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.     

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.     

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     

Long-term effect of cardioversion on peak oxygen consumption in chronic atrial fibrillation: A 2-year follow-up

Restoration of sinus rhythm may improve functional capacityin atrial fibrillation in the short-term. Little is known, however,about its long-term effect on functional status. The aim ofthe present study was to evaluate the long-term effect of cardioversionon peak oxygen consumption (VO₂) in patients with chronic atrialfibrillation. Patients with such a condition and due to undergoelectrical cardioversion were eligible for the study. Patients underwent treadmill exercise testing with measurementof peak VO₂ before cardioversion, and at 1 month and 2 yearsthereafter. Based on the rhythm present at those times aftercardioversion, patients were categorized into three groups:those in sinus rhythm after 1 month and 2 years (Group I); thosein sinus rhythm after 1 month, but with atrial fibrillationafter 2 years (Group II); and those who were in atrial fibrillationboth at 1 month and 2 years following cardioversion (Group III).Thirty-nine patients were included, and underlying heart diseasewas present in 24 of them (62%). In the comparison of the baseline characteristics of Group I(n = 17), Group II (n =11), and Group III (n = 11), underlyingheart disease was more frequent in Group I (88%, 45%, and 36%,respectively); otherwise they were similar. In Group I, peakVO₂ showed an insignificant increase from 21.1 ± 50 to22.3 ± 50 ml. min ^–1. kg^–1 1 month aftercardioversion. After 2 years of sinus rhythm, peak VO₂ showeda further increase to 23.8 ±5.0 ml. min^–1. kg^–1(P<0.05). In Group II patients, peak VO₂ improved after 1month of sinus rhythm (from 25.2 ± 7 to 27.8 ±8 ml. min^–1. kg^–1, P<0.05) but returned to baselineafter 2 years, when atrial fibrillation had relapsed. In GroupIII patients, peak VO₂ was unchanged 1 month after cardioversion,when atrial fibrillation had already relapsed. After 2 years,however, peak VO₂ had decreased from 22.1 ± 4.0 to 20.6± 4.0 (P<0.05), when compared to baseline. In conclusion, restoration of sinus rhythm is associated witha modest but significant improvement of peak VO₂, which persistsafter the first month following cardioversion. In addition,in patients with sustained atrial fibrillation functional capacitydecreases during long-term follow-up. These findings suggestthat, to prevent progressive deterioration of functional capacityin atrial fibrillation, a treatment approach aimed at restoringand maintaining sinus rhythm may be warranted.     

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.     

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.     

Facilitating influence of procainamide on conversion of atrial flutter by rapid atrial pacing

In a prospective, double-blind, randomized, placebocontrolledstudy we investigated the facilitating influence of intravenousprocainamide on conversion of atrial flutter by rapid atrialpacing. Fifty consecutive patients with spontaneous sustained atrialflutter were 1:1 randomized into two homogenous groups: groupA received 10 mg. kg^–1 procainamide intravenously, groupB placebo. After infusion there was a significant (P<0·01)lengthening of the flutter cycle with respect to baseline ingroup A, exceeding the flutter cycle length of the control group(P<0·05). The overall success rate of rapid atrialpacing in restoring sinus rhythm was significantly higher afterpre-treatment with procainamide compared to placebo (100% vs76% P<0·05): 20 patients of group A reverted immediatelyafter pacing to sinus rhythm, the remaining five after a briefepisode of atrial fibrillation. In the placebo group, 16 patientsshowed a prompt conversion to sinus rhythm and three after transientatrial fibrillation. In the remaining six patients, due to sustainedpacing-induced atrial fibrillation, direct current cardioversionwas necessary. After administration of procainamide a less aggressivestimulation protocol with significantly (P<0·01) longerpaced cycles to interrupt atrial flutter was achievable. In conclusion, intravenous procainamide augments the efficacyof atrial pacing to convert atrial flutter to sinus rhythm.     

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.     

A comparison of treatment of atrial fibrillation with low-energy intracardiac cardioversion and conventional external cardioversion

AIM: Low-energy (1 to 15 J), catheter-based intracardiac cardioversionwas compared with transthoracic external cardioversion (360J) in a prospective, cross-over clinical trial. METHODS AND RESULTS: In 187 consecutive patients with chronic atrial fibrillation,over a period of a mean of 10·0±7·3 (SD)months, 217 cardioversion attempts were made. Intracardiac shockswere randomly applied between two 6-F catheters located in eitherthe right atrium and coronary sinus or between the right atriumand left pulmonary artery. When a cardioversion attempt withone method failed, the other method was implemented. After cardioversion,all patients were treated orally with sotalol with a mean dailydose of 174±54 mg. Internal cardioversion was more effective than external cardioversion(65/70=93% vs 92/177 =79%, P<0·01). The mean energyfor successful cardioversion was 5·8±3·2J for the internal and 313±71 J for the external cardioversiongroup. At a mean follow-up of 12·5±6·4months, 48% (38%) of the patients treated with internal (external)cardioversion were in sinus rhythm (P<0·05). In 22 of 25 patients in whom external cardioversion failed,sinus rhythm was restored with internal cardioversion at a meanenergy of 6·5±3·0 J. Overweight patientshad twice the risk of unsuccessful external cardioversion. CONCLUSION: Internal cardioversion is effective in restoring sinus rhythm.It might be indicated in patients in whom external cardioversionhad failed or in whom external cardioversion is assumed to bedifficult or even contraindicated.     

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.     

Arm-leg pressure gradients on late follow-up after coarctation repair: Possible causes and implications

Seventeen years after coarctation repair, 36 patients were studiedby magnetic resonance imaging and exercise testing to measureresidual anatomical stenosis and hormonal response to exercise,and to evaluate their effect on arm–leg gradients andon exercise hypertension. The systolic arm pressure, leg pressureand arm–leg gradient were measured at rest and duringexercise. Active renin and catecholamines were measured in theplasma at rest and after peak exercise. On magnetic resonanceimaging 18 patients had residual stenosis of less than 30% (groupI) and 18 had residual stenosis of equal to or more than 30%(group II). At peak exercise, the arm pressure was 235 (133–296)mmHg in group I and 241 (157–286) mmHg in group II (ns),the leg pressure was 138 (111–173) mmHg in group I and114 (75–154)mmHg in group II (P=0·002). The adrenalinincrease from rest to exercise was 32·7 ± 9·1pg . ml ^–1 in the patients with exercise hypertensionand 3·1 ± 4·7 pg. ml^–1 in the patientswho remained normotensive during exercise (P=0·02). Inconclusion, residual anatomical stenosis leads to a pressuredrop in the legs, which influences the arm-leg gradient. Armhypertension is not related to anatomical narrowing but to interactionof enhanced sympathetic nerve activity and structural and functionalabnormality of the precoarctation vessels. (Eur Heart J 1996; 17: 1572–1575)     

Re-evaluation of the role of P-wave duration and morphology as predictors of atrial fibrillation and flutter after coronary artery bypass surgery

To evaluate the significance of P-wave duration and morphologyfor the development of post-operative atrial fibrillation/flutter,we investigated 189 consecutive patients scheduled for electivecoronary artery bypass surgery. The longest pre-operative totalP-wave duration was measured from the standard electrocardiogramat a paper speed of 50 mm. s^–1 (mean of two independentobservers). By the signal averaging technique we determinedthe pre-operative total P-wave duration, and root-mean squarevoltage of the last 10, 20, and 30 ms of the filtered (40–250Hz) P-wave from a vector composite of three orthogonal leadsat noise level 0·2 µV. Forty-two (22%) of the patientsdeveloped atrial fibrillation/flutter. Older age (mean ±SD) 62 ± 8 vs 56 ± 8 years (P<0·000),increasing body weight 83 ± 11 vs 79 ± 12kg (P=0·05),treatment for hypertension 26 vs 13% (P=0·04), and alonger P-wave duration in the standard electrocardiogram 129± 12 vs 124 ± 12 ms (P=0·01 were associatedwith development of atrial fibrillation/flutter documented bya 12-lead electrocardiogram. Logistic regression analysis identifiedindependent predictors, estimated adjusted relative risk (95%confidence interval) of atrial fibrillation/flutter: with age>60 years, the relative risk was 4·46 (2·05–9·73),and body weight >80 kg, the relative risk was 3·81(l·71–8·46). Thus, P-wave duration and morphologydid not provide significant information on the risk of atrialfibrillation/flutter when controlling for the effects of increasingage and body weight.     

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 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.     

Relationship between plasma atrial natriuretic factor and opioid peptide levels in healthy subjects and in patients with acute congestive heart failure

We evaluated plasma atrial natriuretic factor (ANF), ß-endorphin,met-enkephalin, dynorphin and noradrenaline levels in 20 healthysubjects and 20 acute congestive heart failure (CHF) patients.In all acute CHF patients plasma values of these hormones werehigher than in healthy subjects. The hormonal pattern differedin patients with the more severe acute CHF (group 1) from patientswith less severe acute CHF (group 2) (ANF 53.8 ± 1.0vs 34.6 ± 1.5 pg.ml^–1, noradrenaline 563.8 ±13.4 vs 202.4 ± 10.6 pg.ml^–1, met-enkephalin 41.0± 3.2 vs 17.0 ± 1.6 fmol. ml^–1, dynorphin46.8 ± 3.7 vs 25.2 ± 2.0 fmol. ml^–1, P <0.01;ß-endorphin 50.6 ± 5.2 vs 41.8 ± 4.1fmol. ml^–1, ns). Administration of an opioid antagonist(naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentrationin healthy subjects. in group 1 naloxone administration significantlyraised ANF (68.0 ± 1.4 pg. ml^–1), noradrenaline(776.6 ± 18.7 pg. ml^–1), blood pressure and heartrate, whereas in group 2 it significantly decreased ANF values(21.9 ± 0.5 pg. ml^–1)and did not modify the otherparameters. Our findings suggest that the opioid system affectsANF release in acute CHF. In patients with severe CHF opioidpeptides may attenuate ANF secretion reducing noradrenergicstimulation. On the other hand, when CHF is less severe andthe sympathetic activity is moderate, opioid peptides may directlystimulate ANF secretion.     

Physical training improves exercise capacity in patients with mitral stenosis after balloon valvuloplasty

BACKGROUND: Haemodynamic measurements taken at rest and during exerciseshowed that percutaneous transvenous mitral commissurotomy resultsin both acute and long-term improvement. However, the time lagbefore there is an increase in exercise and in peak oxygen uptakeappears to be delayed and irregular. PATIENTS AND METHODS: To assess the potential of physical training to restore betterphysical capacity after percutaneous transvenous mitral commissurotomy,26 patients with mitral stenosis were studied after the procedure.The group was split into two. Thirteen underwent a 3-month rehabilitationprogramme, and the other 13, who did not, acted as controls. RESULTS: The mitral valve orifice area increased similarly, from 1·;12±017to 1·88 ±0·28 cm² in the training groupand from 1·04±0·16 to 1·88±0·19cm² in the control group. Cardiopulmonary parameters were similarbefore percutaneous transvenous mitral commissurotomy (peako₂: 19·9±2·4 vs 18·9±4·5ml. min^–1. kg^–1; peak workload: 94·6±29·3vs 96·1±25 watts; o₂ at anaerobic threshold: 17±3·4vs 16·1±5·2 ml. .min^–1. kg^–1;all P=ns). Three months later the results were higher in thetraining group (peak o₂: 26·6±4·7 vs 21·6±3·8ml. min^–1. kg^–1, P=0·001; peak workload:125·4±26·6 vs 108·5±23 watts,p=0·03; o₂ at anaerobic threshold: 19·6±5·8vs 15·8±2·9 ml. min^–1. kg^–1;P=0·02). CONCLUSION: These results indicate that patients should take up exerciseafter successful percutaneous transvenous mitral commissurotomyfor better functional improvement.     

Pro-inflammatory cytokines and endothelium-dependent vasodilation in the forearm. Serial assessment in patients with congestive heart failure

Background In patients with heart failure endothelium-dependent vasodilationof the forearm conduit vessels is impaired possibly becauseof elevated plasma levels of pro-inflammatory cytokines. Theeffect of elevated plasma cytokines on endothelium-dependentvasodilation of forearm conduit vessels was therefore seriallyinvestigated in 16 patients with congestive heart failure duringan episode of acute failure and at the time of recompensation. Methods and Results Pro-inflammatory cytokine levels and hyperaemic brachial arterydiameters were obtained shortly after admission for an episodeof acute heart failure and 11±3 days later at the timeof recompensation, which was obtained using diuretic therapywithout changing other cardiovascular medications. Serum concentrations(Mean±SD) of tumour necrosis factor alpha (TNF-) (decompensationvs recompensation: 25±23pg.ml^–1vs 26±17pg.ml^–1)and interleukine 6 (IL-6) (decom-pensation vs recompensation:27±24pg.ml^–1vs 20±18pg.ml^–1), determinedin venous blood using immunoradiometric assays were elevatedbut remained unaltered following recompensation. Brachial arterydiameter, derived from high-resolution ultrasound scans at restand during reactive hyperaemia, 90s after forearm cuff deflation,increased significantly during reactive hyperaemia at the timeof admission (3·4±0·7mm vs 4·0±0·5mm;P=0·014)and following recompensation (3·4±0·5mmvs 3·8±0·2mm;P=0·032). The brachialartery diameter during recompensation expressed as a percentageof the baseline value was similar at both intervals (decompensationvs recompensation: 117±14% vs 116±10%;P=ns). Atthe time of decompensation, the correlation between TNF- andthe percentage change in brachial artery diameter followingreactive hyperaemia was absent (r=0·098;P=0·719).The same correlation became significant at the time of recompensation(r=0·750;P=0·001). Conclusions In patients with congestive heart failure, plasma levels ofpro-inflammatory cytokines correlate with endothelium-dependentvasodilation of the brachial artery following recompensation,but not during an acute episode of heart failure.     

Clinical cardiac electrophysiologic evaluation of the positive inotropic agent, DPI 201-106

DPI 201–106 is a new positive inotropic agent. The cardiacelectrophysiology of 16 patients was studied before and duringDPI 201–106 administration (loading dose of intravenousDPI 201–106, 1·8 mg kg^–1 h^–1 administeredover 10 min, followed by a maintenance dose of 0·2 mgkg^–1 h^–1). DPI 201–106 had no effect on thesinus node. The AH interval during fixed-rate atrial pacingbecame prolonged during DPI 201–106 infusion. There wasa significant prolongation of the QT interval [QT (corrected),417 ± 22 to 502 ± 35 ms, P<0·05; QT(atrial pacing at 600 ms), 374 ±17 to 419 ± 23ms, P<0·05; QT (ventricular pacing at 600 ms), 409± 37 to 449 ± 30 ms, P<0·05]. The ventriculareffective refractory period significantly prolonged during DPI201–106 administration (242 ± 21 to 287 ±56 ms, P < 0·05), but the supernormal-period durationdecreased. The atrial effective refractory period was shortenedin four patients and prolonged in one (261 ± 67 to 240± 53 ms, NS). The corrected atrial repolarization time(PT_ac) shortened significantly during DPI 210–106 infusion(479 ± 26 to 445 ± 22 ms at 20 min of the maintenancedose, P<0·05). Atrial fibrillation was initiated infive patients during DPI infusion, but no ventricular arrhythmiawas provoked. These findings suggest that DPI 201–106has novel differential electrophysiological effects on atriaand ventricles.     

Dyspnoea and exercise intolerance during cardiopulmonary exercise testing in patients with univentricular heart: The effects of chronic hypoxaemia and Fontan procedure

BACKGROUND: Patients with univentricular hearts have decreased exercisetolerance and may demonstrate exertional dyspnoea. It is notknown if chronic hypoxaemia exacerbates exercise intoleranceand contributes to symptomatic limitation. The extent to whichsurgical correction of a right-to-left shunt by a Fontan-typeprocedure can increase exercise tolerance by reducing arterialdeoxygenation is not well documented. The cardiopulmonary exerciseresponses and the symptomatic status in two groups of univentricularpatients, those who are cyanotic and those who are acyanoticwith Fontan-type circulation, were compared. METHODS AND FINDINGS: Cardiopulmonary exercise testing was performed in 10 univentricularpatients with rest or stress-induced cyanosis (age 30·5±2·3[SE] years; 5 men) who had palliative or no surgery and eightpatients (age 29·4±1·5 years; 4 men) withFontan-type circulation. Peak oxygen consumption was comparablein both groups of univentricular patients (21·7±2·5vs 21·0±1·9 ml. kg^–1 . min^–1,P=0·85) but was less than an age-matched group of 10healthy subjects (34·7±1·9 ml. kg^–1. min^–1, P<0·001 for both). Arterial oxygensaturation was 90·6% at rest in the cyanotic patientscompared with 95·1% in the Fontan patients (P<0·001)and at peak exercise, 66·2% compared with 90·5%(P<0·001). Using a modified Borg scale (0–10),the symptoms of dyspnoea and fatigue were also assessed duringexercise in the patient groups. The Borg scores for dyspnoeain the cyanotic and the corrected univentricular patients were,respectively, as follows: Stage 1: 0·5 vs 1·7;P=0·04; Stage 2: 1·8 vs 2·3, P=0·5;Stage 3: 3·0 vs 3·5, P=0·7; Peak Exercise:4·9 vs 4·8, P=0·9. In addition, the Borgscores for fatigue were: Stage 1: 0·4 vs 1·6,P=0·08; Stage 2: 2·0 vs 2·2, P=0·9;Stage 3: 3·0 vs 4·3, P=0·5; Peak Exercise:4·9 vs 5·4, P=0·5. The major limiting symptomat peak exercise was dyspnoea in four cyanotic patients comparedwith one in the Fontan group (Chi-square 0·982, P>0·10).The arterial oxygen desaturation at peak exercise in the cyanoticpatients limited by dyspnoea was not different from those limitedby fatigue (67·5±10·1% vs 66·7±13·7%,P=0·92). Exercise tolerance was also not related to thearterial oxygen saturation at peak exercise (r=0·47,P=0·17) in these patients. CONCLUSION: Despite correction with Fontan-type surgery, the exercise toleranceand symptoms of these univentricular patients remained similarto those who were cyanosed. Cyanotic patients have adjustedto chronic hypoxaemia and it does not appear to determine theexercise tolerance or the genesis of dyspnoea in these patients.Further randomized prospective studies are required to investigatethe long-term benefits of Fontan-type procedures in these patientson exercise tolerance, symptoms and prognosis.     

Skeletal muscle lactate accumulation and creatine phosphate depletion during heavy exercise in congestive heart failure: Cause of limited exercise capacity?

OBJECTIVE: To study the mechanisms of limited exercise capacity and skeletalmuscle energy production in male patients with congestive heartfailure. DESIGN: Muscle biopsy study. PATIENTS: Skeletal muscle metabolic response to maximal bicycle exercisewas studied in 10 patients with chronic congestive heart failure(ejection fraction 0·22±0·05; peak oxygenconsumption, Vo₂ 15·1±4·9 ml. min^–1.kg^–1) and in nine healthy subjects (peak Vo₂ 33·5±6·7ml. min^–1. kg^–1). Activities of skeletal muscleenzymes were measured from the vastus lateralis muscle of 48patients (ejection fraction 0·24±0·06,peak Vo₂ 17·4±5·4 ml. min^–1. kg^–1)and 36 healthy subjects (peak Vo₂ 38·3±8·4ml. min^–1. kg^–1). RESULTS: Although blood lactate levels were lower in patients than inhealthy subjects (2·2±0·3 vs 5·2±0·6mmol. 1^–1; P<0·001) at peak exercise (96±11W for patients and 273±14 W for controls), skeletal musclelactate was similarly elevated (25·6±3·2vs 22·7±2·7 mmol.kg^–1) and creatinephosphate was equally depressed (P<0·02) to low levels(7·0±1·9 vs 6·7±0·9mmol.kg^–1). The muscle ATP decreased by 21% (P<0·05)and 8% (P<0·01) in the patients and controls, respectively.Activities of rate limiting enzymes of the citric acid cycle(alpha-ketoglutarate dehydrogenase) and oxidation of free fattyacids (carnitine palmitoyltransferase II) were 48% and 21% lowerthan in controls, but the mean phosphofructokinase activitywas unchanged in congestive heart failure. CONCLUSIONS: It seems that the main limiting factor of exercise performanceduring heavy exercise is the same in congestive heart failureand healthy subjects, a high rate of skeletal muscle lactateaccumulation and high-energy phosphate depletion. In congestiveheart failure, the low activity of aerobic enzymes is likelyto impair energy production and lead to lactate acidosis atlow workloads.