What are the management options for a 65-year-old male with non-sustained ventricular tachycardia (NSVT) symptoms, heart failure with reduced ejection fraction (HFrEF), and severe chronic obstructive pulmonary disease (COPD) requiring home oxygen therapy, currently on mexiletine (mexiletine) 150 mg three times a day?

Management Options for Refractory NSVT in HFrEF with Severe COPD

In this 65-year-old with symptomatic NSVT despite mexiletine 150 mg TID, HFrEF, and severe O2-dependent COPD, the priority is optimizing guideline-directed medical therapy for heart failure first, then cautiously escalating mexiletine dosing or adding amiodarone, while recognizing that ICD therapy may be limited by his advanced disease burden and prognosis.

Immediate Assessment Priorities

Optimize Heart Failure Therapy First

• Ensure the patient is on maximal guideline-directed medical therapy (GDMT) for HFrEF, including ACE inhibitors/ARBs or sacubitril/valsartan, beta-blockers (despite COPD), mineralocorticoid receptor antagonists, and SGLT2 inhibitors, as these reduce mortality and may decrease arrhythmic burden 1.
• Beta-blockers should be used in COPD patients with HFrEF unless absolutely contraindicated; cardioselective agents are preferred and underuse is common but inappropriate 2.
• In the PARADIGM-HF trial, patients with both HFrEF and COPD had higher rates of heart failure hospitalization and cardiovascular events, but sacubitril/valsartan showed consistent benefit regardless of COPD status 2.

Assess Disease Severity and Prognosis

• Determine if this patient meets criteria for advanced heart failure (Stage D), which includes recurrent hospitalizations, inability to tolerate GDMT, severely reduced exercise capacity, or escalating diuretic requirements 1.
• The presence of severe O2-dependent COPD combined with HFrEF significantly impacts prognosis and may influence the risk-benefit ratio of aggressive antiarrhythmic therapy versus device therapy 2.

Antiarrhythmic Medication Options

Escalate Mexiletine Dosing

• The current dose of 150 mg TID (450 mg/day total) is subtherapeutic; mexiletine can be titrated up to 300-400 mg every 8 hours (maximum 1200 mg/day) 3.
• Increase by 50-100 mg increments every 2-3 days while monitoring for CNS side effects (tremor, dizziness) and GI symptoms (nausea), which increase with total daily dose 3, 4.
• Mexiletine has minimal negative inotropic effects and does not depress myocardial function, making it safer than Class IA agents in HFrEF 5, 6.
• In patients with severe liver disease or marked right-sided heart failure, lower doses may be required due to reduced hepatic metabolism 3.

Add Combination Antiarrhythmic Therapy

• Combining mexiletine with a Class IA agent (quinidine or procainamide) may enhance efficacy in refractory cases, with studies showing improved arrhythmia suppression rates from 23% with mexiletine alone to 29% with combination therapy 7.
• This combination approach showed possible improved arrhythmia-free survival, though adverse effects require close monitoring 7.
• Mexiletine combined with amiodarone is another option for refractory ventricular arrhythmias 4.

Consider Amiodarone

• Amiodarone is the most effective antiarrhythmic for ventricular arrhythmias but carries significant toxicity concerns, particularly pulmonary toxicity in a patient with severe COPD 1.
• In HFrEF with hemodynamic instability or inadequate rate control, IV amiodarone can be useful when other measures fail 1.
• Amiodarone should be used with extreme caution given the severe underlying COPD and need for home oxygen 1.

Device Therapy Considerations

ICD Evaluation

• ICD therapy should be considered if the patient has reasonable life expectancy (>1 year) and is not in advanced Stage D heart failure with multiple comorbidities 1.
• The combination of severe O2-dependent COPD and HFrEF suggests limited life expectancy, which may make ICD less appropriate 1.
• If an ICD is already present, ensure it is programmed appropriately with extended detection times to avoid inappropriate shocks for NSVT 1.

Cardiac Resynchronization Therapy

• Evaluate for CRT eligibility if the patient has LBBB with QRS ≥150 ms and LVEF ≤35%, as this improves outcomes in HFrEF 1.

Critical Management Pitfalls

Avoid Medications That Worsen Heart Failure

• Do not use non-dihydropyridine calcium channel blockers (verapamil, diltiazem) in HFrEF, as they worsen outcomes 1.
• Avoid NSAIDs and corticosteroids, which promote fluid retention and can precipitate decompensation in severe HFrEF 8.
• Even single doses of corticosteroids can cause significant fluid retention in patients with severe heart failure 8.

Beta-Blocker Management in COPD

• Do not withhold beta-blockers solely due to COPD diagnosis; they are essential for mortality reduction in HFrEF and were used in 87% of COPD patients in PARADIGM-HF 2.
• Cardioselective beta-blockers (metoprolol, bisoprolol, carvedilol) are preferred and generally well-tolerated 1, 2.

Monitor for Proarrhythmia

• While mexiletine has low proarrhythmic potential compared to other antiarrhythmics, any dose escalation requires ECG monitoring 5, 6.
• CNS side effects (tremor, dizziness, memory loss) occur in ~10% and GI effects in up to 40% of patients on mexiletine 6.

Palliative Care Discussion

Address Goals of Care

• Given the combination of advanced HFrEF, severe COPD requiring home oxygen, and refractory arrhythmias, discuss goals of care and end-of-life planning 1.
• Options for end-of-life care should be discussed when severe symptoms persist despite all recommended therapies 1.
• If an ICD is present, discuss the option to inactivate defibrillation function if consistent with patient goals 1.

Symptom Management

• Continuous intravenous inotropes may be considered for palliation of symptoms in refractory end-stage HF, though routine intermittent infusions are not recommended 1.