REGN5381 in Heart Failure Adult Participants With Elevated Pulmonary Capillary Wedge Pressure

Key Inclusion Criteria: 1. Body mass index (BMI) between 18 and 35 kg/m\^2, inclusive, rounded to the nearest whole number 2. Ambulatory participants with New York Heart Association (NYHA) class II/III heart failure and at least 1 sign and/or symptom of congestion (eg, dyspnea on exertion, worsening edema, orthopnea, etc.) 3. Left ventricular ejection fraction (LVEF) ≥20 % and \<50% on echocardiogram (ie, HFrEF participants) within 90 days prior to randomization (only for HFrEF participants in Group A and Group B). 4. Participants who, in the opinion of the investigator, require a right heart catheterization (not applicable for HFrEF patients not taking sacubitril/valsartan \[Group A\]). 5. Left ventricular ejection fraction (LVEF) ≥50% on echocardiogram (ie, HFpEF participants) within 90 days prior to randomization (only for HFpEF participants in Group C) 6. NT-proBNP \>1000 pg/mL or Brain Natriuretic Peptide (active form) (BNP) \>300 pg/mL as described in the protocol within 30 days prior to randomization measured by the local laboratory (only for HFrEF participants \[Group A and Group B\]). 7. Pulmonary capillary wedge pressure (PCWP) ≥15 mmHg and right artrial pressure (RAP) \>5 mmHg on right heart catheterization (RHC) the morning of anticipated study drug dose administration (not applicable for HFrEF participants not taking sacubitril/valsartan \[Group A\] as described in the protocol). 8. Systolic blood pressure (SBP) ≥110 mmHg at the screening visit and on day -1 9. Hematocrit \>30% at the screening visit and day -1 Key Exclusion Criteria: 1. Currently taking IV vasodilators and/or inotropes 2. Taking sacubitril/valsartan (only for HFrEF and HFpEF participants not taking sacubitril/valsartan \[Group A and Group C, respectively\]) 3. Taking a phosphodiesterase (PDE) inhibitor (eg, sildenafil), or a soluble guanylate cyclase stimulator (SGCS; ie, vericiguat) within 2 weeks of the screening visit or planning on taking valsartan/sacubitril, a PDE inhibitor, or a SGCS at any point during the study 4. More than moderate valvular regurgitation/stenosis (ie, moderate-to-severe or severe) on echocardiogram within 90 days prior to randomization 5. Known infiltrative or hypertrophic cardiomyopathy 6. Acute coronary syndrome within prior 6 months of randomization 7. History of cardiac arrest 8. Cardiac surgery within 3 months of randomization 9. Pacemaker or defibrillator placement within prior 30 days of randomization 10. Severe chronic obstructive pulmonary disease (COPD) (defined as Forced Expiratory Volume in 1st second \[FEV1\] \<50% of predicted or Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] 3 or 4) 11. Pulmonary arterial hypertension (World Health Organization \[WHO\] Group 1) and any medical history at any time of more than moderate pulmonary hypertension (ie, moderate-to-severe, or severe pulmonary hypertension, as described in the protocol 12. Congenital heart disease (repaired or unrepaired) 13. Inability to lie flat for cardiac catheterization Note: Other protocol-defined Inclusion/ Exclusion Criteria apply