Genetic and Phenotypic Characterization of Community Hospital Patients With QT Prolongation

Abstract

BackgroundCongenital long‐QT syndrome (LQTS) is a genetic disorder characterized by prolongation of the corrected QT interval (QTc) on an ECG. The aim of the present study was to estimate the prevalence of pathogenic and likely pathogenic sequence variants in patients who had at least 1 ECG with a QTc ≥500 ms.Methods and ResultsTelemark Hospital Trust is a community hospital within the Norwegian national health system, serving ≈173 000 inhabitants. We searched the ECG database at Telemark Hospital Trust, Norway, from January 2004 to December 2014, and identified 1531 patients with at least 1 ECG with a QTc ≥500 ms. At the time of inclusion in this study (2015), 766 patients were alive. A total of 733 patients were invited to participate, and 475 accepted. The 17 genes that have been reported to cause monogenic LQTS were sequenced among the patients. Pro‐QTc score was calculated for each patient. A molecular genetic cause of LQTS was detected in 31 (6.5%) of 475 patients. These patients had a lower pro‐QTc score than those without pathogenic or likely pathogenic variants (1.7±1.0 versus 2.8±1.6; P<0.001).ConclusionsCompared with the general population, hospitalized patients with a QTc ≥500 ms in at least 1 ECG recording had an increased likelihood for pathogenic and likely pathogenic variants in LQTS genes. We recommend increased awareness of the possibility of LQTS in patients with at least 1 ECG with a QTc ≥500 ms.

QT prolongation predicts short-term mortality independent of comorbidity

“…Assuming that our findings are representative for patients admitted to Norwegian hospitals, one would expect that among 100 patients with an ECG taken, two to three will have prolonged QTc ≥500 ms 4 , 8 . A prolonged QTc is often missed or even ignored 4 .…”

“…Only a small minority of the patients in our study had arrhythmia as registered cause of death, but the vast majority of patients did not have their heart rhythm monitored at the time of death. Furthermore, the patients were admitted according to their main clinical condition to relevant community hospital wards having low awareness of QT prolongation 4 , 8 . Thus, the occurrence of life-threatening arrhythmias may have been underestimated in our population.…”

“…After the manual review of the ECGs, a total of 1531 patients with at least one ECG with QTc ≥500 ms were identified in the ECG database. The patients with QTc ≥500 ms have been described previously 4 , 8 …”

“…This reserve is a product of the interaction between different risk factors, including genetic predisposition 6 , 7 . Several QT prolonging risk factors are identifiable and reversible, including transient QT prolongation during acute non-cardiac illness 8 , 9 …”

ERG1 plays an essential role in rat cardiomyocyte fate decision by mediating AKT signaling

“…Kcnh2 is the typical pathogenic gene involves in LQT syndrome which is associated with sudden cardiac death and high risk of torsade de pointes ventricular tachycardia. 35 Kcnh2 N629D/N629D mouse has been reported to induce embryonic lethality with developmental defects in the outflow tract and right ventricle. 6 Here, we further elucidated that ERG1 could interact with Integrin β1, FAK, and PI3K to maintain both AKT/GSK3β/β-catenin and AKT/IKKβ/NF-κB axis to induce specific cardiac lineage commitment with inhibition of cell apoptosis during differentiation.…”