Proarrhythmic and antiarrhythmic effects of intravenous prostacyclin in man

Prostacyclin (PGI2) has been shown to reduce the occurrenceof experimental ventricular arrhythmias. To assess potentialbeneficial effects in man, the electrophysiological action ofPG12 was studied in 16 non medicated patients. The protocolused in incremental pacing and programmed stimulation in theright atrium and ventricle. This protocol and measurement ofeffective refractory periods (ERP) were performed before andduring the injection of 2.5, 5 and 10 ng kg^–1 min^–1of PGI2. The atrial functional refractory period decreased significantly(P<0.05); PGI2 had no influence on the occurrence of induciblenon-sustained (NS) atrial tachycardias and was responsible forthe occurrence of 2 non-sustained atrial tachycardias in 8 patientswith inducible atrial echo beats under basal conditions. Thirteenpatients did not have inducible ventricular tachycardia ( VT)under basal conditions. Non-sustained VT was induced after PGI2in 4 of them but in only 1 of them after the administrationof propranolol. Three patients had inducible VT under basalconditions (1 non-sustained, 2 sustained VT). PG12 did not preventthe occurrence of VT (1 non-sustained, 1 sustained VT), exceptin 1 patient with ischaemic-related VT, who had non-sustainedVT after PGI2. In conclusion, PGI2 does not seem to have a cardiacantiarrhythmic effect and may increase the atrial and ventricularrepetitive response. This effect could be related to an increaseof adrenergic tone.     

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.     

Supraventricular arrhythmia as the cause of sudden death in hypertrophic cardiomyopathy

Electrophysiological studies with simultaneous echocardiographiccontrol and invasive measurement of intravascular pressureswere carried out in a 13-year-old boy with hypertrophic cardiomyopathywho was hospitalized after an episode of aborted sudden death. Ventricular stimulation did not induce ventricular tachycardia,but atrial stimulation induced atrial fibrillation, atrial flutterand non-sustained ventricular tachycardia. Atrial stimulation(S₁) at 200 beats. min^–1 (10–15s) also induced significantrepolarization abnormalities in the 5–10 post-stimulationbeats. Akinesia of the ventricular septum and posterior wallwithout opening of the mitral valve was documented by echocardiography.A complete anterior systolic motion, not observed under basalconditions, was detected in the first post-stimulation beat.Atrial stimulation at rates over 120 beats. min_–1 causeda drop in systolic blood pressure, a rise in pulmonary arterypressure, and a decrease in cardiac output. Despite therapy with propranolol and amiodarone, the patientdied suddenly.     

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.     

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.     

Dromotropic effects of oral theophylline in patients with atrial fibrillation and a slow ventricular response

Theophylline increases sinus rate, but as yet its use has notbeen investigated in patients with chronic atrio ventricularconduction disturbances. Resting electrocardiogram, 24-h Holterrecording and treadmill test were performed in 17 patients withchronic atrialfibrillation and a slow ventricular response notrelated to drugs (age: 75±8 years). Then slow-releasetheophylline was administered (700mg daily) and after 5 daysthese investigations were repeated with the same methods. Theophyllineincreased mean resting heart rate (51±6 versus 67±13beats.min^–1, P<0·01 mean 24-h heart rate (51±6versus 68±14 beats.min^–1, P<0·01 andminimal 24-h heart rate (32±6 versus 42±11 beats.min^–1,P<0·01 Cardiac pauses >2·5 s were presentin 13 patients during control recording; after theophyllinethey disappeared in 11 and markedly decreased in the remainingtwo. The longest R-R interval decreased in all patients (3218±943versus 2121±518ms, P<0·01). The daily numberof wide QRS complexes increased in 16 out of 17 patients (428±752versus 1146±1464 ms, P<0·01). Exercise heartrate, evaluated at the end offirsi andsecondstage, was higherafter theophylline than during control test (P<0·01). These data suggest that oral theophylline can represent a validtherapy in most patients with atrialfibrillation and a slowventricular response.     

Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone: A randomized, digoxin-controlled study

A 24 h intravenous dosing regimen of amiodarone was designedto reach a peak plasma concentration at 1 h and to maintainthe concentration above a certain level during the infusionperiod A randomized, open-label, digoxin-controlled study wasundertaken to observe the efficacy and safety of the dosingregimen of amiodarone in treating recent-onset, persistent,atrial fibrillation and flutter with ventricular rates above130 beats. min^–1. Fifty patients with a mean age of 70± 7 (SD) years were enrolled and randomly assigned toreceive either amiodarone intravenously (n=26) or digoxin (n=24).Amiodarone HCl was infused over 24 h according to the followingregimen: 5 mg. min^–1, 3 mg. min^–1, 1 mg. min^–1and 0.5 mg. min^–1 for 1, 3, 6 and 14 h, respectively,for a 70-kg subject. Digoxin (0.013 mg. kg^–1) was infusedin three divided doses, each dose 2 h apart and infused over30 min. The mean heart rates in the amiodarone group decreased significantlyfrom 157 ± 20 beats. min^–1 to 122 ± 25 beats.min^–1 after 1 h (P<005 vs baseline), and then decreasedfurther to stabilize at 96 ± 25 beats. min^–1 after6 h (P<0.05). The digoxin group had fewer dramatic alterationsin heart rates, compared to the amiodarone group, in the first8h (P<0.05, respectively). Maximum reduction was reachedonly after 8 h. The amiodarone infusion was prematurely abortedin two patients due to severe bradycardia and death after conversionin one patient and aggravation of heart failure in the other.Overall, 24 of 26 patients (92%) in the amiodarone group and17 of 24 (71%) in the digoxin group were restored to sinus rhythmwithin 24 h. The accumulated rates of conversion over 24 h weresignificantly different between the two groups (P=0.0048). Digoxin,while not as effective as amiodarone in the treatment of recent-onsetatrial fibrillation and flutter, appears to be safer. Therefore,we suggest the use of digoxin as the first line drug for thetype of patients that formed the basis of the current studyand reserve amiodarone for refractory cases or those in whomdigoxin is not suitable.     

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     

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.     

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.     

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.     

Serial electrophysiologic studies after single chamber atrial pacemaker implantation in patients with symptomatic sinus node dysfunction

After single chamber atrial pacemaker implantation, serial electrophysiologicstudies were performed noninvasively at intervals of 3 monthsover a total period of 3 years in 24 patients with symptomaticsinus node dysfunction. All patients underwent invasive electrophysiologicstudies before pacemaker implantation and demonstrated intactanterograde AV conduction. Patients were divided into 2 groupsgroup I did not require antiarrhythmic drugs during follow-upwhereas group 2 received antiarrhythmic drugs. In group 1(11 patients) the atrial paced heart rate producingAV Wenckebach phenomenon (AVWHR) remained stable during a meanfollow-up of 22±10 months, with a variability not exceeding10 beats min^–1 with respect to the initial AVWHR obtainedduring preoperative electrophysiologic study. In group 2 (13patients) with a mean follow-up of 15±8 months a meandecrease of AVWHR of 19.2±17.5 beats min^–1 waspresent between AVWHR before and 3 months after initiation oforal antiarrhythmic drugs (P<0.01) During chronic (>3months) antiarrhythmic drug therapy the variability of the AVWHRnever exceeded 10 beats min^–1 with respect to the AVWHRobtained 3 months after the initiation of oral drug therapy. Deterioration of anterograde AV conduction during long-termfollow-up of patients with symptomatic sinus node dysfunctionand intact anterograde AV conduction at the time of pacemakerimplantation is a consequence of orally taken antiarrhythmicdrugs, rather than a consequence of degeneration of the AV conductingsystem.     

A clinical study of amiodarone as a single oral dose in patients with recent-onset atrial tachyarrhythmia

Forty-five patients with recent-onset sustained atrial tachyarrhythmia(mean heart rate at entry; 140.0± 3.5 beats. min^–1)associated with various cardiovascular diseases were treatedby oral amiodarone, given as a single loading dose of 25.7±0.9 mg. kg–1 body weight. Conversion to sinus rhythm wasobserved in 29 patients during the first 24 h of treatment,leading to a success rate of 64.4%. Five additional patientsconverted to sinus rhythm with continuation of oral amiodarone,(10–15 mg. kg^–1 by day) with a mean delay of 4.2days. A similar population of 27 patients (mean heart rate atentry; 140 ± 3 beats. min^–1) was treated by intravenousamiodarone, given as a bolus infusion of 3–5mg. kg^–1over 30min (mean; 41±02 mg. kg^–1), followed bya continuous infusion of 10–15mg. kg^–1 for 24 h(mean; 11.1±0.7 mg. kg^–1). Eighteen patients convertedto sinus rhythm during the first 24 h of therapy, leading toa success rate of 66.7%. Minor adverse effects of therapy wereobserved in two patients given oral amiodarone, and in sevengiven intravenous amiodarone. No major effect was observed.We suggest that amiodarone given as a single oral loading doseof 25–30mg. kg^–1 body weight is an effective, simpleand well-tolerated therapy, suitable for most patients withrecent-onset ATA.     

Reduction of cerebral blood flow with induced tachycardia in rats and in patients with coronary artery disease and premature ventricular contractions

A reduction of cerebral blood flow (CBF) was observed in experimentalstudies in rats immediately after the onset of parasystolicrhythm or with stable, but haemodynamically compromising, tachycardias.Based on these data and with a view to studying the effectsof premature ventricular contractions (PVCs) on the cerebralcirculation in humans, CBF was measured using the 133-Xenoninhalation method in 24 age matched human controls (group Al:age 58.5 ± 6.2 years; group A2: 52.2 ± 7.8 years)in nine coronary artery disease (CAD) patients without PVCs(B), in 11 CAD patients with frequent PVCs (>300. h^–1)(C) and in nine patients, after exclusion of CAD by angiography,also with frequent PVCs (>300. h^–1) (D). Holier monitoringwas performed during the CBF measurement. CBF determined in the human control groups Al and A2 was 79.9±9.9ml.100g. ^–1min^–1 and 81.5–13.0ml. 100 g^–1min^–1 respectively. CBF was 74.1 ± 13.6 ml. 100g. ^–1min^–1 (P = 0.267 vs Al) in group B, 65.8 ±11.8ml. 100g^–1 min^–1 (P=0.004 vs Al) in group C and74.2 ± 15.6 ml. 100 g.^–1 min^–1 (P=0.218 vsA2) in group D. The significant reduction of CBF in CAD patientswith frequent PVCs suggests that arrhythmias have a significantimpact on CBF. Non-CAD patients with frequent PVCs did not showsignificant CBF decreases in comparison with controls. One canhypothetize that an impairment of electrical postextrasystolicpotentiation, due to premature ventricular depolarization, andhence myocardial dysfunction leads to CBF reduction in CAD patients.The CBF reduction with CAD could also reflect concomitant coronaryand cerebral arteriosclerosis.     

Safety of dobutamine stress echocardiography: A 24 h Holter monitoring study

BACKGROUND: Dobutamine-atropine stress echocardiography is an efficientmethod in the evaluation of patients with coronary artery disease.However, because high-dose dobutamine is potentially arrhythmogenic,the safety of this stress modality has been questioned. METHODS: We performed a 24 h Holter monitoring, before and immediatelyafter this test, in 73 consecutive patients (60 men and 13 women),mean age 60 ± 12 years. Twentyeight patients had hada recent myocardial infarction, 25 had stable chronic angina,10 chronic ischaemic cardiomyopathy and 10 idiopathic dilatedcardiomyopathy. Dobutamine was progressively increased (5–40µg . kg^–1. min^–1) and atropine was injectedin 30 patients. Arrhythmias and ST-segment deviation beforeand after the stress test were evaluated. RESULTS: The mean peak dobutamine dose was 32 ± 11 µg .kg^–1. min^–1. The heart rate at rest and at peakdose was, respectively, 69 ± 16 and 110 ± 28 beats.min^–1. Side effects during the injection of dobutaminewere mainly ventricular (n=14) or atrial (n=4) premature contractions.Three patients had non-sustained ventricular tachycardia andfive had hypotension during the test. No sustained episode ofsupraventricular or ventricular tachycardia was observed duringthe study. Nonsustained supraventricular and ventricular tachycardiaswere detected in 8 and 21 patients before and in 11 and 16 patientsafter dobutamine stress echocardiography (P=ns). AsymptomaticST-segment deviation was observed in two patients before andfour after dobutamine stress echocardiography. An increase intotal ischaemic time (20 vs 102 mn) was observed after the test,but only five patients had ST modifications. A separate analysisof patients with and without beta-blocker did not alter theseresults. In addition, when the occurrence of significant arrhythmiaswas stratified according to a left ventricular ejection fractionthreshold of 45%, we observed no difference in frequency andseverity of cardiac arrhythmias. CONCLUSION: This study demonstrates that dobutamine stress echocardiographydoes not significantly increase arrhythmia during the following24 h. Further studies are required to evaluate the influenceof the test on ST-segment modification during the same period.     

Atrial electrophysiologic properties of patients with asymptomatic Wolff-Parkinson-White syndrome

To evaluate the existence of a peculiar atrial electrophysiologicsubstrate, we studied 18 patients with asymptomatic Wolff-Parkinson-White(WPW) syndrome. These patients were compared with 10 agematchednormal subjects (N). Effective and functional refractory periodswere determined at two right atrial sites (high and low in thelateral wall), during atrial pacing (100 min^–1) and attwice diastolic threshold. Disperson (D) of effective (ERP)and functional (FRP) refractoriness was evaluated as the differencebetween refractory periods at the two atrial sites. WPW patientsshowed significantly lower mean values of effective and functionalrefractoriness at both atrial sites and significantly highermean values of D-ERP and D-FRP. Moreover, in calculating thehighest normal values of D-ERP and D-FRP (as mean values ofN plus 2SD) it was observed that WPW with abnormal values ofD showed a statistically (x² test) higher incidence (100%) ofinduced atrial fibrillation (AF). These findings indicate theexistence of both an abnormal atrial electrophysiologic substrateand of a higher vulnerability in WPW. Finally, AF was inducedgenerally at the site with the lower refractoriness (i.e. lowlateral site). This should be taken into account when consideringhow atrial fibrillation can be induced more easily.     

Assessment of coronary reserve by transoesophageal Doppler echocardiography: Direct comparison between different modalities of dipyridamole and adenosine administration

BACKGROUND: This study was undertaken to compare the coronary vasodilatorresponse to different application modalities of intravenousvasodilators, in order to identify the optimal pharmacologicalprotocol for the evaluation of coronary reserve by means oftransoesophageal Doppler echocardiography. METHODS: Blood flow velocity in the left anterior descending artery,coronary vascular resistance and left main coronary artery cross-sectionalarea were assessed by transoesophageal echo-Doppler during ani.v. adenosine bolus (5 mg), a 5-min adenosine infusion (infusionrate 140µg.kg^–1.min^–1), and low (0·56mg.kg^–1.min^–1),and high-dose (0·84mg.kg^–1.9min^–1) dipyridamoleinfusions in 10 healthy normals (Group 1) and in 20 patients(Group 2) with either coronary microvascular disease (11 patients)or coronary artery disease (nine patients). RESULTS: In both groups, the highest flow velocity and the lowest coronaryvascular resistance were observed during the adenosine infusion.Flow velocity values and indices of coronary vasodilator capacityobserved after the adenosine bolus and the high-dose dipyridamoleinfusion were very close to those obtained during the adenosineinfusion, especially in Group 1. Coronary flow velocity waslower and coronary vascular resistance higher after low-dosedipyridamole, significantly in Group 2. The maximal flow responseto the adenosine bolus was observed within a few seconds afterthe injection, and was very short. The peak response to theadenosine infusion was observed 57±27 s after its start.The coronary flow velocity response to dipyridamole was dosedependent and differed between Groups 1 and 2. CONCLUSION: In combination with transoesophageal Doppler echocardiography,a short-lasting adenosine infusion at a rate of 140µg.kg^–1.min^–1seems to be preferable to an adenosine bolus and dipyridamoleinfusion. The effect of the bolus is too short for an accuratemeasurement of coronary flow velocity, while the dipyridamoleinfusion, especially at a low dose, induces a submaximal vasodilatorresponse.     

Haemodynamic and cardiac metabolic effects of the new {beta}1 agonist prenalterol in patients with cardiac failure

Prenalterol, a ß₁ selective agonist, exerts a positiveinotropic action in animal studies as well as in human volunteersand is effective when administered orally. To assess its immediatehaemodynamic and myocardial metabolic effects, we studied theresponse to prenalterol (50 and 100 µg kg^–1 givenintravenously by cardiac catheterization) in 15 patients withcongestive heart failure secondary to coronary artery diseaseor non-ischaemic cardiomyopathy. At peak effect, cardiac indexincreased from 2.6 ± 0.5 to 3.2 ± 0.81 min^–1m² (mean ± S.D.) (P <0.001); peak rate of left ventricularpressure development rose from 963 ± 242 to 1335 ±411 mmHg s^–1 (P < 0.001); left ventriuclar end-diastolicpressure fell from 25 ± 6 to 17 ± 7 mgHg (P <0.001);coronary sinus blood flow increased from 113 ± 39 to148 ± 55 ml min^–1 (P <0.01); myocardial oxygenconsumption was augmented from 12.7 ± 3.9 to 16.4 ±5.8 ml min^–1 (P < 0.001); and heart rate increasedslightly (from 76 ± 12 to 86 ± 14 beats min^–1;(P <0.05)). No significant changes occurred in left ventricularsystolic pressure, stroke volume index, myocardial lactate extractionrate and myocardial arteriovenous oxygen difference, and nopatients developed angina, ECG changes or ventricular arrhythmias.Infusion of prenalterol effectively improved haemodynamic functionand cardiac metabolism in cardiomyopathy. Therefore this agentdeserves further investigation to evaluate its possible rolefor the long-term therapy of patients with chronic heart failure.     

Influence of the force--frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy

In isolated human myocardium it was shown that a positive force-frequencyrelationship occurs in non-failing myocardium; however, theforce-frequency relationship was found to be inverse in myocardiumfrom failing human hearts. In order to investigate the clinicalrelevance of these experimental findings, the influence of heartrate changes on haemodynamics and left ventricular functionwas studied in eight patients without heart failure and in ninewith failing dilated cardiomyopathy (NYHA II–III). Rightventricular pacing was performed at a rate slightly above sinusrate and at 100, 120 and 140 beats. min^–1 Haemodynamicparameters were obtained by right heart catheterization andby high-fidelity left ventricular pressure measurements. Leftventricular angiography was performed at basal pacing rate andat 100 and 140 beats. min^–1 With increasing heart rate,cardiac index increased in patients with normal left ventricularfunction from 2·9 ± 0·2 to 3·5 ±0·21. min^–1. m^–2 (P<0·01) and decreasedcontinuously in patients with dilated cardiornyopathy from 2·6± 0·1 to 2·2 ± 0·11. min^–1. m^–2 (P<0·05). With increasing heart rate,the maximum rate of left ventricular pressure rise increasedin non-failing hearts from 1388 ± 86 to 1671 ±88 mmHg. s^–1 (P<0·01) and did not change infailing hearts. Ejection fraction decreased from 27 ± 3% to 19 ±2% in patients with dilated cardiomyopathy (P<0·05)when the pacing rate was changed from 84 ± 2 beats. min^–1to 140 beats. min^–1, which was associated with a significantlyincrease in end-systolic volume without significantly changesin end-diastolic volume. In patients with normal left ventricularfunction, when the pacing rate was changed from 85 ±3 beats. min^–1 to 140 beats. min^–1, end-diastolicvolume decreased significantly by 13%, whereas left ventricularend-systolic volume and ejection fraction did not significantlychange. Left ventricular systolic and end-diastolic pressuresdid not significantly change with pacing tachycardia in eithergroup. The frequency-related changes in left ventricular volumesand pressures indicate that the differrent haemodynamic effectsof pacing tachycardia in both groups of patients result predominantlyfrom frequency effects on myocardial function and not from frequencyeffects on preload or afterload. These data indicate that recentexperimental findings of positive force-frequency effects innon-failing and negative force-frequency effects in failinghuman myocardium are relevant for the intact heart.     

The link between acute haemodynamic adrenergic beta-blockade and long-term effects in patients with heart failure: A study on diastolic function, heart rate and myocardial metabolism following intravenous metoprolol

The present study was performed to find possible mechanismslinking the early effects of beta-blockade with the observedlong-term effects in patients with heart failure. In 57 patients with heart failure, 13±3.1 mg of metoprololwas given intravenously. The patients were investigated by invasivehaemodynamics (n = 34), including collection of myocardial metabolicdata during atrial pacing stress (n = 16), by radionuclide angiographyduring physiological atrial pacing (n = 13), and by a bedsideevaluation (n = 10). Diastolic function, measured by early peak filling rate, followedchanges in heart rate, but was similar when heart rate was heldconstant by atrial pacing before and after beta-blockade. Followingbeta-blockade and slower heart rates, diastolic filling volumeswere redistributed to late diastole. Metoprolol induced a paralleldecrease in coronary sinus flow and myocardial oxygen consumption.Myocardial oxygen consumption following beta-blockade decreasedboth during spontaneous rhythm (25±15 to 16±8.8ml. min^–1; P = 0.006), and during atrial pacing stress(30±13 to 23±11 ml.min^–1; P = 0.004). Cardiacindex decreased owing to reduction of heart rate (2.3±1.0to 1.9±0.64 l.min^–1.m²; P = 0.0003), while leftventricular filling pressure was unchanged. Ejection fractionand ventricular volumes were unaltered following atrial pacingor beta-blockade. There was a reflex increase in noradenalineconcentration after beta-blockade injection (0.96±0.66to 1.20±0.91 nmol.l^–1; P = 0.002), whereas myocardialnoradrenaline overflow was unchanged. There was a trend towardsan increase in myocardial lactate consumption after beta-blockadeadministration during atrial pacing stress. It is suggested that the surprisingly good tolerability seenafter acute administration of beta-blockers to patients withsevere heart failure may be explained by prolongation of thediastolic filling phase, which outweighs the negative ino tropiceffects. The reduced myocardial metabolic demand may allow thefailing myocardium to recover and explain the excellent long-termeffect on heart function following beta-blockade treatment.