L15 - CHF Therapeutics

What is heart failure (HF)?

Structural or functional impairment that affects ventricular filling and/or ventricular ejection of blood; associated with ↓ cardiac output (CO) and ↑ preload.

What are the 3 types of HF based on ejection fraction (EF)?

HFrEF = systolic HF, EF ≤40%, impaired LV contractility; HFmrEF = EF 41–49%; HFpEF = diastolic HF, EF ≥50%, impaired LV filling (heart can pump normally but filling is impaired).

What major conditions/risk factors are associated with HF?

Cardiac: uncontrolled HTN, atrial fibrillation, atherosclerotic disease (IHD/CAD, ACS, PAD), dyslipidemia, diabetes, obesity, metabolic syndrome. Non-cardiac: pulmonary infections, pulmonary embolus, thyroid disorders.

What patient-related factors can precipitate/exacerbate HF?

Medication nonadherence, dietary nonadherence (Na+/H2O restriction), emotional stress, alcohol, and illicit drugs such as cocaine and marijuana.

What medications/substances can precipitate or worsen HF?

Negative inotropes: non-DHP CCBs (diltiazem, verapamil) and certain antiarrhythmics (disopyramide, flecainide, propafenone); cardiotoxic agents: anthracyclines, cyclophosphamide, trastuzumab, alcohol, cocaine, methamphetamine; Na+/H2O retention: NSAIDs/COX-2 inhibitors, TZDs (pioglitazone, rosiglitazone), glucocorticoids/steroids, and androgens.

What are the 2 major clinical presentations of HF?

Volume overload (pulmonary and/or systemic congestion) and reduced cardiac output/poor perfusion.

What symptoms/signs suggest pulmonary congestion in HF?

Symptoms: dyspnea/SOB, orthopnea (SOB lying flat), paroxysmal nocturnal dyspnea (PND), tachypnea (>20 breaths/min). Signs: rales, pulmonary edema, pleural effusion, hypoxemia, left-sided S3 gallop.

What symptoms/signs suggest systemic congestion in HF?

Symptoms: peripheral edema and abdominal/hepatic swelling or pain. Signs: peripheral edema, JVD, hepatojugular reflux, hepatic enlargement/tenderness, ascites, right-sided S3 gallop.

What symptoms/signs suggest hypoperfusion in HF?

Symptoms: extreme fatigue/tiredness, poor appetite, nausea, early satiety, mental-status changes. Signs: ↓ BP, ↓ CO, worsening renal function, cool extremities.

What laboratory/diagnostic findings help diagnose HF?

Labs include Chem-7/BMP, CBC, LFTs, lipid profile, BNP, and NT-proBNP. BNP >100 pg/mL supports HF; NT-proBNP >450 pg/mL if

What are ACC/AHA Stages A–D of HF?

A = at risk for HF but NO structural/functional heart disease and NO HF symptoms; B = structural/functional heart disease but NO HF symptoms; C = structural heart disease + prior/current HF symptoms; D = refractory HF with marked symptoms/recurrent hospitalizations despite optimal GDMT. A+B are NOT clinical HF; C+D are HF. Patients do NOT move backward between ACC/AHA stages.

What are examples of patients in ACC/AHA Stages A–D?

A: HTN, CAD/atherosclerotic disease, DM, obesity, metabolic syndrome without structural disease/symptoms. B: previous MI, ventricular hypertrophy, or ventricular dysfunction without HF symptoms. C: structural disease + current/previous symptoms such as dyspnea, fatigue, reduced exercise tolerance. D: treatment-refractory symptoms at rest despite maximal therapy.

What are NYHA Classes I–IV?

I = no limitation; ordinary activity does NOT cause symptoms. II = slight limitation; ordinary activity causes symptoms. III = marked limitation; LESS than ordinary activity causes symptoms. IV = HF symptoms at rest.

What is the difference between ACC/AHA stage and NYHA class?

ACC/AHA describes disease progression and patients do not move backward; NYHA describes CURRENT functional symptoms and patients can move between classes. NYHA applies to Stage C/D patients: Stage C can be NYHA I–IV; Stage D is NYHA IV.

What are the overall goals of HF treatment?

Relieve/reduce symptoms, improve quality of life, prevent/minimize HF hospitalizations, slow disease progression, and prolong survival.

What are general nonpharmacologic measures for HF?

Monitor symptoms, weigh daily, restrict Na+, restrict H2O when appropriate, physical activity, weight loss if obese, adherence to medications, influenza vaccination, and pneumococcal vaccination.

How is ACC/AHA Stage A HF treated?

Control cardiovascular risk factors and promote healthy lifestyle habits (physical activity, normal weight, healthy diet, smoking cessation). Treat HTN, dyslipidemia, DM, and CVD according to appropriate guidelines; SGLT2i may be indicated in type 2 DM with CVD/high CVD risk.

How is ACC/AHA Stage B HF treated?

All Stage A recommendations + ACEI or ARB + evidence-based beta blocker when previous MI and/or LVEF <40%. Add statin if previous MI or ACS; no MI/ACS = do not add statin solely for HF.

What are the 4 pillars of Stage C HFrEF GDMT?

1) ARNI (preferred; ACEI/ARB alternatives), 2) evidence-based beta blocker, 3) mineralocorticoid receptor antagonist (MRA), 4) SGLT2 inhibitor. These reduce morbidity AND mortality and should reach target/maximally tolerated doses as soon as possible (<3 months).

When is ARNI preferred in Stage C HFrEF?

Sacubitril/valsartan (Entresto) is recommended in HFrEF with NYHA II–III symptoms to reduce morbidity and mortality. If tolerating an ACEI/ARB, replacement with ARNI is recommended for further benefit.

When are ACEIs or ARBs used instead of an ARNI in HFrEF?

ACEI = alternative when ARNI is not feasible in HFrEF with prior/current symptoms. ARB = use when ARNI is not feasible AND the patient is intolerant to ACEI.

What are the 3 evidence-based beta blockers for HFrEF?

Bisoprolol, carvedilol, and metoprolol SUCCINATE. Beta-blocker benefit in HF is NOT a class effect.

When should a beta blocker be started in HFrEF?

Start in STABLE HFrEF patients who are NOT volume overloaded. If acutely volume overloaded/decompensated, manage congestion first before initiating the beta blocker. If already taking a beta blocker, it may generally be continued unless contraindicated.

When can an MRA be used in HFrEF?

HFrEF + current NYHA II–IV symptoms with eGFR >30 mL/min AND serum K+ <5.0 mEq/L. Spironolactone and eplerenone reduce morbidity and mortality.

When are SGLT2 inhibitors used in HFrEF?

HFrEF + current NYHA II–IV symptoms, WITH OR WITHOUT type 2 diabetes; they reduce morbidity and mortality.

When is hydralazine/isosorbide dinitrate (BiDil) used in HFrEF?

Add-on therapy in African American patients with symptomatic NYHA III–IV HFrEF despite maximally tolerated ARNI/ACEI/ARB + BB + MRA + SGLT2i; reduces morbidity and mortality. It may also be considered when ARNI/ACEI/ARB cannot be used because of intolerance or renal insufficiency.

What is the role of diuretics in HF?

Use in HF with volume overload to relieve congestion, improve symptoms/exercise tolerance/quality of life, and reduce HF hospitalizations. Diuretics reduce MORBIDITY/symptoms but DO NOT improve survival.

What are the goals and monitoring parameters of diuretic therapy?

Goal = ↑ urine output and approximately 1–2 lb/day weight loss. Monitor Na+, K+, Mg+, volume status/congestion, BP/weakness for volume depletion, BUN, and SCr.

What are important counseling/clinical pearls for loop diuretics?

Dose in morning and afternoon if needed to reduce nocturnal diuresis; check weight every morning; loop diuretics remain effective with impaired renal function (CrCl <30 mL/min) but higher doses may be needed; excessive dietary Na+ reduces efficacy. Ethacrynic acid is the exception for patients with sulfonamide allergy.

What furosemide dose should be known for HF?

Initial furosemide (Lasix) = 20–40 mg PO once or BID. Professor specifically marked furosemide dosing to know.

What can cause diuretic resistance and how can it be managed?

Causes: large dietary Na+ intake, NSAIDs/COX-2 inhibitors, or drugs that impair renal function/perfusion. Management: IV loop diuretic (bolus or continuous) or add a different diuretic class; metolazone 2.5–10 mg PO can be given 30 minutes before the loop diuretic.

What are sacubitril/valsartan (Entresto) adverse effects, monitoring, and contraindications?

AEs: hypotension, hyperkalemia, transient ↑ SCr, angioedema. Monitor BP, K+, SCr in 2–4 weeks. Contraindications: pregnancy, bilateral renal artery stenosis, history of angioedema, concomitant/recent ACEI use, another ARB, or renin inhibitor.

What is the required washout when switching an ACEI to sacubitril/valsartan?

Wait at least 36 HOURS after stopping an ACEI before starting sacubitril/valsartan because of angioedema risk.

What sacubitril/valsartan doses should be known?

Low initial dose = sacubitril 24 mg/valsartan 26 mg PO BID for patients not taking ACEI/ARB, taking low doses, or CrCl <30 mL/min. Higher initial dose = 49/51 mg PO BID if previously taking high-dose ACEI/ARB. Increase every 2–4 weeks as tolerated. TARGET/MAX = 97/103 mg PO BID.

What are ACEI adverse effects, monitoring, and contraindications in HF?

AEs: hypotension, hyperkalemia, transient ↑ SCr, cough, angioedema. Monitor BP, K+, SCr in 2–4 weeks. Contraindications: pregnancy, bilateral renal artery stenosis, history of angioedema.

What lisinopril dose should be known for HF?

Initial lisinopril = 2.5–5 mg PO daily Target dose is 20-40 mg. Professor specifically marked lisinopril dosing to know.

What are beta-blocker adverse effects, monitoring, and contraindications in HF?

AEs: bradycardia/heart block, orthostatic hypotension, fatigue, weakness, bronchospasm, blunting of hypoglycemia symptoms, and possible worsening HF. Monitor BP and HR. Contraindications include symptomatic bradycardia, 2nd/3rd-degree heart block, acute decompensated HF, and cardiogenic shock.

What metoprolol succinate dose should be known for HFrEF?

Initial = 12.5–25 mg PO daily; target = 200 mg PO daily. Use metoprolol SUCCINATE (Toprol XL), NOT metoprolol tartrate.

What are MRA adverse effects and monitoring parameters?

Major AE = dose-dependent hyperkalemia. Spironolactone can cause gynecomastia, impotence, and menstrual irregularities; eplerenone can ↑ triglycerides. Monitor Na+, K+, BUN, and SCr at baseline, 2 weeks, monthly ×3 months, then every 3 months.

When should MRAs be avoided because of hyperkalemia/renal risk?

Avoid if CrCl

What spironolactone dose should be known for HF?

If CrCl ≥50 mL/min and K+ <5: initial 12.5–25 mg PO daily; target 25 mg daily or BID. If CrCl 30–49: initial 12.5 mg every other day or daily; target 12.5–25 mg daily.

What are the major considerations with hydralazine/isosorbide dinitrate?

AEs: hypotension, headache, lightheadedness. Hydralazine can additionally cause rash, arthralgia, tachycardia, and drug-induced lupus. Monitor BP and HR. Major obstacles include frequent dosing, adverse effects, cost, and pill burden.

When can ivabradine be considered in HFrEF?

Current symptomatic HFrEF (NYHA II–III) + sinus rhythm + resting HR ≥70 bpm + maximally tolerated beta blocker OR contraindication to beta blocker. Can reduce HF hospitalization and CV death; can cause bradycardia.

When can vericiguat be considered in HFrEF?

HFrEF with recent worsening HF despite GDMT; may reduce HF hospitalization and CV death.

What is the role of digoxin in HFrEF?

May be considered in persistently symptomatic HFrEF despite adequate therapy to decrease HF hospitalizations; reduces MORBIDITY only, NOT mortality. May be considered earlier if another indication exists, such as atrial fibrillation.

When is anticoagulation used in HFrEF?

ONLY when there is a specific indication such as atrial fibrillation, prior thromboembolic event, or cardioembolic source of thrombus. Do NOT anticoagulate solely because a patient has HFrEF.

When are statins used in HF?

Do NOT initiate a statin solely because the patient has HF. Use only when another indication/statin-benefit condition exists, such as previous MI or ACS.

Which pharmacologic therapies should be avoided or are not recommended in HFrEF?

Avoid ACEI + ARB/ARNI + MRA combinations because of life-threatening hyperkalemia; NSAIDs; TZDs (pioglitazone, rosiglitazone); non-DHP CCBs (verapamil, diltiazem); DPP-4 inhibitors saxagliptin/alogliptin; Class IC antiarrhythmics (flecainide, propafenone) and dronedarone. Nutritional supplements/vitamins/hormones are not recommended except to correct deficiencies.

Can dihydropyridine CCBs be used in HFrEF?

They are NOT recommended as HF treatment, but may be used for another indication such as HTN. Amlodipine is preferred; AVOID nifedipine.

How is Stage C HFmrEF (EF 41–49%) treated?

Volume overload → diuretics (Class 1). SGLT2i can decrease HF hospitalization/CV mortality (Class 2a). ARNI/ACEI/ARB, evidence-based BB, and MRA may be considered, especially when EF is toward the lower end of 41–49% (Class 2b).

How is Stage C HFpEF (EF ≥50%) treated?

Treat concomitant conditions such as HTN, dyslipidemia, DM, and AFib. Volume overload → diuretics. SGLT2i can decrease HF hospitalization/CV mortality. MRA and ARNI/ARB may be considered in selected patients, particularly when EF is toward the lower end of the preserved range.

What is the role of finerenone (Kerendia) in HFmrEF/HFpEF according to this lecture?

Newly approved to reduce CV death, HF hospitalization, and urgent HF visits in adults with HF and LVEF ≥40%. It is a nonsteroidal MRA and was not yet integrated into the clinical practice guidelines/recommendations presented in the lecture.

How is ACC/AHA Stage D HF treated?

Stage D = advanced/end-stage/refractory HF. IV inotropes such as dobutamine, dopamine, or milrinone may be used as bridge therapy to mechanical circulatory support/cardiac transplantation or for palliation.

What device therapies may be used in HF?

Certain Stage B/C patients: implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT). Certain Stage D patients: mechanical circulatory support (MCS), including LVAD.

A patient has previous MI, EF 35%, but has NEVER had HF symptoms. What stage/type is this?

HFrEF based on EF ≤40%; ACC/AHA Stage B because there is structural heart disease/LV dysfunction but no current or previous HF symptoms. NYHA classification is not assigned because the lecture applies NYHA to Stage C/D.

A Stage B patient has previous MI and EF 35%. What core therapies are indicated?

Stage A measures + ACEI/ARB + evidence-based BB; add statin because of previous MI/ACS.

A patient has EF 30%, SOB at rest, DOE, edema, JVD, and S3. What type, stage, and NYHA class?

HFrEF (EF ≤40%), ACC/AHA Stage C (structural disease + current HF symptoms), NYHA Class IV because symptoms occur at rest.

A symptomatic HFrEF patient presents with significant JVD/volume overload and is not taking a beta blocker. What should be addressed first?

Treat fluid overload/congestion with a loop diuretic FIRST. Initiate the evidence-based beta blocker after the patient is stable/not volume overloaded.

A symptomatic Stage C HFrEF patient is taking an ACEI but otherwise lacks GDMT. What medication strategy should be considered?

If appropriate, switch ACEI → ARNI (with 36-hour washout), then ensure the 4 pillars: ARNI + evidence-based BB + MRA (if eGFR >30 and K+ <5) + SGLT2i. Use a loop diuretic if volume overloaded.

What is the high-yield distinction between mortality-reducing and symptom-only therapy in HFrEF?

4 pillars (ARNI/ACEI/ARB, evidence-based BB, MRA, SGLT2i) reduce morbidity AND mortality. Hydralazine/ISDN reduces morbidity/mortality in selected patients. Loop diuretics and digoxin primarily reduce symptoms/hospitalizations (morbidity) and DO NOT improve survival.