Long-lasting Atrial Fibrillation Research Articles

Relation of Interleukin-6 and C-Reactive Protein Levels to Sinus Maintenance After Pharmacological Cardioversion in Persistent Atrial Fibrillation

The aim of this study was to investigate whether interleukin-6 (IL-6) and C-reactive protein (CRP) have significant relation to sinus maintenance after pharmacological conversion of long-lasting atrial fibrillation (AF) with respect to use of renin-angiotensin-aldosterone system (RAS) inhibitors. We studied 35 consecutive patients with AF lasting > or =1 month who had successful pharmacological cardioversion with bepridil alone or in combination with aprindine. The IL-6 and CRP levels in plasma were measured after pharmacological restoration of sinus rhythm. During the 1-year follow-up period, sinus rhythm was maintained in 20 patients (Group I), and the other 15 patients had recurrence of AF (Group II). Both plasma levels of IL-6 and CRP were significantly lower in Group I than in Group II (IL-6: 1.19 +/- 0.51 versus 1.84 +/- 0.66 ng/L, P < 0.005; CRP: 0.59 +/- 0.40 versus 1.24 +/- 0.79 mg/L, P < 0.005). The use of RAS inhibitors and left atrial dimension and the left ventricular ejection fraction showed no differences between the 2 groups. There was significant positive correlation between levels of IL-6 and CRP. In long-lasting persistent AF, lower levels of IL-6 and CRP appear to be associated with maintenance of sinus rhythm after pharmacological cardioversion irrespective of the use of RAS inhibitors. Further studies are needed to clarify the role of RAS inhibitors.

Pharmacological Cardioversion of Long-Lasting Atrial Fibrillation

Pharmacological therapy for atrial fibrillation (AF) is difficult because AF induces atrial remodeling. Randomized prospective studies using amiodarone could not show the superiority of rhythm control strategy to rate control strategy for treatment of AF. Bepridil is a multichannel blocker like amiodarone and expected to be effective for termination of AF without exacerbation of extracardiac adverse effects. Efficacy and safety of bepridil in pharmacological cardioversion of long-lasting AF (≥3 months) was assessed. To avoid the risk of excessive QT prolongation, bepridil dosage was limited to ≤200 mg/day and aprindine (class Ib) was added if necessary. Bepridil alone or in combination with aprindine restored sinus rhythm in 69% of patients. No adverse effects necessitating drug termination occurred. The average time to conversion after starting bepridil was 30 days and cardioversion was associated with significant increase in fibrillation cycle length. After cardioversion, atrial contraction recovered faster within 1 week and sinus rhythm was maintained better than conventional electrical cardioversion. The history of drug-resistant AF did not affect efficacy of bepridil. These observations suggest that pharmacological cardioversion of long-lasting AF could become a new therapeutic option. Although the precise mechanism of cardioversion by bepridil is not clear, reversal of the remodeled atria may play an important role.

Efficacy of Amiodarone for Preventing the Recurrence of Symptomatic Paroxysmal and Persistent Atrial Fibrillation After Cardioversion

It has been previously reported that the efficacy of class I antiarrhythmics in preventing the recurrence of symptomatic paroxysmal and persistent atrial fibrillation (AF) is limited when AF lasts for 48 h or more. However, it is unclear whether the efficacy of amiodarone, a class III drug, is superior to class I antiarrhythmics in patients with long-lasting AF. The relationship between the duration of tachycardia and the efficacy of amiodarone in preventing recurrence of tachycardia was examined in 55 patients (37 men, 18 women, mean age 68+/-9 years) to whom amiodarone was administered after electrical or pharmacological cardioversion for paroxysmal and persistent AF. In 26 patients, paroxysmal and persistent AF ceased within 48 h after onset (Group A), and in the other 29 patients, it ceased after 48 h (Group B). Patient characteristics and actuarial recurrence-free rates were compared between the 2 groups. The mean follow-up period was 30+/-11 months. No statistically significant difference between the groups was found in patient characteristics. Actuarial recurrence-free rates in Group A and B at 1, 3, 6, 9, and 12 months were 100%, 81%, 69%, 62%, and 54%, and 93%, 79%, 66%, 52%, and 48%, respectively (p=NS at 12 months). The period of maintenance of sinus rhythm was 14.7+/-3.2 months in group A and 13.3+/-3.3 months in group B (mean+/-SE, p=NS). In the case of amiodarone, efficacy for maintaining sinus rhythm after cardioversion of AF was not biased by the duration of arrhythmia. This observation suggests amiodarone is effective in maintaining normal sinus rhythm after cardioversion, even in patients with long-lasting AF and electrical atrial remodeling.

After the London tragedy, is it still possible to consider Phase I is safe?

The recent London tragedy [1] induces a huge emotion in the clinical pharmacology world. As decided by the Medicines and Healthcare products Regulatory Agency, the main point is to redefine the acceptable conditions for fully humanized agonist monoclonal antibodies in man. Such anxiety could also be reinforced by the fact that three deaths in healthy subjects have recently been reported in the USA [2–4]. Therefore, based on all the available data, it is necessary to reassess whether Phase I – early drug development in healthy subjects – is still safe: In the literature, only 15 deaths have been published during the last 30 years in Western countries, although probably 100 000 healthy subjects are dosed every year; moreover, only three deaths could not have been avoided if accurate common rules had been strictly adhered to. However, there is probably a higher risk in elderly subjects [5, 6]. Recently, a register has been initiated in France under the responsibility of the ‘Club Phase I’ (http://www.clubphase1.org/). This annual register is focused on serious adverse events (SAEs) and is limited to healthy subjects – young and elderly, men and women – and to Phase I studies. SAE refers to good clinical practice (GCP): death, life-threatening, requires hospitalization, disability, congenital anomaly and medically important event. It was implemented in 2004 and 2005; 15 386 healthy subjects have been included and dosed during the 2-year period (see Table 1). Two deaths occurred: one motorbike accident in a young man within a wash-out period and one lung cancer in an elderly woman undetected at screening in a study without drug administration (biomarker pilot study). No deaths were related to the tested drug. Sixty other SAEs were reported (not including the two above-mentioned deaths) (see Table 2). Only eight SAEs were really clinically serious, i.e. worrying with high risk, three out of eight only being related to the study drug: rash and fever, agranulocytosis and long-lasting atrial fibrillation. The others were not related: unstable angina, peritonitis, thrombosis (retina central vein), coma (car accident) and acute leukemia. Total SAE incidence is 0.4%, including worrying SAE 0.05%, of which related SAE 0.02%. In young subjects SAE incidence is 0.3%, but it is much higher in the elderly 2%, particularly in elderly women (3%). This register reporting more than 90% of the actual French activity in healthy subjects suggests clear conclusions: Phase I is safe, without related deaths and only 0.02% worrying and related SAEs; but a higher risk incidence is reported in elderly subjects, particularly in women. A recent Japanese register draws the same conclusions: from 1993 to 2004, 95 780 subjects, no deaths, low incidence of SAEs [47 (0.05%)], of which only 23 (0.02%) were related to drugs, all reversible without sequelae [7]. Thus, one can conclude: The risk of SAE in a Phase I study is low when common safety rules are applied: quality of drug supplies, use of a relevant method for the choice of doses, prudent progression from dose to dose using stopping criteria defined in protocols and approved by an ethics committee, resuscitation track and permanent presence of trained physicians on site . . . all, in fact, from GCP. The new data suggest reinforcing safety rules in two areas: Drug administration practice: define the number of subjects to administer at the same time, especially for first-in-class compounds, parenteral route, or possible immunogenicity of the drug. The same prudent approach is relevant in the case of possible low predictability of animal data: CNS, immune targets, fully humanized and recombinant compounds. Elderly subjects: special scrutiny and a more prudent approach are required. The authors thank all the French Clinical Research Organizations and Centres d’Investigations Cliniques that have provided data.

Atrial Fibrillation Recurrence: The Roles of Hypertension, Duration of Atrial Fibrillation Disease, and Prolonged Signal-Averaged P Wave Duration

Objective - To assess the risk of atrial fibrillation (AF) recurrence requiring hospitalisation or its transition to long-lasting AF in patients with earlier or present AF from the clinical characteristics, the duration of AF-disease, and the signal-averaged P wave duration (SAPWD). Design -We studied 111 consecutive patients (40 women; median age 65 years, range 30-85 years) with earlier or present AF. The SAPWD was measured on inclusion; the follow-up median follow-up time was 184 days (range 171-437). Endpoints were hospitalisation due to recurrent AF or transition to AF lasting longer than two days. Results -During follow-up 5 patients died, 33 patients were hospitalised with AF, and 9 patients developed long-lasting AF. Multiple logistic regression analysis showed three risk factors of interest: history of hypertension, OR=3.67 (95% CI 1.61 to 8.37), duration of AF disease longer than two years, OR=3.22 (95% CI 1.31 to 7.86), and non-significantly prolonged SAPWD above 140 ms, OR=1.87 (95% CI 0.60 to 5.82). The probability of relapse in patients without risk factors was 9%, with one risk factor 16-27%, with two risk factors 37-54%, and with three risk factors 74% (p=0.0005). Conclusions -Hypertension and long history of AF disease were associated with an increased risk of AF-relapse.

Maintenance of Sinus Rhythm and Recovery of Atrial Mechanical Function After Cardioversion With Bepridil or in Combination With Aprindine in Long-Lasting Persistent Atrial Fibrillation

The aim of this study was to evaluate pharmacological cardioversion of long-lasting persistent atrial fibrillation (AF) using bepridil in terms of recovery of atrial mechanical function and maintenance of sinus rhythm. Bepridil alone or in combination with aprindine is effective for termination of persistent AF. The study group comprised 38 consecutive patients (24 men, 58.8+/-9.3 years) with successful conversion of persistent AF lasting >1 month either pharmacologically (Group I) or electrically (Group II). Fast Fourier transform analysis of fibrillation waves was performed and fibrillation cycle length (FCL) was calculated from the peak frequency. In Group I, sinus rhythm was pharmacologically restored in 22 patients after an average 30 days (7-49 days) of bepridil administration, either alone (11) or in combination with oral aprindine (11); they were followed up while using the same drugs. In Group II, electrical conversion restored sinus rhythm in 16 patients, and they were followed up with conventional antiarrhythmic drugs other than bepridil and aprindine. After bepridil treatment FCL increased and became significantly longer in Group I than in Group II (190+/-39 vs 150+/-29 ms, p<0.001). Atrial peak velocity in transmitral flow within the first week after cardioversion was greater in Group I than in Group II (68+/-35 vs 32+/-20 cm/s, p<0.05). By Kaplan-Meier analysis, 83% of Group I patients were free of AF recurrence at the 12-month follow-up, compared with 36% in Group II (p<0.005). In patients with long-lasting AF, pharmacological conversion with bepridil alone or in combination with aprindine recovered atrial mechanical function better and maintained sinus rhythm longer than electrical conversion.

Pharmacological Cardioversion of Atrial Fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia, carrying high social costs. It is usually first seen by general practitioners or in emergency departments. Despite the availability of consensus guidelines, considerable variations exist in treatment practice, especially outside specialised cardiological settings. Cardioversion to sinus rhythm aims to: (i) restore the atrial contribution to ventricular filling/output; (ii) regularise ventricular rate; and (iii) interrupt atrial remodelling. Cardioversion always requires careful assessment of potential proarrhythmic and thromboembolic risks, and this translates into the need to personalise treatment decisions. Among the many clinical variables that affect strategy selection, time from onset is crucial. In selected patients, pharmacological cardioversion of recent-onset AF can be a safely used, feasible and effective approach, even in internal medicine and emergency departments. In most cases of recent-onset AF, pharmacological cardioversion provides an important--and probably more cost effective--alternative to electrical cardioversion, which can then be employed as a second-line therapy for nonresponders. Class IC agents (flecainide or propafenone), which can be safely used in hospitalised patients with recent-onset AF without left ventricular dysfunction, can provide rapid conversion to sinus rhythm after either intravenous administration or oral loading. Although intravenous amiodarone requires longer conversion times, it is still the standard treatment for patients with heart failure. Ibutilide also provides good conversion rates and could be used for AF patients with left ventricular dysfunction (were it not for high costs). For long-lasting AF most pharmacological treatments have only limited efficacy and electrical cardioversion remains the gold standard in this setting. However, a widely used strategy involves pretreatment with amiodarone in the weeks before planned electrical cardioversion: this provides optimal prophylaxis and can sometimes even restore sinus rhythm. Dofetilide may also be capable of restoring sinus rhythm in up to 25-30% of patients and can be used in patients with heart failure. The potential risk of proarrhythmia increases the need for careful therapeutic decision making and management of pharmacological cardioversion. The results of recent trials (AFFIRM [Atrial Fibrillation Follow-up Investigation of Rhythm Management] and RACE [Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation]) on rate versus rhythm control strategies in the long term have led to a generalised shift in interest towards rate control. Although carefully designed studies are required to better define the role of pharmacological rhythm control in specific AF settings, this alternative option remains a recommendable strategy for many patients, especially those in acute care.

Long-term risk of recurrent atrial fibrillation as documented by an implantable monitoring device: Implications for optimal patient care

ObjectivesThe present study determined the incidence and time course of atrial fibrillation (AF) recurrences in patients with a history of AF and fitted with an implantable monitoring device. BackgroundThe long-term risk of undetected recurrence of AF in patients receiving stable antiarrhythmic therapy remains uncertain. MethodsIn 110 patients with a class I indication for physiologic pacing and a history of AF, a pacemaker with dedicated functions for AF detection and electrogram storage was implanted, and antiarrhythmic drug treatment was optimized. Patients were regularly followed up with evaluation of AF-related symptoms, a resting electrocardiogram (ECG), and interrogation of device memory. The incidence of AF recurrences lasting >48 h in asymptomatic patients presenting in sinus rhythm (SR) at the respective follow-up visit constituted the primary end point of this prospective study. ResultsDuring 19 ± 11 months, 678 follow-up visits were performed. Atrial fibrillation was documented in 51 patients (46%) by ECG recording and in 97 patients (88%) by a review of stored electrograms (p < 0.0001). Device interrogation revealed AF recurrences lasting >48 h in 50 patients, 19 of whom (38%) were completely asymptomatic and in SR at subsequent follow-up. In 11 (16%) of 67 patients with device-confirmed freedom from AF for ≥3 months, AF lasting >48 h recurred subsequently. ConclusionsThis prospective study demonstrates a high incidence of recurrent AF despite optimized antiarrhythmic therapy. Of particular note, AF relapses >48 h remained totally asymptomatic in a significant proportion of patients. Freedom from AF for ≥3 months did not preclude subsequent long-lasting AF recurrence.

Drug-Induced Changes in Fibrillation Cycle Length and Organization Index Can Predict Chemical Cardioversion of Long-Lasting Atrial Fibrillation With Bepridil Alone or in Combination With Aprindine

The aim of this study was to investigate whether drug-induced changes in fibrillation wave characteristics can predict pharmacological conversion of long lasting persistent atrial fibrillation (AF). The study group comprised 23 consecutive patients with AF lasting > or =1 month. Patients first received bepridil (200 mg/day) for 2-4 weeks. When sinus rhythm was not restored with bepridil, oral aprindine (40 or 60 mg/day) was added to bepridil. Fast Fourier transform analysis of fibrillation waves using lead V1 was performed to calculate the fibrillation cycle length (FCL). The spectral areas were measured and the maximum area divided by the total area was termed the fibrillation organization index (FOI). Sinus rhythm was restored in 16 of 23 patients (70%); 8 of these 16 patients received only bepridil (Group I) and the other 8 responders received bepridil and aprindine (Group II). In Group I bepridil increased both FCL (p<0.001) and FOI (p<0.01) and terminated AF after 20+/-12 days. In Group II bepridil increased FCL (p<0.001), but did not change FOI. The addition of aprindine terminated AF in association with an increase in both FCL (p<0.005) and FOI (p<0.005) within 19+/-8 days. In the remaining 7 patients who did not have restoration of sinus rhythm, bepridil increased both FCL and FOI significantly, but less than in Group I, and the addition of aprindine did not further increase either of them. Chemical cardioversion of AF occurred in all patients with FCL > or =190 ms and FOI > or =45% after drug administration. Bepridil alone or in combination with aprindine converted long lasting persistent AF in association with an increase in both FCL and FOI. The combination of FCL and FOI after drug administration is helpful in predicting chemical cardioversion of persistent AF.

Atrial fibrillation: the remodelling phenomenon

Atrial fibrillation (AF) is a progressive disease and may be self-sustaining. The processes that lead to the worsening of AF over time include electrical, contractile, neurohormonal, macroanatomical and ultrastructural changes, and these may occur over different periods of time. The term ‘electrical remodelling’ indicates long-term changes in atrial electrophysiological parameters that result from prolonged changes in atrial rate. The mechanism of tachycardia-induced remodelling is associated with altered ion channel function, the most important of which is a reduction in L-type calcium current, which is responsible for a reduction in the duration of the action potential, atrial refractory period and refractory period adaptation to rate. Recovery from atrial electrical remodelling occurs within a few days, even in cases of very long-lasting AF, although clinically the atria remain vulnerable for weeks after cardioversion. A so-called ‘second factor’ may play a role in this prolonged vulnerability to recurrent AF. In animals tachycardia-induced electrophysiological modification is reduced by verapamil and angiotensin II receptor antagonists, but the effect of these drugs in preventing atrial electrical remodelling in humans is disputed. Despite these findings, there is growing clinical evidence that verapamil and angiotensin II receptor antagonists could reduce the recurrence of AF after cardioversion. In this report current knowledge of the mechanisms and clinical consequences of AF-induced electrical remodelling is discussed. © 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved

Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm

The aim of this study was to investigate the efficacy and safety of bepridil (a multichannel blocker including several potassium channels) for conversion of long-lasting atrial fibrillation (AF). Bepridil restored sinus rhythm alone or in combination with aprindine in 69% of 32 patients with persistent AF lasting ≥3 months. The time to conversion after starting bepridil was 30 ± 12 days. An increase in fibrillation cycle length with bepridil was greater in responders (31 ± 10%), but an increase in QTc did not differ between responders and nonresponders. Bepridil is effective and safe for terminating long-lasting persistent AF.

Effects of verapamil and metoprolol on recovery from atrial electrical remodeling after cardioversion of long-lasting atrial fibrillation

The aim of this prospective, randomized study was to investigate the effect of pretreatment with two different intracellular calcium-lowering drugs (verapamil and metoprolol) on recovery from atrial effective refractory period (AERP) shortening after internal electrical cardioversion (EC) of persistent atrial fibrillation (AF) in patients on amiodarone. Twenty-one patients on amiodarone for at least 30 days were referred to our hospital for internal EC of a persistent AF refractory to external EC. They were randomized to receive only amiodarone (group AMI, n=7), or amiodarone and verapamil 240 mg/day (group VER, n=7), or amiodarone and metoprolol 100 mg/day (group MET, n=7). Left AERP was measured 10 min and 24 h after EC. AERP was also determined in 13 controls. The AERP after 10 min was significantly shorter in group AMI (201 (31) ms, P<0.02) and group MET (203 (34) ms, P<0.03) than in controls (249 (45) ms), but not in group VER (237 (51) ms, P=NS). The AERP after 24 h was still significantly shorter in group AMI (204 (38) ms, P<0.04) than in controls, but not in group MET (225 (52) ms, P=NS) or in group VER (290 (36) ms, P=NS). Pretreatment with amiodarone and verapamil prevents AERP shortening, while pretreatment with amiodarone and metoprolol only accelerated AERP recovery.

Low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion: results and long-term follow-up.

Low-energy internal cardioversion is a new electrical treatment for patients with persistent atrial fibrillation. This paper evaluates the efficacy and safety of low-energy internal cardioversion in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion, and the clinical outcome of such patients. The study population consisted of 55 patients [32 male, mean age 65 +/- 10 years, 48 (87%) with underlying heart disease] with long-lasting (mean 18 +/- 34 months) atrial fibrillation in whom external cardioversion had failed to restore sinus rhythm. Two custom-made catheters were used: one positioned in the right atrium and one in the coronary sinus or the left pulmonary artery. A standard catheter was inserted into the right ventricular apex to provide R wave synchronization. Sinus rhythm was restored in 52 patients (95%) with a mean defibrillating energy of 6.9 +/- 2.6 J (320 +/- 60 V). No complications were observed. During follow-up (mean 18 +/- 9 months), 16 patients (31%) suffered early recurrence (< or = 1 week) of atrial fibrillation and 20 patients (38%) had late recurrence (> 1 week, mean 3.5 +/- 3.6 months) of atrial fibrillation. Six patients with a late recurrence again underwent cardioversion and five of these maintained sinus rhythm. Therefore, a total of 21/52 patients (40%) were in sinus rhythm at the end of follow-up. No clinical difference was found between patients with and without recurrences. Low-energy internal cardioversion is a useful means of restoring sinus rhythm in patients with long-lasting atrial fibrillation refractory to external electrical cardioversion. More than one-third of patients maintained sinus rhythm during long-term follow-up.

L-type calcium currents in atrial myocytes from patients with persistent and non-persistent atrial fibrillation

In patients with persistent atrial fibrillation (AF), the atrial myocardium is characterized by a reduced contractile force, by a shortened duration of the action potential and a recently demonstrated reduction of the L-type Ca2+ currents. We analyzed potential effects on L-type Ca2+ currents of the patients' medication and of the duration of AF. Human atrial myocytes were prepared from the right auricles of patients undergoing open-heart surgery. Three groups of patients were studied: a control group with sinus rhythm (SR, n = 26 patients) and a group with persistent AF (> 3 months duration; n = 10), a group with non-persistent AF (3 patients with SR but with documented episodes of AF in their history). L-type Ca2+ currents were measured during depolarizing pulses from a holding potential of -70 mV to a test potential of +10 mV and are given as mean +/- SEM of current densities (currents normalized to the cell capacitance). Ca2+ current densities were significantly (p < 0.0001) smaller in cells from patients with persistent AF than in control cells (0.54 +/- 0.08 pA/pF vs. 1.96 +/- 0.12 pA/pF). No indication was found that these changes were caused by medication with Ca2+ channel antagonists, beta blockers, or digitalis. Stimulation with the dihydropyridine Bay K 8644 (1 microM) or with isoproterenol (0.1 microM) increased Ca2+ currents in control cells 3.5 +/- 0.2 and 3.5 +/- 0.3-fold. In persistent AF, this increase was significantly larger (6.0 +/- 0.5 and 5.2 +/- 0.6-fold) but stimulated currents were still significantly lower than in control cells. Patients with non-persistent AF exhibited Ca2+ currents well within the control range. A reduction in Ca2+ currents, due to a reduction in number as well as a depression of L-type channels, is a characteristic and pathophysiologically important part of the myocardial remodeling during long-lasting atrial fibrillation. It is not present in patients with non-persistent AF and not caused by medication.

Early relapses of atrial fibrillation after internal cardioversion of long-lasting atrial fibrillation: Relation with autonomic nervous system

Early relapses of atrial fibrillation after internal cardioversion of long-lasting atrial fibrillation: Relation with autonomic nervous system

Early relapses of atrial fibrillation after internal cardioversion of long-lasting atrial fibrillation: Relation with autonomic nervous system

Early relapses of atrial fibrillation after internal cardioversion of long-lasting atrial fibrillation: Relation with autonomic nervous system

Contraction-excitation feedback in human atrial fibrillation.

Contraction-excitation feedback, that is, electrophysiologic changes that are caused or preceded by mechanical changes of the myocardium, has been extensively studied in the ventricles. The role of contraction-excitation feedback in the atria, and more particularly in the genesis and maintenance of atrial fibrillation, has been less adequately investigated. The aim of the present study was to determine whether increased right atrial pressure (RAP) facilitates the induction of atrial fibrillation (AF) in patients with a history of lone AF. Sixteen patients with a history of paroxysmal AF but without structural heart disease were included in the study. All patients underwent electrophysiologic study at both a lower (3.1 +/- 2.0 mmHg) and (in 13 cases) a higher (6.4 +/- 2.5 mmHg) RAP. "Higher" was considered the pressure following rapid (in about 30 min) intravenous administration of normal saline or before the administration of a diuretic. Rapid atrial pacing induced AF in 19 of 29 attempts. At a lower pressure, rapid pacing induced brief (3 s to 3 min) AF in 3 of 16 patients, long-lasting (> 3 min) AF in 3 of 16 patients, and no AF in 10 of 16 patients. At a higher pressure, brief AF was induced in 3 of 10 patients in whom no AF could be induced at a lower pressure, and long-lasting AF in 10 patients in whom either brief AF (3 cases) or no AF (7 cases) was induced at a lower pressure. In 11 patients, in whom Wenckebach periodicity was determined at both higher and lower pressure, the critical cycle length at which atrioventricular block appeared was significantly (p < 0.001, paired t-test) longer (349.1 +/- 44.4 ms, i.e., +15.5 +/- 11.3 ms) at higher than at lower atrial pressure (333.6 +/- 41.0 ms). In nine patients, in whom Wenckebach periodicity was determined and two rhythms occurred at different pressures, the critical cycle length was 332.2 +/- 45.8 ms when associated with sinus rhythm, and significantly (p < 0.01) longer (344.4 +/- 48.0 ms, i.e., +12.2 +/- 8.3 ms) when associated with induction of AF. In patients with lone atrial fibrillation, modest increases in atrial pressure may facilitate the induction of atrial fibrillation.

Spontaneous reversion of long-lasting chronic atrial fibrillation to sinus rhythm

We report a case of a 72-year-old lady with rheumatic heart disease and chronic, long-lasting atrial fibrillation, who reverted spontaneously to sinus rhythm. Doppler study showed evidence of mechanical contraction of the right but not of the left atrium. This may be a sign of marked histologic changes in the atria and may require the insertion of a permanent pacemaker, because of subsequent development of sinus bradycardia.

Hepatic disease during long-lasting atrial fibrillation.

Long-standing ascites of benign nature, associated with Peripheral edema and minimal liver functioin disturbance was observed in 15 cases of 472 patients suffering from atrial fibrillation without any other apparent signe of cardiac disease. The duration of ascites and edema correlated with the durationof uncomplicated atrial fibrillation.

Effect of tremorine and oxotremorine on the S-A node of the dog heart in vivo.

The effects of tremorine and oxotremorine were investigated in seven vagotomized dogs, using direct perfusion technique of the S-A node under constant perfusion pressure of 100mm Hg. 1) Tremorine (30 μg to 1mg) and oxotremorine (0.003 to 0.03 μg) injected into the sinus node artery induced a negative chronotropic effect. This negative chronotropic effect was blocked by atropine, but was not influenced by tetrodotoxin and propranolol. 2) Higher doses of oxotremorine produced long-lasting atrial fibrillation. At doses larger than 0.3 μg, oxotremorine induced atrial fibrillation in all animals. The induction and maintenance of atrial fibrillation were blocked by atropine. The induction was also prevented by a large amount of tetrodotoxin and propranolol in some animals. A large dose of propranolol occasionally blocked the maintenance of atrial fibrillation.