Conversion of supraventricular arrhythmias to sinus rhythm using flecainide

We evaluated the efficacy of flecainide acetate (given intravenouslyto a maximal dose of2 mg kg^–1 and then orally in a doseof 100 mg b.d. or 100 mg t.d.s.) in the conversion to sinusrhythm of 50 patients exhibiting supraventricular arrhythmias(39 with atrial fibrillation, 6 with atrial flutter, 4 withsupraventricu tachycardia and onewith supraventricular tachycardiain association with the Wolff—Parkinson—White syndrome).Conversion was achieved in 36 patients (72%) (29 cases withatrial fibrillation, 4 cases with supraventricular tachycardia,2 cases with atrial flutter and one case with Wolff—Parkinson–Whitesyndrome), over a mean period of 7.4 ± 9 h. The patientsin which conversion was achieved had arrhythmias which had beenin existence for a shorter time (5.3 ± 9.8 days) thanthose in which conversion was not achieved (16.7 ± 26.2days) (P<0.01). The mean dosage of flecainide used to achieveconversion was 2.5 ± 2.36 mg kg^–1. Flecainide appearsto be an effective agent for the conversion to sinus rhythmof atrial fibrillation and supraventricular tachycardias. Itsefficacy in cases of atrial flutter has not yet been demonstrated.     

Laser catheter coagulation of atrial myocardium for ablation of atrioventricular nodal reentrant tachycardia: First clinical experience

A new technique for ablation of atrioventricular nodal reentranttachycardia, using catheter-directed continuous wave Nd-YAGlaser light, 1064 nm, via a novel pin-electrode laser catheter,was applied in 10 patients aged 15–63 years (mean 43 years).A total of 22 laser pulses, 1–5 per patient, at 20 or30 W, of 10–45 s (mean 27 s) were aimed at the postero-inferioraspect of the tricuspid annulus. In all patients the tachycardia was rendered non-inducible atbaseline as well as during orciprenaline administration. Theamplitudes of the local atrial potentials diminished from 2·0±0·5before to 0·4±0·4 mV after ablation, atrio-Hisintervals increased from 73±7 to 157±36 ms. Anterogradeatrioventricular nodal refractory periods (212+31 vs 238+31ms) and Wenckebach rate (174±8 vs 167±8 beats.min^–1)did not change significantly (P>0·05) There were nocomplications or recurrent arrhythmias in a follow-up of 12–35(mean 27) months. Anatomically guided laser catheter coagulation of the postero-inferioraspect of the tricuspid valve ring is a safe and effective methodfor the cure of patients with common atrioventricular reentranttachycardia.     

Atrial natriuretic peptide response to postural changes in patients with left atrial hypertension

Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate(GMP) and renin activity (PRA) were measured in 13 patientswith mitral stenosis 24 h before and 48 h after balloon valvotomyresulting in a fall in LA pressure from 23.4 ± 2.2 to10.5 ± 0.8 mmHg (P<0.01). Before treatment, plasmaANP was higher during ambulation (128.1 ± 18.5 pg ml^–1)than in the supine posture (93.3± 15.0 pg ml^–1;P<0.01) and did not diminish after return to the erect posture(86.4± 14.1 pg ml^–1). A physiological responsewas restored after valvotomy with ANP plasma levels of 49.2± 7.8pg ml^–1 in the initial ambulant period, 63.1± 12.6 pg ml^–1 in the supine posture and 44.6 ±8.7 pg ml^–1 in the final erect posture. Postural variationsof cyclic GMP were parallel to those of ANP. In contrast, LAhypertension did not abolish PRA postural response. During thethree successive periods of ambulation, supine posture and erectposture PRA was 5.4± 10, 2.8 ± 0.6 and 5.5±1.2ng h^–1 ml^–1, respectively, before treatment,whereas after treatment the values measured were 10.3 ±2.9, 2.3 ± 0.7 and 7.0 ± 2.5 ngh^–1 ml^–1respectively. Variations of plasma ANP, cyclic GMP and PRA inresponse to postural changes were also studied in 10 healthyvolunteers and in 12 uraemic patients with high plasma ANP.Similar physiological results were obtained in these two controlgroups, suggesting that the dysregulation of ANP response inpatients with high LA pressure was not related to the high valuesof plasma ANP. In conclusion, persistent elevation of plasmaANP in response to postural changes appears to be the consequenceof LA hypertension.     

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.     

Acute increase in right atrial pressure by intracardiac stimulation releases atrial natriuretic peptide

We studied the effect of an increase in heart rate and/or inright atrial pressure (RAP) on the release of at rial natriureticpeptide (ANP) in 18 patients. In group 1 (n = 6), right ventricularstimulation (100, 120, 140 and 150 bpm) was used to increaseRA P by asynchronous contraction of the right atrium and ventricle.Mean RA P increased from 3.9 ±0.2 to 8.3±0–6mmHg(mean±SEM). Median ANP levels increased from 120 to 440pgml^–1(P<0.05). In group 2 (n = 6), right atrial stimulation below140 bpm did not have any effect on ANP or RAP, but at a rateabove 140 bpm RAP increased from 5.8 ± 0.5 to 7.5 ±0.5mmHg and ANP from 226 to 396 pg ml^–1 (P < 0.05). Ingroup 3 (n - 6), RA P or ANP were not influenced by continuousright atrial stimulation at 110 bpm. Plasma cyclic GMP levelsparalleled the changes in plasma ANP. Thus, an acute incrementof RAP results in a release of ANP, but acceleration of heartrate alone has no effect on ANP secretion.     

Right atrial contractile performance in patients with myocardial infarction

To evaluate right atrial (RA) contractile performance in patientswith myocardial infarction, we validated a cineangiographicmethod of RA volume measurement, and investigated RA volumechange in ‘normal’ individuals and patients witha previous myocardial infarction. Sixteen silicone rubber RAcasts made from human cadavers were filmed in the postero-anteriorand left lateral projections. The cast volumes calculated followingSimpson's rule were in good agreement with those measured bywater replacement (r=0.992, P<.001). At cardiac catheterization,biplane RA cineangiography was performed in 19 ‘normal’individuals (N group), in 14 patients with a previous antero-septalinfarction (AM1 group) and in seven patients with apreviousinferior infarction (IMI group). The RA volume-time curve wasconstructed at 20–40 ms intervals for one cardiac cycle.RA volume at the beginning of the atrial contraction (RAVd),which was defined as the ‘preload’ of the RA, tendedto be larger in both the AMI and IMI groups compared with ‘normal’individuals. The RA ejection volume was significantly largerin both the AMI (18.4 ± 2.1 ml. m^–2, P <0.01)and IMI groups (l9.4±2.8, P<0.01) than in the N group(14.5±1.9), even for a comparable level of RAVd (rangefrom 26 to 36ml.m^–2) (18.6±2.1, P<0.01, 18.2±2.0,P<0.01, 14.7±1.9, respectively). These results suggestthat RA contraction increases in patients with myocardial infarctionby increasing both the ‘preload’ and ‘contractility’of the RA.     

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.     

Some observations on the mechanism of pressure related atrial fibrillation

In order to investigate the effect of atrial pressure on thepropensity of the atria to fibrillate and the mechanism of thisassociation, the right atrial pressure was changed acutely bytransfusion-bleeding in 12 anaesthetized open-chest dogs. Undervarious atrial pressures the conduction time was measured betweentwo pairs of hook electrodes positioned on the two atrial appendagesrespectively. The effective refractory period was measured bycontinuous pacing of the right atrium at a 250 ms cycle lengthat double threshold intensity and interpolating a progressivelyearlier stimulus after each eighth paced beat. The propensityof fibrillation was studied by rapid (450 min^–1) pacingof the atria at double threshold intensity for 10 s at differentatrial pressures. At a high (14 mmHg) atrial pressure the conductiontime (45.7 ± 14.2 ms) was significantly (P<0.01) longer,the effective refractory period (157.9 ± 15.2 ms) significantly(P<0.01) longer and the atrial fibrillation (11/19 or 57.9%)significantly (X² = 9.95, P<0.001) more common than at alow ( 10 mmHg) pressure (35.2 ± 11.6, 146.2 ±12.4, 3/24 or 12.5%, respectively). Analysis of variance showedthat the probability of atrial fibrillation was significantlyaffected by the atrial pressure but not by either the conductiontime or the effective refractory period The findings suggestthat an increase in right atrial pressure by acute volume overloadprolongs the inter-atrial conduction time and right atrial refractorinessand increases the propensity of the atria tofibrillate by rapidatrial stimulation. The effect of atrial pressure on fibrillationdoes not seem to be mediated by the prolonged atrial refractorinessor conduction time.     

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.     

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.     

Evaluation of atrial vulnerability with transoesophageal stimulation in patients with atrioventricular junctional: Comparison with patients with ventricular pre-excitation and with normal subjects

The aim of our work was to evaluate the inducibility of atrialfibrillation in a group of patients with atrioventricular junctionalreentrant tachycardia and to compare it with that of patientswith a Kent-type ventricular pre-excitation (Wolff-Parkinson-Whitesyndrome) and a control group. One hundred and twenty-five subjects were separated into groups.Group 1 comprised 49 Wolff-Parkinson-White patients, with amean age of 26.4, range 10.66 years; group 2, 51 patients withatrioventricular junctional reentrant tachycardia inducibleby transoesophageal atrial stimulation andlor clinically documented,with a mean age of 43.4, range 16–78 years; group 3, 25control subjects with a mean age of2.64, range 13–76 years. Each subject underwent atrial transoesophageal stimulation withthe following protocol: programmed atrial stimulation with 1and 2 stimuli during atrial pacing of 100. min^–1 and 150.min^–1; atrial stimulation for 10 s at a rate of 200–300–400–500–600.min^–1 with intervals of 10 s between stimulations, fivesuccessive ‘ramp-up’ atrial stimulations for 9 swith the rate increasing from 100 to 800. min^–1 with intervalsof 10 s between stimulations. The end point was the completionof the protocol or induction of sustained atrial fibrillation(>1 min). The chi-square test was used for statistical analysis. Our resultsshowed that in group 1 atrial fibrillation was induced in 27149patients (55.1%); this was sustained in 13149 (26.5%) and non-sustainedin 14149 (28.5%); in group 2, atrial fibrillation was inducedin 22151 patients (43.0%); it was sustained in 7151 (13.7%)and non-sustained in 15151 (29.4%); in group 3, sustained atrialfibrillation was not induced in any subject and in only onesubject was a non-sustained atrial fibrillation (4 s) induced. The chi-square test showed that group 2 vs group 1 were non-significant,while group 2 vs group 3 and group 1 vs group 3 were significant(P<0.003 and P<0.0007, respectively). Therefore group 2 patients showed a greater atrial vulnerabilityin comparison to the control subjects and a similar vulnerabilityto group 1 patients. It is possible that the greater atrialvulnerability in the patients of group 2 was due to the doublenodal pathway.     

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.     

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.     

Age-related transmural peak mean velocities and peak velocity gradients by Doppler myocardial imaging in normal subjects

Doppler myocardial imaging is a new cardiac ultrasound techniquebased on the principles of colour Doppler imaging which candetermine myocardial velocities by detecting the changes ofphase-shift of the ultrasound signal returning directly fromthe myocardium. To determine the normal range of transmuralvelocities in healthy hearts a prospective study was carriedout involving 42 normal subjects (age from 21 to 78, mean 47±16years). Using M-mode Doppler myocardial imaging the peak valuesof the mean velocity and velocity gradient across the left ventricularposterior wall were measured during standardized phases of thecardiac cycle. Peak mean velocities had the following valuesduring the cardiac cycle: isovolumic contraction –1·3±1·2cm.s^–1, early ventricular ejection 4·2±1·2cm.s^–1, late ventricular ejection 1·8±1·1cm.s^–1, isovolumic relaxation –2·0±0·8cm.s^–1, rapid ventricular filling –6·6±2·2cm.s^–1, atrial contraction –2·8±1·8cm.s^–1, atrial relaxation 1·2±1·1cm.s^–1. Peak velocity gradients were: isovolumic contraction1·3±1·9 s^–1, early ventricular contraction4·7±1·9s^–1, late ventricular contraction1·1 ±1·0 s^–1, isovolumic relaxation–0·6±0·5 s^–1, rapid ventricularfilling 6·1±3·4 s^–1, atrial contraction2·6±1·7 s^–1, atrial relaxation 0·0±0·3s^–1. Linear regression analysis showed that with the increaseof age, peak velocity gradient decreases during rapid ventricularfilling (r=0·83; P<0·0001) and increases duringatrial contraction (r=0·86; P<0·0001) whilepeak mean velocity increases only during atrial contraction(r=0·80, P<0·0001). Thus, there was no correlationbetween increasing age and systolic peak mean velocity and peakvelocity gradient but both diastolic filling phases rapid ventricularfilling and atrial contraction demonstrated age-related changes. In summary, this study has determined the age-related rangeof normal transmural myocardial velocities within the left ventricularposterior wall in healthy hearts during the cardiac cycle. Weconclude that these measurements of peak mean velocities andpeak velocity gradients, should form the baseline for subsequentDoppler myocardial imaging clinical studies on myocardial diseasesprocesses.     

Effect of altered loading conditions during haemodialysis on left ventricular filling pattern

Changes in the circulating volume associated with haemodialysisresult in modification of left ventricular loading conditions.To determine the influence of haemodialysis on Doppler indicesof left ventricular filling, 12 patients (mean age 40.8 ±2.7(SEM) years) with renal insufficiency but without overt heartdisease were studied by Doppler-echocardiography immediatelybefore and after haemodialysis. Haemodialysis resulted in adecrease in body weight from 68.0±3.8 kg to 65.0 ±3.7kg (P< 0.01). Heart rate and blood pressure did not changesignificantly during haemodialysis. Left ventricular diastolicdimension (M-mode) decreased from 53.5±1.1 mm to 49.5±1.9mm (P < 0.05), whereas the shortening fraction did not change.Haemodialysis elicited marked changes in the early diastolicrapid filling wave (E wave) recorded by pulsed Doppler at thelevel of the mitral annulus. Peak velocity of the early rapidfilling phase (peak E) decreased significantly from 95.3 ±8.2 cm .s^–1 to 63.0 ±5.7cm .s^–1 (P< 0.001)and mid-diastolic deceleration of transmitral velocity decreasedfrom 437.3 ±54.2 cm . s^–2 to 239.7 ±54.4cm . s^–2 (P<0.01). The peak filling velocity duringatrial contraction (peak A) did not change (79.7 ±6.3cm .s^–1 vs 74.1±4.7 cm.s^–1;P=NS). The ratiopeak E/peak A decreasedfrom 1.19±0.06 to 0.85 ±0.04 (P < 0.01) during haemodialysis. The results providefurther evidence for the pronounced preload-dependence of Dopplerindices of left ventricular diastolic function.     

Felodipine in ventricular dysfunction

The systemic and coronary haemodynamic effects of felodipinewere evaluated at rest and during stress induced atrial pacingin fourteen patients with chronic cardiac failure, secondaryto coronary heart disease. Felodipine was an effective arteriolarvasodilator producing increases in cardiac index from 2.6 ±0.l to 3.5 ± 0.2 l min^–1 m^–2 (P<0.001)and stroke volume 35.3 ± 2.7 to 41.4 ± 2.4 mlbeat^–1 m^–2 (P<0.002). Coronary venous flow also increased significantly (126 ±8 to 168 ± 13 ml min^–1) (P<0.005) and this didnot appear to be accompanied by an increase in myocardial oxygenusage, as myocardial oxygen consumption was essentially unchanged.When the myocardium was stressed by atrial pacing the increasein cardiac output and stroke volume was maintained—25%and 23%, respectively (P<0.01). These results suggest thatfelodipine may well have a significant role in the managementof patients with congestive cardiac failure.     

Left ventricular function in children with the Marfan syndrome

Aortic dilatation and heart valve lesions are common in theMarfan syndrome but whether primary alterations occur in leftventricular (LV) function has not been studied hitherto. LVsize, mass and systolic as well as diastolic function were studiedby M-mode and Doppler echocardiography and cine magnetic resonanceimaging in 22 Marfan children aged 3.0–15.4 years andin 22 age-matched healthy children. No child had significantvalve disease. Heart rate and systolic blood pressure were comparablein the groups but diastolic blood pressure was higher in thecontrols (67 ± 7 mmHg vs 62 ± 8 mmHg, P=0.030).No statistically significant differences were found in LV size,mass or systolic function. The Marfan children had slower LVpeak diameter lengthening rates (106 ± 27 mm s^–1vs 132 ± 29 mm. s^–1, P=0.004), prolonged relaxationtimes (155 ± 22 ms vs 140 ± 19ms, P=0.023), slowerdeceleration of the early transmitral velocity (580 ±144 cm.s^–2 vs 720 ± 160 cm. s^–2, P=0.006),and smaller early-to-late peak velocity ratios (1.99 ±0.40 vs 2.29 ± 0.46, P=0.031). These data indicate thatI.V early diastolic function (relaxation) is impaired in theMarfan syndrome. Weakened elastic recoil due to the underlyingconnective tissue abnormality may best explain this novel observation.     

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.     

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.     

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.