Alteration of peripheral vasodilatory reserve capacity after cardioversion of atrial fibrillation

In atrial fibrillation, exercise capacity is often reduced.This is usually ascribed to a decreased cardiac output as comparedwith sinus rhythm. Very few studies, however, have focused onchanges in the peripheral blood flow during atrial fibrillationas a potential mechanism for exercise limitation. The aim ofthe present study was to determine the effect of conversionof atrial fibrillation to sinus rhythm on peripheral blood flow. Calf blood flow, using an electrocardiogram-triggered venousocclusion plethysmograph, and peak oxygen consumption (peakVO₂), using treadmill exercise testing, were studied in 28 patientswith chronic atrial fibrillation eligible for electrical cardioversion.Measurements were performed before cardioversion, and repeated1 day and 1 month thereafter. Calf blood flow at rest, maximalcalf blood flow, and minimal calf vascular resistance duringthe hyperaemic response immediately following 700 J of calfexercise were determined plethysmographically. One day and 1 month after cardioversion, 23 and 14 patientswere still in sinus rhythm, respectively. In patients who stillhad sinus rhythm after 1 month, maximal calf blood flow increasedfrom 33·7±12 to 40·0±13 ml. 100ml ^{–1 min –1} (P<0.01) and minimal calf vascularresistance fell from 3·2±0·9 to 2·7±0·7mmHg.ml^–1. 100 ml^–1. min^–1 (P<0·01);peak VO₂ increased from 21·3±4 to 24·2±5ml. min^–1. kg^–1 (P<0·001). Calf bloodflow at rest did not improve. In contrast, no significant changesin maximal calf blood flow, minimal calf vascular resistanceand peak VO₂ occurred in patients who had atrial fibrillation1 month after cardioversion. A significant correlation was foundbetween changes in maximal calf blood flow and peak VO₂ 1 monthafter cardioversion (r=0·53, P<0·01). One dayafter cardioversion, no changes in calf blood flow or peak VO₂,were found, either in patients with sinus rhythm or atrial fibrillation. In conclusion, transition from chronic atrial fibrillation tosinus rhythm is associated with a (delayed) improvement in maximalcalf blood flow, minimal calf vascular resistance, and peakVO₂. Our findings suggest that increase in vasodilatory reserve capacitymay contribute to the improvement of exercise capacity aftercardioversion of atrial fibrillation.     

Clinical, adrenergic and heart endocrine measures in chronic atrial fibrillation as predictors of conversion and maintenance of sinus rhythm after direct current cardioversion

The aim of this study was to evaluate clinical, adrenergic andendocrine factors that could predict sinus rhythm maintenanceafter direct current cardioversion in chronic atrial fibrillation. Nineteen patients with chronic non-rheumatic atrial fibrillation(mean duration 6±5 months) were studied. They were exercised24 h before cardioversion at maximum effort with the Naughtonprotocol. Heart rate and blood pressure at rest and exercisewere recorded and blood samples were taken for the assessmentof adrenergic activity, by measuring cyclic adenosine monophosphate,heart endocrine function, atrial natriuretic peptide and itssecond messenger, cyclic guanosine monophosphate. Fifteen ofthe 19 patients were initially converted to sinus rhythm (eightpatients with external and seven patients with internal DC shocks).After 3 months eight patients remained in sinus rhythm and 11had relapsed, most of them within the first month. On exercisethe chronotropic response was lower in the group who remainedin sinus rhythm than in the group in atrial fibrillation (peakheart rate 147±11 beats.min^–1 vs 165±24beats.min^–1 p=0·02). During exercise, the systolicblood pressure in the sinus group reached higher values thanin the group who relapsed (192±17 mmHg vs 176±18mmHg, p=0·03). Cyclic adenosine monophosphate increasedsignificantly from rest to peak exercise in the sinus rhythmgroup (from 23±9 pmol.ml^–1 to 31±15 mol.ml^–1,p=0·02) while it remained unchanged in the atrial fibrillationgroup (25±10 pmol.ml^–1 to 24±8 pmol.ml^–1,p=0·02). For all 19 patients the differ ence in cyclicadenosine monophosphate between rest and exercise was negativelycorrelated with maximum heart rate (r=0·58, p=0·009).Atrial natriuretic peptide increased from rest to peak exercisein the sinus rhythm group (from l29±58 fmol.ml^–1to 140±66fmol.ml^–1 while it remained unchangedin the group in which atrial fibrillation persisted or recurred(from 112±58 fmol.ml^–1 to 111±53 fmol.ml^–1p=0· A significant correlation between atrial natriureticpeptide and cyclic guanosine monophosphate levels at exercisebefore cardioversion was found for the sinus rhythm group only(r=0·76, p=0·02). In patients with non-rheumatic chronic atrial fibrillation evaluationof clinical parameters such as heart rate and blood pressurechanges during maximal exercise can be useful in the choiceof suitable therapy. An inadequate increase in plasma cyclic-adenosinemonophosphate and atrial natriuretic peptide on exercise couldpredict patients with more severe underlying disease, wherecardioversion should not be recommended.     

Atrial natriuretic peptide in atrial fibrillation before and after electrical cardioversion therapy

In eight patients with atrial fibrillation of less than 3 monthsduration and without congestive heart failure the plasma concentrationof atrial natriuretic peptide was determined one day before,the day after and again 30 days after electrical cardioversiontherapy. The pretreatment plasma concentration of the peptidewas 99 pg mg^–1 (23–480, median and range). The dayafter cardioversion to sinus rhythm the peptide concentrationhad normalized to 36 pg ml^–1 (18–151). The plasmaconcentration of atrial natriuretic peptide remained stablein all but one patient for a period of 30 days (46 pg ml^–1,16–695) (P = 0·03). In conclusion, the plasma concentration of atrial natriureticpeptide in patients with atrial fibrillation was significantlyreduced after electrical cardioversion to sinus rhythm and remainedstable for a period of 30 days.     

Peak oxygen uptake during exercise in mitral stenosis with sinus rhythm or atrial fibrillation: lack of correlation with valve area: A study in 70 patients

Although the haemodynamic response during submaximal supineexercise in mitral stenosis has been well described, the determinantsof peak oxygen uptake during maximal upright exercise are poorlycharacterized and may differ in sinus rhythm and atrial fibrillation.Seventy patients with isolated mitral stenosis underwent Doppler-echocardiographyand bicycle exercise with respiratory gas analysis. Forty-twopatients were in sinus rhythm (Group I) and 28 in atrial fibrillation(Group II). Peak oxygen uptake it was 21·3±5·6ml. min^–1 kg^–1 in group I and 18·1 ±5·1 ml min^–1 kg^–1 in group II (P<0·05).There was no significant correlation between indices of exercisetolerance (exercise duration, ventilatory threshold, peak oxygenuptake, indexed peak oxygen uptake, peak oxygen pulse) and valvearea or gradient in either group. Indexed peak oxygen uptakewas not correlated to oxygen pulse but was linearly related(r=0·43) to heart rate ( heart rate =peak heart rate=restheart rate) in Group I but not in Group II. Thus, in patientswith mitral stenosis, no correlation was found between the mitralvalve area or the gradient at rest and maximal upright exercisetolerance, suggesting that peripheral adaptation and, in sinusrhythm, chronotropic reserve, are important compensatory mechanisms.     

Comparison of flecainide and procainamide in cardioversion of atrial fibrillation

In this prospective, controlled and randomized cross-over studywe tried to establish the efficiency and safety of flecainidevs procainamide for the treatment of acute atrial fibrillation.Eighty patients (30 females, 50 males, mean age: 55 ±14 years) were included. Patients entered into the study ifthey had atrial fibrillation of recent onset (<24 h) witha ventricular rate >100 beats. min^–1 at rest and were<75 years of age. Exclusion criteria were any sign of heartfailure, conduction disturbances, sick sinus syndrome or acuteischaemic events. Randomly 40 patients received flecainide and40 procainamide as the first treatment. There were no significantclinical dfference between the two groups. Procainamide wasgiven at a dose of 1 g infused over 30 min, and followed byan infusion of 2 mg.min^–1 over 1 h. Flecainide was givenat a dose of 1.5 mg.kg^–1 over 15 min followed by an infusionof 1.5 mg.kg^–1 over 1 h. Drug infusion was continued untilmaximal dose, intolerance or reversion to sinus rhythm. After1 h of wash out, patients remaining in atrial fibrillation werestarted on the second drug. Left atrial size was measured byecho. Serum levels of drug and atrial size did not dffer betweenpatients who returned to sinus rhythm and those who remainedin atrial fibrillation. Conversion to sinus rhythm was achieved in 37 (92%) of the 40patients treated with flecainide and 25 (65%) of those treatedwith procainamide (P<0.001). The time required for reversionto sinus rhythm was similar between the two groups. Flecainideis a highly effective drug, superior to procainamide, for thetreatment of paroxysmal atrial fibrillation.     

Effect of flecainide on atrial and ventricular refractoriness and conduction in patients with normal left ventricle: Implications for possible antiarrhythmic and proarrhythmic mechanisms

We studied the effects of intravenous fiecainide (2 mg.kg^–1)on atrial and ventricular refractoriness and conduction duringsinus rhythm, induced atrial fibrillation and atrial pacingat rates of 100, 120 and 150 ppm, in 14 patients with normalleft ventricle. Flecainide caused a significant increase inQRS duration during sinus rhythm (mean ± SD: 87.2 ±8.4 ms vs 102.8 ± 9.1 ms, P<0.001) atrial fibrillation(87.8 ± 10.0 ms vs 108.8 ± 13.7 ms, P<0.001)and at all paced rates. The duration of the atrial electrogramwas significantly increased during sinus rhythm (54.9 ±13.2 ms vs 64.8 ± 16.6 ms, P=0.003) and at all pacingrates. The PA interval was also signficantly prolonged, as wasthe pacing stimulus-to-atrial-electrogram interval at all pacingrates. There was increased QRS duration and atrial electrogramprolongation at higher pacing rates. Atrial refractoriness wasprolonged during sinus rhythm (216.4 ± 28.2 vs 228.6± 36.1, P=0.02), but not during atrial pacing at anyrate. The QT interval, but not the JT interval or ventricularrefractoriness, was significantly prolonged during sinus rhythmand at all pacing rates. Flecainide slows atrial conductionin a use-dependent manner and increases atrial refractorinessduring sinus rhythm but not during faster atrial pacing, thusnot displaying a use-dependent effect. QRS duration is prolongedin a use-dependent manner without a commensurate increase inventricular refractoriness. In the presence of rapidly conductedatrial fibrillation, which was not found to be slowed by flecainide,this effect may constitute a proarrhythmic mechanism even inpatients with no apparent myocardial abnormality.     

Effect of atrial fibrillation on pulmonary venous flow patterns: transoesophageal pulsed Doppler echocardiographic study

The effect of atrial fibrillation on pulmonary venous flow patternsis still not well known. Twenty-four patients in atrial fibrillationand 21 patients in sinus rhythm were studied by transoesophagealechocardiography. In ninety-five percent (20/21) of sinus rhythmpatients, the early systolic wave due to atrial relaxation orreverse wave due to atrial contraction could be distinguishedon pulsed Doppler tracings by transoesophageal echocardiography.However, there was no early systolic wave and/or reverse atthe end of diastole in any atrial fibrillation patients. Inatrial fibrillation patients without mitral regurgitation (n= 14), the onset of systolic flow was delayed (165±38vs 50±46 ms, P < 0.05), and systolic peak velocities,time-velocity integrals and systolic fractions were reduced(31 ± 13 vs 54±17 cm.s^–1, P < 0.05; 5± 2 vs 13 ± 6 cm, P < 0.05 and 36 ±8 vs 61±15%, P < 0.05, respectively) as compared tothose in sinus rhythm. Significant mitral regurgitation (n =10) reduced systolic velocity parameters considerably in atrialfibrillation patients but the diastolic flow parameters werenot significantly different between sinus rhythm and atrialfibrillation patients. Stepwise multiple regression analysis identified atrial fibrillationas an important independent predictor for changes in systolicflow parameters. The R-R interval is also an important factorfor diastolic flow parameters. Thus, the present study demonstratesthat atrial fibrillation significantly modifies pulmonary venousflow pattern and is an important factor for systolic flow parameters.Significant mitral regurgitation can further modify systolicflow pattern in atrial fibrillation patients.     

Left ventricle filling abnormalities prior to and following treatment of thyrotoxicosis -- is diastolic dysfunction implicated in thyrotoxic cardiomyopathy?

Despite cardiac failure being a well recognised complicationofthyrotoxicosis, systolic function has generally been reportedas maintained or enhanced. In this study, left ventricular diastolicfunction was assessed in 16 thyrotoxic patients and 18 age-matchedcontrols by pulsed-Doppler echocardiography. Patients were re-studiedafter 3 and 12 months of treatment. Prior to treatment all standardDoppler-;derived indices of diastolic function were significantlydifferent to control (isovolumic relaxation time (IVRT) 63±18.9vs 84.0±14.8 ms, peak early filling velocity (E_max) 79.2±15.2vs 61.9±10.7 cm . s^–1, peak atrial filling velocity(A_max) 68.2±17.9 vs42.2±9.4 cm . s^–1, decelerationof early filling (E/F slope) 6.1±1.8 vs3.7±1.1m . s^–1, thyrotoxic vs control). However, these fillingabnormalities appear likely to reflect the tachycardia and reducedsystemic vascular resistance (SVR) found in the patients (heartrate 102±15 vs 76 ± 9, SVR 874 ± 207 vs1293 ± 362 dynes .s^–1. cm^–5, both P<0.001).After 3 months of treatment haemodynamics were similar in thetwo groups but filling remained abnormal in patients with apattern suggesting increased transmitral pressure gradients(E_max 73.1 ± 15.1 cm.s^–1, A_max 55.8 ± 19.2cm.s^–1,E/F slope 4.9 ± 2.0m . s^–1, all P<0.05 comparedto controls). After 12 months of treatment most parameters hadreturned to normal but the atrial contribution to left ventricularfilling remained high (A_max54.7 ± 13.9 vs control 42.2± 9.4 cm . s^–1 .flow velocity integral of atrialfilling 4.7 ± 1.3 vs 3.6±11 control, both P0.01).Left ventricular filling is therefore highly abnormal beforeand during the treatment ofthyrotoxicosis. However, these changesappear unlikely to reflect an intrinsic thyrotoxic cardiomyopathyand are more likely to represent a combination of prolongedincreases in left ventricular filling pressures along with abnormalitiesof left atrial function. The abnormal Doppler parameters emphasisethe importance of sinus rhythm in maintaining left ventricularfilling in thyrotoxicosis and may explain why marked haemodynamicdeterioration may result from the development of atrial fibrillationin these patients.     

Functional capacity before and after cardioversion of atrial fibrillation: a controlled study.

OBJECTIVE--To evaluate the effect of cardioversion on peak oxygen consumption (peak VO2) in patients with long-standing atrial fibrillation, to assess the importance of underlying heart disease with respect to the response to exercise, and to relate functional capacity to long-term arrhythmia outcome. DESIGN--Prospective controlled clinical trial. SETTING--Tertiary referral centre. PATIENTS--63 consecutive patients with chronic atrial fibrillation accepted for treatment with electrical cardioversion. Before cardioversion all patients were treated with digoxin, verapamil, or a combination of both to attain a resting heart rate < or = 100 beats per minute. INTERVENTIONS--Electrical cardioversion. MAIN OUTCOME MEASURES--Peak VO2 measured before and 1 month after electrical cardioversion to compare patients who were in sinus rhythm and those in atrial fibrillation at these times. Maintenance of sinus rhythm for a mean follow up of 19 (7) months. RESULTS--Mean (1SD) peak VO2 in patients in sinus rhythm after 1 month (n = 37) increased from 21.4 (5.8) to 23.7 (6.4) ml/min/kg (+11%, P < 0.05), whereas in patients with a recurrence of atrial fibrillation 1 month after cardioversion (n = 26) peak VO2 was unchanged. In patients who were in sinus rhythm both those with and without underlying heart disease improved, and improvement was not related to functional capacity or left ventricular function before cardioversion. Baseline peak VO2 was not a predictive factor for long-term arrhythmia outcome. CONCLUSION--Restoration of sinus rhythm improved peak VO2 in patients with atrial fibrillation, irrespective of the presence of underlying heart disease. Peak VO2 was not a predictive factor for long-term arrhythmia outcome after cardioversion of atrial fibrillation. These findings suggest that cardioversion is the best method of improving functional capacity in patients with atrial fibrillation, whether or not they have underlying heart disease and whatever their functional state.     

Intravenous digoxin in acute atrial fibrillation: Results of a randomized, placebo-controlled multicentre trial in 239 patients

AIMS: The DAAF Trial was designed to investigate whether digoxin,within 16 h of its use, increases the rate of conversion tosinus rhythm in patients with acute atrial fibrillation. METHODS AND RESULTS: In a randomized, double-blind multicentre trial the effectsof intravenous digoxin and placebo, (mean dose 0·88±0·35mg and 0·96±0·37 mg) were compared in 239patients with a mean age of 66·2±13·0 yearsand atrial fibrillation of, at most, 7 days' duration. The meanarrhythmia duration was 21·7±30·4 h andbaseline heart rate 122·0±23·0 beats. min^–1.At 16 h, 46% of the placebo group and 51% of the digoxin grouphad converted to sinus rhythm, (ns). Time to sinus rhythm wasshorter in the digoxin group, but the difference was not significant.Digoxin had a pronounced and rapid effect on heart rate, whichwas already significant at 2 h; 104·6±20·9beats. min^–1 vs 116·8±22·5 beats.min^–1 (P=0·0001). CONCLUSION: Acute intravenous treatment with digoxin does not increase therate of conversion to sinus rhythm, but has a fast acting andclinically significant effect on heart rate and should remainan alternative in haemodynamically stable patients     

Assumed oxygen consumption based on calculation from dye dilution cardiac output: an improved formula

This study was performed because of observed differences betweendye dilution cardiac output and the Fick cardiac output, calculatedfrom estimated oxygen consumption according to LaFarge and Miettinen,and to find a better formula for assumed oxygen consumption.In 250 patients who underwent left and right heart catheterization,the oxygen consumption VO₂ (ml. min^–1) was calculatedusing Fick's principle. Either pulmonary or systemic flow, asmeasured by dye dilution, was used in combination with the concordantarteriovenous oxygen concentration difference. In 130 patients,who matched the age of the LaFarge and Miettinen population,the obtained values of oxygen consumption VO₂(dd) were comparedwith the estimated oxygen consumption values VO₂(lfm), foundusing the LaFarge and Miettinen formulae. The VO₂(lfm) was significantlylower than VO₂(dd); – 21.8 ±29.3 ml. min^–1(mean±SD),P<0.001, 95% confidence interval (95% CI) –26.9 to–16.7, limits of agreement (LA) –80.4 to 36.9. Anew regression formula for the assumed oxygen consumption VO₂(ass)was derived in 250 patients by stepwise multiple regressionanalysis. The VO₂(dd) was used as a dependent variable, andbody surface area BSA (m²), Sex (0 for female, 1 for male),Age (years), Heart rate (min^–1) and the presence of aleft to right shunt as independent variables. The best fittingformula is expressed as: VO₂(ass)=(157.3 x BSA+10.0 x Sex –10.5 x In Age+4.8) ml.min^–1, where In Age=the natural logarithm of the age.This formula was validated prospectively in 60 patients. A non-significantdifference between VO₂(ass) and VO₂(dd) was found; mean 20±23.4ml.min^–1,P=0.771, 95% CI= –4.0 to +8.0, LA –44.7 to +48.7.In conclusion, assumed oxygen consumption values, using ournew formula, are in better agreement with the actual valuesthan those found according to LaFarge and Miettinen's formulae.     

Effect of flecainide on atrial and ventricular refractoriness and conduction in patients with normal left ventricle: Implications for possible antiarrhythmic and proarrhythmic mechanisms

We studied the effects of intravenous fiecainide (2 mg.kg^–1)on atrial and ventricular refractoriness and conduction duringsinus rhythm, induced atrial fibrillation and atrial pacingat rates of 100, 120 and 150 ppm, in 14 patients with normalleft ventricle. Flecainide caused a significant increase inQRS duration during sinus rhythm (mean ± SD: 87·2± 8·4 ms vs 102·8 ± 9·1 ms,P<0·001) atrial fibrillation (87·8 ±10·0 ms vs 108·8 ± 13·7 ms, P<0·001)and at all paced rates. The duration of the atrial electrogramwas significantly increased during sinus rhythm (54·9± 13·2 ms vs 64·8 ± 16·6ms, P=0·003) and at all pacing rates. The PA intervalwas also signficantly prolonged, as was the pacing stimulus-to-atrial-electrograminterval at all pacing rates. There was increased QRS durationand atrial electrogram prolongation at higher pacing rates.Atrial refractoriness was prolonged during sinus rhythm (216·4± 28·2 vs 228·6 ± 36·1, P=0·02),but not during atrial pacing at any rate. The QT interval, butnot the JT interval or ventricular refractoriness, was significantlyprolonged during sinus rhythm and at all pacing rates. Flecainideslows atrial conduction in a use-dependent manner and increasesatrial refractoriness during sinus rhythm but not during fasteratrial pacing, thus not displaying a use-dependent effect. QRSduration is prolonged in a use-dependent manner without a commensurateincrease in ventricular refractoriness. In the presence of rapidlyconducted atrial fibrillation, which was not found to be slowedby flecainide, this effect may constitute a proarrhythmic mechanismeven in patients with no apparent myocardial abnormality.     

Exercise heart rate acceleration patterns during atrial fibrillation and sinus rhythm

Background: Patients with atrial fibrillation sustain a significant lower exercise tolerance compared to those in sinus rhythm, even while seemingly in adequate rate‐control. Methods: Exercise testing was performed during atrial fibrillation and after electric cardioversion for 30 patients who were initially treated with AV modifying agents and were considered in adequate rate control. Heart rate parameters were obtained during all exercise stages, and a graphic display of heart rate acceleration was obtained. For those patients who remained in sinus rhythm, an additional exercise test was performed after 1 month. Results: During atrial fibrillation, heart rate at the completion of Bruce stage 1 and the peak exercise heart rate were significantly higher when compared to sinus rhythm (120 ± 10 bpm vs. 98 ± 11 bpm and 164 ± 16 bpm vs. 129 ± 11 bpm respectively, p < 0.001 for both). The time to peak exercise heart rate was significantly shorter during atrial fibrillation (3.5 ± 1 min vs. 6.5 ± 1.5 min, p < 0.001), and the total exercise duration was subsequently shorter as well (6 ± 2 min vs. 8.5 ± 2 min, p < 0.001). Treatment with beta‐blockers prior to exercise did not affect the earlier peaking of the heart rate. After 1 month, similar time to peak heart rate and similar exercise performance were observed among patients, who remained in sinus rhythm, when compared to to the post‐cardioversion exercise test. Conclusions: In patients with atrial fibrillation, exercise heart rate acceleration displays a specific pattern of early peaking. Earlier heart rate peaking occurs regardless of ample rate control while at rest or mild physical activity and contributes to overall lower exercise performance. Ann Noninvasive Electrocardiol 2011;16(4):357–364     

Right atrial free wall conduction velocity and degree of anisotropy in patients with stable sinus rhythm studied during open heart surgery

Aims Although the perpetuation of several supraventricular arrhythmiasis critically dependent upon intra-atrial conduction, the literaturelacks detailed information on normal values of conduction velocityand degree of anisotropy. In order to explore these factorsfurther, we have measured conduction velocities at the rightatrial free wall during sinus rhythm and during atrial pacingin four directions parallel and perpendicular to the atrioventriculargroove in patients with normal atria and stable sinus rhythm. Methods and Results Using a Bard Cardiac Mapping System, atrial ECGs were recordedusing a 3x4cm electrode array with 56 equally spaced bipolarelectrodes in 12 patients undergoing open heart surgery dueto ischaemic heart disease or Wolff–Parkinson–Whitesyndrome. A bipolar pen probe connected to a Medtronic 5328stimulator was used for pacing at a 10% higher rate than sinusrhythm. The local activation times were manually set and isochronalactivation maps were created for each recording. The conductionvelocities were calculated from the activation maps over a distanceranging from 2·2 to 4·2cm. The majority of the activation maps showed no signs of anisotropy;the others had less than 15% spatial inhomo-geneity of conduction.Mean conduction velocity, calculated from five consecutive beats,was 88±9cm.s^–1(mean±SD), ranging between68±4 and 103±3cm.s^–1during sinus rhythm.Mean conduction velocity during atrial pacing was 81±16cm.s^–1ata propagation direction of 0°, 74±14cm.s^–1ata 90° direction, 79±12cm.s^–1at 180° and78±20cm.s^–1at 270°, where 0° was parallelto the atrioventricular groove in the cranial direction andthe angle increased counter-clockwise. Mean conduction velocityduring sinus rhythm was significantly higher (P<0·05)than during atrial pacing at the 90° and 180° directionsbut not compared to atrial pacing at 0° or 270°. Therewas no significant difference in mean conduction velocity indifferent directions during atrial pacing. Conclusion Although anisotropy was documented during conduction velocityin individual cases, conduction velocity was not dependent onpropagation direction at the epi-cardial right atrial free wallin patients with stable sinus rhythm. These findings do notexclude the presence of internodal preferential pathways asthese are located subepicardially and a marked transmural discordancein activation has previously been documented in the vicinityof such pathways.     

The effect of the angiotensin converting enzyme inhibitor, enalapril, on exercise tolerance and abnormalities of limb blood flow and respiratory function in patients with severe heart failure

Ten patients with severe (NYHA III) heart failure were comparedwith 10 age-matched healthy subjects in terms of oxygen uptakeand minute ventilation at rest and during exercise and calfand forearm blood flow measured by venous occlusion plethysmographyat rest and after a standardized exercise test. Patients performeda symptom-limited treadmill exercise test and were then treatedwith enalaprilfor 5 weeks; the various measurements were repeatedat weekly intervals. Oxygen consumption (VO₂) at rest was similar in the patientsand controls. During exercise, patients VO₂, tended to be lowerat each workload, but this was not affected by enalapril treatment.Minute ventilation was higher at rest and at each exercise stagein the patients than in the control subjects, and this was significantlyreduced by enalapril treatment. Compared with the controls (2.94±0.10 and 2.93±0.20ml, 100 ml^–1min^–1) forearm and calf blood flow measuredby venous occlusion plethysmography was reduced at rest in thepatients (1.34±0.18 and 1.24±0.11 ml. 100 ml .min^–1min^–1), but was significantly increased byenalapril treatment (1.73±0.15 and 1.60±0.16 ml.100 ml^–1 . min^–1). Submaximal leg exercise to afixed VO₂, showed attenuation of the normal vasoconstrictionin the forearm and vasodilatation of the calf; enalapril treatmentchanged these responses significantly towards normal but a markedabnormality of flow pattern persisted.     

持续性心房颤动药物复律后心房收缩功能恢复的观察

目的　观察持续性心房颤动药物复律后心房收缩功能的恢复过程。方法　5 3例持续性心房颤动患者在药物复律后第1、1 4、2 8天运用超声心动图检测舒张期跨二尖瓣血流。结果　复律后A峰、A波积分逐步升高(0 . 3 5±0 . 1 0cm/s至0 . 62±0 . 1 1cm/s、4 .43±1 . 3 6cm/s2至6. 0 2±1. 5 0cm/s2 ) ,A波积分占总积分比例由2 6±7%上升至3 4±8%。结论　持续性心房颤动经药物复律后心房收缩功能逐步缓慢恢复。     

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.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.     

Alternations in atrial natriuretic peptide release after DC cardioversion of non-valvular chronic atrial fibrillation

The response of atrial natriuretic peptide (ANP) release tohaemodynamic influences after cardioversion of atrial fibrillationhas not been fully examined. We measured plasma concentrationsof ANP and assessed haemodynamic changes 60–120 min afterDC cardioversion in 22 patients with non-valvular chronic atrialfibrillation. Passive leg elevation to enhance volume expansionwas performed 60 min after DC cardioversion. Sinus rhythm wasrestored in 18 of the 22 patients (successful DC cardioversiongroup). The control group consisted of seven patients with non-valvularchronic atrial fibrillation who did not undergo DC cardioversion(atrial fibrillation control group). In the successful DC cardioversiongroup, the mean pulmonary artery wedge pressure decreased significantly15 min after cardioversion (P<0.05) and then remained unchanged.Plasma concentrations of ANP also decreased significantly 15min after cardioversion (P<0.05). Furthermore, there wasan additional significant decrease in ANP levels for up to 60min after cardioversion (P<0.05 from 15 min). Passive legelevation for 15 min led to an increase in the mean pulmonaryartery wedge pressure (P<0.01) and right atrial pressure(P<0.05), but did not result in increased plasma concentrationsof ANP (47.1 ± 27.6 vs 43.9 ± 34.4 pg. ml^–1,mean ± SD, P=ns). In the atrial fibrillation controlgroup, passive leg elevation increased the mean pulmonary arterywedge pressure (P<0.01), the mean right atrial pressure (P<0.05)and plasma concentrations of ANP (139.9 ± 85.8 vs 1681±108.2, P<0.05). In summary, after successful DC cardioversionof non-valvular chronic atrial fibrillation, plasma concentrationsof ANP decreased in conjunction with decreased mean pulmonaryartery wedge pressure. The response of ANP release to volumeexpansion, however, appears to be dysregulated in this patientpopulation.     

Success of serial external electrical cardioversion of persistent atrial fibrillation in maintaining sinus rhythm; a randomized study.

AIMS: The aim of this prospective, randomized study was to determine the efficacy of a serial external electrical cardioversion strategy in maintaining sinus rhythm after 12 months in patients with recurrent persistent atrial fibrillation. METHODS AND RESULTS: Ninety patients with persistent atrial fibrillation lasting more than 72 h but less than 1 year were randomized in a one to one fashion to repetition of up to two electrical cardioversions in the event of relapse of atrial fibrillation detected within 1 month of the previous electrical cardioversion (Group AGG), or to non-treatment of atrial fibrillation relapse (Group CTL). ECGs were scheduled at 6 h, 7 days, and 1 month. Clinical examination and ECGs were repeated during the 6-month and 12-month follow-up examinations. Echocardiography was repeated during the 6-month follow-up examination. Clinical and echocardiographic characteristics were similar in the two groups. All patients were treated with antiarrhythmic drugs before electrical cardioversion and throughout follow-up. After 12 months, sinus rhythm was maintained in 53% of Group AGG patients and in 29% of Group CTL patients (P<0.03). After 6 months, left ventricular ejection fraction had recovered significantly only in Group AGG (56.8 +/- 9.0% at enrollment vs 60.4 +/- 9.4% at 6 months,P <0.001). CONCLUSION: These results demonstrate that an aggressive policy towards persistent atrial fibrillation by means of repetition of electrical cardioversion after early atrial fibrillation recurrence is useful in maintaining sinus rhythm after 12 months.     

Determinants of heart rate variability in heart transplanted subjects during physical exercise

Respiratory sinus arrhythmia has been described in heart transplantedsubjects. In order to investigate the mecha nisms involved inthe generation of this condition in the transplanted heart andits evolution after surgery, graded exercise was performed (0–75W in 25 W steps) on a cycle ergometer by 41 subjects (mean age44 years) who had undergone heart transplantation 28 months(range 3–60) earlier and by six age matched-control subjects.R-R interval, respiratory signal, O₂ consumption (VO₂ and CO₂production (VCO were measured. Respiratory sinus arrhythmiawas assessed by the autoregressive power spectrum of the R-Rinterval and respiration. All subjects reached the anaerobicthreshold (heart transplants: 60% at 50 W, 40% at 75W Controls:150 W). In control subjects, the respiratory sinus arrhythmiawas higher than in heart transplanted subjects (5·80± 0·30 vs 1·45 ± 0·16 lnms²) and it decreased significantly (4·66 ± 0·30In ms² P<0·05) during exercise, despite the increasein breathing rate and depth. When the group of heart transplantedsubjects was considered as a whole, respiratory sinus arrhythmiawas found to be present in all conditions. It significantlyincreased at 25 W (from 1·45 ± 0·16 to2·00 ± 0·17 In ms² P<0·01), thensignificantly fell below baseline during recovery (to 0·97± 0·23 In ms P<0·01). Multiple regressionanalysis showed that a linear combination of heart rate (inversecorrelation) and VO² (direct correlation) together with monthshaving passed since transplantation surgery, could explain theobserved changes in heart rate during exercise (multiple regression:r=0·658, P<0·0001). In five long-term transplantedsubjects, non respiratory-related low frequency (0·1Hz) waves were present on the R-R spectrum, but respiratorysinus arrhythmia is also present in the recently transplantedheart and depends on the opposing effects of ventilation andheart rate. In a few cases, sympathetic modulation (re-innervation)could not be excluded. (Eur Heart J 1996; 17: 462–471)