Simultaneous Recording of Atrial and Ventricular Monophasic Action Potentials: Monophasic Action Potential Duration During Atrial Pacing, Ventricular Pacing, and Ventricular Fibrillation

A newly developed transvenous suction electrode was used in dogs to record monophasic action potentials (MAPs) from the right atrium and right ventricle simultaneously. Continuous MAP recordings could be made from the same endocardial site for test periods of 1.5 hours. Left ventricular pacing at increasing heart rates resulted in a statistically significant decrease of right ventricular MAP duration. A high degree of correlation was found between right ventricular MAP duration at 90% of repolarization and the QT interval during both right atrial and left ventricular pacing. At the onset of ventricular fibrillation (VF), right ventricular MAP duration shortened to 25% of the value obtained during left ventricular pacing at a cycle length of 250 ms. A cyclic alternation in amplitude of the right ventricular MAPs was observed during VF. Fast Fourier Transform Analysis of right ventricular MAPs during VF showed a significant dominant frequency at 12 Hz, with no levels of interest beyond this frequency. This observation might prove to be useful in elaborating a new algorithm for the automatic detection of ventricular fibrillation.     

Vasoactive Peptide Release in Relation to Hemodynamic and Metabolic Changes During Rapid Ventricular Pacing

Plasma atrial natriuretic peptide (ANP) concentration increases during ventricular arrhythmias and rapid ventricular pacing but less is known about plasma brain natriuretic peptide (BNP) and endothelin (ET-1). In the present study concentrations of ANP, the amino terminal part of the proANP (NT-proANP), BNP, and ET-1 were measured in the coronary sinus and femoral artery before and at the end of rapid ventricular pacing in 15 patients with coronary arterial disease. The changes were compared with the changes in mean arterial blood pressure, pulmonary capillary wedge pressure (PCWP), transcardiac differences in pH, pCO2, lactate, and norepinephrine. There was an increase in PCWP and a transient decrease in blood pressure after initiation of pacing. Pacing caused a decrease in ST-segment, transcardiac difference of norepinephrine, lactate extraction, pCO2 difference, and an increase in pH difference. Concentration of ANP in the coronary sinus and femoral artery and its transcardiac difference increased during pacing (P < 0.001), whereas changes in NT-proANP were small and BNP and ET-1 levels remained unchanged. The change in transcardiac ANP difference correlated with the change in lactate (r = 0.53, P < 0.05) but not that of norepinephrine, PCWP, or blood pressure. The results show that the plasma concentration of ANP increases more than that of NT-proANP during rapid ventricular pacing. Ischemia-induced release of ANP and its diminished elimination may contribute to the increased plasma ANP level.     

Beat-to-Beat Variability in Stroke Volume During VVI Pacing as Predictor of Hemodynamic Benefit from DDD Pacing

To determine whether the magnitude of Beat-to-Beat variability in stroke volume (SVJ during VVI pacing can predici hemodynamic benefit from DDD pacing, we undertook Doppier recordings of systolic and diastolic LV flow during VVI and DDD pacing in 20 patients (age 54 ± 9 years)with DDD pacemakers implanted due to AV block. SV increased by 19%± 10% from VVI to DDD (P < 0.01). This increase was greater (29%± 9%)in patients with a ratio of early (E)/late (A) filling < 1 compared to those with E/A > 1 (10%± 9%) (P < 0.001). Beat-to-Beat variability in SV was greater in VVI (13%± 8%)compared to DDD (4%± 1%) (P < 0.001). Patients with E/A < 1 showed greater Beat-to-Beat variability in SV during VVI pacing (19 ± 6%)compared to those with E/A > 1 (8%± 4%) (P < 0.001). Beat-to-Beat variability in SV during VVI pacing correlated with both percent change in SV from VVI to DDD (r = 0.89, P < 0.001)and E/A (r = -0.71, P < 0.001). In conclusion, patients with E/A < 1 derive greater hemodynamic benefit at rest from DDD pacing compared with E/A > 1. In addition, patients with complete AV block who show large variations in SV during VVI pacing may obtain greater hemodynamic benefit at rest from DDD pacing than patients with small variations.     

Monophasic Action Potential Duration During Programmed Electrical Stimulation

To examine changes in monophasic action potential duration (APD) with a pacing protocol similar to that used during electrophysiological testing, action potentials were recorded in vivo from the left ventricular apical endocardium of 12 normal mongrel dogs. The atrioventricular node was ablated and the dogs paced from the anterior right ventricle at a baseline cycle length of 1000 ms between interventions. Mean steady-state APD (APDss) was 266 +/- 7 ms at a pacing cycle length (PCL) of 1000 ms. Two pacing protocols were used. The first consisted of a sudden acceleration in pacing from a cycle length of 1000 ms to one between 300 and 600 ms. The second consisted of an 8-beat train at a cycle length of 400 ms followed by a premature beat at a coupling interval of 280 ms followed by a pause. The inter-train pause varied between 1 second and 32 seconds. With a sudden acceleration in pacing rate, steady-state values for APD at the faster PCLs were significantly smaller than APDss at 1000 ms with a change to cycle lengths of 600 ms (247 +/- 29 ms), 500 ms (229 +/- 21 ms), 400 ms (220 +/- 17 ms), and 300 ms (203 +/- 31 ms; P less than 0.01 for all comparisons). The time constant of the change in APD was shorter at a PCL of 300 ms (14.9 +/- 0.8 s) than 600 ms (20.3 +/- 4.7 s; P less than 0.05). With drive train pacing and incorporating an inter-train pause, the percent drop in steady-state APD compared to APD for the first train ranged from 10.1% with a 1-second inter-train pause to 2.1% with a 32-second pause. The difference in APD between the first drive train and drive trains after at least 3 minutes of pacing when APD had stabilized was not significant for an inter-train pause exceeding 8 seconds. In conclusion: (1) with a sudden acceleration in pacing rate, endocardial APD in vivo decreases exponentially. The faster the new rate, the shorter the new steady-state APD and the shorter the time constant. (2) When pacing using an 8-beat drive train and an inter-train pause, there is a decremental shortening in APD for pause lengths shorter than 16 seconds. Thus, while performing programmed stimulation using a pause, a conditioning period of at least 2 minutes should be used prior to diastole scanning to allow APD to achieve a steady state.     

Short-Term and Long-Term Changes of Left Ventricular Volumes During Rate-Adaptive and Single-Rate Pacing

To evaluate the adaptation of the heart to exercise during pacing, 15 patients with permanent endocardial pacemakers were studied; nine patients had atrioventricular universal (DDD) pacemakers (Symbios 7005) and six patients had activity detecting rate-responsive ventricular (VVIR) pacemakers (Activitrax 8403). Left ventricular function in each patient during rate variable pacing was compared to ventricular function during VVI single-rate pacing. End-systolic and end-diastolic volume changes during exercise were measured by radionuclide angiography and the amount of volume change was used to assess left ventricular function. Both short-term (within 4 hours) and long-term measurements (after at least 4 weeks) were made at rest and at 50% of the maximal exercise capacity in DDD or VVIR mode and were compared with VVI single-rate pacing. All patients, when changed from DDD or VVIR mode to VVI single-rate pacing showed a significant increase of the end-diastolic volume during exercise, which increased even more after long-term VVI pacing. During long-term rate variable pacing, there was no increase of the end-diastolic volume during exercise. DDD or VVIR pacing initially showed a substantial increase of the end-systolic volume during exercise combined with a decrease of left ventricular ejection fraction, suggesting a decrease of the left ventricular contractility. After 4 weeks, contractility improved both with DDD and VVIR pacing. We conclude that short-term DDD and VVIR pacing induces a temporary impairment of left ventricular function that improves after 4 weeks, whereas long-term VVI pacing is associated with left ventricular dilatation even at moderate levels of exercise.     

Clinical Significance of QRS Duration During Ventricular Pacing

To clarify the clinical significance of an abnormally prolonged paced QRS duration, we studied 114 patients who had undergone pacing for atrioventricular block (AVB). Patients were divided into two groups: group I consisted of 29 patients with at least one paced QRS duration greater than or equal to 180 msec during the follow-up period; group II consisted of 85 patients with paced QRS durations less than 180 msec. The clinical background, QRS complexes before pacing, and the echocardiographic findings were assessed. Males (P less than 0.05), those with H-V block (P less than 0.05) and a wider QRS complex of conducted and escape beats (both P less than 0.01) were dominant in group I. The incidence of underlying heart disease was greater in group I than in group II (83% vs 32%, P less than 0.01). Reduced left ventricular ejection fraction (LVEF) and increased left ventricular end-diastolic dimension (LVDd) were more prominent in group I than in group II (LVEF 0.49 +/- 0.17 vs 0.68 +/- 0.10, P less than 0.01, LVDd 57.1 +/- 7.9 mm vs 48.5 +/- 5.6 mm, P less than 0.01). The paced QRS duration correlated with LVEF (r = -0.61) and LVDd (r = 0.81). A paced QRS duration greater than or equal to 180 msec was sensitive and specific for a LVEF less than 0.5 (83.3% and 85.2%) and LVDd greater than or equal to 60 mm (100% and 81.4%). We conclude that patients with a prolonged paced QRS duration have more serious heart disease, and the paced QRS duration can be a useful indicator of impaired LV function.     

Relationship of the Effective Refractory Period and Monophasic Action Potential Duration after a Step Increase in Pacing Frequency

Adaptation of effective refractory period (ERP) and monophasic action potential (MAP) shortening after a step increase in drive frequency was determined at adjacent endocardial sites in the right ventricle of six patients without myocardial disease. ERP and MAP shortening occurred simultaneously. ERP shortening and MAP shortening were similar in time course in individuals, although the degree of shortening varied between individuals as the size of the step increase in pacing frequency varied. Shortening of both ERP and MAP was complete after a mean of 67 +/- 7.5 seconds. To allow group analysis, the percent change from baseline of action potential duration and ERP was calculated for each patient at intervals during adaptation and mean percent change for the group plotted against time from the beginning of the step rate increase. A mean step increase in pacing frequency of 49.3% of baseline for the group caused the ERP to shorten by a mean of 18.12%, and MAP90 by 17.43% of baseline. There was no significant difference (P = 0.05) between the action potential and ERP adaptation curves of the group. We conclude that in normal myocardium, there is a close relationship between shortening of ventricular ERP and action potential duration after a change in rate.     

Frequency Dependent Effects of d-Sotalol and Amiodarone on the Action Potential Duration of the Human Right Ventricle

Frequency dependent effects of d-Sotalol (2.0 mg/kg IV, n = 6) and amiodarone (400 mg/day for 3 months, n = 9) were studied on the action potential duration (APD) in 14 patients who underwent electrophysiological testing. Monophasic action potentials were recorded from the right ventricle at five different steady-state paced cycle lengths (700 msec, 600 msec, 500 msec, 400 msec, and 350 msec), and during ventricular extra stimuli with coupling intervals between 300 msec and 1000 msec, before and after d-sotalol and amiodarone, respectively. D-sotalol caused a prolongation of the APD at slow steady-state stimulation rates (11 ± 5% at cycle length of 700 msec), which became attenuated at faster cycle lengths (5 ± 3% at cycle length of 350 msec). Prolongation of APD after amiodarone was independent of pacing rate, e.g., 12 ± 9% at cycle length of 700 msec, and 11 ± 6% at cycle length of 350 msec. Similar frequency dependent prolongation of the APD was observed during abrupt changes of cycle lengths after d-sotalol, whereas amiodarone caused uniform prolongation of the APD at different extrasfimulus intervals. Thus, d-sotalol, a nonselective potassium channel blacker, has reverse use-dependent effects on the human ventricular APD, while amiodarone with greater potassium channel selectivity, has equal ability to prolong the ventricular APD at fast and slow heart rates.     

Transarterial Permanent Pacing of the Left Ventricle

Clinical evaluation of a 64-year-old male patient with a permanent pacemaker showed a right bundle branch block in his ECG that led to the suspicion of catheter misplacement. A two-dimensional echocardiogram and bilateral venogram demonstrated that the pacemaker lead was not in the venous system and that its course was from the axillary artery to the left ventricle passing through the aortic valve. Thirty-three days after implant, replacement of the pacemaker lead through the venous system to stimulate the right ventricular endocardium was performed. At 7 month follow-up the patient has had no complication from his previous arterial pacemaker implantation.     

Comparison of Resting Hemodynamic Indices and Exercise Performance During Atrial Synchronized and Asynchronous Ventricular Pacing

Resting hemodynamic indices and exercise tolerance were measured during atrial synchronized (VAT) and asynchronous ventricular pacing (VOO) in 35 patients with implanted pacemakers which could be externally programmed to function in either pacing mode. Cardiac output and mean systemic arterial pressure were significantly greater during VAT pacing (VAT: 4.5 ± 1.21 /min, 115 ± 28 mmHg; VOO: 3.7 ± 0.8 1/min 105 ± 25 mmHg respectively), although there was no difference in pulmonary artery end-diastolic pressure. Maximal exercise performance was assessed using the Bruce protocol in both pacing modes. Neither the patient nor the supervising physician was aware of the preselected pacing mode; a second physician monitored the electrocardiogram and blood pressure but influenced the point of exercise termination only if a potentially dangerous arrhythmia or hypotension occured. Blood pressure responses were superior and atrial rates lower during VAT pacing, In all but five patients, exercise tolerance was improved by VAT pacing. This amounted to 33 percent or more in 23/35 patients. This improvement was shown to be maintained in the 20 patients who had repeat exercise tests several weeks later. Ventricular arrhythmias, hypotension, and lightheadedness frequently complicated exercise during asynchronous pacing but occurred rarely with atrial synchronized pacing. Resting hemodynamic indices did not predict the extent of improvement gained by physiological pacing.     

Hemodynamic Findings During Sinus Rhythm, Atrial and AV Sequential Pacing Compared to Ventricular Pacing In a Dog Model

The hemodynamic responses of atrial lAF], atrioventricu-lar sequential (AVP) and ventricuJar pacing (VP) were compared to sinus rhythm (SfiJ in seventeen anesthetized dogs with intact AV conduction. The atrium and/or ventricle were paced at fixed rates above the control sinus rate. An AV interval shorter than normal conduction was selected to capture the ventricle. The changes of pulmonary capillary wedge pressure (PCWP, mmHg). mean aortic pressure (MAP, mmHg), cardiac output (CO, L/min), systemic vascular resistance (SVR, dynes/s/cm⁻⁵), left ventricular stroke work index (SWI) and mean systolic ejection rate (MSER, ml/s) during sinus rhythm, atrial pacing and atrio-ventricular sequential pacing (expressed in percentages of the individual values during ventricular pacing) were:
The importance of atrial systole for cardiac performance was clearly demonstrated in dogs with normally compliant hearts. In both atrial and atrioventricular sequential pacing compared to ventricular pacing there was a reduction of pulmonary capillary wedge pressure (PCWP) (p < 0.01) and systemic vascular resistance (SVR) (p < 0.01) despite an increase in cardiac output (CO). The lesser mean systolic ejection rate (MSER) found during atrioventricular sequential pacing compared to sinus rhythm and atrial pacing may be explained by the abnormal ventricular depolarization in this pacing mode; nevertheless, the mean systolic ejection rate was still greater than that found during ventricular pacing (p < 0.05).     

Acute Changes in Left Atrial and Left Ventricular Diameters After Physiological Pacing

The present study examined alterations in left atria! diameter (LAD) and diastolic left ventricular diameter (LVDd) in 37 patients (72.2 ± 9.8 years old) who received physiological pacemakers; 22 with atrioventricular (AV) block and 15 with sick sinus syndrome (SSS). After pacemaker implantation, LAD and LVDd were serially measured using echocardiography, and their diameters ware expressed per body surface area (LADI and LVDdl; mm/m). Pulmonary capillary wedge pressure (PCWP) and cardiac output (CO) were measured in ten patients with SSS and ten with AV block during both right ventricular and AV sequential pacing. After AV sequential pacing, CO increased in 19 of 20 patients (3.2 ± 0.9 L/min to 3.9 ± 1.0 L/min: P < 0.001). LADI decreased from 24.9 ± 4.2 mm/m² to 21.8 ± 4.4 mm/m² (P < 0.001) in 22 patients with AV block and from 24.1 ± 3.4 mm/m² to 20.4 ± 3.8 mm/m² (P < 0.001) in 15 SSS patients. However, LVDdl did not change significantly in either group of patients. The changes in LAD after the implantation of a physiological pacemaker occurred rapidly, i.e. LAD began to decrease within 1 minute after the procedure, and then reached a plateau. This plateau phase continued for at least 7 days during physiological pacing. There was a positive correlation between the changes in LADI after pacemaker implantation and those in PCWP observed during the AV sequential pacing performed prim- to the implantation (r = 0.86; P < 0.001). The reduction in LAD following pacemaker implantation was rapid and seemed to be accompanied by improvement of cardiac function. Thus, it is suggested that the serial measurement of LADI is useful to predict the efficacy of physiological pacemaker implantation.     

Inadvertent Left Ventricle Endocardial or Uncomplicated Right Ventricular Pacing: How to Differentiate in the Emergency Department

Background

Temporary transvenous pacemaker implantation is an important and critical procedure for emergency physicians. Traditionally, temporary pacemakers are inserted by electrocardiography (ECG) guidance in the emergency department because fluoroscopy at the bedside in an unstable patient can be limited by time and equipment availability. However, in the presence of atrial septal defect, ventricular septal defect, and patent foramen ovale, the pacemaker lead can be implanted inadvertently into the left ventricle or directly into the coronary sinus instead of right ventricle. Regular pacemaker rhythm can be achieved despite inadvertent implantation of the pacemaker lead into the left ventricle, leading to ignorance of the possibility of lead malposition.

Noninvasive Beat-to-Beat Arterial Blood Pressure Measurement During VVI and DDD Pacing: Relationship to Symptomatic Benefit from DDD Pacing

To noninvasively assess the hemodynamic effects of VVI and DDD pacing modes we measured beat-to-beat arterial blood pressure during VVI and DDD pacing in 30 patients with complete heart block (CHB), using fingertip photoplethysmography. Of these patients, 15 undertook a double-blind cross-over comparison of the symptomatic effects of VVI versus DDD pacing to determine the relationship between blood pressure changes and the occurrence of symptoms suggestive of the pacemaker syndrome during ventricular pacing. Mean (SD) systolic blood pressure was 11.7 (15.4) mmHg lower during VVI pacing compared to DDD pacing (P < 0.0005). The mean (SD) beat-to-beat variability of systolic blood pressure was 5.20 (2.87%) in VVI mode versus 2.12 (1.07%) in DDD mode (P < 0.0000005). In comparison with DDD pacing, the excess of symptoms experienced by patients during VVI pacing did not correlate with the change in mean systolic blood pressure, but was significantly correlated with the increase in beat-to-beat systolic blood pressure variation during VVI pacing (r = 0.58, P = 0.024). We conclude that noninvasive measurement of fingertip arterial beat-to-beat blood pressure is a rapid and simple method of assessing the hemodynamic effect of VVI pacing. Beat-to-beat blood pressure variability was related to symptomatic intolerance of VVI pacing and may have potential utility as an aid to diagnosis or as a predictor of pacemaker syndrome.     

Hemodynamic Effects of Atrial Synchronization in Acute and Long-Term Ventricular Pacing

The acute and long-term hemodynamic benefit from atrial synchronization in ventricular (VAT) pacing has been investigated at rest and during exercise in 10 patients undergoing pacemaker implantation for complete A-V block. The results were compared to conventional (VOO) ventricular stimulation at rates of 70 BPM and 96 BPM. Cardiac index (CI) in VAT-pacing increased at rest by 8% and during exercise by 15% more than with VOO pacing (p < 0.01). No significant change between the two different rates of asynchronous pacing was observed. CI at rest and during exercise was unchanged after 10 weeks of VAT-pacing. CI is regulated by change of stroke volume in VOO-pacing and by heart rate only with VAT-pacing. In contrast to earlier results with asynchronous ventricular pacing, the hemodynamic benefit of pacing in an atrial synchronized mode is long-lasting. Physiologic mechanisms regulate hemodynamics during exercise and in heart failure. (PACE, Vol. 5, September-October, 1982)     

Relation Between the Pacing Induced Sequence of Activation and Left Ventricular Pump Function in Animals

PRINZEN, F.W., et al. : Relation Between the Pacing Induced Sequence of Activation and Left Ventricu-lar Pump Function in Animals. The main goal of this article was to review animal experimental work on the effect of asynchronous activation on ventricular pump function. During normal sinus rhythm and atrial pacing, the Purkinje system contributes significantly to the rapid electrical activation of the ventricles. In contrast, during ventricular pacing the impulse is almost exclusively conducted through the normal myocardium. As a consequence, electrical activation of the ventricles becomes asynchronous and has an abnormal sequence. The abnormal impulse conduction causes considerable disturbances to occur in regional systolic fiber shortening, mechanical work, blood flow, and oxygen consumption; low values occurring in early activated regions and values above normal being present in late activated regions. Many animal studies have now shown that the abnormal electrical activation, induced by ventricular pacing, leads to a depression of systolic and diastolic LV function. Pacing at the right ventricular apex (the conventional pacing site) reduces LV function more than pacing at the high ventricular septum or at LV sites. In canine hearts with experimental LBBB, LV pacing significantly improves LV pump function. Differences in LV pump function between (combinations of) pacing sites are poorly correlated with QRS duration. Therefore, the cause of the depression of LV function during abnormal electrical activation appears to be a combination of the asynchrony and the sequence of activation. These experimental findings justify continuing attention for optimizing the site(s) of ventricular pacing in patients with normal and abnormal ventricular impulse conduction.     

Atrial Natriuretic Peptide During Different Pacing Modes in a Comparison with Hemodynamic Changes

The study investigates the response of atrial natriuretic peptide (ANP) to different cardiac pacing modes in comparison with hemodynamic changes. Ten patients underwent Swan-Ganz catheterization during pacemaker implant. Atrioventricular and ventricular pacing were performed consecutively at three pacing rate levels (80, 100, and 110 ppm). Blood samples were taken from the pulmonary artery for ANP determination, both basally and at the end of each pacing period. Concomitantly, mean pulmonary capillary wedge pressure (PCWP) and mean pulmonary artery pressure (PAP) were measured. Cardiac output (CO) was determined by thermodilution both basally and during the 110 ppm steps. During atrioventricular pacing, whereas no significant changes were observed for ANP, PCWP and PAP, CO increased significantly (P less than 0.0005). At the beginning of ventricular pacing hemodynamic parameters and ANP levels were comparable with those of baseline conditions. During subsequent ventricular pacing PCWP and ANP increased significantly at the 110 ppm rate step (P less than 0.05). PAP did not change significantly, whereas CO decreased in all cases (P less than 0.01). A positive correlation was observed between ANP and PCWP during ventricular (P less than 0.001), but not atrioventricular pacing. The results, while confirming the hemodynamic advantages of atrioventricular pacing, point to a major stimulation of ANP secretion during ventricular pacing. This fact, together with the observed drop in CO and the correlation between ANP and PCWP, suggest that the increase of ANP in ventricular pacing may be the expression of a compensatory mechanism to the hemodynamic disadvantages of atrioventricular asynchrony.     

实时三维超声心动图评价右室不同部位起搏对左室收缩功能及收缩同步性的影响

目的:应用实时三维超声心动图评价右室不同部位起搏对左室收缩功能及收缩同步性的影响。方法:将行双腔起搏器植入术的20例房室传导阻滞患者按起搏部位的不同分为右室心尖部起搏组(RVA组)和右室流出道起搏组(RVOT组)。两组患者均于术前及术后3个月应用二维及三维超声心动图检查左室容积、射血分数、LV区域壁运动,并比较两组患者的左室收缩功能及收缩同步性指标。结果:术后两组16节段、12节段、6节段达到最小容积时间的最大差值和标准差(Tmsv-dif,Tmsv-dif%,Tmsv-sd,Tmsv-sd%),差异无统计学意义(P0.05),但RVOT组左室收缩同步性高于RVA组(P0.05);两组常规二维超声参数及左室整体收缩功能差异无统计学意义(P0.05)。结论:短期内,右室不同部位起搏不影响左室整体收缩功能和左室收缩同步性。     

Adequacy of Pacing Rate During Exercise in Rate Responsive Ventricular Pacing

Our objective was to determint; the adequate pacing rate during exercise in ventricular pacing by measuring exercise capacity, cardiac output, and sinus node activity. Eighteen patients with complete AV block and an implanted pacemaker underwent cardiopulmonary exercise tests under three randomized pacing rates: fixed rate pacing (VVJ) at 60 beats/min and ventricular rate-responsive pacing (VVIR) programmed to attain a heart rate of about 110 beats/min ar 130 beats/min (VVIR 110 and VVIR 130, respectively) at the end of exercise. Compared with VVI and VVIR 130, VVIR 110 was associated with an increased peak oxygen uptake(VVIR 110:20.3 ± 4.5 vs VVI: 16.9 ± 3.1; P < 0.01; and VVIR 130: 19.0 ± 4.1 mL/min per kg, respectively; P < 0.05) and a higher oxygen uptake at anaerobic threshold (15.3 ± 2.7, 12.7 ± 1.9; P < 0.01, and 14.6 ± 2.6 mL/min per kg; P < 0.05). The atrial rate during exercise expressed as a percentage of the expected maximal heart rate was lower in VVIR 110 than in VVI or VVIR 130 (VVIR 110: 75.9%± 14.6% vs VVI: 90.6%± 12.8%; P < 0.01; VVIR 110 vs VVIR 130: 89.1%± 23.1%; P < 0.05). There was no significant difference in cardiac output at peak exercise between VVIR 110 and VVIR 130. We conclude that a pacing rate for submaximal exercise of 110 beats/min may be preferable to that of 130 beats/min in respect to exercise capacity and sympathetic nerve activity.