Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis

Abstract Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy c...

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Main Authors: Pia Dahlberg, Karl‐Jonas Axelsson, Steen M. Jensen, Gunilla Lundahl, Farzad Vahedi, Rosie Perkins, Lennart Gransberg, Lennart Bergfeldt
Format: Article
Language:English
Published: Wiley 2022-11-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.15487
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author Pia Dahlberg
Karl‐Jonas Axelsson
Steen M. Jensen
Gunilla Lundahl
Farzad Vahedi
Rosie Perkins
Lennart Gransberg
Lennart Bergfeldt
author_facet Pia Dahlberg
Karl‐Jonas Axelsson
Steen M. Jensen
Gunilla Lundahl
Farzad Vahedi
Rosie Perkins
Lennart Gransberg
Lennart Bergfeldt
author_sort Pia Dahlberg
collection DOAJ
description Abstract Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss‐of‐function mutations affecting the repolarizing potassium channel current IKs, presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine‐induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p < 0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono‐exponential function and the time for 90% of ΔQT; p < 0.01); however, there was some overlap between the groups, possibly a beta‐blocker effect. The shorter QT adaptation time to atropine‐induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra‐rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect‐size of the loss‐of‐function mutation, but its clinical implications need to be shown.
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spelling doaj.art-ccf39a68611240a59f0e0f44718e6b0b2022-12-22T02:52:26ZengWileyPhysiological Reports2051-817X2022-11-011021n/an/a10.14814/phy2.15487Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresisPia Dahlberg0Karl‐Jonas Axelsson1Steen M. Jensen2Gunilla Lundahl3Farzad Vahedi4Rosie Perkins5Lennart Gransberg6Lennart Bergfeldt7Department of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenDepartment of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenDepartment of Public Health and Clinical Medicine, and Heart Centre Umeå University Umeå SwedenDepartment of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenDepartment of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenDepartment of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenDepartment of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenDepartment of Molecular and Clinical Medicine Institute of Medicine, Sahlgrenska Academy, University of Gothenburg Gothenburg SwedenAbstract Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss‐of‐function mutations affecting the repolarizing potassium channel current IKs, presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine‐induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p < 0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono‐exponential function and the time for 90% of ΔQT; p < 0.01); however, there was some overlap between the groups, possibly a beta‐blocker effect. The shorter QT adaptation time to atropine‐induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra‐rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect‐size of the loss‐of‐function mutation, but its clinical implications need to be shown.https://doi.org/10.14814/phy2.15487atropinecardiac memoryhysteresislong QT syndromeQT adaptation
spellingShingle Pia Dahlberg
Karl‐Jonas Axelsson
Steen M. Jensen
Gunilla Lundahl
Farzad Vahedi
Rosie Perkins
Lennart Gransberg
Lennart Bergfeldt
Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis
Physiological Reports
atropine
cardiac memory
hysteresis
long QT syndrome
QT adaptation
title Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis
title_full Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis
title_fullStr Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis
title_full_unstemmed Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis
title_short Accelerated QT adaptation following atropine‐induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis
title_sort accelerated qt adaptation following atropine induced heart rate increase in lqt1 patients versus healthy controls a sign of disturbed hysteresis
topic atropine
cardiac memory
hysteresis
long QT syndrome
QT adaptation
url https://doi.org/10.14814/phy2.15487
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