Systolic time intervals during submaximal and maximal exercise in man

This study describes the serial responses of the systolic time intervals (STI) to submaximal and maximal supine exercise in normal subjects. Regression equations relating STI and heart rate during supine submaximal and maximal exercise are derived. It is shown that within the heart rate range of 120 to 170 beats per minute, total electromechanical systole (QS₂) and left ventricular ejection time (LVET) are related inversely and linearly to heart rate for both levels of exercise. At comparable heart rates, the QS₂ and LVET are greater during maximal than submaximal exercise, with differences widening significantly with increasing heart rate. This finding points out the importance of taking into account the intensity of exercise when evaluating STI responses to exercise stress in different groups.The pre-ejection period (PEP) significantly decreases from rest to the initial phase of both maximal and submaximal exercise with a subsequent tendency to plateau, indicating that a minimum PEP is reached early during exercise and that cardiovascular adaptation no longer includes additional shortening.This study also shows that STI obtained during exercise cannot be corrected for heart rate according to regression equations which were developed in resting supine subjects. Thus, there appears to be no justification for extrapolating the heart rate range of resting supine subjects to the exercise state for correcting intervals in this manner. In addition, STI measurements made during the immediate recovery period following supine exercise are significantly different from those obtained just prior to cessation of exercise. Therefore, recovery STI do not reflect the true hemodynamic changes occurring during the course of exercise.The application of the levels of exercise described in this study to the assessment of changes in STI in patients with documented or suspected cardiac dysfunction appears warranted. Alterations in left ventricular performance not evident at rest or following mild exercise might be detected employing these more strenuous exercise protocols. Using the regression equations established in this study, exercise-induced deviation in STI corrected for heart rate may now be determined with the realization that these relationships were derived from relatively young men. However, in the adult population the duration of LVET corrected for heart rate varies little with advancing age, and PEP shows only a slight increase.^34,35     

Relationship between systolic time intervals and arterial blood pressure

It has been suggested that systolic time intervals (STI) can be used to monitor the cardiac effects of antihypertensive treatments and also to evaluate hypertensive patients. STI changes observed in hypertensives have been ascribed to myocardial disease, although they could be due to the existence of a relationship between STI and blood pressure. A group of 37 subjects (18 normotensives and 19 hypertensives) with no signs of heart failure and left ventricular dysfunction were studied to examine the relationship of STI to blood pressure. Pacing with an external battery pulse generator was performed at the rate of 95 beats/min in order to eliminate differences in heart rate. STI were measured from good quality high speed (100 mm/s) recordings and the average value of 10 consecutive cardiac cycles was used for statistical analysis. Normal subjects showed significantly lower values of pre-ejection period (PEP), electromechanical systole (QS2), and pre-ejection period/left ventricular ejection time ratio (PEP/LVET). Moreover, a significant inverse relationship between diastolic pressure and LVET and significant direct relationships between diastolic pressure and PEP, systolic pressure and PEP, diastolic pressure and PEP/LVET, and between systolic pressure and PEP/LVET were demonstrated. We suggest to consider the relation of STI to blood pressure to provide regression equations to best appreciate and use STI.     

A comparison between the effects of dynamic and isometric exercise as evaluated by the systolic time intervals in normal man

Systolic time intervals (STI) were measured externally in 21 healthy male adults at rest, during isometric exercise (handgrip), and dynamic exercise (bicycle ergometer). Dynamic exercise produced significant abbreviation of the mean QS₂, LVET, PEP, and ICT (p < 0.005). Isometric exercise at comparable heart rates produced significant abbreviation of the mean QS₂ and LVET (p < 0.005), but not of the PEP and ICT.Significant linear regressions against heart rate were found for QS₂, LVET, and PEP during rest, isometric exercise, and dynamic exercise (p < 0.025). Major differences in the slopes of the regression lines were noted for the PEP under the three conditions studied.Although the pressor response during the isometric exercise was marked, the differences in the responses of the STI to the two exercise maneuvers could not be correlated with either mean or systolic arterial blood pressure.The triple product (HR LVET systolic BP) was significantly higher (p < 0.001) during isometric handgrip than in dynamic exercise, thereby indicating increased myocardial oxygen demands.The results indicate that careful consideration must be given to both the type of exercise and protocol used when evaluating the systolic time intervals.     

Left ventricular function at similar heart rates during tachycardia induced by exercise and atrial pacing: an echocardiographic study

M mode echocardiography was used in 10 normal subjects to study left ventricular dimension and function variables at identical heart rates during tachycardia induced by supine bicycle exercise or atrial pacing. Echocardiographic data were analysed independently by two observers. The maximum heart rate reached during atrial pacing was lower (mean (1SD) 148 (17) beats/min) than that reached during exercise (mean (1SD) 167 (14) beats/min). The left ventricular end diastolic dimension was greater before supine exercise than before atrial pacing, probably as a result of leg raising. At each graded exercise step the end diastolic dimension remained greater than during atrial pacing and the differences became progressively greater with increasing heart rates. The left ventricular end systolic dimension was not significantly different at each step during the two stresses. During recovery the end systolic dimension was significantly smaller after exercise than at corresponding heart rates induced by atrial pacing. Left ventricular function indices--fractional shortening and peak rates of left ventricular systolic and diastolic dimensional change--were significantly higher during exercise than during atrial pacing and the differences increased with heart rate. It is concluded that the intervention used to change heart rate has an important effect on M mode echocardiographic left ventricular dimensions; indices of left ventricular performance increase progressively during exercise and differ from those measured at the same heart rate during atrial pacing; it is important to consider heart rate, stroke volume, and loading conditions when reference values are used and when the effects of a particular stress are to be interpreted.     

Left ventricular function at similar heart rates during tachycardia induced by exercise and atrial pacing: an echocardiographic study.

M mode echocardiography was used in 10 normal subjects to study left ventricular dimension and function variables at identical heart rates during tachycardia induced by supine bicycle exercise or atrial pacing. Echocardiographic data were analysed independently by two observers. The maximum heart rate reached during atrial pacing was lower (mean (1SD) 148 (17) beats/min) than that reached during exercise (mean (1SD) 167 (14) beats/min). The left ventricular end diastolic dimension was greater before supine exercise than before atrial pacing, probably as a result of leg raising. At each graded exercise step the end diastolic dimension remained greater than during atrial pacing and the differences became progressively greater with increasing heart rates. The left ventricular end systolic dimension was not significantly different at each step during the two stresses. During recovery the end systolic dimension was significantly smaller after exercise than at corresponding heart rates induced by atrial pacing. Left ventricular function indices--fractional shortening and peak rates of left ventricular systolic and diastolic dimensional change--were significantly higher during exercise than during atrial pacing and the differences increased with heart rate. It is concluded that the intervention used to change heart rate has an important effect on M mode echocardiographic left ventricular dimensions; indices of left ventricular performance increase progressively during exercise and differ from those measured at the same heart rate during atrial pacing; it is important to consider heart rate, stroke volume, and loading conditions when reference values are used and when the effects of a particular stress are to be interpreted.     

Influence of heart rate increase on uncorrected pre-ejection period/left ventricular ejection time (PEP/LVET) ratio in normal individuals.

In 26 normal volunteers, increase in heart rate from mean 73-94 +/- 1-97 to 103-61 +/- 2-72/min, by either intravenous atropine administration or rapid right atrial pacing, produced definite changes in the uncorrected systolic time intervals. As expected, total electromechanical systole (QS2) and left ventricular ejection time (LVET) were shortened, while the pre-ejection period (PEP) was unaffected. There was a consistent and significant increase of the PEP/LVET ratio (P less than 0-001). It is postulated that when this ratio is taken to express left ventricular contractility, it should probably be corrected for heart rate. Appropriate regression equations for such a correction were calculated (PEP/LVET=0-249 + 0-0168 HR).     

Systolic time interval. Heart rate relationship during atrial or ventricular pacing

In order to evaluate the relative importance of heart rate (HR) and A-V synchrony during pacing, 16 patients with VVI pacemakers were compared with 8 patients with AAI pacemakers using systolic time intervals. The patients were examined at rest at increasing HR with increments of 10 beats/min until a maximum of 150 beats/min was reached or for AAI pacing until 2 degrees A-V block occurred. The slopes of the linear regression equations for PEP versus HR and PEP/LVET versus HR were used. To compensate for differences in baseline values, delta PEP% versus delta HR% and delta PEP/LVET% versus delta HR% were also calculated and used to evaluate the response to the two different pacing modes. PEP seemed in this situation to be less dependent on HR than expected from earlier data concerning spontaneous differences in heart rate. This is probably due to a lower catecholamine level during pacing. During AAI pacing the slopes were slightly more normal than during VVI pacing, but the differences did only reach statistical significance using PEP/LVET versus HR (p less than 0.05). At heart rates above 80 blood pressure had a tendency to be higher during AAI pacing, a trend which was only significant for the diastolic blood pressure at HR from 130-150. These results support the view, that the ability to increase heart rate is more crucial for left ventricular function than A-V synchrony in these patients.     

Systolic time-interval evaluation by thermistor plethysmography during uninterrupted dynamic stress test in normals and in patients with coronary artery disease

18 patients with coronary artery disease (CAD) and 21 normal subjects underwent a triangular bicycle exercise test. Systolic time intervals (STI) were calculated at rest and every 2 min during exercise. Under resting conditions, STI were similar in the two groups. During exercise, the ejection time index (ETI), i.e. left ventricular ejection time (LVET) corrected for HR, rose significantly more in CAD patients, as compared to normals. Pre-ejection period (PEP) was also differently affected by exercise in CAD patients, who showed a more shortened PEP (p less than 0.001) in the early stage of dynamic stress. PEP/LVET ratio, which in the control group decreased continuously, in CAD patients fell during exercise at lower work loads (p less than 0.001), whilst rose during strenuous exercise. Finally, significant differences (p less than 0.001) were found in the percent change (% delta) PEP/LVET ratio between the two groups during the early phase of exercise, in which no superimposition of single values was present. Therefore, this last parameter seems the most reliable to differentiate clearly CAD patients from normal subjects, but its use must be limited at early exercise.     

Systolic time intervals in Duchenne muscular dystrophy: evaluation of left ventricular performance

The purpose of this study was to evaluate the prevalence of latent cardiac heart failure in Duchenne's muscular dystrophy (DMD). Systolic time intervals (STI) were measured in a cross-sectional study of a group of 177 patients 6-21 years old. Total electromechanical systole (QS2), left ventricular ejection time (LVET), and pre-ejection period (PEP), were corrected for heart rate by means of regression equations obtained from 33 normal subjects (QA2 I, LVET I, PEP I). Mean STI values were significantly different from those observed in an age-matched control group. PEP I was prolonged, LVET I was abbreviated, while QS2 I remained unaltered. STI varied significantly with age. Abnormal values were uncommon before age 10 years. The most critical period was 14-16 years, with an abrupt increase in prevalence from 35 to 72%. Such changes point to the practical use of the STI for clinical decision making especially for surgery.     

运动负荷对左室收缩时间间期的影响

用多道生理记录仪对６７例被检者（其中正常人３７例，高血压病人３０例）分别测定双倍二级梯运动前、运动后１、３、５、７ｍｉｎ的收缩时间同期（ＳＴＩ）。结果显示，运动后１ｍｉｎ和运动前相比，表现为ＥＭＴＬＶＥＴ、ＰＥＰ、ＥＭＬ、ＩＣＴ、ＨＷＴ缩短，ＰＥＰ／ＬＶＥＴ、ＩＣＴ／ＬＶＥＴ、ＴＨ／ＴＨ比值减小。运动停止后，以上各指标逐渐恢复，但正常人组的恢复过度较高血压病组快，提示高血压病人尽管安静休息时ＳＴＩ正常，但心功能代偿能力和调节能力已有所下降。本文分析了运动负荷对ＳＴＩ影响的可能机理，并认为，测定动态下的ＳＴＩ能更好地显示心脏的储备和调节能力。     

A noninvasive study of the response of ischemic heart to exercise

The response to exercise during increasing workloads (supine bicycling), was studied in 105 men, of whom 70 had ischemic heart disease and 35 did not, clinically classed into 6 groups. Heart rates, blood pressures and systolic time intervals (STI) were measured in relation to exercise tolerance and capacity. The ischemic heart disease (IHD) subjects differed from the nonischemic by an increased PEP/LVET ratio at rest and by a tendency of the diastolic blood pressure to increase upon exercise. Two main types of abnormal reaction of STI to workload were ascertained: (1) prolonged LVETc with respect to controls (prevailing in angina pectoris), and (2) prolonged PEPEc together with shorter LVETc (typical for left ventricular failure). The dominant feature appears to be the depressed contractility in the latter and a decreased compliance (or rate of relaxation) in the former. Estimation of STI may contribute to the evaluation of the exercise tolerance test in long-term examination of ischemic patients.     

Non-invasive evaluation of left ventricular function (systolic time interval) in patients using double-chamber pacemakers programmed on DDD and VVI

OBJECTIVE: To evaluate changes on left ventricular function as assessed by systolic time intervals (STI), by programming "physiological" pacemakers either on VVI or DDD mode. STUDY DESIGN: Comparison of STI values--electromechanical systole (QS2); left ventricular ejection time (LVET); pre-ejection period (PEP); PEP/LVET--in patients submitted to double chamber pacing programmed in DDD or VVI mode. SETTING: Cardiac Pacing Center in a Department of Cardiology at a University Hospital. PATIENTS: We have studied 12 patients (3 men, 9 women), mean age 56.16 years (range 25-76 years) treated with double chamber pacing. INTERVENTIONS: Initial measurements of STI in DDD or one week in VVI mode, and again after one week in DDD mode. RESULTS: Significant changes were found after the first week in VVI pacing, versus baseline determination in DDD pacing, for LVET, PEP, and PEP/LVET (p less than 0.05). At the end of the second week (DDD pacing), there were also statistically significant differences for QS2 (P less than 0.05), LVET (P less than 0.01) and PEP/LVET (P less than 0.05) values when compared with the ones obtained in VVI pacing, at the end of the preceding week. No significant changes were found between the initial and the final STI determinations (both in DDD pacing). CONCLUSION: We concluded for a better performance of the left ventricle at rest when "physiological" pacing is compared with VVI pacing.     

Mechanocardiographic assessment of systolic time intervals in normal children

Summary Systolic time intervals (STI) were measured in 469 normal children, aged 5.0 to 16.9 years, using simultaneous recordings of the electrocardiogram, phonocardiogram and an external carotid pulse tracing. The data were analyzed to define the influence of sex, age, cardiac cycle length, body weight (BW), body length (BL), and body surface area (BSA) on the left ventricular STI. Regression equations were evaluated for the calculation of normal standards for the following STI: electromechanical systole (QS2), left ventricular ejection time (LVET), pre-ejection period (PEP), systolic quotient (PEP/LVET), isovolumic contraction time (IVCT), electroacustical delay (QS1), and additionally for the so-called tension time (TT), upstroke time (UT), and the ascending index (UT/LVET) of the carotid pulse wave. Heart rate was found to influence all of the STI but the ratio UT/LVET, which revealed to be independent of any variable. Besides heart rate, BSA proved to be a second relevant independent variable for QS2 and LVET, respectively BL for PEP, PEP/LVET and QS1. These findings are in accordance to the results of comparable echocardiographic studies but disagree previous mechanocardiographic studies in smaller groups of children in whom age and not the above-mentioned parameters of the individual development seemed to influence the STI.A second set of equations was evaluated for the calculation of 95%-prediction intervals for the particular STI permitting to define abnormalities of the STI in individual children.Supported by Stiftung Volkswagenwerk, Grant No. I/35708.     

Changes in systolic time intervals during physical training in patients with ischemic heart disease. Effect of beta-blockade

Systolic time intervals (STI) were measured at rest before and after an exercise training programme in 37 patients with ischemic heart disease; 17 patients were treated with a beta-blocking drug (BB-group) and 20 were not (nBB-group). After the training period peak oxygen uptake had increased by 37% in the BB-patients and by 41% in the nBB-group. During the training period electromechanical systole (QS2) and pre-ejection period (PEP), when corrected for heart rate, shortened significantly in all 37 patients. Left ventricular ejection time (LVET) increased but when corrected for heart rate no significant changes occurred. The ratio of PEP/LVET decreased significantly. The changes in STI were similar in the patients treated with beta-blocking drugs than in those without such treatment. The changes in STI in both groups suggest that left ventricular function improves during the training period and that beta-adrenergic blockade does not alter this outcome.     

Systolic time intervals reconsidered: Reevaluation of the preejection period: Absence of relation to heart rate

Within limits, systolic time intervals are reliable reflectors of cardiac status and responses to physiologic and pharmacologic challenges, with various functional correlates. That heart rate (HR) is an important determinant of the duration of systole is well accepted, owing to its effect on left ventricular ejection time (LVET). An independent rate effect on preelection period (PEP) is disputed. Some studies in pooled normal subjects at rest showed some degree of HR-PEP covariance, leading to wide-spread rate correction in practical use. However, although right atrial pacing showed the expected HR-LVET relation, it consistently failed to show an HR-PEP relation. Systolic time intervals were examined from echocardiograms of a deliberately heterogenous group comprising 50 consecutively appearing persons with sinus rhythm. There was no HR-PEP covariance (r = 0.23; p = not significant). However, our subjects were otherwise comparable to those of other investigators, in that all other relations in these subjects were as expected from studies in both pooled and paced subjects: HR with LVET (r = -0.74; p < 0.001), PEP/LVET with ejection fraction (r = ? 0.85; p < 0.001), and PEP/ LVET with velocity of circumferential fiber shortening (r = ? 0.65, p < 0.001). Thus, HR correction of PEP is inappropriate. All other relations are substantiated in routinely encountered, unselected subjects.     

Evaluation of systolic time intervals in a group of healthy children 10-12 years old.

The normal values of the systolic time intervals (STI) in children and their possible relationship with heart rate have not been studied thoroughly. From a group of 9760 healthy school-children 10-12 years old, 488 subjects of both sexes were randomly selected in order to measure the STI and calculate the respective indices. The final population study was composed of 479 children, 249 males and 230 females, aged from 10/1 to 12/2 years/months (mean age 11/1 +/- 0/4 years/months). In each child, the following STI were measured: total electromechanical systole (Q-S2), left ventricular ejection time (LVET), mechanical systole (S1-S2), preejection period (PEP), PEP/LVET ratio and isovolumic contraction time (ICT). For each parameter, the regression equation with heart rate was calculated using a linear model and was verified if a real difference existed between linear regressions of males and females. Moreover, for each parameter, the index from the respective regression equation was calculated as well as its normal value and the standard deviation. Finally, the diastolic time (% diastole) and its correlation with heart rate were calculated. Our results demonstrate that in children, a close correlation exists between the STI and heart rate, although less striking than in adults; only the PEP/LVET ratio appears independent from heart rate, as in adults. The % diastole versus heart rate non-linear relationship shows the same behaviour as in adults. Finally, in agreement with other authors, our results show that in childhood the relationship between the STI and heart rate behaves alike in males and females.     

Relation between QT interval and heart rate. Applications and limitations of Bazett's formula

We studied the relationship between QT interval and RR interval when the heart rate was changed by atrial pacing, atropine, isoproterenol, and exercise in nine healthy adult males. The following results were obtained: (1) QT shortening with an increase in heart rate was minimal in atrial pacing and an equation QT=k⁴√RR was obtained from the QT-RR relationship during atrial pacing (r=0.64, p<0.001); (2) shortening of QT with shortening of RR was least in atrial pacing; (3) during recovery from exercise it was largest and almost coincident with Bazett's formula; (4) Bazett's formula, therefore, is clearly applicable in the evaluation of ECGs recorded at rest or after exercise; (5) Bazett's formula can not be applied in the evaluation of an effect of some drug or maneuver on the QT when such a drug or maneuver can affect both the QT and the RR directly. The RR-dependent QT change can be estimated from the equation QT=k⁴√RR and the difference between a measured QT and the estimated RR-corrected QT would be a genuine effect of the drug or maneuver on the QT at that heart rate. We conclude that atropine, isoproterenol and exercise actually shorten the QT interval.     

Relationships of left ventricular systolic time intervals with hemodynamic variables in intact and failing hearts.

Deviation of systolic time intervals (STI) from the regression lines obtained from 122 normal subjects was studied in 22 healthy adults (Group 1), 18 N.Y. functional class I cardiac patients (Group II) with ischemic (IHD) or primary myocardial disease (PMD), and 15 similar patients (pts) but N.Y. functional class II with prior heart failure (Group III). STIc (corrected for heart rate) were normal in Groups I and II. Supine exercise caused shortening of pre-ejection period PEPc and prolongation of left ventricular ejection time ETc in both groups. Group III pts had a significantly longer PEPc and shorter ETc at rest. Supine exercise caused further prolongation of PEPc and a slight prolongation of ETc in this group. In 8 mongrel dogs, the effect of controlled changes of hemodynamic variables on STI was studied with intact hearts and repeated after myocardial impairment has been induced by pentobarbital. Doubling of venous return while the heart was intact produced changes in STI similar to the effects of supine exercise in Groups I and II human subjects. With myocardial impairment, comparable increase in venous return had an effect on STI similar to the effect of supine exercise Group III patients. Controlled increase in each of heart rate or blood pressure, with other hemodynamic variables kept constant, produced changes in STI different from the effect of supine exercise on human subjects. The study suggests that the value of supine exercise induced changes in STI in reflecting left ventricular performance is attributable primarily to increased volume load. In this resepct supine exercise is probably superior to other forms of exercise in disclosing impaired left ventricular performance.     

The antihypertensive and cardiac hemodynamic effects of nebivolol.

Acute, subacute, and chronic treatment with nebivolol, a novel beta 1-selective adrenergic antagonist, significantly lowered systolic and diastolic blood pressure and heart rate in patients with essential hypertension. No orthostatism and bradycardia were reported. A comparison between a normal control group and 23 hypertensive patients revealed that the ratio between the preejection period (PEP) and the left ventricular ejection time (LVET) of the systolic time intervals (STI) was significantly increased in the hypertensive patients, owing to a prolongation of the PEPc (PEP corrected for heart rate). Treatment with nebivolol 5 mg once a day significantly improved the PEP/LVET, in acute conditions from 0.42 +/- 0.023 to 0.39 +/- 0.018, after one month of treatment from 0.40 +/- 0.013 to 0.36 +/- 0.013 and after one year of treatment from 0.41 +/- 0.012 to 0.36 +/- 0.010, owing to a significant shortening of the PEPc. There was no correlation between changes of blood pressure and changes of STI. Diastolic dysfunction is an early finding in hypertension and may well be reflected in the prolongation of the PEPc. The improvement of left ventricular performance, as measured with STI, suggests that treatment with nebivolol may favorably influence the underlying diastolic dysfunction and be of therapeutic value for hypertensive patients with left ventricular damage.     

Atrial rate-responsive pacing in sinus node disease

Patients with sinus node disease (SND) who are unable to achieve an adequate increase in heart rate during exercise are candidates for atrial rate-responsive pacing (AAI-R). We have implanted 40 AAI-R systems in SND patients with an average follow-up of 12.5 +/- 8 (range 3-30) months. All the patients received an activity-sensing pulse generator (Activitrax, Medtronic or Sensolog, Siemens-Pacesetter) with a single atrial lead. Only patients with an intraoperative AV nodal block cycle-length above 100 beats min-1 were included. During follow-up, one patient was observed to have transient asymptomatic 2:1 AV-block during sleep. No patient developed persistent AV-block or chronic atrial fibrillation. Twelve patients with persistent chronotropic incompetence were assigned for a randomized double-blind crossover study, comparing exercise treadmill capacity in AAI-R with conventional atrial inhibited pacing (AAI). During AAI-R pacing the maximum heart rate during exercise was 120 +/- 1 beats min-1 compared with 97 +/- 21 beats min-1 during AAI pacing (P less than 0.01). The average exercise time increased from 11.2 +/- 2 min during AAI-pacing to 13.4 +/- 3 min during AAI-R pacing (P less than 0.01). AAI pacing should be considered for patients with SND and chronotropic incompetence.