Cardiac Outcomes in Adults With Mitochondrial Diseases

Konstantinos Savvatis; Christoffer Rasmus Vissing; Lori Klouvi; Anca Florian; Mehjabin Rahman; Anthony Béhin; Abdallah Fayssoil; Marion Masingue; Tanya Stojkovic; Henri Marc Bécane; Nawal Berber; Fanny Mochel; Denis Duboc; Bertrand Fontaine; Bjørg Krett; Caroline Stalens; Julie Lejeune; Robert D S Pitceathly; Luis Lopes; Malika Saadi; Thomas Gossios; Vincent Procaccio; Marco Spinazzi; Céline Tard; Pascal De Groote; Claire-Marie Dhaenens; Claire Douillard; Andoni Echaniz-Laguna; Ros Quinlivan; Michael G Hanna; Ali Yilmaz; John Vissing; Pascal Laforêt; Perry Elliott; Karim Wahbi

doi:10.1016/j.jacc.2022.08.716

Cardiac Outcomes in Adults With Mitochondrial Diseases

Konstantinos Savvatis, Christoffer Rasmus Vissing, Lori Klouvi, Anca Florian, Mehjabin Rahman, Anthony Béhin, Abdallah Fayssoil, Marion Masingue, Tanya Stojkovic, Henri Marc Bécane, Nawal Berber, Fanny Mochel, Denis Duboc, Bertrand Fontaine, Bjørg Krett, Caroline Stalens, Julie Lejeune, Robert D S Pitceathly, Luis Lopes, Malika SaadiThomas Gossios, Vincent Procaccio, Marco Spinazzi, Céline Tard, Pascal De Groote, Claire-Marie Dhaenens, Claire Douillard, Andoni Echaniz-Laguna, Ros Quinlivan, Michael G Hanna, Ali Yilmaz, John Vissing, Pascal Laforêt, Perry Elliott, Karim Wahbi^*

^*Corresponding author for this work

Abstract

BACKGROUND: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE).

OBJECTIVES: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population.

METHODS: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases.

RESULTS: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively.

CONCLUSIONS: We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.

Original language	English
Journal	Journal of the American College of Cardiology
Volume	80
Issue number	15
Pages (from-to)	1421-1430
Number of pages	10
ISSN	0735-1097
DOIs	https://doi.org/10.1016/j.jacc.2022.08.716
Publication status	Published - 11 Oct 2022

Keywords

Adult
DNA, Mitochondrial/genetics
Heart
Heart Failure/epidemiology
Humans
Hypertrophy, Left Ventricular
Mitochondrial Diseases/complications
Prognosis
Risk Factors
Stroke Volume
Ventricular Function, Left

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10.1016/j.jacc.2022.08.716

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Savvatis, K., Vissing, C. R., Klouvi, L., Florian, A., Rahman, M., Béhin, A., Fayssoil, A., Masingue, M., Stojkovic, T., Bécane, H. M., Berber, N., Mochel, F., Duboc, D., Fontaine, B., Krett, B., Stalens, C., Lejeune, J., Pitceathly, R. D. S., Lopes, L., ... Wahbi, K. (2022). Cardiac Outcomes in Adults With Mitochondrial Diseases. Journal of the American College of Cardiology, 80(15), 1421-1430. https://doi.org/10.1016/j.jacc.2022.08.716

Savvatis, K, Vissing, CR, Klouvi, L, Florian, A, Rahman, M, Béhin, A, Fayssoil, A, Masingue, M, Stojkovic, T, Bécane, HM, Berber, N, Mochel, F, Duboc, D, Fontaine, B, Krett, B, Stalens, C, Lejeune, J, Pitceathly, RDS, Lopes, L, Saadi, M, Gossios, T, Procaccio, V, Spinazzi, M, Tard, C, De Groote, P, Dhaenens, C-M, Douillard, C, Echaniz-Laguna, A, Quinlivan, R, Hanna, MG, Yilmaz, A, Vissing, J, Laforêt, P, Elliott, P & Wahbi, K 2022, 'Cardiac Outcomes in Adults With Mitochondrial Diseases', Journal of the American College of Cardiology, vol. 80, no. 15, pp. 1421-1430. https://doi.org/10.1016/j.jacc.2022.08.716

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title = "Cardiac Outcomes in Adults With Mitochondrial Diseases",

abstract = "BACKGROUND: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE).OBJECTIVES: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population.METHODS: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases.RESULTS: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively.CONCLUSIONS: We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.",

keywords = "Adult, DNA, Mitochondrial/genetics, Heart, Heart Failure/epidemiology, Humans, Hypertrophy, Left Ventricular, Mitochondrial Diseases/complications, Prognosis, Risk Factors, Stroke Volume, Ventricular Function, Left",

author = "Konstantinos Savvatis and Vissing, {Christoffer Rasmus} and Lori Klouvi and Anca Florian and Mehjabin Rahman and Anthony B{\'e}hin and Abdallah Fayssoil and Marion Masingue and Tanya Stojkovic and B{\'e}cane, {Henri Marc} and Nawal Berber and Fanny Mochel and Denis Duboc and Bertrand Fontaine and Bj{\o}rg Krett and Caroline Stalens and Julie Lejeune and Pitceathly, {Robert D S} and Luis Lopes and Malika Saadi and Thomas Gossios and Vincent Procaccio and Marco Spinazzi and C{\'e}line Tard and {De Groote}, Pascal and Claire-Marie Dhaenens and Claire Douillard and Andoni Echaniz-Laguna and Ros Quinlivan and Hanna, {Michael G} and Ali Yilmaz and John Vissing and Pascal Lafor{\^e}t and Perry Elliott and Karim Wahbi",

year = "2022",

month = oct,

day = "11",

doi = "10.1016/j.jacc.2022.08.716",

language = "English",

volume = "80",

pages = "1421--1430",

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

issn = "0735-1097",

publisher = "Elsevier Inc",

number = "15",

}

TY - JOUR

T1 - Cardiac Outcomes in Adults With Mitochondrial Diseases

AU - Savvatis, Konstantinos

AU - Vissing, Christoffer Rasmus

AU - Klouvi, Lori

AU - Florian, Anca

AU - Rahman, Mehjabin

AU - Béhin, Anthony

AU - Fayssoil, Abdallah

AU - Masingue, Marion

AU - Stojkovic, Tanya

AU - Bécane, Henri Marc

AU - Berber, Nawal

AU - Mochel, Fanny

AU - Duboc, Denis

AU - Fontaine, Bertrand

AU - Krett, Bjørg

AU - Stalens, Caroline

AU - Lejeune, Julie

AU - Pitceathly, Robert D S

AU - Lopes, Luis

AU - Saadi, Malika

AU - Gossios, Thomas

AU - Procaccio, Vincent

AU - Spinazzi, Marco

AU - Tard, Céline

AU - De Groote, Pascal

AU - Dhaenens, Claire-Marie

AU - Douillard, Claire

AU - Echaniz-Laguna, Andoni

AU - Quinlivan, Ros

AU - Hanna, Michael G

AU - Yilmaz, Ali

AU - Vissing, John

AU - Laforêt, Pascal

AU - Elliott, Perry

AU - Wahbi, Karim

PY - 2022/10/11

Y1 - 2022/10/11

N2 - BACKGROUND: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE).OBJECTIVES: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population.METHODS: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases.RESULTS: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively.CONCLUSIONS: We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.

AB - BACKGROUND: Patients with mitochondrial diseases are at risk of heart failure (HF) and arrhythmic major adverse cardiac events (MACE).OBJECTIVES: We developed prediction models to estimate the risk of HF and arrhythmic MACE in this population.METHODS: We determined the incidence and searched for predictors of HF and arrhythmic MACE using Cox regression in 600 adult patients from a multicenter registry with genetically confirmed mitochondrial diseases.RESULTS: Over a median follow-up time of 6.67 years, 29 patients (4.9%) reached the HF endpoint, including 19 hospitalizations for nonterminal HF, 2 cardiac transplantations, and 8 deaths from HF. Thirty others (5.1%) reached the arrhythmic MACE, including 21 with third-degree or type II second-degree atrioventricular blocks, 4 with sinus node dysfunction, and 5 sudden cardiac deaths. Predictors of HF were the m.3243A>G variant (HR: 4.3; 95% CI: 1.8-10.1), conduction defects (HR: 3.0; 95% CI: 1.3-6.9), left ventricular (LV) hypertrophy (HR: 2.6; 95% CI: 1.1-5.8), LV ejection fraction <50% (HR: 10.2; 95% CI: 4.6-22.3), and premature ventricular beats (HR: 4.1; 95% CI: 1.7-9.9). Independent predictors for arrhythmia were single, large-scale mtDNA deletions (HR: 4.3; 95% CI: 1.7-10.4), conduction defects (HR: 6.8; 95% CI: 3.0-15.4), and LV ejection fraction <50% (HR: 2.7; 95% CI: 1.1-7.1). C-indexes of the Cox regression models were 0.91 (95% CI: 0.88-0.95) and 0.80 (95% CI: 0.70-0.90) for the HF and arrhythmic MACE, respectively.CONCLUSIONS: We developed the first prediction models for HF and arrhythmic MACE in patients with mitochondrial diseases using genetic variant type and simple cardiac assessments.

KW - Adult

KW - DNA, Mitochondrial/genetics

KW - Heart

KW - Heart Failure/epidemiology

KW - Humans

KW - Hypertrophy, Left Ventricular

KW - Mitochondrial Diseases/complications

KW - Prognosis

KW - Risk Factors

KW - Stroke Volume

KW - Ventricular Function, Left

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U2 - 10.1016/j.jacc.2022.08.716

DO - 10.1016/j.jacc.2022.08.716

M3 - Journal article

C2 - 36202532

SN - 0735-1097

VL - 80

SP - 1421

EP - 1430

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 15

ER -

Cardiac Outcomes in Adults With Mitochondrial Diseases

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