How to manage a patient with heart failure and pulmonary sarcoidosis presenting with elevated Lactate Dehydrogenase (LDH)?

Management of Heart Failure and Pulmonary Sarcoidosis with Elevated LDH

Optimize heart failure management first, then aggressively evaluate and treat both cardiac and pulmonary sarcoidosis with corticosteroids if clinically manifest disease is confirmed, while simultaneously screening for pulmonary hypertension given the high-risk presentation. 1, 2

Initial Diagnostic Priorities

Determine the Source and Severity of Cardiac Involvement

• Obtain transthoracic echocardiography (TTE) immediately to assess left ventricular function, right ventricular function, and screen for pulmonary hypertension, as cardiac sarcoidosis presents with heart failure in 5-10% of cases and carries the worst prognosis. 1, 3, 4

• Perform cardiac MRI with late gadolinium enhancement (LGE) as it is emerging as the gold standard for detecting cardiac sarcoidosis and the extent of LGE is an important prognostic factor for outcomes. 5

• Consider FDG-PET/CT to assess the extent of active cardiac and systemic sarcoidosis involvement, particularly when multiorgan disease is suspected, as this guides immunosuppression decisions. 6, 5

• Obtain high-resolution CT chest without IV contrast to evaluate the extent of pulmonary sarcoidosis, assess for fibrosis versus active inflammation, and exclude other causes of heart failure such as pulmonary embolism. 6

Screen for Pulmonary Hypertension

• If TTE suggests pulmonary hypertension (elevated estimated pulmonary artery pressure based on tricuspid regurgitation), proceed with right heart catheterization to definitively confirm or exclude sarcoidosis-associated pulmonary hypertension (SAPH), as this distinction is critical for management. 1

• Clinical indicators warranting PH screening include: exertional chest pain, syncope, prominent P2 or S4 on exam, reduced 6-minute walk distance, desaturation with exercise, reduced DLCO, elevated brain natriuretic peptide, and fibrotic lung disease on imaging. 1

• Distinguish between postcapillary PH (WHO Group II) from left heart disease versus precapillary PH (WHO Group V) from sarcoidosis itself, as these are managed differently. 1

Optimize Heart Failure Management Before Immunosuppression

• Ensure optimal volume status and guideline-directed medical therapy for heart failure before assessing the contribution of sarcoidosis-related PH, as volume overload confounds hemodynamic assessment. 1

• Identify and treat concomitant disorders contributing to heart failure or PH, including COPD, sleep apnea syndrome, and pulmonary embolism, before attributing symptoms solely to sarcoidosis. 1

• Measure BNP or NT-proBNP for risk stratification and to help differentiate heart failure from other causes of dyspnea when the diagnosis is uncertain. 1

Immunosuppressive Therapy for Cardiac and Pulmonary Sarcoidosis

Indications for Treatment

• Initiate corticosteroids for clinically manifest cardiac sarcoidosis presenting with ventricular arrhythmias, conduction abnormalities, or heart failure, despite limited evidence, as this is standard expert consensus. 2, 3, 4

• Treat pulmonary sarcoidosis with corticosteroids if there is reduced lung function (FVC, FEV1, DLCO), moderate to severe pulmonary fibrosis, or precapillary pulmonary hypertension, as these are high-risk features associated with mortality and disability. 7

• Plan for at least 12 months of corticosteroid therapy for symptomatic pulmonary, cardiac, or neurologic sarcoidosis involvement. 2

Steroid-Sparing Agents

• Add methotrexate as the most commonly used second-line agent when patients require prolonged immunosuppression or develop corticosteroid-related toxicity. 2

• Consider infliximab (anti-TNF therapy) for refractory cases not responding to corticosteroids and methotrexate, as it has demonstrated effectiveness in cardiac sarcoidosis. 2

Monitoring Treatment Response

• Use FDG-PET/CT to detect active inflammation and guide immunosuppression on a case-by-case basis, though it should not be used for routine follow-up due to cost and radiation exposure. 6, 5

• Perform follow-up CT chest without IV contrast based on clinical symptoms, pulmonary function changes, or treatment decisions rather than on a predetermined schedule. 6

Device Therapy and Advanced Heart Failure Management

• Place an implantable cardioverter-defibrillator (ICD) in patients with clinically manifest cardiac sarcoidosis and significant left ventricular dysfunction, as the extent of LV dysfunction is the most important predictor of prognosis and sudden cardiac death risk. 3, 4, 5

• Consider pacemaker placement for patients with complete heart block or other significant conduction abnormalities from cardiac sarcoidosis. 8

• Evaluate for cardiac transplantation in refractory cases with end-stage heart failure despite optimal medical and immunosuppressive therapy. 8

Critical Pitfalls to Avoid

• Do not use PAH-approved therapies (prostanoids, endothelin receptor antagonists, PDE-5 inhibitors) for PH due to left heart disease, as there is no evidence supporting their use and they may cause harm. 1

• Do not perform routine screening for SAPH in asymptomatic patients without clinical indicators, as this is unnecessary. 1

• Do not rely on serum ACE levels as a standalone diagnostic test or to exclude sarcoidosis, as it has limited sensitivity and specificity and must be combined with clinical, radiological, and histological evidence. 9

• Recognize that up to two-thirds of clinically manifest cardiac sarcoidosis cases present as isolated cardiac disease with minimal extra-cardiac involvement, so absence of obvious systemic sarcoidosis does not exclude cardiac involvement. 5