Gender-related differences in left ventricular filling dynamics in older subjects after endurance exercise training

The present study was designed to determine if gender affects the adaptive response to endurance exercise training of left ventricular filling dynamics in older individuals. Recently, it was shown that gender influences the cardiovascular responses to endurance exercise training in older subjects. Older men improve left ventricular systolic performance and increase maximal cardiac output in response to endurance exercise training, whereas older women do not. Twelve men (65 +/- 1 years old; mean +/- SE) and 10 women (64 +/- 1) were studied before and after 9 months of endurance exercise training. Maximal O2 uptake was determined during treadmill exercise. Left ventricular filling dynamics and ejection fraction (EF) at rest and during supine exercise were assessed by Tc-99m radionuclide ventriculography. When expressed relative to body weight, maximal O2 uptake (VO2 max) was increased by 24% (27.3 +/- 1.5 to 34.0 +/- 1.5 ml/kg/min; p < .01) in men and 27% (21.9 +/- 1.0 to 27.8 +/- 1.0 ml/kg/min; p < .01) in women in response to endurance exercise training. In men, the time-to-peak filling rate (TPFR) decreased (-19.8 +/- 6.7 ms; p < .05) during exercise at a comparable heart rate in response to training. In contrast, the change in TPFR in women (+2.7 +/- 6.0 ms) was small and insignificant. Peak filling rate (PFR) at rest and during exercise was similar before and after training in men and women. The change in left ventricular systolic reserve at a comparable heart rate from pre-to posttraining improved in men (delta EF 4 +/- 3%; p < .05), but not in women (-2 +/- 3%). The results indicate that the adaptive response of left ventricular filling dynamics to endurance exercise training is influenced by gender in older subjects. Older men show improvement in left ventricular filling dynamics, whereas older women do not.     

Combined assessment of myocardial perfusion and left ventricular function with exercise technetium-99m sestamibi gated single-photon emission computed tomography can differentiate between ischemic and nonischemic dilated cardiomyopathy

The purpose of this study was to determine whether exercise technetium-99m sestamibi gated single-photon emission computed tomography (SPECT) accurately distinguishes between patients with ischemic cardiomyopathy and patients with nonischemic left ventricular systolic dysfunction. Noninvasive tests have previously failed to accurately separate patients with ischemic cardiomyopathy from those with nonischemic cardiomyopathy. Technetium-99m gated SPECT imaging offers advantages that have the potential to overcome the limitations of previous studies. Thirty-seven adults with a left ventricular ejection fraction < or = 35%, including 24 patients with nonischemic cardiomyopathy and 13 patients with ischemic cardiomyopathy, were prospectively evaluated using symptom-limited metabolic exercise treadmill testing with technetium-99m sestamibi gated SPECT imaging. Interpretation of myocardial perfusion and regional wall motion was performed, using a 17-segment model. Summed stress, rest, and reversibility perfusion defect scores were determined, and the variance of segmental wall motion scores was computed. Summed stress, rest, and reversibility perfusion defect scores were significantly lower in nonischemic cardiomyopathy patients, compared with those with ischemic cardiomyopathy (summed stress defect score: 6.9 +/- 3.8 vs 32.9 +/- 7.7, respectively, p <0.001). Variability in segmental wall motion was also significantly lower in patients with nonischemic cardiomyopathy compared with those with ischemic cardiomyopathy (variance: 0.3 +/- 0.3 vs 1.2 +/- 0.8, respectively, p <0.001). Thus, assessment of myocardial perfusion and regional ventricular function with exercise technetium-99m sestamibi gated SPECT imaging can reliably distinguish between patients with ischemic cardiomyopathy and patients with nonischemic dilated cardiomyopathy.     

Effects of systolic anterior motion of the mitral valve on haemodynamics. Evaluation by a direct method

We evaluated the effects of systolic anterior motion systolic anterior motion of the mitral valve on cardiac haemodynamics. Seven adult mongrel dogs in which systolic anterior motion-septal contact was observed after dobutamine administration were used. To exclude the effects of left ventricular function and morphology, a stone removal basket catheter was placed in the left ventricular outflow tract, and haemodynamics were compared with the basket closed and opened. The basket was opened five times in three dogs not showing systolic anterior motion-septal contact, but the basket itself did not effect the haemodynamics. In the seven dogs that showed systolic anterior motion-septal contact without left ventricular hypertrophy, the basket was opened a total of 33 times in the presence of various degrees of systolic anterior motion-septal contact. After opening the basket, systolic anterior motion was reduced echocardiographically, and significant (P<0.01) changes were observed in the left ventricle-aorta pressure gradient (from 68 +/- 22 to 25 +/- 15 mm Hg), the systolic ejection period (from 146 +/- 19 to 135 +/- 16 ms), and the stroke volume (SV; from 9.4 +/- 2.9 to 10.1 +/- 3.3 ml). After basket inflation, aortic pressure and aortic flow waveforms changed but the peak pressure and flow velocity did not. The temporal distribution of left ventricular ejection also definitely changed after the basket was opened. No changes were observed in the peak dp/dt, peak negative dp/dt, time constant, left ventricular end-diastolic pressure, or left atrial pressure. These observations in this animal model of systolic anterior motion without left ventricular hypertrophy suggest that: (1) there is no potential for generation of an intra-cavity gradient in the absence of systolic anterior motion of the mitral valve, so that (2) systolic anterior motion narrowed the left ventricular outflow tract and, consequently, produced the systolic ejection period, and affected the left ventricular ejection dynamics, and that (3) the basket catheter is useful because it allows these assessments in the same heart with a nearly fixed left ventricular contractility, at least in our animal model.     

Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect

STUDY OBJECTIVES: Pulmonary hypertension is the most important complication in patients with atrial septal defect (ASD), but its role in limiting exercise has not been examined. This study sought to evaluate exercise performance in adults with ASD and determine the contribution of elevated pulmonary artery pressure in limiting exercise capacity. DESIGN: We used Doppler echocardiography during exercise in 10 adults (aged 34 to 70 years) with isolated ASD (New York Heart Association class I, II) and an equal number of matched control subjects. Incremental exercise was performed on an electrically braked upright cycle ergometer. Expired gases and VE were measured breath-by-breath. Two-dimensional and Doppler echocardiographic images were obtained at rest prior to exercise to determine ASD size, stroke volume (SV), shunt ratio (Qp:Qs), right ventricular outflow tract (RVOT) size, and right ventricular systolic pressure at rest (RVSPr). Doppler echocardiography was repeated at peak exercise to measure right ventricular systolic pressure during exercise (RVSPex). RESULTS: Resting echocardiography revealed that RVOT was larger (21+/-4 vs 35+/-8 mm, mean+/-SD; p=0.0009) and RVSPr tended to be higher (17+/-8 vs 31+/-8 mm Hg; p=0.08) in ASD; however, left ventricular SV was not different (64+/-23 vs 58+/-23 mL; p>0.05), compared with control subjects. Despite normal resting left ventricular function, ASD patients had a significant reduction in maximum oxygen uptake (VO2max) (22.9+/-5.4 vs 17.3+/-4.2 mL/kg/min; p=0.005). RVSPex was higher (19+/-8 vs 51+/-10 mm Hg; p=0.001) and the mean RVSP-VO2 slope (1+/-2 vs 18+/-3 mm Hg/L/min; p=0.003) and intercept (17+/-4 vs 27+/-4 mm Hg; p=0.05) were higher in the ASD group. VO2max correlated inversely with both RVSPr (r=-0.69; p=0.007) and RVSPex (r=-0.67; p=0.01). CONCLUSION: These findings suggest that adults with ASD have reduced exercise performance, which may be associated with an abnormal increase in pulmonary artery pressure during exercise.     

Continuous ambulatory radionuclide monitoring of left ventricular function: effect of body position during ergometer exercise

We assessed the reliability of a continuous ambulatory radionuclide monitoring system (the VEST system, Capintec, Inc., Ramsey, NJ) for measurement of left ventricular performance during exercise in the upright and supine positions. METHODS: Sixteen healthy male volunteers (aged 32-46 yr; mean age 37 +/- 4 yr) were studied. All volunteers underwent ergometer exercise testing in both the upright and supine positions, and left ventricular performance was determined with the VEST system. RESULTS: The resting heart rate, systolic blood pressure, pressure rate product, relative end-diastolic volume, relative end-systolic volume and left ventricular ejection fraction (LVEF) all showed no differences between the upright and supine positions. At peak exercise, the heart rate, systolic blood pressure and pressure rate product showed no differences between the upright and supine positions. In the upright position at peak exercise the relative end-diastolic volume was increased (83% +/- 9% to 91% +/- 11%, p < 0.001); the relative end-systolic volume remained unchanged (34% +/- 3% to 33% +/- 15%), and LVEF was significantly increased from 58% +/- 6% to 66% +/- 11% (p < 0.01). In the supine position at peak exercise, the relative end-diastolic volume remained unchanged (85% +/- 5 to 83% +/- 7%), the relative end-systolic volume was increased (35% +/- 5% to 43% +/- 13%, p < 0.01), and LVEF was decreased from 58% +/- 5% to 48% +/- 17% (p < 0.01). These results indicated inferior data collection by the VEST system in the supine position. CONCLUSION: Since the detector of the VEST system may be too small, the data collection is impaired during exercise in the supine position by shifting the heart with deep respiration. The VEST system is very useful for determining left ventricular performance when applied in the sitting or upright position. However, in the supine position during exercise, the use of the VEST system should be avoided because it might indicate an artifactual deterioration of left ventricular performance.     

Tyrosine hydroxylase- and/or aromatic L-amino acid decarboxylase-containing cells in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus)

We assessed forearm vascular and blood pressure responses to dynamic leg exercise in patients 7 and 28 days postmyocardial infarction. To determine a possible association between abnormal exercise vascular responses and baroreflex dysfunction, integrated and carotid baroreflex sensitivity and forearm vascular responses (during application of subhypotensive lower body negative pressure) were assessed. On day 7, 42 patients were compared with 21 age- and sex-matched controls. All subjects were assessed for (1) forearm vascular resistance during semierect exercise, (2) blood pressure measurements during erect treadmill exercise, and (3) integrated, cardiopulmonary, and carotid baroreceptor sensitivity. These studies were repeated in 13 patients on day 28. Forearm vascular resistance increased during exercise by 36% +/- 63% in patients versus 121% +/- 105% in controls (P = 0.0001), and fell in 15 patients, a response seen in none of the controls. Exercise hypotension was demonstrated in 5 patients, all of whom had abnormal vasodilator vascular responses. Those patients with vasodilator responses had a lower left ventricular ejection fraction (52% +/- 12% vs 62% +/- 9%; P = 0.007), and lower cardiopulmonary mechanoreceptor sensitivity (-6.6 +/- 3.9 units vs +6.4 +/- 10.4 units, P = 0.02) than those with constrictor responses, respectively. In the 13 patients studied on day 28, the change in forearm vascular resistance was similar to that observed on day 7 (36% +/- 63% vs 46% +/- 73%). Paradoxical vasodilation of forearm vessels during leg exercise is common in patients studied 7 and 28 days postmyocardial infarction, and is associated with lower left ventricular ejection fraction and abnormal vascular responses during subhypotensive lower body negative pressure.     

Left ventricular hypercontractility and ST segment depression in patients with syndrome X

OBJECTIVES: This study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X. BACKGROUND: Clinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise. METHODS: The pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise. RESULTS: Left ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients. CONCLUSIONS: These findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.     

Left ventricular function during dynamic exercise in untrained and moderately trained subjects

The influence of exercise training on left ventricular function at rest (R), at anaerobic threshold (AT), and during peak exercise (PE) was evaluated in 12 healthy untrained and 13 trained (T) subjects who underwent Doppler echocardiography at R and radionuclide ventriculography at R and during exercise. The end-diastolic volume and stroke volume were significantly higher in the T group than in the untrained group at R. The ejection fraction rose significantly from R to AT and from AT to PE (80.0 +/- 0.84 vs. 83.6 +/- 0.91%), but no significant difference was observed between groups. The peak diastolic filling rate rose significantly during exercise, with a further significant increase observed in the T group (AT, 6.38 +/- 0.40 vs. 5.01 +/- 0.16 end-diastolic counts/s; PE, 8.24 +/- 0.42 vs. 7.15 +/- 0.35 end-diastolic counts/s). The percent variation of minimal systolic counts fell significantly at AT and PE in relation to R. Our data demonstrate that exercise training produces a significant increase in peak diastolic filling rate but no change in systolic function during exercise and that metabolic acidosis caused by exercise does not limit systolic function.     

Efficacy of mononitrate retard therapy in patients with advanced congestive heart failure

To determine the efficacy of mononitrate retard therapy in congestive heart failure 54 pts (42 males and 12 females, aged 67.2 +/- 8.7 yrs.) with NYHA functional class 1-3 and left ventricular ejection fraction less than 40% were investigated. Clinical examination, exercise treadmill test (ETT), ecg holter monitoring and echocardiography (echo-2D) were performed before and after 4 weeks of therapy with Olicard 40 mg Retard. 4 weeks treatment with mononitrate improved clinical parameters. The shift to lower functional NYHA class was observed in 12 cases (p < 0.01). Number of anginal pains per week was reduced from average 3.15 to 1.55 (p < 0.01). Mononitrate therapy improved exercise tolerance during ETT. Exercise time increased from 424 +/- 168 to 568 +/- 143 sec. (p < 0.001) as well as total workload in METS (3.6 +/- 1.4 vs. 4.9 +/- 1.9, p < 0.001). The time to 0.1 mV ischemic ST segment depression was extended from 215 +/- 149 to 357 +/- 173 sec. (p < 0.01). Holter monitoring revealed moderate increase in heart rate and significant reduction of ventricular arrhythmia (p < 0.05). No changes in systolic and diastolic echo-2D parameters were observed.     

Expanded blood volumes contribute to the increased cardiovascular performance of endurance-trained older men

To determine whether expanded intravascular volumes contribute to the older athlete's higher exercise stroke volume and maximal oxygen consumption (VO2 max), we measured peak upright cycle ergometry cardiac volumes (99mTc ventriculography) and plasma (125I-labeled albumin) and red cell (NaCr51) volumes in 7 endurance-trained and 12 age-matched lean sedentary men. The athletes had approximately 40% higher VO2 max values than did the sedentary men and larger relative plasma (46 vs. 38 ml/kg), red cell (30 vs. 26 ml/kg), and total blood volumes (76 vs. 64 ml/kg) (all P < 0.05). Athletes had larger peak cycle ergometer exercise stroke volume indexes (75 vs. 57 ml/m2, P < 0.05) and 17% larger end-diastolic volume indexes. In the total group, VO2 max correlated with plasma, red cell, and total blood volumes (r = 0.61-0.70, P < 0.01). Peak exercise stroke volume was correlated directly with the blood volume variables (r = 0.59-0.67, P < 0.01). Multiple regression analyses showed that fat-free mass and plasma or total blood volume, but not red cell volume, were independent determinants of VO2 max and peak exercise stroke volume. Plasma and total blood volumes correlated with the stroke volume and end-diastolic volume changes from rest to peak exercise. This suggests that expanded intravascular volumes, particularly plasma and total blood volumes, contribute to the higher peak exercise left ventricular end-diastolic volume, stroke volume, and cardiac output and hence the higher VO2 max in master athletes by eliciting both chronic volume overload and increased utilization of the Frank-Starling effect during exercise.     

Impairment of exercise capacity and peak oxygen consumption in patients with mild left ventricular dysfunction and coronary artery disease

AIMS: Most studies in chronic heart failure have only included patients with marked left ventricular systolic dysfunction (i.e. ejection fraction < or =0.35), and patients with mild left ventricular dysfunction are usually excluded. Further, exercise capacity strongly depends on age, but age-adjustment is usually not applied in these studies. Therefore, this study sought to establish whether (age-adjusted) peak VO2 was impaired in patients with mild left ventricular dysfunction. METHODS: Peak VO2 and ventilatory anaerobic threshold were measured in 56 male patients with mild left ventricular dysfunction (ejection fraction 0.35-0.55; study population) and in 17 male patients with a normal left ventricular function (ejection fraction >0.55; control population). All patients had an old (>4 weeks) myocardial infarction. By using age-adjusted peak VO2 values, a 'decreased' exercise capacity was defined as < or = predicted peak VO2 - 1 x SD (0.81 of predicted peak VO2), and a severely decreased exercise capacity as < or = predicted peak VO2 - 2 x SD (0.62 of predicted peak VO2). RESULTS: Patients in the study population (age 52+/-9 years; ejection fraction 0.46+/-0.06) were mostly asymptomatic (NYHA class I: n=40, 76%), while 16 patients (24%) had mild symptoms, i.e. NYHA class II. All 17 controls (age 57+/-8 years) were asymptomatic. Mean peak VO2 was lower in patients with mild left ventricular dysfunction (23.6+/-5.7 vs 27.1+/-4.6 ml x min(-1) x kg(-1) in controls, P<0.05). In 75% of the study population patients (n=42) age-adjusted peak VO2 was decreased (NYHA I/II: n=29/13) and in 18% of them severely decreased (n=10; NYHA I/II: n=6/4). In contrast, only three patients (18%) in the control population had a decreased and none a severely decreased age-adjusted peak VO2. CONCLUSION: In patients with mild left ventricular dysfunction, who have either no or only mild symptoms of chronic heart failure, a substantial proportion has an impaired exercise capacity. By using age-adjustment, impairment of exercise capacity becomes more evident in younger patients. Patients with mild left ventricular dysfunction are probably under-diagnosed, and this finding has clinical and therapeutic implications.     

Very Long-Term Memory for Information Taught in School

The long-term relative benefits of thrombolysis and mechanical reperfusion therapy following acute myocardial infarction (AMI) have not been established. The purpose of this study was to compare left ventricular function, left ventricular remodeling and late outcome after AMI for different reperfusion therapies. Thirty consecutive patients suffering their first anterior wall myocardial infarction with coronary stenoses limited to the left anterior descending coronary artery were studied. They included 10 patients who underwent intracoronary thrombolysis (ICT), 10 who underwent PTCA and 10 who underwent noninterventional medical treatment. All patients underwent coronary angiography (CAG) during the acute phase of AMI and also during the follow-up period, and left ventriculography during the follow-up period and clinical follow-up was performed (mean clinical follow-up period: 53 +/- 31 months). No significant difference in global ejection fraction was noted among the groups, although the end-diastolic volume index (EDVI) in the PTCA group (79.4 +/- 17.5 ml/m2) was significantly smaller than in the noninterventional (106.1 +/- 25.1 ml/m2) and ICT (107.9 +/- 28.3 ml/m2) group (p < 0.05). The regional wall motion index (RWMI) for the anterior region in the PTCA group (-2.7 +/- 0.8) was greater (p < 0.05) than in the noninterventional (-3.4 +/- 0.6) and ICT (-3.3 +/- 0.6) groups. A significant linear correlation was found between EDVI and % diameter stenosis and also between RWMI and % diameter stenosis following reperfusion (p = 0.01). There was no difference in the incidence of cardiac death, nonfatal reinfarction, bypass surgery or congestive heart failure among the groups. Disturbed left ventricular regional wall motion and remodeling benefit most from angioplasty because of prompt restoration of adequate blood flow. However, there was no difference in late outcomes following AMI among the three groups.     

Effects of exercise on plasma level of brain natriuretic peptide in congestive heart failure with and without left ventricular dysfunction

This study was designed to determine whether plasma brain natriuretic peptide (BNP) increases in response to exercise in patients with congestive heart failure and to show what kind of hemodynamic abnormalities induce increased secretion of BNP during exercise. Plasma levels of atrial natriuretic peptide (ANP) and BNP and hemodynamic parameters were measured during upright bicycle exercise tests in seven patients with dilated cardiomyopathy and nine with mitral stenosis. At rest, there were no intergroup differences in cardiac output or pulmonary capillary wedge pressure; however, the group with dilated cardiomyopathy had higher left ventricular end-diastolic pressures and lower left ventricular ejection fractions than did the group with mitral stenosis. Plasma ANP levels were comparable between the dilated cardiomyopathy group (170 +/- 77 [SE] pg/ml) and the mitral stenosis group (106 +/- 33 pg/ml) (p, not significant), whereas BNP was significantly higher in the dilated cardiomyopathy group (221 +/- 80 pg/ml) than in the other group (37 +/- 10 pg/ml) (p < 0.05). The plasma concentration of BNP but not of ANP significantly correlated with left ventricular end-diastolic pressure and volume. Exercise increased plasma ANP and BNP in the two groups. The dilated cardiomyopathy group had a larger increment in BNP (+157 +/- 79 pg/ml) than did the mitral stenosis group (+17 +/- 5 pg/ml) (p < 0.05), although the increase in pulmonary capillary wedge pressure was greater in the mitral stenosis group. Thus exercise increases plasma levels of BNP, and impaired left ventricular function may be a main factor in the greater increment in BNP during exercise in patients with congestive heart failure.     

Stress-induced left ventricular outflow tract obstruction: a potential cause of dyspnea in the elderly

OBJECTIVES: We sought to identify the pattern of disturbed left ventricular physiology associated with symptom development in elderly patients with effort-induced breathlessness. BACKGROUND: Limitation of exercise tolerance by dyspnea is common in the elderly and has been ascribed to diastolic dysfunction when left ventricular cavity size and systolic function appear normal. METHODS: Dobutamine stress echocardiography was used in 30 patients (mean [+/-SD] age 70 +/- 12 years; 21 women, 9 men) with exertional dyspnea and negative exercise test results, and the values were compared with those in 15 control subjects. RESULTS: Before stress, left ventricular end-diastolic and end-systolic dimensions were reduced, fractional shortening was increased, and the basal septum was thickened (2.3 +/- 0.5 vs. 1.4 +/- 0.2 cm, p < 0.001, vs. control subjects) in the patients, but posterior wall thickness did not differ from that in control subjects. Left ventricular outflow tract diameter, measured as systolic mitral leaflet septal distance, was significantly reduced (13 +/- 4.5 vs. 18 +/- 2 mm, p < 0.001). Isovolumetric relaxation time was prolonged, and peak left ventricular minor axis lengthening rate was reduced (8.1 +/- 3.5 vs. 10.4 +/- 2.6 cm/s, p < 0.05), suggesting diastolic dysfunction. Transmitral velocities and the E/A ratio did not differ significantly. At peak stress, heart rate increased from 66 +/- 8 to 115 +/- 20 beats/min in the control subjects, but blood pressure did not change. Transmitral A wave velocity increased, but the E/A ratio did not change. Left ventricular outflow tract velocity increased from 0.8 +/- 0.1 to 2.0 +/- 0.2 m/s, and mitral leaflet septal distance decreased from 18 +/- 2 to 14 +/- 3 mm, p < 0.001. In the patients, heart rate rose from 80 +/- 12 to 132 +/- 26 beats/min and systolic blood pressure from 143 +/- 22 to 170 +/- 14 mm Hg (p < 0.001 for each), but left ventricular dimensions did not change. Peak left ventricular outflow tract velocity increased from 1.5 +/- 0.5 m/s (at rest) to 4.2 +/- 1.2 m/s; mitral leaflet septal distance fell from 13 +/- 4.5 to 2.2 +/- 1.9 mm (p < 0.001); and systolic anterior motion of mitral valve appeared in 24 patients (80%) but in none of the control subjects (p < 0.001). Measurements of diastolic function did not change. All patients developed dyspnea at peak stress, but none developed a new wall motion abnormality or mitral regurgitation. CONCLUSIONS: Although our patients fulfilled the criteria for "diastolic heart failure," diastolic dysfunction was not aggravated by pharmacologic stress. Instead, high velocities appeared in the left ventricular outflow tract and were associated with basal septal hypertrophy and systolic anterior motion of the mitral valve. Their appearance correlated closely with the development of symptoms, suggesting a potential causative link.     

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells

OBJECTIVES: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.     

Effect of physical training on exercise-induced hyperkalemia in chronic heart failure. Relation with ventilation and catecholamines

BACKGROUND: The exercise-induced rise in arterial potassium concentration ([K+]a) may contribute to exercise hyperpnea and could play a role in exertional fatigue. This study was designed to determine whether the exercise-induced rise in [K+]a is altered in patients with chronic heart failure (CHF) and whether physical training affects K+ homeostasis. METHODS AND RESULTS: We evaluated 10 subjects with CHF (ejection fraction, 23 +/- 3.9%) and 10 subjects with normal left ventricular function (NLVF) who had undergone previous coronary artery graft surgery (ejection fraction, 63 +/- 8.6%). Subjects performed an incremental cycle ergometer exercise test before and after a physical training or detraining program. Changes in [K+]a and ventilation (VE) during exercise were closely related in both groups. Subjects with CHF did less absolute work and had reduced maximal oxygen consumption (VO2max) compared with subjects with NLVF (P < .01). Exercise-induced rises in [K+]a, VE, norepinephrine, lactate, and heart rate were greater at matched absolute work rates in subjects with CHF than in subjects with NLVF (P < .01). However, when the rise in [K+]a was plotted against percentage of VO2max to match for relative submaximal effort, there were no differences between the two groups. Physical training resulted in reduced exercise-induced hyperkalemia at matched submaximal work rates in both groups (P < .01) despite no associated change in the concentration of arterial catecholamines. At maximal exercise when trained, peak increases in [K+]a were unaltered, but peak concentrations of catecholamines were raised (P < .05). The decrease in VE at submaximal work rates after training was not significant with this incremental exercise protocol, but both groups had an increased peak VE when trained (P < .01). CONCLUSIONS: Exercise-induced rises in [K+]a, catecholamines, and VE are greater at submaximal work rates in subjects with CHF than in subjects with NLVF. Physical training reduces the exercise-induced rise in [K+]a but does not significantly decrease VE during submaximal exercise with this incremental cycle ergometry protocol. The reduction in exercise-induced hyperkalemia after training is not the result of altered concentrations of arterial catecholamines. The pathophysiological significance of the increased exercise-induced hyperkalemia in CHF and the mechanisms of improved K+ homeostasis with training have yet to be established.     

Inhaled nitric oxide reduction in systolic pulmonary artery pressure is less in patients with decreased left ventricular ejection fraction

OBJECTIVE: To assess whether inhaled nitric oxide decreases pulmonary artery pressure in patients with depressed left ventricular ejection fraction. DESIGN: Randomized, blinded, crossover clinical trial. SETTING: Tertiary care university referral hospital. PATIENTS: Thirty-three patients with pulmonary hypertension and left ventricular dysfunction or valvular heart disease were recruited by convenience. INTERVENTIONS: Systolic pulmonary artery pressure was measured by Doppler echocardiography during randomized inhalation of either 20 ppm or 40 ppm nitric oxide in 30% oxygen as well as during control periods without nitric oxide. MAIN RESULTS: Systolic pulmonary artery pressure was significantly (P < 0.05) decreased with 20 ppm nitric oxide (53.4 +/- 13.9 mmHg) and 40 ppm nitric oxide (53.1 +/- 14.4 mmHg) compared with either initial control (55.8 +/- 15.3 mmHg) or terminal control (56.3 +/- 15.2 mmHg) values. The regression equation for the change in systolic pulmonary artery pressure (y) as predicted by the left ventricular ejection fraction (x) alone for 20 ppm nitric oxide was y = 13.8x-2.9; R2adj = 0.30, P < 0.0001. For 40 ppm nitric oxide alone, the regression equation was y = 16.3x-3.3; R2adj = 0.25, P < 0.0001. Left ventricular ejection fraction was the most explanatory independent variable in the multivariate equation for nitric oxide-induced change in systolic pulmonary artery pressure (R2 = 0.61, P = 0.0000). The change in systolic pulmonary artery pressure was -5.1 +/- 5.2 versus 0.8 +/- 4.9 mmHg (P < 0.0000) in patients with left ventricular ejection fractions greater than 0.25, and 0.25 or less, respectively. CONCLUSIONS: These data imply that in patients with left ventricular ejection fraction of 0.25 or less, nitric oxide may not decrease systolic pulmonary artery pressure. Nitric oxide inhalation may result in a paradoxical increase in systolic pulmonary artery pressure in patients with severely depressed left ventricular ejection fraction. This effect would significantly limit the therapeutic role of nitric oxide in patients with severe heart failure.     

Effect of chronotropic and inotropic stimulation on the coronary pressure-flow relation in left ventricular hypertrophy

Left ventricular hypertrophy (LVH) secondary to chronic pressure overload is associated with increased susceptibility to myocardial hypoperfusion and ischemia during increased cardiac work. The present study was performed to study the effects of chronotropic and inotropic stimulation on the coronary pressure-flow relation of the hypertrophied left ventricle of dogs and to determine the individual contributions of increases in heart rate and contractility to the exaggerated exercise-induced increases in effective back pressure (pressure at zero flow; Pzf). Ascending aortic banding in seven dogs increased the LV to body weight ratio to 7.7 +/- 0.3 g/kg compared to 4.8 +/- 0.2 g/kg in 10 normal dogs (p < or = 0.01). Maximum coronary vasodilation was produced by intracoronary infusion of adenosine. During resting conditions maximum coronary blood flow in the pressure overloaded hypertrophied left ventricle was impaired by both an increase in Pzf (25.1 +/- 2.6 vs 13.8 +/- 1.2 mmHg in hypertrophied vs normal ventricles, respectively, p < or = 0.01) and a decrease in maximum coronary conductance (slope of the linear part of the pressure-flow relation, slopep > or = linear) (8.6 +/- 1.1 vs 12.7 +/- 0.9 ml/min/mmHg, p < or = 0.01). Right atrial pacing at 200 and 250 beats/min resulted in similar rightward shifts of the pressure-flow relation in hypertrophied and normal hearts with 3.1 +/- 0.8 and 4.7 +/- 0.8 mmHg increases in Pzf in LVH and normal dogs, respectively; stepwise multivariate regression analysis indicated that the exaggerated decrease in filling pressure (10 +/- 2 vs 6 +/-2 mmHg) and decrease in left ventricular systolic pressure (45 +/- 5 vs 3 +/- 3 mmHg, p < or = 0.01) may have blunted a greater rightward shift of the pressure-flow relation produced by atrial pacing in the hypertrophied hearts. Inotropic stimulation with dobutamine (10-20 micrograms/kg/min, i.v.) resulted in minimal flow changes in normal hearts but produced a 4.4 +/- 1.5 mmHg (p < or = 0.05) rightward shift of the pressure-flow relation in hypertrophied hearts. which correlated with a greater increase in left ventricular systolic pressure (83 +/- 16 vs 18 +/- 4 mmHg. p < or = 0.05). Exercise resulted in a rightward shift in both normal and hypertrophied left ventricles, but the increase in Pzf was significantly greater in the hypertrophied hearts (15.2 +/- 0.9 vs 10.3 +/- 0.9 mmHg. p < or = 0.05). Stepwise multivariate regression analysis indicated that not only increases in left ventricular filling pressure, but also increases in heart rate and LV systolic pressure contributed to the abnormally great increase in effective coronary back pressure which results in limitation of myocardial perfusion during exercise in the pressure overloaded hypertrophied left ventricle.     

Value of tomoscintigraphy with Fourier analysis in the diagnosis of arrhythmogenic right ventricular cardiomyopathy

ECG gated blood pool tomography has been performed in sixteen patients with right ventricular arrhythmias in whom the diagnosis of arrhythmogenic right ventricular cardiomyopathy was made based on the finding of abnormalities on contrast angiography. They were compared both to control subjects and to patients with primary dilated cardiomyopathy. Thick slices of ventricles were obtained throughout the cardiac cycle in three orthogonal planes: horizontal long axis and short axis thick slices for analysis of right and left ventricular regional wall motion abnormalities and analysis of the spread of the contraction by means of Fourier phase imaging, vertical long axis slices (one for each ventricle) for ejection fractions, because of easy and reproducible determination of valvular planes and analysis of all right ventricular segments, especially the pulmonary infundibulum. Five typical right ventricular abnormalities were seen: decreased ejection fraction (32 +/- 15% vs 55 +/- 3% in control; p < 0.001), increased diameter (ratio of right to left diameters = 1.2 +/- 0.3 vs 0.9 +/- 0.1; p < 0.01), global delayed contraction versus that of the left ventricle (22 +/- 20 degrees vs -2 +/- 6%; p < 0.01), increased dispersion of contraction (32 +/- 16 degrees vs 13 +/- 4 degrees; p < 0.01) and presence of segments with decreased and/or delayed contraction. Right ventricular disease was observed in all the patients: localized form (56%), diffused form (44%). This method provides accurate functional data for diagnosis and follow-up of patients. In future, this wall motion evaluation method may replace planar nuclear angiography as myocardial SPECT have replaced myocardial planar scintigraphy.