Decreased Heart Rate Variability in Patients with Congestive Heart Failure and Chronotropic Incompetence

Heart rate variability was studied in 41 patients (aged 48 ± 12 years) with congestive heart failure secondary to idiopathic dilated cardiomyopathy. All patients underwent a treadmill exercise test and 24-hour Holter ECC monitoring. Chronotropic incompetence was defined as the failure to achieve > 80% of the predicted maximal heart rate response given by 220 – age (years) at peak exercise. Spectral heart rate variability was analyzed from 24-hour Holter ECCs and was expressed as total (0.01–1.00 Hz), low (0.04–0.15 Hz), and high (0.15–0.40 Hz) frequency components. The standard deviation of all normal RR intervals (SDNN) was also computed. Chronotropic incompetence was observed in ten patients. Peak oxygen consumption was significantly lower in patients witb chronotropic incompetence compared with those without chronotropic incompetence. The total (5.11 ± 1.26 In [ms²] vs 6.41 ± 0.92 In [ms²]; P = 0.009) and low (3.38 ± 1.65 In [ms²] vs 5.45 ± 1.34 In [ms²];P = 0.003), but not the high (3.42 ± 1.04 In [ms²] vs 4.00 ± 1.12 in [ms²]; P = 0.249) frequency components of heart rate variability were significantly lower in patients with chronotropic incompetence, although there was no significant difference in mean heart rate (88 ± 20 beats/min vs 86 ± 15 beats/min; P = 0.831) or left ventricular ejection fraction (22%± 10% vs 24%± 10%; P = 0.619). SDNN was also significantly lower in patients with chronotropic incompetence compared witb those without chronotropic incompetence (64 ± 34 ms vs 102 ± 37 ms; P = 0.030). Conclusions: The observation that heart rate variability is significantly decreased in patients with congestive heart failure who have chronotropic incompetence suggests that chronotropic incompetence may relate to an abnormal autonomic influence on the heart in these patients.     

Evaluation by Cardiopulmonary Exercise Test of DDDR Versus DDD Pacing

In eight patients (age 62 ± 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited Cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. Results: DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 ± 20 vs 110 ± 27 beats/min, P < 0.02), higher (VO₂ max (25.4 ± 6.1 vs 21.5 ± 7.8 mL/kg/per min, P < 0.03) and higher VO₂ at the anaerobic threshold (20.3 ± 5.0 vs 15.8 ± 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 ± 193 vs 472 ± 216 sec, NS). The increase in VO₂ max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO₂ at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02). In patients with chronotropic incompetence the improvement obtained in DDDR versus DDD was even more significant (VO₂ max = 22.7 ± 5.9 vs 16.1 ± 4.4 mL/kg per min, P < 0.03; VO₂ at the anaerobic threshold = 18.4 ± 5.1 vs 13.2 ± 2.8 mL/kg per min, P < 0.05; exercise time = 438 ± 132 vs 352 ± 150 sec, P < 0.02). In the population as a whole, no significant differences were found relative to subjective symptoms, meanwhile in patients with chronotropic incompetence a better subjective tolerance was apparent with DDDR than with DDD pacing. In conclusion, DDDR pacing induces a significant improvement of exercice capacity, in comparison to DDD pacing, related to the ability to reach higher heart rates during exercise. This phenomenon is particulary evident in patients with chronotropic incompetence in whom DDDR pacing also is subjectively better tolerated.     

Chronotropic incompetence in persons with down syndrome

OBJECTIVE: To investigate the chronotropic response to exercise through peak heart rate and the Chronotropic Response Index (CRI) in participants with Down syndrome (DS) and in nondisabled control participants. DESIGN: Comparative study describing the acute exercise heart rate response. SETTING: University sports medicine facility. PARTICIPANTS: Twenty participants with DS (mean age +/- standard deviation, 24.2+/-3.5y) and 20 control participants without disabilities (age, 21.2+/-2.8y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Maximal treadmill exercise tests with metabolic and heart rate measurements. Maximal heart rate and the CRI were considered main outcomes. RESULTS: The peak oxygen consumption (41.7 vs 31.8mL. kg(-1).min(-1)) and peak heart rate (165+/-14.7 vs 192+/-7.7 beats/min) were significantly lower in participants with DS than in controls (P<.05). The CRI was below normal (.84+/-.25) in participants with DS and was normal (.97+/-.07) in controls. CONCLUSION: Both the CRI and the peak heart rates were indicative of chronotropic incompetence in participants with DS, but not in controls. The CRI of the participants with DS was similar to that reported for nondisabled populations who have a true chronotropic response to exercise. The CRI indicated that the low peak heart rate in our participants with DS was a true chronotropic response.     

Chronotropic incompetence in patients with an implantable cardioverter defibrillator: prevalence and predicting factors

Chronotropic incompetence (CI), which has not been systematically examined in the ICD patient population, may have implications for device programming. A total of 123 ICD patients were classified into three groups: single-chamber ICD with sinus rhythm, dual-chamber ICD with sinus rhythm, and single-chamber ICD with permanent atrial fibrillation. Heart rate response, maximum oxygen uptake, and oxygen uptake at the anaerobic threshold were measured during treadmill exercise testing. In addition, clinical variables such as antiarrhythmic drug therapy, underlying heart disease, and left-ventricular (LV) ejection fraction were recorded. Of the patients studied, 38% were chronotropically incompetent (47/123). Significant predictors of CI were as follows: presence of a coronary disease (P = 0.036), prior cardiac surgery (P = 0.037), chronic drug therapy with beta-blockers (P = 0.032), administration of amiodarone (P = 0.025), and a combination of these two forms of treatment (P = 0.01). Spiroergometry revealed reduced exercise capacity (P = 0.041) and lessened VO2max (P = 0.034) among chronotropically incompetent patients. A large percentage of ICD patients demonstrates CI with subsequently reduced physical stress tolerance. In light of the DAVID study, we believe that a closer examination of rate-adaptive modes for ICD patients is warranted under enhanced conditions: (1) optimized AV interval programming; (2) utilization of new algorithms to reduce ventricular pacing in combination with rate-adaptive atrial pacing, with the goal of addressing CI while minimizing ventricular pacing; and (3) an optimized upper heart-rate limit.     

Temperature May Be an Appropriate Sensor for Chronotropically Incompetent Patients with Postural Syncope

Chronotropically incompetent patients benefit most from sensor driven rate response during exercise. Postural syncope may occur despite the chronotropic response because of the failure of currently available sensors to respond physiologically to postural changes. Seven chronotropically incompetent patients with postural syncope who had a dual chamber rate adaptive pacemaker (Circadia^R) that modulates heart rate in response to temperature change were studied with respect to: (1) response to exercise: and (2) head-up tilt (HUT). During exercise, continuous-wave Doppler of aortic velocities and two-dimensional echocardiographic derived measurements of left ventricular systolic function were used to assess cardiac function. Patients exercised longer (by an average of 168 sec) in the DDDF/compared to the DDl mode (P = 0.013). Increase in exercise duration was due mostly to the sensor driven increase during DDDH pacing. During DDDR pacing, heart rate increased from 71 ± 6 to 121 ± 17 ppm compared to 70 ± 1 to 103 ± 21 ppm for the DDl pacing (P = 0.038). Stroke volume as assessed by Doppler derived stroke distance (SD) contributed more significantly to the cardiac output increase during exercise in the DDl mode (SD increased from 13.4 ± 4 to 18 ± 7 cm in DDl compared to 13 ± 4 to 14 ± 2 cm in DDDR mode), although these mechanisms were insufficient to fully compensate for failure of appropriate chronotropic response. In response to the HUT, right ventricular temperature increased from 36.78°C ± 0.29°C to 36.89±± 0.28°C (P = 0.0002), and heart rate increased from 54 ± 3 to 71 ± 8 ppm (P = 0.0003) in the DDDR mode. No significant change in heart rate occurred in the DDl mode in response to the HUT. Strong positive correlation of temperature and heart rate was noted in all patients in response to HUT (P = 0.001, R²= 0.755–0.976). We conclude that temperature sensor responds physiologically to exercise and HUT. Therefore, temperature sensing rate adaptive dual chamber pacing may be appropriate for chronotropically incompetent patients with posture related syncope.     

Comparison of Low Rate Dual Chamber Pacing to Activity Responsive Rate Variable Ventricular Pacing

A study was undertaken to evaluate exercise performance in 18 dual chamber pacemaker patients believed to be chronotropically incompetent. All patients were paced in a DDD AV synchronous mode at 80 beats per minute (beats/min) as well as an externally triggered, activity responsive VVIR mode. Patients underwent two single blind, randomized symptom-limited treadmill tests (Sheffield protocol). Four of the 18 patients achieved intrinsic rates greater than 100 beats/min and were deleted from the primary study. It was noted that all four of these patients performed best with intrinsic rate response and AV synchrony. Thirteen of the remaining 14 patients demonstrated improved exercise tolerance in the VVIR mode. Average exercise time in the VVIR mode (7:25 +/- 3:12 min) was significantly greater (P less than 0.05) than the DDD mode (6:01 +/- 2:27 min). Work performed was significantly greater (P less than 0.05) in the VVIR mode (4.77 +/- 1.97 METS) than in the DDD mode (3.78 +/- 0.77 METS). Maximum heart rates were 83.86 +/- 5.11 beats/min in DDD mode versus 116.00 +/- 10.56 beats/min in VVIR mode. The results demonstrated that improved exercise tolerance can be achieved with single chamber rate variable pacing compared to DDD pacing in patients with chronotropic incompetence. However, potential symptoms associated with loss of AV synchrony should be ruled out.     

Effect of Chronotropic Response Pattern on Oxygen Kinetics

Background: The sinus node is considered to be the model of chronotropic response for pacemakers that use artificial rate modulating sensors. Maximal metabolic exercise testing with measurement of oxygen consumption (VO₂) is frequently used to evaluate chronotropic response. Since activities of daily living are generally transient and involve submaximal effort, maximal exercise testing may not provide the most clinically relevant method of assessing rate modulation. The purpose of this study was to determine if an abrupt increase in heart rate (HR) at the onset of submaximal exercise provides improved oxygen kinetics compared with a linear response. Methods and Results: Thirteen patients with complete heart block and permanent rate modulating pacemakers implanted following catheter ablation of the atrioventricular junction for refractory atrial fibrillation were chosen for study. The patients first completed a maximal treadmill exercise test using the chronotropic assessment exercise protocol with breath-by-breath analysis of expired gases. The expected HR at 50% of metabolic reserve was calculated for each patient. Three submaximal constant workload exercise tests were then performed at 50% of each patient's metabolic reserve, with the pacemaker randomly programmed to provide three different patterns of chronotropic response: linear (in which HR increased from 70 beats/min to the expected HR at 50% of metabolic reserve), fast(in which HR was abruptly increased to the expected HR at 50% of metabolic reserve), and slow (VVI at 70 beats/ min). Oxygen kinetics were compared for the three patterns of chronotropic response. Cumulative oxygen (O₂) consumption was significantly greater for the fast pattern (3610 mL) as compared with the linear (3487 mL, P = 0.004) or slow pattern (3277 mL). The O₂ deficit was lower for the fast (361 ± 139 mL) than for the linear (539 ± 225 ml, P = 0.003) or slow chronotropic pattern (559 ± 194). Similar improvements in the rate constant of O₂ uptake and Borg perceived exertion scores were observed with the fast chronotropic response pattern. Conclusion: A rapid increase in pacing rate at the onset of exercise improves oxygen kinetics and results in less perceived exertion as compared to a more gradual rate increase that is more characteristic of sinus node behavior.     

Rate Adaptive Cardiac Pacing Using Right Ventricular Venous Oxygen Saturation: Quantification of Chronotropic Behavior During Daily Activities and Maximal Exercise

Central venous oxygen saturation (S_vO_z) closely reflects cardiac output and tissue oxygen consumption. In the absence of an adequate chronotropic response during exercise, S_vO₂ will decrease and the extent of desaturation maybe used as a parameter for rate adaptive cardiac pacing. Eight patients with sinoatrial disease received a DDDR pacemaker capable of DDDR pacing by sensing either S_VO₂ or piezoelectric detected body movement. Both sensors were programmed to attain a rate of about 100 beats/min during walking, and with the lower and upper rates set at 50% and 90% of age predicted maximum, respectively. Chronotropic behavior of the two sensors were compared in the DDD mode with measurement of sensor responses, during everyday activities (walking, stair climbing, postural changes, and physiological stresses) and at each quartile of workload during a continuous treadmill exercise test. During walking at 2.5 mph, both sensors showed no significant difference in delay time (both react within 15 sees) or half-time (S_VO₂= 36 ± 12 sec and activity 24 ± 3 sec; P = NS), although S_VO₂ driven pacing achieved 90% target rate response slowerthan activity sensing (124 ± 16 sec vs 77 ± 10 sec; P < 0.02). S_VO₂ pacing was associated with a more physiological rate response during walking upslope (68 ± 12 beats/min vs 57 ± 10 beats/ min; P < 0.05), ascending stairs (59 ± 10 beats/min vs 31 ± 6 beats/min; P < 0.05), and standing (34 ± 7 beats/min vs 9 ± 2 beats/min; P < 0.05). The S_vO₂ sensor significantly overpaced in the first quartile of exercise (51.8 ± 25.6% in excess of heart rate expected from workload), but the rate was within 20% of expected for the remainder of exercise. “Underpacing” was observed with the activity sensor at the higher workload. In conclusion, the S_vO₂ sensor demonstrated a more physiological response to activities of daily living compared with the activity sensor. Using a quantitative method, the speed of onset of rate response of the S_vO₂ sensor was comparable to activity sensing, and was more proportional in rate response. Significant overpacing occurs at the beginning of exercise during S_VO₂ driven pacing, which may be improved with the use of a curvilinear algorithm.     

Rate Adaptive Atrial Pacing in the Bradycardia Tachycardia Syndrome

In 42 patients (26 men, 16 women; mean age 69 ± 10 years), who were paced and medicated with antiarrhythmic drugs for the bradycardia tachycardia syndrome, chronotropic response and AV conduction with rapid atrial pacing during exercise were studied. Patients were included if they had no second- or third-degree AV block, no complete bundle branch or bifascicular block, and a PQ interval ≤ 240 ms during sinus rhythm at rest. The interval between the atrial spike and the following Q wave (SQ) was measured in the supine position at rest with an AAI pacing rate of 5 beats/min above the sinus rate (SQ-R+5), and at the end of exercise with 110 beats/min (SQ-E110). Bicycle ergometry was performed using the Chronotropic Assessment Exercise Protocol with the pacemakers being programmed to AAI with a fixed rate of 60 beats/min. Chronotropic incompetence was defined as peak exercise heart rate: (1) < 100 beats/min; (2) < 75% of the maximum predicted heart rate; or (3) the heart rate at half the maximum workload < 60 + 2 beats/min per mL O₂/kg per minute (calculated O₂ consumption). During exercise, one patient developed atrial fibrillation. Chronotropic incompetence was present in 71 % (29/41) of the patients according to definition 2, and in 76% (31/41) according to definition 1 or 3. Ten out of 41 patients (24%) exhibited a second-degree AV block with atrial pacing at 110 beats/min at the end of exercise. Only 9 out of the remaining 31 patients (29%) showed a physiological adaptation of the SQ-E110, and 21 patients (68%) exhibited a paradoxical increase of the SQ interval with rapid atrial pacing at the end of exercise as compared to the SQ-R+5. These observations indicate that the pacing system to be used in most patients paced and medicated for the bradycardia tachycardia syndrome should be dual chamber, and the option of rate adaptation should be considered.     

Rate Modulated Pacing Based on Right Ventricular dP/dt: Quantitative Analysis of Chronotropic Response

Right ventricular contractility increases in response to catecholamine stimulation and greater ventricular preload, factors that increase with exercise workload. Thus, the maximum systolic dP/dt may be a potentially useful sensor to control the pacing rate of a permanent pacing system. The present study was designed to test the long-term performance of a permanent pacemaker that modulates pacing rate based on right ventricular dP/dt and to quantitatively analyze the chronotropic response characteristics of this sensor in a group of patients with widely varying structural heart diseases and degrees of hemodynamic impairment. A permanent pacing system incorporating a high fidelity pressure sensor in the lead for measurement of right ventricular dP/dt was implanted in 13 patients with atrial arrhythmias and AV block, including individuals with coronary artery disease, hypertension, severe obstructive pulmonary disease with prior pneumonectomy, atrial septal defect, dilated cardiomyopathy, restrictive cardiomyopathy, and mitral stenosis. Patients underwent paired treadmill exercise testing in the VVI and VVIR pacing modes with measurement of expired gas exchange and quantitative analysis of chronotropic response using the concept of metabolic reserve. The peak right ventricular dP/dt ranged from 238–891 mmHg/sec with a pulse pressure that ranged from 19–41 mmHg. There was a positive correlation between the right ventricular dP/dt and pulse pressure (r = 0.70, P = 0.012). The maximum pacing rate and VO_2max were 72 ± 6 beats/min and 12.61 ± 4.0 cc O₂/kg per minute during VVI pacing and increased to 124 ± 18 beats/min and 15.89 ± 5.9 cc 0₂/kg per minute in the VVIR pacing mode (P < 0.0003 and P < 0.002, respectively). The integrated area under the normalized rate response curve was 96.7 ± 45.7% of expected during exercise and 100.1 ± 43.4% of expected during recovery. One patient demonstrated an anomalous increase in pacing rate in response to a change in posture to the left lateral decubitus position. Thus, the peak positive right ventricular dP/dt is an effective rate control parameter for permanent pacing systems. The chronotropic response was proportional to metabolic workload during treadmill exercise in this study population with widely varying forms of structural heart disease.     

Relationship Between Heart Rate and Oxygen Kinetics During Constant Workload Exercise

Background: Oxygen uptake during constant workload exercise increases exponentially from its resting value before reaching a steady state. The difference between the actual rate of oxygen consumption at the onset of exercise and the steady state is an oxygen deficit. Similarly, the normal sinus node increases its rate at the onset of exercise before achieving a steady state, thereby producing a heart rate deficit. The purpose of this study was to test the hypothesis that elimination of the heart rate deficit by an instantaneous increase in heart rate at the onset of constant workload exercise to the steady-state level would reduce the oxygen deficit and improve the perceived difficulty of exertion as compared with the chronotropic response of the normal sinus node. Methods and Results: Ten subjects with normal sinus node function who had DDD pacemakers implanted for A V block completed a symptom-limited maximal treadmill exercise test using the Chronotropic Assessment Exercise Protocol (CAEP) to assess sinus node function, maximal heart rate, and VO_{2 max}. The subjects then performed constant workload exercise tests (6-min duration) at a workload equal to approximately 50% of metabolic reserve with the pacemaker randomly programmed to each of three patterns of chronotropic response: (1) DDD (lower rate 60 beats/ min); (2) Fast (lower rate abruptly programmed to the expected value at 50% metabolic reserve); and (3) Overpaced (lower rate at least 80% of the age predicted maximum). The oxygen deficit was lower with the fast chronotropic response (434 ± 238 ml O₂) than with either the DDD (512 ± 233; P = 0.02), or overpaced chronotropic patterns (488 ± 238; P = 0.02 vs fast). The rate constant for change in VO₂ was highest with the fast chronotropic pattern (2.85 ± 1.38) compared with either the DDD (2.25 ± 0.64; P = 0.01) or overpaced (2.38 ± 0.43; P = 0.02) patterns. The Borg perceived exertion rating was lowest with the fast chronotropic response (P = 0.02 vs DDD and P = 0.02 vs overpaced). Conclusions: The results of this study suggest that oxygen kinetics and exertional symptoms are improved by an abrupt increase in pacing rate at the onset of exercise to a value that is appropriate for metabolic demand as compared with the DDD pacing mode in patients with normal sinus node function. In contrast, an overly aggressive chronotropic response was not associated with improved oxygen kinetics or exertional symptoms.     

Relationship Between Atrioventricular Delay and Oxygen Consumption in Patients with Sick Sinus Syndrome: Relevance to Rate Responsive Pacing

To develop a dromotropic-controlled rate adaptive algorithm for patients with sick sinus syndrome (SSS) and intact AV conduction, 14 pace-maker patients with SSS underwent cardiopulmonary exercise testing (CPX). During exercise, the pace-maker was programmed in an AAT mode without rate adaptation, whereby 3 patients developed supraventricular arrhythmia and 11 patients kept sinus rhythm. Chronotropic incompetence (CI) at heart rate (HR) < 95 beats/min at the anaerobic threshold (AT) was found in five patients. In patients with chronotropic competence (CC), the HR increase was significantly greater than in CI patients (rest: 73.2 +/- 12.6 vs. 64.2 +/- 4.0 beats/min;AT:101.2 +/- 6.2 vs. 82.0 +/- 5.1 beats/min;peak: 135.2 +/- 10.7 vs. 103.2 +/- 10.9 beats/min). There was no significant difference in the AVD between CC and CI patients (rest: 167.7 +/- 38.6 vs. 170.8 +/- 22.5 ms, AT: 156.2 +/- 30.7 vs. 163.6 +/- 21.6 ms, peak: 144.7 +/- 29.0 vs. 152.4 +/- 15.0 ms). The correlation coefficient between HR increase and VO2 was +1.0 and between AVD decrease and VO2 - 1.0 in both groups. An increase in pacing rate from 75 beats/min to 120 beats/min without exercise (overpacing) led to a prolongation of the AV interval of about 30.6 +/- 14.2 ms. Based on this closed loop control with negative feedback, a dromotropic rate adaptive algorithm for patients with SSS and intact AV conduction could be developed.     

Improvement of exercise tolerance by single lead VDD pacemaker: evaluation using cardiopulmonary exercise test

We used a cardiopulmonary test to assess the physiological benefit of single lead VDD pacing in ten patients (six men, four women; aged 32-84 years, mean 69 years) with atrioventricular block. Maximal symptom-limited treadmill exercise test using a ramp protocol was performed under VDD and VVIR or VVI pacing (VVI) in random sequence. The pacemaker was then programmed to the VDD mode, and Holter ECG was recorded in nine patients. Compared with findings during the VVI, the VDD mode had a greater chronotropic response (mean maximal heart rate, VDD 106 +/- 17 beats/min vs VVI 79 +/- 19 beats/min, P = 0.03), and was associated with prolongation of exercise duration (VDD 11.2 +/- 2.9 minute vs VVI 10.5 +/- 3.1 minute; P = 0.01), and the onset of anaerobic threshold at a higher oxygen uptake (VDD 12.4 +/- 3.4 mL/min per kilogram vs VVI 10.0 +/- 2.1 mL/min per kilogram; P < 0.01). Atrial sensing was recognized in almost all normal sinus P waves for all cases examined using Holter ECG. Thus, chronotropic response during exercise by VDD pacemaker improved exercise tolerance, indicating that a VDD pacemaker might be useful for patients requiring physical activity.     

Aerobic Capacity in Rate Modulated Pacing

Whether heart rate or AV synchrony is the most important factor for an increase in aerobic capacity was evaluated in a comparative study between sinus bradycardia, VVIR, DDD, and DDDR stimulation. Sixteen patients (mean age 67 years) with chronotropic incompetence and impJanted DDDR pacemaker (Telectronics META 1250) were randomly studied by cardiopulmonary exercise testing. All patients were exercised to their anaerobic threshold (ATJ with the following heart rates: DDD 84 ± 3, WIR 110 ± 5, and DDDR 116 ± 6 beats/min. Mean oxygen uptake (VO₂, mL/kg per min) at AT was 7.4 ± 0.3 in DDD and WIR modes. A 12% increase was measured in DDDR mode (8.3 ± 0.4). Compared to VVIR work capacity in the DDDR mode was improved by 17% (41 vs 48 W/min). In patients with isolated sinus node disease (n = 9) the increase of VO₂ and work capacity at AT during DDDR mode was more pronounced (16% and 20%, respectively, compared to VVIR). In patients with intermittent second or third degree AV block (n = 7) the differences between the pacing modes were not significant. This might partly be due to a lesser degree of chronotropic incompetence in this subgroup. In conclusion only the conjunction of heart rate increase and preservation of AV synchrony provides a significant improvement in aerobic capacity during exercise.     

Chronotropic incompetence and abnormal heart rate recovery early after left ventricular assist device implantation

Background: Chronotropic response to exercise and heart rate recovery immediately after exercise (HRR₁) are valid prognostic markers in patients with chronic heart failure (CHF). The aim of this study was to evaluate heart rate profile during and after exercise in CHF patients early after left ventricular assist device (LVAD) implantation. Methods: We enrolled seven stable consecutive CHF patients (five males, mean age: 45 ± 16 years) after 1 month of LVAD (HeartMate II; Thoratec Corp, Pleasanton, CA, USA) implantation, seven healthy subjects, and 14 patients with advanced HF (HF control group) who performed an incremental symptom‐limited cardiopulmonary exercise testing (CPET). CHF patients performed CPET at 1 and 3 months after LVAD. HRR₁ was defined as the HR difference from peak to 1 minute after exercise and chronotropic response to exercise as the chronotropic reserve ([CR, %]=[peak HR‐resting HR/220‐age‐resting HR]× 100). Results: LVAD patients 3 months after implantation had a significantly different HR profile during exercise compared to healthy controls, with significantly lower CR (57 ± 31 vs 90 ± 14, %, P < 0.001) and HRR₁ (14 ± 6 vs 28 ± 8, bpm, P < 0.01). HR profile during exercise did not significantly change 1 and 3 months after LVAD implantation. There was no statistical difference compared to HF control group and LVAD group regarding cardiopulmonary parameters. Conclusions: LVAD patients present an impaired CR and an abnormal HRR₁ after implantation, indicating significant cardiac autonomic abnormalities. These alterations seem to remain unaltered 3 months after LVAD implantation. (PACE 2011; 34:1607–1614)     

The Effect of Maximum Heart Rate On Oxygen Kinetics and Exercise Performance at Low and High Workloads

The normal heart rate is lineurly related to oxygen consumption during exercise. The maximum heart rate of the normal sinus node is approximated by the formula: HR_max= (220-age) with a variance of approximately 15%. However, the nominal upper rate of most permanent pacemakers is 120 beats/min, a value that remains unchanged for many patients. As this nominal setting falls well below the maximum predicted heart rate for most patients, it is possible that the chronotropic response of rate adaptive pacemakers during moderate und maximal exercise workloads may be less than optimal. The purpose of this study was to determine the effect of the upper programmed rate on oxygen kinetics during submaximal exercise workloads and maximum exercise performance during symptom-limited treadmill exercise. Exercise performance with an upper rate programmed to 220-age was compared with an upper rate of 120 beats/min. Eleven patients (5 men and 6 women, mean age 54 ± 10 years) with complete heart block following catheter ablation of the atrioventricular junction for refractory atrial fibrillation who were implanted with permanent, rate-modulating VVIR pacemakers comprised the study population. The rate adaptive sensors were based on activity in 8 patients, minute ventilation in 2 patients, and mixed venous oxygen saturation in 1 patient. After performing a symptom-limited treadmill exercise test to determine maximum exercise capacity and to optimize programming of the rate adaptive sensor, each subject performed two treadmill exercise tests in random sequence with a rest period of at least 1 hour between tests. During one of the tests the upper rate was programmed to a value calculated by the formula: HR_max= (220-age). During the other exercise test the upper rate was programmed to 120 beats/min. Patients were blinded as to their programmed values and to the hypothesis of the study. A novel treadmill exercise protocol was used that consisted of a 6 minute, constant-workload phase at approximately 50% of maximum workload followed immedictely by incremental, symptom-limited exercise using a modified Chronotropic Assessment Exercise Protocol (CAEP) with 1 minute stages until peak exertion. Breath-by-breath analysis of expired gases was performed with subjective scoring of exertional difficulty at the end of the constant workload phase and during each stage of incremental exercise using the Borg Perceived Exertion Scale. Exercise duration was significantly longer (6.37 ± 47 vs 611 ±48 seconds. P < 0.005) with the higher programmed upper rate. Oxygen kinetics were also significantly improved with an age predicted upper rate with a lower O₂ deficit (258 ± 88 vs 395 ± 155 ml, P = 0.002) and higher VO₂ rate constant (3.6 ± 1.0 vs 2.4 ± 0.7. P < 0.001.). The V0_2maxduring peak exertion was higher with an age predicted upper rate than with an upper rate of 120 beats/min (1807 ± 751 vs 1716 ± 702 mL/min, P = 0.01). The mean Borg score was lower during the last common treadmill stage during maximum exercise with an age predicted upper rate than with an upper rate of 120 beats/min (15.7 ± 2.0 vs 16.5 ± 1.9. P = 0.04). The mean Borg score during submaximal. constant workload exercise was also lower with a higher upper rate (9.0 ±2.5 vs 9.6 ± 2.2, P = 0.10). Programming the upper rate of rate adaptive pacemakers based on the age of the patient improves exercise performance and exertional symptoms during both low and high exercise workloads as compared with a standard nominal value of 120 beats/min.     

Incidence and Significance of Chronotropic Incompetence in Patients with Indications for Primary Pacemaker Implantation or Pacemaker Replacement

This prospective study was undertaken to evaluate the incidence and significance of chronotropic incompetence in 211 patients [age 71.1 6 10.6 years (mean 6 SD)] by means of maximum exercise test in order to determine the indication for rate-responsive pacing before primary pacemaker implantation (147 patients) or pacemaker replacement (64 patients). There were 112 (53%) patients with second- or third-degree AV block, 63 (30%) with sick sinus syndrome, and 36 (17%) with chronic atrial fibrillation. Chronotropic incompetence was defined as maximum heart rate lower than age-adjusted norm calculated by the formula: 0.7x(220 - age) and its significance as the difference between the two rates. The overall incidence of chronotropic incompetence was 42%. The incidence was significantly higher in patients with atrial fibrillation (67%, P<0.0005) and sick sinus syndrome (49%, P<0.012) than in those with AV block (30%). The mean difference between maximum heart rate and the age-adjusted norm was 18% (range 2%-63%). The mean difference was significantly higher in patients with atrial fibrillation (27%, range 8-63%) than in those with sick sinus syndrome (19%, range 2%-45%, P<0.01), or with AV block (12%, range 6%-26%, P<0.000001). The rate-responsive pacemakers were implanted in 44% of 211 patients studied and in 43% of 196 patients excluded from the study due to the apparent (contra)indication of rate-responsive pacing (NS). Thus, chronotropic incompetence seems to be common in the pacemaker patient population. The highest incidence and significance was found in patients with chronic atrial fibrillation. Systematic evaluation of chronotropic competence can double the rate of implantation of rate-responsive pacemakers; however, further studies are needed to clarify relation between the significance of chronotropic incompetence and functional benefit of rate-responsive pacing.     

Assessment of pacemaker chronotropic response: implementation of the Wilkoff mathematical model

There are few practical guidelines for proper adjustment of rate responsive pacemaker sensor parameters. This study describes the application of the chronotropic assessment exercise protocol (CAEP) and the Wilkoff model of chronotropic response to assess the adjustment of pacemaker sensor parameters. In 31 patients implanted 1 month previously with a dual sensor pacemaker, pacemaker sensor parameters were adjusted to yield a peak sensor rate of 100 beats/min on a simple 6-minute walk (low intensity treadmill exercise [LITE] protocol); the maximum sensor rate was set to the age predicted maximum heart rate (220-age). The rate response behavior of the pacemaker was then assessed using the slope of metabolic-chronotropic relation (MCR) during CAEP exercise. After adjustments based on the LITE protocol, CAEP exercise yielded MCR slopes of 0.92 +/- 0.25 for the entire study group, which compares well with the predicted normal slope of 1. However, 7 of the 31 patients had sensor MCR slopes during CAEP exercise that were 2 SD or more below expected. To test the sensitivity of this approach to suboptimal pacemaker programming or suboptimal exercise, simulations were performed with the maximum sensor rate programmed below age-predicted maximum heart rate or with exercise truncated before maximum exertion; with these conditions, MCR slopes were sharply lower for the entire group. The authors conclude that a simple treadmill walk (LITE) allowed for optimum programming of sensor parameters in most patients, but in a minority the chronotropic behavior was underresponsive. Failure to appropriately adjust pacemaker maximum sensor rate or failure to achieve peak exercise sharply limits the accuracy of this methodology.     

Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty-two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom-limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night-time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free-living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI-; -35.1 +/- 8.7% versus -26.1 +/- 10.7%; P<0.05). Obviously, patients with a lower body mass index (BMI < 16 kg m(-2), n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo(2), and a lower maximal O(2) pulse (P<0.05). BMI was significantly correlated to peak Vo(2), maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.     

Chronotropic Response to Exercise in Patients with Atrial Fibrillation

The exercise chronotropic response of patients with chronic atrial fibrillation requiring pacemaker therapy for bradycardia was assessed to characterize the chronotropic response and identify patients who would potentially benefit from a rate adaptive pacemaker. The population consisted of all patients who received a VVI pacemaker between January 1980 and November 1987 who underwent exercise tolerance testing (n = 130) and were in atrial fibrillation (n = 19). There were 11 males and 8 females with a mean age of 62 +/- 14 years. Left ventricular function was normal in eight patients, mildly impaired in three, and severely impaired in two. Long-term medications were continued until the morning of the test; digoxin 73%, beta blockers 21%, calcium channel blockers 26%, and nitrates 21%. Maximal exercise tolerance tests were performed. Parameters assessed were: (a) heart rate at rest, the end of each stage, and at peak exercise; (b) percent heart rate reserve per stage; and (c) percent metabolic reserve per stage. Results were compared to 100 normal subjects on no medications and without evidence of medical illness or cardiac disease. Heart rates were depressed in 58% of the study patients (21% early, 53% late) and elevated in 74% (74% early, 32% late). All 19 (100%) patients had abnormal heart rate responses at some point during the exercise test. Only four patients (21%) had a response within one standard deviation from the mean of the normal population during either the early or late segment of the exercise test. Patients in chronic atrial fibrillation requiring pacemakers for bradycardiac support at rest have an abnormal chronotropic response to exercise.(ABSTRACT TRUNCATED AT 400 WORDS)