Comorbidities Can Make Long-QT Syndrome a Package Deal

November 12, 2019

People with congenital long-QT syndrome (LQTS) are more likely than the general population to also have diabetes or neurologic or psychiatric disorders along with an increased risk for atrial fibrillation (AF) and myocardial infarction (MI), suggests a nationwide matched cohort study from Denmark.

The findings, published October 28 in Open Heart, "support the multimorbid nature of LQTS," which is likely driven by a shared genetic predisposition; LQTS is associated with ion-channel conduction abnormalities linked to several gene polymorphisms.

The excess of diabetes in people with LQTS was accompanied by the novel finding of a higher rate of prescriptions for antidiabetic drugs, note the authors, led by Peter Marstrand, MD, of the University Hospital of Copenhagen.

Epilepsy accounted for much of the neurologic association with LQTS, but among the related psychiatric disorders, there was no one diagnosis that seemed to predominate.

LQTS is well known to be associated with AF and malignant ventricular arrhythmias, but the observed link with MI is more novel. Why LQTS and MI are associated "remains uncertain, but it may be hypothesized that the increased prevalence of diabetes among patients with LQTS may contribute to an increased risk of myocardial infarction," the authors write.

"LQTS is a multiorgan disease with a complex phenotype. Clinicians treating LQTS patients should be aware of the increased risk of diabetes, AF, and neurological disorders to be able to detect and start relevant treatment earlier," Marstrand told | Medscape Cardiology.

Also, "patients should be informed of the symptoms and signs of these comorbidities associated with LQTS, so they will be able to react earlier to new symptoms and seek medical attention."

The group looked at 463 patients with a new diagnosis of congenital LQTS in nationwide registries, including the Danish National Prescription Registry and Danish National Patient Register. They were age- and sex-matched with 2315 control subjects from the Danish National Population Register. The mean age was about 35 years and 38% were male in both groups.

Mortality over a mean follow-up of about 4.3 years was 4.2% in the LQTS group and 3.6% for the matched control group (P = .49).

Patients with LQTS showed greater rates of AF, MI, and diabetes but no significant differences in venous thromboembolism or peripheral vascular disease.

Prevalence of Cardiac and Metabolic Comorbidities in LQTS, General Population Matched Pairs
Comorbidity LQTS Group, % (n = 463) Control Group, % (n = 2315) P Value
Atrial fibrillation 6.5 2.3 <.001
Acute MI 3.0 1.5 .019
Diabetes 3.7 1.8 .011

Patients with LQTS also showed an increased rate of psychiatric disorders overall (13.0% vs 9.1% for control group; P = .010).

"The difference could not be attributed to a specific psychiatric disease subgroup, such as organic mental disorders, mental disorders due to substance use, affective disorders, or anxiety," the group writes.

They also showed a greater overall prevalence of neurologic disorders, driven by a higher rate of episodic and paroxysmal disorders, especially epilepsy, and of nerve and plexus disorders, including hearing loss.

Prevalence of Neurologic Comorbidities in LQTS, General Population Matched Pairs
Comorbidity LQTS Group, % (n = 463) Control Group, % (n = 2315) P Value
Neurologic overall 22.0 12.3 <.001
Episodic, paroxysmal 13.6 6.3 <.001
Epilepsy 6.7 1.6 <.001
Nerve and plexus disorders 6.5 4.2 .031
Hearing loss 3.2 1.7 .027

The analysis was based on registries, so it included only "cases that physicians have reported through normal care," Marstrand observed.

"We can speculate that with screening, we would find even more cases of the comorbidities, especially in relatives of patients with a multimorbid phenotype. We encourage physicians to be aware of the multimorbid nature of LQTS when obtaining medical history and blood testing."

Marstrand and the other authors report no competing interests.

Open Heart. Published online October 28, 2019. Full text

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