Trial Assessing the Effectiveness of Ivabradine Started at Discharge From the Observation Unit

Subjects will be enrolled at the time of discharge from the observation unit (visit 1), all
baseline procedures will be performed at this time, these would include blood draw for
biomarker assessments, vitals, physical examination, and IP dispensation. At the baseline
visit, the study team will schedule a follow-up appointment post Day 28 +/- 2 (Visit 3) with
the subject's primary care physician(PCP)/cardiologist, if the subject does not have their
own PCP/cardiologist the study team will schedule and facilitate this appointment with the
Gateway Clinic. A list of current medications and doses will be provided. At Day 14 +/-1
(visit 2) the subject will return for a follow up visit for IP accountability and titration
(if needed), BB uptitration (if needed), replacement of the HR monitor (Zio patch),
assessment of any adverse events, ECG, vital signs, and will undergo a physical examination.
At Day 28 +/-2 (visit 3), the patient will return for study exit procedures, which include
blood draw for biomarker assessments, vitals, physical examination, assessment of adverse
events (if any), and IP return.

As with any clinical trial, no un-blinding will occur unless there is a concern for patient
safety, as this could affect the integrity of data. The study team will provide the patient
and patient's PCP/cardiologist a clinical summary, inclusive of ECGs. On-going management for
the patient's condition will be at the discretion of their PCP/cardiologist and will not be
influenced directly by participation in this study.

At Randomization the initial Ivabradine dose will be 5 mg BID. At Day 14 follow up,
medication adjustments will be made (if needed). At Day 28 follow up, IP will be permanently
stopped.

At the last visit, the study team will contact the patient's primary care physician and/or
the cardiologist to notify that the patient has completed the study and is off study drug and
it is now the PCP/cardiologist's discretion to prescribe open label ivabradine (Corlanor) to
the patient or not, as clinically indicated. If the patient's primary care physician and/or
cardiologist prescribes open label ivabradine (Corlanor) after the completion of the study,
the patient or patient's insurance will be responsible for payment as this would then be part
of routine clinical care.

The Zio patch will be placed at discharge from the observation unit. At the 14-day follow-up
the original Zio patch will be collected and a second one will be placed. At the 28-day
follow-up the second Zio patch will be collected

Based on the SHIFT1 study, the mean heart rate reduction with IVA is 8 bpm with a standard
deviation of 13 bpm. A sample size of 57 in each group will have 90% power to detect a
difference in means of 8.0 assuming that the common standard deviation is 13.0 using a two
group t-test with a 0.05 two-sided significance level. To account for a projected dropout
rate of 15%, 66 subjects will be enrolled in each group (132 total for the study over a
2-year period). Furthermore, the investigators expect that the enrollment centers will
recruit a cohort that is 75% self-identified African Americans. This number (n=99) will
provide 80% power to detect the same effect size when analyzed in African Americans only.

For the safety endpoint (unplanned presentation for medical care), assuming an event rate of
25% at 1 month (estimated based on local hospital readmission rates), the sample size will
provide 80% power to detect a doubling of the relative risk. If the Control group event rate
is higher there will be greater power; for example, with an event rate of 35% we would have
98% power for risk ratio of 2.0 and 83% power for risk ratio of 1.75.

Inclusion Criteria:

1. Age >18 and <90.

2. Established HF with reduced ejection fraction (EF ≤35 %), assessment done within 12
months of index visit.

3. Admitted under observation unit for management of AHF.

4. Heart rate ≥70 beats per minute, with sinus rhythm.

5. Receiving guideline based medical therapy in the judgement of the treating physician.

6. Patient currently on a Beta Blocker regimen. Achieved clinically determined
stabilization during treatment under observation unit such that the treating physician
is planning to discharge home without hospital admission.

Exclusion Criteria:

1. Known intolerance to study drug.

2. End stage renal disease.

3. Plan to titrate BB at the time of discharge from the observation unit.

4. Any condition that in the opinion of the investigators will interfere with the ability
to complete the study (e.g. history of extreme non-adherence, extreme psychosocial
instability).

5. Inability to provide written informed consent.

6. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (women of childbearing age will be included only if they
agree to use adequate contraceptive methods or engage in sexual abstinence).

7. Systolic Blood pressure less than 100 mmHg.

8. Sick sinus syndrome, sinoatrial block or 3rd degree AV block, unless a functioning
demand pacemaker is present.

9. Severe hepatic impairment.

10. Pacemaker dependence (i.e. heart rate maintained exclusively by the pacemaker).

11. Concomitant use of strong CYP3A4 inhibitors. Examples of strong CYP3A4 inhibitors
include azole antifungals (e.g., itraconazole), macrolide antibiotics (e.g.,
clarithromycin, telithromycin), HIV protease inhibitors (e.g., nelfinavir), and
nefazodone.

12. Concomitant use of diltiazem or verapamil that are not planned for discontinuation.

13. Severe, left sided valvular abnormalities (severe aortic stenosis, severe mitral
stenosis, severe aortic insufficiency or severe mitral regurgitation.

14. Documented, prior to or at the time of randomization, restrictive amyloid
cardiomyopathy, or acute myocarditis, or hypertrophic obstructive, restrictive, or
constrictive cardiomyopathy.