Short-term effects of atrial versus atrio-ventricular pacing on myocardial ischaemia in coronary artery disease patients

This investigation was undertaken to evaluate the effects ofshort-term atrial vs atrio-ventricular pacing on myocardialischaemia. The study was in two parts. In part one, 12 coronary arterydisease patients were studied to investigate the effects ofthe two pacing modes on angina pectoris, coronary sinus O₂ saturationand lactate. The two pacing modes were each applied for 5 minat 25 beats. min^–1 more than the maximum heart rate ofthe exercise test. Coronary sinus O₂ saturation and lactatewere estimated before and after pacing. In part two, 13 patientswith left anterior descending coronary artery disease were studiedto investigate the effects of the two pacing modes on coronaryflow reserve, using a Doppler catheter in the above mentionedbranch after the administration of 10 mg intracoronary papaverine.The pacing rate was 15 beats . min^–1 greater than theresting heart rate. Coronary sinus lactate and O₂ saturation changes were the sameand angina pectoris developed at about the same time from thebeginning of pacing under both modes. Coronary flow reservewas 2.1±0.7 during atrial pacing and 2.1±1.1 duringatrio-ventricular pacing (ns). It is concluded that short-term atrial and atrio-ventricularpacing have the same effects on myocardial ischaemia in coronaryartery disease patients.     

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.     

Intravenous isosorbide dinitrate in acute left ventricular failure--a dose--response study

The haemodynamic effects of intravenous isosorbide dinitrate(Cedocard) in patients with severe acute left ventricular failurehave been assessed using incremental infusion rates from 50to 800µmin^–1. For most patients most of the fallin pulmonary arterial diastolic pressure occurred by 200µgmin^–1, with little further fall at higher doses. At 200µgmin^–1pulmonary arterial diastolic pressure fell from 29 to 23 mgHg(P<0.001), there was no significant change in cardiac index(1.9 to 2.0Lmin^–1m^–2) or heart rate (108 to 108beats min^–1). Despite high doses, no side effects wereobserved. Intravenous isosorbide dinitrate is effective and safe in themanagement of acute severe left ventricular failure. In mostpatients an infusion rate of about 200µg min^–1 producesoptimal haemodynamic effects.     

Total sympathetic activity and atrial natriuretic factor levels in VVI and DDD pacing with different atrioventricular delays during daily activity and exercise.

The purpose of the study was to assess at rest and during exercise total sympathetic activity, as expressed by plasma cyclic AMP (cAMP) blood levels and sinus node activity (SNA), as well as atrial natriuretic factor (ANF) blood levels in VVI and DDD pacing with long and short atrioventricular delays in DDD paced patients suffering from complete heart block. Clinical parameters, such as exercise time, and arterial blood pressure (ABP) were also taken into consideration. Thirteen patients (six males, mean age 65 +/- 2 years), were examined randomly in VVI and DDD pacing with 100 and 150 ms atrioventricular delays (AVD). Plasma cAMP and ANF were measured at rest, at peak exercise and 15 and 30 min after the test. The cAMP at rest remained unchanged whatever the pacing mode or the AVD, but 30 min after exercise, the cAMP levels were statistically lower in DDD pacing with short AVD (100 ms) than in DDD with long AVD (150 ms) or VVI pacing (cAMP DDD/100 ms: 16 +/- 0.8 pmol.ml-1, cAMP DDD/150 ms: 20 +/- 2 pmol.ml-1, P < 0.01, cAMP VVI: 29 pmol.ml-1, P < 0.001). ANF plasma levels at rest were significantly higher in VVI pacing than in DDD modes, with either long or short AVD (ANF DDD/100 ms: 93 +/- 10 pg.ml-1, ANF DDD/150 ms: 100 +/- 13 pg.ml-1, ANF VVI: 150 +/- 16 pg.ml-1, P < 0.001, P < 0.03 respectively compared to VVI).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dipyridamole slows the rate of isovolumic pressure fall in patients with normal coronary arteries

Dipyridamole is currently used for thallium imaging and stressechocardiography. The coronary and haemodynamic effects of dipyridamoleare well documented while its effects on left ventricular relaxationremain to be determined. The aim of the present study was toevaluate the effects of dipyridamole on left ventricular relaxationrate in healthy subjects. High fidelity pressure recordingswere obtained at fixed atrial pacing (89 ±2 beats. min^–1)in 10 subjects with normal left ventricular angiography andcoronary arteriograms. Left ventricular pressure was recordedat rest and 5 min after a 4 min infusion of dipyridamole (0.14mg. kg^–1. min^–1). Dipyridamole infusion decreasedleft ventricular systolic pressure (P<0.01) and time to leftventricular systolic pressure (P<0.01)r with no changes inend-diastolic pressure or peak rate of pressure rise. The peakrate of isovolumic pressure fall decreased (from 1957 ±105 to 1488 ± 100 mmHg. s^–1, Y<0.01) and thetime constant of isovolumic relaxation increased (from 37 ±2to 44±3 ms, P<0.02). In conclusion, our study indicatesthat acute administration of clinically relevant doses of dipyridamoledisplays deleterious effects on heart relaxation in healthyhumans.     

Determination of the optimal atrioventricular delay in DDD pacing. Comparison between echo and peak endocardial acceleration measurements.

The goal of this study was to compare two methods determining the optimal atrioventicular delay (AVD) in 19 patients implanted with the BEST-Living system for complete heart block. The definition of the optimal AVD was: the AVD with the echo method that provided the longest diastolic filling time without interruption of the A wave, and the AVD with the peak endocardial acceleration (PEA) method, corresponding to the knee of the PEA curve vs AV delay. The amplitude of the PEA was measured for every AVD programmed via an automatic scanner in steps of 60 to 300 ms (40 ms steps): in the VDD pacing mode with a low base rate, to obtain 100% sensed P waves; in DDD with a base rate = sinus rate + 20%, to obtain 100% paced P waves. Echocardiographic (Echo) measurement of the left ventricular filling time were performed in the same AV delay settings in VDD and DDD as the ones tested in the PEA method, which were manually programmed. The optimal AVDs obtained in DDD and those obtained in VDD were compared in the echo and the PEA tests by a paired Student's t-test. The optimal AVDs obtained by both Echo and by PEA were also compared by a paired Student's t-test in VDD and DDD. The r value of the correlation between the optimal AVDs obtained by Echo and those obtained by PEA was calculated. Similar values of optimal AVD were obtained with both methods. The optimal AVDs given by the Echo technique (179 +/- 25 ms in DDD and 124 +/- 18 ms in VDD) were slightly, but significantly shorter than the ones obtained with the PEA method (202 +/- 21 ms in DDD and 145 +/- 18 ms in VDD, P < 0.05). A highly significant difference between AVD VDD and AVD DDD was found with both methods (P < 0.001). The correlation between the AVDs obtained with the echo and the PEA methods was highly significant (r = 0.78, P < 0.01). Pacemaker software could be modified to determine automatically the optimal AVDs to be applied throughout the heart rate range.     

不同房室间期对双腔起搏左室收缩功能的影响

为探讨双腔起搏不同房室间期对左室收缩功能的影响及最佳房室间期 ,选择 18例置入DDD起搏器的病窦综合征患者 ,在DOO起搏方式下随机将房室 (AV)间期程控为 10 0 ,130 ,15 0 ,170 ,2 0 0ms,在超声心动图下观察左室收缩功能指标 ,每次测量间隔 5min以上。结果 :AV间期为 15 0ms时左室收缩功能最好 ,与AV间期为 10 0ms时相比 ,左室收缩功能明显改善。以心输出量 (CO)为标准 ,18例中有 9例AV间期在 15 0ms时CO最佳 ,5例在 2 0 0ms时CO最佳 ,3例在 170ms时CO最佳 ,1例在 130ms时CO最佳 ;以CO为标准 ,DOO起搏方式最佳AV间期为 16 6±2 4ms。结论 :双腔起搏的AV间期对左室收缩功能有重要的影响 ,以CO为标准 ,个体化地选择双腔起搏的最佳AV间期对改善患者的心脏功能有重要的意义。     

The effect of different atrioventricular delays on left atrium and left atrial appendage function in patients with DDD pacemaker

Background: Although it has been known that optimization of atrioventricular delay (AVD) has favorable effect on the left ventricular functions in patients with DDD pacemaker, the effect of different AVDs on left atrium (LA) and left atrial appendage (LAA) functions has not been exactly evaluated. The aim of the present study was to assess the effect of different AVDs on LA and LAA functions in DDD pacemaker implanted patients with atrioventricular block. Methods: Forty‐eight patients with DDD pacemaker were enrolled into the study. Patients were divided into two groups according to the echocardiographic diastolic function: Group I (normal diastolic function) and Group II (diastolic dysfunction). LAA emptying velocity on pulsed wave Doppler and LAA late systolic wave velocity by using tissue Doppler were recorded. Patients were paced for five successive continuous pacing periods of 10 minutes duration using five selective AVDs (80–250 ms). Results: Significant effect on LA and LAA functions has not been observed by the setting of AVD in Group I. However, when the AVD was gradually shortened form 150 ms to 80 ms, LA and LAA functions gradually decreased in Group II patients. When AVD increased to 200 ms, LA and LAA functions were improved. Further increase in AVD resulted in decreased LA and LAA functions. Conclusion: Setting of AVD has not significant effect on the LA and LAA functions in patients with normal diastolic function, but moderate prolongation of AVD in physiological limits improved LA and LAA functions in DDD pacemaker implanted patients with diastolic dysfunction. (Echocardiography 2011;28:626‐632)     

The effect of atrio-ventricular delay programming in patients with DDDR pacemakers.

Modern DDDR (dual chamber universal, rate responsive) pacemakers are complex, hugely capable devices incorporating new features that theoretically should enhance haemodynamics and therefore quality of life. Ten patients (mean age 48 years) with chronotropic incompetence and high grade A-V block had activity sensing DDDR devices implanted and underwent a randomized double-blind crossover assessment of rate responsive and different fixed atrio-ventricular delay (AVD) settings during 2 weeks of out-of-hospital activity in DDDR mode. Subjective assessment showed improved 'general wellbeing' and preference for 175 ms rate responsive AVD (P less than 0.01) or 125 ms fixed AVD (P less than 0.05). The longest fixed AVD setting (250 ms) was least acceptable and had increased symptom prevalence (P less than 0.02). Perceived exercise capacity and exercise treadmill tolerance was not significantly different at any setting in DDDR mode but was less in DDD mode. Echocardiographically derived stroke distance was greater at 125 ms AVD than 250 ms at 100 b.min-1 (P less than 0.05) but did not differ at slower heart rates at any AVD. Colour Doppler assessed mitral and tricuspid regurgitation was greatest at 250 ms AVD at all heart rates but did not correlate with increased symptomatology. Stroke distance evaluated from the mitral inflow velocity profile allows improved AVD programming during DDDR pacing. Rate adaptive A-V delay is a useful feature during DDDR pacing.     

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.     

Optimal Atrioventricular Delay in CRT Patients Can Be Approximated Using Surface Electrocardiography and Device Electrograms

Electrocardiographic AV Delay Adjustment . Background: Optimization of the atrioventricular (AV) delay (AVD) may result in an improvement in cardiac resynchronization therapy (CRT) outcome. Previous studies have shown positive correlation between interatrial conduction time measured invasively during the implant procedure and optimal AVD determined postimplant using Doppler echocardiography. We hypothesized that the optimal AVD can be predicted noninvasively from surface electrocardiogram (ECG). Methods: The optimal sensed (SAV) and paced (PAV) AVDs were determined for CRT patients (n = 63) by programming different AVDs (in 20 ms steps, in random sequence) and evaluating Doppler images of the mitral flow (iterative method). The time intervals between atrial sensing (As) and pacing (Ap) to the end of the P‐wave (Pend) and to the right ventricular sensing (RVs) were measured from 5 ECG leads (limb, V1, and V3) and device telemetry during sinus rhythm and atrial pacing. Results: Optimal SAV was 120 ± 30 ms and correlated with As‐Pend (R = 0.69, P < 0.0001) and As‐RVs (R = 0.45, P = 0.0003). Optimal PAV was 172 ± 38 ms and correlated with Ap‐Pend (R = 0.65, P < 0.0001) and Ap‐RVs (R = 0.60, P < 0.0001). Regression analysis suggested a simple method of AVD adjustment by pacing the ventricles 40 ms after the end of the sensed P‐wave or 30 ms after the end of the paced P‐wave but not at the expense of biventricular capture. Such a method would have resulted in significantly lower deviation from echo‐optimal AVDs compared with programming fixed values. Conclusion: A simple method of providing 30–40 ms separation between the end of the P‐wave and ventricular pacing pulse can be used to approximate echocardiographically optimal AV delays. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1226‐1232, November 2010)     

Efficacy of flecainide in pacing-induced sustained ventricular tachyarrhythmias: correlation to clinical parameters and tachycardia-characteristics

Seventy-two patients with sustained ventricular tachycardiaor syncope of unknown origin underwent electrophysiologic evaluationbefore and after therapy with flecainide (200–300 mg day^–1).In all patients, sustained ventricular tachycardia or ventricularfibrillation was inducible during control electrophysiologicstudy. During flecainide therapy, sustained ventricular tachycardia(VT) was no longer inducible in 18 patients (25%) whereas in54 patients, VT was still inducible. In five of the latter patients,VT became more difficult to induce (overall efficacy 32%). Therate of VT decreased from 214±49 beats min^–1 duringthe control electrophysiologic study to 178±48 beatsmin^–1 during flecainide (P<0.01). The ERP of the rightventricle increased from 251±27 ms during the controlstudy to 267±34 ms on flecainide (P<0.01). Mean ejectionfraction and mean LVEDP did not differ between responders andnon-responders, yet the presence of a left ventricular aneurysmcorrelated with a lack of antiarrhythmic response to flecainide.VT rate as well as VT morphology during the control study discriminatedbetween responders and non-responders; 11% of patients withVT-rate 230 beats min^–1 responded to oral flecainidecompared with 31% with a VT rate > 230 beats min^–1at control. 26% with induced monomorphic VT responded, comparedwith 100% with induced VF during the control study. 18 of 23responders were discharged on flecainide. During a mean follow-upof 26±18 months, two patients experienced a recurrenceof VT and in one patient, flecainide had to be discontinueddue to side-effects. Thus, the acute efficacy of flecainide, evaluated by serialdrug testing, correlates with haemodynamic parameters and thecharacteristics of tachycardia.     

Arrhythmias and ST segment deviation during prolonged exhaustive exercise (ski marathon) in healthy middle-aged men

To evaluate the occurrence of arrhythmias and silent ischaemiaduring a prolonged exhaustive exercise in cold climate conditions,we monitored 37 healthy middle-aged men (age 40–56 years)who were randomly selected from participants of a ski marathon.Completing the 75–90 km race took 7–12 h. The highestand lowest mean hourly heart rates during skiing were 150 ±9(mean ± SD) and 138 ± 11 beats. Min¹. The maximumheart rate was 161 ±9 beats. min¹, and occurred in mostskiers during the first hour. Ventricular premature complexes(VPCs) were present in 33 of 37 men (89%) with a median frequencyof five beats during skiing (range 0–425). Complex formsoccurred in eight men (22%), and atrial ectopics appeared in33 of 35 participants (94%). The frequency of the arrhythmiasdid not increase over the skiing period At control monitoringduring a representative period the highest mean hourly heartrate was 74 ± 12 beats. min¹ and VPCs were seen in 21men (57%) at a median frequency of one beat during the controlperiod (range 0–338) and complex forms occurred in threemen (8%). Three men had asymptomatic ST segment depression of 0·2–0·3m V lasting 2–10 min during the first hour of skiing.One of them had marginal ST segment depression (0·1 mV) at exercise electrocardiography, but all had normal resultsat exercise thallium scintigraphy and echocardiography. Thus, arrhythmias were significantly (P<0001) increased inmiddle-aged men during exhaustive prolonged exercise as comparedto those observed during a similar period of time of normaldaily life. Transient ST segment depression was found in 8%of skiers at the beginning of the race, although they had notdemonstrated coronary artery disease. This, however may indicatean increased risk during the initial part of the race It is obvious that the risk of cardiac events is increased atthe start of long lasting exhaustive exercise before adaptationto stress, but prolongation of exercise even in cold climatesdoes not increase the risk of arrhythmia or other cardiac complications.However, cold climate conditions and symptoms of respiratoryinfection may increase the risk of cardiac arrhythmias.     

Dopexamine hydrochloride, a {beta}2 adrenergic and dopaminergic agonist; haemodynamic effects following cardiac surgery

Twelve patients recovering from open heart surgery receivedan intravenous infusion of dopexamine hydrochloride, a novelß₂, adrenergic and dopamine receptor agonist. Themean cardiac index increased from 2.58 to a maximum of 3.641 min^–1 m^–2 (P<0401) and the systemic vascularresistance (SVR) decreased from 1527 to 11 I6 dynes cm^–5(P <0.001) at a dose of 3 pg kg^–1 min^–1. Heartrate increased with dose from 85 beats min^–1 to a maximumof 119 beats min^–1 (P<0.001). There was no significantchange in the pulmonary vascular resistance (PVR) with treatmentin the group as a whole. However, PVR decreased (P <0.05)in patients who had aortic-valve replacement ( AVR) only, whereasin patients who had mitral-valve replacement ( MVR) the PVRincreased (P<0.05). We conclude that dopexamine hydrochloridewas well tolerated in patients following cardiac surgery. Itproduced a significant increase in cardiac output with evidenceof afterload reduction and, although the increase in heart ratemay limit its use in some patients, dopexamine hydrochlorideis potentially of value in the treatment of low cardiac outputstate following cardiac surgery.     

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.     

Short-term haemodynamic effects of dopexamine in patients with chronic congestive heart failure

Dopexamine (FPL 60278) is a new dopamine analogue which possessesa combination of dopamine receptor and beta-2-adrenoreceptoragonist properties. The aim of our study was to evaluate theshort-term haemodynamic effects of dopexamine administered byintravenous infusion at different dosage rates. Eight patientswith chronic congestive heart failure were studied. A dose of1 µg kg^–1 min^–1 produced a 27% decrease insystemic vascular resistance index (32.6 to 23.9 res. unitsm², P<0.001 and a significant increase in cardiac index (2.7to 3.61min^–1 m^–2, P<0.001). Stroke volume indexand heart rate increased significantly by 22% and 7%, respectively.An increase in left ventricular stroke work index was also seenat the dose level inducing the maximum cardiac output. Leftventricular filling pressures and arterial blood pressures werenot affected. We conclude that administration of dopexamineto patients with congestive heart failure augments cardiac performanceat rest.     

Coronary reserve, extent of coronary disease, recurrent angina and ECG changes during pain in the in-hospital prognosis of acute coronary syndromes

The prognostic value of recurrent angina, severity of coronarydisease, ECG changes during pain and coronary reserve (ischaemicthreshold measured by atrial pacing: heart rate with ST segmentshift = 1 mm), was evaluated in 383 consecutive patients withacute coronary syndromes. Univariate analysis showed a significantrelationship between occurrence of complications (death, infarctionor coronary surgery) and number of anginal episodes, extentof coronary disease, ischaemic threshold and ST depression withpain. A multivariate analysis indicated that the first threeparameters were the main independent predictors. Coronary reservewas reduced (threshold 150 beats. min^–1) in 83% of patientswho had a myocardial infarction (40), in 91% of those who died(11), in 87% of those who underwent coronary surgery (52) andin 47% of uncomplicated cases (301). Also, a low ischaemic thresholdwas associated with a larger number of anginal episodes thana high threshold ( 130 beats. min^–1, 6.1 ± 5.6vs > 150 beats. min^–1, 2.9± 4.1, P<0.0001),and in complicated patients with one-, two- or three-vesseldisease ischaemic threshold (137.3± 21.2, 133.3 ±18.9, and 135.1 ± 21.2 beats. min^–1, respectively)was lower than in the uncomplicated ones (153.4±20.1,P < 0.005; 148.2± 19.1 P < 0.005; and 139.2 ±23.0 ns, beats, min^–1). A threshold <150 beats. min^–1and ECG changes during pain identified the subset with the highestrisk for complications (59/137, 45%), whereas a threshold >150 beats. Min^–1 and absence of pain or ECG changes duringpain identified those with the lowest risk (5/109, 5%, p <0.001). Thus, our findings document the prognostic significance of coronaryreserve for in-hospital complications in patients with acutecoronary syndromes and confirm the prognostic value of previouslyknown risk markers. They also indicate that some of them maybe significantly influenced by the status of coronary reserve.     

Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation?

The purpose of the study was to evaluate whether infusion ofa beta-adrenergic agonist, prior to and during exercise, couldcompensate for reduced sympathetic stimulation and correct deficientacceleration of left ventricular relaxation, so preventing arise in left ventricular filling pressures during exercise aftercardiac transplantation. Abnormal left ventricular relaxationkinetics can contribute to exercise-induced diastolic dysfunctionof the cardiac allograft. This was demonstrated in transplantrecipients whose acceleration of left ventricular relaxationduring exercise was almost negligible recently and whose elevationof left ventricular end-diastolic pressure was high. Decreasedadrenergic tone due to denervation could be involved in deficientleft ventricular lusitropic response to exercise, because accelerationof left ventricular relaxation during exercise depends on adequatesympathetic stimulation. Serial supine bicycle exercise was performed at an identicalworkload in eight transplant recipients while in the controlstate and during continuous infusion of dobutamine, titratedbefore exercise to achieve a heart rate matching the heart rateat peak exercise in the control state. During control exercise,heart rate rose from 87 ± 8 to 104 ± 12 beats.min^–1 (P<0.05), left ventricular end-diastolic pressurefrom 14 ± 5 to 20 ± 4 mmHg (P<0.05), left ventriculardP/dt_max from 1374 ± 172 to 1854 ± 278 mmHg. s^–1(P<0.05), and cardiac output from 5.8 ± 0.9 to 8.5± 1.11. min^–1 P<0.05). There was a small butsignificant decrease of the time constant of left ventricularpressure decay (T) from 42 ± 6 to 38 ± 6 ms (P<0.05).During dobutamine infusion, exercise resulted in a further increasein heart rate from 108± 11 to 122 ± 17 mmHg (P<0.05),in cardiac output from 7.4 ± 0.9 to 10.3 ± 2.5l. min^–1 (P<0.05), and in left ventricular dP/dt_maxfrom2181 ± 220 to 2620 ± 214 mmHg. s^–1 (P<0.05).These values were higher than the measurements obtained at theend of the control exercise run (P<0.05). T failed to change(29 ± 4 vs 27 ± 5 mmHg, P>0.05) and left ventricularend-diastolic pressure increased from 5 ± 3 to 11 ±5 mmHg (P<0.05) but remained lower than at the end of thecontrol exercise run (11 ± 5 vs 20 ± 4 mmHg, P<0.05). Compensation for reduced sympathetic stimulation by administrationof dobutamine improves exercise haemodynamics in cardiac transplantrecipients, but cannot prevent the exercise-induced rise inleft ventricular end-diastolic pressure and correct deficientacceleration of left ventricular relaxation. Abnormal exercisehaemodynamics after heart transplantation are therefore onlypartly related to deficient sympathetic stimulation.     

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.     

Effects of tilt and exercise on signal-averaged electrocardiogram after acute myocardial infarction

To determine whether enhanced sympathetic activity could altera non-invasive index of cardiac instability, we analysed theeffects of 90° head-up tilt and submaximal exercise stresstest on high amplification signal-averaged electrocardiogramin 64 patients after acute myocardial infarction. At rest, ventricularlate potentials were detected in 25% of patients, characterizedby a significant prolongation of filtered QRS complex (137 ±3vs 115 ±2 ms) and of its components smaller than 40 fiV(38 ±2 vs 16 ±1 ms), as well as by a reduced rootmean square voltage calculated for the terminal 40 ms of QRScomplex (RMS40 voltage) (19 ± 1 vs 75 ± 9µV)in comparison to patients without micropotentials. Sympathetic activation induced by tilt caused a significantincrease in heart rate (from 67 ±3 to 79 ±3 beatsmin^–1) but did not modify either the incidence of ventricularlate potentials or the values of any of the signal-averagedelectrocardiogram parameters considered. In 19 patients, recordingswere also obtained during a submaximal bicycle exercise stresstest at a heart rate of 114 ±4 beats min^–1 andwith systolic arterial blood pressure at 153 ±6 mmHg.No effect on signal-averaged electrocardiogram parameters wasdetectable during this experimental intervention. These data indicate that after myocardial infarction, sympatheticactivation does not seem to modify signal-averaged electrocardiogramparameters.