How to manage a patient with LVEF of 36%, no wall motion abnormalities, and comorbid hypertension, type 2 diabetes, and hyperlipidemia?

Management of LVEF 36% Without Wall Motion Abnormalities

This patient has heart failure with reduced ejection fraction (HFrEF) requiring comprehensive guideline-directed medical therapy (GDMT) with four foundational medication classes, plus aggressive management of all cardiovascular comorbidities to reduce mortality and prevent hospitalization. 1

Immediate Pharmacological Management

First-Line Foundational Therapy (All Four Classes Required)

Initiate SGLT2 inhibitor immediately at full dose (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) as this class can be started first without titration, has no blood pressure or heart rate effects, and provides rapid clinical benefit within weeks. 1, 2 This is the safest GDMT medication to start in any hemodynamic state once adequate organ perfusion is confirmed. 2

Add mineralocorticoid receptor antagonist (MRA) next - start spironolactone 12.5-25 mg once daily if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L, targeting 25-50 mg daily. 1, 2, 3 This provides a 30% reduction in all-cause mortality and 23% reduction in sudden cardiac death specifically. 1, 3 The mortality benefit is independent of other therapies and adds value even before optimizing other GDMT components. 2

Initiate evidence-based beta-blocker (carvedilol, metoprolol succinate, or bisoprolol) at low dose and titrate to target over weeks to months as tolerated. 1 Beta-blockers reduce mortality by 35% and have specific anti-arrhythmic effects that reduce sudden death. 1

Start ACE inhibitor (or ARB if ACE-I intolerant, or consider ARNI [sacubitril/valsartan] as initial therapy or replacement for ACE-I after stabilization). 1, 4 ACE inhibitors reduce all-cause mortality by 15-25%. 1 ARNI should replace ACE-I in patients with persistent symptoms despite optimal therapy to further reduce HF hospitalization and death. 4

Critical Dosing Strategy

• Do not wait to achieve target dosing of one medication before initiating the next. 1 Start all four foundational therapies sequentially within days to weeks, then uptitrate each as tolerated. 1
• Check blood pressure, renal function, and electrolytes 1-2 weeks after each medication adjustment. 2
• Modest creatinine increases (up to 30% above baseline) are acceptable and should not prompt GDMT discontinuation. 2

Management of Comorbidities

Hypertension Control

Titrate GDMT medications to blood pressure targets per contemporary hypertension guidelines. 1 The foundational HFrEF therapies (ACE-I/ARB/ARNI, beta-blockers, MRA) will simultaneously treat both HF and hypertension. 1

• Asymptomatic low blood pressure (systolic 80-100 mmHg) with adequate perfusion should NOT prevent GDMT initiation or uptitration. 2
• If symptomatic hypotension occurs, reduce diuretics first (if no congestion present) rather than stopping foundational GDMT. 2
• Avoid these agents: diltiazem, verapamil (increase HF worsening risk), moxonidine and centrally-acting agents (increased mortality), alpha-blockers like doxazosin (2-fold increased HF risk), and minoxidil (fluid retention). 1, 4

Type 2 Diabetes Management

The SGLT2 inhibitor prescribed for HFrEF simultaneously treats diabetes - this is the preferred glucose-lowering agent as it reduces cardiovascular mortality and HF hospitalization regardless of diabetes status. 1, 5

• Avoid thiazolidinediones (glitazones) completely - they increase HF worsening and hospitalization risk (Class III-A contraindication). 1, 4

Hyperlipidemia Management

Initiate high-intensity statin therapy given the absence of wall motion abnormalities suggests non-ischemic cardiomyopathy, but cardiovascular risk reduction remains essential with multiple comorbidities. 1

Device Therapy Evaluation

ICD Consideration

Reassess for ICD candidacy after 3 months of optimal medical therapy if LVEF remains ≤35% with NYHA class II-III symptoms and life expectancy >1 year with good functional status. 1, 2

• ICD is recommended (Class I-A for ischemic, Class I-B for non-ischemic cardiomyopathy) to reduce sudden death and all-cause mortality. 1, 4
• Do NOT implant ICD within 40 days of MI if one occurs - implantation at this time does not improve prognosis (Class III-A). 1, 4
• The absence of wall motion abnormalities suggests non-ischemic etiology, where ICD still provides mortality benefit but requires 3 months of optimal medical therapy first. 1

CRT Consideration

Obtain ECG to assess QRS duration and morphology. 1

• If QRS ≥150 msec with LBBB morphology: CRT is Class I-A recommendation to improve symptoms and reduce morbidity and mortality. 1, 4
• If QRS 130-149 msec with LBBB morphology: CRT is Class I-B recommendation. 1
• CRT is contraindicated if QRS <130 msec. 1

Monitoring Strategy

Serial natriuretic peptide measurements (BNP/NT-proBNP) should guide therapy optimization and assess treatment response. 4

Regular cardiac rhythm monitoring is essential as atrial fibrillation risk increases with HFrEF. 4 If AF develops, anticoagulation and rate/rhythm control become additional priorities. 1

Monitor for hyperkalemia when using MRA, especially with concurrent ACE-I/ARB/ARNI - potassium and renal function checks every 1-2 weeks initially, then every 3 months after stabilization. 2, 3, 6

Critical Medications to Avoid

• NSAIDs and COX-2 inhibitors (Class III-B) - increase HF worsening and hospitalization. 1, 4
• Triple neurohormonal blockade - do NOT add ARB to combination of ACE-I plus MRA (Class III-C) due to increased renal dysfunction and hyperkalemia risk. 1, 4
• Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) - Class III-C contraindication. 1, 4

Expected Outcomes

Approximately 25% of patients with HFrEF treated with comprehensive GDMT experience LVEF recovery to >35%. 7, 8 These patients have significantly improved mortality and morbidity compared to those with persistent reduced LVEF. 7 With sacubitril/valsartan specifically, LVEF improvement of 14.6% has been observed in responders. 8

However, even if LVEF recovers, continue all GDMT medications indefinitely unless contraindications develop, as the long-term benefits of these therapies persist. 7