Cardiac Evaluation Valuable in Children With a Close Family History of Sudden Death

By Reuters Staff

August 12, 2019

NEW YORK (Reuters Health) - A new study provides "quantitative justification" for guidelines that recommend cardiac evaluation in close relatives of someone who dies suddenly at a young age, although findings of uncertain significance increase the challenge to clinical management, the researchers say.

After a young person dies suddenly, it's recommended that first-degree family members undergo clinical screening for occult cardiac disease, but the diagnostic yield from screening is not well-defined.

Dr. Gregory Webster from the Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, and colleagues took a look back at 419 individuals (median age, 9.8 years) who underwent a cardiac evaluation at their center for a family history of sudden death.

More than a quarter of them (27%) were diagnosed with a cardiac disease or had a clinical finding of uncertain significance. Ultimately, 9.3% of patients were diagnosed with a heritable cardiac disease and a nonheritable cardiac disease was found in another 5.5%.

"All of these patients required therapy and/or lifelong cardiac follow up," the researchers report.

Clinical findings of uncertain significance were found in 52 patients (12.4%), which primarily included electrical findings in 41 patients - including intraventricular conduction delay, prolonged repolarization, left ventricular hypertrophy by ECG, bradycardia, and arrhythmia - and imaging findings in 11 - including ventricular hypertrophy or dilation and pulmonary artery dilation.

Mild changes that were "variations of normal" were found in 25 patients (6%), while 280 (66.8%) had a normal phenotype.

Among patients diagnosed with a heritable cardiac disease, the nearest affected relative was almost always a first-degree relative (95%). "The strongest predictors for a successful diagnosis in the patient were an abnormal electrocardiogram and a first-degree relationship to the nearest affected relative (odds ratios: 24.2 and 18.8, respectively)," Dr. Webster and colleagues report.

The study, they add, shows that the yield of cardiac evaluation in children without an affected first-degree relative is "low and incidental findings are common. These data provide quantitative support for prioritizing the screening of the most closely-related family members."

Sudden cardiac death (SCD) accounts for nearly 450,000 deaths in the U.S. each year, note Dr. Michael Ackerman and Dr. John Giudiccessi from the Mayo Clinic, in Rochester, Minnesota, in a linked editorial.

The new study demonstrates that the utility of clinical screening for SCD-predisposing genetic heart disorder (GHD) is "highly dependent on degree of relatedness and brings to light, for the first time, the substantial burden of incidental findings and findings of uncertain significance (FUS) encountered when screening children with a family history of SCD," they write.

"Ultimately, well-powered longitudinal studies, hopefully with accompanying genetic testing, are needed to determine which FUS, if any, are indicative of concealed/pre-clinical SCD-predisposing GHDs in individuals with a family history of SCD," the authors write.

"While we await further guidance from the upcoming 2020 APHRS/HRS Expert Consensus Statement on the Investigation of Decedents and Patients with Sudden Cardiac Arrest and of Their Families, cardiovascular health providers are urged to resist the temptation of assigning unwarranted clinical significance to non-diagnostic findings observed in individuals (especially distant relatives) with a family history of SCD," Drs. Ackerman and Giudiccessi add.

"Just like genetic purgatory is filling up with both variants of uncertain significance (VUS) and now genes of uncertain significance, clinical purgatory is overflowing with FUS as elegantly shown here, and the emerging nightmare revolving around the over diagnosis of ventricular non-compaction. Keeping with the theme of temptation and purgatory, this is creating one hell of a situation," they conclude.


J Am Coll Cardiol 2019.