Action: a 30,000 patient-years double-blind, placebo-controlled trial of nifedipine GITS in stable angina. ACTION Research Group.

To assess the overall balance between efficacy and safety of the long-action calcium antagonist nifedipine gastrointestinal therapeutic system (GITS) in patients with stable symptomatic coronary artery disease (CAD), a large multicentre placebo-controlled double-blind trial called ACTION has been mounted (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS). Patients are eligible if they have proven CAD on antianginal treatment in stable clinical condition for at least 3 months without heart failure. The left ventricular ejection fraction must be above 40%.

The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure.

Background: The influence of age, skeletal muscle function and peripheral blood flow on exercise capacity in chronic heart failure patients is controversial, possibly due to variations in skeletal muscle atrophy.

Methods And Results: To assess predictors of exercise capacity in patients with clinical cardiac cachexia, we studied 16 cachectic and 39 non-cachectic male chronic heart failure patients of similar age and ejection fraction. All cachectic patients were wasted (% ideal body weight: 81.

Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients with chronic heart failure.

Objectives: We sought to test the hypothesis that suppression of chemosensitivity (respiratory response to arterial blood gases) with dihydrocodeine may improve dyspnea and exercise tolerance in patients with chronic heart failure.

Background: Exertional dyspnea is a common limiting symptom in patients with chronic heart failure. The mechanisms underlying this symptom are not fully understood but may be related to increased ventilation caused, in part, by the augmentation of chemosensitivity.

17-beta-Estradiol therapy lessens angina in postmenopausal women with syndrome X.

Objectives: We sought to investigate the hypothesis that estrogen replacement therapy ameliorates symptoms in postmenopausal women with syndrome X.

Background: Syndrome X (angina pectoris, positive findings on exercise electrocardiography and normal results on coronary angiography) frequently occurs in menopausal women. This observation, in conjunction with the known vasoactive properties of estrogens, suggests that estrogen depletion may contribute to the pathogenesis of syndrome X in some women.

Exercise limitation in chronic heart failure: central role of the periphery.

The symptoms of chronic heart failure (CHF) are predominantly shortness of breath and fatigue during exercise and reduced exercise capacity. Disturbances of central hemodynamic function are no longer considered to be the major determinants of exercise capacity. The two symptoms of fatigue and breathlessness are often considered in isolation.

Mode of death in chronic heart failure. A request and proposition for more accurate classification.

The proportion of patients reported to die suddenly or from progressive circulatory failure is not consistent among studies of heart failure. Lack of an adequate or consistent classification of how patients die contributes to the current confusion over the mode of death in heart failure. Defining how patients with heart failure die could be important in developing strategies to reduce the continuing high mortality associated with this condition.

Histological abnormalities of muscle from limb, thorax and diaphragm in chronic heart failure.

The aim of the study was to compare histological findings in limb and respiratory muscles from control subjects and patients with heart failure of two different aetiologies. Biopsies of the quadriceps femoris, strap, diaphragm and pectoralis major muscles were taken from each group. The control subjects all had normal left ventricular function, and comprised seven undergoing surgical ablation of electrical pathways and 10 undergoing coronary artery surgery.

Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries. Evaluation by continuous coronary sinus pH monitoring and lactate metabolism.

Background: Whether myocardial ischaemia is the mechanism underlying chest pain in patients with angina and normal coronary arteriograms is controversial. We sought to detect the presence of transient myocardial ischaemia using continuous monitoring of coronary sinus blood pH during atrial pacing.

Methods And Results: We studied 14 patients (eight women, six men, mean age 51 +/- 3 years) with typical exertional angina and normal coronary arteriograms and nine patients with coronary artery disease (two men, seven women, mean age 61 +/- 7 years).

Neuroendocrine response to standing and mild exercise in patients with untreated severe congestive heart failure and chronic constrictive pericarditis.

Objectives: Plasma hormones at rest in patients with untreated severe congestive cardiac failure are similar to those occurring during heavy exercise in healthy people. This study examines the hypothesis that the neuroendocrine effects of exercise are modified in untreated congestive cardiac failure.

Design: The effect of lying, standing, upright exercise, and recovery on several plasma hormones was measured in healthy controls and 2 groups of patients with severe untreated heart failure.

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill.

Background: No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight.

Methods And Results: Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV).

Angiotensin II and contraction of isolated myocytes from human, guinea pig, and infarcted rat hearts.

The effects of angiotensin II on myocardial contractility were assessed in isolated cardiac myocyte preparations, using video microscopy with a computerized edge-detection system. Angiotensin II (1 nM-10 microM) did not affect the contraction of rat (n = 10), guinea pig (n = 11), or human ventricular myocytes (n = 8) or of human atrial myocytes (n = 12). Isoproterenol or raised extracellular calcium increased the contraction amplitude of the cardiac myocytes to a maximum of between 150 and 560% above basal, and there were corresponding increases in the velocities of contraction and relaxation.

Endothelin-1 is involved in norepinephrine-induced ventricular hypertrophy in vivo. Acute effects of bosentan, an orally active, mixed endothelin ETA and ETB receptor antagonist.

Background: Endothelin-1 (ET-1) has potent effects on cell growth and induces hypertrophy of cultured ventricular myocytes. Catecholamines increase expression of ET-1 mRNA by cultured myocytes. We investigated the role of endogenous ET-1 in catecholamine-induced hypertrophy in vivo by studying the effects of continuous norepinephrine infusion on physical and molecular markers of ventricular hypertrophy, ventricular and noncardiac expression of ET-1 mRNA, and the acute effects of bosentan, an orally active ETA and ETB receptor antagonist.

Endothelial control of lower limb blood flow in chronic heart failure.

Background: Limitation of the blood supply to skeletal muscle in chronic heart failure may contribute to the symptoms of fatigue and diminished exercise capacity. The pathophysiology underlying this abnormality is not known. The purpose of this study was to assess the effect of endothelium dependent and independent vasodilator agents on blood flow in the leg of patients with heart failure.

Transient autonomic dysfunction precedes ST-segment depression in patients with syndrome X.

Increased sympathetic drive has been suggested to play a role in the pathogenesis of syndrome X (angina pectoris, positive exercise testing, and angiographically normal coronary arteries). Heart rate variability (HRV) studies have shown that patients with syndrome X have an imbalance in autonomic nervous system activity (sympathetic predominance). However, it is not known if transient ST-segment depression which occurs in syndrome X during daily activities is related to this autonomic nervous system dysfunction.