How to clinically manage a patient with Heart Failure with Reduced Ejection Fraction (HFrEF) and End-Stage Renal Disease (ESRD)?

Clinical Management of HFrEF with ESRD

Patients with HFrEF and ESRD on dialysis should receive guideline-directed medical therapy (GDMT) with careful dose adjustments and close monitoring, as the mortality benefits of these medications extend to this high-risk population despite their exclusion from major trials.

Core Pharmacological Therapy

Beta-Blockers (First Priority)

• Initiate one of the three evidence-based beta-blockers: bisoprolol, carvedilol, or metoprolol succinate at very low doses with gradual uptitration 1
• Bisoprolol may accumulate in renal impairment but should still be titrated to target dose (10 mg daily) or maximum tolerated dose based on clinical response 2
• Carvedilol and metoprolol succinate do not require dose adjustment in ESRD 2
• Start at very low doses and increase gradually every 2-4 weeks as tolerated, monitoring for hypotension and bradycardia 1

Mineralocorticoid Receptor Antagonists (MRAs)

• MRAs can be safely used in ESRD patients on dialysis despite traditional concerns about hyperkalemia 3
• Start with very low doses: spironolactone 6.25-12.5 mg daily or 12.5 mg every other day 2
• The risk of hyperkalemia is substantially lower in oliguric/anuric patients on regular dialysis 3
• Monitor potassium levels closely, particularly in the first 1-2 weeks after initiation 2
• Small trials show potential clinical benefits with minimal risk in dialysis patients 3

ARNI (Sacubitril/Valsartan)

• Sacubitril/valsartan is contraindicated in patients with eGFR <30 mL/min/1.73 m² per FDA labeling 1
• However, emerging evidence suggests it may be safe and effective in HFrEF patients with ESRD on dialysis 4
• In a retrospective study, sacubitril/valsartan (mean dose 123 mg/day) significantly reduced troponin T and ST2 levels and improved LVEF from 29.7% to 40.8% in dialysis patients 4
• If used off-label in dialysis patients, start at low doses (24/26 mg twice daily) with close monitoring for symptomatic hypotension 4
• Monitor blood pressure closely; down-titration may be needed but discontinuation is rarely required 4

ACE Inhibitors or ARBs (If ARNI Not Used)

• Use ACE inhibitors or ARBs if ARNI is not accessible or contraindicated 1
• Start at low doses and titrate cautiously, monitoring blood pressure and potassium 1
• Check renal function 1-2 weeks after initiation, though changes in creatinine are less relevant in dialysis patients 1

SGLT2 Inhibitors

• Dapagliflozin is contraindicated with eGFR <30 mL/min/1.73 m² and in patients on dialysis 1
• Empagliflozin is contraindicated with eGFR <20 mL/min/1.73 m² and in patients on dialysis 1
• These agents cannot be used in ESRD patients on dialysis per current FDA labeling 1

Management of Common Complications

Hypotension

• If symptomatic hypotension occurs with heart rate >70 bpm, reduce ACEi/ARB/ARNI first 5
• If symptomatic hypotension occurs with heart rate <60 bpm, reduce beta-blocker first 5
• MRAs have the least effect on blood pressure and should be maintained when possible 5
• Do not reduce or discontinue GDMT for asymptomatic or mildly symptomatic low blood pressure 5

Hyperkalemia

• Monitor potassium closely, especially within 1-2 weeks of medication changes 2
• Consider potassium binders to optimize GDMT rather than reducing life-saving medications 1
• In anuric dialysis patients, hyperkalemia risk is primarily managed through dialysis frequency and dietary restriction 3

Volume Management

• Diuretics are essential for managing congestion and should not be withheld before initiating beta-blockers 1
• Loop diuretics (furosemide equivalent >160 mg/day) are often required, with supplemental metolazone for refractory congestion 1
• Coordinate diuretic dosing with dialysis schedule to optimize volume status 1

Medication Sequencing and Titration

• Initiate beta-blockers and MRAs early, even at low ACEi/ARB doses 1
• Adding a beta-blocker to low-dose ACEi produces greater benefit than increasing ACEi dose alone 1
• Uptitrate medications every 2-4 weeks as tolerated, doubling doses with each step 1
• Reassess blood pressure, heart rate, and electrolytes 1-2 weeks after each dose change 1, 2

Advanced Therapy Considerations

Indications for Advanced Therapies

• Persistent NYHA class III-IV symptoms despite optimal GDMT 1
• Frequent hospitalizations (≥2 in past 6 months) requiring IV diuretics 1
• Progressive deterioration in clinical status with cardiac cachexia 1
• Refractory ventricular arrhythmias or frequent ICD shocks 1

Inotropic Support

• Continuous IV inotropic support is reasonable as bridge therapy to mechanical circulatory support or transplantation in eligible patients 1
• May be considered as palliative therapy for symptom control in patients ineligible for advanced therapies 1
• Long-term intermittent inotropic therapy is potentially harmful outside of bridge or palliative contexts 1

Device Therapy

• ICD, CRT, or CRT-D should be considered in ESRD patients with HFrEF using the same criteria as the general HF population 1
• ESRD should not preclude device therapy in otherwise appropriate candidates 1

Critical Monitoring Parameters

• Blood pressure (including orthostatic measurements) at each visit 1
• Heart rate, particularly when titrating beta-blockers or considering ivabradine 1
• Potassium levels within 1-2 weeks of medication changes 1, 2
• Volume status and weight trends between dialysis sessions 1
• Functional capacity and symptom burden using NYHA classification 1

Common Pitfalls to Avoid

• Do not withhold GDMT solely based on ESRD diagnosis—these patients have the highest mortality risk and stand to benefit most 3
• Do not discontinue medications for asymptomatic laboratory abnormalities (mild hyperkalemia, stable creatinine elevation) 5
• Do not delay beta-blocker initiation until ACEi/ARB is at target dose 1
• Do not use thiazolidinediones or saxagliptin in patients with HF risk, as they increase HF hospitalization 1
• Avoid routine triple combination of ACEi + ARB + aldosterone antagonist due to harm risk 1