Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

Feddo P. Kirkels; Nick van Osta; Christine Rootwelt-Norberg; Monica Chivulescu; Tim van Loon; Eivind W. Aabel; Anna I. Castrini; Øyvind H. Lie; Folkert W. Asselbergs; Tammo Delhaas; Maarten J. Cramer; Arco J. Teske; Kristina H. Haugaa; Joost Lumens

doi:10.1016/j.jacc.2023.05.065

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

Feddo P. Kirkels^*, Nick van Osta, Christine Rootwelt-Norberg, Monica Chivulescu, Tim van Loon, Eivind W. Aabel, Anna I. Castrini, Øyvind H. Lie, Folkert W. Asselbergs, Tammo Delhaas, Maarten J. Cramer, Arco J. Teske, Kristina H. Haugaa, Joost Lumens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. Objectives: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. Methods: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and =50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. Results: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. Conclusions: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.

Original language	English
Pages (from-to)	785-797
Number of pages	13
Journal	Journal of the American College of Cardiology
Volume	82
Issue number	9
DOIs	https://doi.org/10.1016/j.jacc.2023.05.065
Publication status	Published - 29 Aug 2023

Keywords

arrhythmogenic cardiomyopathy
ARVC
deformation imaging
Digital Twin
early detection
family screening

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Kirkels, F. P., van Osta, N., Rootwelt-Norberg, C., Chivulescu, M., van Loon, T., Aabel, E. W., Castrini, A. I., Lie, Ø. H., Asselbergs, F. W., Delhaas, T., Cramer, M. J., Teske, A. J., Haugaa, K. H., & Lumens, J. (2023). Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum. Journal of the American College of Cardiology, 82(9), 785-797. https://doi.org/10.1016/j.jacc.2023.05.065

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title = "Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum",

abstract = "Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. Objectives: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. Methods: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and =50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. Results: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. Conclusions: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.",

keywords = "arrhythmogenic cardiomyopathy, ARVC, deformation imaging, Digital Twin, early detection, family screening",

author = "Kirkels, {Feddo P.} and {van Osta}, Nick and Christine Rootwelt-Norberg and Monica Chivulescu and {van Loon}, Tim and Aabel, {Eivind W.} and Castrini, {Anna I.} and Lie, {{\O}yvind H.} and Asselbergs, {Folkert W.} and Tammo Delhaas and Cramer, {Maarten J.} and Teske, {Arco J.} and Haugaa, {Kristina H.} and Joost Lumens",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

day = "29",

doi = "10.1016/j.jacc.2023.05.065",

language = "English",

volume = "82",

pages = "785--797",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Science",

number = "9",

}

Kirkels, FP, van Osta, N, Rootwelt-Norberg, C, Chivulescu, M, van Loon, T, Aabel, EW, Castrini, AI, Lie, ØH, Asselbergs, FW, Delhaas, T, Cramer, MJ, Teske, AJ, Haugaa, KH & Lumens, J 2023, 'Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum', Journal of the American College of Cardiology, vol. 82, no. 9, pp. 785-797. https://doi.org/10.1016/j.jacc.2023.05.065

TY - JOUR

T1 - Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

AU - Kirkels, Feddo P.

AU - van Osta, Nick

AU - Rootwelt-Norberg, Christine

AU - Chivulescu, Monica

AU - van Loon, Tim

AU - Aabel, Eivind W.

AU - Castrini, Anna I.

AU - Lie, Øyvind H.

AU - Asselbergs, Folkert W.

AU - Delhaas, Tammo

AU - Cramer, Maarten J.

AU - Teske, Arco J.

AU - Haugaa, Kristina H.

AU - Lumens, Joost

PY - 2023/8/29

Y1 - 2023/8/29

N2 - Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. Objectives: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. Methods: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and =50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. Results: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. Conclusions: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.

AB - Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. Objectives: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. Methods: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age <30 years, 30 to 50 years, and =50 years. Longitudinal biventricular deformation characteristics were used to monitor disease progression. To link deformation abnormalities to underlying myocardial disease substrates, Digital Twins were created using an imaging-based computational modeling framework. Results: We included 313 echocardiographic assessments from 82 subjects (57% female, age 39 ± 17 years, 10% probands) during 6.7 ± 3.3 years of follow-up. Left ventricular global longitudinal strain slightly deteriorated similarly in all age groups (0.1%-point per year [95% CI: 0.05-0.15]). Disease progression in all age groups was more pronounced in the right ventricular lateral wall, expressed by worsening in longitudinal strain (0.6%-point per year [95% CI: 0.46-0.70]) and local differences in myocardial contractility, compliance, and activation delay in the Digital Twin. Six patients experienced VA during follow-up. Conclusions: Disease progression was similar in all age groups, and sustained VA also occurred in patients aged >50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age.

KW - arrhythmogenic cardiomyopathy

KW - ARVC

KW - deformation imaging

KW - Digital Twin

KW - early detection

KW - family screening

U2 - 10.1016/j.jacc.2023.05.065

DO - 10.1016/j.jacc.2023.05.065

M3 - Article

C2 - 37612010

SN - 0735-1097

VL - 82

SP - 785

EP - 797

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 9

ER -