Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction

BACKGROUND: A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction. METHODS: Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design. RESULTS: Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 +/- 9 (SE) seconds; exercise time for those taking placebo increased 66 +/- 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3. 4% +/- 0.5% in amlodipine-treated patients and 1.5% +/- 0.5% in placebo-treated patients (P =.007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups. CONCLUSIONS: The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.     

Relation between left ventricular diastolic function and exercise tolerance in patients with left ventricular dysfunction

Previous studies show no correlation between resting systolic left ventricular performance assessed as the ejection fraction and exercise tolerance. This study examined the relation between left ventricular diastolic performance and exercise tolerance in 63 patients with left ventricular dysfunction (ejection fraction less than 50%) due to known or suspected coronary artery disease. The 51 men and 12 women, aged 54 +/- 8 years (mean +/- standard deviation), underwent symptom-limited upright exercise testing on a bicycle ergometer. The exercise end-points were angina (n:5), dyspnea (n:16), and fatigue (n:42). The patients were divided into three groups: group 1 (n:28) with normal exercise tolerance (9.5 +/- 2.4 minutes), group 2 (n:18) with mild exercise intolerance (5.8 +/- 0.5 minutes), and group 3 (n:17) had severe exercise intolerance (3.7 +/- 0.9 minutes). The three groups did not differ in age, ejection fraction, end-diastolic volume, exercise end-point, exercise heart rate, and left ventricular peak filling rate at rest. The exercise peak filling rate was, however, significantly higher in group 1 (p = 0.03). Stepwise multivariate discriminant analysis of important variables identified the exercise peak filling rate as the only predictor of exercise tolerance (F = 6.0). Thus, variation in exercise peak filling rate may in part explain the variability of exercise tolerance in patients with left ventricular dysfunction; patients with preserved exercise capacity have higher exercise peak filling rate than those with exercise intolerance.     

康复运动对老年心血管病患者左室功能及运动耐量的影响

目的:探讨康复运动训练对老年心血管疾病患者左室功能及运动耐量的影响。方法:102例冠心病患者被随机分为冠心病康复组和对照组,各51例,另有高血压病患者51例(高血压康复组)。冠心病康复组和高血压康复组进行有指导的康复运动训练,对照组未进行运动训练。运动训练前及24周后查血压、血脂、心脏超声、颈动脉超声、心电图平板负荷试验、6 min步行试验等项目。结果:与对照组比较,冠心病康复组和高血压康复组的左室射血分数(LVEF)明显增加[(66.2±6.26)%:(69.53±5.04)%:(68.41±5.08)%,P0.05],颈动脉斑块明显缩小[左斑块(2.14±1.62)mm:(1.21±0.87)mm:(1.35±1.35)mm,右斑块(1.81±0.93)mm:(1.01±0.89)mm:(1.12±0.95)mm,P均0.05],6 min步行距离明显增加[(359.27±89.58)m:(457.12±62.05)m:(426.45±52.68)m,P0.01],自感劳累分级减少[(14.84±0.78):(14.35±0.66):(14.39±0.60),P0.01]。上述指标冠心病康复组和高血压康复组间的比较无显著性差异(P0.05)。结论:康复运动训练可改善心血管疾病患者的心脏功能,提高运动耐量和生活质量,减少心血管疾病的危险因素,有利患者回归社会和家庭。     

Hemodynamic and metabolic basis of impaired exercise tolerance in patients with severe left ventricular dysfunction

Hemodynamic and metabolic changes were measured at rest and during exercise in 23 patients with chronic heart failure and in 6 control subjects. Exercise was limited by leg fatigue in both groups and capacity was 40% lower in the patients with failure. At rest, comparing patients with control subjects, heart rate and right atrial and pulmonary wedge pressure were higher; cardiac output, stroke volume and work indexes and ejection fraction were lower; mean arterial and right atrial pressure and systemic resistance were similar. During all phases of exercise in patients with heart failure, pulmonary wedge pressure and systemic vascular resistance were higher and pulmonary vascular resistance remained markedly elevated compared with values in control subjects. Cardiac output was lower in the patients with failure, but appeared to have the same physiologic distribution in both groups during exercise. Although arterial-femoral venous oxygen content difference was higher in patients with heart failure, this increase did not compensate for the reduced blood flow. Even though the maximal oxygen consumption was significantly reduced, femoral venous lactate and pH values were higher than values in control subjects, but femoral venous pH was similar in both groups at their respective levels of maximal exercise. Ejection fraction was lower in those with heart failure at rest and did not increase with exercise. Ventilation in relation to oxygen consumption was higher in patients with failure than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of exercise training on heart rate variability in patients with new-onset left ventricular dysfunction after myocardial infarction

BACKGROUND: Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability (HRV) toward parasympathetic dominance in patients after acute myocardial infarction (MI). However, its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown. We aimed to investigate the effects of 8 weeks of supervised, high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population. METHODS AND RESULTS: Twenty-five men with an acute MI and a low ejection fraction were randomly assigned to enter or not to enter a training program in a regional rehabilitation center. HRV was evaluated before and after 1 and 2 months of training and at 12 months. Maximal exercise testing with respiratory gas exchange was performed at baseline and after training. Resting heart rate decreased (P <. 01) and the percentage of R-R intervals differing >50 ms from the preceding one (pNN50) increased (P <.05) after training. The standard deviation of R-R intervals (SDRR) tended to increase, but frequency-domain indexes remained unchanged. There was a significant decrease in SDRR (P <.05) and high-frequency power (P <.01) at 12 months in untrained patients. Exercise time increased by 38% and maximal oxygen uptake increased by 29% in the training group (P <. 01). CONCLUSIONS: Despite beneficial effects on clinical variables, exercise training did not markedly alter HRV indexes. A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction.     

Effect of physical training on the magnitude of left ventricular ischaemic dysfunction in patients with chronic ischaemic heart disease

Twenty-two patients with chronic ischaemic heart disease (IHD) and reversible myocardial ischaemia after a load as recorded by single photon emission computed tomography (SPECT) participated in an eight-week rehabilitation programme. Before exercise their efficiency was tested by spiroergometric examinatin and the patients were randomized into two groups. Group A (10 patients) took exercise at the level of the anaerobic threshold (high intensity training), group B (12 patients) trained at the level of the 60 % anaerobic threshold (low intensity training). The exercise unit including the warming up and relaxation stage lasted 50 minutes and was repeated three times per week. Before and after the rehabilitation programme in all patients spiroergometry was performed as well as exercise pulsed tissue Doppler echocardiography to evaluate regional systolic and diastolic left ventricular function in the ischaemic area, localized beforehand by the SPECT. The following parameters were evaluated by echocardiograpphy: the peak velocity of motion in the ischaemic area in systole (Si), the peak velocity of motion in the ischaemic area in early diastole (Ei) ad in atrial contraction (Ai), and the ratio Ei/Ai was calculated. With the exception of the decline of the value at rest Ai from 8.4 +/- 1.3 cm/sec to 7.3 +/- 1.3 cm/s (p < 005) in the exercising group A none of the parameters of left ventricular regional function changed significantly after an eight-week rehabilitation programme. The maximal performance achieved in spiroergometry increased however after rehabilitation in group A (from 145 +/- 36 W to 162 +/- 39 W, p < 0.01) as well as in group B (from 112 +/- 36W to 122 +/- 36W, p < 0.05). I It may be concluded that a rehabilitation programme of high and low intensity improved the load tolerance during spiroergometry but did not lead to significant improvement of regional systolic and diastolc left ventricular function in the area of reversible ischaemia.     

Effect of losartan and hydrochlorothiazide on exercise tolerance in exertional hypertension and left ventricular diastolic dysfunction

A randomized, double-blind study of 6 months of losartan 50 mg or hydrochlorothiazide (HCTZ) 12.5 mg was performed in 40 subjects with left ventricular diastolic dysfunction (mitral flow velocity E/A ratio < 1), exercise systolic blood pressure (BP) > 200 mm Hg, systolic BP at rest < 150 mm Hg, ejection fraction > 50%, and no ischemia. Before treatment, exercise systolic BP was 213 +/- 13 mm Hg (mean +/- SD) in the 19 patients randomized to losartan and 209 +/- 11 mm Hg in the 21 patients who received HCTZ. After 6 months, exercise systolic BP was similarly reduced in patients who received losartan (197 +/- 23 mm Hg, p < 0.01) and HCTZ (191 +/- 11 mm Hg, p < 0.01). With losartan, treadmill exercise time increased from 894 +/- 216 to 951 +/- 225 seconds (p = 0.011), and quality of life improved from 15 +/- 12 to 7 +/- 10 (p = 0.015) without a change in oxygen consumption (1,895 +/- 470 to 1,954 +/- 539 ml/min, p = 0.30). With HCTZ, exercise time (842 +/- 225 to 872 +/- 239 seconds, p = 0.32) and quality of life (19 +/- 21 vs 19 +/- 24, p = 0.43) did not change, whereas oxygen consumption decreased from 2,144 +/- 788 to 1,960 +/- 706 ml/min (p = 0.022). In conclusion, in patients with diastolic dysfunction and hypertensive responses to exercise, 6 months of losartan and HCTZ blunted systolic BP during exercise. Only losartan increased exercise tolerance and improved quality of life.     

Combined training in patients with systolic left ventricular dysfunction

The objective of the work was to evaluate the effect of eight-week combined training on the performance, aerobic capacity and basic haemodynamic parameters in patients with systolic dysfunction of the left ventricle and to assess its safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/- 11.1 years with coronarographically verified chronic ischaemic heart disease and with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before the beginning and after completion of the rehabilitation programme (eight weeks) a spiroergometric examination was made, up to the symptom-limited maximum. Fitness elements were included after 2 weeks of aerobic training. The lesson lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer with an intensity of the load at the level of the anaerobic threshold (20 mins.), the stage of fitness training on a combined training machine (20 mins) and the relaxation stage (10 mins). In the fitness stage the patients started to exercise at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum) The results showed after eight-week combined training a significant (p < 0.05) increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in patients with systolic left ventricular dysfunction. There was a significant increase in the capacity of the transport system expressed by the value of the maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from 5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood pressure at rest, systolic and diastolic, and of the baseline value of the heart rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not significant.     

老年性高血压患者左心功能不全康复训练效果研究

目的:分析老年性高血压患者左心功能不全康复训练效果。方法:选取我院2015年03月至2016年09月,收治的高血压伴左心功能不全老年患者114例为研究对象,按随机数字表法分为观察组、对照组。对照组57例患者给予常规治疗,观察组57例患者在对照组的基础上给予康复训练。对比两组患者治疗后相关指标变化情况。结果:观察组的运动时间与对照组相比明显升高;观察组的血压、心率、左心室质量指数、脑钠肽以及自感劳累分级与对照组相比明显降低,差异有统计学意义(P0.05)。结论:老年性高血压伴左心功能不全患者应用康复训练的效果显著,有效降低患者的左心室质量指数、脑钠肽等指标,提高其运动时间,改善其预后水平。     

左室舒张性心功能障碍超声左心形态、功能及运动耐量的改变50例分析

对核素心血池扫描证实的５０例左室舒张性心功能障碍（ＬＶＤＤ）病例、２６例左室收缩性心功能障碍（ＬＶＳＨＦ）病例进行Ｍ型、二维、多普勒超声心动图及活动平板运动试验检测，并以２０例正常人为对照组（ＣＧ）。结果表明：（１）左心形态学改变：与ＬＶＳＨＦ组比较，ＬＶＤＤ组左房内径（ＬＡＤ）、左室内径（ＬＶＤ）无明显增加，室间隔厚度（ＩＶＳＴ）、左室后壁厚度（ＰＷＴ）增加。与ＣＧ组比较，ＬＶＤＤ组ＬＡＤ、ＩＶＳＴ、ＰＷＴ增加，但ＬＶＤ差异无显著性。（２）ＬＶＤＤ组收缩功能指标：左室射血分数（ＬＶＥＦ）、心脏指数（ＣＩ）与ＣＧ组比较差异无显著性，ＬＶＳＨＦ组与ＣＧ组比较，ＬＶＳＨＦ组ＬＶＥＦ、ＣＩ减低。与ＣＧ组比较，ＬＶＤＤ组左室舒张功能指标：二尖瓣舒张早期流速峰值（ＥＰＦＶ）、二尖瓣舒张早、晚期流速峰值比（Ｅ／Ａ）、舒张早期减速度（ＤＣ）比ＣＧ组减低，二尖瓣舒张晚期流速峰值（ＡＰＦＶ）、等容舒张时间（ＩＲＴ）较ＣＧ组增高。ＬＶＤＤ组各左室舒张功能指标与ＬＶＳＨＦ组差异无显著性。（３）ＬＶＤＤ组运动时间、运动当量显著低于ＣＧ组，但高于ＬＶＳＨＦ组。     

Influence of physical training on cardiac performance in patients with coronary artery disease and exercise-induced left ventricular dysfunction

OBJECTIVE: The aim of the study was to assess the influence of physical training on systolic and diastolic left ventricular (LV) function using seismocardiography (SCG) and its relationship to the exercise capacity in CAD patients with exercise-induced LV dysfunction. METHODS AND RESULTS: Eighty men aged 52.5 +/- 7.5 y with stable CAD were assigned to either a control group (CG, n = 40) or a training group (TG, n = 40).TG patients underwent a 4.5-month training programme (TP). Before and at the end of the study all patients underwent a cardiopulmonary test (CPET) and SCG. After TP the following CPET parameters improved significantly: duration (776 +/-120 vs. 879 +/- 89 s, P<0.001), METs (8 +/- 2 vs. 10 +/- 1, P<0.01), maxVO2 (22 +/- 4 vs. 25 +/- 3 ml/kg/min, P < 0.001). During SCG performed before (SCG(REST)) and immediately after each CPET (SCG(CPET)) the following variables improved significantly, but only in TG patients: the pre-ejection period (PEP; 126 +/- 15 vs. 119 +/- 14, P < 0.05 ms), PEP/LVET ratio (PEP/LV ejection time, ms; 0.42 +/- 0.08 vs. 0.38 +/- 0.06, P < 0.05). There was a negative correlation between training-induced changes in maxVO2 and PEP(CPET) (r =-0.4, P = 0.01) and PEP/LVET(CPET) (r =-0.52, P = 0.001), and a positive correlation between maxVO2 and LVET(CPET) (r = 0.51, P = 0.01). After TP, there was also a negative correlation between maxVO2 and isovolumetric relaxation time (ms; r =-0.46, P = 0.01). CONCLUSIONS: The training programme resulted in a significant improvement in the physical capacity and cardiac performance in CAD patients with exercise-induced left ventricular dysfunction. An improvement of systolic left ventricular function suggested an increase in exercise capacity.     

Effect of high- versus low-frequency exercise training in multidisciplinary cardiac rehabilitation on health-related quality of life

BACKGROUND: The authors examined the importance of the frequency of aerobic exercise training in multidisciplinary rehabilitation in improving health-related quality of life in the short run in patients with documented coronary artery disease. METHODS: Patients (114 males and 16 females; age range, 32-70 years) were randomized into either a high-frequency or a low-frequency exercise training program (10 versus 2 sessions per week, respectively) as part of a 6-week multidisciplinary cardiac rehabilitation program. The General Health Questionnaire and the RAND-36 were used to assess changes in psychological distress and subjective health status. RESULTS: After 6 weeks, high-frequency patients reported significantly more positive, change in "psychological distress" (P < 0.05), "mental health" (P = 0.05), and "health change" (P < 0.01), than low-frequency patients. Apart from changes in mean scores, individual effect sizes indicated that a significantly greater percentage of high-frequency patients experienced substantial improvements in "psychological distress" (P < 0.01), "physical functioning" (P < 0.05), and "health change" (P < 0.05), compared with low-frequency patients. In addition, deterioration of quality of life was observed in a considerable number of high-frequency patients (ranging from 1.7% to 25.8% on the various measures). CONCLUSIONS: The frequency of aerobic exercise has a positive, independent effect on psychological outcomes after cardiac rehabilitation. However, this benefit after high-frequency rehabilitation appears to be limited to a subgroup of patients. Further investigation is required to identify these patients. Results provide input into recent controversies regarding the role of exercise training in cardiac rehabilitation.     

Worsening of left ventricular diastolic dysfunction during exercise causes decreased exercise tolerance in hypertension

BACKGROUND: Exercise tolerance is reduced in hypertension. Hypertension affects left ventricular (LV) diastolic filling by causing abnormal relaxation and decreasing compliance. HYPOTHESIS: This study was designed to determine whether worsening of LV diastolic dysfunction during exercise causes decreased exercise tolerance in hypertension. METHODS: Left ventricular diastolic filling parameters were examined at mitral valve by Doppler echocardiography at rest and at peak exercise in hypertensive patients and were compared with those of age- and gender-matched normotensive individuals. Treadmill exercise stress test was performed according to the Bruce protocol and the exercise time was recorded. RESULTS: Exercise time was significantly shorter in the hypertensive group than that in the normotensive group (320 +/- 29 vs. 446 +/- 38 s, p 0.03). The hypertensive group demonstrated abnormal relaxation pattern of diastolic mitral inflow at rest, which became pseudonormal at peak exercise (E/A velocity ratio, rest 0.86 +/- 0.06 vs. exercise 1.19 +/- 0.09, p < 0.001). The diastolic mitral inflow pattern remained normal at peak exercise in the normotensive group. The deceleration time and the pressure half time of early mitral inflow at peak exercise were significantly shorter in the hypertensive group than those in the normotensive group (deceleration time, 182 +/- 20 vs. 238 +/- 22 ms, p 0.02: pressure half time, 54 +/- 5 vs. 70 +/- 12 ms, p 0.01). CONCLUSIONS: This study demonstrates that reduced exercise tolerance in hypertension is associated with worsening of diastolic dysfunction during exercise consistent with an increase in left atrial pressure.     

Effect of isotonic exercise training on left ventricular volume during upright exercise

To determine the changes in left ventricular volume and their time course during exercise we studied 30 runners. Left ventricular end-diastolic and end-systolic volumes were measured from biapical two-dimensional echocardiograms recorded during graded upright bicycle exercise. The validity of this echocardiographic technique was assessed by comparing measurements at rest and exercise with results obtained by gated equilibrium radionuclide angiography in 10 patients with coronary artery disease. Although the absolute volume measurements were lower by echocardiography, ejection fraction was not significantly different and the directional changes in volume during exercise were comparable. In the runners, resting left ventricular end-diastolic volume measurements by echocardiography correlated with their maximum bicycle exercise endurance times (r = .80). Left ventricular end-diastolic volume, stroke volume, and ejection fraction increased during exercise with the most marked changes occurring in the first half of exercise. Systolic blood pressure/end-systolic volume (SBP/ESV) also increased during exercise, but the largest change occurred during the second half of exercise. Left ventricular volumes were larger in the 12 competitive marathon runners (maximum exercise duration greater than or equal to 27 min) as compared with the 18 noncompetitive runners (exercise duration less than or equal to 23 min): resting end-diastolic volume 130 +/- 29 (SD) ml vs 87 +/- 20 ml (p less than .001), respectively. During exercise the competitive runners exhibited a larger increase in end-diastolic volume and the noncompetitive athletes showed a greater increase in SBP/ESV. Therefore, highly trained competitive marathon runners make greater use of the less energy-consuming Frank-Starling mechanism to accomplish high levels of isotonic exercise performance as compared with less well-trained runners.     

Left ventricular function during strength testing and resistance exercise in patients with left ventricular dysfunction

PURPOSE: Deterioration in left ventricular function is a more sensitive marker of myocardial ischemia during exercise than ST segment depression. The current study was designed to evaluate left ventricular function during one-repetition-maximum (1-RM) strength testing and resistance exercise in cardiac patients with moderate left ventricular dysfunction. METHODS: Using echocardiographic methods, left ventricular function was evaluated in 15 patients with left ventricular dysfunction (age, 65 +/- 6.5 years; ejection fraction, 42.1 +/- 5.8). Measurements were performed during 1-RM testing and resistance exercise (20%, 40%, and 60% of 1-RM using 10 to 15 repetitions) on the one-arm biceps curl (BIC) and bilateral knee extension exercises and compared with measurements of left ventricular function during the symptom-limited graded exercise test (SL-GXT). RESULTS: During the knee extension exercise, there was a slight but significant reduction (P< or =.05) in ejection fraction values at the end of 60% 1-RM, as compared with rest and previous workloads. Significant increases in systolic blood pressure and left ventricular end-systolic volume ratio values (P< or =.05) from rest to exercise were observed across test modes and for all workloads. The prevalence of new wall motion abnormalities during knee extension and BIC 1-RM strength testing was comparable with that observed during SL-GXT. The greatest increase in new wall motion abnormalities was seen during 60% 1-RM of knee extension exercise, as compared with prior workloads, BIC exercises, and SL-GXT. CONCLUSIONS: Despite an increase in occurrence of ischemic changes during the highest resistance exercise workloads and with larger muscle mass, the findings are small in magnitude and do not suggest reduced cardiac performance.