What is the next step for a 36-year-old male patient with severe cardiomyopathy and an ejection fraction of severely impaired left ventricular function, who shows no improvement after 3 months on guideline-directed medical therapy with Entresto (sacubitril/valsartan), spironolactone, carvedilol, Jardiance (empagliflozin), and Lasix (furosemide)?

From the Guidelines

The patient should be referred to an advanced heart failure center for evaluation and consideration of advanced therapies, including cardiac device therapy such as implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT), as well as heart transplantation. According to the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1, patients with persistently reduced left ventricular ejection fraction (LVEF) ≤35% despite guideline-directed medical therapy (GDMT) for ≥3 months should be referred for consideration of device therapy.

Given the patient's severe cardiomyopathy and severely impaired left ventricular function with an ejection fraction of 10-15%, the lack of improvement after 3 months on comprehensive GDMT with Entresto, spironolactone, carvedilol, Jardiance, and Lasix indicates a need for advanced therapies. The patient's young age and severe heart failure that has not responded to optimal medical therapy put him at high risk for disease progression, life-threatening arrhythmias, and cardiovascular mortality.

Key considerations include:

• Evaluation for ICD therapy for primary prevention of sudden cardiac death, as recommended by the 2006 ACC/AHA/ESC guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1.
• Assessment for CRT if there is evidence of electrical dyssynchrony (QRS duration ≥130 ms), as indicated by the 2013 ACCF/AHA guideline for the management of heart failure 1.
• Simultaneous evaluation for heart transplant candidacy, including comprehensive cardiopulmonary testing, evaluation of end-organ function, psychosocial assessment, and screening for contraindications.
• Consideration of mechanical circulatory support with a left ventricular assist device (LVAD) if transplantation is not immediately feasible or available.
• Continuation of the current medication regimen with possible optimization of doses if tolerated, as recommended by the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1.

This approach is supported by the most recent and highest quality evidence, including the 2021 ACC expert consensus decision pathway 1 and the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, which prioritize advanced therapies for patients with severe heart failure who have not responded to optimal medical therapy.

From the FDA Drug Label

The Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) was a randomized, double-blind trial comparing ivabradine and placebo in 6,558 adult patients with stable New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 bpm Patients had to have been clinically stable for at least 4 weeks on an optimized and stable clinical regimen, which included maximally tolerated doses of beta-blockers and, in most cases, ACE inhibitors or ARBs, spironolactone, and diuretics, with fluid retention and symptoms of congestion minimized. SHIFT demonstrated that ivabradine reduced the risk of the combined endpoint of hospitalization for worsening heart failure or cardiovascular death based on a time-to-event analysis (hazard ratio: 0.82,95% confidence interval [CI]: 0.75,0.90, p < 0. 0001)

The patient has severe cardiomyopathy with an ejection fraction of 10-15% and has been on guideline-directed medical therapy with Entresto, spironolactone, carvedilol, Jardiance, and Lasix for 3 months with no improvement.

• The patient's current heart rate is not provided, but if the patient has a resting heart rate ≥ 70 bpm, ivabradine could be considered as an add-on therapy to reduce the risk of hospitalization for worsening heart failure, as demonstrated in the SHIFT trial 2.
• However, the patient's current regimen and clinical status should be optimized and stabilized before considering additional therapies.
• It is also important to note that the SHIFT trial excluded patients with severe hypotension, and ivabradine can cause bradycardia, so careful consideration of the patient's clinical status and vital signs is necessary before initiating ivabradine therapy.

From the Research

Patient Assessment and Guideline-Directed Medical Therapy

The patient is a 36-year-old male with severe cardiomyopathy and an ejection fraction of 10-15%, indicating severely impaired left ventricular function. Despite being on guideline-directed medical therapy (GDMT) with Entresto (sacubitril/valsartan), spironolactone, carvedilol, Jardiance (empagliflozin), and Lasix (furosemide) for 3 months, there has been no improvement in the ejection fraction.

Considerations for Next Steps

Given the lack of improvement, several considerations should be taken into account:

• The patient's condition and the fact that the current medication regimen has not yielded the desired improvement in ejection fraction.
• The potential for device therapy, such as an implantable cardiac defibrillator (ICD), which is recommended for patients with symptomatic heart failure and reduced ejection fraction (HFrEF) despite optimal medical therapy 3.
• The role of sacubitril/valsartan in inducing beneficial reverse cardiac remodeling in eligible HFrEF patients, although the patient is already on this medication 3.
• The importance of maximizing GDMT, as evidenced by studies showing that a focused GDMT titration program can improve outcomes in patients with heart failure with reduced ejection fraction 4.

Potential Next Steps

Potential next steps for this patient could include:

• Re-evaluation of the patient's medication regimen to ensure that doses are optimized and that the patient is tolerating the medications as expected.
• Consideration of device therapy, such as an ICD, given the patient's severe left ventricular dysfunction and lack of response to medical therapy.
• Discussion of the potential benefits and risks of other treatment options, such as surgical revascularization or mitral valve surgery, in patients with severe left ventricular dysfunction 5.
• Further evaluation to determine the underlying cause of the patient's cardiomyopathy and to guide treatment decisions.

Key Points

Key points to consider in the management of this patient include:

• The importance of maximizing GDMT and considering device therapy in patients with severe left ventricular dysfunction.
• The potential benefits and risks of different treatment options, including surgical interventions.
• The need for ongoing monitoring and evaluation to guide treatment decisions and optimize patient outcomes.
• The consideration of sacubitril-valsartan's benefits in patients with heart failure and multimorbidity, as it has been shown to improve functional class and reduce hospitalization 6.