- Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: Class II, III, or IV heart failure as defined by the New York Heart Association functional classification system; uncontrolled angina; clinically significant pericardial disease; severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. Other clinically significant ECG abnormalities including second degree (Type II) or 3rd degree atrioventricular (AV) block; history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening; pulmonary hypertension