First Derivative of Right Ventricular Pressure, dP/dt, as a Sensor for a Rate Adaptive VVI Pacemaker: Initial Experience

Ten patients underwent implantation of a rate adaptive ventricular pacing system with a new pulse generator and lead. The unipolar lead has a steroid eluting tip and a pressure sensor. The first derivative of the signal from this sensor, dP/dt, is determined and the pacemaker rate is varied in response to changes in the right ventricular dP/dtMAX. During implantation, dP/dt values were in the range of 180-720 mm Hg/sec. The autothreshold for pacing at 2.5 V remained unchanged 1 month after implantation (0.065 +/- 0.045 msec, range 0.05-2.00 msec) and only slightly increased after 3 months (0.075 +/- 0.045 msec, range 0.05-2.00 msec). A significant correlation existed between the dP/dt measured during implantation and the right ventricular pressure measured by telemetry at follow-up visits (r = 0.93, P = 0.0001). Initial pacemaker programming was performed on the second day after implantation following a short walk and was adjusted subsequent to follow-up visits according to the patient's subjective assessment and in accordance with the results of exercise tests and Holter monitoring. Exercise and Holter tests did not significantly change initial programming. There was a significant correlation between right ventricular systolic pressure and the rate response setting (r = -0.66, P less than 0.05). During dP/dt pacing, all patients felt well, and eight of these reported an improvement compared to nonrate adaptive pacing. The heart rate response to effort and recovery was appropriate. It was concluded that: (1) right ventricular dP/dt is a suitable parameter for controlling the pacing rate; (2) appropriate programming of the dP/dt pacemaker results in a suitable heart rate response to exercise and recovery.     

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.     

Development of a Rate Adaptive Pacemaker Based on the Maximum Rate-of-Rise of Right Ventricular Pressure (RV dP/dtmax)

The maximum rate of rise of right ventricular pressure (RV dP/dtmax) may change in response to physiological stress and thereby provide an appropriate parameter upon which to base rate adaptive pacing. Initial feasibility testing was carried out in six patients using externally closed loop rate adaptive pacing with a pressure sensing lead (Model 6220) and an investigational VVI pulse generator (Medtronic, Model 2451). During exercise, maximum positive RV dP/dtmax increased from 223 +/- 55 to 405 +/- 181 mmHg.sec.1 (P less than 0.05). Based on these results, rate adaptive pulse generators using maximum positive RV dP/dt were implanted in 12 patients (Medtronic, Model 2503). Exercise treadmill testing in the VVI mode resulted in heart rates ranging from 69 +/- 6 beats/min at rest to 79 +/- 14 beats/min (n = 12; P greater than 0.05). In contrast, VVIR mode pacing rates ranged from 71 +/- 11 beats/min to 115 +/- 24 beats/min (n = 17; P less than 0.05). Holter recording showed heart rates ranging from 51 +/- 6 to 110 +/- 22 beats/min during activities of normal daily living (n = 9; P less than 0.05). Passive postural tilt resulted in rates of 69 +/- 8 beats/min in the supine position increasing to 74 +/- 14 beats/min with 60 degrees upright tilt (n = 16; P greater than 0.05). With up to 5-year follow-up data, there have been no late failures of pacing but one lead showed insulation failure with over- and undersensing after 4.5 years. A number of deficiencies were identified in the prototypes leading to modifications of a subsequent generation of rate responsive pacemaker based on RV dP/dtmax. These initial data demonstrate that rate adaptive pacing based on RV dP/dtmax responds in a physiological manner. This rate responsive system is of particular interest as it is based on a beat-to-beat parameter of cardiac mechanical function.     

Quantitative Comparison of Rate Response and Oxygen Uptake Kinetics Between Different Sensor Modes in Multisensor Rate Adaptive Pacing

Although multisensor pacing may mitigate the inadequacy of rate adaptation in a single sensor system, the clinical role of multisensor driven rate adaptive pacing remains unclear. The cardiopulmonary performance of six patients (mean age 63.5 ± 10 years) who had undergone the implant of combined QT and activity VVIR (Topaz®) pacemakers was assessed during submaximal and maximal treadmill exercise with the rate response sensor randomly programmed to either single sensor mode. QT and activity (ACT), or dual sensor mode, with equal contribution of QT and ACT (QT = ACT). The rate of response, the proportionality, oxygen kinetics, and maximal exercise performance of the various sensor modes during exercise were measured and compared. The ACT sensor mode “overpaced” and the QT and QT = ACT sensor modes “underpaced” during the first three quartiles of exercise (P < 0.05). The ACT sensor mode also gave the fastest rate of response with the shortest delay (13 ± 1.5 sec vs 145 ± 58 sec and 41 ± 17 sec, P < 0.05), time to 50% rate response (39 ±2.7 sec vs 275 ± 48 sec and 203 ± 40 sec, P < 0.05), and time to 90% of rate response (107 ± 21 sec vs 375 ± 34 sec and 347 ± 34 sec, P < 0.05) and a smaller oxygen debt (0.87 ± 0.16 L vs 1.10 ± 0.2 L and 1.07 ± 0.18 L, P < 0.05) compared to the QTand QT = ACT sensor modes, respectively. These differences were most significant at low exercise workloads. Thus, different sensor combinations resuh in different rate response profiles and oxygen delivery, especially during low level exercise. However, the observed oxygen kinetics difference was workload dependent, and its clinical relevance remains to be tested. Despite the marked difference in exercise rate profile and oxygen kinetics, there was no difference in the maximal oxygen uptake, anaerobic threshold, and exercise duration between the various sensor modes during maximal exercise.     

Influence of Exercise Induced Myocardial Ischemia on Right Ventricular dP/dt: Potential Implications for Rate Responsive Pacing

Background : Right ventricular (RV) dP/dt_max has been used as a simple parameter for rate responsive pacing to simulate the normal sinus node function. However, the effect of acute myocardial ischemia on RV dP/dt_max has not yet been evaluated. Methods : RV high fidelity pressure was measured in 21 patients at rest and during supine bicycle exercise. Nine patients (Group 1 = controls) had no or only minimal alterations of the coronary arteries and 12 (Group 2 =CAD) had significant coronary artery disease with exercise induced left ventricular (LV) wall-motion abnormalities (n = 10) and/or angina pectoris (n = 6). RV pressure and its first derivative (RV dP/dtj were determined by an 8 French micromanometer catheter. The time constant of RV pressure decay (Tau) was calculated from the negative reciprocal of RV pressure versus negative dP/dt during isovolumic relaxation. RV volumes and ejection fraction were calculated from RV biplane angiograms (multiple slice method) at rest and during exercise. Results : Heart rate (HR), RV dP/dt_max and dP/dt_min increased significantly during exercise, whereas Tau decreased. There were no significant differences between the two groups, although RV ejection fraction increased from 67% to 72% in the control group but decreased from 63% to 51% in the CAD group (P < 0.05). An exponential relationship was found between HR and dP/dt_max with a correlation coefficient of 0.82 (P < 0.01; SEE = 7% of the mean value). Conclusions : Acute exercise induced myocardial ischemia does not significantly influence RV dP/dt_max during sinus rhythm. Consequently, this index of RV contractility may be used in patients with coronary artery disease as a simple parameter for rate responsive pacing.     

Systolic and Diastolic Function with Alternate and Combined Site Pacing in the Right Ventricle

We hypothesized that pacing at two ventricular sites simultaneously would activate the myocardium more rapidly and improve ventricular function. We studied the effect of pacing at the right ventricular outflow tract (RYOT) and the RV apex (EVA) on systolic and diastolic function. In 14 patients with a reduced systolic ejection fraction < 40% (mean EF 32%±4%)we measured RV pressures, left ventricular pressures, EF, cardiac output, peak dP/dt, peak negative dP/dt, and the time constant of relaxation, Tau, during intrinsic rhythm, atrial pacing and DVI pacing at the RVA, the RVOT, and both RV sites combined in random order. Repeated measures analysis of variance showed no significant differences in any of these parameters. The highest absolute values of dP/dt were observed during sinus rhythm and the lowest with RVA pacing. This parameter tended to improve progressively with pacing in the RVOT and at both sites. Peak negative dP/dt showed a similar nonsignificant trend. Conclusion: These data suggest that in patients with poor LV function, there may be subtle improvements in diastolic and systolic function with pacing in the RVOT and at combined sites in the RV compared to traditional RVA pacing.     

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.     

Bifocal Right Ventricular Resynchronization for the Failing Right Ventricle

The present case illustrates that in patients with right ventricular (RV) failure and right bundle branch block it is possible to resynchronize the RV without further worsening RV or left ventricular (LV) pump function, even in cases with various degrees of atrioventricular block. The acute response to different pacing configurations was analyzed in terms of dP/dt variations. Bifocal RV pacing (His bundle plus RV outflow tract pacing) achieved the best acute results and was chosen for permanent pacing. This pacing configuration was associated to clinical and echocardiographic improvement. (PACE 2011; 34:e78–e81)     

Invasive optimization of cardiac resynchronization therapy: role of sequential biventricular and left ventricular pacing

BACKGROUND: Aim of this invasive study was to characterize and quantify changes in left ventricular (LV) systolic function due to sequential biventricular pacing (BV) as compared to right atrial triggered simultaneous BV (BV(0)), LV, and right ventricular (RV) pacing in patients with congestive heart failure (CHF). METHODS: In 22 CHF patients, all in sinus rhythm, temporary multisite pacing was performed prior to implantation of a permanent system. LV systolic function was evaluated invasively by the maximum rate of LV pressure increase (dP/dt(max)). Sequential BV pacing was performed with preactivation of either ventricle at 20-80 ms. RESULTS: In comparison to RV pacing, LV and BV(0) pacing increased dP/dt(max) by 33.9 +/- 19.3% and 34.0 +/- 22.6%, respectively (P < 0.001). In 9 patients, optimized sequential BV pacing further improved dP/dt(max) by 8.5 +/- 4.8% compared to BV(0) (range 3.3-17.1, P < 0.05). In 10 patients exhibiting a PR interval < or =200 ms, LV pacing was either superior (n = 6) or equal to BV(0) pacing (n = 4). In these 10 patients, LV pacing yielded a 7.4 +/- 8.0% higher dP/dt(max) than BV(0) pacing (P < 0.05). CONCLUSIONS: Using sequential BV pacing, generally with LV preactivation, moderate improvements in LV systolic function can be achieved in selected patients. Baseline PR interval may aid in the selection of the optimum cardiac resynchronization therapy (CRT) mode, favoring LV pacing in patients with a PR interval < or =200 ms.     

Two-Year Experience with Rate-Modulated Pacing Controlled by Mixed Venous Oxygen Saturation

Mixed venous oxy-hemoglobin saturation (M_VO₂) is a physiological variable with several features that might be desirable as a control parameter for rate adaptive pacing. Despite these desirable characteristics, the long-term reliability of the M_VO₂ sensor in vivo is uncertain. We, therefore, designed a study to prospectively evaluate the long-term performance of a permanently implanted M_VO₂ saturation sensor in patients requiring VVIR pacing. Under an FDA approved feasibility study, eight patients were implanted with a VVIR pulse generator and a right ventricular pacing lead incorporating an M_VO₂ sensor. In order to accurately assess long-term stability of the sensor, patients underwent submaximal treadmill exercise using the Chronotropic Assessment Exercise Protocol (CAEP) at 2 weeks, 6 weeks, and 3, 6, 9, 12, 18, and 24 months following pacemaker implantation. Paired maximal exercise testing using the CAEP was also performed with the pacing system programmed to the VVI and VVIR modes in randomized sequence with measurement of expired gas exchange after 6 weeks and 12 months of follow-up. During maximal treadmill exercise the peak exercise heart rate (132 ± 9 vs 71.5 ± 5 beats/min, P < 0.00001) and maximal rate of oxygen consumption (1,704 ± 633 vs 1382 ± 407 mL/min, P = 0.01) were significantly greater in the VVIR than in the VVI pacing mode. Similarly, the duration of exercise was greater in the VVIR than the VVI pacing mode (8.9 ± 3.6 min vs 7.6 ± 3.7 min, P = 0.04). The resting M_VO₂ and the M_VO₂ at peak exercise were similar in the VVI and VVIR pacing modes (P = NS). However, the M_VO₂ at each comparable treadmill exercise stage was significantly higher in the VVIR mode than in the VVI mode (CAEP stage 1 (P = 0.005), stage 2 (P = 0.04), stage 3 (P = 0.008), and stage 4 (P = 0.04). The correlation between M_VO₂ and oxygen consumption (VO₂) was excellent (r = -0.93). Telemetry of the reflectance of red and infrared light and M_VO₂ in the right ventricle during identical exercise workloads revealed no significant change over the first 12 months of follow-up (ANOVA, P = NS). The chronotropic response to exercise remained proportional to VO₂ in all patients over the first 12 months of follow-up. The time course of change in M_VO₂ during maximal exercise was significantly faster than for VO₂. At the 18- and 24-month follow-up exercise tests, a significant deterioration of the sensor signal with attenuation of chronotropic response was noted for 4 of the 8 subjects with replacement of the pacing system required in one patient because of lack of appropriate rate modulation. Rate modulated VVIR pacing controlled by right ventricular M_VO₂ provides a chronotropic response that is highly correlated with VO₂. This parameter responds rapidly to changes in workload with kinetics that are more rapid than those of VO₂. Appropriate rate modulation provides a higher M_VO₂ at identical workloads than does VVI pacing. Although the M_VO₂ sensor remains stable and accurate over the first year following implantation, significant deterioration of the signal occurs by 18–24 months in many patients.     

Heart Rate Correlation, Response Time and Effect of Previous Exercise Using an Advanced Pacing Rate Algorithm for Temperature-Based Rate Modulation

A temperature-based algorithm to produce pacing rate that resembles chronotropic response to activity was developed. Measurement criteria for the algorithm included workload dependent rate increases with activity and response time within 60 seconds of exercise onset. To evaluate the aigorithm, right ventricular blood temperature was recorded during rest and treadmill exercise in 25 patients with implanted Kelvin 500 pacemakers (Cook Pacemaker). Patients included 16 maies and nine femaies, ages 44–81 (mean 72). Indications for pacing were sinus node disease, atrioventricular block and atrial fibrillation with siow ventricular response. Temperature changes reflected physical activity as well as emotional stress. The algorithm was based on the rate of change (dT/dt), the relative change (AT) and the baseline history (T) of temperature. At exercise onset, a rapid, brie/drop in temperature (dT/dt) typically occurred due to peripheral vasodilation, causing prompt increase in pacing rate. As exercise continued, the increase in metabolic rate caused dT/dt as well as AT to increase, further increasing pacing rate. After exercise, temperature returned to resting level which correspondingly decreased the pacing rate. Sensitivity of the algorithm to temperature variations, and the upper and lower pacing rate limits were programmable to adapt to individual patient needs. The rates produced by the algorithm mimicked intrinsic rate response for various activity levels and produced a mean response time of 16 seconds from exercise onset. Previous exercise had no significant effect on response time. Correlation between normal chronotropic response and simulated pacing rate from five exercise tests was 0.92. These results show good specificity and refute the statement that blood temperoture yields a slow response.     

The Ventricular Depolarization Gradient: Effects of Exercise, Pacing Rate, Epinephrine, and Intrinsic Heart Rate Control on the Right Ventricular Evoked Response

A new pacing technique is described that permits high fidelity recording of the paced ventricular evoked response, including cardiac depolarization. Integration of the paced R wave yields the ventricular depolarization gradient (G_D), which is dependent on activation sequence and the spatial dispersion of activation times. G_Dwas studied in 27 dogs to determine the ejects of treadmill exercise at fixed rate pacing (n = 10), elevation of heart rate in the absence of stress (n = 20), epinephrine at fixed rate (n = 6), and exercise in the presence of normal chronotrophic response (n = 7). Low level exercise (1 mph, 2 min, 15°) at a fixed heart rate produced significant (P < 0.0005) decreases in G_Dthat averaged —-10.8 ± 4.0% (mean ± SD). The rate of change in G_Dwas faster at the onset of exercise than at its cessation (P < 0.0005). Artificial elevation of heart rate at rest produced significant (P < 0.0005) increases in G_D; mean sensitivity of G_Dto rote was 0.27 ± 0.12%/beats/min. Intravenous injection of epinephrine produced significant (P < 0.001) decreases in G_D at two dosage levels (2.5 and 5.0 μg/kg) when evaluated at two baseline pacing rates (150 and 190 beats/min); mean changes in G_Dwere –20.64 ± 0.53% (2.5 μ/kg at 150 beats/min), –25.19 ± 4.20% (5.0 μ/kg at 150 beats/min), –14.18 ± 5.19% (2.5 μ/kg at 190 beats/min), and –24.22 ± 4.94% (5.0 μ/kg at 190 beats/min). Sensitivity of G_Dto epinephrine was dose-dependent (P < 0.01) at each baseline rate, but was independent (P > 0.05) of the rate itself. In the presence of a normal chronotropic response. G_D remained unchanged (P > 0.5) during exercise in spite of significant elevation in heart rate (105.0 to 167.1 beats/min, P < 0.001). These data suggest the presence of an intrinsic negative-feedback control mechanism that maintains G_Dconstant in the healthy heart during homeostatic disturbance. Applications in closed-loop rate adaptive pacing are described.     

The Optimal Pacing Rate: An Unpredictable Parameter

A three phase relation has been demonstrated between increasing heart rate and cardiac output at rest. Phase I with cardiac output increasing with increasing heart rate, phase II a plateau, and phase III decreasing cardiac output with any further increase in heart rate. The “optimal rate” can be defined as the heart rate at the onset of phase II. Twenty patients were studied, 13 male, mean age 60 years (range 31–71 years). All had chronic complete heart block and established DDD pacing. A maximal exercise test was performed to determine peak sinus rate. Exercise hemodynamics were measured using an ambulatory monitor (Capintec Vest), which permits measurement of relative cardiac output and relative ejection fraction. The patients were programmed to VVI pacing at a rate of 60 beats/min and performed three exercise tests at different workloads. The order of workloads was randomized and selected from a range (0, 25, 50, or 75 W) depending on fitness. After 3-minute stabilization, the VVI pacing rate was increased at 1-minute intervals until higher than peak sinus rate giving a total exercise time of 12 minutes. The “optimal rate band” was determined at each workload. The mean of this “optimal rate band” for each workload varied in a nonlinear manner. There was no correlation between “mean optimal rate” and age or the peak rate predicted by the Astrand formula. Current definitions of chronotropic incompetence are inaccurate. Are some of these people at their “optimal rate” already? The arbitrary selection of rate response curves on age related criteria may lead to an impaired hemodynamic response.     

Does RV Lead Positioning Provide Additional Benefit to Cardiac Resynchronization Therapy in Patients with Advanced Heart Failure?

BACKGROUND AND OBJECTIVES: The left ventricular (LV) stimulation site is currently recommended to position the lead at the lateral wall. However, little is known as to whether right ventricular (RV) lead positioning is also important for cardiac resynchronization therapy. This study compared the acute hemodynamic response to biventricular pacing (BiV) at two different RV stimulation sites: RV high septum (RVHS) and RV apex (RVA). METHODS AND RESULTS: Using micro-manometer-tipped catheter, LV pressure was measured during BiV pacing at RV (RVA or RVHS) and LV free wall in 33 patients. Changes in LV dP/dt(max) and dP/dt(min) from baseline were compared between RVA and RVHS. BiV pacing increased dP/dt(max) by 30.3 +/- 1.2% in RVHS and by 33.3 +/- 1.7% in RVA (P = n.s.), and decreased dP/dt(min) by 11.4 +/- 0.7% in RVHS and by 13.0 +/- 1.0% in RVA (P = n.s.). To explore the optimal combination of RV and LV stimulation sites, we assessed separately the role of RV positioning with LV pacing at anterolateral (AL), lateral (LAT), or posterolateral (PL) segment. When the LV was paced at AL or LAT, the increase in dP/dt(max) with RVHS pacing was smaller than that with RVA pacing (AL: 12.2 +/- 2.2% vs 19.3 +/- 2.1%, P < 0.05; LAT: 22.0 +/- 2.7% vs 28.5 +/- 2.2%, P < 0.05). There was no difference in dP/dt(min) between RVHS- and RVA pacing in individual LV segments. CONCLUSIONS: RVHS stimulation has no overall advantage as an alternative stimulation site for RVA during BiV pacing. RVHS was equivalent with RVA in combination with the PL LV site, while RVA was superior to RVHS in combination with AL or LAT LV site.     

Left Ventricular Response to Severe Exertion in Untethered Dogs

The left ventricular response to severe exercise was studied by telemetering direct measurements of left ventricular diameter (D) and pressure (P) and aortic blood flow from healthy dogs running at speeds up to 30 mph in the field. Severe exercise increased cardiac output from 101 to 478 ml/kg per min, heart rate from 95 to 297 beats/min, stroke volume from 31 to 44 ml, left ventricular isolength (iso) systolic pressure from 120 to 186 mm Hg, left ventricular end diastolic pressure from 6 to 18 mm Hg, and left ventricular end diastolic diameter from 58.9 to 60.1 mm, while end systolic diameter decreased from 53.0 to 52.2 mm. Two indices of myocardial contractility, (dP/dt)/P increased from 37 to 92 sec(-1), while dD/dt, the velocity of myocardial fiber shortening at isolength, rose from 54 to 119 mm/sec. All of these changes were statistically significant. When, in resting dogs, heart rate was first raised to exercise levels by electrical stimulation, severe exercise subsequently increased left ventricular end diastolic diameter more profoundly, from 55.7 to 59.7 mm, while end systolic diameter remained constant and the increases in left ventricular pressure, (dP/dt)/P and velocity(iso) were roughly comparable to those occurring during exercise in spontaneous rhythm. After propranolol, 1.0 mg/kg, severe exercise resulted in significantly smaller increases in cardiac output (from 82 to 240 ml/kg), in heart rate (from 87 to 186 beats/min), in left ventricular pressure(iso) (from 122 to 150 mm Hg), in (dP/dt)/P (from 32 to 44 sec(-1)), in velocity(iso) (from 47 to 59 mm/sec), and in slightly greater increases in end diastolic diameter, from 59.8 to 62.0 mm and pressure from 8 to 22 mm Hg, while end systolic diameter did not change significantly.Thus, the left ventricle responds to severe exercise with near maximal increases in heart rate and contractility, while significant increases in end diastolic diameter (Frank-Starling mechanism) and stroke volume occur as well. When heart rate was held constant severe exercise produced similar increases in contractility but end systolic size failed to diminish and the increases in end diastolic size were greater. Beta adrenergic receptor blockade interfered with the chronotropic and particularly the inotropic response to severe exercise and while the participation of the Frank-Starling mechanism was somewhat greater, the latter was not sufficient to increase cardiac output normally.     

Stimulation rate and the optimal interventricular interval during cardiac resynchronization therapy in patients with chronic atrial fibrillation

Background: Optimization of cardiac resynchronization therapy (CRT) with respect to the interventricular (V‐V) interval is mainly limited to pacing at a resting heart rate. We studied the effect of higher stimulation rates with univentricular and biventricular (BiV) pacing modes including the effect of the V‐V interval optimization. Methods: In 36 patients with heart failure and chronic atrial fibrillation (AF), the effects of right ventricular (RV), left ventricular (LV), simultaneous BiV, and optimized sequential BiV (BiVopt) pacing were measured. The effect of the pacing mode and the optimal V‐V interval was determined at stimulation rates of 70, 90, and 110 ppm using invasive measurement of the maximum rate of left ventricular pressure rise (LV dP/dt_max). Results: The average LV dP/dt _max for all pacing modalities at stimulation rates of 70, 90, and 110 ppm was 781 ± 176, 833 ± 197, and 884 ± 223 mmHg/s for RV pacing; 893 ± 178, 942 ± 186, and 981 ± 194 mmHg/s for LV pacing; 904 ± 179, 973 ± 187, and 1052 ± 206 mmHg/s for simultaneous BiV pacing; and 941 ± 186, 1010 ± 198, and 1081 ± 206 mmHg/s for BiVopt pacing, respectively. In BiVopt pacing, the corresponding optimal V‐V interval decreased from 34 ± 29, 28 ± 28, and 21 ± 27 ms at stimulation rates of 70, 90, and 110 ppm, respectively . In two individuals, LV dP/dt_max decreased when the pacing rate was increased from 90 to 110 ppm. Conclusion: In patients with AF and heart failure, LV dP/dt_max increases for all pacing modalities at increasing stimulation rates in most, but not all, patients. The rise in LV dP/dt_max with increasing stimulation rates is higher in biventricular (BiV and BiVopt) than in univentricular (LV and RV) pacing. The optimal V‐V interval at sequential biventricular pacing decreases with increasing stimulation rates.     

Right Ventricular Pressure, dP/dt, and Preejection Interval During Tilt Induced Vasovagal Syncope

This study examined the potential utility of monitoring right ventricular dP/dt as a means of detecting imminent vasovagal syncope. To assess this possibility, continuous right ventricular pressure measurements were recorded in nine patients during induction of syncope by head-up tilt testing. Findings indicated that arterial pressure tended to fall prior to drop in heart rate. RV pressure exhibited a significant, but very small, fall during tilt. DP/dt max increased by 15–20% during tilt, then fell by a median of 30% from maximum value beginning aboutr 2 minutes prior to syncope. Thus, further investigation of dP/dt as a potential marker of impending vasovagal syncope is warranted.     

Contribution of Atrioventricular Synchrony to Left Ventricular Systolic Function in a Closed-Chest Canine Model of Complete Heart Block: Implications for Single-Chamber Rate-Variable Cardiac Pacing

This study assessed the impact of atrioventricular (AV) synchrony on characteristics of left ventricular (LV) systolic function during ventricular pacing over a wide heart rate range in a conscious closed-chest canine model of complete AV block. Ten healthy adult dogs underwent thoracotomy during which complete AV block was created by formaldehyde injection, and paired ultrasonic sonomicrometers were positioned on the LV anterior-posterior minor axis. Following recovery from surgery, peak and end-diastolic LV transmural pressure, maximum dP/dt, stroke work, end-diastolic minor axis dimension, and maximum velocity of shortening, were quantitated at heart rates of 80, 100, 120, 140, and 160 beats per minute (bpm) during both ventricular pacing alone and AV sequential pacing with increasing AV intervals (0, 50, 100, 150, 200, 250, and 300 ms). Over the heart rate range tested, parameters of LV systolic function did not differ significantly during ventricular pacing with or without AV synchrony. For example, during ventricular pacing alone maximum LV dP/dt varied from 2110 +/- 70 mmHg/s to 2463 +/- 567 mmHg/s, a range essentially identical to that observed in the presence of AV synchrony. On the other hand, although the impact on LV performance of varying AV interval from 0 to 300 ms was small, differences tended to become more pronounced at higher pacing rates. At 80 bpm, neither stroke work nor maximum LV dP/dt were affected by change in AV interval, while at heart rates greater than or equal to 120 bpm both stroke work and LV dP/dt tended to maximize at AV intervals of 50 and 100 ms and thereafter declined.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myopotential Interference in Unipolar Rate Responsive Pacemakers

The effects of myopotential interference on unipolar rate responsive pacemakers were assessed in 22 patients. Six types of pacemakers (from four manufacturers) were studied: five TX2 (QT sensing), seven Biorate (five RDP3 and two MB-1, respiratory rate sensing), seven Activitrax (activity sensing), two Medtronic 2503 (dP/dt sensing), and one Sensolog P703 (activity sensing). Provocative tests using arm exercises were performed in both VVI and rate responsive modes. At nominal sensitivity settings (1.8-2.5 mV), 55% of these patients were myopotential positive for at least 1 provocative test. Pressing the palms together was found to be the most sensitive provocative test. Rate response was achieved with treadmill exercise (all patients), hyperventilation (RDP3 and MB-1) and tapping (Activitrax) or wobbling the pacemaker in its pocket (Sensolog). During continued rate acceleration, myopotential interference was induced by arm exercises. The duration of inhibition was shorter when the provocative tests were performed during rate response compared to that occurred at rest. Short periods of myopotential interference resulted in temporary inhibition of pacing but rate response continued immediately on removal of the interference. In one patient with a RDP3 pacemaker, a prolonged episode of myopotential interference during treadmill exercise resulted in reversion of the pacemaker to the interference mode. Appropriate adjustment of the sensitivity setting effectively controlled the symptoms in most patients. However, one patient with a QT sensing pacemaker and symptomatic myopotential interference required programming to the VVT pacing mode. Two out of five patients with RDP3 required pacemaker replacement because of uncontrolled myopotential interference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative Left Ventricular Function Following Atrial, Septal, and Apical Single Chamber Heart Pacing in the Young

Ventricular pacing, typically initiated from a RV apical electrode, inherently causes abnormal biventricular activation, decreases LV function, and causes histopathological changes. Since pacing initiated in childhood can he expected to have a more protracted course compared with the adult, the consequences of this alteration in LV hemodynamics gain added significance among the young pacemaker recipient. The purpose of this study was to evaluate the potential of improving paced LV function by a septal electrode implant site. Acute alterations in cardiac index, LV pressure, and contraction indices, including dP/dt, Vmax. and Vpm, were compared among 22 patients (median age 10 years) with normal cardiac anatomy during intracardiac electrophysiological studies. LV hemodynamics were measured during intrinsic rhythms and following 15 minutes of atrial, HV apical, and septal pacing at an appropriate exercise rate for age of 150 ppm. Results showed a significant decrease in LV dP/dt, Vmax, and Vpm, and increase in LV end-diastolic pressure only with apical pacing. Septal pacing, in spite of loss of any atrial contribution to ventricular filling, maintained comparable indices with intrinsic and atrial paced rhythms. This study demonstrates that normalized LV function is maintained by septal and deteriorates with apical pacing acutely among young, nonischemic hearts. Continued evaluation of appropriate pacing electrode designs to permit septal implant is needed to ensure optimal chronically paced LV function.