diagnosis of multiple sclerosis (MS) presently relies on radiographic assessments of imperfect specificity. Recent data using T2* methodology for the detection of the "central vessel sign" (CVS) in MS lesions suggests this novel MRI technique may distinguish MS from other disorders. Our aim was to determine if evaluation for CVS on 3T FLAIR* MRI differentiates MS from migraine., Methods: Patients with MS or migraine and a prior brain MRI demonstrating at least two hyperintense lesions ≥3 mm were recruited. Exclusion criteria included any additional comorbidity known to cause brain MRI abnormalities. 3T MRI was performed in each participant with administration of gadopentetate dimeglumine, and FLAIR* images were generated in postprocessing. The total number of discrete ovoid lesions ≥3 mm were counted on FLAIR, per participant, and subsequently evaluated for presence of CVS on FLAIR*. An exploratory method evaluating for CVS in a maximum of 12 lesions per subject was also completed., Results: Ten participants with MS and 10 with migraine completed the study. The median percentage (quartiles) of lesions in MS participants with CVS was 84 (79, 94) compared to 22 (15, 54) in migraine (P = 0.008). In a subanalysis by brain region, in the subcortical and deep white matter, the median percentage (quartiles) of lesions in MS participants with CVS was 88 (81, 100) compared to 19 (11, 54) in migraine (P = 0.004). This difference was not identified in juxtacortical, periventricular, or infratentorial regions., Interpretation: Identification of CVS using FLAIR* on 3T MRI helps differentiate MS from migraine, particularly in the subcortical and deep white matter.

Background: Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices., Objective: To understand attitudes of patients with multiple sclerosis concerning disclosure of potential physician-industry conflicts of interest created by clinical trials and how such disclosures may influence study participation, Methods: An anonymous online instrument was developed., Results: 597 people with multiple sclerosis participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence patients' decisions to participate in these studies., Conclusions: Findings from this study support a call for uniform guidelines regarding disclosure of physician-industry relationships to prospective research participants for industry-sponsored clinical trials., (© The Author(s), 2015.)

Background: Common clinical neurological exams can be insensitive to balance and mobility impairment at the early stages of multiple sclerosis (MS) and may not correspond with patient reports. Instrumented measurement of standing postural sway with inertial motion sensors may provide sensitive measures of balance impairment and better correspond with patient reports., Methods: While wearing wireless inertial sensors, 20 subjects with MS - Expanded Disability Status Scale of less than 3.0 and a Timed 25 Foot Walk of 5 sec or less - and 20 age- and sex-matched control subjects stood with eyes open and eyes closed on a foam surface. Forty-six outcome measures of postural sway were derived. A stepwise logistic regression model determined which measures of instrumented sway provide independent predictors of group status. Subjects with MS also completed the Activities-Specific Balance Confidence (ABC) scale and the 12-Item MS Walking Scale (MSWS-12) as measures of subject-reported balance and mobility impairment., Results: The regression model identified medio-lateral sway path length and medio-lateral range of sway acceleration amplitude, each in the eyes-open condition, as the only two significant independent predictors to differentiate subjects with MS from those without MS (model chi-squared = 34.55, p < 0.0001): accuracy = 87.5 %, positive likelihood ratio = 6 (2.09-17.21), negative likelihood ratio = 0.12 (0.03-0.44). Range of sway acceleration amplitude significantly correlated with both ABC (Spearman's r = -0.567, p = 0.009) and MSWS-12 scores (Spearman's r = -0.590, p = 0.006)., Conclusions: Postural sway abnormalities in subjects with MS who are minimally disabled were detected using wireless inertial sensors and may signify a superior sensitivity to identify balance impairment prior to developing clinically evident disability or impaired gait speed. Further study is needed to confirm the clinical significance and predictive value of these objectively identified balance impairments.

The diagnostic criteria for multiple sclerosis (MS) rely on clinical, paraclinical, and radiographic findings of limited specificity. Many disorders mimic MS, and the decision of when to investigate an alternative diagnosis can be challenging. Reliance on extensive ancillary testing to exclude potential mimics, however, is unnecessary in most cases. Rather, recognition and rigorous interpretation of "classic" clinical and radiographic features of MS are often sufficient to establish the diagnosis. Misinterpretation of the clinical and radiographic diagnostic criteria for MS in the setting of more common diseases and syndromes and a lack of vigilance for "red flags" are important contributors to misdiagnosis. A clinical framework for the differential diagnosis of MS that emphasizes phenotypes atypical for MS and suggests diseases or syndromes in which they more commonly occur may be an important diagnostic guide for clinicians in contemporary practice.

A diagnosis of multiple sclerosis is heavily influenced by clinical judgment. Misdiagnosis of multiple sclerosis is common and has important consequences for patients and the cost of healthcare. Although rigorous data about the frequency and causes of misdiagnosis are lacking, misinterpretation and misapplication of clinical and radiographic diagnostic criteria and terminology are likely important factors. Appropriate and stringent application of diagnostic criteria and continued vigilance for "red flags" suggesting alternative diagnoses are strategies critical for prevention of misdiagnosis.

Background: Risk stratification of atrial fibrillation patients with a congestive heart failure (C), hypertension (H), age ≥ 75 (A), diabetes (D), stroke or transient ischemic attack (TIA) (S2) (CHADS2) score of <2 remains imprecise, particularly in women. Our objectives were to validate the CHADS2 and congestive heart failure (C), hypertension (H), age ≥ 75 (A2), diabetes (D), stroke, TIA or prior thromboembolic disease (S2)- vascular disease (V), age 65-74 (A), female gender (S) (CHA2DS2-VASc) stroke risk scores in a healthy cohort of American women with atrial fibrillation and to determine whether CHA2DS2-VASc further risk-stratifies individuals with a CHADS2 score of <2., Methods: We identified a cohort of 5981 women with atrial fibrillation not on warfarin at baseline (mean age 65.9 ± 7.2 years) enrolled in the Women's Health Initiative and followed for a median of 11.8 years. Univariate and multivariate proportional hazards analyses were used to examine these 2 risk scores, with main outcome measures being annualized event rates of ischemic stroke or transient ischemic attack stratified by risk score., Results: Annualized stroke/transient ischemic attack rates ranged from 0.36% to 2.43% with increasing CHADS2 score (0-4+) (hazard ratio [HR] 1.57; 95% confidence interval [CI], 1.45-1.71 for each 1-point increase) and 0.20%-2.02% with increasing CHA2DS2-VASc score (1-6+) (HR 1.50; 95% CI, 1.41-1.60 for each 1-point increase). CHA2DS2-VASc had a higher c statistic than CHADS2: 0.67 (95% CI, 0.65-0.69) versus 0.65 (95% CI, 0.62-0.67), P <.01. For CHADS2 scores <2, stroke risk almost doubled with every additional CHA2DS2-VASc point., Conclusions: Although both CHADS2, and CHA2DS2-VASc are predictive of stroke risk in postmenopausal women with atrial fibrillation, CHA2DS2-VASc further risk-stratifies patients with a CHADS2 score <2., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The difficulty of diagnosing multiple sclerosis (MS) has been well documented. However, recent data also suggests that neurologists frequently encounter the clinical challenge of having to undo a misdiagnosis of MS. Undiagnosing MS has important clinical, psychosocial, and economic consequences for the patient, the treating neurologist, and the healthcare system at large. This article presents a case of misdiagnosed MS and discusses ethical challenges and obligations for the neurologist.

Background: Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS., Objectives: To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren's Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren's Syndrome., Methods: Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center., Results: Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren's Syndrome., Conclusions: Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease.

Objectives: The aim of this study was to estimate the annual incidence rate of sudden cardiac death (SCD) and to identify risk factors for SCD in post-menopausal women., Background: With the aging U.S. population, post-menopausal women now have the greatest population burden of cardiovascular disease including SCD., Methods: We examined 161,808 women who participated in the Women's Health Initiative clinical trials and observational study. The women were recruited at 40 clinical sites across the United States, enrolled between 1993 and 1998, and followed until August 2009. Our primary endpoint is incident SCD, defined as death occurring within 1 h of symptom onset or within 1 h after the participant was last seen without symptoms and death that occurred in the absence of a potentially lethal non-coronary disease process., Results: Four hundred eighteen women experienced adjudicated SCD. The incidence rate of SCD was 2.4/10,000 women/year (95% confidence interval: 2.2 to 2.7). We identified the following independent risk factors for SCD: older age, African-American race, tobacco use, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, history of heart failure, diabetes, history of myocardial infarction, previous carotid artery disease, and hypertension. Population-attributable fractions were greatest for hypertension, waist-to-hip ratio, and myocardial infarction., Conclusions: Besides traditional risk factors for coronary heart disease, risk factors for sudden cardiac death in post-menopausal women include African-American race, higher pulse, higher waist-to-hip ratio, elevated white blood cell count, and heart failure. Nearly one-half of women who experienced sudden cardiac death had no previous diagnosis of coronary heart disease., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval., Methods and Results: First, individual estimates of African and European ancestry were inferred from genome-wide single-nucleotide polymorphism (SNP) data in 7 population-based cohorts of African Americans (n=12,097) and regressed on measured QT interval from ECGs. Second, imputation was performed for 2.8 million SNPs, and a genome-wide association study of QT interval was performed in 10 cohorts (n=13,105). There was no evidence of association between genetic ancestry and QT interval (P=0.94). Genome-wide significant associations (P<2.5 × 10(-8)) were identified with SNPs at 2 loci, upstream of the genes NOS1AP (rs12143842, P=2 × 10(-15)) and ATP1B1 (rs1320976, P=2 × 10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low probability values (P<10(-5)) were observed for SNPs at several other loci previously identified in genome-wide association studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF, and PLN., Conclusions: We observed no difference in duration of cardiac repolarization with global genetic indices of African American ancestry. In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry.

Background: TNF alpha inhibitor (TNFAI) therapy has been associated with inflammatory neurological syndromes., Objectives: To present 10 new cases of TNFAI associated neurological disease and a review of the literature., Methods: The design and methods were based on case series collected from Oregon Health & Sciences University and the Department of Veterans Affairs Hospital in Portland, Oregon and PubMed review., Results: We describe eight demyelinating central nervous system syndromes and two peripheral nervous system syndromes associated with TNFAI therapy. Characteristics from these cases are analyzed with data from 141 additional cases from the literature. Onset was between the ages of 36 and 65 years in 84% of CNS cases, distinguishing TNFAI-associated disease from sporadic multiple sclerosis. Symptoms occurred within one year of TNFAI therapy in 71%. Etanercept therapy was reported in the majority of cases of CNS syndromes and infliximab therapy in the majority of neuromuscular syndromes. Significant disability remained in 67% of cases although 82% had been followed for less than one year., Conclusions: Our case series and literature review demonstrates an association between TNFAI therapy and inflammatory neurological disease. While a causal relationship is suggested, this remains uncertain. TNFAI-associated neurological syndromes are associated with significant disability and longer follow-up is needed to better determine natural history and evaluate appropriate treatment interventions.

A relationship between vitamin D and several diseases, including multiple sclerosis (MS), has recently received interest in the scientific community. Vitamin D appears to have important actions beyond endocrine function, particularly for the immune system. Risk of development of MS, as well as disease severity, has been associated with vitamin D in a variety of studies. There remains a need for prospective studies to further establish this relationship. Given the current evidence of the potential benefits of vitamin D, it appears to be reasonable and safe to consider vitamin D supplementation at dosing adequate to achieve normal levels in patients with MS and clinically isolated syndrome.

Rate-control and rhythm-control strategies in the management of atrial fibrillation (AF) have been shown to have similar effects on morbidity and mortality. Data are lacking as to whether specific electrocardiographic features of AF affect the ability to achieve rate or rhythm control. This study evaluated the relation between initial resting ventricular rate (IRVR) during AF and the subsequent achievement of rate control and rhythm control in the AFFIRM Study. The independent relations between IRVR and the achievement of rate and rhythm control were assessed using multivariate Cox's proportional hazards modeling. In addition, we evaluated whether IRVR was associated with major cardiovascular end points. IRVR was analyzed in 4,059 patients. IRVR was higher in women, smokers, patients who had a first episode of AF, and in patients who had preserved left ventricular systolic function but lower in patients who had coronary artery disease, hypertension, left atrial enlargement, and a qualifying episode of AF that lasted >48 hours. A higher IRVR was independently associated with the achievement (p <0.0001) and maintenance (p = 0.0002) of sinus rhythm, whereas the ability to achieve adequate rate control was independent of IRVR. A higher IRVR was associated with an increased risk of cardiovascular hospitalization (p <0.0001). In the appropriate clinical setting, a rhythm-control strategy should be considered for patients who have a higher IRVR.

Objectives: We investigated whether inhibition of endogenous angiotensin II signaling reduces the recurrence rate of atrial fibrillation (AF) in patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study., Background: Structural and electrical remodeling contribute to AF. Previous experimental studies have implicated the angiotensin II signaling pathway in this process, and recent clinical evidence supports a beneficial effect of inhibiting angiotensin II activity., Methods: Using the AFFIRM database, we retrospectively identified a cohort of patients randomized to the rhythm-control arm who were in sinus rhythm. Exposure to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ANGI) was determined, and the time to first recurrence of AF was compared between ANGI users and nonusers., Results: The study cohort included 732 patients not taking ANGI through the initial 2-month follow-up and 421 patients taking ANGI during this time. Patients in the ANGI group more likely had hypertension, diabetes, coronary artery disease, and congestive heart failure compared to patients not taking ANGI. Risk of AF recurrence in the ANGI treatment group did not differ from the risk observed in patients not taking the drugs (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.77-1.09). However, in patients with congestive heart failure or impaired left ventricular function, ANGI use was associated with a lower risk of AF recurrence., Conclusions: This analysis provides evidence that ANGI use may be beneficial in some patient subgroups with AF and underscores the need for randomized clinical trials defining more fully the role of angiotensin II inhibition in treating AF.

Background: Long distance trucking is associated with significant health risks. However, to our knowledge no published data exist regarding healthcare service access by the estimated two million long-haul truckers in the United States., Methods: A cross-sectional study was designed to assess access to healthcare among these workers. Five hundred-twenty-one anonymous self-administered surveys were completed at 16 truck stops in 14 states from July through August 2002., Results: Forty-seven percent of those surveyed lack a regular healthcare provider, 20% frequent emergency rooms and urgent care centers, 32% were unable to receive needed healthcare within the last year, and 56% had difficulty utilizing healthcare services at home. Individuals lacking health insurance (31%) experienced more difficulty with healthcare access than the insured within the last year, were more often without a regular provider (P = 0.002 and P < 0.001), and utilized urgent care centers and emergency rooms more often than the insured (25 vs. 17%)., Conclusions: Long distance truck drivers are at risk for poor health outcomes and experience significant difficulty accessing healthcare services. Further studies concerning how to best provide healthcare to this vulnerable, underserved population are needed., (Copyright 2004 Wiley-Liss, Inc.)

Objectives: We sought to evaluate approaches used to control rate, the effectiveness of rate control, and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study., Background: The AFFIRM study showed that atrial fibrillation (AF) can be treated effectively with rate control and anticoagulation, but drug efficacy to control rate remains uncertain., Methods: Patients (n = 2,027) randomized to rate control in the AFFIRM study were given rate-controlling drugs by their treating physicians. Standardized rate-control efficacy criteria developed a priori included resting heart rate and 6-min walk tests and/or ambulatory electrocardiographic results., Results: Average follow-up was 3.5 +/- 1.3 years. Initial treatment included a beta-adrenergic blocker (beta-blocker) alone in 24%, a calcium channel blocker alone in 17%, digoxin alone in 16%, a beta-blocker and digoxin in 14%, or a calcium channel blocker and digoxin in 14% of patients. Overall rate control was achieved in 70% of patients given beta-blockers as the first drug (with or without digoxin), 54% with calcium channel blockers (with or without digoxin), and 58% with digoxin alone. Adequate overall rate control was achieved in 58% of patients with the first drug or combination. Multivariate analysis revealed an association between first drug class and several clinical variables. There were more changes to beta-blockers than to the other two-drug classes (p < 0.0001)., Conclusions: Rate control in AF is possible in the majority of patients with AF. Beta-blockers were the most effective drugs. To achieve the goal of adequate rate control in all patients, frequent medication changes and drug combinations were needed.

Atrial fibrillation (AF) is a common complication of cardiovascular surgery. The two most important risk factors for its development are advancing age and a preoperative history of AF. Long-term sequelae, such as a stroke, are uncommon, however, atrial fibrillation frequently results in increased length and cost of hospitalization. Strategies to prevent postoperative AF include perioperative beta-blockers, amiodarone, and atrial pacing. These strategies are most effective in high-risk patients. When AF does occur, treatment includes control of the ventricular rate, systemic anticoagulation, and conversion to sinus rhythm.

Atrial fibrillation in patients undergoing cardiovascular surgery is a common problem, occurring in 25-50% of patients. Older patients and those with a prior history of atrial fibrillation are at highest risk, as are those patients in whom preoperative treatment with beta-blockers has been discontinued. The immediate sequelae of this common complication include hemodynamic instability and congestive heart failure with long-term consequences including thromboembolic phenomena and increased cost and length of hospitalization. beta-Blockers, amiodarone, and sotalol have all been shown to decrease the incidence of postoperative atrial fibrillation, but their use may be limited by their adverse effects. Other agents have some promise as prophylactic agents, but need further verification. Biatrial pacing has been shown to be effective, especially when beta-blockers are used simultaneously. The goals for the treatment of atrial fibrillation include maintaining hemodynamic stability, controlling ventricular rate, preventing thromboembolic complications, and restoring sinus rhythm. The most effective strategy for the prevention of atrial fibrillation is to identify the highest-risk patients and target them for prophylaxis with beta-blockers, amiodarone, sotalol or pacing.

Background: Amiodarone has been shown to be safe in patients with acute myocardial infarction (AMI) who are at risk for sudden cardiac death. However, there is limited data concerning the safety of amiodarone in patients who experience AMI complicated by atrial fibrillation., Methods: To determine the safety of amiodarone therapy, we conducted a retrospective analysis of elderly patients hospitalized with AMI who experienced atrial fibrillation and had survived to hospital discharge (n = 17,597). Amiodarone prescribed at discharge was evaluated for its association with short-term and long-term mortality in crude and adjusted analyses employing propensity score methods., Results: Of the 17,597 patients, 550 patients (3.1%) were prescribed amiodarone, 2317 patients (13.2%) were prescribed other antiarrhythmic agents (excluded from analysis), and 14,730 (83.7%) were prescribed no antiarrhythmic medication at discharge. Thirty-day mortality rates were similar for patients prescribed amiodarone and those not prescribed amiodarone (6.8% amiodarone vs 5.4% no amiodarone, P =.21), but mortality at 1 year was higher among patients prescribed amiodarone (35.6% vs 31.6%, P =.001). However, amiodarone was not associated with mortality at 30 days (odds ratio 0.80, 95% CI 0.53-1.20) or at long-term follow-up (mean duration 612 days, hazard ratio 1.04, 95% CI 0.92-1.18) after multivariable modeling., Conclusions: Amiodarone was not independently associated with short-term or long-term mortality in elderly patients discharged after a hospitalization for AMI complicated by atrial fibrillation. Although our data suggest that amiodarone may be safe to use in this population, randomized controlled trial data are needed to confirm this finding.

Background: Both amiodarone and beta-blockers have been shown to decrease the incidence of atrial fibrillation after cardiovascular surgery. However, the superior agent has not been identified., Methods: We performed a pilot study on 102 patients (68 men, mean age 65 +/- 10 years, mean left ventricular ejection fraction 0.53 +/- 0.12) undergoing cardiovascular surgery (94 coronary artery bypass grafting [CABG], 5 valvular surgery only, and 3 CABG + valvular surgery). The patients were randomized to receive amiodarone (1 g/d intravenously x 48 hours, then 400 mg/d orally until discharge) or propranolol (1 mg intravenously every 6 hours x 48 hours, then 20 mg orally four times a day until discharge). Atrial fibrillation was defined as lasting longer than 1 hour or resulting in hemodynamic compromise., Results: The incidence of postoperative atrial fibrillation was 16.0% (8/50) in the amiodarone group and 32.7% (17/52) in the propranolol group (P =.05). The mean length of stay was 8.8 +/- 3.5 days for amiodarone-treated patients and 8.4 +/- 2.7 days for propranolol-treated patients (P not significant). Serious adverse events were uncommon and similar in each group., Conclusion: Early intravenous amiodarone, followed by oral amiodarone, appears to be superior to propranolol in the prevention of postoperative atrial fibrillation. It is well tolerated and can be started at the time of surgery. However, the use of amiodarone did not result in a reduction in the length of hospital stay.

Background/objective: Our purpose was to evaluate the effectiveness of reperfusion therapy among elderly paced patients with acute myocardial infarction (MI). Current guidelines make no recommendation for the use of reperfusion therapy among patients who have a paced rhythm during MI., Methods: We evaluated 1954 Medicare beneficiaries 65 years and older treated for acute MI between 1994 and 1996 who had a paced rhythm for use of reperfusion therapy. Use of reperfusion therapy was evaluated for associations with outcomes by logistic regression and Cox proportional hazards models incorporating propensity score analysis., Results: Reperfusion therapy was used in 171 (8.8%) patients; 70 were treated with primary PTCA and 101 with thrombolytic therapy. Patients who received reperfusion therapy had 30-day mortality rates similar to those who did not receive reperfusion (26.3% vs 25.7%, P =.87). Multivariate adjustment for mortality risk factors and treatment propensity indicated no survival benefit associated with reperfusion therapy at 30 days (relative risk [RR] 1.07, 95% confidence interval [CI] 0.77-1.43) or long-term follow-up (hazard ratio [HR] 0.86, 95% CI 0.68-1.10). Mortality risks varied by type of reperfusion therapy. Patients treated with primary percutaneous transluminal coronary angioplasty were at comparable risk of mortality at 30 days (RR 0.73, 95% CI 0.40-1.23) but at lower risk at long-term follow-up (HR 0.60, 95% CI 0.40-0.88). Mortality risks were unchanged among patients treated with thrombolytics at 30 days (RR 1.32, 95% CI 0.92-1.79) and long-term follow-up (HR 1.08, 95% CI 0.82-1.43)., Conclusion: We find suggestive evidence that primary percutaneous transluminal coronary angioplasty provides a long-term survival benefit in the treatment of elderly patients with acute MI who have a paced rhythm.

Background: A paced rhythm can mask the electrocardiographic features of an acute myocardial infarction, complicating timely recognition and treatment., Objective: To evaluate characteristics, treatment, and outcomes among patients presenting with paced rhythms during myocardial infarction., Design: Retrospective cohort study., Setting: U.S. acute care hospitals., Patients: 102 249 Medicare beneficiaries at least 65 years of age who were treated for acute myocardial infarction between 1994 and 1996., Measurements: Provision of three treatments for acute myocardial infarction (emergent reperfusion, aspirin, and beta-blockers), death at 30 days, and long-term follow-up., Results: 1954 patients (1.9%) presented with paced rhythms during myocardial infarction. These patients were older; were predominantly male; and had higher rates of congestive heart failure, diabetes, and previous infarction. They were significantly less likely to receive emergent reperfusion (relative risk [RR], 0.27 [95% CI, 0.22 to 0.33]), aspirin (RR at admission, 0.91 [CI, 0.88 to 0.94]; RR at discharge, 0.87 [CI, 0.83 to 0.92]), and beta-blockers at admission (RR, 0.89 [CI, 0.82 to 0.96]). In addition, there was a trend toward decreased use of beta-blockers at discharge (RR, 0.91 [CI, 0.76 to 1.06]). Crude mortality rates were higher among patients with paced rhythms than among those without at 30 days (25.8% vs. 21.3%; P = 0.001) and at 1 year (47.1% vs. 36.1%; P = 0.001). Among patients with paced rhythms, risk for death at 30 days decreased after adjustment for illness severity and decreased use of therapy (RR, 1.03 [CI, 0.93 to 1.14]). Patients with paced rhythms remained at additional risk for long-term mortality (hazard ratio, 1.12 [CI, 1.06 to 1.18])., Conclusions: Patients with paced rhythms were less likely than those without to receive treatment for acute myocardial infarction and had poorer short- and long-term outcomes. However, this mortality risk diminished after adjustment for treatment. This suggests that improved recognition and treatment of myocardial infarction may improve outcomes, particularly in the short term.

Background: Although second- and third-degree heart block (HB) are common conduction disorders associated with acute myocardial infarction (MI), patient characteristics and HBs association with outcomes, particularly among the elderly, remain poorly defined., Methods: We evaluated 106,780 Medicare beneficiaries aged 65 years and older treated for acute MI between January 1994 and February 1996 for development of HB. HB and non-HB patients were compared by univariate analysis, and the influence of HB on outcomes was evaluated by unadjusted and multiple logistic regression., Results: HB was documented in 5048 (4.7%) patients; 1646 presented with HB and 3402 developed HB during hospitalization. HB was more common among patients with inferior infarctions than anterior infarctions (7.3% vs 3.0%, P =.001), particularly the cohort of patients with inferior MI treated with reperfusion therapy (8.3%). HB patients had higher rates of in-hospital mortality (29.6% vs. 17.5% vs. non-HB patients, P =.001). After adjustment for demographic and clinical factors, HB remained an independent predictor of in-hospital mortality (relative risk [RR] 1.41, 95% confidence interval [CI] 1. 34-1.48), but HB had no prognostic significance at 1 year among hospital survivors (RR 0.94, 95% CI 0.88-1.01). Mortality risks varied on the basis of MI location. Both anterior MI (RR 1.46, 95% CI 1.30-1.63) and inferior MI (RR 1.52, 95% CI 1.39-1.66) patients with HB had increased risks of in-hospital mortality. There was a trend toward increased mortality among patients with anterior MI (RR 1.15, 95% CI 0.99-1.32) at 1 year, whereas those with inferior MI were at lower risk (RR 0.83, 95% CI 0.75-0.98)., Conclusions: HB is a common complication of acute MI in elderly patients, particularly among patients with inferior MIs who received reperfusion therapy. HB is independently associated with short-term but not long-term mortality.

Cardiovascular disease is the leading cause of death in patients receiving dialysis. This is attributed in part to the shared risk factors of cardiovascular disease and end-stage renal disease. The risk factors for coronary artery disease include the classic cardiac risk factors of diabetes mellitus, hypertension, dyslipidemia, and smoking. Also in this population, hyperparathyroidism, hypoalbuminemia, hyperhomocysteinemia, elevated levels of apolipoprotein (a), and the type of dialysis membrane may play a role. Management begins with risk factor modification and medical therapy including aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors, and lipid-lowering agents. Revascularization is often important, and coronary artery bypass grafting appears to be preferable to percutaneous transluminal coronary angioplasty. This is especially true for those with multivessel disease, impaired left ventricular function, severe symptoms, or ischemia. Congestive heart failure is another common problem in dialysis patients. The management includes correction of underlying abnormalities, optimal dialysis, and medical therapy. Data obtained from the general population indicate obvious benefits from ACE inhibitors and beta blockers, and these agents would be considered the therapies of choice. Erythropoetin is also an essential component of therapy, but the ideal hemoglobin concentration has yet to be determined. Peritoneal dialysis may be helpful in severe cases of heart failure. Pericarditis is seen in less than 10% of dialysis patients and is best diagnosed by clinical examination and echocardiography. Intensive dialysis is often the best initial therapy. Pericardiocentesis is reserved for the setting of pericardial tamponade, but a pericardial window is more definitive.

Objective: The purpose of this study was to determine the efficacy of atrial pacing in the prevention of atrial fibrillation following cardiovascular surgery., Background: Although pharmacologic therapy has been used to help prevent postoperative atrial fibrillation, it suffers from limited efficacy and adverse effects. In the nonoperative setting, novel pacing strategies have been shown to reduce recurrences of atrial fibrillation and prolong arrhythmia-free periods in patients with paroxysmal atrial arrhythmias., Methods: A total of 154 patients (115 men; mean age, 65 +/- 10 years; ejection fraction, 53 +/- 10%) undergoing cardiac surgery (coronary artery bypass surgery, 88.3%; aortic valve replacement, 4.5%; coronary bypass + aortic valve replacement, 7.1%) had right and left atrial epicardial pacing electrodes placed at the time of surgery. Patients were randomized to either no pacing, right atrial (RAP), left atrial (LAP) or biatrial pacing (BAP) for 72 h after surgery. Beta-adrenergic blocking agents were administered concurrently to all patients following surgery., Results: There was a reduction in the incidence of postoperative atrial fibrillation from 37.5% in patients receiving no postoperative pacing to 17% (p < 0.005) in patients assigned to one of the three pacing strategies. The length of hospital stay was reduced by 22% from 7.8 +/- 3.7 days to 6.1 +/- 2.3 days (p = 0.003) in patients assigned to postoperative atrial pacing. The incidence of atrial fibrillation was lower in each of the paced groups (RAP, 8%; LAP, 20%; BAP, 26%) compared with patients who did not receive postoperative pacing (37.5%)., Conclusion: Postoperative atrial pacing, in conjunction with beta-blockade, significantly reduced both the incidence of atrial fibrillation and the length of hospital stay following cardiovascular surgery. Additional studies are needed to determine the most effective anatomic pacing site.

Background: Although atrial fibrillation (AF) is a common complication of acute myocardial infarction (MI), patient characteristics and association with outcomes remain poorly defined in the elderly., Methods and Results: We evaluated 106 780 Medicare beneficiaries > or =65 years of age from the Cooperative Cardiovascular Project treated for acute MI between January 1994 and February 1996 to determine the prevalence and prognostic significance of AF complicating acute MI in elderly patients. Patients were categorized on the basis of the presence of AF, and those with AF were further subdivided by time of AF (present on arrival versus developing during hospitalization). AF and non-AF patients were compared by univariate analysis, and logistic regression modeling was used to identify clinical predictors of AF. The influence of AF on outcomes was evaluated by unadjusted Kaplan-Meier survival curves and logistic regression models. AF was documented in 23 565 patients (22. 1%): 11 510 presented with AF and 12,055 developed AF during hospitalization. AF patients were older, had more advanced heart failure, and were more likely to have had a prior MI and undergone coronary revascularization. AF patients had poorer outcomes, including higher in-hospital (25.3% versus 16.0%), 30-day (29.3% versus 19.1%), and 1-year (48.3% versus 32.7%) mortality. AF remained an independent predictor of in-hospital (odds ratio [OR], 1. 21), 30-day (OR, 1.20), and 1-year (OR, 1.34) mortality after multivariate adjustment. Patients developing AF during hospitalization had a worse prognosis than patients who presented with AF., Conclusions: AF is a common complication of acute MI in elderly patients and independently influences mortality, particularly when it develops during hospitalization.

Background: Atrial fibrillation is a common complication of cardiovascular surgery. Beta-blockers have been shown to decrease the incidence of postoperative atrial fibrillation. However, the use of magnesium is more controversial. It was our hypothesis that adjunctive magnesium sulfate would improve the efficacy of beta-blockers alone in the prevention of postoperative atrial fibrillation., Methods: We prospectively randomized 167 coronary artery bypass patients (mean age 61+/-10 years, 115 men) to receive propranolol alone (20 mg four times daily) or propranolol and magnesium (18 g over 24 hours). Magnesium was begun intraoperatively, and propranolol was started on admission to the intensive care unit., Results: Using an intention-to-treat analysis, the incidence of postoperative atrial fibrillation was 19.5% in the propranolol-treated patients and 22.4% in propranolol + magnesium-treated patients (p = 0.65). Because combination therapy resulted in an excess of postoperative hypotension, which required withholding doses of propranolol, an on-treatment analysis was also performed. In this analysis, the incidence of atrial fibrillation was still not significantly different (18.5% in propranolol-treated patients and 10.0% in propranolol + magnesium-treated patients, p = 0.20)., Conclusions: Adjunctive magnesium sulfate, in combination with propranolol, does not decrease the incidence of postoperative atrial fibrillation.

Ischemic heart disease is one of the most common disorders managed by family physicians. Stratifying patients according to risk is important early in the course of the disease to identify patients who require invasive (percutaneous or surgical) treatment. Physical examination, clinical history, noninvasive tests and angiography are all helpful in determining who will benefit most from medical therapy, percutaneous revascularization or coronary artery bypass surgery. Surgery improves morbidity and mortality in a well-defined group of patients with left ventricular dysfunction and left main coronary artery disease or triple-vessel disease. Patients with proximal left anterior descending artery disease and moderate or severe ischemia benefit from surgery as well. In all other patients, definitive treatment includes aspirin, beta-adrenergic blockers and lipid-lowering agents. Percutaneous revascularization should be considered primarily a palliative measure, because it has never been shown to improve mortality more than medical therapy.

Atrial fibrillation is a common complication of cardiovascular surgery. The 2 most important risk factors for its development are advancing age and a preoperative history of atrial fibrillation. Long-term sequelae, such as a stroke, are uncommon; however, atrial fibrillation frequently results in an increased length and cost of hospitalization. Strategies to prevent postoperative atrial fibrillation include perioperative beta-blockers, amiodarone, and atrial pacing. These strategies are most effective in high-risk patients. When atrial fibrillation does occur, treatment includes control of the ventricular rate, systemic anticoagulation, and conversion back to sinus rhythm.

Aims: Defibrillator generator changes are frequently performed on patients with an implantable cardioverter defibrillator in an abdominal pocket. These patients usually have epicardial patches or older endocardial lead systems. At the time of a defibrillator generator change defibrillation may be unsuccessful as a result of lead failure. We tested the hypothesis that an active can defibrillator implanted in the abdominal pocket could replace a non-functioning endocardial lead or epicardial patch., Methods and Results: An abdominal defibrillator generator change was performed in 10 patients, (mean age = 67 +/- 13 years, nine men). Initially, a defibrillation threshold (DFT) was obtained using a passive defibrillator and the chronic endocardial or epicardial lead system. DFTs were then performed using an active can emulator and one chronic lead to simulate endocardial or epicardial lead failure. We tested 30 lead configurations (nine endocardial and 21 epicardial). Although a DFT of 7.3 +/- 4.2 joules was obtained with the intact chronic lead system, the active can emulator and one endocardial or epicardial lead still yielded an acceptable DFT of 19.9 +/- 6.1 joules. In addition, a successful implant (DFT < or = 24 joules) could have been accomplished in 28 of 30 (93%) lead configurations., Conclusion: An active can defibrillator in an abdominal pocket may allow for a successful generator change in patients with defibrillator lead malfunction. This would be simpler than abandoning the abdominal implant and moving to a new pectoral device and lead or tunnelling a new endocardial electrode. However, loss of defibrillation capability with a particular complex lead may be a warning of impending loss of other functions (eg. sensing and/or pacing).

The most common indication for a permanent pacemaker is symptomatic bradycardia. An atrial-based pacemaker (dual-chamber or atrial) usually is preferred, except in patients with chronic atrial fibrillation. Several prospective, randomized trials recently have been completed to evaluate new indications for permanent pacemakers. A dual-chamber pacemaker with an optimal atrioventricular interval can reduce the left ventricular outflow tract gradient by >50% in patients with hypertrophic cardiomyopathy. This has been associated with symptomatic improvement in the majority of patients, but an important placebo effect appears likely. Pacing also has been evaluated in patients with medically refractory dilated cardiomyopathy. Despite encouraging initial studies, routine implantation of a permanent pacemaker in dilated cardiomyopathy is not indicated. In patients with cardioinhibitory or mixed vasovagal syncope and carotid sinus hypersensitivity, implantation of a pacemaker markedly decreases syncopal episodes. Pacemaker therapy is clearly indicated in patients with atrial fibrillation associated with symptomatic bradycardia, and exciting new data on the use of pacing to prevent atrial fibrillation appear promising. The best pacing modality for this indication may be dual-site atrial pacing. Finally, permanent pacemakers play an important role in the treatment of symptomatic long QT syndrome, usually in combination with beta-blockers.

The current era has witnessed dramatic improvement in the treatment of acute myocardial infarction, due in large part to the more widespread use of thrombolytic therapy aimed at quickly restoring perfusion in the infarct-related artery. This review addresses the role of adjunctive pharmacologic therapy in the thrombolytic era, recognizing that much of the available clinical trial data supporting the role of adjunctive pharmacologic treatment strategies was conducted in patient populations not widely exposed to reperfusion therapy. This review, therefore, explores the data supporting the incremental benefit of therapy with beta blockers, nitrates, angiotensin-converting enzyme inhibitors, or magnesium in addition to thrombolytic therapy. Heparin and aspirin will not be discussed.

Background: Atrial fibrillation is one of the most frequent complications after cardiovascular surgery. It may result in thromboembolic events, hemodynamic deterioration, and an increased length and cost of hospitalization., Methods: We retrospectively studied 504 consecutive adult patients undergoing cardiovascular surgery to determine whether patients with new-onset postoperative atrial fibrillation could be safely discharged in atrial fibrillation after ventricular rate had been controlled and anticoagulation initiated., Results: Postoperative atrial fibrillation occurred in 79 (16.2%) of the 487 survivors. Of these patients, 67 were discharged in sinus rhythm, whereas the remaining 12 were discharged in atrial fibrillation. Patients discharged in atrial fibrillation tended to be older, have higher Parsonnet risk scores, and have an increased incidence of valvular heart surgery. Despite this result, this cohort had a shorter length of hospital stay (7.3+/-2.0 days vs 10.9+/-9.3 days, p = 0.006), decreased hospital costs ($14,188+/-$2635 vs $23,016+/-$21,963, p = 0.002), and decreased hospital charges ($37,878+/-$7420 vs $58,289+/-$50,980, p = 0.003) compared with patients with atrial fibrillation discharged in sinus rhythm. In the 12 persons discharged home in atrial fibrillation, no repeat hospitalizations, bleeding complications, or thromboembolic events occurred., Conclusion: A strategy of early discharge of patients with persistent postoperative atrial fibrillation appears promising and deserves prospective testing on a larger scale.

Purpose: To review the available data on the treatment of chronic stable angina and formulate a rational approach to the use of pharmacologic therapy, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass graft surgery (CABG)., Data Sources: A MEDLINE search of English-language literature published between 1976 and 1996 and the bibliographies of relevant articles., Study Selection: Primary research articles, meta-analyses, and meeting abstracts related to the management of chronic stable angina with an emphasis on comparisons of medical therapy, PTCA, and CABG., Data Extraction: Three trials comparing medical therapy with PTCA, seven trials comparing medical therapy with CABG, and nine trials comparing PTCA with CABG., Data Synthesis: Low-risk patients with single-vessel coronary artery disease and normal left ventricular function had greater alleviation of symptoms with PTCA than with medical treatment; mortality rates and rates of myocardial infarction were unchanged. In high-risk patients (risk was defined by severity of ischemia, number of diseased vessels, and presence of left ventricular dysfunction), improvement of survival was greater with CABG than with medical therapy. In moderate-risk patients with multivessel coronary artery disease (most had two-vessel disease and normal left ventricular function), PTCA and CABG produced equivalent mortality rates and rates of myocardial infarction., Conclusions: In low-risk patients, a strategy of initial medical therapy is reasonable. In moderate-risk patients, PTCA and CABG produce similar mortality rates and rates of myocardial infarction but PTCA-treated patients require more revascularization procedures. In high-risk patients, CABG is usually preferred.

To determine the relation between the creation of endocardial lesions and alterations in autonomic tone, we analyzed heart rate variability in patients undergoing radiofrequency catheter ablation for symptomatic supraventricular tachycardia. Elevated heart rates are frequently noted after radiofrequency catheter ablation for supraventricular arrhythmias. It has been postulated that this elevation may be secondary to alterations in cardiac autonomic tone. Since heart rate variability is a measure of autonomic nervous system activity, we used this technique to examine the heart rate elevation and to characterize postablation autonomic changes. Thirty-eight patients undergoing 44 radiofrequency catheter ablation procedures were included in the study. Total arrhythmic substrates treated included 34 accessory pathways and 13 AV nodes with dual physiology. Twenty-four hour ambulatory electrocardiographic recordings were obtained in a drug-free state prior to, ablation early postablation, and late postablation. Spectral and nonspectral analyses of heart rate variability were performed. Subgroup analyses were also done on specific cohorts. Subgroups included patients undergoing accessory pathway ablations, AV node modifications, and ablation of septal and nonseptal targets. To determine whether the amount of tissue damage was related to changes in heart rate variability, we analyzed the relation between the total energy delivered to the endocardium and the peak change in creatine kinase and heart rate variability. In this population, a significant transient increase in heart rate was noted following radiofrequency ablation. All time and frequency domain parameters of heart rate variability showed significant reversible decreases. These changes were independent of target site and arrhythmia substrate. There was no correlation noted between the changes in heart rate variability and either the total amount of energy applied to the endocardium or the change in creatine kinase. Increased heart rates and decreased heart rate variability occur following radiofrequency catheter ablation for supraventricular tachycardia. Clinically, the predominant effect is that of decreased parasympathetic tone. Since these transient changes are independent of arrhythmic substrate or ablation site in the atria, a rich parasympathetic innervation of the heart is proposed.

Successful implantation of a biphasic nonthoracotomy implantable cardioverter defibrillator may not be achieved with a conventional system. We describe a successful device implantation using a pectoral and abdominal patch electrode system.

Nonthoracotomy defibrillator systems can be implanted with a lower morbidity and mortality, compared to epicardial systems. However, implantation may be unsuccessful in up to 15% of patients, using a monophasic waveform. It was the purpose of this study to prospectively examine the efficacy of a second chest patch electrode in a nonthoracotomy defibrillator system. Fourteen patients (mean age 62 +/- 11 years, ejection fraction = 0.29 +/- 0.12) with elevated defibrillation thresholds, defined as > or = 24 J, were studied. The initial lead system consisted of a right ventricular electrode (cathode), a left innominate vein, and subscapular chest patch electrode (anodes). If the initial defibrillation threshold was > or = 24 J, a second chest patch electrode was added. This was placed subcutaneously in the anterior chest (8 cases), or submuscularly in the subscapular space (6 cases). This resulted in a decrease in the system impedance at the defibrillation threshold, from 72.3 +/- 13.3 omega to 52.2 +/- 8.6 omega. Additionally, the defibrillation threshold decreased from > or = 24 J, with a single patch, to 16.6 +/- 2.8 J with two patches. These changes were associated with successful implantation of a nonthoracotomy defibrillator system in all cases. In conclusion, the addition of a second chest patch electrode (using a subscapular approach) will result in lower defibrillation thresholds in patients with high defibrillation thresholds, and will subsequently increase implantation rates for nonthoracotomy defibrillators.

Background: Conventional clinical electrophysiological techniques cannot accurately differentiate between local stimulus response latency and propagation time of the atrial response. The purpose of this study was to identify and distinguish local stimulus response latency from impulse propagation time in the human right atrium during programmed electrical stimulation., Methods: Pacing was performed from two atrial sites (high and low right atrium) in 19 patients, using monophasic action potential recording/pacing combination catheters (interelectrode distance < 2 mm). Local stimulus response latency (interval between stimulus artifact and upstroke of the local monophasic action potential), and propagation time (interval between local and remote monophasic action potential upstroke) were evaluated at a basic cycle length (S1-S1) of 600 ms and as a function of the extrastimulus proximity (interval between extrastimulus and effective refractory period). Data are presented as means +/- SEM., Results: During basic stimulation, local latency was very small (3.8 +/- 1.7 ms). During premature extrastimulation (proximity < 70 ms), local latency increased progressively with decreasing coupling intervals. Prolongation of local latency was most pronounced during stimulation close to the effective refractory period with local stimulus response latency increasing to 18.3 +/- 1.4 ms (380 +/- 7.9%) at 10 ms proximity (P < 0.002) and to 27.9 +/- 3.7 ms (630 +/- 13.2%) at 5 ms proximity, respectively (P < 0.0001). The impulse propagation time between the stimulation site and the remote recording site was on average 54.5 +/- 14.3 ms during basic stimulation, and increased up to 62.1 +/- 13.5 ms (14.0 +/- 8.4%), which was not significant., Conclusions: The intra-atrial impulse propagation remained essentially unchanged during the entire range of premature stimulation. Local stimulus response latency was negligible and constant during late coupling intervals but increased dramatically when extrastimulation approached the preceding repolarization phase. This has the following clinical impact: first, local stimulus response latency during premature extrastimulation curbs the targeted atrial response interval second, local stimulus response latency, not propagation time, seems responsible for the greater functional than effective refractory period during electrical stimulation; third, local stimulus response latency should be considered in pace mapping for accurate comparison of conduction time before pacing with that during pacing.

Radiofrequency ablation has gained acceptance in the treatment of patients with symptomatic Wolff-Parkinson-White syndrome. The purpose of this study was to characterize the relation between temperature and other electroconductive parameters in patients undergoing atrial insertion accessory pathway ablation utilizing a thermistor equipped catheter. The mean temperature and power at sites of atrial insertion ablation are lower than has been previously associated with creation of radiofrequency lesions in the ventricle. While high cavitary blood flow in the atrium may result in cooling, the thinner atrial tissue may require less energy to achieve adequate heating than ventricular myocardium.

The 5-HT3-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an 86Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 microM), but is not shared by other 5-HT3-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205-930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT3 agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(1H)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT3 receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.