Decreased Variability of the 6-Minute Walk Test by Heart Rate Correction in Patients with Neuromuscular Disease

Objective

The 6-minute walk test is widely used to assess functional status in neurological disorders. However, the test is subject to great inter-test variability due to fluctuating motivation, fatigue and learning effects. We investigated whether inter-test variability of the 6MWT can be reduced by heart rate correction.

Methods

Sixteen patients with neuromuscular diseases, including Facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, Charcot-Marie-Tooths, Dystrophia Myotonica and Congenital Myopathy and 12 healthy subjects were studied. Patients were excluded if they had cardiac arrhythmias, if they received drug treatment for hypertension or any other medical conditions that could interfere with the interpretation of the heart rate and walking capability. All completed three 6-minute walk tests on three different test-days. Heart rate was measured continuously.

Results

Successive standard 6-minute walk tests showed considerable learning effects between Tests 1 and 2 (4.9%; P = 0.026), and Tests 2 and 3 (4.5%; P = 0.020) in patients. The same was seen in controls between Tests 1 and 2 (8.1%; P = 0.039)). Heart rate correction abolished this learning effect.

Conclusion

A modified 6-minute walk test, by correcting walking distance with average heart rate during walking, decreases the variability among repeated 6-minute walk tests, and should be considered as an alternative outcome measure to the standard 6-minute walk test in future clinical follow-up and treatment trials.     

Exercise hyperpnea in chronic heart failure: relationships to lung stiffness and expiratory flow limitation.

The changes in breathing pattern and lung mechanics in response to incremental exercise were compared in 14 subjects with chronic heart failure and 15 normal subjects. In chronic heart failure subjects, exercise hyperpnea was achieved by increasing breathing frequency more than tidal volume. The rate of increase in breathing frequency with carbon dioxide output was inversely correlated (r = -0.61, P < 0.05) with dynamic lung compliance measured at rest, but not with static lung compliance either at rest or at maximum exercise. Although decrease in expiratory flow reserve near functional residual capacity in chronic heart failure occurred earlier with exercise than in the normal subjects (P < 0.01), it was not correlated with changes in breathing pattern or occurrence of tachypnea. Tachypnea was achieved in chronic heart failure subjects with an increase in duty cycle because of a greater than normal decrease in expiratory time with exercise. We conclude that in chronic heart failure preexisting increase in lung stiffness plays a significant role in causing tachypnea during exercise. The results of the present study do not support the hypothesis that dynamic compression of the airways downstream from the flow-limiting segment occurring during exercise contributes to hyperpnea.     

Cognitive Function in Ambulatory Patients with Systolic Heart Failure: Insights from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

We sought to determine whether cognitive function in stable outpatients with heart failure (HF) is affected by HF severity. A retrospective, cross-sectional analysis was performed using data from 2, 043 outpatients with systolic HF and without prior stroke enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial. Multivariable regression analysis was used to assess the relationship between cognitive function measured using the Mini-Mental Status Exam (MMSE) and markers of HF severity (left ventricular ejection fraction [LVEF], New York Heart Association [NYHA] functional class, and 6-minute walk distance). The mean (SD) for the MMSE was 28.6 (2.0), with 64 (3.1%) of the 2,043 patients meeting the cut-off of MMSE <24 that indicates need for further evaluation of cognitive impairment. After adjustment for demographic and clinical covariates, 6-minute walk distance (β-coefficient 0.002, p<0.0001), but not LVEF or NYHA functional class, was independently associated with the MMSE as a continuous measure. Age, education, smoking status, body mass index, and hemoglobin level were also independently associated with the MMSE. In conclusion, six-minute walk distance, but not LVEF or NYHA functional class, was an important predictor of cognitive function in ambulatory patients with systolic heart failure.     

Mejoría de la capacidad funcional tras tratamiento con levotiroxina en pacientes con insuficiencia cardíaca crónica e hipotiroidismo subclínico

AimTo assess whether levothyroxine treatment improves functional capacity in patients with chronic heart failure (New York Heart Association class i-iii) and subclinical hypothyroidism.MethodsOne hundred and sixty-three outpatients with stable chronic heart failure followed up for at least 6 months were enrolled. A physical examination was performed, and laboratory tests including thyroid hormone levels, Doppler echocardiogram, radionuclide ventriculography, and Holter monitoring were requested. Functional capacity was assessed by of the 6-min walk test. Patients with subclinical hypothyroidism were detected and, after undergoing the s6-min walk test, were given replacement therapy. When they reached normal thyrotropin (TSH) levels, the 6-min walk test was performed again. The distance walked in both tests was recorded, and the difference in meters covered by each patient was analyzed.ResultsPrevalence of subclinical hypothyroidism in patients with heart failure was 13%. These patients walked 292 ± 63 m while they were hypothyroid and 350 ± 76 m when TSH levels returned to normal, a difference of 58 ± 11 m (P < .011). Patients with normal baseline TSH levels showed no significant difference between the 2 6-min walk tests.ConclusionsPatients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached.     

Visualization of elusive structures using intracardiac echocardiography: Insights from electrophysiology

Echocardiography has the ability to noninvasively explore hemodynamic variables during pharmacologic or exercise stress test in patients with heart failure. In this review, we detail some important potential applications of stress echocardiography in patients with heart failure. In patients with coronary artery disease and chronic LV dysfunction, dobutamine stress echocardiography is able to distinguish between viable and fibrotic tissue to make adequate clinical decisions. Exercise testing, in combination with echocardiographic monitoring, is a method of obtaining accurate information in the assessment of functional capacity and prognosis. Functional mitral regurgitation is a common finding in patients with dilated and ischaemic cardiomyopathy and stress echocardiography in the form of exercise or pharmacologic protocols can be useful to evaluate the behaviour of mitral regurgitation. It is clinical useful to search the presence of contractile reserve in non ischemic dilated cardiomyopathy such as to screen or monitor the presence of latent myocardial dysfunction in patients who had exposure to cardiotoxic agents. Moreover, in patients with suspected diastolic heart failure and normal systolic function, exercise echocardiography could be able to demonstrate the existence of such dysfunction and determine that it is sufficient to limit exercise tolerance. Finally, in the aortic stenosis dobutamine echocardiography can distinguish severe from non-severe stenosis in patients with low transvalvular gradients and depressed left ventricular function.     

Exhaled nitric oxide and exercise performance in heart failure

BACKGROUND: In heart failure abnormalities of pulmonary function are frequently observed particularly during exercise, which is characterized by hyperpnea, low tidal volume, early expiratory flow limitation and reduced lung compliance. Exhaled nitric oxide (NO) is increased in asthma. We evaluated whether a correlation between exhaled NO and lung mechanics exists during exercise in heart failure. METHODS: We studied 33 chronic heart failure patients and 11 healthy subjects with: a) standard pulmonary function, b) lung diffusion for carbon monoxide (DLCO) including its subcomponents, capillary volume and membrane resistance and eNO both at rest and during light exercise, c) maximal cycloergometer cardiopulmonary exercise test. RESULTS: Forced expiratory volume in 1 second (FEV1) was reduced in heart failure patients (83 +/- 17% of predicted) as was DLCO (75 +/- 18% of predicted) due to reduced membrane resistance (32.6 +/- 10.3 ml/mmHg/min vs. 39.9 +/- 6.9 in patients vs. controls, p < 0.02). eNO was lower in patients vs. controls (9.7 +/- 5.4 ppm vs. 14.4 +/- 6.4, p < 0.05) and was, during exercise, constant in patients and reduced in controls. No significant correlation was found between eNO and lung function. Vice-versa eNO changes during exercise were correlated with peak exercise oxygen consumption (r = 0.560, p < 0.001). CONCLUSIONS: The hypothesis of a link between eNO and lung function in heart failure was not proved. The correlation between eNO changes during exercise and peak VO2 might be due to hemoglobin oxygenation which binds NO to hemoglobin.     

左旋卡尼汀联合环磷腺苷葡胺治疗慢性充血性心力衰竭

目的:探究左旋卡尼汀联合环磷腺苷葡胺治疗慢性充血性心力衰竭(chronic congestive heart failure,CHF)的临床疗效。方法:选取我院心内科CHF患者58例,随机分为对照组28例与实验组30例,其中对照组28例,予地高辛、氢氯噻嗪、环磷腺苷葡胺常规治疗;实验组30例,在常规治疗的基础上加用左旋卡尼汀治疗。观察两组患者治疗前后心功能分级(NYHA)、6 min步行距离、左心室射血分数(LVEF)及左心室舒张末容积(LVEDD)等。结果:与对照组比较,实验组患者治疗后心率和NYHA心功能分级明显改善,6 min步行实验明显提高,患者LVEDD、LVEF明显改善,差异具有统计学意义(P<0.05);两组患者接受相应治疗后均未出现任何不良反应(P>0.05)。结论:左旋卡尼汀联合环磷腺苷葡胺能够明显改善慢性充血性心力衰竭,对临床具有指导意义,值得临床推广。     

富马酸比索洛尔对老年慢性心力衰竭患者血清胆红素、NT-proBNP及运动耐力的影响

摘要 目的：探究富马酸比索洛尔对老年慢性心力衰竭患者血清胆红素、N-末端B型利钠肽原（N-Terminal pro-brain natriuretic peptide,NT-proBNP）及运动耐力的影响。方法：选择我院于2017年1月~2020年1月收治的老年慢性心力衰竭患者80例,根据入院顺序经随机数字表法分成两组,对照组40例患者仅采用常规治疗方案进行治疗,研究组40例患者在常规治疗基础上联合富马酸比索洛尔进行治疗。对比两组患者治疗总有效率、左心室射血分数（left ventricular ejection fraction,LVEF）、心排量（cardiac output,CO）、每搏输出量（stroke volume,SV）、血清 NT-proBNP水平、6 min 步行测试距离、总胆红素、直接胆红素水平。结果：研究组的治疗总有效率90.00 %,显著高于对照组72.50 %（P＜0.05）; 治疗前,两组的LVEF、CO、SV水平对比无差异（P＞0.05）;治疗后,两组的LVEF、CO、SV水平均升高,且研究组更高（P＜0.05）;治疗前,两组的NT-proBNP水平及6 min 步行测试距离对比无显著性差异（P＞0.05）;治疗后,两组的NT-proBNP水平比治疗前均显著降低、6 min 步行测试距离比治疗前均显著升高,且研究组更优（P＜0.05）;治疗前,两组的总胆红素、直接胆红素水平对比无差异（P＞0.05）;治疗后,两组的总胆红素、直接胆红素水平均比治疗前显著降低,且研究组显著低于对照组（P＜0.05）。结论：在常规治疗基础上联合富马酸比索洛尔治疗老年慢性心力衰竭的临床效果显著,其可有效改善患者心功能及运动耐力,值得推荐至临床广泛应用。     

Controlled trial of supervised exercise training in chronic bronchitis.

In a controlled trial of exercise retraining in patients with severe chronic bronchitis, 33 subjects were followed for a mean period of 10.3 months. The exercise programme was supervised once a week, and daily training comprised a 12-minute walk and simple stair climbing exercises. The subjects in the exercise group showed a highly significant improvement in their walking distance, attaining a maximum increase of 24% after eight to 12 months. There was also considerable subjective improvement. The control group did not improve. No significant changes in cardiorespiratory function or muscle strength were seen. Simple exercise rehabilitation is of benefit to patients with disabling obstructive lung disease.     

Effect of attitudes and beliefs on exercise tolerance in chronic bronchitis.

In 50 patients with chronic bronchitis the relation was assessed between exercise tolerance and pulmonary function and psychological factors, including subjective perception of exertion, mood, general psychiatric disturbance, and the attitudes and beliefs held by patients concerning themselves, their illness, and its treatment. Ventilatory capacity was significantly correlated with but a poor predictor of exercise tolerance. Subjective perception of exertion was most closely correlated with exercise tolerance. The distance walked in a 12-minute exercise test was significantly correlated with measurements of mood and with several attitudes and beliefs. Attitudes and beliefs greatly outweighed measurements of mood and ventilatory capacity as components in a multiple regression predicting distance walked in 12 minutes. This method of psychological assessment emphasises the importance of attitudes and beliefs in respiratory disability and may have useful applications in rehabilitation in other chronic diseases.     

Nordic walking in fibromyalgia: a means of promoting fitness that is easy for busy clinicians to recommend

A total of 67 women with fibromyalgia were recruited to an exercise study and were randomized to moderate-to-high-intensity Nordic walking (age 48 ± 7.8 years) or to a control group engaging in supervised low-intensity walking (age 50 ± 7.6 years). A total of 58 patients completed. Significantly greater improvement in the 6-minute walk test was found in the Nordic walking group (P = 0.009), compared with the low-intensity walking group. A significantly larger decrease in exercise heart rate (P = 0.020) and significantly improved scores on the Fibromyalgia Impact Questionnaire Physical function (P = 0.027) were found in the Nordic walking group as compared with the low-intensity walking group. No between-group difference was found for the Fibromyalgia Impact Questionnaire total or pain scores. The authors conclude that moderate-to-high intensity aerobic exercise by means of Nordic walking twice a week for 15 weeks was found to be a feasible mode of exercise, resulting in improved functional capacity and a decreased level of activity limitations.     

CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial

Background

Single-limb knee extension exercises have been found to be effective at improving lower extremity exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Since the positive local physiological effects of exercise training only occur in the engaged muscle(s), should upper extremity muscles also be included to determine the effect of single limb exercises in COPD patients.

Methods/design

Trial design: a prospective, assessor-blind, block randomized controlled, parallel-group multicenter trial. Participants: stage II-IV COPD patients, > 40?years of age, ex-smokers, with stable medical treatment will be included starting May 2011. Recruitment at three locations in Sweden. Interventions: 1) high-repetitive single limb exercise (HRSLE) training with elastic bands, 60 minutes, three times/week for 8?weeks combined with four sessions of 60 minutes patient education, or 2) the same patient education alone. Outcomes: Primary: determine the effects of HRSLE on local muscle endurance capacity (measured as meters walked during 6-minute walk test and rings moved on 6-minute ring and pegboard test) and quality of life (measured as change on the Swedish version of the Chronic Respiratory Disease Questionnaire). Secondary: effects on maximal strength, muscular endurance, dyspnea, self-efficacy, anxiety and depression. The relationship between changes in health-related variables and changes in exercise capacity, sex-related differences in training effects, feasibility of the program, strategies to determine adequate starting resistance and provide accurate resistance for each involved movement and the relationship between muscle fatigue and dyspnea in the different exercise tests will also be analyzed. Randomization: performed by a person independent of the recruitment process and using a computer random number generator. Stratification by center and gender with a 1:1 allocation to the intervention or control using random block sizes. Blinding: all outcome assessors will be blinded to group assignment.

Discussion

The results of this project will contribute to increase the body of knowledge regarding COPD and HRSLE.

Trial registration

ClinicalTrials.gov Identifier: NCT01354067. Registration date: 2011-05-11. First participant randomized: 2011-09-02     

Clinical impact of atrial fibrillation in patients with pulmonary hypertension

Background

Pulmonary hypertension (PH) is associated with progressive impairment of right ventricular function, reduced exercise capacity and a poor prognosis. Little is known about the prevalence, clinical manifestation and impact of atrial fibrillation (AF) on cardiac function in PH.

Methods

In a four year single-centre retrospective analysis 225 patients with confirmed PH of various origins were enrolled to investigate the prevalence of AF, and to assess the clinical manifestation, 6-minute walk distance, NT-proBNP levels, echocardiographic parameters and hemodynamics obtained by right heart catheterization in PH with AF.

Results

AF was prevalent in 31.1%. In patients with PH and AF, parameters of clinical deterioration (NYHA/WHO functional class, 6-minute walk distance, NT-proBNP levels) and renal function were significantly compromised compared to patients with PH and sinus rhythm (SR). In the total PH cohort and in PH not related to left heart disease occurrence of AF was associated with an increase of right atrial pressure (RAP) and right atrial dilatation. While no direct association was found between pulmonary artery pressure (PAP) and AF in these patients, right ventricular function was reduced in AF, indicating more advanced disease. In PH due to left heart failure the prevalence of AF was particularly high (57.7% vs. 23.1% in other forms of PH). In this subgroup, left atrial dilatation, increase of pulmonary capillary wedge pressure, PAP and RAP were more pronounced in AF than in SR, suggesting that more marked backward failure led to AF in this setting.

Conclusion

PH is associated with increased prevalence of AF. Occurrence of AF in PH indicates clinical deterioration and more advanced disease.     

Oxygen uptake kinetics in chronic heart failure: clinical and physiological aspects

One of the hallmark symptoms of patients with chronic heart failure (CHF) is exercise intolerance. Therefore, exercise testing has become an important tool for the evaluation and monitoring of heart failure. Whereas the maximal aerobic capacity (peak VO₂) is a reliable indicator of the severity and prognosis of heart failure, submaximal exercise parameters may be more closely related to the ability to perform daily activities. As such, oxygen (O₂) uptake kinetics, describing the rate change of O₂ uptake during onset or recovery of submaximal constant-load exercise (O₂ onset and recovery kinetics, respectively), have been shown to be useful parameters for objectively evaluating the functional capacity of CHF patients. However, their evaluation in this population is not a routine part of daily clinical practice. Possible reasons for this include a lack of standardisation of the assessment methodology and a limited number of studies evaluating the clinical use of O₂ uptake kinetics in CHF patients. In addition, the pathophysiological mechanisms underlying the delay in O₂ uptake kinetics in these patients are not completely understood. This review discusses the current literature on the clinical potency and physiological determinants of O₂ uptake kinetics in CHF patients and provides directions for future research. (Neth Heart J 2009;17:238–44.)     

左西孟旦联合沙库巴曲缬沙坦钠对慢性心衰患者血流动力学和运动能力的影响

摘要 目的：探讨左西孟旦联合沙库巴曲缬沙坦钠（诺欣妥）对慢性心衰患者血流动力学和运动能力的影响。方法：2018年1月至2019年5月选择在本院心内科诊治的慢性心衰患者80例,根据随机数字表法分为联合组50例,对照组30例。两组入院后均进行常规治疗,在此基础上,对照组给予沙库巴曲缬沙坦钠治疗,联合组给予沙库巴曲缬沙坦钠联合左西孟旦治疗,两组都治疗观察1个月,记录血流动力学和运动能力的变化情况。结果：治疗后联合组的总有效率显著高于对照组(98.0 % vs 80.0 %,P<0.05)。治疗后联合组的总有效率显著高于对照组(98.0 % vs 80.0 %,P<0.05)。两组治疗前(left ventricular ejection fraction,LVEF)值和(Left ventricular end-systolic diameter,LVSD)值比较无统计学意义(P>0.05),治疗1个月后,两组的的LVEF值显著高于治疗前,LVSD值显著低于治疗前(P<0.05),且上述指标的变化联合组更为显著(P<0.05)。两组治疗后的6 min步行距离都显著高于治疗前(P<0.05),且联合组也显著高于对照组(P<0.05)。结论：左西孟旦联合沙库巴曲缬沙坦钠治疗慢性心衰能改善患者的血流动力学状况和运动能力,从而提高治疗疗效。     

Quantitative analysis of changes occurring in muscle vastus lateralis in patients with heart failure after low-intensity training

OBJECTIVE: To quantitate the changes occurring in muscle vastus lateralis after exercise training of low intensity adopted for the rehabilitation of patients with chronic heart failure. STUDY DESIGN: Nine consecutive males with a clinical diagnosis of idiopathic dilated and ischemic cardiomyopathy underwent an eight-week period of training. The intensity of the work was calculated as 40% of peak VO2. The program consisted of 30 minutes of cycling three times per week. A cardiopulmonary exercise test, hemodynamic measurements and echocardiographic studies were carried out. Needle biopsies were taken from muscle vastus lateralis before starting and after completing training. Quantitative analysis was carried out on sections stained with ATPase at pH 9.5 for measurement of the lesser diameter of type 1 and 2 fibers (by using an image analyzer) and on UEA 1-stained sections for capillary density and capillary/fiber ratio (by using a frame in the eyepiece of the microscope). The Wilcoxon test was applied to identify significant differences before and after training. Spearman's rank correlation coefficient was also calculated to highlight any correlation between the morphologic data and results of clinical tests. RESULTS: After completing the training program, all the patients experienced an improvement in exercise tolerance and a significant increase (P < .004) in the VO2 and VCO2 peak. Skeletal muscle showed a significant (P < .02) increase in the capillary/fiber ratio. The changes were not significantly correlated with any of the clinical findings. CONCLUSION: Low-intensity training can improve the functional capacity of patients with heart failure while producing only mild morphologic changes in their muscles.     

Exercise training in chronic heart failure: mechanisms and therapies

Decreased exercise capacity negatively affects the individuals’ ability to adequately perform activities required for normal daily life and, therefore, the independence and quality of life. Regular exercise training is associated with improved quality of life and survival in healthy individuals and in cardiovascular disease patients. Also in patients with stable heart failure, exercise training can relieve symptoms, improve exercise capacity and reduce disability, hospitalisation and probably mortality. Physical inactivity can thus be considered a major cardiovascular risk factor, and current treatment guidelines recommend exercise training in patients with heart failure in NYHA functional classes II and III. Exercise training is associated with numerous pulmonary, cardiovascular, and skeletal muscle metabolic adaptations that are beneficial to patients with heart failure. This review discusses current knowledge of mechanisms by which exercise training is beneficial in these patients.     

Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of "Q-symbio"--a multinational trial

Energy starvation of the myocardium is probably a dominant feature of heart failure and attention has been directed towards agents which may stabilize myocardial metabolism and maintain adequate energy stores. A reduced myocardial tissue content of the essential redox-component and natural antioxidant Coenzyme Q10 (CoQ10) has been detected in patients with heart failure and the observed level of CoQ10 deficiency was correlated to the severity of heart failure. CoQ10 fulfills various criteria of an obvious adjunct in patients with symptomatic heart failure: it is devoid of significant side effects and it improves symptoms and quality of life. Till this date, several double-blind placebo-controlled trials with CoQ10 supplementation in more than 1000 patients have been positive and statistically significant with respect to various clinical parameters, e.g. improvement in NYHA Class, exercise capacity and reduced hospitalisation frequency. Also treatment with CoQ10 led to a significant improvement of relevant hemodynamic parameters. In only 3 out of 13 double-blind studies comprising 10% of the total number of patients treated the results were neutral. Thus, based on the available controlled data CoQ10 is a promising, effective and safe approach in chronic heart failure. This is why a double-blind multicenter trial with focus on morbidity and mortality has been planned to start in 2003: Q-SYMBIO. Patients in NYHA classes III to IV (N=550) receiving standard therapy are being randomized to treatment with CoQ10 100 mg t.i.d. or placebo in parallel groups. End-points in a short-term evaluation phase of 3 months include symptoms, functional capacity and biomarker status (BNP). The aim of a subsequent 2-year follow-up study is to test the hypothesis that CoQ10 may reduce cardiovascular morbidity (unplanned cardiovascular hospitalisation due to worsening heart failure) and mortality as a composite endpoint. This trial should help to establish the future role of CoQ10 as part of a maintenance therapy in patients with chronic heart failure.     

运动康复训练对冠心病多支病变患者运动耐量及血脂的影响

目的:探讨运动康复训练对冠心病多支病变患者活动耐量及血脂的影响。方法:选取冠心病多支病变患者,所有患者均进行不完全血运重建术,分为运动康复训练组及对照组,运动康复训练组自术后第三日起治疗组进行运动康复训练,对照组对运动量无要求。3月后,测量两组患者血脂水平及6分钟步行试验,比较两组患者步行距离、心绞痛发作次数、运动至心绞痛出现时间、6分钟内累积运动时间及血脂水平。结果:经运动康复训练治疗3月后,治疗组6分钟步行距离、运动至心绞痛出现时间及运动累积时间较对照组均明显增加,发生心绞痛次数较对照组明显减少。运动康复训练组治疗后甘油三酯、总胆固醇及低密度脂蛋白水平较治疗前明显降低,对照组仅总胆固醇有所降低,甘油三酯及低密度脂蛋白水平较治疗前无统计学差异。结论:运动康复训练可减少冠心病多支病变患者心绞痛发作次数,增加患者运动耐量并调节血脂代谢。