Efficacy of atropine as a chronotropic agent in heart transplant patients undergoing dobutamine stress echocardiography

BACKGROUND: After heart transplant (HTX), the heart is completely denervated. While sympathetic reinnervation is likely to occur, there is conflicting evidence regarding parasympathetic reinnervation. Accordingly, it is unclear if atropine is efficacious as a chronotropic agent in HTX patients undergoing dobutamine stress echocardiography (DSE), since cholinergic cardiac stimulation is required for atropine to exert its effect. The purpose of this study was to demonstrate that atropine can sufficiently increase the heart rate (HR) in HTX patients undergoing DSE. METHODS: A retrospective review was performed on 68 HTX patients who underwent DSE as part of their routine annual HTX follow-ups. Dobutamine was administered in the standard fashion of 10, 20, 30, 40, 50 mcg/kg per minute with blood pressure and electrocardiographic monitoring. If target HR was not attained, atropine was administered to aid in achieving 85% of maximum age-predicted HR. RESULTS: Mean patient age was 58 +/- 10 years. Mean period since transplant was 9 +/- 4 years. Forty-seven (69%) patients received dobutamine only, and 21 (31%) required additional atropine to reach target HR. Of the 21 patients who received atropine, 10 (48%) reached target HR. Neither time from transplant, age, gender, resting HR, medications, nor atherosclerotic risk factors predicted responsiveness to atropine. Those responding to dobutamine had a significantly greater resting HR than those receiving additional atropine. CONCLUSIONS: The adjunctive use of atropine in HTX patients during DSE aids in reaching 85% of maximum predicted HR in some patients. Furthermore, resting HR may predict the additional need of atropine during DSE.     

Alterations in heart rate variability in patients undergoing dobutamine stress echocardiography, including patients with neurocardiogenic hypotension

Frequency-domain analysis of heart rate variability (HRV) appears to distinguish sympathetic and parasympathetic modulation of heart rate. The effects of acute reflex, as opposed to tonically augmented, cardiac vagal tone on HRV are not clearly defined. Power spectral components of HRV were measured in 36 patients undergoing dobutamine stress echocardiography including during episodes of neurocardiogenically mediated hypotension. The low-frequency (LF; 0.04 to 0.15 Hz) and high-frequency (HF; 0.15 to 0.40 Hz) components of HRV decreased with increasing dose of dobutamine (5 to 40 μg/kg/min) in patients whose systolic blood pressure, compared with baseline, remained within 20 mm Hg (normotensive) or increased >20 mm Hg (hypertensive). The ratio of became <1 in the hypertensive group at 30 and 40 μg/kg/min of dobutamine. In eight patients in whom apparent neurocardiogenically mediated hypotension developed (decrease in systolic blood pressure >20 mm Hg from baseline), LF and HF measures became significantly higher than those in the patients without hypotension, whereas the ratio was unchanged. These findings suggest that the HF component of HRV is a reliable measure of reflex-augmented cardiac vagal activity and lend further support to the importance of parasympathetic modulation of the LF component of HRV.     

Prognostic significance of chronotropic response to dobutamine stress echocardiography in patients with peripheral arterial disease

Chronotropic response is important during exercise stress testing. Less is known about its role after dobutamine stress echocardiography. In addition, limited information exists regarding the long-term prognostic value of dobutamine stress echocardiography in patients who have peripheral arterial disease. We studied 2,138 patients who had peripheral arterial disease (1,317 men, 70 +/- 10 years old) and who underwent dobutamine stress echocardiography. Follow-up was completed for all-cause mortality and cardiovascular morbidity (nonfatal myocardial infarction and coronary revascularization). Death and cardiovascular morbidity occurred in 961 patients (45%) and 348 patients (16%), respectively, during a follow-up of 6.1 +/- 2.7 years. Failure to achieve 85% of age-predicted maximal heart rate (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.16 to 1.54, p = 0.0001) and percent of abnormal segments at peak stress (HR/10% increment 1.04, 95% CI 1.01 to 1.07, p = 0.02) were independent predictors of mortality and morbidity (HR 1.35, 95% CI 1.06 to 1.71, p = 0.01 and HR 1.14, 95% CI 1.08 to 1.20, p <0.0001, respectively). The effect of not achieving the target heart rate during normal dobutamine stress echocardiography on 1-, 3-, 5-, and 10-year survival probabilities was comparable to that of ischemia (86% vs 88%, 75% vs 71%, 62% vs 59%, and 33% vs 32%, respectively; p = 0.8). In a stepwise multivariate model, dobutamine stress echocardiography had incremental value over clinical data and echocardiographic data at rest for predicting rates of mortality (model chi-square increase from 301 to 322, p <0.0001) and morbidity (model chi-square increase from 37 to 118, p <0.0001). In conclusion, chronotropic response and extent of abnormal segments at peak dobutamine stress provide incremental prognostic information in patients who have peripheral arterial disease.     

Comparison of arm and treadmill exercise at 85% predicted maximum heart rate

Both treadmill exercise and arm exercise are used for evaluating coronary artery disease, but arm exercise has lower diagnostic sensitivity. We compared the two exercise modalities with respect to the rate-pressure product at 85% predicted maximal heart rate, a parameter frequently used to denote performance of sufficient exercise to derive clinical conclusions. At this heart rate, treadmill exercise resulted in a significantly greater systemic oxygen consumption (2.7 +/- .8 vs. 2.1 +/- .6 l/min) and rate-pressure product (30.6 +/- 4.4 X 10(3) vs. 28 +/- 3.3 X 10(3)) than arm ergometry. An inability to generate sufficient imbalance of myocardial oxygen supply and demand may account for the relatively higher incidence of false negative exercise tests seen with arm ergometry, especially if the exercise test is stopped when the patient attains 85% predicted maximal heart rate.     

NT-proBNP response to dobutamine stress echocardiography predicts left ventricular contractile reserve in dilated cardiomyopathy

BACKGROUND: Brain natriuretic peptide (BNP) and left ventricular (LV) inotropic reserve are major prognostic indexes in heart failure (HF). AIMS: To investigate the relationship between N-terminal-proBNP (NT-proBNP) changes in response to dobutamine stress echocardiography (DSE) and the LV inotropic reserve, in HF patients with dilated cardiomyopathy (DC). METHODS: We studied 41 patients with DC, LVEF 31.6+/-7.7%, NYHA class II-III and 15 controls. Plasma NT-proBNP levels were measured before and 60 min after three 5-min stages of dobutamine (5 to 15 microg/kg/min). RESULTS: Based on NT-proBNP changes in response to dobutamine, patients were categorized into two groups: In Group A circulating NT-proBNP levels fell (-16.6+/-7.8%), and in Group B they increased (8.4+/-9.1%). Group A had a marked improvement in WMSI compared to Group B (32.1+/-9.7% vs. 18.8+/-15.9%, p<0.001). Multivariate analysis showed that NT-proBNP changes were an independent predictor of LV inotropic reserve (b= -0.55, p<0.001). A reduction of 21.3% in plasma NT-proBNP levels in response to dobutamine predicted an improvement in WMSI of >25% with a sensitivity of 100% and a specificity of 92.3%. CONCLUSIONS: NT-proBNP changes in response to dobutamine reflect improvement in LV contractility and constitute an independent predictor of LV inotropic reserve in patients with DC.     

Variability of inotropic and chronotropic response during dobutamine stress echocardiography and possible implications for diagnostic accuracy

Chronotropic and inotropic response patterns were assessed during dobutamine stress echocardiography. Three heart rate response patterns were noted: nonresponders (48% of patients), slow responders (30% of patients), and fast responders (21% of patients). There was no relation between heart rate and contractile response.     

Abnormal chronotropic reserve and heart rate recovery in patients with SLE: a case-control study

Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5?±?1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5?±?1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (ΔHRR) was defined as the difference between HR at peak exercise and at both first (ΔHRR1) and second (ΔHRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6?±?0.9 vs. 36.7?±?1.1?ml/kg/min, p?=?0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8?±?2.4 vs. 98.2?±?2.6%, p?=?0.001), ΔHRR1 (22.1?±?2.5 vs. 32.4?±?2.2%, p?=?0.004) and ΔHRR2 (39.1?±?2.9 vs. 50.8?±?2.5%, p?=?0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed ΔHRR.     

The incremental prognostic value of percentage of heart rate reserve achieved over myocardial perfusion single-photon emission computed tomography in the prediction of cardiac death and all-cause mortality: superiority over 85% of maximal age-predicted heart rate

OBJECTIVES: We sought to determine whether chronotropic incompetence (CI) adds incremental value in predicting cardiac death (CD) and all-cause mortality and to determine which marker of CI is superior. BACKGROUND: Chronotropic incompetence, defined by either a low percent heart rate (HR) reserve achieved or failure to achieve 85% maximal age-predicted heart rate (MA-PHR), is a predictor of mortality. These variables have not been examined together in a comprehensive myocardial perfusion single-photon emission computed tomographic (SPECT), or MPS, model. METHODS: A total of 10,021 patients who underwent exercise MPS, evaluated by a summed stress score (SSS), were followed up for 719 +/- 252 days. Percent HR reserve = (peak HR - rest HR)/(220 - age - rest HR) x 100, with <80% considered abnormal. RESULTS: A total of 2,956 patients (29.5%) had low %HR reserve; 1,331 (13.3%) achieved <85% MA-PHR; and 1,296 (13.0%) had both. There were 234 deaths (93 CDs). On multivariate analysis, the SSS, %HR reserve, and inability to achieve 85% MA-PHR were predictors of all-cause mortality and CD (all p < 0.01). Myocardial perfusion SPECT was the most powerful predictor of CD (chi-square = 50). When the %HR reserve and ability to achieve 85% MA-PHR were considered, only the former remained a predictor of CD (p = 0.006 vs. p = 0.59). CONCLUSIONS: In a comprehensive MPS model, CI was an important predictor of CD and all-cause mortality. Percent HR reserve was superior to the ability to achieve 85% MA-PHR in predicting CD; MPS was superior to both. Combined with previous studies, the findings suggest that %HR reserve should become the standard for assessing the adequacy of HR response during exercise testing, and that it should be routinely incorporated in risk stratification algorithms.     

Abnormal heart rate recovery after exercise as a reflection of an abnormal chronotropic response

Abnormal decline in heart rate (HR) after exercise has been linked to increased cardiac mortality. This study compares the decrease in HR in different patient types, elucidates the relation between the increase and decrease of HR with exercise, and studies the role of beta blockers on the recovery of HR after exercise. One hundred patients with coronary artery disease (CAD), 50 subjects with a very low likelihood of CAD (normals), and 21 postcardiac transplant (Tx) patients underwent Bruce protocols. Peak HR, percent of peak HR achieved, HR reserve percent, and decline in HR at 1, 3, 5, and 8 minutes were obtained for all groups and also for subgroups based on the use of beta blockers. HR recovery at 1, 3, 5, and 8 minutes differed significantly between patients with CAD, normals, and Tx patients. HR recovery at 1, 3, 5, and 8 minutes also differed significantly within the groups (normal and CAD) based on the use of beta blockers. There was highly significant correlation between decrease in HR and peak HR, percent peak HR and HR reserve percent in normal and CAD groups. After correction of the HR recovery for dependence on peak HR and HR reserve percent, the difference in HR recovery between normal and CAD groups was markedly reduced. The difference in the decrease of HR within each group (normal and CAD), based on the use of beta blockers or not, was also markedly reduced. beta blockers have a significant impact on the decrease in HR due to its effect on chronotropism. HR recovery rate is highly dependent on the chronotropic response. Hence, the main portion of the abnormality in HR recovery after exercise can be explained by chronotropic incompetence.     

Assessment of myocardial viability by dobutamine stress echocardiography in patients with ischemic heart disease

Detection of viable (hibernating) myocardium is necessary for determination of prognosis and tactics of treatment of patients with ischemic heart disease. For detection of viable myocardium and investigation of possibilities of its restoration 60 patients with ischemic heart disease (54 men, mean age 52+/-8 years) were examined before coronary artery bypass grafting or coronary angioplasty. Presence of viable myocardium was characteristic for patients with multivessel coronary artery disease (83%) with stenoses >90%, with well developed collateral circulation (81%). Sustained restoration of contractility of hibernating segments for 1 year after revascularization was noted in 70% of cases. Dobutamine stress echocardiography was found to have high diagnostic potential for detection of viable myocardium.     

Diagnostic accuracy of dobutamine stress echocardiography for detection of coronary heart disease in hypertensive patients

To compare the diagnostic accuracy between dobutamme echocardiographyand treadmill exercise electrocardiography in detecting coronaryartery disease in hypertensive patients, 43 patients withoutelectrocardiographic evidence of left ventricular hypertrophyand basal ST-T changes, who had also undergone coronary angiography,were further evaluated by dobutamine echocardiography. The patientsalso underwent treadmill exercise echocardiography. Left ventricularmass index was calculated by echocardiography. Twenty-nine patientshad coronary artery disease, of whom 22 had multi-vessel diseaseand 14 a normal coronary anatomy. Twenty-eight patients hadan increased left ventricular mass index. The sensitivitiesof dobutaniine echocardiography and exercise electrocardiographyfor detecting coronary artery disease were 93% and 72% (P=0·08)respectively, and the specificities were 100% and 29%(P<0·005),respectively. Logistic regression analysis showed exercise electrocardiographyto be a poor predictor of coronary artery disease (P<0·09)but dobutamine echocardiography was significantly better (P<0·00l).When patients with increased left ventricular mass index wereexcluded, prediction of coronary anatomy by exercise electrocardiographyimproved only marginally (P=0·4) while dobutamine echocardiographywas significantly better (P<0·00l). Thus dobutamineechocardiography is superior to exercise electrocardiographyfor diagnosis of coronary artery disease in hypertensive patients.     

Usefulness of low-dose dobutamine echocardiography to predict response and outcome in patients undergoing cardiac resynchronization therapy

A substantial proportion of patients who meet the current guidelines for cardiac resynchronization therapy (CRT) fail to respond to this pacing modality. Although appropriate patient selection and left ventricular (LV) lead location have been ascribed as determinants of CRT response, the interaction among contractile reserve, dynamics of dyssynchrony, and lead location is not well understood. The present study prospectively evaluated the effect of contractile reserve and dobutamine-induced changes in LV synchrony, in relation to the LV lead location, as predictors of the response to CRT. In the present study, 31 patients were prospectively evaluated and underwent low-dose dobutamine echocardiography. The dobutamine-induced increase in ejection fraction (contractile reserve [CR]) was measured, and the most mechanically delayed segment was identified to classify patients into 2 groups. Group 1 had a CR of >20% and a LV lead position concordant with the mechanically delayed segment. Group 2 included the remaining patients (i.e., low CR, discordant LV lead position, or both). Patients in group 1 were significantly more likely to have an echocardiographic response at 6 months (80% of group 1 vs 29% of group 2, p = 0.018) and had an improved 2-year heart failure hospitalization-free survival rate (90% in group 1 vs 33% in group 2, p = 0.006). In conclusion, low-dose dobutamine echocardiography provides information that can help to predict responders to CRT. The response rates and heart failure hospitalization-free survival were improved in those patients with a CR >20% and an LV lead tip concordant with the most delayed mechanical segment.     

Safety of dobutamine stress echocardiography in patients with aortic stenosis

BACKGROUND AND AIM OF THE STUDY: Aortic valve disease is becoming one of the most important cardiac diseases in western society. Low-dose dobutamine stress echocardiography (DSE) is recommended in patients with low-gradient aortic stenosis (AS) and severe left ventricular (LV) dysfunction. DSE is also used in patients with AS and moderately reduced or normal LV function for diagnostic purposes. The study aim was to assess the safety of DSE in the setting of AS and various degrees of LV dysfunction. METHODS: A total of 75 patients with AS who underwent DSE at the authors' center between 1997 and 2001 was reviewed. Group A patients (n = 20) had severely reduced mean LV ejection fraction (LVEF) of 25 +/- 6% and underwent low-dose DSE; group B patients (n = 55) had moderate to normal LV function (LVEF 51 +/- 8%) and underwent high-dose DSE. The mean pressure gradient, valve area and side effects after DSE were evaluated. RESULTS: Serious cardiac arrhythmias occurred in 10 patients. In group A, four patients (20%) developed non-sustained ventricular tachycardia. In group B, two patients (4%) had non-sustained ventricular tachycardia (VT), four (7%) had paroxysmal supraventricular tachycardias, and two (4%) severe symptomatic hypotension. Among the 20 patients with evidence of ischemia on DSE, three developed adverse side effects (no difference compared with patients without ischemia; p = 0.922). Fourteen patients received atropine during DSE, and 1 of these developed non-sustained VT after atropine administration. CONCLUSION: Serious cardiac arrhythmias occur frequently during both low-dose and high-dose DSE in patients with AS. Adverse side effects do not relate to stress-induced ischemia or atropine addition.     

Results of dobutamine stress echocardiography in patients with Syndrome X

This study describes the results of Dobutamine stress echocardiography in 10 patients with Syndrome X. The diagnosis of Syndrome X was made on the basis of the presence of exertional angina, positive exercise stress test, negative ergonovine stress test and normal coronary arteries at angiography. All patients underwent Dobutamine stress echocardiography after interruption of any antianginal therapy. Dobutamine was infused starting with a dose of 5 mcg/kg/min over 3 minutes with incremental steps of 5 mcg/kg/min every 3 minutes up to a maximal dose of 40 mcg/kg/min. Two-dimensional echocardiography and 12-lead electrocardiography was monitored during the infusion of the drug. Nine patients received the maximal dose while one patient prematurely stopped the test for the occurrence of side effects. None of the ten patients developed segmental left ventricular wall motion abnormalities indicative of myocardial ischemia; ST-segment depression diagnostic for ischemia developed in 30% of patients; angina was elicited in one of these patients and in two additional patients. A hyperkinetic response to Dobutamine infusion involving all the segments of the left ventricle was observed both in patients with and without chest pain or electrocardiographic changes.In patients with Syndrome X Dobutamine induces a hyperkinetic left ventricular response indicative of normal contractile reserve despite the presence in some cases of angina and electrocardiographic signs of ischemia.     

Comparison of the chronotropic response to exercise and heart rate recovery in predicting cardiovascular mortality.

BACKGROUND: Both an impaired capacity to increase heart rate during exercise testing (chronotropic incompetence), and a slowed rate of recovery following exercise (heart rate recovery) have been shown to be associated with all-cause mortality. It is, however, unknown which of these responses more powerfully predicts risk, and few data are available on their association with cardiovascular mortality or how they are influenced by beta-blockade. METHODS: Routine symptom-limited exercise treadmill tests performed on 1910 male veterans at the Palo Alto Veterans Affairs Medical Center from 1992 to 2002 were analyzed. Heart rate was determined each minute during exercise and recovery. Chronotropic incompetence was defined as the inability to achieve > or =80% of heart rate reserve, using a population-specific equation for age-predicted maximal heart rate. An abnormal heart rate recovery was considered to be a decrease of <22 beats/min at 2 min in recovery. Cox proportional hazards analyses including pretest clinical data, chronotropic incompetence, heart rate recovery, the Duke Treadmill Score (abnormal defined as <4), and other exercise test responses were performed to determine their association with cardiovascular mortality. RESULTS: Over a mean follow-up of 5.1+/-2.1 years, there were 70 deaths from cardiovascular causes. Both abnormal heart rate recovery and chronotropic incompetence were associated with higher cardiovascular mortality, a lower exercise capacity, and more frequent occurrence of angina during exercise. Both heart rate recovery and chronotropic incompetence were stronger predictors of risk than pretest clinical data and traditional risk markers. Multivariately, chronotropic incompetence was similar to the Duke Treadmill Score for predicting cardiovascular mortality, and was a stronger predictor than heart rate recovery [hazard ratios 3.0 (95% confidence interval 1.9-4.9), 2.8 (95% confidence interval 1.7-4.8), and 2.0 (95% confidence interval 1.1-3.5) for abnormal Duke Treadmill Score, chronotropic incompetence, and abnormal heart rate recovery, respectively]. Having both chronotropic incompetence and abnormal heart rate recovery strongly predicted cardiovascular death, resulting in a relative risk of 4.2 compared with both responses being normal. Beta-blockade had minimal impact on the prognostic power of chronotropic incompetence and heart rate recovery. CONCLUSION: Both chronotropic incompetence and heart rate recovery predict cardiovascular mortality in patients referred for exercise testing for clinical reasons. Chronotropic incompetence was a stronger predictor of cardiovascular mortality than heart rate recovery, but risk was most powerfully stratified by these two responses together. The simple application of heart rate provides powerful risk stratification for cardiovascular mortality from the exercise test, and should be routinely included in the test report.