Adults with congenital heart disease face a high sudden cardiac death risk. Learn the No. 1 red flag (unexplained syncope), key electrical changes and clinical warning signs. Understand risk and know when to refer patients to a specialist.

Published: December 5, 2025

As more children with congenital heart disease survive into adulthood, primary care physicians are managing a growing population of adults with these conditions. Chief among the new challenges presented by these patients is an elevated risk of sudden cardiac death.

Sudden cardiac death accounts for about 25% of all mortality in patients with congenital heart disease, compared with just 15% in the general population. Perhaps most striking is that the median age at death falls in the third and fourth decades of life.

The annual incidence of sudden cardiac death among congenital heart disease patients is about 0.1% — significantly higher than age-matched controls. The rate continues to rise as more congenital heart patients survive into adulthood.

Unexplained syncope: The No. 1 red flag

Among all the risk factors and warning signs, one stands out across all types of congenital heart conditions: unexplained syncope.

“While symptoms like dizziness, lightheadedness or weakness warrant evaluation, true loss of consciousness requires immediate and thorough investigation,” Nicholas E. Rebhan, M.D., said during a recent continuing medical education opportunity.

Dr. Rebhan is a pediatric and congenital electrophysiologist with Norton Children’s Heart Institute, affiliated with the UofL School of Medicine.

Unexplained syncope in patients with moderate or severe adult congenital heart disease (ACHD) should prompt thorough evaluation, including electrophysiological assessment, as it may signal increased sudden cardiac death risk.

Understanding risk by complexity

Not all congenital heart conditions carry the same risk. The complexity of the underlying lesion and subsequent surgical repairs directly correlates with sudden cardiac death risk.

Moderate complexity lesions

These include tetralogy of Fallot, aortic stenosis, coarctation of the aorta and Ebstein anomaly. Risk factors to monitor include:

• History of prior palliative shunts
• Wide or fractionated QRS complex on electrocardiogram (ECG)
• Ventricular dysfunction
• Frequent ventricular ectopy

High complexity lesions

Patients with univentricular physiology (including Fontan circulation), transposition of the great arteries (especially those with Mustard or Senning repairs) and truncus arteriosus face substantially elevated risk. Additional warning signs include:

• Atrial tachyarrhythmias
• Progressive ventricular dysfunction
• Protein-losing enteropathy or ascites (in Fontan patients)
• Symptomatic heart failure
• Severe valve regurgitation

Key clinical indicators

Beyond syncope, primary care physicians should maintain heightened vigilance for these features:

Electrocardiographic changes:

• Prolonged QRS duration (and progressive lengthening over time)
• Frequent ventricular arrhythmias

Clinical findings:

• Reduced ventricular function (especially progressive decline)
• New or worsening heart failure symptoms
• Ischemic heart disease

Historical factors:

• Multiple prior intracardiac surgeries
• History of atrial tachycardias

Importantly, temporal trends matter more than single measurements. Progressive QRS prolongation and worsening ventricular function over time are independently associated with markedly higher risk, underscoring the value of serial monitoring rather than isolated assessments.

Genetic testing

Genetic testing has emerged as an important tool in this population. A genetic cause can be identified in approximately 35% of congenital heart disease cases, and certain genetic variants may influence sudden cardiac death risk through associations with ventricular dysfunction or arrhythmias.

Genetic testing is particularly valuable in cases of:

• Unexplained cardiac arrest
• Family clustering of congenital heart disease or sudden cardiac death
• Presence of syndromic features

When a pathogenic variant is identified, cascade testing of at-risk family members enables targeted clinical evaluation and preventive strategies. Primary care physicians should consider referring appropriate patients for genetic counseling and testing.

Risk stratification tools

Two important risk-prediction models have emerged to help clinicians identify high-risk patients:

• The PREVENTION-ACHD score: Combines disease-specific factors with lesion-specific baseline risk to provide annual sudden cardiac death risk estimates. A web-based calculator is available for clinical use.
• Spanish ACHD Network model: Groups lesions into four risk categories and generates five-year risk estimates.

Both models identify systolic dysfunction, wide QRS complex, and ischemic heart disease as high-risk features common across lesion types.

When to refer

Given the complexity and heterogeneity of the ACHD population, primary care physicians should maintain a low threshold for referral to specialized ACHD centers like the Norton Children’s Heart Institute Adult Congenital Heart Disease team. Early identification and management of arrhythmias, along with referral to specialized centers, are associated with reduced mortality.

Refer immediately for:

• Any episode of unexplained syncope
• New or frequent ventricular arrhythmias
• Progressive QRS prolongation on serial ECGs
• Declining ventricular function
• Development of atrial arrhythmias

“In patients with adult congenital heart disease, we need to maintain a very high index of suspicion,” Dr. Rebhan said. “The heterogeneity of the ACHD population in anatomy and repair complicates risk stratification and necessitates very individualized assessments and discussions to prevent these devastating events.”

While the landscape of sudden cardiac death in ACHD patients is complex, primary care physicians play a crucial role in surveillance and early recognition of warning signs. Maintaining awareness of high-risk features — particularly unexplained syncope — and ensuring appropriate specialty referral can help prevent these devastating events in a vulnerable population that depends on coordinated, lifelong care.