Structural heart disease management during cancer treatment

KEY POINTS

Baseline transthoracic echocardiogram is important for the assessment of heart structure and function, and the determination of the presence or absence of pericardial or valvular heart disease prior to initiation of cancer treatment.
On autopsy, pericardial involvement is noted in 1% to 20% of patients with cancer, most commonly lung cancer, but also breast and esophageal cancer, melanoma, lymphoma, and leukemia.
Pericardial disease in patients with cancer can manifest as pericarditis, pericardial effusion, cardiac tamponade, or constrictive pericarditis.
Pericarditis during cancer treatment typically responds to anti-inflammatory therapy, but can pose a risk for tamponade acutely and for recurrent pericarditis later on.
Patients with cancer are at an increased risk of infective endocarditis; nonbacterial thrombotic endocarditis may be an associated complication of cancer.
Preexisting valvular heart disease can complicate cancer therapy owing to increased pressure and/or volume load and predispose to heart failure presentations.
Valve repair or replacement is recommended for severe valve disease, especially with the advances in percutaneous techniques and when cardiotoxic cancer therapy is unavoidable.
Guidelines recommend valve intervention if life expectancy is more than 12 months.

Pericardial disease

Incidence

Malignancy is newly diagnosed in 5% to 10% of patients presenting with pericarditis, and chances are higher (20% to 30%) in those presenting with a large pericardial effusion, cardiac tamponade, and lack of response to anti-inflammatory therapy or recurrent/persistent pericarditis.
Around 50% of pericardial effusions are malignancy-related (including patients with known cancer), and pericardial effusion can complicate 5% to 15% of late-stage cancers.
Pericardial disease can be seen in 6% to 30% of patients with cancer undergoing radiation therapy, but pericardial constriction is usually a late (20 to 30 years) complication seen in survivors (see Chapter 28 ).

Risk factors

Risk factors include types of cancer, chemotherapy drugs, radiation, and infection related to a compromised state.

Causes

Drugs

Anthracyclines, cyclophosphamide, cytarabine, (pericarditis ± myocarditis)
Tyrosine kinase inhibitors (imatinib, dasatinib, bosutinib, and ceritinib (pericarditis ± pleural effusion)
Interferon-α (for melanoma)
Retinoic acid (retinoic acid syndrome = fever, systemic hypotension, acute renal failure, pleural effusion, pericardial effusion)
Busulfan (late pericardial and myocardial fibrosis)
Methotrexate, arsenic trioxide, 5-fluorouracil, and docetaxel
High-dose chemotherapy (circulating tumor cell [CTC] regimen consisting of four courses daily of fluorouracil, epirubicin, cyclophosphamide every three weeks, followed by high-dose chemotherapy with cyclophosphamide, carboplatin, and thiotepa divided over four days is the reported cause of constrictive pericarditis that began as an effusion two months after chemotherapy and 2 weeks later had no effusion, but needed pericardiectomy for constrictive pericarditis)
Immune checkpoint inhibitors, such as anti-PD1 (e.g., nivolumab, pembrolizumab) and anti-PDL1 agents (e.g., atezolizumab)

Radiation

6% to 30% of patients receiving radiation therapy

Direct or metastatic tumor invasion/extension

Primary involvement of the pericardium is seen with pericardial mesothelioma and pericardial fibrosarcoma or angiosarcoma.
Direct local extension into the pericardium is seen with lung, breast, or esophageal cancer.
Hematogenous and/or lymphangitic spread is seen with leukemia, lymphoma, and melanoma.

Infectious causes

Infections related to the immunocompromised state of patients
Infections following thoracic or cardiac surgery

Obstruction of mediastinal lymphatic drainage

Compression by mediastinal tumor mass
Mediastinal lymph node removal
Radiation therapy

Diagnosis

Pericarditis

Symptoms suggesting pericarditis include positional sharp chest pain, dyspnea, and palpitations. Physical examination and detection of a pericardial friction rub is important in the assessment of patients suspected of having pericarditis because pericarditis may or may not be accompanied by a pericardial effusion. Electrocardiogram changes can be seen in pericarditis, such as tachycardia, PR depression or ST-segment elevation.

Cardiac magnetic resonance imaging or computed tomography show enhancement or thickening of the pericardium in acute pericarditis.

Pericardial effusion

Pericardial effusion could result in hemodynamic compromise based on the size and rapidity of accumulation of pericardial fluid. ^, A pericardial effusion should be suspected when there is an enlarging cardiac silhouette. Cardiomegaly on chest X-ray does not manifest until the pericardial fluid reaches at least 200 mL. Some patients report fatigue, dyspnea, and chest heaviness. Transthoracic echocardiography is the diagnostic tool of choice for the evaluation of presence, size, and hemodynamic sequelae of a pericardial effusion. It is not uncommon for the pericardial effusion to be detected first by computed tomography or cardiac magnetic resonance imaging during chest imaging prior to echocardiography. Electrocardiographic findings of pericardial effusion include tachycardia, low voltage, and electrical alternans. Pericardial fluid should be sent for testing to investigate the cause of pericardial effusion including cytology, aerobic and anaerobic cultures, protein, glucose, and lactate dehydrogenase, pH, specific gravity, and hemoglobin if the effusion is bloody.

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