Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban: an insight into the mechanism of atrial electrical remodeling.
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OBJECTIVES: We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation. BACKGROUND: Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear. METHODS: A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. RESULTS: The mRNA of L-type calcium channel and of Ca(2+)-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/-0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there was no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation. CONCLUSIONS: L-type calcium channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation. (+info)
A community survey of patients with atrial fibrillation: associated disabilities and treatment preferences.
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BACKGROUND: Anticoagulants are effective in preventing stroke in those with atrial fibrillation, but most patients remain untreated. AIM: To investigate the prevalence of disability, cognitive impairment, and problems with compliance in a representative sample of the elderly with atrial fibrillation, and to determine whether they would want treatment and how they would like services to be arranged. METHOD: In a survey of a random sample of 4843 elderly subjects, those with atrial fibrillation were identified using electrocardiograms. Views on treatment were obtained using a structured interview. Disability was assessed using the Office of Population Censuses and Surveys Disability Scale and cognitive status using the Mini Mental State Examination. General practitioners were asked, via questionnaire, for their views on each subject's compliance. RESULTS: Two hundred and seven elderly people with atrial fibrillation were identified. Almost all subjects expressed a willingness to undertake treatment to prevent stroke and preferred blood testing performed outside of hospital. Disability (82.7%), cognitive impairment (25.7%), and problems with compliance (25.0%) were common, but the prevalence of these difficulties was not substantially different from the general elderly population, and in many cases they could be overcome (e.g. only 10% of subjects had problems with compliance and no-one who could help them to comply). CONCLUSIONS: Most elderly people with atrial fibrillation would accept treatment to prevent stroke. Disability, cognitive impairment, and problems with compliance may make it difficult to treat this patient group. An increase in the use of anticoagulants should be accompanied by the development of services appropriate to this frail population. (+info)
Effect of butorphanol tartrate on shock-related discomfort during internal atrial defibrillation.
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BACKGROUND: In patients with atrial fibrillation, intracardiac atrial defibrillation causes discomfort. An easily applicable, short-acting analgesic and anxiolytic drug would increase acceptability of this new treatment mode. METHODS AND RESULTS: In a double-blind, placebo-controlled manner, the effect of intranasal butorphanol, an opioid, was evaluated in 47 patients with the use of a step-up internal atrial defibrillation protocol (stage I). On request, additional butorphanol was administered and the step-up protocol continued (stage II). Thereafter, if necessary, patients were intravenously sedated (stage III). After each shock, the McGill Pain Questionnaire was used to obtain a sensory (S), affective (A), evaluative (E), and total (T) pain rating index (PRI) and a visual analogue scale analyzing pain (VAS-P) and fear (VAS-F). For every patient, the slope of each pain or fear parameter against the shock number was calculated and individual slopes were averaged for the placebo and butorphanol group. All patients were cardioverted at a mean threshold of 4.4+/-3.3 J. Comparing both patient groups for stage II, the mean slopes for PRI-T (P=0.0099), PRI-S (P=0.019), and PRI-E (P=0.015) became significantly lower in the butorphanol group than in the placebo group. Comparing patients who received the same shock intensity ending stage I and going to stage II, in those patients randomized to placebo the mean VAS-P (P=0.023), PRI-T (P=0. 029), PRI-S (P=0.030), and PRI-E (P=0.023) became significantly lower after butorphanol administration. CONCLUSIONS: During a step-up internal atrial defibrillation protocol, intranasal butorphanol decreased or stabilized the value of several pain variables and did not affect fear. Of the 3 qualitative components of pain, only the affective component was not influenced by butorphanol. The PRI evaluated pain more accurately than the VAS. (+info)
Mapping of atrial activation with a noncontact, multielectrode catheter in dogs.
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BACKGROUND: Endocardial mapping of sustained arrhythmias has traditionally been performed with a roving diagnostic catheter. Although this approach is adequate for many tachyarrhythmias, it has limitations. The purpose of this study was to evaluate a novel noncontact mapping system for assessing atrial tachyarrhythmias. METHODS AND RESULTS: The mapping system consists of a 9F multielectrode-array balloon catheter that has 64 active electrodes and ring electrodes for emitting a locator signal. The locator signal was used to construct a 3-dimensional right atrial map; it was independently validated and was highly accurate. Virtual electrograms were calculated at 3360 endocardial sites in the right atrium. We evaluated right atrial activation by positioning the balloon catheter in the mid right atrium via a femoral venous approach. Experiments were performed on 12 normal mongrel dogs. The mean correlation coefficient between contact and virtual electrograms was 0.80+/-0.12 during sinus rhythm. Fifty episodes of atrial flutter induced in 11 animals were evaluated. In the majority of experiments, complete or almost complete reentrant circuits could be identified within the right atrium. Mean correlation coefficient between virtual and contact electrograms was 0.85+/-0.17 in atrial flutter. One hundred fifty-six episodes of pacing-induced atrial fibrillation were evaluated in 11 animals. Several distinct patterns of right atrial activation were seen, including single-activation wave fronts and multiple simultaneous-activation wave fronts. Mean correlation coefficient between virtual and contact electrograms during atrial fibrillation was 0.81+/-0.18. The accuracy of electrogram reconstruction was lower at sites >4.0 cm from the balloon center and at sites with a high spatial complexity of electrical activation. CONCLUSIONS: This novel noncontact mapping system can evaluate conduction patterns during sinus rhythm, demonstrate reentry during atrial flutter, and describe right atrial activation during atrial fibrillation. The accuracy of electrogram reconstruction was good at sites <4.0 cm from the balloon center, and thus the system has the ability to perform high-resolution multisite mapping of atrial tachyarrhythmias in vivo. (+info)
Pilsicainide intoxication in a patient with dehydration.
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An 81-year-old woman developed pilsicainide intoxication associated with dehydration. The patient had been taking pilsicainide (100 mg/day) for 1 year because of paroxysmal atrial fibrillation. Her renal function was within normal limits. One week before admission, she was suffering from pneumonia, and had appetite loss, fever, and severe fatigue. Physical examination revealed dehydration. The electrocardiogram (ECG) on admission showed atrioventricular dissociation, idioventricular rhythm with marked QRS widening and QTc prolongation. The plasma concentration of pilsicainide on admission was markedly elevated at 6.2 microg/ml, approximately 6 times the therapeutic range (0.25-1.0 microg/ml). Continuous saline infusion was initiated for the treatment of dehydration,which progressively improved. As a result, sinus rhythm was recovered 2 h after admission, and the QRS and JT intervals gradually normalized. This is an interesting case because the proarrhythmia of pilsicainide was induced by dehydration. (+info)
Cardioversion for atrial fibrillation: the views of consultant physicians, geriatricians and cardiologists.
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BACKGROUND AND AIMS: Atrial fibrillation (AF) increases the risk of stroke and also has adverse haemodynamic consequences. Cardioversion of AF to sinus rhythm may obviate the need for long-term anticoagulation and improve cardiovascular haemodynamics, but is probably underused. We therefore investigated the views of hospital consultants about cardioversion for AF. METHODS: 336 Postal questionnaires were sent to all 186 consultant physicians, 54 cardiologists and 96 geriatricians in Scotland, followed by one reminder letter to non-responders. RESULTS: 71% Of questionnaires were returned. Cardiologists referred 18% of AF patients for cardioversion, while physicians referred 11% and geriatricians 5%. Cardiologists had better access to cardioversion facilities and were less likely to consider an enlarged left atrium and organic heart disease to be contra-indications to cardioversion. Anticoagulation was given for less than 3 weeks before cardioversion by 9% of cardiologists, 39% of physicians and 65% of geriatricians (P<0.001), and for less than 3 weeks after cardioversion by 17% of cardiologists, 45% of physicians and 47% of geriatricians (P = 0.7). SUMMARY: The wide variation in practice both between and within the different specialties suggests that consensus guidelines based on the best available evidence should be developed. (+info)
Molecular mechanisms underlying ionic remodeling in a dog model of atrial fibrillation.
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The rapid atrial rate during atrial fibrillation (AF) decreases the ionic current density of transient outward K+ current, L-type Ca2+ current, and Na+ current, thereby altering cardiac electrophysiology and promoting arrhythmia maintenance. To assess possible underlying changes in cardiac gene expression, we applied competitive reverse transcriptase-polymerase chain reaction to quantify mRNA concentrations in dogs subjected to 7 (group P7 dogs) or 42 (group P42 dogs) days of atrial pacing at 400 bpm and in sham controls. Rapid pacing reduced mRNA concentrations of Kv4.3 (putative gene encoding transient outward K+ current; by 60% in P7 and 74% in P42 dogs; P<0.01 and P<0.001, respectively, versus shams), the alpha1c subunit of L-type Ca2+ channels (by 57% in P7 and 72% in P42 dogs; P<0.01 versus shams for each) and the alpha subunit of cardiac Na+ channels (by 18% in P7 and 42% in P42; P=NS and P<0.01, respectively, versus shams) genes. The observed changes in ion channel mRNA concentrations paralleled previously measured changes in corresponding atrial ionic current densities. Atrial tachycardia did not affect mRNA concentrations of genes encoding delayed or Kir2.1 inward rectifier K+ currents (of which the densities are unchanged by atrial tachycardia) or of the Na+,Ca2+ exchanger. Western blot techniques were used to quantify protein expression for Kv4.3 and Na+ channel alpha subunits, which were decreased by 72% and 47%, respectively, in P42 dogs (P<0.001 versus control for each), in a manner quantitatively similar to measured changes in mRNA and currents, whereas Na+,Ca2+ exchanger protein concentration was unchanged. We conclude that chronic atrial tachycardia alters atrial ion channel gene expression, thereby altering ionic currents in a fashion that promotes the occurrence of AF. These observations provide a potential molecular basis for the self-perpetuating nature of AF. (+info)
Doppler sonographic evaluation of left atrial function after cardioversion of atrial fibrillation.
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Restoration of sinus rhythm is not always followed by immediate return of effective atrial contraction. Left atrial mechanical function can be assessed by Doppler echocardiography; in the present study we measured the atrial ejection force, which is a noninvasive Doppler-derived parameter that measures the strength of atrial contraction. The aim of the present study was to evaluate the influence of clinical and echocardiographic parameters: duration and cause of atrial fibrillation, different modality of cardioversion, and left atrial size with respect to the delay in the return of effective atrial contraction after cardioversion. Seventy patients were randomly chosen to undergo cardioversion by either direct current shock or intravenously administered procainamide hydrochloride. The 52 patients who had sinus rhythm restored underwent a complete Doppler echocardiographic examination 1 h after the restoration of sinus rhythm and after 1 day, 7 days, and 1 month. The relation between clinical variables and atrial ejection force was tested. Atrial ejection force was greater immediately and 24 h after cardioversion in patients who underwent pharmacologic therapy compared to patients treated with direct current shock (11.3+/-3 versus 5+/-2.9 dynes; P<0.001). In both groups atrial ejection force increased over time. The mode of cardioversion was significantly associated with recovery of left atrial mechanical function by day 1 in univariate and multivariate analysis (odds ratio, 0.14; 95% confidence interval, 0.02-1.2). The other variable associated with the delay in the recovery of atrial function was a dilated left atrium (odds ratio, 0.16; 95% confidence interval, 0.12-1.6). Atrial ejection force is a noninvasive parameter that can be easily measured after cardioversion and gives accurate information about the recovery of left atrial mechanical function. The recovery of left atrial function was influenced by the mode of cardioversion and left atrial size. (+info)