Nationwide insights into QTc prolongation, demographic disparities, and cardiovascular risk factors in Denmark

The QT interval is a key electrocardiographic parameter that reflects ventricular repolarization with adapting properties to internal and external stimulation. Genetic mutations, electrolyte disturbances, and various medications all contribute to this prolongation. Prolongation of the corrected QT (QTc) is linked to higher risks of arrhythmias and sudden cardiac death. Despite its clinical importance, the prevalence and determinants of QTc prolongation remain inadequately characterized.

To study the QTc interval distribution among the Danish population and identify key socioeconomic, demographic, and clinical factors associated with prolonged QTc.

We utilized the Danish Nationwide ECG Cohort to find patients with sinus rhythm electrocardiograms (ECGs) performed in a hospital setting. The study group was defined as patients with prolonged QTc and compared to the control group with normal QTc. Data were stratified by sex and age.

The inclusion criteria were age between 18 and 100 years and did not have any of the following ECG characteristics: 1) atrioventricular block type 2-3 or atrioventricular dissociation, 2) complete or incomplete branch bundle block (left or right), fascicular block, or retrograde conduction, 3) ventricular tachycardia, aberrant conduction, preexcitation, or significant ST elevation, and 4) did not have a registered socioeconomic status. We calculated QTc using Fredericia's formula for heart rate <60 and >60, Bazett's for 60-90 bpm.

We included 2,000,249 patients with sinus rhythm ECGs, of those 10% had a prolonged QTc interval. Patients with prolonged QTc were on average older (median age 64 vs. 56 years) and predominantly male (13% female compared to 49% in the normal QTc group). They exhibited higher median heart rates (77 vs 71 bpm) and more frequently ECG abnormalities—such as left ventricular hypertrophy. Moreover, they had higher prevalence of comorbidities such as hypertension, stroke, atrial fibrillation, and type 2 diabetes. They were also more frequently on cardiac medications (e.g., acetylsalicylic acid and betablockers). Of note, only 0.9% of the prolonged QTc group were on amiodarone.

In the total population, men had on average longer QTc distributions compared to women (Figure 1). Furthermore, we found a progressively increasing QTc interval with age with a steady slope (Figure 2). Socioeconomically, the prolonged QTc group had lower income and lower education levels. They were also slightly more likely to be living in rural areas in Denmark.

Prolonged QTc was identified in 10% of a nationwide cohort. Patients with prolonged QTc were generally older, predominantly male, had more comorbidities, lower socioeconomic status, and more frequently ECG abnormalities compared to those with normal QTc. The observed trends of higher median QTc in males and increasing QTc with advancing age emphasize the need for age- and gender-specific reference ranges.