Exercise release of cardiac natriuretic peptides is markedly enhanced when patients with coronary artery disease are treated medically by beta-blockers

OBJECTIVES: This study sought to identify determinants of the exercise rise in plasma levels of cardiac natriuretic peptides (NPs) in patients with coronary artery disease (CAD). BACKGROUND: During stress, there is a variable rise in the plasma level of NPs, but this rise frequently reaches levels that are known to lower the cardiac load and that thus might be beneficial to CAD patients. METHODS: Plasma venous concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined at rest and peak exercise in 104 patients with chronic CAD who were referred to exercise thallium-201 ((201)Tl) single-photon emission computed tomography (SPECT) and radionuclide angiography. RESULTS: The extent of scarred myocardium by (201)Tl-SPECT and patient age were the best independent predictors of NP concentrations at rest, but also of increases in NP concentration during exercise (all p < 0.001). Moreover, beta-blocking treatment was an additional and strong independent predictor of the increase in NP concentrations at exercise (p < 0.001 for ANP; p = 0.001 for BNP). On average, exercise increases in NP concentrations were more than twice as high in patients with (n = 55) than in those without (n = 49) beta-blocker treatment (ANP: +49 +/- 63 vs. +22 +/- 25 ng/l, p = 0.01; BNP: +24 +/- 5 vs. +11 +/- 15 ng/l, p = 0.04), whereas NP concentrations at rest were equivalent in the two groups (ANP: 34 +/- 34 vs. 30 +/- 33 ng/l, p = NS; BNP: 85 +/- 152 vs. 57 +/- 101 ng/l, p = NS). CONCLUSIONS: Patients with chronic CAD exhibit much higher exercise releases of ANP and BNP when they are treated with beta-blockers. This enhanced secretion of potent vasodilating and natriuretic agents constitutes an original therapeutic mechanism for further protecting diseased hearts against stress.     

Augmented response in plasma brain natriuretic peptide to dynamic exercise in patients with left ventricular dysfunction and congestive heart failure

OBJECTIVES: We have previously demonstrated that patients with symptomatic congestive heart failure (CHF), but not with asymptomatic left ventricular dysfunction (LVD), have augmented plasma atrial natriuretic peptide (ANP) response to exercise. Plasma brain natriuretic peptide (BNP) response to exercise is less extensively studied. The aim of this study was to determine whether responses of plasma BNP during exercise normalized for exercise workload are altered in patients with LVD and CHF. SUBJECTS AND METHODS: Twenty-nine patients with LVD, 32 patients with CHF (NYHA classes II-III) and 27 age-matched control subjects were studied. Ventilatory, plasma ANP and BNP responses were assessed during symptom-limited cardiopulmonary exercise testing. Plasma natriuretic peptide levels were measured at rest and immediately after peak exercise. The increment in plasma BNP was divided by the increment in oxygen uptake (VO2) from rest to peak exercise, and this ratio [BNP exercise ratio: (peak BNP - rest BNP)/(peak VO2 - rest VO2)] was compared amongst the three groups. RESULTS: Peak VO2 (Control, LVD and CHF: 28.2 +/- 1.7, 21.1 +/- 1.8, 16.2 +/- 0.6 ml, min(-1) kg(-1), respectively), anaerobic threshold and peak workload became smaller as heart failure worsened. Resting and peak plasma ANP levels were significantly higher only in CHF, whilst resting and peak plasma BNP levels displayed a significant and continuous increase from normal subjects to LVD and CHF. The ANP exercise ratio (1.25 +/- 0.36, 2.61 +/- 0.57, 7.72 +/- 1.65, ANOVA P = 0.0002) was significantly higher only in patients with CHF, whilst the BNP exercise ratio (0.35 +/- 0.10, 2.60 +/- 0.69, 4.98 +/- 0.97, ANOVA P = 0.0001) was significantly higher in patients with LVD and became progressively higher in patients with CHF. CONCLUSIONS: These data showed that the BNP exercise ratio, an exercise plasma BNP response normalized with exercise workload, was augmented in patients with LVD, and became progressively higher in CHF, suggesting that an augmented exercise BNP ratio exists early in the course of developing CHF.     

Exercise-induced ST-segment depression: imbalance between myocardial oxygen demand and myocardial blood flow

OBJECTIVE: ST-segment depression is believed as a common electrocardiographic sign of myocardial ischemia during exercise testing. Ischemia is generally defined as oxygen deprivation due to reduced perfusion. However, the exact relationship of the ischemic definition to ST-segment depression remains unclear. This study was conducted to evaluate the correlation between myocardial oxygen demand and myocardial blood flow (MBF) when ischemic (horizontal or downsloping) ST-segment depression of > or = 0.1 mV 80 ms after the J point developed during low-level exercise. METHODS AND RESULTS: Seventy-two patients with angiographically proven coronary artery disease (CAD) and 9 healthy volunteers underwent exercise positron emission tomography (PET). Myocardial oxygen demand was defined as a rate-pressure product (RPP, heart rate x systolic blood pressure) during exercise and MBF was quantified by nitrogen-13 ammonia perfusion PET. The myocardial demand-supply balance (MDSB) index was calculated from the MBF ratio (values during exercise/values at rest) against the RPP ratio (values during exercise/values at rest). The MDSB index was significantly lower in patients with ischemic ST-segment depression than in patients with non-ischemic ST depression and healthy volunteers (0.82 +/- 0.16 vs. 1.02 +/- 0.17, p < 0.0001 and vs. 0.99 +/- 0.14, p = 0.0109). Further, the presence of inadequate increase in MBF of < or = 10% (2 SD below the mean % value of healthy volunteers) during exercise in regional myocardium perfused by stenotic CAD significantly correlated with exercise-induced ischemic ST-segment depression (p = 0.0105). CONCLUSIONS: Our study could demonstrate that exercise-induced ischemic ST-segment depression is associated with myocardial ischemia due to exercise-induced imbalance between myocardial oxygen demand and global and regional MBF supply in patients with proven CAD.     

QT peak dispersion, not QT dispersion, is a more useful diagnostic marker for detecting exercise-induced myocardial ischemia.

BACKGROUND: The electrocardiographic indices of QT dispersion (QTd), QT peak dispersion (QTpd), and the principal component analysis ratio (PCAr) are related to the occurrence of fatal arrhythmia and are influenced by physical exercise. OBJECTIVE: The purpose of this study was to investigate whether or not the QT parameters can be used as markers for exercise-induced myocardial ischemia. METHODS: We measured these QT parameters at rest and at 3 minutes after exercise using exercise-stress thallium-201 scintigraphy (SPECT), compared with conventional ST segment changes in 161 patients with suspected or known coronary artery disease. The patients were classified into four groups (normal, redistribution, fixed defect, and redistribution with fixed defect) according to SPECT. RESULTS: At rest, QTd and PCAr were greater in the fixed defect and redistribution with fixed defect groups. PCAr, however, increased after exercise in the redistribution and redistribution with fixed defect groups. Although QTpd at rest was not significantly different among the four groups, it increased in the redistribution and redistribution with fixed defect groups after exercise (QTpd after exercise: normal, 36 +/- 16 ms vs. redistribution, 51 +/- 23 ms, redistribution with fixed defect, 53 +/- 19 ms; P<.05). For myocardial infarction reflected by fixed defect, QTd at rest was the most useful indicator, while QTpd after exercise was the most useful indicator for exercise-induced myocardial ischemia according to multiple logistic regression analysis with receiver operating characteristic curves. In addition, the change in PCAr by exercise was an independent predictor for exercise-induced ischemia. CONCLUSIONS: QTpd and PCAr could be useful indices for exercise-induced myocardial ischemia. Determining the QTpd of a patient after exercising can improve the diagnostic accuracy of ischemia in a routine clinical setting.     

Effect of bypass operation and balloon angioplasty on heart function at rest]

Improvement of exercise left-ventricular ejection fraction after successful aortocoronary bypass operation and transluminal coronary angioplasty has been demonstrated. The purpose of this study was to investigate in which patients improvement of left-ventricular function at rest can be observed. Radionuclide ventriculography and exercise stress test was carried out in 34 patients before and after successful aortocoronary bypass operation (Group 1), and in 69 patients before and after successful transluminal coronary angioplasty (Group 2). After bypass surgery, mean ejection fraction at rest increased from 42 +/- 11 to 49 +/- 13% (p less than 0.001). Marked improvement (greater than or equal to 5%) was observed in 19 patients (56%) in whom severe myocardial ischemia could be documented during exercise ECG (Group 1.1: Increase of ejection fraction from 40 +/- 14 to 54 +/- 12%, p less than 0.001; ischemia score during exercise test 8.8 +/- 10). In the remaining 15 patients no significant improvement occurred (Group 1.2: 43 +/- 16 vs. 43 +/- 16%, p = n.s.; ischemia score during exercise test 3.2 +/- 2.4, p = 0.02 vs. Group 1.1). After angioplasty, resting left-ventricular ejection fraction increased, on average, from 50 +/- 11 to 52 +/- 12% (p less than 0.001). Comparable to the results observed in patients after surgery, improvement was most pronounced in patients with severe exercise-induced ST-depression (Group 2.1: Increase of ejection fraction from 49 +/- 10 to 58 +/- 10%, p less than 0.001; ischemia score during exercise 2.5 +/- 2.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise-induced QTc-interval changes for predicting improvement in regional blood flow in ischemic myocardium and cardiac output after coronary angioplasty in patients with right bundle-branch block

BACKGROUND: We have previously shown that QT-interval changes are more useful than ST-T changes in evaluating the severity of exercise-induced myocardial ischemia in patients with right bundle-branch block (RBBB). HYPOTHESIS: The purpose of this study was to evaluate whether the improvement in regional myocardial blood flow (RMBF) in ischemic areas and cardiac output after percutaneous transluminal coronary angioplasty (PTCA) can be predicted by exercise-induced QT-interval changes prior to PTCA. METHODS: The RMBF and cardiac output were quantified with nitrogen-13 ammonia positron emission tomography at rest and during exercise in 20 patients with RBBB and ischemic heart disease before and 6 months after PTCA, and in 9 healthy volunteers. RESULTS: Before PTCA, exercise-induced prolongation by < 20 ms or shortening of the Bazett-corrected QT (QTc) interval (454 +/- 38 to 451 +/- 41 ms, p = NS) was observed in 13 patients (Group 1) and prolongation by > or = 20 ms (429 +/- 44 to 466 +/- 50 ms, p < 0.002) was observed in 7 (Group 2). The number of regions of exercise-induced ischemia was significantly greater in Group 2 than in Group 1 (4.0 +/- 1.2 vs. 2.1 +/- 1.2, p < 0.01). The RMBF in regions of exercise-induced ischemia and cardiac output at rest was not significantly different between Groups 1 and 2, whereas during exercise both the parameters were significantly lower in Group 2 than in Group 1 (both p < 0.05). After successful PTCA, RMBF both at rest and during exercise improved significantly in Group 1 (0.67 +/- 0.04 to 0.71 +/- 0.06 ml/min/g, 0.74 +/- 0.05 to 0.84 +/- 0.08 ml/min/g; both p < 0.0001), but did not improve significantly in Group 2 (0.63 +/- 0.05 to 0.65 +/- 0.07 ml/min/g, 0.65 +/- 0.04 to 0.69 +/- 0.11 ml/ min/g; both p = NS). Cardiac output during exercise improved significantly in Group 1 (6.4 +/- 0.7 to 7.4 +/- 0.9 l/min; p < 0.002) but not in Group 2 (5.7 +/- 0.6 to 5.9 +/- 0.6 l/min; p = NS). CONCLUSIONS: Our results suggest that the marked prolongation of the QTc interval induced by pre-PTCA exercise may predict a lack of improvement in RMBF in ischemic areas and cardiac output after PTCA in patients with RBBB and ischemic heart disease.     

Increased plasma level of atrial natriuretic peptide in patients with stress-induced coronary insufficiency: stretch-independent release of atrial natriuretic peptide?

Plasma levels of atrial natriuretic peptide (ANP) were determined in 34 male patients undergoing diagnostic right heart catheterization. Patients with effort angina exhibited significant higher ANP levels at rest (259 +/- 42 pg/ml; n = 7) than patients without signs of coronary heart disease (78 +/- 30 pg/ml; n = 8). Patients with effort angina also had higher ANP levels at rest than patients exhibiting impaired cardiac function on exertion without signs of ischemia (105 +/- 15 pg/ml; n = 4), patients with only minimal functional alterations due to infarction residues (95 +/- 27 pg/ml; n = 7), or patients with only borderline changes of ST-segments during exertion (61 +/- 19 pg/ml; n = 8). In contrast, mean pulmonary capillary or right atrial pressures were not significantly different between the various groups of patients. The patients with effort angina also exhibited the highest ANP levels during bicycle exercise (846 +/- 238 pg/ml). There was only a weak to moderate linear correlation between ANP levels and pulmonary or right atrial pressures in the whole group of patients (r = 0.1-0.6). The plasma levels of epinephrine and norepinephrine and of ANP were not significantly correlated, with the exception of norepinephrine levels during exercise (r = 0.54). Our observations suggest that in patients with effort angina there may exist additional stretch-independent factors stimulating the release of ANP, possibly associated with repetitive myocardial ischemia.     

Early recognition of exercise-induced myocardial ischemia by plasma free fatty acid

To investigate whether or not myocardial free fatty acid (FFA) uptake is useful for early recognition of exercise-induced myocardial ischemia compared with myocardial lactate uptake, we studied in 8 patients with stable effort angina pectoris by measuring hemodynamic and metabolic parameters during supine multistage bicycle ergometer exercise (BEx). Analysis of FFA composition was performed by high performance liquid chromatography. The exercise endpoint in the control study was moderate chest pain in all cases. In all cases, BEx testing using the same method, duration and workload was repeated 1.5 hours after the oral administration of 6 mg of nilvadipine (a new calcium antagonist). Exercise time of the subjects studied was 463 +/- 40 sec (mean +/- SE, 180-540 sec). After administration of nilvadipine, chest pain was not induced in 6 patients and was lessened in severity in 2 patients. Mean ST segment depression was 0.21 +/- 0.05 mV in the control period and it was significantly reduced to 0.08 +/- 0.03 mV after nilvadipine administration (p less than 0.05). Myocardial FFA uptake decreased from 21.1 +/- 4.4% at rest to 8.1 +/- 2.1% at peak exercise in the control study (p less than 0.05). Myocardial lactate uptake was unchanged at rest and peak exercise in the control study (21.6 +/- 2.7 vs 22.2 +/- 3.3%). After administration of nilvadipine, myocardial FFA uptake did not change during BEx (25.3 +/- 2.7 at rest and 21.3 +/- 3.6% at peak exercise). At peak exercise, myocardial FFA uptake increased significantly after administration of nilvadipine (21.3 +/- 3.6 vs 8.1 +/- 2.1%, p less than 0.05). In FFA composition, the percentage of each of 12 FFA did not change during myocardial passage at rest and peak exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial ischemia during physical exercise in patients with stable coronary artery disease: predictability and prevention

AIMS: We assessed whether exercise-induced myocardial ischemia during intensive group exercise sessions can be predicted in patients with coronary artery disease and stable angina pectoris. METHODS AND RESULTS: Twenty-three patients underwent cardiac catheterization, 201-thallium scintigraphy, and exercise testing prior to participation in group training sessions. Heart rates and myocardial ischemia were documented by Holter monitoring. The individual training heart rate was calculated as a percentage of the maximal heart rate achieved during symptom-limited exercise testing. Myocardial ischemia occurred significantly more often during group exercise sessions (15 of 23 patients) than during treadmill testing (4 of 23 patients, P<0.001). Maximal heart rate (145+/-23 vs. 134+/-21 beats/min, P<0.004) and maximal plasma lactate concentrations (6.0+/-2.9 vs. 4.3+/-2.0 mmol/l, P<0.05) were significantly higher than during symptom-limited exercise testing. Ischemic episodes occurred significantly more often during jogging than during competitive ball games or interval training. Myocardial ischemia occurred in patients who exceeded their individual target training heart rates (43 of 44 episodes; P<0.001). Duration of ischemic episodes did not correlate with any marker obtained at the beginning of the study. CONCLUSION: These data demonstrate that routine diagnostic procedures do not sufficiently identify patients at risk for exercise-induced myocardial ischemia. Ischemic events are only effectively prevented by choosing adequate types of exercise and, above all, by the strict adherence to individual target heart rates.     

Exercise-induced ST-segment depression and systolic dysfunction in patients with nonobstructive hypertrophic cardiomyopathy

BACKGROUND: ST-segment depression is common in patients with hypertrophic cardiomyopathy (HCM). However, it is not clear whether exercise-induced ST-segment depression in patients with HCM and patent coronary arteries is associated with changes in left ventricular function. METHODS: Left ventricular function was continuously evaluated in 53 patients with nonobstructive HCM during supine ergometer exercise with a radionuclide ventricular function monitor equipped with a cadmium telluride detector. On the basis of the ST-segment changes during exercise, the patients were divided into 2 groups: group N had no ST-segment depression, and group D had >/=0.1 mV ST-segment depression. RESULTS: Exercise duration, blood pressure, heart rate, and rate-pressure product during exercise did not differ between the 2 groups. End-diastolic volume at rest and at peak exercise did not differ between groups D and N. In contrast, the end-systolic volume in group N decreased during exercise, whereas in group D it increased. As a result, the left ventricular ejection fraction in group D decreased from 70% +/- 7% to 59% +/- 15% (P <.0001), whereas ejection fraction in group N increased from 65% +/- 8% to 71% +/- 11% (P =.0002). There was a strong correlation between exercise-induced ST-segment depression and changes in ejection fraction from rest to peak exercise (P <.0001). CONCLUSIONS: These results suggest that the exercise-induced ST-segment depression seen in patients with nonobstructive HCM is associated with systolic dysfunction during exercise.     

Persistent ST segment depression in precordial leads V5-V6 after Q-wave anterior wall myocardial infarction is associated with restrictive physiology of the left ventricle

OBJECTIVES: To examine the relationship between the persistence of ST segment depression in leads V5-V6 after Q-wave anterior wall myocardial infarction (MI) and the filling pattern of the left ventricle (LV). BACKGROUND: Precordial ST segment depression predominantly in leads V5-V6 is associated with increased in-hospital morbidity and mortality after acute myocardial ischemia, perhaps due to reduced diastolic distensibility of the LV. METHODS: We prospectively studied 19 patients after Q-wave anterior wall MI (>6 months). All patients underwent 12-lead ECG recording, symptom-limited treadmill exercise testing with single photon emission computed tomography thallium-201 imaging, transthoracic Doppler echocardiography, cardiac catheterization and measurement of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels. Patients were classified based on the presence of ST segment depression in leads V5-V6: Group I = ST segment depression <0.1 mV (n = 10); Group II = ST segment depression > or =0.1 mV (n = 9). RESULTS: Patients in Group II had greater LV end diastolic pressures (32.4 +/- 6.5 mm Hg vs. 14.8 +/- 6.1 mm Hg; p = 0.0001), higher plasma ANP (44.4 +/- 47.1 pg/ml vs. 10.7 +/- 14 pg/ml; p = 0.04) and BNP levels (89.4 +/- 62.7 pg/ml vs. 23.6 +/- 33.1 pg/ml; p = 0.01), greater left atrium area (20.6 +/- 3.1 cm2 vs. 17.8 +/- 2.4 cm2; p = 0.05), lower peak atrial (A), higher early (E) mitral inflow velocities, a higher E/A ratio and a lower deceleration time (167 +/- 44 ms vs. 220 +/- 40 ms; p = 0.05). Lung thallium uptake during exercise was more common in Group II (78% vs. 10%, p = 0.04). CONCLUSIONS: Persistent ST segment depression in leads V5-V6 in survivors of Q-wave anterior wall MI is associated with increased LV filling pressure and a restrictive LV filling pattern.     

Effects of prolonged strenuous exercise on plasma levels of atrial natriuretic peptide and brain natriuretic peptide in healthy men

BACKGROUND: Now that marathon racing is growing in popularity, many thousands of enthusiastic athletes are participating in various ultramarathons all over the world each year. However, it remains controversial whether such a sport contributes to the promotion of health. The occurrence of transient cardiac dysfunction and irreversible myocardial injury has been reported in association with such exercise in healthy individuals. Brain natriuretic peptide (BNP) is a cardiac hormone, as is atrial natriuretic peptide (ANP), and its measurement has been widely used for clinical evaluation of cardiac dysfunction. However, little is known about the response of plasma BNP to prolonged strenuous exercise. We hypothesized that confirmation of minimal cardiac dysfunction or myocardial injury may be made by measurements of plasma BNP. METHODS: Levels of plasma ANP, BNP, catecholamines, blood lactate, and serum cardiac troponin T (cTnT) were determined before and after a 100-km ultramarathon in 10 healthy men to examine the effects of the exercise on levels of ANP and BNP and correlations between the natriuretic peptides and cTnT as a marker for myocardial damage. RESULTS: Whereas all variables significantly increased after the race, increased levels of ANP and BNP were most strongly correlated with increases in cTnT levels. The cTnT level after the race was greater than the upper reference limit in 9 of 10 men. CONCLUSIONS: Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.     

The changes in circulating levels of vasoactive intestinal polypeptide during exercise and its reproducibility for detection of myocardial ischemia

Vasoactive intestinal polypeptide (VIP) contributes to the regulation of coronary vasomotor tone and circulating levels of VIP have been reported to increase during acute myocardial infarction. However, the changes in VIP concentration during exercise-induced ischemia have not been studied yet. Therefore, we sought to determine whether circulating levels of VIP change during treadmill exercise testing and whether they could be used as a marker of exercise-induced myocardial ischemia. Twenty-nine subjects with definitive positive (group-I) and 20 subjects (group-II) with negative results on treadmill exercise testing were included in this study. In order to assess circulating levels of VIP, blood samples were collected in both groups before exercise, at 5 minutes of exercise, at peak exercise, and at 10 minutes in the recovery period. There were no differences between the two groups with respect to the baseline demographics of age, sex, heart rate, or blood pressure. The metabolic equivalents (METs) values, peak heart rate achieved, peak systolic-diastolic blood pressure, and exercise duration did not differ between the two groups. No significant differences were found in the circulating levels of VIP at any stage of the exercise between the two groups (10.5 +/- 2.5 versus 11.0 +/- 3.5 pmol/L, P = 0.5, 10.6 +/- 2.3 versus 10.6 +/- 3.3 pmol/L, P = 0.9, 10.9 +/- 3.1 versus 11.5 +/- 3.4 pmol/L, P = 0.5, and 10.7 +/- 1.8 versus 11.7 +/- 4.1 pmol/L, P = 0.3, respectively). There was no relationship between the circulating level of VIP and exercise-induced myocardial ischemia, and therefore it could not be used as a marker of exercise-induced myocardial ischemia.     

Relation of B-type natriuretic peptide levels before and after exercise and functional capacity in patients with idiopathic dilated cardiomyopathy

Although much is known about the value of B-type natriuretic peptide (BNP) at rest, the significance of the responsiveness of BNP during exercise in patients with chronic heart failure (HF) without coronary artery disease remains to be established. A role of BNP release during exercise in the functional disability of patients with chronic HF and idiopathic dilated cardiomyopathy (IDC) was hypothesized. One hundred five consecutive patients with an established diagnosis of HF and IDC who underwent symptom-limited cardiopulmonary exercise testing were studied. BNP was measured immediately before exercise and within 1 minute of the end of exercise. BNP at rest increased significantly at peak exercise (median from 66.5 (first, third quartiles 18, 168) to 72.0 pg/ml (26, 208), p <0.001), but BNP response was not uniform. BNP response increased in 63% of patients, did not change in 22%, and decreased in 15%. BNP at rest and BNP response showed an inverse correlation (p <0.001, r = -0.523). Aging and low left ventricular ejection fraction were independent predictors of higher BNP levels at rest, but lower BNP response. Beta-blocker therapy did not influence BNP response. BNP at rest correlated negatively with functional capacity (p <0.001, r = -0.516), whereas BNP response correlated positively (p = 0.002, r = 0.326). Patients with BNP release (vs patients without) had higher maximum oxygen consumption (19.2 +/- 5.1 vs 15.9 +/- 3.6, p <0.001), better functional capacity (59 +/- 13% vs 50 +/- 15%, p = 0.002), and lower minute ventilation/carbon dioxide production slope (33.6 +/- 4.8 vs 36.5 +/- 7.7, p = 0.026) independent of other clinical parameters. In conclusion, BNP release during exercise could be a determinant of functional capacity in patients with chronic HF and IDC.     

Effect of beta-blockade on low heart rate-related ischemia during mental stress.

To explore the effect of beta-adrenergic blockade on low heart rate-related (mental stress) ischemia, 19 patients with coronary artery disease were randomized into a double-blind crossover trial of metoprolol, 100 mg twice daily, and underwent serial mental stress/bicycle exercise studies. Mental stress-induced wall motion abnormalities occurred at a lower heart rate than exercise-induced wall motion abnormalities during placebo administration (81 +/- 16 vs. 123 +/- 20 beats/min, p less than 0.05). Metoprolol reduced the mean magnitude of exercise-induced wall motion abnormalities (2.8 +/- 2.0 vs. 1.6 +/- 2.4, p = 0.003); improvement was related to the magnitude of hemodynamic beta-blockade effect. Metoprolol did not significantly reduce the mean magnitude of mental stress-induced wall motion abnormalities (3.0 +/- 2.2 vs. 2.6 +/- 2.2), although individual responses predominantly either improved (50%) or worsened (29%). Unlike exercise, the magnitude of hemodynamic beta-blockade did not predict mental stress response and metoprolol did not block mental stress-induced blood pressure elevations. Patients with abolition of exercise-induced ischemia were more likely to have reduction of mental stress-induced ischemia. Patients whose ischemia worsened with metoprolol during mental stress had more easily inducible ischemia, as assessed by exercise-induced placebo wall motion abnormality, chest pain and prior myocardial infarction. Beta-blockade was associated with a lowering of ischemia-related hemodynamic thresholds compared with placebo. These results suggest that beta-blockade has a variable effect on low heart rate-related ischemia that may be due to a lack of effect on mental stress-induced blood pressure elevation in patients with easily induced ischemia or to effects on coronary vasomotor tone, or both.     

Interleukin-6 and tumor necrosis factor-alpha levels increase in response to maximal exercise in patients with chronic heart failure

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.     

Natriuretic peptide response to dynamic exercise in patients with atrial fibrillation

BACKGROUND: In patients with atrial fibrillation (AF) information regarding exercise release of atrial natriuretic peptide (ANP) is sparse and data on plasma brain natriuretic peptide (BNP) response to exercise is lacking. The aim of this study was to investigate plasma ANP and BNP response to exercise in patients with permanent AF and to assess if the response was different from the response in healthy age- and sex-matched control subjects. METHODS: Plasma venous concentrations of ANP and BNP were determined at rest, at peak exercise and 30 min from the end of exercise in 38 patients with permanent AF and in 43 age- and sex-matched healthy control subjects. RESULTS: Plasma concentrations of ANP and BNP were significantly higher in AF patients compared with the healthy control group at rest, peak exercise and after 30 min of recovery (p<0.0001). ANP and BNP increased significantly during exercise in both patients with AF and in the healthy control subjects (p<0.05). The increase in plasma concentration of ANP and BNP during exercise was significantly higher in AF patients compared with healthy controls (p=0.0002 for ANP; p<0.0001 for BNP). In the recovery period plasma BNP decreased significantly (p<0.0001) where as the decrease in plasma ANP was insignificant (p=0.4). CONCLUSIONS: Patients with permanent AF have elevated levels of ANP and BNP at rest and exhibit much higher exercise release compared to healthy control subjects. This enhanced secretion of potent vasodilating and natriuretic agents may represent an important compensatory mechanism to improve exercise capacity in patients with AF.     

Early detection of myocardial ischemia by myocardial free fatty acid extraction in patients with exercise-induced angina pectoris

This study investigated whether the measurement of plasma free fatty acids (FFAs) could assist in the early detection of exercise-induced myocardial ischemia. Fifteen subjects with effort angina pectoris underwent angina-limited supine bicycle ergometer exercise testing. Myocardial FFA extraction decreased significantly from 22.8 +/- 3.1% at rest to 7.7 +/- 1.5% at peak exercise (p less than 0.05). Myocardial lactate extraction showed no significant change between rest and peak exercise. After control exercise testing, 8 subjects were given a single oral dose of nilvadipine (6 mg) and then again underwent exercise testing for the same duration. Nilvadipine lessened or abolished chest pain and there was less depression of the ST segment at peak exercise. Furthermore, myocardial FFA extraction showed no significant change between rest and peak exercise after nilvadipine administration. These results suggest that myocardial FFA extraction can be used to assess the presence of exercise-induced myocardial ischemia at an earlier stage than myocardial lactate extraction.     

Prognostic value of exercise-induced QT dispersion in patients after acute myocardial infarction

BACKGROUND: Electrocardiographic exercise tests are widely recommended for patients before discharge after myocardial infarction, what justify the search for new variables which may improve their prognostic value. QT dispersion in 12 lead ECG reflects the heterogeneity of ventricular repolarisation. Increased QT dispersion is a noninvasive marker of ischaemia and electrical instability. AIM: Evaluation of the prognostic value of exercise-induced changes of QT dispersion in patients after an acute myocardial infarction. METHODS: Heart rate limited treadmill exercise test according to modified Bruce was performed 14+/-5 days after infarction in 77 patients (age 56+/-11,8 female). QT dispersion was measured at rest and on peak exercise. Patients were followed up for mean 88 months. RESULTS: QT dispersion was higher at peak exercise in those patients who died due to cardiovascular causes (n=8) or suffered from non-fatal myocardial infarction during follow-up (n=15), than in remaining group (71+/-20 vs 58+/-22 msec, p<0.01). At rest QT dispersion was similar in both groups (64+/-17 vs 66+/-20 msec, NS). CONCLUSIONS: The lack of an exercise-induced decrease in QT dispersion identifies a subgroup of patients after myocardial infarction with a poor long-term prognosis.     

Usefulness of exercise-induced changes in plasma levels of brain natriuretic peptide in predicting right ventricular contractile reserve after repair of tetralogy of Fallot

Elevated levels of brain natriuretic peptide (BNP) have been associated with ventricular dysfunction, and exercise tests have been used for assessing cardiac contractile reserve. We examined the relation between BNP and right ventricular (RV) contractile reserve during exercise in patients after repair of tetralogy of Fallot (TOF). A total of 45 patients, 26 of whom underwent repair of TOF at 2 to 3 years of age and 19 age-matched healthy children, were studied. Plasma levels of BNP were measured at baseline and at maximal exercise. Echocardiography combined with tissue Doppler imaging (TDI) was performed at rest and during supine bicycle submaximal exercise. The peak value of the first derivation of RV pressure (peak dP/dt) was measured by the continuous-wave Doppler method. The severity of pulmonary regurgitation (PR) (mild, moderate, or severe) was based on color Doppler findings. Plasma BNP levels were significantly higher in patients with TOF than in controls (44 +/- 34 vs 6 +/- 4 pg/ml, p <0.01). Exercise was associated with increased plasma BNP levels in both groups. A larger increment in BNP was noted in patients with TOF than in normal subjects (15 +/- 12 vs 2 +/- 2 pg/ml, p <0.01). The peak systolic myocardial velocity (Sa) and peak dP/dt values increased significantly in both groups during exercise; however, the magnitude of increase in both of these values was significantly less in patients with TOF than in controls (36 +/- 19% vs 70 +/- 19% and 42 +/- 11% vs 81 +/- 12%, respectively; p <0.01). There were significant correlations between the increment in BNP and changes in Sa and peak dP/dt values (r = -0.67 and -0.53, p <0.01, respectively), and the severity of PR (r = 0.74, p <0.01). Thus, exercise increases plasma levels of BNP, and greater increases are associated with impaired RV contractile reserve in patients with TOF with various degrees of PR.