What strategies would optimize heart failure management in a patient with reduced ejection fraction (EF), chronic kidney disease (CKD), and recurrent hyperkalemia?

From the Guidelines

Optimizing heart failure management in a patient with reduced ejection fraction, chronic kidney disease, and recurrent hyperkalemia requires a careful and stepwise approach, prioritizing the use of beta-blockers, hydralazine, and isosorbide dinitrate, while cautiously introducing ACE inhibitors or ARBs, and utilizing potassium binders and loop diuretics as needed, as recommended by the European Society of Cardiology guidelines 1.

Key Considerations

• Start with a beta-blocker like carvedilol (3.125 mg twice daily, titrated slowly to target dose of 25 mg twice daily) or metoprolol succinate (25 mg daily, titrated to 200 mg daily), as these medications don't significantly impact potassium levels.
• Add hydralazine (25 mg three times daily, titrated to 75 mg three times daily) and isosorbide dinitrate (20 mg three times daily, titrated to 40 mg three times daily) to reduce afterload and preload.
• For diuresis, use loop diuretics like furosemide (20-40 mg daily, adjusted based on volume status) rather than potassium-sparing options.
• Consider adding a potassium binder such as patiromer (8.4 g daily, titrated based on potassium levels) or sodium zirconium cyclosilicate (5-10 g daily) to manage hyperkalemia while cautiously introducing low doses of ACE inhibitors or ARBs.

Monitoring and Management

• Monitor renal function and potassium levels closely (weekly initially, then monthly once stable).
• Dietary potassium restriction (2-3 g/day), treatment of metabolic acidosis with sodium bicarbonate if present, and optimization of glucose control in diabetic patients are also essential components of management.
• The use of ACE inhibitors or ARBs should be guided by the patient's renal function and potassium levels, with careful titration and monitoring, as recommended by the American Heart Association and the Heart Failure Society of America 1.

Guideline-Directed Medical Therapy

• The concept of guideline-directed medical therapy for heart failure is evolving, and a novel framework has been proposed to describe the level of adherence to evidence-based drug treatments for patients with a reduced ejection fraction, recognizing that all landmark survival trials in heart failure were 'strategy trials' that mandated a standardized forced-titration treatment plan 1.

From the FDA Drug Label

For patients with heart failure with reduced ejection fraction (HFrEF), administration of sacubitril and valsartan resulted in a significant non-sustained increase in natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP compared to valsartan In a 21-day study in HFrEF patients, sacubitril and valsartan significantly increased urine ANP and cGMP and plasma cGMP, and decreased plasma NT-proBNP, aldosterone and endothelin-1. The recommended dose of LOKELMA is 10 g once daily for continued treatment, monitor serum potassium and adjust the dose based on the serum potassium level and desired target range.

To optimize heart failure management in a patient with reduced ejection fraction, chronic kidney disease, and recurrent hyperkalemia, consider the following strategies:

• Use of sacubitril-valsartan: This medication has been shown to improve outcomes in patients with HFrEF by increasing natriuresis and decreasing plasma NT-proBNP levels 2.
• Potassium management: Use of sodium zirconium cyclosilicate (LOKELMA) can help manage hyperkalemia in patients with chronic kidney disease, with a recommended dose of 10 g once daily and monitoring of serum potassium levels to adjust the dose as needed 3.
• Monitoring and adjustment: Regular monitoring of serum potassium levels, renal function, and heart failure symptoms is crucial to adjust the treatment plan and prevent complications.
• Dose adjustment: Adjust the dose of LOKELMA based on serum potassium levels, and consider decreasing the dose or discontinuing if serum potassium falls below the desired target range.
• Consideration of comorbidities: Take into account the patient's comorbidities, such as chronic kidney disease and heart failure, when adjusting the treatment plan.

From the Research

Optimizing Heart Failure Management

To optimize heart failure management in a patient with reduced ejection fraction, chronic kidney disease, and recurrent hyperkalemia, several strategies can be employed:

• Monitoring of renal function and serum potassium levels is crucial, as the presence of chronic kidney disease (CKD) can affect the dosing of heart failure medications 4, 5.
• The use of renin-angiotensin system inhibitors, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, can be beneficial in patients with heart failure with reduced ejection fraction (HFrEF) and CKD, but requires close monitoring of renal function and serum potassium levels 4, 6.
• Sacubitril/valsartan is not recommended in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m2 4.
• Beta-blockers, such as bisoprolol, can be used in patients with HFrEF and CKD, but may require dose adjustment in patients with renal impairment 4.
• Sodium-glucose cotransporter 2 inhibitors can be effective in reducing adverse cardiovascular and renal outcomes in patients with HFrEF and CKD, but require careful monitoring of renal function and serum potassium levels 4, 6.
• Mineralocorticoid receptor antagonist therapy can be considered in patients with HFrEF and an eGFR ≥ 30 mL/min per 1.73 m2, but requires careful monitoring of renal function and serum potassium levels 4.

Managing Worsening Renal Function

In patients with HFrEF and CKD, worsening renal function can be managed by:

• Monitoring renal function and serum potassium levels closely 5.
• Adapting medication according to clinical scenarios, such as congestion, dehydration, hypotension, or hyperkalemia 5.
• Using therapeutic management algorithms to guide treatment decisions 5.
• Considering the use of novel classes of drugs, such as sodium-glucose cotransporter 2 inhibitors, which have shown safety and efficacy in patients with HFrEF and CKD 6.

Evidence-Based Medical Therapy

Evidence-based medical therapy for patients with HFrEF and CKD includes:

• The use of quadruple therapy, including angiotensin receptor blocker/neprilysin inhibitors, evidence-based beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors 7.
• The consideration of other medications, such as intravenous iron, ivabradine, hydralazine/nitrates, and vericiguat, in certain subgroups of patients with HFrEF 7.
• The use of device therapies, such as implanted cardioverter defibrillators, cardiac resynchronization therapy, and trans catheter mitral valve repair, in specific groups of patients with HFrEF 7.