Long-QT Syndrome Overdiagnosed, Overtreated in Cohort Study

Veronica Hackethal, MD

January 12, 2016

ROCHESTER, MN — A significant number of patients given implantable cardioverter defibrillators (ICDs) for long-QT syndrome (LQTS) receive them for reasons outside of current guidelines, and many patients are misdiagnosed with LQTS in the first place, according to a large case series published December 8, 2015 in Heart Rhythm[1].

"In this present study, not only are patients continuing to be overdiagnosed, but among those patients correctly diagnosed with LQTS, there appears to be a premature rush to an ICD," write the authors, led by Dr Michael Ackerman (Mayo Clinic, Rochester, MN).

QT-interval prolongation can result from medications, electrolyte abnormalities, and other noncongenital conditions; true congenital LQTS is fairly rare, they write. "Difficulties in making the LQTS diagnosis accompanied by the possible dire outcomes of a missed diagnosis sometimes lead to overdiagnosis of the disease and possibly overaggressive treatment, including overzealous implantation of an ICD."

Their cohort consisted of 1227 patients referred to their center for "borderline or definite QT prolongation and suspicion of LQTS." An LQTS diagnosis was made by retrospective review in 670; the remaining 557 (45.4%) were declared not to have LQTS. Of the 170 patients (14% of the entire cohort) who were given an ICD, 157 were in the LQTS group and 13 were in the non-LQTS group. Most of the latter 13 patients "had no specific indication for an ICD," according to the group.

In an editorial published online December 24, 2015 in the same journal[2], Dr Charles I Berul (George Washington University, Washington, DC) noted the "remarkable" number of patients misdiagnosed with LQTS, the "alarming" number of patients with serious adverse events related to implanted ICDs, and the "shockingly high" number of patients who needed ICD removal. The findings, he continued, emphasize the need for reeducation of physicians about the need for implanting ICDs.

While no gold standard exists for diagnosing LQTS and current diagnostic tests have limitations, doctors can use "very good" clinical guidelines, genetic testing, detailed clinical history, family history, and diagnostic tests like catecholamine challenge, he proposed.

Ultimately, though, "the diagnosis should be made by someone familiar with LQTS, as it can be confused with simply having a long QT interval without actually having the syndrome," Berul told heartwire from Medscape. "An individual with syncope and a slightly prolonged QT interval should not automatically be diagnosed with LQTS until complete evaluation is performed."

In the current series, the authors assessed misdiagnosis of LQTS by reviewing patients' clinical notes, including ECGs, family history, and genetic data. They also used the most recent guidelines to evaluate overtreatment with ICD implantation, and reviewed details of ICD removal.

Only 34 patients with confirmed LQTS who were given ICDs (22%) had class I indications for such a device. Of the 13 non-LQTS patients given ICDs, nine had no specific ICD indication. Twelve patients (1% of the total cohort) went on to ICD removal; of those, seven had LQTS and five had been misdiagnosed. Over 5.5 years of follow-up, no patients who had their ICDs removed experienced breakthrough cardiac events.

The authors noted that patients with ICD problems may be more likely to seek a second opinion at the Mayo Clinic, a tertiary referral center. If so, the results may have overestimated the true nature of this problem. Nevertheless, they concluded, their findings "demonstrate the gravity of the complications caused by ICD overtreatment and mandate improved physician understanding of what phenotype warrants a LQTS diagnosis and, when appropriately diagnosed, what compels an ICD recommendation."

They emphasized stepwise treatment of LQTS, with a sufficient trial of beta-blockers and left cardiac sympathetic denervation (LCSD) when indicated before rushing to implantation of an ICD, whose placement should occur as the last resort.

According to Berul when interviewed, a correct diagnosis of LQTS in youth is particularly important; complicating the diagnosis, symptoms can masquerade as other inherited arrhythmias or benign conditions like fainting with transient QT-interval prolongation.

"ICD implantation in young patients carries a lifetime of risk, and the decision to implant must be seriously weighed before jumping to the ICD as a safety net," he emphasized. Doctors should carefully weigh the risks and benefits of removal vs simple deactivation of inappropriately placed devices, he added.

Ackerman declares being a consultant to Boston Scientific, Gilead Sciences, Medtronic, and St Jude Medical and receiving royalties from Transgenomics; disclosures for the coauthors are listed in the article. Berul reports grant support from Medtronic.


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