Acquired Heart Disease

The common acquired heart disorders among children are Kawasaki disease (primarily in children <5 years), rheumatic heart disease (most common in children aged 5 to 15 years), myocarditis, pericarditis, and infective endocarditis, and multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (Covid-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this section, we review these conditions according to the most common age group affected (infants and toddlers, 1 month to 2 years; children and adolescents, 2 to <16 years); however, many of these conditions can affect children at any age.

Infant and Toddlers

Kawasaki Disease

Presentation: Kawasaki disease is an acute vasculitis of unknown cause characterized by:

• high fever for >5 days

• rash

• cervical lymphadenopathy

• redness and swelling of the hands and feet

• conjunctivitis

• erythematous and cracked lips and/or strawberry tongue

Diagnosis: Kawasaki disease typically affects children younger than age 5 years and can lead to coronary artery aneurysms if left untreated. If Kawasaki disease is suspected, a baseline echocardiogram is recommended to evaluate the coronary arteries.

Treatment: Treatment for Kawasaki disease typically involves intravenous immunoglobulin and aspirin. According to the 2017 American Heart Association guidelines, patients should undergo follow-up echocardiograms 1 to 2 weeks and 4 to 6 weeks after treatment. Frequency of follow-up thereafter should be based on risk stratification.

Multisystem inflammatory syndrome in children (MIS-C) is a new syndrome associated with the coronavirus 2019 (Covid-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has some overlapping clinical features as Kawasaki disease. (See more on MIS-C below.)

Children and Teenagers

Myocarditis

Presentation: Myocarditis is inflammation of the heart muscle that can cause heart failure in previously healthy infants and children. The signs and symptoms can be nonspecific, highly variable, and may include:

• chest pain

• mild flu-like symptoms

• dyspnea

• tachypnea

• palpitations

• syncope

• fatigue

• arrythmia

• sudden cardiac death

Pathogenesis: The exact mechanism of myocardial inflammation is dependent on the pathogen that causes acute myocarditis. Generally, the acute pathogen triggers the release of acute inflammatory mediators, leading to lymphocytic infiltration of the myocardium, which causes myocardial edema. Myocarditis may be fulminant and lead to cardiogenic shock.

Diagnosis: Etiologies of myocarditis include:

• viral infections

• autoimmune

• toxins

• medications

• hypersensitivity

(Source: Recognition and Management of Fulminant Myocarditis: A Scientific Statement from the American Heart Association. Circulation 2020.)

Diagnostic evaluation may include:

• chest x-ray

• electrocardiogram (ECG)

• echocardiogram

• cardiac MRI

• laboratory tests (e.g., cardiac enzymes, viral serologies, brain natriuretic peptide)

Although endomyocardial biopsy is considered the gold standard for diagnosis of myocarditis, its use remains controversial in pediatric patients given the invasive nature and relatively low sensitivity due to the patchy nature of inflammation. A negative biopsy does not exclude acute myocarditis. Rates of biopsy in myocarditis are declining and cardiac MRI has been increasingly used to support the diagnosis.

The American Heart Association (AHA) AHA provides a framework to confirm the diagnosis of myocarditis, and classifies the diagnosis into the following four categories:

• biopsy proven

• CMR-confirmed clinically suspected

• clinically suspected

• possible myocarditis

Treatment: Treatment of myocarditis is supportive. In children with fulminant myocarditis, extracorporeal membrane oxygenation (ECMO) may be required to maintain end-organ perfusion while allowing for myocardial recovery. Occasionally, if recovery does not occur, a patient may require heart transplantation. Ventricular arrhythmias are common and might require treatment and intervention. Follow up with a pediatric cardiologist and repeat echocardiography are recommended.

Pericarditis

Presentation: Pericarditis is inflammation of the pericardium (the sac that surrounds the heart). Pericarditis can be seen in the postoperative period after heart surgery or after an infection, chest trauma, or connective tissues disorder such as systemic lupus erythematosus. Signs and symptoms include:

• chest pain with inspiration

• low-grade fever

• fatigue

• loss of appetite

On exam, the patient may exhibit Beck triad (distant heart sounds, distended neck veins, and hypotension with a narrowed pulse pressure).

Diagnosis: Diagnostic evaluation may include chest x-ray, ECG, echocardiogram, and laboratory tests (e.g., inflammatory markers).

Treatment: Treatment of pericarditis is supportive, typically with anti-inflammatory medications. If a hemodynamically significant pericardial effusion is present, pericardiocentesis may be required.

Infective Endocarditis

Risk Factors: Infective endocarditis (IE) is an infection of the endocardium and less common in children than adults. Patients who are at risk for infective endocarditis include those with unrepaired cyanotic congenital heart disease (CHD), postoperative CHD repaired with prosthetic material or devices, prosthetic cardiac valves, repaired CHD with residual shunts near prosthetic patch or device, previous endocarditis, rheumatic heart disease, or central indwelling venous catheters. The causative agents in children and adolescents are Staphylococcus aureus, strep species, and various oral flora. Good dental hygiene is highly recommended for all CHD patients, given the risk of IE from oral pathogens.

Although IE is rare in neonates, it can occur as a complication of an indwelling central venous line. In neonates, the most common causative organisms include Staphylococcus aureus, coagulase-negative staphylococci strains, gram-negative bacteria, and Candida.

Presentation: The clinical findings in children and adolescents are variable, typically progress slowly, and include the following

• fatigue

• arthralgias

• myalgias

• weight loss

• rigors

• diaphoresis

Given the indolent course of IE, a high index of suspicion is needed in patients with CHD, especially those with prosthetic materials The clinical findings in neonates are nonspecific and can be difficult to distinguish from septicemia and congestive heart failure from other causes.

Diagnosis: The modified Duke criteria can be used to guide diagnosis of infective endocarditis in children.

Treatment: Affected patients require a prolonged course (approximately 6 to 8 weeks) of intravenous antibiotic therapy.

(Source: Native-Valve Infective Endocarditis. N Engl J Med 2020.)

Acute Rheumatic Heart Disease

Presentation: Rheumatic heart disease is the most serious complication of acute rheumatic fever, which is caused by untreated or inadequately treated group A streptococcus infection. Acute rheumatic fever is most common in children between the ages of 5 and 15 years. Symptoms of acute rheumatic fever include:

• polyarthritis

• subcutaneous nodules

• Sydenham chorea

• carditis

• erythema marginatum

Diagnosis: The revised Jones criteria is used to diagnosis acute rheumatic fever.

(Source: Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography: A Scientific Statement from the American Heart Association. Circulation 2015.)

Treatment: Acute rheumatic fever can lead to mitral and aortic insufficiency, pericarditis, myocarditis, or heart failure. The best treatment is prevention.

Multisystem Inflammatory Syndrome in Children (MIS-C)

Multisystem inflammatory syndrome in children (MIS-C) is a condition associated with the coronavirus disease 2019 (Covid-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

MIS-C is unique in that it is typically a postinfectious immune-mediated phenomenon that presents 2-6 weeks after infection or exposure to the SARS-CoV2 virus, in a child with serologic evidence of positive IgG antibodies to SARS-CoV-2.

Diagnosis: Although the symptoms of MIS-C are similar to those of Kawasaki disease, MIS-C appears to be a unique entity with specific diagnostic criteria. Guidelines from the American Association of Pediatrics (AAP) recommend using the following case definition for MIS-C:

• fever

• clinical severity requiring hospitalization

• C-reactive protein >3.0 mg/dL

• new onset of two or more clinical manifestations:

  • cardiac: coronary artery dilatation/aneurysm, left ventricular ejection fraction <55%, troponin elevated above normal

  • shock

  • mucocutaneous: rash, oral mucosal inflammation, conjunctivitis/conjunctival injection or extremity findings (erythema, edema)

  • gastrointestinal: abdominal pain, vomiting or diarrhea

  • hematologic: platelet count <150,000/µL, absolute lymphocyte count <1000/µL

• detection of SARS-CoV-2 up to 6- days prior to or during hospitalization

Presentation: Children afflicted with MIS-C present some or all of the following findings:

• persistent fever (usually 4-6 days)

• gastrointestinal symptoms (e.g., abdominal pain, vomiting, and diarrhea)

• Kawasaki disease type features, including conjunctivitis, mucosal lethargy, myalgia, rash

• toxic shock syndrome-like features with poor cardiac function

• shortness of breath

• cytokine storm and hyperinflammatory features

Cardiac involvement: Common specific cardiac involvement in MIS-C described in published case reports includes:

• myocardial dysfunction

• coronary artery dilation or aneurysms

• electrocardiogram (ECG) abnormalities (e.g., ST and T wave changes)

• first- and second-degree heart block

• ventricular arrythmia

• elevated B-type natriuretic peptide (BNP) levels

• elevated troponins

Evaluation:

• Common laboratory tests include inflammatory markers such as erythrocyte sedimentation rate (ESR), C- reactive protein (CRP), ferritin, lactic dehydrogenase (LDH), lymphopenia (<1000), thrombocytopenia (<150,000), neutrophilia, hyponatremia, D-dimer, B-type natriuretic peptide, troponin.

• COVID-19 testing should be performed with RT-PCR assay and serological testing.

• Cardiac evaluation generally includes ECG and echocardiogram.

Treatment: Protocols have been developed that are somewhat institutional specific, but typically start with intravenous immunoglobulin (IVIg) and additional medications can be used if there is limited or no clinical improvement including the following:

• steroid therapy

• biologic agents (e.g., anakinra)

• aspirin (unless contraindicated)

Outcomes: Based on the current literature, most patients with MIS-C who presented with clinically significant myocardial dysfunction have had good clinical and echocardiographically documented recovery of cardiac function. The current practice in cardiology is to continue long-term follow up with ECG and echocardiogram for at least 1 year after presentation.