Intravenous Vasodilator vs. Inotropic Therapy in Patients With Heart Failure

Inclusion Criteria:

* History of heart failure reduced ejection fraction (HFrEF), New York Heart Association (NYHA) class IV and known left ventricular ejection fraction (LVEF ) ≤ 40% within the last 6 months by any of the following imaging techniques: echocardiogram, radio-nuclear stress test, ventriculogram or cardiac magnetic resonance imaging (CMR) performed within 6 months.
* Hospitalized or presented to the emergency department for acute decompensated heart failure (ADHF) with the anticipated requirement if intravenous (IV) therapy (including IV diuretics). ADHF is defined as including all of the following measured at any time between the presentation (including the emergency department) and the end of the screening:

1. Persistent dyspnea or orthopnea or edema at screening and at the time or randomization, despite standard background therapy for heart failure.
2. Pulmonary congestion on chest radiograph.
3. N-terminal pro b-type natriuretic peptide (NT-proBNP) ≥ 2000 pg/ml; for patients ≥ 75 years old or with current atrial fibrillation, NT-proBNP ≥ 3000 pg/ml.
* Clinical suspicious of low cardiac output state; consider by the presence of any of the following signs or symptoms of hypoperfusion: narrow pulse pressure, cold extremities, mental obtundation, declining renal function, and/or low serum sodium.
* Systolic blood pressure (SBP) measured ≥ 90 but \< 120 mmHg at the start and the end of the screening, without use of an intravenous vasopressor therapy.
* Hemodynamic criteria: CI ≤ 2.2 L·min-1·m-2 based on CO calculated by Fick formula and PCWP ≥ 20 mmHg measured by right heart catheterization at the time of the enrollment and confirmed by Swan-Ganz measurement upon arrival to the Cardiac Care Unit (CCU).
* Able to be randomized within the first 24 hours from the presentation to the hospital, including the emergency department.

Exclusion Criteria:

* Clinical evidence of acute coronary syndrome (ACS) currently or within 30 days prior to enrollment. (Note that the diagnosis of ACS is a clinical diagnosis and that the sole presence of elevated troponin concentrations is not sufficient for a diagnosis of ACS).
* Significant, uncorrected left ventricular outflow track obstruction, such us obstructive cardiomyopathy or severe aortic stenosis (i.e. aortic valve area \< 1.0 cm2 or mean gradient \> 40 mmHg on prior or current echocardiogram).
* Severe mitral stenosis.
* Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated.
* Documented, prior to or at the time of the randomization, restrictive amyloid myocardiopathy or acute myocarditis or hypertrophic obstructive, restrictive or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).
* Complex congenital heart disease.
* Significant arrhythmias, which include any of the following: sustained ventricular tachycardia; atrial fibrillation or atrial flutter with sustained heart rate \> 130 beats per minute.
* Bradycardia with sustained ventricular rate \< 45 beats per minute.
* Temperature \> 38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment.
* History of malignancy (other than localized basal cell carcinoma of the skin), treated or untreated or any terminal illness (other than heart failure) with a current life expectancy less than a year.
* Major surgery or major neurologic event including cerebrovascular events, within 30 days prior to enrollment.
* Need for mechanical circulatory support (MCS), including intra-aortic balloon pump, Extracorporeal Membrane Oxygenation (ECMO) or any ventricular assist device.
* Need for mechanical ventilatory support (endotracheal intubation or mechanical ventilation).
* Patient with chronic heart failure and inotropic-depended.
* Current (within 2 hours prior to screening) treatment with any IV vasoactive therapies, including vasodilators, inotropic agents and vasopressors.
* Patients with severe renal impairment defined as pre-randomization estimated Glomerular Filtration Rate (eGFR) \< 25 ml/min/1.73m2 calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equalization and/or those receiving current or planned dialysis or ultrafiltration.
* Patients with acute kidney injury defined as an increase in serum creatinine 3 times of baseline, or reduction in urine output to \<0.3 mL/kg per hour for ≥12 hours, or anuria for ≥12 hours, or patients undergoing renal replacement therapy.
* Patients with Child C cirrhosis or history of cirrhosis with evidence of portal hypertension such as varices.
* Patients with acute liver failure and serum transaminase: aspartate transaminase (AST) and/or alanine transaminase (ALT) \> 3 times above the upper limit of normal.
* Any major solid organ transplant recipient or planned/anticipated organ transplant within 1 year.
* Patients with hematocrit \< 25%, or a history of blood transfusion within 14 days prior to screening, or active life-threatening gastrointestinal bleeding.
* 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 human chorionic gonadotropin (hCG) laboratory test. .
* History of hypersensitive to dobutamine or sodium nitroprusside.
* Inability to follow instructions or comply with follow-up procedures.
* Any other medical condition (s) that the investigator deems unsuitable for the study, including drug or alcohol use or psychiatric, behavioral or cognitive disorder.