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PubMed1999

[Left ventricular relaxation in lone atrial fibrillation and atrial fibrillation with heart disease].

Atrial fibrillation with organic heart disease shows a steady value for the time constant of left ventricular isovolumetric relaxation (TC), whereas left ventricular contractility varies from beat to beat. However, there is no report on left ventricular relaxation in lone atrial fibrillation. This study assessed left ventricular relaxation in 5 patients with lone atrial fibrillation, 3 with ischemic heart disease and one with hypertrophic cardiomyopathy. Left ventricular pressure was recorded at 3 msec intervals, with a high fidelity micromanometer-tipped catheter. Maximal positive dP/dt (dP/dtmax) and TC of isovolumetric left ventricular relaxation period [P(t) = (P0-P infinity) exp (-t/TC) + P infinity] were measured as indices of left ventricular contractility and left ventricular relaxation, respectively. Correlation coefficients of dP/dtmax and TC versus the ratio of the preceding to the pre-preceding RR-interval (RR2/RR1) were calculated. A good correlation was found between dP/dtmax and RR2/RR1 in all patients (r = 0.71-0.84, p < 0.0001). No correlation between TC and RR2/RR1 was found in patients with atrial fibrillation with organic heart disease, but a good correlation was found between TC and RR2/RR1 in patients with lone atrial fibrillation (r = 0.74-0.95, p < 0.0001). The correlation between TC and RR2/RR1 is well preserved in lone atrial fibrillation. The mechanism of the variation of TC with the RR2/RR1 interval in lone atrial fibrillation may be similar to the change of TC in postextrasystolic potentiation, which is attributed to the change of intracellular Ca2+ concentration. Absence of correlation between TC and RR2/RR1 interval may indicate that left ventricular relaxation is disturbed in patients with atrial fibrillation with organic heart disease.

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PubMed1996

Drug therapy for prevention of atrial fibrillation.

Atrial fibrillation is not a homogeneous entity, and many factors are responsible for a number of different behaviors, clinical consequences, and reactions to therapy. Therefore, the conventional evaluation of preventive treatments is not really adapted to provide the correct answers to difficult problems of therapeutic indications, as the 2 components of the benefit-risk ratio are not really known. Like ventricular fibrillation, atrial fibrillation may be primary or secondary to organized tachyarrhythmias, and reentrant flutter or automatic atrial tachycardia may well form the actual target for treatment. The automatic nervous system is never absent as a determinant of the onset of arrhythmia, and the vagal as well as the sympathetic action may predominate and explain why a treatment may or may not be effective in situations that are identical only in appearance. The electrophysiologic milieu formed by the atrial tissue probably accounts for the perpetuation of the process of atrial fibrillation or its self-termination, and drugs themselves may contribute to modify the milieu in a way that in the end may be favorable or not. Finally, the presence or the absence of heart disease and heart failure largely contributes to the state of the vagosympathetic balance, to the hemodynamic consequences of atrial fibrillation, and ultimately to the proper toxic effects of drugs. The overall consequence of these complex situations is that any precise therapeutic decision algorithm for atrial fibrillation is always simplistic and that any global evaluation of drug efficacy or toxicity is not really meaningful as long as the category of patients treated is not precisely determined: no drug appears better or worse than others, but simply more or less adapted to various situations.

Anti-Arrhythmia Agents↗

PubMed1999

Should ablation of atrial flutter be discouraged in patients with documented atrial fibrillation?

Atrial fibrillation and atrial flutter often coexist in the same patient. The purpose of this article is to provide an analysis of the mechanisms underlying the transformation from atrial fibrillation into atrial flutter and to investigate the long-term clinical benefits following ablation of atrial flutter in relation to recurrences of atrial fibrillation. Experimental studies in the human atrium demonstrated that in most instances atrial fibrillation is a triggering rhythm for atrial flutter. However, a review of the most recent studies shows a low percentage of recurrence of atrial fibrillation after successful catheter ablation for atrial flutter. The risk factors for this recurrence are the presence of structural heart disease, increased left atrial dimension and volume, a previous history of atrial fibrillation, and the failure of multiple antiarrhythmic drugs, inducibility of atrial fibrillation by a standard programmed electrical stimulation protocol after catheter ablation. These data, together with the high success rate of catheter ablation for atrial flutter, suggest to perform radiofrequency catheter ablation for atrial flutter in patients with documented atrial fibrillation.

Atrial Fibrillation↗

PubMed1997

Propafenone for conversion and prophylaxis of atrial fibrillation. Propafenone Atrial Fibrillation Trial Investigators.

Pharmacologic therapy is widely used for restoration of sinus rhythm and prevention of recurrences of atrial fibrillation. Because concerns have been raised about their potential proarrhythmic effects, therapeutic regimens should be evaluated by placebo-controlled studies to determine their efficacy and safety. One hundred thirty-six patients with persistent atrial fibrillation were randomized to receive propafenone 2 mg/kg over 30 minutes, followed by oral propafenone 150 mg 3 times daily or matching placebo. Nonresponders to intravenous therapy underwent direct-current cardioversion. Both responders to intravenous therapy and converters to sinus rhythm after direct-current cardioversion were followed for 6 months in a double-blind oral treatment period of propafenone 150 mg 3 times daily or matching placebo. Pharmacologic conversion to sinus rhythm was achieved in 29% of the patients taking propafenone and in 17% of patients taking placebo (p > or = 0.10). Subsequent direct-current cardioversion in nonresponders was equally successful (70%) in both groups (p > or = 0.10). The proportion of patients free from recurrent symptomatic arrhythmia at 6 months was 67% for the propafenone and 35% for the placebo group (p < 0.01). Time to atrial fibrillation relapse was more favorable with propafenone than with placebo (p < 0.001). The incidence of drug-related side effects was 10% in the propafenone group and 14% in the placebo group. Thus, "slow" infusion of propafenone seems to be of limited value for terminating atrial fibrillation. Oral propafenone at a low dosage 150 mg 3 times daily is well tolerated and effective in maintaining sinus rhythm for 6 months after pharmacologic or electrical restoration of sinus rhythm.

Administration, Oral↗

PubMed2003

Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: the Atrial Fibrillation Suppression Trial II (AFIST II).

BACKGROUND: The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. METHODS AND RESULTS: Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2x2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P=0.037 and P=0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P=0.047 and P=0.040, respectively). CONCLUSIONS: Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.

Administration, Oral↗

PubMed2000

Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study.

BACKGROUND: This double-blind, multicenter, placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation (AF) or atrial flutter (AFl) to sinus rhythm (SR) and maintaining SR for 1 year. METHODS AND RESULTS: Patients with AF or AFl (n=325) were randomized to 125, 250, or 500 microgram dofetilide or placebo twice daily. Dosages were adjusted for QTc response and, after 105 patients were enrolled, for calculated creatinine clearance (Cl(Cr)). Pharmacological cardioversion rates for 125, 250, and 500 microgram dofetilide were 6.1%, 9.8%, and 29.9%, respectively, versus 1.2% for placebo (250 and 500 microgram versus placebo; P=0.015 and P<0.001, respectively). Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91% in 36 hours. For the 250 patients who successfully cardioverted pharmacologically or electrically, the probability of remaining in SR at 1 year was 0.40, 0.37, 0.58 for 125, 250, and 500 microgram dofetilide, respectively, and 0.25 for placebo (500 microgram versus placebo, P=0.001). Two cases of torsade de pointes occurred, 1 on day 2 and the other on day 3 (0.8% of all patients given active drug); 1 sudden cardiac death, classified as proarrhythmic, occurred on day 8 (0.4% of all patients given active drug). CONCLUSIONS: Dofetilide, a new class III antiarrhythmic agent, is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year. In-hospital initiation and dosage adjustment based on QTc and Cl(Cr) are necessary to minimize a small but nonnegligible proarrhythmic risk.

Administration, Oral↗

PubMed2000

Mitral valve surgery and atrial fibrillation: is atrial fibrillation surgery also needed?

OBJECTIVE: Atrial fibrillation (AF) persisting after mitral valve surgery reduces survival due to heart failure and thrombo-embolisms, and impairs quality of life. Arrhythmia surgery for AF shows today very satisfying results and therefore mitral valve surgery with AF surgery appears appealing. This study explores whether combined surgery in view of today's results of mitral valve surgery is indicated. METHODS AND RESULTS: An outcome analysis of the arrhythmia outcome of patients undergoing exclusive mitral valve surgery with or without tricuspid repair was done. Preoperative baseline characteristics including arrhythmia pattern, surgical methods and follow-up findings were reviewed. Postoperative management of AF was not protocolized. Between 1990 and 1993, 162 consecutive patients underwent mitral valve surgery; follow-up was a mean of 3.3+/-1.9 years. In-hospital and late mortality were 1 and 9%, respectively. Sinus rhythm was preserved in 40 of 57 (70%) patients with preoperative sinus rhythm whereas AF persisted in 58 of 68 (85%) of patients with preoperative chronic AF (>1 year present). Sinus rhythm without AF was observed in 10 of 29 (34%) patients with preoperative paroxysmal AF. The 4-year Kaplan-Meier survival did not differ between patients with preoperative sinus rhythm (95.2%), paroxysmal AF (89.2%) and chronic AF (82.9%) but AF persisting after surgery tended to determine survival (P=0.05). Gender, age and right ventricular pressure and tricuspid valve repair were risk factors for postoperative recurrence of AF in patients with sinus rhythm at discharge, relative risk 0.35, 1.06, 1. 04 and 2.9, respectively. CONCLUSION: Current mitral valve surgery with or without tricuspid valve repair does not eliminate preoperative paroxysmal or chronic AF. Secondly, because preoperative AF did not determine survival after mitral valve surgery, whereas postoperatively persisting AF was weakly associated with survival, atrial arrhythmia surgery primarily aims to reduce morbidity due to AF. Some characteristics can identify patients with increased propensity for persisting AF after surgery. Randomized studies of AF surgery are needed to identify suitable candidates for combined surgery.

Adult↗

PubMed1995

Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats.

BACKGROUND: In this study we tested the hypothesis that atrial fibrillation (AF) causes electrophysiological changes of the atrial myocardium which might explain the progressive nature of the arrhythmia. METHODS AND RESULTS: Twelve goats were chronically instrumented with multiple electrodes sutured to the epicardium of both atria. Two to 3 Weeks after implantation, the animals were connected to a fibrillation pacemaker which artificially maintained AF. Whereas during control episodes of AF were short lasting (6 +/- 3 seconds), artificial maintenance of AF resulted in a progressive increase in the duration of AF to become sustained (> 24 hours) after 7.1 +/- 4.8 days (10 of 11 goats). During the first 24 hours of AF the median fibrillation interval shortened from 145 +/- 18 to 108 +/- 8 ms and the inducibility of AF by a single premature stimulus increased from 24% to 76%. The atrial effective refractory period (AERP) shortened from 146 +/- 19 to 95 +/- 20 ms (-35%) (S1S1, 400 ms). At high pacing rates the shortening was less (-12%), pointing to a reversion of the normal adaptation of the AERP to heart rate. In 5 goats, after 2 to 4 weeks of AF, sinus rhythm was restored and all electrophysiological changes were found to be reversible within 1 week. CONCLUSIONS: Artificial maintenance of AF leads to a marked shortening of AERP, a reversion of its physiological rate adaptation, and an increase in rate, inducibility and stability of AF. All these changes were completely reversible within 1 week of sinus rhythm.

Animals↗

PubMed2005

Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial.

BACKGROUND AND PURPOSE: Although the efficacy of anticoagulant therapy for primary prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) has been established, efficacy of antiplatelet therapy for low-risk patients is disputable in Japanese patients because of the frequent hemorrhagic complications. We examined the efficacy and safety of aspirin therapy in Japanese patients with NVAF in a prospective randomized multicenter trial. METHODS: Patients with NVAF were randomized to an aspirin group (aspirin at 150 to 200 mg per day) or a control group without antiplatelet or anticoagulant therapy. Primary end points included cardiovascular death, symptomatic brain infarction, or transient ischemic attack. RESULTS: A total of 426 patients were randomized to aspirin group and 445 to no treatment. The trial was stopped earlier because there were 27 primary end point events (3.1% per year; 95% CI, 2.1% to 4.6% per year) in the aspirin group versus 23 (2.4% per year; 95% CI, 1.5% to 3.5% per year) in the control group, suggesting a low possibility of superiority of the aspirin treatment for prevention of the primary end point. In addition, treatment with aspirin caused a marginally increased risk of major bleeding (7 patients; 1.6%) compared with the control group (2 patients; 0.4%; Fisher exact test P=0.101). CONCLUSIONS: For prevention of stroke in patients with NVAF, aspirin at 150 to 200 mg per day does not seem to be either effective or safe. Further prospective studies are needed to determine the best preventive therapy for cerebrovascular events in Japanese patients with NVAF.

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PubMed2000

Role of transthoracic echocardiography in atrial fibrillation.

Atrial fibrillation is a major clinical problem that is predicted to be encountered more frequently as the population ages. The clinical management of atrial fibrillation has become increasingly complex as new therapies and strategies have become available for ventricular rate control, conversion to sinus rhythm, maintenance of sinus rhythm, and prevention of thromboembolism. Clinical and transthoracic echocardiographic features are important in determining etiology and directing therapy for atrial fibrillation. Left atrial size, left ventricular wall thickness, and left ventricular function have independent predictive value for determining the risk of developing atrial fibrillation. Left atrial size may have predictive value in determining the success of cardioversion and maintaining sinus rhythm in selected clinical settings but has less value in the most frequently encountered group, patients with nonvalvular atrial fibrillation, in whom the duration of atrial fibrillation is the most important feature. When selecting pharmacological agents to control ventricular rate, convert to sinus rhythm, and maintain normal sinus rhythm, transthoracic echocardiography (TTE) allows noninvasive evaluation of left ventricular function and hence guides management. The combination of clinical and transthoracic echocardiographic features also allows risk stratification for thromboembolism and hemorrhagic complications in atrial fibrillation. High-risk clinical features for thromboembolism supported by epidemiological observations, results of randomized clinical trials, and meta-analyses include rheumatic valvular heart disease, prior thromboembolism, congestive heart failure, hypertension, older (> 75 years old) women, and diabetes. Small series of cases also suggest those with hyperthyroidism and hypertrophic cardiomyopathy are at high risk. TTE plays a unique role in confirming or discovering high-risk features such as rheumatic valvular disease, hypertrophic cardiomyopathy, and decreased left ventricular function. Validation of the risk stratification scheme used in the Stroke Prevention in Atrial Fibrillation-III trial is welcomed by clinicians who are faced daily with balancing the benefit and risks of anticoagulation to prevent thromboembolism in patients with atrial fibrillation.

Atrial Fibrillation↗

PubMed2000

Randomized crossover comparison of DDDR versus VDD pacing after atrioventricular junction ablation for prevention of atrial fibrillation. The atrial pacing peri-ablation for paroxysmal atrial fibrillation (PA (3)) study investigators.

BACKGROUND: Some clinical data suggest that atrial-based pacing prevents paroxysmal atrial fibrillation (AF). This study tested the hypothesis that DDDR pacing compared with VDD pacing prevents AF after atrioventricular (AV) junction ablation. METHODS AND RESULTS: Patients were randomized to DDDR pacing (n=33) or to VDD pacing (n=34) after AV junction ablation and followed every 2 months for 6 months. Patients then crossed over to the alternate pacing mode and were followed for an additional 6 months. Primary analysis included the time to first recurrence of sustained AF (duration >5 minutes), total AF burden, and the development of permanent AF. The time to first episode of AF was similar in the DDDR group (0.37 days, 95% CI 0.1 to 1.3 days) and the VDD pacing group (0.5 days, 95% CI 0.2 to 1.7 days, P=NS). AF burden increased over time in both groups (P<0.01). At the 6-month follow-up, AF burden was 6.93 h/d (95% CI 4. 37 to 10.96 h/d) in the DDDR group and 6.30 h/d (95% CI 3.99 to 9.94 h/d) in the VDD group (P=NS). Twelve (35%) patients in the DDDR group and 11 (32%) patients in the VDD group had permanent AF within 6 months of ablation. Within 1 year of follow-up, 43% of patients had permanent AF. CONCLUSIONS: DDDR pacing compared with VDD pacing does not prevent paroxysmal AF over the long term in patients in the absence of antiarrhythmic drug therapy after total AV junction ablation. Many patients have permanent AF within the first year after ablation.

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PubMed1995

Clinical significance of serum TSH in euthyroid patients with paroxysmal atrial fibrillation.

Atrial fibrillation may occur in patients with a variety of cardiovascular or chronic disease as well as in normal subjects. Many authors reported that atrial fibrillation occurs in patients with thyrotoxicosis. It is reported that a low serum thyrotrophin concentration in an asymptomatic person with normal serum thyroid hormone concentrations can be a independent risk factor for developing atrial fibrillation. But we focused on the significance of serum thyroid stimulating hormone (TSH) in the euthyroid patient with atrial fibrillation whose serum level of T3, T4, fT4, and even TSH were absolutely within normal range. On our results, there was no significant differences in age, sexual distribution, and left ventricular ejection fraction between the patients group of paroxysmal and chronic persistent atrial fibrillation (p > 0.05), but there was larger left atrial dimension (LAD) and more cases of rheumatic heart disease in the chronic persistent atrial fibrillation group and there was more cases of lone atrial fibrillation in the paroxysmal atrial fibrillation group (p < 0.05). There was no significant differences in serum levels of T3, T4, fT4 between paroxysmal and chronic persistent atrial fibrillation, but significantly lower serum TSH was found in patients with paroxysmal atrial fibrillation (p < 0.001), and these findings were more significant after the control of hemodynamic change (p < 0.001 vs p < 0.05). The discriminant value in serum TSH between the paroxysmal and chronic atrial fibrillation group was 1.568U/mL with about 76% of predictive power. There was significantly lower serum TSH in paroxysmal atrial fibrillation in all age groups (p < 0.05). There was a significantly higher prevalence of cerebral thromboembolic events in chronic persistent (27.7%) and disease-associated (15.0% atrial fibrillation than in the paroxysmal (3.3%) and lone (4.5%) atrial fibrillation group (p < 0.001). Therefore, we suggest that serum TSH below the serum concentration of 1.5U/mL can be a risk factor for developing atrial fibrillation when the serum level of T3, T4, fT4, and even TSH were within absolutely normal range.

Adult↗

PubMed2003

Molecular genetic studies in atrial fibrillation.

Atrial fibrillation is a complex disease. Its etiologies are diverse and genetic factors may also contribute to this disease. With the advent of modern molecular biology technology, it is now possible to explore the genetic components in the pathogenesis of atrial fibrillation. Past molecular genetic studies on atrial fibrillation in the literature can be divided into linkage analysis studies and association studies. The subjects for linkage analysis studies are pedigrees of probands with Mendelian hereditary atrial fibrillation. The first locus identified for autosomal dominant atrial fibrillation locates at 10q22-q24. However, the exact gene is still unknown. Another linkage analysis study in Chinese revealed that LQT1 gene (I(Ks) alpha-subunit) was the responsible gene. A missense mutation in the I(Ks) alpha-subunit results in a gain of function, which is important in causing atrial fibrillation. The third known locus for familial atrial fibrillation locates at 6q14-16. The responsible gene remains still unknown. The other type of studies takes the case-control design (association studies) and the subjects have multigenic atrial fibrillation. In a study in a Japanese population, it was reported that the angiotensin-converting enzyme insertion/deletion polymorphism was not associated with atrial fibrillation. On the other hand, researchers in Taiwan reported that a nonsynonymous single nucleotide polymorphism of the LQT5 gene (I(Ks) beta-subunit) is associated with atrial fibrillation. In summary, there is growing evidence showing that genetic factors are important in the pathogenesis of atrial fibrillation. We expect that more genes responsible for or contributing to atrial fibrillation will be identified in the future and these will elucidate the molecular mechanisms of atrial fibrillation.

Animals↗

PubMed2002

[Mechanisms of initiation in atrial fibrillation].

Atrial fibrillation is the most relevant arrhythmia in daily clinical practice. The pathophysiology is determined by multiple independent reentrant wavelets in both atria. Repetitive triggers and an underlying substrate may favor the initiation and maintenance of atrial fibrillation. Mapping studies in patients with drug-refractory paroxysmal atrial fibrillation identified potentials from the ostia of pulmonary veins as a main source of triggers that initiate atrial fibrillation. In ongoing clinical trials, catheter ablation of pulmonary vein foci is used to eliminate atrial premature beats and thereby prevent the initiation of atrial fibrillation. The autonomic modulation of the heart rate and the occurrence of other supraventricular tachycardias that degenerate into atrial fibrillation are also considered as triggering mechanisms of atrial fibrillation. Since symptomatic bradycardia is associated with an increased incidence of atrial fibrillation, atrial pacing therapies for prevention of atrial fibrillation are another concept. Ongoing clinical trials evaluating the efficacy of pacing in patients with and without a primary pacemaker indication are currently under investigation. To date, data to which extent anatomical and electrophysiological characteristics of the atria influence the initiation and maintenance of atrial fibrillation are still missing. The myocardial adaptation to atrial fibrillation, the so-called "atrial remodeling", includes shortening of the atrial refractory period, slowing of atrial conduction, shortening of the atrial action potential, a progressive reduction of L-type calcium channel expression and microfibrosis of the myocardial tissue. New drug developments target atrial remodeling by modulating ion channel function and receptors of the angiotensin metabolism.

Action Potentials↗

PubMed2003

Atrial electrophysiology and mechanisms of atrial fibrillation.

Atrial fibrillation is the most common cardiac arrhythmia in clinical practice, and its management remains challenging. A solid understanding of the scientific basis for atrial fibrillation therapy requires insight into the mechanisms underlying the arrhythmia, about which an enormous amount has been learned over the past 10 years. The basic information presently available about atrial fibrillation mechanisms is reviewed. The particular properties of normal atrial electrophysiology are discussed, including salient ionic determinants of the atrial action potential and key anatomic features. Reviewed are three crucial arrhythmia mechanisms long held to be involved in atrial fibrillation: 1) rapid ectopic activity, 2) single-circuit reentry with fibrillatory conduction, and 3) multiple-circuit reentry. The determinants of each and the evidence for their involvement in clinical and/or experimental atrial fibrillation are noted. The physiological consequences, various contributing mechanisms, and clinical implications of the role of atrial-tachycardia remodeling are analyzed. Atrial-tachycardia remodeling links the potential mechanisms of atrial fibrillation, since atrial fibrillation beginning by any mechanism is likely to cause tachycardia-remodeling and thus promote the maintenance of atrial fibrillation by multiple-circuit reentry. Atrial structural remodeling is discussed as a paradigm of atrial fibrillation in which the classic features required for reentry (reduced refractory period and reentrant wavelength) may be lacking. Finally, the importance of recent insights into potential genetic determinants of atrial fibrillation is reviewed. The classic understanding of atrial fibrillation pathophysiology saw the different possible mechanisms as being alternative and opposing hypotheses. We now consider the multiple potential mechanisms as contributing to the pathophysiology of the arrhythmia to a different extent in different clinical settings and interacting with each other in a dynamic way at various stages of the natural history in many patients. It is hoped that this improved mechanistic understanding will lead to the development of improved therapeutic options.

Action Potentials↗

PubMed1982

The effects of atrial fibrillation on atrial pressure-volume and flow relationships.

To study whether atrial fibrillation might produce local changes in the atrium which could facilitate the tendency of this arrhythmia to become chronic and self-perpetuating, we compared the effect of atrial fibrillation, atrial pacing, and acute volume loading on the perfusion and oxygen consumption of the atrium in anesthetized dogs. Measurement of atrial perfusion with microspheres indicates that during atrial fibrillation, atrial blood flow increases 2- to 3-fold. Right atrial pacing is a significantly less potent metabolic stimulus for atrial vasodilation. Using Doppler velocity recordings of sinus node artery blood flow velocity, a marked increase in velocity is observed within 5 seconds after the initiation of atrial fibrillation. During atrial fibrillation, the sinus node artery reactive hyperemia response is markedly attenuated. Atrial fibrillation acutely decreases atrial distensibility; atrial pressure increased 81 +/- 19% with only a small increase (9.7 +/- 3%) in atrial diameter measured by echocardiography. During sinus rhythm, volume expansion to equivalent levels of atrial pressure as seen during atrial fibrillation increased atrial diameter 21 +/- 5% P less than 0.05. Atrial oxygen consumption determined by the microspectrophotometric method markedly increases during atrial fibrillation, compared to control conditions (12.3 +/- 2.8 vs. 3.9 +/- 0.6 ml O2/min per 100 g, respectively) P less than 0.05. Atrial O2 extraction was 5.5 +/- 0.4 ml O2/ml blood in the control state, and did not change with interventions. There was a linear relationship between left atrial O2 consumption and blood flow in all experimental conditions. Atrial fibrillation therefore alters atrial hemodynamics and metabolism by increasing atrial blood flow and oxygen consumption and decreasing atrial distensibility. Since atrial perfusion during atrial fibrillation is high and atrial flow reserve is limited, it is possible that additional atrial metabolic requirements might lead to atrial ischemia, fibrosis, and, thereby, perpetuation of the arrhythmia.

Animals↗

PubMed2003

The -174G/C interleukin-6 polymorphism influences postoperative interleukin-6 levels and postoperative atrial fibrillation. Is atrial fibrillation an inflammatory complication?

BACKGROUND: It has been suggested that inflammation can have a role in the development of atrial arrhythmias after cardiac surgery and that a genetic predisposition to develop postoperative complications exists. This study was conceived to verify if a potential genetic modulator of the systemic inflammatory reaction to cardiopulmonary bypass (the -174 G/C polymorphism of the promoter of the Interleukin-6 gene) has a role in the pathogenesis of postoperative atrial fibrillation (AF). Patients and Results- In 110 primary isolated coronary artery bypass patients the -174G/C Interleukin-6 promoter gene variant was determined. Interleukin-6, fibrinogen and C-reactive protein plasma levels were determined preoperatively, 24, 48, and 72 hours after surgery and at discharge. Heart rate and rhythm were continuously monitored for the first 36 to 48 hours; daily 12-lead electrocardiograms were performed thereafter until discharge. GG, CT, and CC genotypes were found in 62, 38, and 10 patients, respectively. Multivariate analysis (which included genotype, age, sex, and classical risk factors for AF) identified the GG genotype as the only independent predictor of postoperative AF. The latter occurred in 33.9% of GG versus 10.4% of non-GG patients (hazard ratio 3.25, 95%CI 1.23 to 8.62). AF patients had higher blood levels of Interleukin-6 and fibrinogen after surgery (P<0.001 for difference between the area under the curve). CONCLUSIONS: The -174G/C Interleukin-6 promoter gene variant appears to modulate the inflammatory response to surgery and to influence the development of postoperative AF. These data suggest an inflammatory component of postoperative atrial arrhythmias and a genetic predisposition to this complication.

Atrial Fibrillation↗

PubMed1995

Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group.

BACKGROUND AND PURPOSE: The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation (NRAF) varies from 2% to 15% in the first year and is approximately 5% yearly thereafter. Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population. METHODS: We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial. The mean follow-up was 1.6 years. RESULTS: By means of multivariate modeling, six independent variables were identified: history of previous thromboembolism, ischemic heart disease, enlarged cardiothoracic ratio on chest roentgenogram, systolic blood pressure greater than 160 mm Hg at study entry, NRAF for more than 1 year, and presence of an ischemic lesion on CT scan. These variables could also be used to stratify patients in low-, medium-, and high-risk subgroups for the other two arms of the trial, those treated with anticoagulation and aspirin. Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment. CONCLUSIONS: Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke.

Aged↗