心肺运动试验评估慢性左心衰竭患者的运动能力

目的:应用心肺运动试验(CPET)评估国人慢性左心衰竭患者的运动能力.方法:入选2010-08至2010-12期间入住本中心的慢性左心衰竭患者20例(心衰组),并选择27例心肺功能正常的匹配人群作为对照组,均进行CPET,同时收集两组人群的临床资料和常规检查结果.结果:运动过程中,心衰组较对照组峰值心率、峰值收缩压、无氧域、峰值氧摄取量、峰值氧摄取量占预计值的百分比(峰值VO2/Pred.)、峰值氧脉搏等指标均显著降低(P<0.001或<0.05),而二氧化碳通气当量(VE/VCO2)斜率显著升高(P<0.01),差异均有统计学意义.校正年龄、性别、体重指数后,偏相关分析结果提示氨基末端B型脑钠肽原(NT-proBNP)仍与VE/VCO2斜率相关性最高(r=0.685,P<0.001);左心室射血分数与峰值氧摄取量相关性最高(r=0.679,P<0.001);峰值心率与峰值VO2/Pred.相关性最高(r=0.791,P<0.001);峰值收缩压与峰值氧摄取量相关性最高(r=0.677,P<0.001);而且,用力肺活量、一秒量均与峰值氧摄取量相关性最高(分别为r=0.559,P<0.001和r=0.589,P<0.001).结论:CPET可以客观、定量地评价慢性左心衰竭患者的运动能力.     

Analysis of Skeletal Muscle Gene Expression Patterns and the Impact of Functional Capacity in Patients With Systolic Heart Failure

BackgroundDeclining physical function is common among systolic heart failure (HF) patients and heralds poor clinical outcomes. We hypothesized that coordinated shifts in expression of ubiquitin-mediated atrophy-promoting genes are associated with muscle atrophy and contribute to decreased physical function.MethodsSystolic HF patients (left ventricular ejection fraction [LVEF] ≤40%) underwent skeletal muscle biopsies (nondominant vastus lateralis) and comprehensive physical assessments. Skeletal muscle gene expression was assessed with the use of real-time polymerase chain reaction. Aerobic function was assessed with the use of cardiopulmonary exercise and 6-minute walk tests. Strength capacity was assessed with the use of pneumatic leg press (maximum strength and power). Serologic inflammatory markers also were assessed.Results54 male patients (66.6 ± 10.0 years) were studied: 24 systolic HF patients (mean LVEF 28.9 ± 7.8%) and 30 age-matched control subjects. Aerobic and strength parameters were diminished in HF versus control. FoxO1 and FoxO3 were increased in HF versus control (7.9 ± 6.2 vs 5.0 ± 3.5, 6.5 ± 4.3 vs 4.3 ± 2.8 relative units, respectively; P ≤ .05 in both). However, atrogin-1 and MuRF-1 were similar in both groups. PGC-1α was also increased in HF (7.9 ± 5.4 vs. 5.3 ± 3.6 relative units; P < .05). Muscle levels of insulin-like growth factor (IGF) 1 as well as serum levels of tumor necrosis factor α, C-reactive protein, interleukin (IL) 1β, and IL-6 were similar in HF and control.ConclusionExpression of the atrophy-promoting genes FoxO1 and FoxO3 were increased in skeletal muscle in systolic HF compared with control, but other atrophy gene expression patterns (atrogin-1 and MuRF-1), as well as growth promoting patterns (IGF-1), were similar. PGC-1α, a gene critical in enhancing mitochondrial function and moderating FoxO activity, may play an important counterregulatory role to offset ubiquitin pathway–mediated functional decrements.     

Improved Right Ventricular Systolic Function After Cardiac Resynchronization Therapy in Patients With Heart Failure

BackgroundSince the introduction of cardiac resynchronization therapy (CRT) to improve left ventricular function, the effect of CRT on the right ventricle in patients with heart failure has not been well described.MethodsWe evaluated the effect of CRT on right ventricular systolic function in 20 patients (80% men; mean [SD] age, 58.5 [9.8] y) with cardiomyopathy and right ventricular systolic dysfunction (New York Heart Association class III or IV, left ventricular ejection fraction ≤35%, and QRS interval ≥120 ms). The median follow-up time was 15 months. Right ventricular systolic function, defined as a tricuspid annular plane systolic excursion (TAPSE) index of 16 mm or less, was evaluated in patients before and after CRT.ResultsTwelve (60%) patients had ischemic cardiomyopathy, and 12 (60%) patients had left bundle branch block detected using surface electrocardiogram. The mean (SD) QRS duration was 160.5 (24.4) ms. From before CRT to the time of follow-up after CRT, the mean (SD) ejection fraction increased significantly from 22.5% (5.6%) to 29.4% (7.4%) (P < .001). The mean (SD) TAPSE index also increased significantly from 13.70 (1.78) mm to 16.50 (4.77) mm (P = .018). Eleven (55%) patients showed improved right ventricular systolic function (TAPSE ≥16 mm) after CRT. Patients with a favorable right ventricular response to CRT were significantly older (64.6 [8.2] y vs 53.6 [8.4] y, respectively) and more likely to have nonischemic origin of cardiomyopathy than were patients with unimproved right ventricular function (66.7% vs 18.2%, respectively).ConclusionOur findings indicate that CRT is associated with improved right ventricular systolic function in patients with heart failure and right ventricular systolic dysfunction. Patients with nonischemic heart disease more often show improved right ventricular function after CRT.     

Cholinergic Stimulation Improves Autonomic and Hemodynamic Profile During Dynamic Exercise in Patients With Heart Failure

BackgroundParasympathetic dysfunction is an independent risk factor for mortality in heart failure for which there is no specific pharmacologic treatment. This article aims to determine the effect of pyridostigmine, an anticholinesterase agent, on the integrated physiologic responses to dynamic exercise in heart failure.Methods and ResultsPatients with chronic heart failure (n = 23; 9 female; age = 48 ± 12 years) were submitted to 3 maximal cardiopulmonary exercise tests on treadmill in different days. The first test was used for adaptation and to determine exercise tolerance. The other tests were performed after oral administration of pyridostigmine (45 mg, 3 times/day, for 24 hours) or placebo, in random order. All patients were taking their usual medication. Pyridostigmine reduced cholinesterase activity by 30%, inhibited the chronotropic response throughout exercise, up to 60% of maximal effort (pyridostigmine = 108 ± 3 beats/min vs. placebo = 113 ± 3 beats/min; P = .040), and improved heart rate reserve (pyridostigmine = 73 ± 5 beats/min vs. placebo = 69 ± 5 beats/min; P = 0.035) and heart rate recovery in the first minute after exercise (pyridostigmine = 25 ± 2 beats/min vs. placebo = 22 ± 2 beats/min; P = .005), whereas peak heart rate was similar to placebo. Oxygen pulse, an indirect indicator of stroke volume, was higher under pyridostigmine during submaximal exercise.ConclusionsPyridostigmine was well tolerated by heart failure patients, leading to improved hemodynamic profile during dynamic exercise.     

Right Ventricular Function and Beneficial Effects of Cardiac Rehabilitation in Patients With Systolic Chronic Heart Failure

Background

It has been recognized that a comprehensive cardiac rehabilitation (CR) program improves mortality in patients with chronic heart failure. On the other hand, the magnitude of the improvement in exercise capacity after CR differs among individuals. The aim of this study was to assess the echocardiographic determinants of responders to CR using preload stress echocardiography.

Increased Exhaled Nitric Oxide Levels After Exercise in Patients With Chronic Systolic Heart Failure With Pulmonary Venous Hypertension

BackgroundFractional exhaled nitric oxide (eNO) is recognized as a marker of pulmonary endothelial function. Oxidative stress is associated with systemic endothelial nitric oxide production, but its correlation with eNO in heart failure (HF) patients has not been described. Previous studies have reported increased eNO levels after exercise in symptomatic HF patients but decreased levels with pulmonary arterial hypertension. Our objective was to prospectively examine the potential myocardial and functional determinants of exercise-induced rise of eNO in HF.Methods and ResultsThirty-four consecutive ambulatory patients with chronic systolic HF (left ventricular ejection fraction [LVEF] ≤45%) underwent symptom-limited cardiopulmonary stress testing and echocardiography. eNO was determined immediately after exercise. Systemic endothelial dysfunction was assessed by asymmetric dimethylarginine (ADMA) and the L-arginine/ADMA ratio. In our study cohort (mean age 53 ± 13 years, 76% male, median LVEF 31%, interquartile range [IQR] 25%–40%), the mean eNO was 23 ± 9 ppb. eNO levels were higher in patients with diastolic dysfunction stages 2 or 3 than stage 1 or normal diastology (26.1 ± 9 vs 19.5 ± 7 ppb; P = .013). eNO had a positive correlation with estimated systolic pulmonary artery pressure (r = 0.57; P = .0009) and indexed left atrium volume (r = 0.43; P = .014), but it did not correlate with cardiopulmonary exercise test parameters, ADMA, or symptom score.ConclusionsIn contrast to earlier reports, the increase in postexercise eNO observed in stable chronic systolic HF patients may be attributed to the presence of underlying pulmonary venous hypertension probably secondary to advanced diastolic dysfunction.     

Effect of Dronedarone on Exercise Capacity and Cardiac Function in Patients With Severe Left Ventricular Dysfunction and Compensated Stable Heart Failure

Purpose

Dronedarone is a novel multichannel blocker with antiadrenergic and vasodilatory properties. The aim of this study was to investigate the effects of dronedarone on functional capacity in patients with severe left ventricular (LV) dysfunction and compensated stable heart failure (HF).

Methods

This was a multicentre, double-blind, randomized, placebo-controlled, dose-escalating study. Patients in sinus rhythm with impaired LV function (LV ejection fraction [LVEF]?≤?30%) and compensated HF (New York Heart Association [NYHA] class I–II), who would continue to receive cardiovascular treatment (excluding antiarrhythmic agents), were eligible. A total of 124 patients were randomized to receive dronedarone (400 mg or 800 mg once daily or 600 mg twice daily) or placebo for 30 days. The primary objective was assessment of the effects of dronedarone on functional capacity, using the 6 min walk test. Secondary objectives included the effects of dronedarone on LVEF, cardiothoracic ratio, NYHA status, and Holter parameters.

Results

A total of 111 patients completed the study. There were no significant differences between dronedarone and placebo with respect to walking distance and LVEF. The cardiothoracic ratio was similar in all treatment groups throughout the study, and the NYHA status did not change in the majority of patients. Dronedarone was well tolerated and, as expected, decreased heart rate. No new arrhythmic events or torsades de pointes were reported.

Conclusions

Short-term treatment with dronedarone did not affect exercise capacity and did not decrease LVEF in patients with severe LV dysfunction and compensated HF.     

Cardiopulmonary Exercise Testing Identifies Low Risk Patients With Heart Failure and Severely Impaired Exercise Capacity Considered for Heart Transplantation

Objectives. The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk.Background. Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (Vo₂) 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size.Methods. Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise Vo₂≤14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk.Results. The 55% 3-year survival rate of the 77 patients with a peak exercise Vo₂≤14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak Vo₂≤50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1.Conclusions. Peak exercise SBP and percent predicted peak exercise Vo₂are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise Vo₂≤14 ml/min per kg.     

Resting Lung Function in the Assessment of the Exercise Capacity in Patients With Chronic Heart Failure

BackgroundDespite the lung involvement in patients with chronic heart failure (CHF), the significance of lung function abnormalities to functional status in these patients is still controversial. We postulated that in patients with CHF, resting lung function assessment may provide information of clinical relevance on exercise capacity, expressed as peak oxygen uptake (VO₂) and ventilatory response to CO₂ production (VE/VCO₂) during a maximal exercise.MethodsWe studied 49 clinically stable patients with CHF (38 men, age range: 25–178 years) (New York Heart Association class range: I-IV) with left ventricular ejection fraction < 40%. Patients with chronic obstructive pulmonary disease were excluded. Patients performed pulmonary function tests and maximal incremental exercise test.ResultsResting spirometry was related to the exercise capacity (P < 0.05), expressed as peak VO₂. By means of receiver operating characteristic curve analysis, the forced expiratory volume at first second (FEV₁) cutoff point, which better identified patients with a peak VO₂ ≤ 14 mL/kg/min, was < 79% of predicted value (0.79 sensitivity and 0.73 specificity). Resting lung diffusion capacity for carbon monoxide and end-tidal pressure of CO₂ (PETCO₂) were inversely correlated to VE/VCO₂ (P < 0.01). The lung diffusion capacity for carbon monoxide and PETCO₂ cutoff points, which better identified patients with VE/VCO₂ value > 34, were < 58% of predicted (0.92 sensitivity and 0.42 specificity) and < 33 mm Hg (0.67 sensitivity and 0.92 specificity), respectively.ConclusionsIn patients with CHF, resting lung function, including spirometry, lung diffusion capacity, and PETCO₂, can provide clinically useful information on exercise capacity, by predicting peak VO₂ and VE/VCO₂ slope. The results of this study highlight the role of resting lung function in the assessment of the functional status of cardiac patients.     

Comparative Effects of Losartan and Enalapril on Exercise Capacity and Clinical Status in Patients With Heart Failure

Objectives. This study was designed to determine 1) whether 12-week oral administration of losartan, an angiotensin II receptor antagonist, in patients with heart failure is well tolerated; and 2) whether functional capacity and clinical status of patients with heart failure in whom treatment with an angiotensin-converting enzyme (ACE) inhibitor is replaced with losartan for 12 weeks will remain similar to that noted in patients in whom treatment with an ACE inhibitor is continued.Background. Losartan is a specific, nonpeptide angiotensin II receptor antagonist. Although specific receptor blockade with losartan has certain theoretic advantages over nonspecific ACE inhibition, definitive demonstration of comparable effects in patients with congestive heart failure is lacking.Methods. A double-blind, multicenter, randomized, parallel, enalapril-controlled study was conducted in 116 patients with congestive heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction ≤45% previously treated with stable doses of ACE inhibitors and diuretic agents, with or without concurrent digitalis and other vasodilators. After a baseline exercise period, open-label ACE inhibitors were discontinued, and patients were randomly assigned to 12 weeks of therapy with losartan, 25 mg/day (n = 38); losartan, 50 mg/day (n = 40); or enalapril, 20 mg/day (n = 38). Drug efficacy was evaluated by changes in maximal treadmill exercise time (using a modified Naughton protocol), 6-min walk test, left ventricular ejection fraction and dyspnea-fatigue index. Safety was measured by the incidence of clinical and laboratory adverse experiences.Results. The treadmill exercise time and the 6-min walk test did not change significantly after replacement of ACE inhibitor therapy with losartan. Similarly, a significant change was not observed in either the dyspnea-fatigue index or left ventricular ejection fraction at the end of double-blind period relative to baseline.Conclusions. Losartan was generally well tolerated and comparable to enalapril in terms of exercise tolerance in this short-term (12-week) study of patients with heart failure. The clinical effects of long-term angiotensin II receptor blockade compared with ACE inhibition remain to be studied.     

Metformin Therapy and Outcomes in Patients With Advanced Systolic Heart Failure and Diabetes

BackgroundAlthough 25% to 44% of patients with heart failure (HF) have diabetes mellitus (DM), the optimal treatment regimen for HF patients with DM is uncertain. We investigated the association between metformin therapy and outcomes in a cohort of advanced, systolic HF patients with DM.Methods and ResultsPatients with DM and advanced, systolic HF (n = 401) were followed at a single university HF center between 1994 and 2008. The cohort was divided into 2 groups based on the presence or absence of metformin therapy. The cohort had a mean age of 56 ± 11 years, left ventricular ejection fraction (LVEF) of 24 ± 7%, with 42% being New York Heart Association (NYHA) III and 45% NYHA IV. Twenty-five percent (n = 99) were treated with metformin therapy. The groups treated and not treated with metformin were similar in terms of age, sex, baseline LVEF, medical history, and baseline glycosylated hemoglobin. Metformin-treated patients had a higher body mass index, lower creatinine, and were less often on insulin. One-year survival in metformin-treated and non-metformin-treated patients was 91% and 76%, respectively (RR = 0.37, CI 0.18-0.76, P = .007). After multivariate adjustment for demographics, cardiac function, renal function, and HF medications, metformin therapy was associated with a nonsignificant trend for improved survival.ConclusionIn patients with DM and advanced, systolic HF who are closely monitored, metformin therapy appears to be safe. Prospective studies are needed to determine whether metformin can improve HF outcome.