The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF

Abstract Background Women are prone to develop heart failure with preserved ejection fraction (HFpEF) and have a longer QT interval compared to men at comparable heart rates, which results in shorter electrical and mechanical diastole. We hypothesize that a shorter electrical diastole increases HFpE...

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Main Authors: A. M. L. N. van Ommen, L. R. Bear, C. Carlos Sampedrano, N. C. Onland-Moret, M. J. Cramer, F. H. Rutten, E. Dal Canto, I. I. Tulevski, G. A. Somsen, N. K. Sweitzer, R. Coronel, H. M. den Ruijter
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Language:English
Published: BMC 2025-05-01
Series:BMC Cardiovascular Disorders
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Online Access:https://doi.org/10.1186/s12872-025-04879-2
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author A. M. L. N. van Ommen
L. R. Bear
C. Carlos Sampedrano
N. C. Onland-Moret
M. J. Cramer
F. H. Rutten
E. Dal Canto
I. I. Tulevski
G. A. Somsen
N. K. Sweitzer
R. Coronel
H. M. den Ruijter
author_facet A. M. L. N. van Ommen
L. R. Bear
C. Carlos Sampedrano
N. C. Onland-Moret
M. J. Cramer
F. H. Rutten
E. Dal Canto
I. I. Tulevski
G. A. Somsen
N. K. Sweitzer
R. Coronel
H. M. den Ruijter
author_sort A. M. L. N. van Ommen
collection DOAJ
description Abstract Background Women are prone to develop heart failure with preserved ejection fraction (HFpEF) and have a longer QT interval compared to men at comparable heart rates, which results in shorter electrical and mechanical diastole. We hypothesize that a shorter electrical diastole increases HFpEF risk, independent of heart rate. Methods In 85,145 women and men visiting the Cardiology Centers of the Netherlands between 2007 and 2018, we calculated electrical diastolic intervals (TQ and TP) by subtracting the QT interval, or the sum of the QT- and PQ intervals, respectively, from the RR interval using 12-lead ECG recordings. Electrical diastolic intervals were compared between patients with prevalent left ventricular diastolic dysfunction (LVDD), HFpEF and controls. We validated the TQ interval’s association with diastolic function using right atrial pacing and sotalol infusion in a pig model (n = 6). Results TQ intervals were approximately 30 ms shorter in women than men. Patients with LVDD or HFpEF had shorter TQ intervals compared to controls (LVDD: 479 ± 128ms, HFpEF: 485 ± 138ms and controls: 523 ± 137ms). Shorter TQ intervals increased the risk of prevalent LVDD/HFpEF (per SD decrease in TQ: OR = 1.37, 95%CI: 1.28, 1.45 and 1.16, 95%CI: 1.01, 1.35, respectively) in fully adjusted models in both sexes. After a median follow-up of 8 [IQR = 6–10] years, shorter TQ intervals were associated with a significant higher risk of death (HR = 1.13, 95%CI:1.02, 1.25) in patients with LVDD and HFpEF. In the subgroup with “delayed relaxation”, beta-blocker use was associated with a significantly lower risk of death, which was not observed in those with “stiff” ventricles showing pseudonormalization or restrictive inflow patterns. Findings were independent of heart rate, and not exclusive to women. In pigs, paced at 100 bpm, sotalol infusion decreased the TQ interval, and TQ shortening was correlated to decreasing e’/a’ ratio (r = 0.371, p = 0.018) and E/A ratio (r = 0.337, p = 0.030). Conclusion A short electrical diastole is associated with a higher risk of prevalent LVDD and HFpEF in both women and men at cardiovascular risk, independent of heart rate. Experimental shortening of the electrical diastole induced functional diastolic abnormalities in pigs. This overlooked mechanism of electrical diastolic shortening may contribute to the complex HFpEF syndrome, with beta-blockers potentially benefiting selected groups. Clinical trial number Not applicable.
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spelling doaj-art-4b21e262475c451d901bc36366100c8f2025-08-20T02:39:03ZengBMCBMC Cardiovascular Disorders1471-22612025-05-0125111510.1186/s12872-025-04879-2The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEFA. M. L. N. van Ommen0L. R. Bear1C. Carlos Sampedrano2N. C. Onland-Moret3M. J. Cramer4F. H. Rutten5E. Dal Canto6I. I. Tulevski7G. A. Somsen8N. K. Sweitzer9R. Coronel10H. M. den Ruijter11Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht UniversityUniv. Bordeaux, INSERM, CRCTB, IHU LirycUniv. Bordeaux, INSERM, CRCTB, IHU LirycDepartment of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityDepartment of Cardiology, University Medical Center UtrechtDepartment of General Practice & Nursing Science, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht UniversityLaboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht UniversityCardiology Centers of the NetherlandsCardiology Centers of the NetherlandsDepartment of Experimental Cardiology, Amsterdam University Medical Centers, Location AMCDivision of Cardiovascular Medicine, Washington University in St. LouisLaboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht UniversityAbstract Background Women are prone to develop heart failure with preserved ejection fraction (HFpEF) and have a longer QT interval compared to men at comparable heart rates, which results in shorter electrical and mechanical diastole. We hypothesize that a shorter electrical diastole increases HFpEF risk, independent of heart rate. Methods In 85,145 women and men visiting the Cardiology Centers of the Netherlands between 2007 and 2018, we calculated electrical diastolic intervals (TQ and TP) by subtracting the QT interval, or the sum of the QT- and PQ intervals, respectively, from the RR interval using 12-lead ECG recordings. Electrical diastolic intervals were compared between patients with prevalent left ventricular diastolic dysfunction (LVDD), HFpEF and controls. We validated the TQ interval’s association with diastolic function using right atrial pacing and sotalol infusion in a pig model (n = 6). Results TQ intervals were approximately 30 ms shorter in women than men. Patients with LVDD or HFpEF had shorter TQ intervals compared to controls (LVDD: 479 ± 128ms, HFpEF: 485 ± 138ms and controls: 523 ± 137ms). Shorter TQ intervals increased the risk of prevalent LVDD/HFpEF (per SD decrease in TQ: OR = 1.37, 95%CI: 1.28, 1.45 and 1.16, 95%CI: 1.01, 1.35, respectively) in fully adjusted models in both sexes. After a median follow-up of 8 [IQR = 6–10] years, shorter TQ intervals were associated with a significant higher risk of death (HR = 1.13, 95%CI:1.02, 1.25) in patients with LVDD and HFpEF. In the subgroup with “delayed relaxation”, beta-blocker use was associated with a significantly lower risk of death, which was not observed in those with “stiff” ventricles showing pseudonormalization or restrictive inflow patterns. Findings were independent of heart rate, and not exclusive to women. In pigs, paced at 100 bpm, sotalol infusion decreased the TQ interval, and TQ shortening was correlated to decreasing e’/a’ ratio (r = 0.371, p = 0.018) and E/A ratio (r = 0.337, p = 0.030). Conclusion A short electrical diastole is associated with a higher risk of prevalent LVDD and HFpEF in both women and men at cardiovascular risk, independent of heart rate. Experimental shortening of the electrical diastole induced functional diastolic abnormalities in pigs. This overlooked mechanism of electrical diastolic shortening may contribute to the complex HFpEF syndrome, with beta-blockers potentially benefiting selected groups. Clinical trial number Not applicable.https://doi.org/10.1186/s12872-025-04879-2Heart failure with preserved ejection fractionLeft ventricular diastolic dysfunctionAbnormal myocardial relaxationSex-differencesDiastolic timeAnimal study
spellingShingle A. M. L. N. van Ommen
L. R. Bear
C. Carlos Sampedrano
N. C. Onland-Moret
M. J. Cramer
F. H. Rutten
E. Dal Canto
I. I. Tulevski
G. A. Somsen
N. K. Sweitzer
R. Coronel
H. M. den Ruijter
The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF
BMC Cardiovascular Disorders
Heart failure with preserved ejection fraction
Left ventricular diastolic dysfunction
Abnormal myocardial relaxation
Sex-differences
Diastolic time
Animal study
title The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF
title_full The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF
title_fullStr The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF
title_full_unstemmed The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF
title_short The contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and HFpEF
title_sort contribution of a short electrocardiographic diastolic interval to diastolic dysfunction and hfpef
topic Heart failure with preserved ejection fraction
Left ventricular diastolic dysfunction
Abnormal myocardial relaxation
Sex-differences
Diastolic time
Animal study
url https://doi.org/10.1186/s12872-025-04879-2
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