This is a randomized, double blind, single center trial to study of the effects of Ivabradine vs. Placebo on patients hospitalized for Stage D heart failure (HF)/ and cardiogenic shock (CS) who will require continuous infusion of Dobutamine and have developed sinus tachycardia (ST) (heart rate >100 beats/min).

The aim of the study will be to assess the potential of Ivabradine to slow ST and improve hemodynamics in patients with stage D HF/CS on Dobutamine treatment.

This study will explore the hypothesis that Ivabradine will decrease heart rate (HR) and improve hemodynamics in patients with advanced HF on inotropic treatment. This is a randomized, double blind, single center trial will include 40 consecutive patients admitted for Stage D HF/ CS who will require continuous infusion of Dobutamine and will develop ST (HR >100 beats/min).

Eligible patients will be randomized (1:1) using blocked randomization with random block sizes of 2 or 4 to start Ivabradine versus placebo. The procedure of randomization to receive either Ivabradine or placebo twice daily will be performed by computerized sequence generation. The hospital pharmacies will be responsible for drug randomization and dispensing, and the investigators and the patients will be blinded to the treatment option.

Ivabradine will be started 3 hours after Dobutamine initiation at dose 5 mg and further increased in 12 hours to 7.5 mg bid if patient is stable with mean BP≥ 60 mmHg, systolic blood pressure ≥ 90 mmHg and HR ≥100 bpm. Increase of Ivabradine dosage will be individually stopped for reasons of safety if three episodes of minimal HRs of less than 70 beats per minute, or a drop in mean blood pressure < 60 mmHg or systolic blood pressure < 80 mmHg occur.

HR, blood pressure and invasive hemodynamics will be monitored, along with standard right heart cath and echocardiogram measurements obtained.

Patients will be followed for a total of 72 hours. The adverse events that will be collected include bradycardia, defined as a heart rate less than 70 bpm, hypotension defined as a systolic blood pressure less than 80 mmHg and any side effect requiring drug discontinuation or dose adjustment. Review of laboratory including renal, hepatic and hematologic counts will be reviewed for any significant changes due to the use of Ivabradine.

Inclusion Criteria:

• Provide written informed consent for the study
• Have current diagnosis of Ischemic and/or non-ischemic cardiomyopathy
• Left ventricular ejection fraction (LVEF) < 30% by echo during the screening
• Sinus rhythm with HR ≥100 bpm
• Systolic blood pressure ≥ 90 mmHg assessed by cuff sphygmomanometer
• CI < 2.2 L/min/m2
• Current symptom(s) of HF (New York Heart Association (NYHA) class IV) at Screening.
• Absence of hypovolemia, defined as a central venous pressure ≥10 mmHg and pulmonary capillary occlusion pressure ≥15 mmHg before administration of Dobutamine

Exclusion Criteria:

• Respiratory support with mechanical ventilation
• Circulatory mechanical support
• Atrial pacing with the presence of sick sinus syndrome or sino-atrial block
• Second or third degree atrioventricular (AV) block,
• Atrial fibrillation/flutter
• Amiodarone treatment
• Ventricular tachycardia
• Acute coronary syndrome
• Bilirubin > 2.5
• Alanine aminotransferase (ALT) >60 IE/L,
• Serum creatinine >2.5 g/ml)
• Fever and significant infection
• Pregnancy
• Anemia, Hgb < 9.0
• Patients required treated with severe cytochrome CYP3A4 inhibitors drugs Concomitant use of strong CYP3A4 inhibitors will be avoided during the study period