Adequate cardiac function, defined as:\r\n* No electrocardiogram (EKG) evidence of acute ischemia\r\n* No EKG evidence of active, clinically significant conduction system abnormalities\r\n* No EKG evidence of > grade  (>  ms) corrected QT (QTc) prolongation \r\n* Prior to study entry, any EKG abnormality at screening not felt to put the patient at risk has to be documented by the investigator as not medically significant\r\n* No uncontrolled angina or severe ventricular arrhythmias\r\n* No clinically significant pericardial disease\r\n* No history of myocardial infarction within  months prior to registration\r\n* No class  or higher New York Heart Association congestive heart failure
Patient has, in the opinion of the treating investigator, any intercurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results; these conditions include, but not limited to: congestive heart failure (New York Heart Association (NYHA) Class III or IV), unstable angina, cardiac arrhythmia requiring treatment, recent (within the prior  months) myocardial infarction, acute coronary syndrome or stroke, severe obstructive pulmonary disease, hypertension requiring more than  medications for adequate control, or diabetes mellitus with more than  episodes of ketoacidosis in the prior  months
Any of the following cardiac abnormalities:\r\n* Unstable angina pectoris\r\n* Congestive heart failure >= New York Heart Association class \r\n* Corrected QT interval (QTc) >=  milliseconds calculated using Fridericias correction\r\n* Current or history of pericardial effusion causing hemodynamic compromise
Clinically significant cardiac disease, including: NYHA Class III or IV congestive heart failure, unstable angina, acute myocardial infarction within six months of planned first dose, arrhythmia requiring therapy (including torsades de pointes, with the exception of extrasystoles, minor conduction abnormalities, or controlled and well treated chronic atrial fibrillation)
Received treatment for unstable angina within the prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Patients with QTc interval >  msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (ex. heart failure, clinically significant hypokalemia, clinically significant hypomagnesemia, family history of long QT syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions are excluded
New York Heart Association (NYHA) stage III/IV congestive heart failure, arrhythmias not adequately controlled, active infections, or other significant co-morbidities [e.g. active central nervous system metastases and/or carcinomatous meningitis, active infection requiring systemic therapy, history of human immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis C.
History of serious organ dysfunction or disease involving the heart (left ventricular ejection fraction < %; unstable angina, acute myocardial infarction within  months prior to randomization, congestive heart failure New York Heart Association [NYHA] III-IV, and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities)
Congestive heart failure (NYHA class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months prior to first dose.
New York Heart Association (NYHA) stage III/IV congestive heart failure, arrhythmias not adequately controlled, or other significant co-morbidities [e.g. active infection requiring systemic therapy, history of human immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis C].
Subject has clinically significant cardiac disease, including significant ischemic coronary disease, congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable arrhythmias, myocardial infarction or unstable angina within  months before randomization, a history of additional risk factors for torsades de pointes (eg, electrolyte abnormalities, family history of long QT syndrome), or a family history of sudden cardiac death before age 
. Those with New York Heart Association functional classification II, III or IV; active cardiac conditions including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
EXCLUSION - PROCUREMENT: Cardiac criteria: prolonged QT syndrome; atrial fibrillation/flutter; myocardial infarction within the last  months; cardiac echocardiography with left ventricular systolic function (LVSF) ? % or left ventricular ejection fraction (LVEF) ? %; cardiac dysfunction New York Heart Association (NYHA) III or IV; cardiac echocardiography with clinically significant pericardial effusion
No history of any of the following =<  months of registration:\r\n* Myocardial infarction or unstable angina\r\n* New York Heart Association grade III or greater congestive heart failure \r\n* Cerebrovascular accident \r\n* Grade  or  peripheral ischemia\r\n* Grade  or  thromboembolic event
Severe, active co-morbidity defined as follows:\r\n* Chronic or current active infectious disease requiring systemic antibiotics, antifungal or antiviral treatment\r\n* Known brain or central nervous system metastases or history of uncontrolled seizures\r\n* Clinically significant cardiac disease including unstable angina, acute myocardial infarction within  months from enrollment, New York Heart Association class III or IV congestive heart failure, and serious arrhythmia requiring medication (this does not include asymptomatic atrial fibrillation with controlled ventricular rate)\r\n* Partial or complete gastrointestinal obstruction
Any of the following cardiac diseases currently or within the last  months as defined by New York Heart Association (NYHA) >= class \r\n* Unstable angina pectoris\r\n* Congestive heart failure\r\n* Acute myocardial infarction\r\n* Conduction abnormality not controlled with pacemaker or medication\r\n* Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)\r\n* AZD should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected; AZD has not been studied in patients with ventricular arrhythmias or recent myocardial infarction
Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic cardiac ischemia, unstable angina or myocardial infarction in the previous  months prior to first dose, or with a known left ventricular ejection fraction (LVEF) <%, cardiomyopathy, pericardial disease, clinically relevant cardiac arrhythmia (CTCAE version . Grade  or higher), clinically significant ECG abnormalities, or screening -lead ECG showing a baseline prolonged QT interval (baseline QT interval as corrected by Fridericia's formula >  msec).
Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
Have clinically significant cardiac disease (New York Heart Association class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction one year prior to study entry, or grade  or higher compromised left ventricular ejection fraction
Known cardiac disorder, including:\r\n* Known inherited coronary disease\r\n* Symptomatic heart failure (New York Heart Association [NYHA] class II-IV prior or current cardiomyopathy, or severe valvular heart disease)\r\n* Current cardiomyopathy\r\n* Severe valvular heart disease\r\n* Atrial fibrillation\r\n* Ejection fraction (ECHO) < %\r\n* QTcF >  msec
Clinically significant heart failure (New York Heart Association [NYHA] > ), recent myocardial infarction, or symptomatic atrial fibrillation
Active congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within four months prior to enrollment
Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a corrected QT interval (QTc) >  msec
No clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >=  within  months prior to registration for protocol therapy
Significant cardiovascular disease or condition including:\r\n* Congestive heart failure (CHF) currently requiring therapy.\r\n* Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria.\r\n* Need for antiarrhythmic medical therapy for a ventricular arrhythmia.\r\n* Severe conduction disturbance (e.g. rd degree heart block).\r\n* Unstable angina pectoris (i.e. last episode =<  months prior to first dose of protocol-indicated treatment).\r\n* Uncontrolled (per investigator judgment) hypertension.\r\n* Myocardial infarction within  months prior to starting trial treatment.\r\n* Fridericia's correction formula (QTcF) >  ms in men, or >  ms in women.
Subject has a history of a major adverse cardiac event, including cerebrovascular accident or myocardial infarction within the prior  months, or uncontrolled congestive heart failure (New York Heart Association class  or ) at Screening.
Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within  months), such as:\r\n* Unstable angina within  months prior to screening;\r\n* Myocardial infarction within  months prior to screening;\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV);\r\n* Cardiac arrhythmias not controlled with medication;\r\n* Corrected QT (QTcF) >  ms at baseline
Any significant medical conditions, laboratory abnormality, or psychiatric illness that would exclude the subject from participation or interfere with study treatment, monitoring and compliance such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association [NYHA] III or IV), myocardial infarction ?  months prior to first study drug, clinically significant and uncontrolled cardiac arrhythmia (e.g. atrial fibrillation/flutter ventricular cardiovascular physiology is allowed), cerebrovascular accidents ?  months before study drug start\r\n* Severely impaired lung function
Research participants with a known history of congestive heart failure (CHF) or cardiac symptoms consistent with New York Heart Association (NYHA) classification III-IV within  months prior to Day  of protocol treatment, cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications or with clinical history suggestive of the above must have an electrocardiogram (EKG) and echocardiogram (ECHO) performed within  days prior to registration and as clinically indicated while on treatment
Research participants does NOT have any known history of congestive heart failure (CHF) or cardiac symptoms consistent with NYHA classification III-IV within  months prior to Day  of protocol treatment, cardiomyopathy, myocarditis, myocardial infarction (MI), exposure to cardiotoxic medications or with clinical history suggestive of the above must have an EKG and echocardiogram (ECHO) performed within  days prior to registration and as\r\nclinical indicated while on treatment
Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last  months
Cardiac conditions: congestive heart failure, New York Heart Association class - heart failure, baseline left ventricular ejection fraction (LVEF) < %, transmural myocardial infarction, uncontrolled hypertension, angina pectoris requiring medication, clinically significant valvular disease, high-risk arrhythmia in the past  months
Not eligible for more intensive cytotoxic chemotherapy or consolidative autologous stem cell transplant based on one or more of the following:\r\n* Clinically significant heart or lung comorbidities, as reflected by at least  of the following:\r\n** Left ventricular ejection fraction (LVEF) =< %\r\n** Chronic stable angina or congestive heart failure controlled with medication\r\n** New York Heart Association (NYHA) class III or IV heart failure\r\n** Symptomatic chronic pulmonary disease or requirement for intermittent or continuous oxygen therapy\r\n* Presence of other medical comorbidity or limitation in functional status which the investigator judges to be incompatible with an acceptable risk to the subject with the use of intensive chemotherapy; the associated comorbidity or functional limitation must be clearly documented in the medical record at the time of enrollment OR
Severe, active co-morbidity defined as follows:\r\n* Chronic or current active infectious disease requiring systemic antibiotics, antifungal or antiviral treatment (with the exception of uncomplicated urinary tract infection [UTI])\r\n* Clinically significant cardiac disease including unstable angina, acute myocardial infarction within  months from enrollment, New York Heart Association class Ill or IV congestive heart failure, and serious arrhythmia requiring medication (this does not include asymptomatic atrial fibrillation with controlled ventricular rate)\r\n* Partial or complete gastrointestinal obstruction
Any significant diseases medical condition, laboratory abnormality, or psychiatric illness that would exclude the subject from participate or interfere with study treatment, monitoring and compliance such as:\r\n* Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association [NYHA] III or IV), myocardial infarction =<  months prior to first study drug, clinically significant and uncontrolled cardiac arrhythmia (e.g. atrial fibrillation/flutter ventricular cardiovascular physiology is allowed), cerebrovascular accidents =<  months before study drug start\r\n* Severely impaired lung function
Impaired cardiac function or clinically significant cardiac disease including the following:\r\n* New York Heart Association grade III or IV congestive heart failure\r\n* Myocardial infarction within the last  months.\r\n* Subjects with impaired left ventricular ejection fraction (LVEF) (< %)
Clinically significant cardiovascular abnormalities such as:\r\n* Corrected QT interval (QTc) >=  msec\r\n* Angina not well-controlled by medication\r\n* Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac/vascular stenting within  months of enrollment\r\n* Symptomatic or documented congestive heart failure that meets New York Heart Association (NYHA) class III to IV definitions\r\n* History of stroke within the last  months prior to screening
History of clinically significant cardiovascular disease including, but not limited to:\r\n* Myocardial infarction or unstable angina =<  months prior to treatment initiation.\r\n* Clinically significant cardiac arrhythmia.\r\n* Deep vein thrombosis, pulmonary embolism, stroke =<  months prior to treatment initiation.\r\n* Congestive heart failure (New York Heart Association class III-IV).\r\n* Pericarditis/clinically significant pericardial effusion.\r\n* Myocarditis.\r\n* Endocarditis.
Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within  months before first dose
Patients with following cardiac conditions will be excluded:\r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure\r\n* Myocardial infarction =<  months prior to enrollment\r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration =<  months prior to enrollment\r\n* History of severe non-ischemic cardiomyopathy with ejection fraction (EF) =< %
Patients with following cardiac conditions will be excluded:\r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure\r\n* Myocardial infarction =<  months prior to enrollment\r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration\r\n* History of severe non-ischemic cardiomyopathy
Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last  months
Impaired cardiac function or clinically significant cardiac disease including the following:\r\n* New York Heart Association class III or IV congestive heart failure\r\n* Myocardial infarction within the last  months\r\n* Subjects known to have impaired left ventricular ejection fraction (LVEF) according to institutional standards
Any life-threatening illness, severe and/or uncontrolled medical condition, or organ system dysfunction, laboratory abnormality, psychiatric illness or other condition which, in the Investigators opinion, could compromise the subjects safety, interfere with the absorption or metabolism of ibrutinib capsules, put the study outcomes at undue risk or affect their participation in the study such as\r\n* Symptomatic, or history of documented congestive heart failure New York Heart Association (NYHA) functional classification III-IV (NYHA) \r\n* Corrected QT interval using Fridericia's formula (QTcF) >  msec (unless related to pacemaker) on echocardiogram (EKG) within  days of initiation of treatment\r\n* Angina not well-controlled by medication\r\n* Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting within  months prior to enrollment
Patient has a clinically significant cardiac disease or impaired cardiac function, such as: \r\n* The presence of cardiac disease, including a myocardial infarction within  months prior to study entry, unstable angina pectoris, New York Heart Association class III/IV congestive heart failure, or uncontrolled hypertension \r\n* Documented major electrocardiogram (ECG) abnormalities (not responding to medical treatments) \r\n* Major abnormalities documented by echocardiography (ECHO) with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular [LV] ejection fraction < %, evaluation based on the institutional lower limit of normal) \r\n* Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography [CT] scan/magnetic resonance imaging [MRI] with contrast)
Ejection fraction (EF) ? %; no uncontrolled angina or active cardiac symptoms consistent with congestive heart failure (class III or IV), by the New York Heart Association criteria; no symptomatic ventricular arrhythmias, or electrocardiogram (ECG) evidence of active ischemia; no evidence by echocardiography of severe valvular stenosis or regurgitation
Significant cardiac conduction abnormalities, including a history of long QTc syndrome and/or pacemaker, or impaired cardiovascular function such as New York Heart Association classification score >.
Have clinically significant cardiac disease (New York Heart Association, class III or IV) including pre-existing arrhythmia, uncontrolled angina pectoris, myocardial infarction  year prior to study entry, or a known history of grade  or higher compromised left ventricular ejection fraction
Cardiac syncope, uncompensated New York Heart Association (NYHA) class  or  congestive heart failure, myocardial infarction within the previous  months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, severe orthostatic hypotension, or clinically important autonomic disease
Any of the following cardiac conditions: \r\n* Clinically significant heart disease (New York Heart Association [NYHA] class III or IV) or symptomatic congestive heart failure \r\n* Myocardial infarction =<  months prior to enrollment \r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration \r\n* History of severe non-ischemic cardiomyopathy with ejection fraction =< %
Patients must not have any of the following: New York Heart Association (NYHA) class  or  congestive heart failure; myocardial infarction within the past  months, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding  months; or any other intercurrent medical condition that contra-indicates treatment with sEphBHSA or places the patient at undue risk for treatment related complications
Have moderate or severe cardiovascular disease:\r\n* Has the presence of cardiac disease, including a myocardial infarction within six months prior to study entry, unstable angina pectoris, New York Heart Association class III/IV congestive heart failure, or uncontrolled hypertension\r\n* Has documented clinically significant electrocardiography (ECG) abnormalities (not responding to medical treatments) or not clinically stable for at least  months\r\n* Has major abnormalities documented by echocardiogram (ECHO) with Doppler (for example, moderate or severe heart valve function defect) that is not stable for at least  months; Note: left ventricular [LV] ejection fraction < % is allowed only if clinically stable for at least  months (evaluation based on the institutional lower limit of normal)\r\n* Has predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by computed tomography [CT] scan/magnetic resonance imaging [MRI] with contrast)
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function; history of documented congestive heart failure (CHF); and documented cardiomyopathy
New York Heart Association class III or greater congestive heart failure within last  months or uncontrolled hyperlipidemia (cholesterol >  mg/dl; triglyceride . X upper limit of normal [ULN] despite lipid lowering agent) within last  months
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infarction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
Active congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia or conduction abnormalities uncontrolled by conventional interventions; myocardial infarction within  months of study entry
Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < %
Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or higher, ventricular arrhythmias requiring antiarrhythmic therapy, recent (within  months) myocardial infarction or unstable coronary artery disease
Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months
Adult patients (>=  years old) with the following cardiac conditions will be excluded: \r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure \r\n* Myocardial infarction =<  months prior to enrollment\r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration\r\n* History of severe non-ischemic cardiomyopathy with ejection fraction (EF) =< %
Those with New York Heart Association functional classification II, III or IV active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia.
History of relevant coronary heart disease or myocardial infarction within last  years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or serious cardiac arrhythmia requiring medication except atrial fibrillation.
Patients with following cardiac conditions will be excluded: \r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure\r\n* Myocardial infarction =<  months prior to enrollment\r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration\r\n* History of severe non-ischemic cardiomyopathy with ejection fraction (EF) =< %
Criteria  Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant electrocardiogram (ECG) abnormalities, screening ECG with corrected QT interval (QTc) of >  msec, pericardial disease, or myocardial infarction within  months prior to randomization
Patients with New York Heart Association Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < %, or significant uncontrolled cardiac disease, current diagnosis of unstable angina, uncontrolled congestive heart failure, new myocardial infarction, or ventricular arrhythmia requiring medication;
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infarction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function\r\n* Other clinically significant heart disease such as congestive heart failure requiring treatment (New York Heart Association [NYHA] Class III or IV) or uncontrolled hypertension (please refer to World Health Organization-International Society of Hypertension [WHO-ISH] guidelines)\r\n* Documented cardiomyopathy
Patients with clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to enrollment, congestive heart failure (New York Heart Association [NYHA ] III-IV), and arrhythmia unless controlled by therapy (with the exception of extra systoles or minor conduction abnormalities), are NOT eligible
Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e. congestive heart failure, myocardial infarction within  months before baseline) Patient with any condition that the physician judges could be detrimental to subjects participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events Previous treatment
Any of the following cardiac diseases currently or within the last  months as defined by New York Heart Association (NYHA) >= class \r\n* Unstable angina pectoris\r\n* Congestive heart failure\r\n* Acute myocardial infarction\r\n* Conduction abnormality not controlled with pacemaker or medication\r\n* Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
Symptomatic arterial peripheral vascular disease or significant cardiovascular disease or condition including:\r\n* Congestive heart failure (CHF) currently requiring therapy\r\n* Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria\r\n* Need for antiarrhythmic medical therapy for a ventricular arrhythmia\r\n* Severe conduction disturbance (e.g. third [rd] degree heart block)\r\n* Unstable angina pectoris (i.e. last episode =<  months prior to first dose of protocol-indicated treatment)\r\n* Uncontrolled (per investigator judgment) hypertension\r\n* Myocardial infarction within  months prior to starting trial treatment\r\n* Corrected QT interval by Fridericia (QTcF) >  ms in men, or >  ms in women
Any of the following cardiac diseases currently or within the last  months as defined by New York Heart Association (NYHA) >= class . a. Unstable angina pectoris; b. Congestive heart failure; c. Acute myocardial infarction; d. Conduction abnormality not controlled with pacemaker or medication; e. Significant ventricular or supraventricular arrhythmias (patients with chronic rate- controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible).
RENAL & BLADDER: History of clinically significant cardiovascular disease including, but not limited to:\r\n* Myocardial infarction or unstable angina ?  months prior to treatment initiation \r\n* Clinically significant cardiac arrhythmia\r\n* Deep vein thrombosis, pulmonary embolism, stroke ?  months prior to treatment initiation\r\n* Congestive heart failure (New York Heart Association class III-IV)\r\n* Pericarditis/clinically significant pericardial effusion\r\n* Myocarditis\r\n* Endocarditis
Myocardial infarction within  months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) grade III or IV heart failure.
Significant cardiovascular abnormalities as defined by any one of the following: \r\n* Congestive heart failure New York Heart Association (NYHA) classes II-IV; patients with asymptomatic class I congestive heart failure (CHF) may participate in conjunction with a cardiology consultation\r\n* Clinically significant hypotension\r\n* Symptoms of coronary artery disease\r\n* Presence of arrhythmias in electrocardiography (EKG) requiring drug therapy
Participant has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infarction within the last  months prior to start of study drug, documents by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documents congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy\r\n* Congenital long QT syndrome
Patient has a history of significant cardiovascular, neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness that could preclude study participation, pose an undue medical hazard, or interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (New York Heart Association [NYHA] class  or ); unstable angina; cardiac arrhythmia; recent (within the preceding  months) myocardial infarction or stroke; hypertension requiring >  medications for adequate control; diabetes mellitus with >  episodes of ketoacidosis in the preceding  months; or chronic obstructive pulmonary disease (COPD) requiring >  hospitalizations in the preceding  months
Patient has abnormal cardiac status, evidenced by any of the following:\r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF)\r\n* Myocardial infarction within the previous  months\r\n* Symptomatic cardiac arrhythmia requiring treatment or persisting despite treatment
Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy
Clinically significant cardiac pathology: myocardial infarction within  months prior to enrollment, class III or IV heart failure according to New York Heart Association (NYHA), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or acute conduction system abnormalities; specifically, any history of cardio-vascular pathology or symptoms, not clearly fitting this exclusion criterion will prompt an evaluation by a Clinical Center Cardiologist and eligibility will be considered on a case-by-case basis; should the cardiologist deem the patients findings on work-up to be not clinically significant pathology, the patient will have met this exclusion criterion
Patients with significant intercurrent medical illness (including New York Heart Association [NYHA] class III or IV heart disease, significant arrhythmias requiring medication, symptomatic coronary artery disease, myocardial infarction) within the previous  months
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function\r\n* History of or documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
Myocardial infarction within  months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
Medically documented cardiac syncope, uncompensated New York Heart Association (NYHA) Class  or  congestive heart failure, myocardial infarction within the previous  months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease.
Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, subject with unstable cardiac disease as defined by: cardiac events such as myocardial infarction (MI) within the past  months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment
Myocardial infarction within  months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure.
Myocardial infarction within  months of study initiation, active cardiac ischemia or New York Heart Association (NYHA) Grade III or IV heart failure
Known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association [NYHA] Class III or IV) and/or myocardial infarction within  months prior to first dose, or severe pulmonary hypertension. As an example, well controlled atrial fibrillation would not be an exclusion whereas uncontrolled atrial fibrillation would be an exclusion.
Any clinically significant pericardial effusion, congestive heart failure (CHF) (New York [NY] Heart Association grade II-IV) or cardiovascular condition that would preclude assessment of mesothelin induced pericarditis or that may worsen as a result of toxicities expected for this study; this determination will be made by a cardiologist if cardiac issues are suspected
Patients with cardiovascular disease including congestive heart failure grade III or IV according to the New York Heart Association (NYHA) classification, left ventricular ejection fraction of < %, myocardial infarction within previous  months or poorly controlled hypertension
Active congestive heart failure (New York Heart Association [NYHA] Class III or IV, refer to Appendix F), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within  months prior to enrollment
Significant cardiovascular disease defined as:\r\n* Myocardial infarction within  months of screening\r\n* Unstable angina pectoris\r\n* Uncontrolled or clinically significant arrhythmia grade >= \r\n* Left ventricular ejection fraction (LVEF) below institutional limits at screening\r\n* Congestive heart failure New York Heart Association (NYHA) class III or IV\r\n* Presence of clinically significant valvular heart disease
Subjects who have a history of major cardiac or neurologic disease including, but not limited to, angina pectoris, symptomatic coronary artery disease, uncontrolled hypertension (at time of study entry), New York Heart Association (NYHA) Class III or IV congestive heart failure, confirmed significant cardiac conduction abnormalities (including QTc > . sec) or arrhythmias, myocardial infarction within  months, cerebrovascular accidents, or transient ischemic attacks.
Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:\r\n* Symptomatic, or history of documented congestive heart failure (New York [NY] Heart Association functional classification III-IV)\r\n* Corrected QT interval using Fridericia's formula (QTcF) >  msec\r\n* Angina not well-controlled by medication\r\n* Poorly controlled or clinically significant atherosclerotic vascular disease including cerebrovascular accident (CVA), transient ischemic attack (TIA), angioplasty, cardiac or vascular stenting in the past  months
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular ejection fraction (LVEF) function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities
Patients with significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within six months of study entry, uncontrolled dysrhythmias, or QTc greater than or equal to  msec
Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within  months before first dose
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities
Uncontrolled, current significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities\r\n* Patients with history of cardiac disease, such as coronary disease, arrhythmia or congestive heart failure that are on appropriate medical therapy and without evidence of current decompensation are eligible
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities
Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association [NYHA] III-IV), and arrhythmia unless controlled by therapy, with the exception of extrasystoles or minor conduction abnormalities
Patients with following cardiac conditions will be excluded:\r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure\r\n* Myocardial infarction =<  months prior to enrollment\r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration\r\n* History of severe non-ischemic cardiomyopathy with ejection fraction (EF) =< %
History of cardiac dysfunction including any one of the following:\r\n* Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricle (LV) function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy
a. Class I and above myocardial ischemia or myocardial infarction, cardiac arrhythmia and Class  or above congestive heart failure classified according to New York Heart Association (NYHA)
Patients with following cardiac conditions will be excluded: \r\n* New York Heart Association (NYHA) stage III or IV congestive heart failure \r\n* Myocardial infarction =<  months prior to enrollment \r\n* History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration \r\n* History of severe non-ischemic cardiomyopathy with ejection fraction (EF) =< %
Patient has a history of cardiac dysfunction including any of the following:\r\n* Myocardial infraction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
Major cardiac abnormalities as defined but not limited to the following: uncontrolled angina or unstable life-threatening arrhythmias, history of myocardial infarction within  weeks prior to Baseline, Class  or higher New York Heart Association (NYHA) congestive heart failure, or severe cardiac insufficiency, persistent ( consecutive electrocardiograms (ECGs) performed ?  minutes apart) prolongation of the QTc (Fridericia) interval to >  msec.
Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years prior to enrollment in the study
Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) <% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ?  months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF >  msec on the screening ECG (using the QTcF formula);
History of cardiac disease: congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); previously diagnosed bradycardia or other cardiac arrhythmia defined as >= grade  according to NCI-CTCAE (version .), or uncontrolled hypertension; myocardial infarction occurred within  months prior to study entry (myocardial infarction occurred >  months prior to study entry is permitted)
Patient has in the opinion of the investigator any intercurrent conditions that could preclude their participation in the study, pose an undue medical hazard, or that could interfere with the interpretation of the study results, including, but not limited to, patients with congestive heart failure (NYHA Class III or IV; refer to Appendix III), unstable angina, cardiac arrhythmia requiring treatment, recent (within the prior  months) myocardial infarction, acute coronary syndrome or stroke, severe obstructive pulmonary disease, hypertension requiring more than medications for adequate control, or diabetes mellitus with more than  episodes of ketoacidosis in the prior  months.
Congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within  months prior to prior to CD for Phase b or prior to randomization for Phase 
The subject has a history of congestive heart failure, unstable angina, myocardial infarction, cardiac conduction abnormalities including Fridericia corrected QT interval (QTcF) prolongation of >  milliseconds (ms) or a pacemaker, clinically relevant impaired cardiovascular function (New York Heart Association (NYHA) class III/IV) or stroke within  months prior to enrollment.
Active congestive heart failure (New York Heart Association [NYHA] class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention; myocardial infarction within  months
History of cardiac heart failure of New York Heart Association Class II or greater or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia)
Patients with serious medical illness, including but not limited to: history of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of grade >  (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], version .), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion restrictive cardiomyopathy) within  months prior to first dose of study drug, or New York Heart Association class III or IV heart failure; chronic stable atrial fibrillation on stable anticoagulant therapy is allowed
History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within  months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as greater than or equal to Grade  according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), or uncontrolled hypertension; myocardial infarction occurring within  months prior to study entry (myocardial infarction occurring more than  months prior to study entry is permitted)
History of cardiac dysfunction including any of the following:\r\n* Myocardial infarction within the last  months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Documented cardiomyopathy
Congestive heart failure (CHF) (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months
Cardiac function:\r\n* Known inherited coronary disease\r\n* Symptomatic heart failure (New York Heart Association [NYHA] class II-IV prior or current cardiomyopathy, or severe valvular heart disease)\r\n* Prior or current cardiomyopathy\r\n* Severe valvular heart disease\r\n* History of atrial fibrillation
Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction [LVEF] <%, active ventricular arrhythmia requiring medication, history of myocardial infarction within  months of treatment initiation, clinically significant electrocardiogram [ECG] abnormalities).
History of congestive heart failure defined as class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); clinically significant bradycardia (<  beats per minute [bpm]) or other uncontrolled, cardiac arrhythmia defined as >= grade  according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version ., or uncontrolled hypertension (as determined by the investigator); myocardial infarction occurring within  months prior to study entry (myocardial infarction occurring >  months prior to study entry is permitted)
Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to randomization.
Compromised cardiovascular function defined as any of the following:\r\n* Electrocardiogram (EKG) evidence of acute ischemia\r\n* EKG evidence of medically significant conduction system abnormalities\r\n* History of myocardial infarction within the last  months\r\n* Unstable angina pectoris or cardiac arrhythmia\r\n* History of class  or class  New York Heart Association congestive heart failure\r\n* Left ventricular ejection fraction (LVEF) < % by either echocardiography or radionuclide-based multiple gated acquisition (Echo or MUGA)
History of cardiac heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment
Those with New York Heart Association functional classification II, III or IV; active cardiac conditions including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia
History of clinically significant cardiovascular disease including, but not limited to: \r\n* Myocardial infarction or unstable angina =<  months prior to treatment initiation \r\n* Clinically significant cardiac arrhythmia \r\n* Deep vein thrombosis, pulmonary embolism, stroke =<  months prior to treatment initiation \r\n* Congestive heart failure (New York Heart Association class III-IV) \r\n* Pericarditis/clinically significant pericardial effusion \r\n* Myocarditis \r\n* Endocarditis
Patients may not have any clinically significant cardiovascular disease including the following:\r\n* Myocardial infarction or ventricular tachyarrhythmia within  months\r\n* Prolonged QTc >  msec at baseline\r\n* Symptomatic congestive heart failure (CHF) of New York Heart Association (NYHA) functional class >= \r\n* Major conduction abnormality (unless a cardiac pacemaker is present)
Patients with pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] grade III-IV), or arrhythmia known to increase the risk or thromboembolic events (e.g., atrial fibrillation)
Patients with any of the following cardiac conditions:\r\n* Symptomatic restrictive cardiomyopathy\r\n* Dilated cardiomyopathy\r\n* Unstable angina within  months prior to enrollment\r\n* New York Heart Association functional class III-IV heart failure on active treatment\r\n* Symptomatic pericardial effusion
Has symptomatic congestive heart failure[New York Heart Association (NYHA) Classes III-IV], unstable angina, or cardiac arrhythmia requiring antiarrhythmic treatment
Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment
Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment