Beta blockers with ACE inhibitors in mild heart failure

ACE inhibitors are standard therapy for treating both symptomatic and asymptomatic patients with left ventricular dysfunction. However, recent clinical trials have shown that beta blockers further reduce mortality in patients with symptomatic heart failure treated with ACE inhibitors. However, the evidence in support of adding beta blockers to ACE inhibitor therapy in patients with asymptomatic left ventricular dysfunction is less certain. The mechanisms by which ACE inhibitors and beta blockers may exert benefit in patients with heart failure are discussed, and studies assessing the association of beta blockade with outcome in patients with mild heart failure receiving ACE inhibitor therapy are reviewed. (c)2000 by CHF, Inc.     

Carvedilol therapy is associated with an improvement in left atrial appendage function in patients with congestive heart failure

Heart failure is one of the leading death reasons in the world. Left atrial appendage (LAA) is of great importance in maintaining cardiac function. We examined the effect of carvedilol therapy on left atrial appendage functions in patients with symptomatic congestive heart failure. Twenty patients with symptomatic congestive heart failure and resting ejection fraction < or = 40% were included in this study. LAA was visualized by transesophageal echocardiography. LAA area change (LAAAC), LAA empty velocity (LAAEV) and LAA empty velocity time integral (LAAEVTI) were calculated as the average of five cardiac cycles. A minimum dose of carvedilol administered to each patient, was titrated up to maximal dose that the patients could tolerate, during an 8-week period. After the third month of completing treatment, a second transthoracic and transesophageal echocardiographic study was performed. Heart rate (P < 0.001), systolic (P = 0.002) blood pressures were reduced by carvedilol therapy at the end of the third month. LAAEV (P < 0.001), LAAEVTI (P < 0.001), and LAAAC (P < 0.001) were significantly increased at the end of the third month of carvedilol therapy. This study indicates that in patients with symptomatic congestive heart failure, carvedilol therapy is associated with an improvement in left atrial appendage function.     

The ability of a submaximal exercise test to predict maximal exercise capacity in patients with heart failure

We investigated the ability of a submaximal exercise test topredict the maximal aerobic potential and hence exercise capacityof patients with chronic heart failure. Heart rate, oxygen consumptionand carbon dioxide production were measured continuously duringtreadmill exercise in 29 patients with chronic heart failure(NYHA Class II-III). The anaerobic threshold was determinedas the oxygen consumption at which carbon dioxide productionincreased non-linearly relative to oxygen consumption.Maximaloxygen consumption could not be predicted from the heart rateresponse to submaximal exercise.Oxygen consumption at the anaerobicthreshold (28 patients) and at a respiratory quotient of 1 (23patients) did predict maximal oxygen consumption (r = 0.93,r = 0.88, respectively). Measurement of oxygen consumption duringsubmaximal exercise can be used to assess maximal exercise capacityin patients with heart failure.     

Atrial fibrillation is associated with a lower exercise capacity in male chronic heart failure patients

Objective—To study the influence of atrial fibrillation on peak oxygen uptake (peak O₂) in chronic heart failure. An unfavourable effect of atrial fibrillation has been shown in several patient populations, but the results have not been consistent in chronic heart failure.
Methods—Data were analysed from male heart transplant candidates who were able to perform graded bicycle ergometry until exhaustion with respiratory gas analysis and measurement of heart rate. Patients in atrial fibrillation (n = 18) were compared with patients in sinus rhythm (n = 93).
Results—Age, weight, height, and aetiology of chronic heart failure did not differ significantly between the two groups. Cardiac catheterisation at supine rest showed that heart rate was comparable, but that stroke volume and cardiac output were lower (p < 0.05) in atrial fibrillation. Systolic and diastolic left ventricular function, assessed by radionuclide angiography at rest, were not significantly different. Peak O₂ (mean (SD): 13.8 (3.6) v 17.1 (5.6) ml/kg/min; p < 0.01) and peak work load (78 (27) v 98 (36) W; p < 0.05) were lower in the patients with atrial fibrillation, though respiratory gas exchange ratio and Borg score were similar in the two groups. Patients with atrial fibrillation had a higher heart rate sitting at rest before exercise (93 (16) v 84 (16) beats/min) and at peak effort (156 (23) v 140 (25) beats/min) (p < 0.05).
Conclusions—Atrial fibrillation is associated with a 20% lower peak O₂ in patients with chronic heart failure, suggesting that preserved atrial contraction or a regular rhythm, or both, are critical to maintain cardiac output and exercise performance.

Keywords: peak oxygen uptake;  exercise capacity;  chronic heart failure;  atrial fibrillation     

Contribution of lung function to exercise capacity in patients with chronic heart failure

BACKGROUND: The importance of exercise capacity as an indicator of prognosis in patients with heart disease is well recognized. However, factors contributing to exercise limitation in such patients have not been fully characterized and in particular, the role of lung function in determining exercise capacity has not been extensively investigated. OBJECTIVE: To examine the extent to which pulmonary function and respiratory muscle strength indices predict exercise performance in patients with moderate to severe heart failure. METHODS: Fifty stable heart failure patients underwent a maximal symptom-limited cardiopulmonary exercise test on a treadmill to determine maximum oxygen consumption (VO2max), pulmonary function tests and maximum inspiratory (PImax) and expiratory (PEmax) pressure measurement. RESULTS: In univariate analysis, VO2max correlated with forced vital capacity (r = 0.35, p = 0.01), forced expiratory volume in 1 s (r = 0.45, p = 0.001), FEV1/FVC ratio (r = 0.37, p = 0.009), maximal midexpiratory flow rate (FEF25-75, r = 0. 47, p < 0.001), and PImax (r = 0.46, p = 0.001), but not with total lung capacity, diffusion capacity or PEmax. In stepwise linear regression analysis, FEF25-75 and PImax were shown to be independently related to VO2max, with a combined r and r2 value of 0. 56 and 0.32, respectively. CONCLUSIONS: Lung function indices overall accounted for only approximately 30% of the variance in maximum exercise capacity observed in heart failure patients. The mechanism(s) by which these variables could set exercise limitation in heart failure awaits further investigation.     

Lactate production during maximal and submaximal exercise in patients with chronic heart failure

In patients with chronic heart failure whose cardiac output response to exercise is impaired, determination of anaerobic threshold may provide a useful and objective approach to grade the severity of heart failure. In such patients performing upright treadmill exercise to exhaustion, this study examined the reproducibility of the response of cardiac output and mixed venous lactate concentration when the exercise test was repeated the same or next day, the nature of this response after rest and exercise cardiac output levels were augmented by the cardiotonic agent amrinone and the response of lactate during symptom-limited submaximal exercise performed at either aerobic or anaerobic levels of work for each patient. Findings were: 1) the response of cardiac output and mixed venous lactate was reproducible (p less than 0.05) when assessed either the same or the next day; 2) when exercise cardiac output was increased (p less than 0.05) by oral amrinone therapy, the increase in lactate was delayed (p less than 0.05) to higher levels of muscular work and this was not true when cardiac output was unchanged; and 3) only submaximal anaerobic exercise was symptom limited and associated with an increase in lactate concentration. Thus, the lactate response and anaerobic threshold determination should prove useful to assess the severity of chronic stable heart failure and its response to pharmacologic intervention. The submaximal anaerobic exercise test may provide additional insights into the effort intolerance these patients experience.     

Short-term sibutramine therapy is associated with weight loss and improved endothelial function in obese patients with coronary artery disease

In obese patients with coronary artery disease (CAD), the vascular endothelium is usually impaired, and the modification or reversal of endothelial dysfunction may significantly enhance treatment. Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment, but its impact on endothelial function in obese patients with CAD has not yet been investigated. Eighty consecutive obese, nonhypertensive, stable patients with CAD (65 men; mean age 65 +/- 11 years, mean body mass index 32 +/- 3 kg/m2) were randomly assigned to either sibutramine 10 mg/day (n = 40) or routine treatment (n = 40; controls) for 4 months. The percentage improvement in endothelium-dependent brachial artery flow-mediated dilation (%FMD) and endothelium-independent nitroglycerin-mediated vasodilation were assessed at baseline and after 4 months using high-resolution ultrasound. At baseline, all patients had %FMD of 5.4 +/- 3.1% and percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation of 9.2 +/- 2.9%, showing no significant differences. After 4 months, however, initial body weight was reduced by 11.4 +/- 1.2% in the sibutramine group compared with only 2.2 +/- 1.3% in controls (p <0.001), demonstrating a significant improvement in postintervention %FMD (8.9 +/- 2.4%, p = 0.01, compared with baseline) in the sibutramine group compared with controls (5.2 +/- 3.6%, p = 0.68, compared with baseline). No significant therapeutic effect on the percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation was seen in either group (9.2 +/- 2.5% vs 9.1 +/- 3.0%, respectively, p = 0.792). In addition, sibutramine therapy was associated with significant C-reactive protein reduction compared with routine treatment (44% vs 9%, p = 0.035). Thus, short-term therapy with sibutramine, together with diet and lifestyle intervention, is associated with improved endothelial function assessed by brachial artery %FMD in nonhypertensive, stable patients with CAD.     

Cold temperature impairs maximal exercise performance in patients with heart failure: attenuation by acute ACE inhibitor therapy

BACKGROUND: Cold exposure decreases ischemic threshold in patients with coronary artery disease and preserved left ventricle (LV) function. The impact of cold exposure and the effect of acute angiotensin-converting enzyme (ACE) inhibitor therapy on maximal exercise capacity have not been studied in patients with symptomatic congestive heart failure. METHODS AND RESULTS: Eleven patients with New York Heart Association class II and III congestive heart failure, aged 61 6 years (mean SD), with LV ejection fraction 25 6%, completed four symptoms-limited maximal exercise tests at 20 C and -8 C in a cold chamber. The exercise tests were performed while the patients were treated with lisinopril for three days, or a placebo. Cold exposure significantly decreased exercise duration in patients treated with a placebo (506 156 s [20 C] versus 419 182 s [-8 C], P<0.01). Rate-pressure products measured at 4 min during the test and at peak performance were significantly increased at -8 C. Patients treated with lisinopril exhibited a significant attenuation of the decrease in exercise time in the cold (-17% for placebo versus -6.6% for lisinopril, P<0.05). CONCLUSIONS: Cold temperature increases cardiac demand in response to exercise and significantly reduces maximal exercise capacity in patients with symptomatic heart failure. Acute treatment with lisinopril attenuates the impact of cold on exercise capacity.     

β-受体阻滞剂在心力衰竭治疗中的应用

β-受体阻滞剂可以分为非选择性、选择性和具有血管扩张作用的β-受体阻滞剂3类。这类药物可以通过β信号系统上调、逆转重构、改善收缩和舒张功能、抗心律失常以及抗缺血等作用改善心力衰竭患者预后。随机对照临床研究已经证实其可以降低心力衰竭患者病死率、提高生存质量。各种指南也推荐其应用于心力衰竭的治疗。应用该类药物应该注意用药的时机、剂量、时程和禁忌证。     

ACE inhibitors and mineralocorticoid receptor blockade in patients with congestive heart failure

The two major outcome trials on the combination of angiotensin-converting enzyme (ACE) inhibitors and mineralocorticoid receptor (MR) antagonists in heart failure are RALES (Randomized Aldactone Evaluation Study) and EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study). There have also been studies in essential hypertension, and in diabetic hypertensive patients, on the cardiac and renal effects of ACE inhibitors and MR antagonists, individually and in combination. In the clinical studies on heart failure, in outcome trials and the smaller studies using surrogate end points, a combination of ACE inhibition and MR blockade is superior to ACE inhibition alone, and in the hypertension studies to either agent alone. Some insight into their distinct sites of protective action may be gained from studies on experimental animal preparations. The principal caveat in the use of combination therapy is the possibility of hyperkalemia, which should be minimal in patients with creatine clearance greater than 30 mL/min and with the low doses of MR antagonist shown to be effective in outcome trials.     

Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation

OBJECTIVES: This study was designed to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition, coronary endothelial function and cytokine activation in heart transplant recipients without angiographically detectable disease. BACKGROUND: Coronary endothelial dysfunction contributes to cardiac allograft vasculopathy. The vasoprotective effects of statins in heart transplant recipients may include restoration of endothelial function and suppression of allograft inflammatory activity. METHODS: Heart transplant recipients (one to three years after heart transplant) were divided into three groups based on the total cholesterol levels: group 1 (n = 21), patients with a history of hypercholesterolemia adequately controlled with simvastatin; group 2 (n = 19), patients with hypercholesterolemia not adequately treated with simvastatin; and group 3 (n = 40), patients without hypercholesterolemia. Coronary vasomotor function and intimal thickness as well as coronary sinus and aortic cytokine concentrations (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6 and soluble IL-2 receptor) were investigated. In a prospective one-year follow-up study, changes in coronary endothelial function and cytokine levels were compared between 11 hypercholesterolemic patients treated with simvastatin and 9 controls. RESULTS: Epicardial and microvascular endothelial functions were better in groups 1 and 3 than they were in group 2 (p < 0.01 and p < 0.05). Transcardiac IL-6 and TNF-alpha gradients were significantly increased in groups 2 and 3 compared with group 1 (IL-6: p < 0.05; TNF-alpha: p < 0.01). Plaque areas were significantly increased in groups 1 and 2 (p < 0.05 vs. group 3), whereas lumen area was increased in group 2 compared with group 1 (p < 0.05), demonstrating adaptive vascular remodeling. In patients treated with simvastatin, coronary endothelial function and cardiac cytokine activity significantly improved during the one-year follow-up. CONCLUSIONS: Inhibition of allograft inflammatory activity and attenuation of the coronary endothelial dysfunction observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of cardiac allograft vasculopathy.