The Development of Tolerance to α1-Adrenoceptor Blockade With Chronic Carvedilol Treatment

Inclusion criteria

• Age of 18 to 85 years
• Symptomatic heart failure, NYHA class I to III
• Left ventricular ejection fraction < 0.40
• Give written informed consent

Exclusion criteria

• active myocarditis
• congenital heart disease
• uncorrected, hemodynamically significant stenotic valvular disease
• hypertrophic cardiomyopathy
• Asthma or other obstructive airway diseases requiring bronchodilators
• Heart rate < 60 beats/min, supine systolic blood pressure < 85 mm Hg, supine diastolic blood pressure > 90 mm Hg
• Uncontrolled Hypertension (Systolic BP >140 mmHg, Diastolic BP > 90 mmHg).
• Sick sinus syndrome, Mobitz type 2 second degree AV block or third degree AV block unless controlled with an artificial implantable pacemaker
• NYHA functional class IV symptoms
• Treatment with an excluded medication (see Excluded Medications below)
• Myocardial infarction or coronary artery intervention (CABG or angioplasty) within three months
• Unstable angina pectoris
• Presence of any progressive systemic disease that would be expected to impact the patient's outcome over the time course of the study
• Uncorrected endocrine disorders including primary aldosteronism, pheochromocytoma, hyperthyroidism, hypothyroidism, brittle type 1 diabetes mellitus
• Evidence of significant renal disease (serum creatinine > 2.5 mg/dl), or hepatic disease (transaminase level > three fold higher than laboratory normal)
• Symptomatic peripheral vascular disease
• Inability or unwillingness to cooperate with study or give written informed consent