Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Mechanistic Study to Assess The Role of Chronotropic Incompetence in Heart Failure With Normal Ejection Fraction (HFNEF)
Brief Summary: What is heart failure with normal ejection fraction? The heart contracts (pumps) and relaxes with each heartbeat. In some people with heart failure, the heart contracts normally but there is reduced relaxation of the heart. As a result, people notice a feeling of breathlessness, ankle swelling and fatigue especially on exertion.

The investigators feel that patients with reduced or impaired relaxation of the heart have less heart filling time and poor energy utilisation during exercise. Therefore, the investigators are conducting a study to more thoroughly understand the disease condition by giving a drug called ivabradine to reduce the heart rate and hence to increase the heart filling time in these patients.


Options:
A: Inclusion Criteria:

* History (Hx) of chronic systolic heart failure of ischemic or non-ischemic etiology of at least 4 weeks duration; Currently, New York Heart Association (NYHA) functional Class II and on optimal dose, or maximally tolerated dose of standard heart failure medicines (advisable to include ACE-I/ARBs; beta-blockers) and diuretics if indicated for fluid overload. Should have participated in the double-blind phase of the EMPHASIS-HF trial

Exclusion Criteria:

* Severe chronic systolic heart failure symptomatic at rest despite optimal medical therapy; estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73m2.
B: Inclusion Criteria:

* Participant who is willing and able to give informed consent for participation in the study.
* Male or Female, aged 60 years and over (Group 1, Oxford).
* Patients diagnosed with HFNEF by ESC criteria and have peak V02 ≤ 85% with a cardiac pattern of exercise limitation during CPEX (Group 1, Oxford).
* Hypertensive controls aged 65 and over without HFNEF and with peak V02 \> 90% (Group 2, Aberdeen)
* Able to perform exercise testing.

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

* LVEF \<50%
* Inability to tolerate MRI scanning (claustrophobia, inability to lie flat)
* Contraindications to CMR imaging (implantable devices or other metal implants, internal cardioverter-defibrillator, cranial aneurysm clips, metallic ocular foreign bodies, hypersensitivity to gadolinium)
* Presence of other significant concomitant diseases such as ischaemic, valvular, pericardial heart disease or cardiomyopathy.
* Presence of asthma (contraindication to adenosine)
* Presence of 2nd or 3rd degree AV block (contraindications to ivabradine and adenosine)
* Presence of sick sinus syndrome
* Presence of atrial fibrillation
* Significant bradycardia (HR \<60 per minute).
* Objective evidence of lung disease on formal lung function testing
* Female participant who is pregnant, lactating or planning pregnancy during the course of the study
* Unable to perform exercise testing
* Patient who is in terminally ill or is inappropriate for medication
* Known hypersensitivity to Ivabradine or adenosine
* Significantly impaired renal function (eGFR\<30ml/min)
C: Inclusion Criteria:

* Coronary artery disease
* Left ventricular systolic dysfunction
* Sinus rhythm: heart rate (HR) \>= 60 beats per minute (bpm)

Exclusion Criteria:

* Unstable cardiovascular condition
* Severe congestive heart failure
D: Inclusion Criteria:

* Age greater than or equal to 18 years.
* Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to randomization. Chronic heart failure is defined as requiring treatment for a minimum of 30 days prior to hospitalization.

The subject must have signs of extracellular volume expansion, defined as two or more of the following: a) jugular venous distention; b) pitting edema (\>1+); or c) dyspnea.

* NYHA Class III or IV at the time of hospitalization.
* Left Ventricular Ejection Fraction \< = 40% within one year.

Exclusion Criteria

* Women who will not adhere to the reproductive precautions as outlined in the Informed Consent form.
* Positive urine pregnancy test.
* Inability to provide written informed consent.
* Cardiac surgery within 60 days of potential study enrollment, excluding percutaneous coronary interventions.
* Planned revascularization procedures, electrophysiologic (EP) device implantation, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study enrollment.
* Subjects who are on cardiac mechanical support.
* History of bi-ventricular pacer placement within the last 60 days.
* Co-morbid condition with an expected survival less than six months.
* Subjects with acute ST segment elevation myocardial infarction at the time of hospitalization.
* History of sustained ventricular tachycardia or ventricular fibrillation within 30 days, unless in the presence of an automatic implantable cardioverter defibrillator.
* History of a cerebrovascular accident within the last 30 days.
* Hemodynamically significant uncorrected primary cardiac valvular disease.
* Hypertrophic cardiomyopathy (obstructive or non-obstructive).
* CHF due to uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
* Subjects with progressive or episodic neurological disease such as multiple sclerosis or history of multiple strokes.
* History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
* History of poorly controlled diabetes mellitus.
* Morbid obesity, defined as \> 159 kg (or 350 lbs) or BMI \> 40.
* Supine systolic arterial blood pressure \< 90 mmHg.
* Serum creatinine \> 3.5 mg/dL or \> 309.4 mmol/L.
* Serum potassium \> 5.5 mEq/L or \> 5.5 mmol/L.
* Hemoglobin \< 9 g/dL or \< 90 g/L.
* History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazapril).
* History of drug or medication abuse within the past year, or current alcohol abuse.
* Inability to take oral medications.
* Participation in another clinical drug or device trial within the past 30 days.
* Previous participation in this or any other tolvaptan clinical trial.

Answer: B