STRONG-HF is a multicenter, randomized, parallel group study designed to evaluate the efficacy and safety of up-titration of standard oral heart failure medications during hospitalization for acute heart failure. Patients admitted for acute heart failure will be randomized within 2 days before discharge to either usual care or intensification of treatment with a beta-blocker, a renin-angiotensin system blocker, and a mineralocorticoid receptor blocker ("high intensity care" arm). In the "high intensity care" arm, patients' clinical signs and symptoms of heart failure will be assessed, and routine laboratory measures and biomarkers will be measured, at frequent post-discharge visits. When these measures indicate that it is safe to do so, the doses of the oral heart failure medications will be increased to optimal levels. Patients will be followed through 180 days from randomization. Patients assigned to the usual care group will be followed by their general physician and/or cardiologist according to local medical standards. Patients who were screened but did not meet eligibility criteria will be followed for 90-day outcome. Randomized patients will be contacted at 180 days to assess outcomes.

STRONG-HF is a multicenter, randomized, parallel group study designed to evaluate the efficacy and safety of up-titration of standard of care medical therapy including beta-blockers; angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blocker (ARB) or angiotensin receptor neprolysin inhibitor (ARNi); and mineralocorticoid receptor antagonist (MRAs), on morbidity and mortality when initiated and up-titrated early during hospitalization for acute heart failure (AHF). Optimal safety conditions will allow physicians to introduce and/or continue oral HF therapies during this "vulnerable phase" in AHF patients. Patients admitted for AHF with clinical signs of congestion and elevated circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) and who are not treated with optimal doses of oral heart failure (HF) therapies within 2 days before hospital discharge for AHF and who are hemodynamically stable will be randomized in a 1:1 ratio to either usual care (named "usual care" arm) or intensification of treatment with beta-blockers, and ACEi (or ARB) or ARNi and a MRA (named "high intensity care" arm). In the latter arm, repeated assessments of clinical signs and symptoms of heart failure, routine clinical laboratory measures including potassium, sodium, and creatinine as well as NT-ProBNP will foster, encourage and ensure the safety of the optimization of oral heart failure therapies. AHF patients who were screened but did not meet inclusion criteria, including low circulating NT-proBNP at visit 2, will be followed for 90-day outcome. Randomized patients will be contacted at 180 days to assess outcomes.

Inclusion Criteria:

1. Hospital admission within the 72 hours prior to Screening for acute heart failure with dyspnea at rest and pulmonary congestion on chest X-ray, and other signs and/or symptoms of heart failure such as edema and/or positive rales on auscultation.
2. All measures within 24 hours prior to Randomization of systolic blood pressure ≥ 100 mmHg, and of heart rate ≥ 60 bpm.
3. All measures within 24 hours prior to Randomization of serum potassium ≤ 5.0 mEq/L (mmol/L).
4. Biomarker criteria for persistent congestion:
5. At Screening, NT-proBNP > 2,500 pg/mL.
6. At the time of Randomization (within 2 days prior to discharge), NT-proBNP > 1,500 pg/mL (to ensure the persistence of congestion) that has decreased by more than 10% compared to Screening (to ensure the acuity of the index episode).
7. At 1 week prior to admission, at Screening, and at Visit 2 (just prior to Randomization) either (a) <= ½ the optimal dose of ACEi/ARB/ARNi (see Table) prescribed, no beta-blocker prescribed, and <= ½ the optimal dose of MRA prescribed or (b) no ACEi/ARB/ARNi prescribed, <= ½ the optimal dose of beta-blocker prescribed, and <= ½ the optimal dose of MRA prescribed.
8. Written informed consent to participate in the study.

Exclusion Criteria:

1. Age < 18 or > 85 years.
2. Clearly documented intolerance to high doses of beta-blockers.
3. Clearly documented intolerance to high doses of renin-angiotensin system (RAS) blockers (both ACEi and ARB).
4. Mechanical ventilation [not including continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BIPAP)] in the 24 hours prior to Screening.
5. Significant pulmonary disease contributing substantially to the patients' dyspnea such as forced expiratory volume during the 1st second (FEV1)< 1 liter or need for chronic systemic or nonsystemic steroid therapy, or any kind of primary right heart failure such as primary pulmonary hypertension or recurrent pulmonary embolism.
6. Myocardial infarction, unstable angina or cardiac surgery within 3 months, or cardiac resynchronization therapy (CRT) device implantation within 3 months, or percutaneous transluminal coronary intervention (PTCI), within 1 month prior to Screening.
7. Index Event (admission for AHF) triggered primarily by a correctable etiology such as significant arrhythmia (e.g., sustained ventricular tachycardia, or atrial fibrillation/flutter with sustained ventricular response >130 beats per minute, or bradycardia with sustained ventricular arrhythmia <45 beats per minute), infection, severe anemia, acute coronary syndrome, pulmonary embolism, exacerbation of chronic obstructive pulmonary disease (COPD), planned admission for device implantation or severe non-adherence leading to very significant fluid accumulation prior to admission and brisk diuresis after admission. Troponin elevations without other evidence of an acute coronary syndrome are not an exclusion.
8. Uncorrected thyroid disease, active myocarditis, or known amyloid or hypertrophic obstructive cardiomyopathy.
9. History of heart transplant or on a transplant list, or using or planned to be implanted with a ventricular assist device.
10. Sustained ventricular arrhythmia with syncopal episodes within the 3 months prior to screening that is untreated.
11. Presence at Screening of any hemodynamically significant valvular stenosis or regurgitation, except mitral or tricuspid regurgitation secondary to left ventricular dilatation, or the presence of any hemodynamically significant obstructive lesion of the left ventricular outflow tract.
12. Active infection at any time during the AHF hospitalization prior to Randomization based on abnormal temperature and elevated white blood cells (WBC) or need for intravenous antibiotics.
13. Stroke or transient ischemic attack (TIA) within the 3 months prior to Screening.
14. Primary liver disease considered to be life threatening.
15. Renal disease or estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 [as estimated by the simplified Modification of Diet in Renal Disease (MDRD) formula] at Screening or history of dialysis.
16. Psychiatric or neurological disorder, cirrhosis, or active malignancy leading to a life expectancy < 6 months.
17. Prior (defined as less than 30 days from screening) or current enrollment in a congestive heart failure (CHF) trial or participation in an investigational drug or device study within the 30 days prior to screening
18. Discharge for the AHF hospitalization anticipated to be > 14 days from admission, or to a long-term care facility. Randomization must occur within 12 days following admission and within 2 days prior to anticipated discharge.
19. Inability to comply with all study requirements, due to major co-morbidities, social or financial issues, or a history of noncompliance with medical regimens, that might compromise the patient's ability to understand and/or comply with the protocol instructions or follow-up procedures
20. Pregnant or nursing (lactating) women.