Is there evidence to support the use and optimization of mineralocorticoid‑receptor antagonists, digoxin, sodium‑glucose co‑transporter‑2 inhibitors, and ACE inhibitors/angiotensin receptor blockers/angiotensin receptor‑neprilysin inhibitors in patients with right‑sided heart failure secondary to chronic lung disease?

No Evidence Supports Using Standard Heart Failure Medications in Right Heart Failure from Chronic Lung Disease

The medications you've listed (MRA, digoxin, SGLT2i, ACE/ARB/ARNI) are specifically indicated for left-sided heart failure with reduced ejection fraction (HFrEF) or heart failure with nonreduced ejection fraction (HFnrEF), not for right heart failure secondary to chronic lung disease (cor pulmonale). None of the provided guidelines address this specific clinical scenario, and these therapies should not be routinely applied to isolated right ventricular failure from pulmonary disease.

Why This Distinction Matters

The evidence base for heart failure pharmacotherapy is built entirely on left ventricular dysfunction:

• SGLT2 inhibitors (dapagliflozin, empagliflozin) reduce HF hospitalizations and cardiovascular death in HFrEF and HFnrEF 1, 2
• MRAs (spironolactone, eplerenone, finerenone) decrease mortality and hospitalizations in left-sided HF 1, 3
• ACE/ARB/ARNI provide neurohormonal blockade beneficial in left ventricular remodeling 4, 3
• Digoxin has limited modern use, primarily for rate control in atrial fibrillation with left-sided HF 3, 5

All major trials excluded patients with primary right heart failure from lung disease. The pathophysiology differs fundamentally: right heart failure from chronic lung disease results from pulmonary hypertension and increased right ventricular afterload, not the neurohormonal activation and ventricular remodeling that characterizes left-sided HF.

The Clinical Reality

Right heart failure secondary to chronic lung disease requires:

• Treatment of the underlying lung disease (bronchodilators, oxygen, pulmonary vasodilators if indicated)
• Judicious diuretic use for volume overload, but with caution as excessive preload reduction can worsen right ventricular output
• Avoidance of medications that lower systemic blood pressure, as the right ventricle depends on adequate coronary perfusion pressure

Critical Pitfalls to Avoid

Do not extrapolate left-sided HF guidelines to right-sided HF from lung disease. The hemodynamic consequences differ:

• ACE/ARB/ARNI can cause hypotension without improving right ventricular function
• MRAs risk hyperkalemia without proven benefit in this population
• Beta-blockers (not mentioned in your question but worth noting) can worsen bronchospasm and are generally contraindicated in severe COPD
• SGLT2 inhibitors have no established role in isolated right heart failure

The only scenario where these medications might be appropriate is if the patient has concurrent left ventricular dysfunction documented by echocardiography (LVEF ≤40% for HFrEF or >40% with evidence of diastolic dysfunction for HFnrEF). In that case, treat according to left-sided HF guidelines 1, 3, 2, but monitor closely for hypotension and worsening right heart function.

What to Do Instead

For isolated right heart failure from chronic lung disease:

1. Optimize pulmonary disease management - maximize bronchodilators, ensure appropriate oxygen therapy
2. Assess for pulmonary hypertension - right heart catheterization if indicated to determine if pulmonary vasodilator therapy is appropriate
3. Use loop diuretics carefully - for symptomatic volume overload only, avoiding excessive preload reduction
4. Monitor for left ventricular involvement - serial echocardiography to detect if biventricular failure develops

If biventricular failure is present, then standard HF medications become appropriate, but the primary lung disease must still be addressed as the root cause of right ventricular dysfunction.