ACE-I/ARB/ARNI
True or False: ARNI therapy can be initiated immediately after stopping an ACE inhibitor.
False; Needs a period of 36 hour washout
Name the three beta blockers proven to reduce mortality in HFrEF.
Carvedilol, metoprolol succinate, bisoprolol
Name two SGLT2 inhibitors proven to reduce heart failure hospitalizations in HFrEF.
Dapagliflozin and empagliflozin
What are the two drugs in this class?
Spironolactone and eplerenone
Define HFrEF according to EF threshold.
</= 40%
A 58-year-old male with HFrEF (EF 25%) on lisinopril 20 mg daily is being switched to sacubitril/valsartan. What key labs and parameters should be monitored after initiation?
Blood pressure, serum creatinine, and potassium (for hypotension, renal dysfunction, hyperkalemia).
Which beta blocker provides both beta and alpha blockade, potentially reducing afterload?
Carvedilol
What is the target dose of sacubitril/valsartan?
97/103 mg BID
What serum potassium and creatinine levels are contraindications for starting an MRA?
K⁺ ≥ 5.0 mEq/L; SCr >2.5 mg/dL (men) or >2.0 mg/dL (women).
List three objective findings that support a diagnosis of heart failure.
Elevated BNP/NT-proBNP, pulmonary congestion on imaging, reduced EF on echo
A patient on lisinopril develops dry cough. What is the preferred next step in therapy?
Switch to an ARB
A 60-year-old male with HFrEF (EF 25%) and resting HR 62 bpm on metoprolol succinate 100 mg daily presents for follow-up. His EF has improved to 40% after 6 months. According to guidelines, what should be done with his beta blocker, and why?
Continue therapy indefinitely. Even if EF improves, beta blockers should be maintained long term
Name one major trial showing that SGLT2 inhibitors benefit patients with HFrEF regardless of diabetes status.
DAPA-HF or EMPEROR-Reduced
Compare spironolactone and eplerenone in terms of receptor selectivity and adverse effects.
Eplerenone is more selective for aldosterone receptors, reducing risk of gynecomastia and sexual side effects.
Why is it important to start all four GDMT agents early rather than titrating each drug to target dose before adding the next?
Early initiation of all four pillars provides additive and rapid mortality reduction.
Sequential titration delays benefit and increases short-term event risk.
Discuss how neprilysin inhibition augments RAAS blockade.
Neprilysin inhibition increases natriuretic peptides leading to vasodilation, natriuresis, and antifibrotic effects, complementing RAAS blockade to reduce preload, afterload, and LV remodeling.
Which trial demonstrated that carvedilol reduced mortality even in severe HFrEF (EF <25%)?
COPERNICUS trial
Explain how SGLT2 inhibitors improve cardiac function beyond glycemic control.
Promote osmotic diuresis and natriuresis, reduce preload/afterload, improve myocardial energetics, and reduce inflammation and fibrosis.
Describe how aldosterone contributes to heart failure progression.
Promotes sodium retention, myocardial fibrosis, endothelial dysfunction, and arrhythmogenic remodeling.
A 70-year-old with EF 25% and low BP cannot tolerate full ARNI dose. What strategies can you employ?
Lower ARNI dose, adjust diuretics, give doses separately, consider midodrine if needed.
Name one landmark trial that established ARNI as superior to ACEI and its key outcome.
PARADIGM-HF
Explain the physiologic basis for why symptoms may transiently worsen after beta blocker initiation.
Initial negative inotropy decreases cardiac output until receptor upregulation and reverse remodeling occur.
A non-diabetic patient with eGFR 35 mL/min/1.73 m² is on loop diuretics and starts dapagliflozin. What monitoring and adjustments are needed?
Monitor volume status, BP, renal function, and adjust loop diuretic dose if hypotension or dehydration occurs; eGFR ≥30 is acceptable for therapy continuation.
The EMPHASIS-HF trial enrolled patients with milder symptoms (NYHA II). Why was this trial practice-changing compared with RALES and EPHESUS?
It showed that even early-stage HFrEF benefits from MRA therapy, confirming survival and hospitalization reduction across the full HF severity spectrum — expanding use to less-symptomatic patients.
Explain the relationship between preload, afterload, and stroke volume in the failing left ventricle, and how GDMT targets these parameters.
In HFrEF, excessive preload and afterload worsen wall stress and lower stroke volume. GDMT agents—ARNI/ACEI/ARB (↓ afterload), diuretics/SGLT2i (↓ preload), and beta blockers/MRAs (↓ neurohormonal activation)—restore optimal loading conditions and improve cardiac efficiency.