Heart rate variability in patients with atrial fibrillation is related to vagal tone

A "reduced retina" preparation, consisting of the photoreceptor layer attached to the pigment epithelium in the eyecup, was used to study the pharmacology of the calcium channels controlling glutamate release by photoreceptors in Xenopus. Glutamate release was evoked either by dark adaptation or by superfusion with elevated (20 mM) potassium medium. Both darkness- and potassium-induced release were blocked by cadmium (200 microM). The N-type calcium channel blocker, omega-conotoxin GVIA (500 nM), the P-type calcium channel blocker, omega-agatoxin IVA (20 nM), and the P- and Q-type channel blocker omega-conotoxin MVIIC (1 microM) had no effect on glutamate release. In contrast, the dihydropyridines, nifedipine (10 microM) and nitrendipine (10 microM), which affect L-type calcium channels, blocked both darkness- and potassium-induced release. Bay K 8644 (10 microM), which promotes the open state of L-type calcium channels, enhanced glutamate release. These results indicate that photoreceptor glutamate release is controlled mainly by dihydropyridine-sensitive calcium channels. A dependence of glutamate release on L-type calcium channels also has been reported for depolarizing bipolar cells of a fish retina. Thus, it appears that non-inactivating L-type calcium channels are appropriate to mediate transmitter release in neurons whose physiological responses are sustained, graded potentials.     

Double ventricular parasystole associated with atrial fibrillation

The case of a 75-year-old man with acute myocardial infarction is presented. Two ventricular parasystolic foci, one in the right bundle branch, the other in the left bundle branch system were demonstrated with the aid of a His bundle recording, in the presence of atrial fibrillation.     

Cerebral embolism in elderly patients with atrial fibrillation

Novalvular (nonrheumatic) atrial fibrillation (NVAF) is the most common cardiac condition associated with presumed embolic stroke, accounting for approximately half of the cardiogenic embolic infarctions. Of autopsied stroke patients in the Tokyo Metropolitan Geriatric Hospital, cerebral infarction was found in 75%, intracranial hemorrhage in 19%, and coexisting cerebral hemorrhage and cerebral infarction in 6%. Twenty-eight percent of the cerebral infarctions were embolic infarctions of cardiac origin, 56% of which were caused by NVAF. The incidence of cardiogenic brain embolism ranged from 6 to 23% of the ischemic strokes, and NVAF is the most frequent substrate for brain embolism. Atrial fibrillation increases in its incidence with increasing age. Chronic AF was observed in 10%, and paroxysmal AF in 7% of the autopsied elderly patients. Most of them were nonrheumatic AF. Twenty-two percent of the AF patients had large cerebral infarction, and 15% had medium-sized cortical infarction at the autopsy. NVAF is a very important cause of fatal massive cerebral infarction in the elderly. Of 56 patients with fatal massive cerebral infarction who died within 2 weeks after the strokes, 25 (45%) had embolic stroke associated with NVAF. Anticoagulant therapy prevents recurrent cerebral embolism of cardiac origin. The proper time to initiate anticoagulant therapy following cardiac brain embolism is controversial. Immediate initiation of anticoagulant therapy can reduce the early recurrence, but can result in secondary brain hemorrhage or hemorrhatic transformation. Patients with NVAF may have a lower risk of recurrence during the first 2 to 4 weeks following the initial embolic stroke compared with other cardioembolic sources. Cerebral embolism with NVAF can recur during a long period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ischemic cerebrovascular disease in patients with atrial fibrillation

The purpose of this retrospective study was to elucidate 1) which subgroups are prone to have ischemic cerebrovascular disease (CVD) among patients with atrial fibrillation (Af), 2) vulnerable period of CVD after the diagnosis of chronic Af and 3) the clinical efficacy of antiplatelet therapy in chronic nonvalvular Af patients. During 9 years, a total of 479 patients included 124 cases with paroxysmal Af, 30 cases with paroxysmal Af initially which later changed to chronic Af and 325 cases with chronic Af were enrolled. Among these 355 cases with chronic Af, 57 cases had valvular heart disease (VHD). The results were as follows: 1) The high risk subgroups (incidence rate/100 person-years is more than 6) were chronic Af with VHD or hypertension. The low risk subgroups (less than 2) were paroxysmal Af under 60 years of age, chronic Af with mitral valve prolapse syndrome or with hyperthyroidism. 2) There was no vulnerable period for occurrence of CVD during 9 years' follow-up from the onset of Af. 3) No significant difference in the incidence of CVD was seen in the groups with antiplatelet therapy and without.     

Influence of heart rate on stroke volume variability in atrial fibrillation in patients with normal and impaired left ventricular function

Both resting tachycardia and irregular ventricular rhythm may contribute to impaired cardiac performance in atrial fibrillation (AF). This study assesses the relation between resting heart rate and beat-to-beat changes in left ventricular (LV) ejection and filling in patients with normal and impaired LV systolic function. Beat-to-beat variation in LV outflow and inflow velocity-time integral was measured using pulsed Doppler ultrasound in 39 patients with chronic AF and normal (n=22) or impaired (n=17) LV systolic function. Aortic velocity-time integral variability increased with mean heart rate (p=0.003) even though RR interval variability decreased (p <0.001). Aortic velocity-time integral was more sensitive to the duration of both the preceding (p <0.001) and prepreceding (p <0.001) RR intervals at higher heart rates. These relations were similar for patients with normal and impaired LV systolic function. The sensitivity of the filling velocity-time integral to RR interval variability also increased with heart rate (p <0.001). However, at higher heart rates the filling velocity-time integral (p=0.009) and filling time (p=0.005) were less sensitive to change in RR intervals in patients with impaired LV function. We conclude that beat-to-beat stroke volume variability in AF increases with heart rate. Stroke volume variability was not influenced by LV systolic function.     

Left atrial spontaneous contrast echoes--markers of thromboembolic risk in patients with atrial fibrillation

A consecutive series of 80 patients with atrial fibrillation were studied with both precordial and transoesophageal echocardiography. Left atrial spontaneous contrast echoes were observed in one patient with precordial echocardiography and in 26 patients (33%) with transoesophageal echocardiography. They were found most commonly in patients with rheumatic mitral valve disease (67%) but were observed in 28% of patients with lone atrial fibrillation. Their presence was unrelated to the age, gender and therapy of the patient. Although they were more common in patients with a large left atrium, they were sometimes observed in a normal sized atrial chamber. They were more common in chronic (40%) than in paroxysmal atrial fibrillation (5.6%). No patient had severe mitral regurgitation, but contrast echoes were observed in some patients with mild or moderate mitral regurgitation. Of the 26 patients with spontaneous contrast echoes, six (23%) had echoes consistent with left atrial thrombus compared to one of the 54 patients without these echoes (1.9%) (P = 0.006); 17 (65%) had suffered a previous thromboembolic event compared to 17 of the 54 without these echoes (32%) (P = 0.009). These data support the concept that spontaneous contrast echoes in the left atrium are associated with sluggish blood flow and a thrombogenic environment. Transoesophageal echocardiography may thus be useful in assessing which patients with atrial fibrillation might most benefit from anticoagulation. This hypothesis needs to be evaluated further in a prospective study.     

The effect of sotalol hydrochloride therapy on atrial signal-averaged ECG in patients with paroxysmal atrial fibrillation

BACKGROUND: There has been a continuing public debate about assisted suicide and the proper role, if any, of physicians in this practice. Legislative bans and various forms of legalization have been proposed. METHODS: We mailed questionnaires to three stratified random samples of Michigan physicians in specialties likely to involve the care of terminally ill patients: 500 in the spring of 1994, 500 in the summer of 1994, and 600 in the spring of 1995. Similar questionnaires were mailed to stratified random samples of Michigan adults: 449 in the spring of 1994 and 899 in the summer of 1994. Several different questionnaire forms were used, all of which included questions about whether physician-assisted suicide should be banned in Michigan or legalized under certain conditions. RESULTS: Usable questionnaires were returned by 1119 of 1518 physicians eligible for the study (74 percent), and 998 of 1307 eligible adults in the sample of the general public (76 percent). Asked to choose between legalization of physician-assisted suicide and an explicit ban, 56 percent of physicians and 66 percent of the public support legalization, 37 percent of physicians and 26 percent of the public preferred a ban, and 8 percent of each group were uncertain. When the physicians were given a wider range of choices, 40 percent preferred legalization, 37 percent preferred "no law" (i.e., no government regulation), 17 percent favored prohibition, and 5 percent were uncertain. If physician-assisted suicide were legal, 35 percent of physicians said they might participate if requested--22 percent would participate in either assisted suicide or voluntary euthanasia, and 13 percent would participate only in assisted suicide. Support for physician-assisted suicide was lowest among the strongly religious. CONCLUSIONS: Most Michigan physicians prefer either the legalization of physician-assisted suicide or no law at all; fewer than one fifth prefer a complete ban on the practice. Given a choice between legalization and a ban, two thirds of the Michigan public prefer legalization and one quarter prefer a ban.     

Cost-effectiveness of therapies for patients with nonvalvular atrial fibrillation

BACKGROUND: The most appropriate treatment(s) for patients with atrial fibrillation remains uncertain. OBJECTIVE: To examine the cost-effectiveness of anti-thrombotic and antiarrhythmic treatment strategies for atrial fibrillation. METHODS: We performed decision and cost-effectiveness analyses using a Markov state transition model. We gathered data from the English-language literature using MEDLINE searches and bibliographies from selected articles. We obtained financial data from nationwide physician-fee references, a medical center's cost accounting system, and one of New England's larger managed care organizations. We examined strategies that included combinations of cardioversion, antiarrhythmic therapy with quinidine, sotalol hydrochloride, or amiodarone, and anticoagulant or antiplatelet therapy. RESULTS: For a 65-year-old man with nonvalvular atrial fibrillation, any intervention results in a significant gain in quality-adjusted life years (QALYs) compared with no specific therapy. Use of aspirin results in the largest incremental gain (1.2 QALYs). Cardioversion followed by the use of amiodarone and warfarin together is the most effective strategy, yielding a gain of 2.3 QALYs compared with no specific therapy. The marginal cost-effectiveness ratios of cardioversion followed by aspirin, with or without amiodarone, are $33800 per QALY and $10800 per QALY, respectively. Cardioversion followed by amiodarone and warfarin has a marginal cost-effectiveness ratio of $92400 per QALY compared with amiodarone and aspirin. Strategies that include cardioversion followed by either quinidine or sotalol are both more expensive and less effective than competing strategies. CONCLUSIONS: Cardioversion of patients with nonvalvular atrial fibrillation followed by the use of aspirin alone or with amiodarone has a reasonable marginal cost-effectiveness ratio. While cardioversion followed by the use of amiodarone and warfarin results in the greatest gain in quality-adjusted life expectancy, it is expensive (ie, has a high marginal cost-effectiveness ratio) compared with aspirin and amiodarone. Finally, for patients who are bothered little by symptoms of atrial fibrillation, cardioversion followed by either aspirin or warfarin without subsequent antiarrhythmic therapy is the treatment of choice.     

Antithrombotic therapy prescribed for patients with non-rheumatic atrial fibrillation

Patients with non-rheumatic atrial fibrillation have a fivefold increased risk of stroke. Warfarin reduces this risk by approximately two thirds, but evidence for benefit from aspirin is less compelling. We assessed whether our current practice reflects the message of the trials. In a retrospective case record study we reviewed notes of 131 patients with atrial fibrillation (AF), mean age 79 (range 53-95) years, admitted to a medical unit (72) or geriatric assessment unit (59). Thirty-two patients had paroxysmal AF. Of 115 patients with nonrheumatic AF, 36 (31%) had one or more recorded contraindication to anti-coagulation. Although 79 patients (69%) had no recorded contraindication to warfarin, only 2 took warfarin and 15 aspirin prior to admission. Ten patients commenced warfarin and 8 aspirin before discharge. Thirty-nine patients (53%) without contraindication, were discharged without antithrombotic therapy. Despite evidence to support anticoagulating patients with non-rheumatic AF, this rarely occurs.     

Underutilization of antithrombotic therapy in elderly rural patients with atrial fibrillation

BACKGROUND: Antithrombotic agents are underutilized in elderly patients with atrial fibrillation. In a peer-review audit of antithrombotic use in Missouri, rural patients were given antithrombotic therapy less often than rural patients for unclear reasons. METHODS AND RESULTS: The charts of 597 hospitalized Medicare patients discharged between October 1, 1993, and December 31, 1994, from urban and rural hospitals in Missouri were reviewed. In addition to antithrombotic therapy prescribed at the time of discharge, patient and physician information, relative contraindications to antithrombotic therapy, and risk factors for stroke were identified. Rural and urban patients were similar in terms of age, sex, and risk factors for stroke. At least one stroke risk factor was noted in 87% of rural patients and in 84% of urban patients. Urban patients were more likely to have a relative contraindication to antithrombotic therapy compared with rural patients (66% vs 54%, P =.04) but received antithrombotic therapy more often (58% vs 47%, P =.02). Cardiologists prescribed antithrombotic therapy significantly more often than noncardiologists (69% vs 52%, P =.003). CONCLUSIONS: Elderly rural patients with atrial fibrillation receive antithrombotic therapy less frequently than urban patients despite having a similar high-risk profile and fewer relative contraindications. Primary care physicians prescribe antithrombotic therapy less often than cardiologists, which is one of the reasons for this underutilization.     

Atrial vulnerability in patients with paroxysmal "lone" atrial fibrillation

Little is known about the electrophysiological properties of the atrium predisposing to paroxysmal atrial fibrillation (AF), especially in patients without structural heart disease. This study was conducted to analyze intraatrial conduction, atrial refractoriness, and arrhythmia inducibility in patients with lone paroxysmal AF. An electrophysiological study was performed in 24 patients with a documented history of lone paroxysmal AF but in sinus rhythm at the time of the electrophysiological study. Twelve patients without any history of atrial arrhythmias served as controls. The patients with lone paroxysmal AF showed a significant prolonged local conduction time S1A1 (70 +/- 21 ms vs 36 +/- 12 ms, P < 0.0001), a lack of rate adaptation of the functional refractory period (FRP changes/cycle length changes < 10% in 15 of 24 patients with lone paroxysmal AF vs 1/12 controls, P = 0.002) and a higher incidence of inducible AF with only one extrastimulus (13/24 vs 0/12, P = 0.0014). The total P wave duration in the surface ECG (89 +/- 14 ms vs 83 +/- 8 ms, P = 0.15), the intraatrial conduction time (36 +/- 14 ms vs 28 +/- 8 ms, P = 0.07), the presence of a fragmented atrial electrogram (16/24 vs 7/12, P = 0.62), the absolute value of the effective refractory period (204 +/- 28 ms vs 212 +/- 23 ms, P = 0.42), and the vulnerability index (3.0 +/- 1.5 vs 3.6 +/- 1.5, P = 0.26) were not statistically different between the two groups. The presence of a prolonged (> 50 ms) S1A1 and/or the presence of a lack of rate adaptation of the FRP and/or the presence of inducible AF identified patients with spontaneous lone paroxysmal AF with a sensitivity of 96%, a specificity of 67%, a positive predictive value of 85%, and a negative predictive value of 89%. In patients with lone paroxysmal AF, the electrophysiological study using conventional techniques allows not only to detect AF inducibility using a nonaggressive protocol, but also to reveal several electrophysiological abnormalities related to the atrial substrate itself. This atrial vulnerability may explain the high incidence of recurrences in patients with lone paroxysmal AF.     

Warfarin reduces silent cerebral infarction in elderly patients with atrial fibrillation

A simple, fast, reliable, and specific immunoassay has been developed to detect and measure AD7C-NTP, a biochemical marker for Alzheimer's disease, in cerebrospinal fluid (CSF). This assay, called the AD7C Test, is an enzyme-linked sandwich immunoassay (ELSIA) using 96 well microtiter plates. The plate surface is coated with a monoclonal antibody (N3I4) which has a high affinity and specificity for AD7C-NTP, capturing it effectively from CSF samples. The detection was achieved using a polyclonal antibody (ADRI). Both N3I4 and ADRI were generated using recombinantly produced AD7C-NTP. The assay is highly sensitive (30-50 pg), linear to 2.0 ng (r2 > 0.99), and reproducible (C.V. < 10%). The utility of the assay has been demonstrated using CSF specimens from early Alzheimer's disease patients and age matched controls (sensitivity of 89% and specificity of 89%).     

Altered protein binding of quinidine in patients with atrial fibrillation and flutter

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine that plays a role in transplant rejection. We tested the hypothesis that IL-6 levels in serum or urine could be of value in predicting acute and chronic allograft rejection. Furthermore, we examined whether or not such levels reflected IL-6 expression in the kidney. METHODS: We measured IL-6 and IL-6 soluble receptor (IL-6sR) in serum and urine of 145 transplant patients and 20 normal controls. In parallel, we studied 108 renal biopsies. IL-6 was measured with a bioassay system using an IL-6 dependent cell line. IL-6sR was measured with enzyme-linked immunosorbent assay. The biopsies were examined for IL-6 and IL-6 receptor (IL-6R) expression with immunohistochemistry. RESULTS: Rejection episodes occurring within 2 months of transplantation were accompanied by elevated IL-6 concentrations in serum (17 +/- 4.8 pg/ml, P < 0.05) and urine (114 +/- 27 pg/ml, P < 0.005), compared to controls. These values returned towards baseline (0-5 pg/ml) after successful rejection treatment. The sensitivity of urine measurements was much higher (93%) than serum (54%). The specificity in serum (70%) and urine (60%) was reduced by infection, acute tubular necrosis, and antithymocyte globulin treatment. Serum and urine IL-6sR values did not correlate with rejection. In biopsy tissue, IL-6 and IL-6R were both elevated during rejection. Especially, mononuclear cells within the interstitial infiltrate stained positive. However, the amount of IL-6 positive cells did not correlate with peripheral IL-6 concentrations. CONCLUSIONS: Urine but not serum IL-6 values are sensitive indicators of rejection; however, they are confounded by infection, acute tubular necrosis, and certain antirejection treatments. These features limit their usefulness.     

Cost-effectiveness of preference-based antithrombotic therapy for patients with nonvalvular atrial fibrillation

BACKGROUND AND PURPOSE: Recent atrial fibrillation guidelines recommend the incorporation of patient preferences into the selection of antithrombotic therapy. However, no trial has examined how incorporating such preferences would affect quality-adjusted survival or medical expenditure. We compared 10-year projections of quality-adjusted survival and medical expenditure associated with two atrial fibrillation treatment strategies: warfarin-for-all therapy versus preference-based therapy. The preference-based strategy prescribed whichever antithrombotic therapy, warfarin or aspirin, had the greater projected quality-adjusted survival. METHODS: We used decision analysis stratified by the number of stroke risk factors (history of stroke, transient ischemic attack, hypertension, diabetes, or heart disease). The base case focused on compliant 65-year-old patients who had nonvalvular atrial fibrillation and no contraindications to antithrombotic therapy. RESULTS: In patients whose only risk factor for stroke was atrial fibrillation, preference-based therapy improved projected quality-adjusted survival by 0.05 quality-adjusted life year (QALY) and saved $670. For patients who had atrial fibrillation and one additional risk factor for stroke, preference-based therapy improved quality-adjusted survival by 0.02 QALY and saved $90. In patients who had atrial fibrillation and multiple additional risk factors for stroke, preference-based therapy increased medical expenditures and did not improve quality-adjusted survival substantially. The benefits of preference-flexible therapy arose from the minority of patients who would have had a longer quality-adjusted survival if they had been prescribed aspirin rather than warfarin. CONCLUSIONS: As do risks of stroke and of hemorrhage, patients' preferences help to determine which antithrombotic therapy is optimal. Preference-based treatment should improve quality-adjusted survival and reduce medical expenditure in patients who have nonvalvular atrial fibrillation and not more than one additional risk factor for stroke.     

Early discharge of patients with new-onset atrial fibrillation after cardiovascular surgery

The feasibility of monitoring intracellular sodium changes using Na triple quantum filtered NMR without a chemical shift reagent (SR) was investigated in an isolated rat heart during a variety of interventions for Na(i) loading. Perfusion with 1 mM ouabain or without K+ present in the perfusate for 30 min produced a rise of the Na TQF signal with a plateau of approximately 190% and approximately 228% relative to the preintervention level, respectively. Stop-flow ischemia for 30 min resulted in a TQF signal growth of approximately 147%. The maximal Na TQF signal increase of 460% was achieved by perfusion without K+/Ca2+, corresponding to an elimination of the Na transmembrane gradient. The observed values of Na NMR TQF growth in the physiological and pathological ranges are in agreement with reported data by other methods and have a linear correlation with intracellular sodium content as determined in this study by Co-EDTA method and by sucrose-histidine washout of the extracellular space. Our data indicate that the increase in Na TQF NMR signal is determined by the growth of Na(i), and the extracellular Na contribution to the total TQF signal is unchanged at approximately 64%. In conclusion, Na TQF NMR without using SR offers a unique and noninvasive opportunity to monitor alterations of intracellular sodium. It may provide valuable insights for developing cardioprotective strategies and for observing the effects of pharmaceutical treatments on sodium homeostasis.     

Transesophageal echocardiographic predictors for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation

The aim of this study was to assess the value of transesophageal echocardiography (TEE) in patients with atrial fibrillation in predicting restoration and maintenance of sinus rhythm after electrical cardioversion. TEE was performed in 62 patients with atrial fibrillation before their first elective cardioversion. Clinical variables evaluated were: age, gender, duration, and etiology of atrial fibrillation. TEE variables included: left atrial (LA) length, width, and size, LA annulus size, as well as presence of LA spontaneous contrast, thrombus and mitral regurgitation, LA appendage size and flow, and left ventricular function. Based on initial outcome of cardioversion, patients were grouped into patients who remained in atrial fibrillation and in whom sinus rhythm was restored. The latter group of patients was followed for 1 year, and grouped into patients who reverted to atrial fibrillation and in whom sinus rhythm was maintained. Successful cardioversion was achieved in 50 of 62 patients (81%). None of the clinical or TEE variables were related to initial outcome. At 1-year follow-up, 29 of 50 patients (58%) who underwent successful cardioversion continued to have sinus rhythm. The following variables were related to maintenance of sinus rhythm: duration of atrial fibrillation (6.7 +/- 7.3 vs 2.0 +/- 2.4 months; p < 0.005); LA length (6.2 +/- 0.7 vs. 5.5 +/- 1.0 cm; p < 0.008); width (5.1 +/- 0.5 vs. 4.5 +/- 0.7 cm; p < 0.002); size (26.4 +/- 5.0 vs 19.8 +/- 6.5 cm2; p < 0.0005); annulus size (4.0 +/- 0.2 vs 3.7 +/- 0.3 cm; p < 0.0005); presence of LA spontaneous contrast (13 [62%] vs 4 [14%]; p < 0.002), and LA appendage flow (19 +/- 8 vs 36 +/- 15 cm/s; p < 0.0005). In multivariate logistic regression analysis, LA annulus size, but especially LA appendage flow, were significantly associated with maintenance of sinus rhythm. Thus, in TEE-guided electrical cardioversion of atrial fibrillation, variables often used to assess thromboembolic risk may also be used to predict 1-year outcome of cardioversion.     

Short deceleration time of mitral inflow E velocity: prognostic implication with atrial fibrillation versus sinus rhythm

The present study retrospectively identified 367 patients who had restrictive physiology as defined by deceleration time < or = 130 msec; 293 were in sinus rhythm (SR) (194 men and 99 women; mean age 64 +/- 14 years) and 74 were in atrial fibrillation (AF) (51 men and 23 women; mean age 72 +/- 11 years; p < 0.001). Both groups had similar underlying diagnoses and no significant difference in Doppler indices (E wave, 96 +/- 23 vs 99 +/- 22 cm/sec in SR and AF, respectively; deceleration time, 116 +/- 12 vs 116 +/- 13 msec; and left ventricular outflow tract time velocity integral, 14.8 +/- 4.8 vs 14.5 +/- 4.4 cm). Left ventricular ejection fraction was significantly lower in SR patients (29% +/- 16% vs 39% +/- 20%; p = 0.0003). There were 120 deaths (41%) in the SR group and 35 (47%) in the AF group (median follow-up for both groups, 2.2 years). Restrictive physiology as defined by Doppler echocardiography (deceleration time < or = 130 msec) appears to predict a similar poor prognosis with AF as with SR.