Alterations in myocardial function and electrocardiology in hypertrophic cardiomyopathy

Mikko Jalanko

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy with a highly variable phenotype. The assessment of arrhythmogenic potential in HCM patients and identification of early signs of the disease in relatives of HCM patients is challenging. The aim of this thesis was to characterize the mechanical and electrical changes in the left ventricle of carriers of either the MYBPC3-Q1061X or TPM1-D175N mutation for hypertrophic cardiomyopathy and to identify novel imaging and electrocardiographic parameters with the potential to enhance sudden cardiac death risk stratification and follow-up. A total of 140 subjects carrying a pathogenic variant for HCM were recruited for these studies from three centers in Finland, divided into two groups: those with left ventricular hypertrophy (G+/LVH+ n = 98) and those without hypertrophy (G+/LVH- n = 42). We studied the association of ventricular arrhythmias on 24h ambulatory electrocardiograms to 2D strain echocardiographic findings and cardiac magnetic resonance imaging variables in 31 G+/LVH+ HCM patients. Mechanical dispersion was significantly increased in HCM patients with episodes of ventricular arrhythmia on ambulatory ECGs and was a better predictor of these episodes than global longitudinal strain or late gadolinium enhancement. Mechanical dispersion may be a useful marker of arrhythmogenic potential in HCM patients. We evaluated conventional and novel ECG parameters in the whole cohort of mutation carriers. An abnormal ECG was present in 97% of G+/LVH+ and 86% of G+/LVH- subjects. The combination criteria of RV1RV3 + Q waves and septal remodeling identified G+/LVH- subjects with a 64% sensitivity and 97% specificity. The proposed novel ECG criteria may increase the efficacy of using electrocardiography in identification of G+/LVH- subjects. A group of 46 HCM patients was assessed with a 24h ambulatory ECG with comprehensive repolarization analysis and these findings were compared with imaging findings. Rate adapted QTe interval was prolonged in HCM patients. Maximal wall thickness was associated with longer maximal QTe and median T wave peak to T wave end interval. HCM patients with late gadolinium enhancement had a steeper QTe/RR slope compared to HCM patients without LGE and control subjects. The presence of LGE may independently affect the repolarization dynamics in HCM. The metabolome of carriers of the MYBPC3-Q1061X mutation was investigated with comprehensive laboratory assays. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction.
Original languageEnglish
Supervisors/Advisors
  • Laine, Mika, Supervisor
  • Heliö, Tiina Maria, Supervisor
  • Kuusisto, Johanna, Supervisor, External person
Award date14 Dec 2018
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-4683-0
Electronic ISBNs978-951-51-4684-7
Publication statusPublished - 2018
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • Cardiomyopathy, Hypertrophic
  • +diagnostic imaging
  • +genetics
  • +metabolism
  • Myocardium
  • Hypertrophy
  • Hypertrophy, Left Ventricular
  • Carrier Proteins
  • Heterozygote
  • Death, Sudden, Cardiac
  • Gadolinium
  • Echocardiography
  • 3121 Internal medicine

Cite this

Jalanko, Mikko. / Alterations in myocardial function and electrocardiology in hypertrophic cardiomyopathy. Helsinki : Helsingin yliopisto, 2018. 90 p.
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title = "Alterations in myocardial function and electrocardiology in hypertrophic cardiomyopathy",
abstract = "Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy with a highly variable phenotype. The assessment of arrhythmogenic potential in HCM patients and identification of early signs of the disease in relatives of HCM patients is challenging. The aim of this thesis was to characterize the mechanical and electrical changes in the left ventricle of carriers of either the MYBPC3-Q1061X or TPM1-D175N mutation for hypertrophic cardiomyopathy and to identify novel imaging and electrocardiographic parameters with the potential to enhance sudden cardiac death risk stratification and follow-up. A total of 140 subjects carrying a pathogenic variant for HCM were recruited for these studies from three centers in Finland, divided into two groups: those with left ventricular hypertrophy (G+/LVH+ n = 98) and those without hypertrophy (G+/LVH- n = 42). We studied the association of ventricular arrhythmias on 24h ambulatory electrocardiograms to 2D strain echocardiographic findings and cardiac magnetic resonance imaging variables in 31 G+/LVH+ HCM patients. Mechanical dispersion was significantly increased in HCM patients with episodes of ventricular arrhythmia on ambulatory ECGs and was a better predictor of these episodes than global longitudinal strain or late gadolinium enhancement. Mechanical dispersion may be a useful marker of arrhythmogenic potential in HCM patients. We evaluated conventional and novel ECG parameters in the whole cohort of mutation carriers. An abnormal ECG was present in 97{\%} of G+/LVH+ and 86{\%} of G+/LVH- subjects. The combination criteria of RV1RV3 + Q waves and septal remodeling identified G+/LVH- subjects with a 64{\%} sensitivity and 97{\%} specificity. The proposed novel ECG criteria may increase the efficacy of using electrocardiography in identification of G+/LVH- subjects. A group of 46 HCM patients was assessed with a 24h ambulatory ECG with comprehensive repolarization analysis and these findings were compared with imaging findings. Rate adapted QTe interval was prolonged in HCM patients. Maximal wall thickness was associated with longer maximal QTe and median T wave peak to T wave end interval. HCM patients with late gadolinium enhancement had a steeper QTe/RR slope compared to HCM patients without LGE and control subjects. The presence of LGE may independently affect the repolarization dynamics in HCM. The metabolome of carriers of the MYBPC3-Q1061X mutation was investigated with comprehensive laboratory assays. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction.",
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Alterations in myocardial function and electrocardiology in hypertrophic cardiomyopathy. / Jalanko, Mikko.

Helsinki : Helsingin yliopisto, 2018. 90 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Alterations in myocardial function and electrocardiology in hypertrophic cardiomyopathy

AU - Jalanko, Mikko

N1 - M1 - 90 s. + liitteet

PY - 2018

Y1 - 2018

N2 - Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy with a highly variable phenotype. The assessment of arrhythmogenic potential in HCM patients and identification of early signs of the disease in relatives of HCM patients is challenging. The aim of this thesis was to characterize the mechanical and electrical changes in the left ventricle of carriers of either the MYBPC3-Q1061X or TPM1-D175N mutation for hypertrophic cardiomyopathy and to identify novel imaging and electrocardiographic parameters with the potential to enhance sudden cardiac death risk stratification and follow-up. A total of 140 subjects carrying a pathogenic variant for HCM were recruited for these studies from three centers in Finland, divided into two groups: those with left ventricular hypertrophy (G+/LVH+ n = 98) and those without hypertrophy (G+/LVH- n = 42). We studied the association of ventricular arrhythmias on 24h ambulatory electrocardiograms to 2D strain echocardiographic findings and cardiac magnetic resonance imaging variables in 31 G+/LVH+ HCM patients. Mechanical dispersion was significantly increased in HCM patients with episodes of ventricular arrhythmia on ambulatory ECGs and was a better predictor of these episodes than global longitudinal strain or late gadolinium enhancement. Mechanical dispersion may be a useful marker of arrhythmogenic potential in HCM patients. We evaluated conventional and novel ECG parameters in the whole cohort of mutation carriers. An abnormal ECG was present in 97% of G+/LVH+ and 86% of G+/LVH- subjects. The combination criteria of RV1RV3 + Q waves and septal remodeling identified G+/LVH- subjects with a 64% sensitivity and 97% specificity. The proposed novel ECG criteria may increase the efficacy of using electrocardiography in identification of G+/LVH- subjects. A group of 46 HCM patients was assessed with a 24h ambulatory ECG with comprehensive repolarization analysis and these findings were compared with imaging findings. Rate adapted QTe interval was prolonged in HCM patients. Maximal wall thickness was associated with longer maximal QTe and median T wave peak to T wave end interval. HCM patients with late gadolinium enhancement had a steeper QTe/RR slope compared to HCM patients without LGE and control subjects. The presence of LGE may independently affect the repolarization dynamics in HCM. The metabolome of carriers of the MYBPC3-Q1061X mutation was investigated with comprehensive laboratory assays. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction.

AB - Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy with a highly variable phenotype. The assessment of arrhythmogenic potential in HCM patients and identification of early signs of the disease in relatives of HCM patients is challenging. The aim of this thesis was to characterize the mechanical and electrical changes in the left ventricle of carriers of either the MYBPC3-Q1061X or TPM1-D175N mutation for hypertrophic cardiomyopathy and to identify novel imaging and electrocardiographic parameters with the potential to enhance sudden cardiac death risk stratification and follow-up. A total of 140 subjects carrying a pathogenic variant for HCM were recruited for these studies from three centers in Finland, divided into two groups: those with left ventricular hypertrophy (G+/LVH+ n = 98) and those without hypertrophy (G+/LVH- n = 42). We studied the association of ventricular arrhythmias on 24h ambulatory electrocardiograms to 2D strain echocardiographic findings and cardiac magnetic resonance imaging variables in 31 G+/LVH+ HCM patients. Mechanical dispersion was significantly increased in HCM patients with episodes of ventricular arrhythmia on ambulatory ECGs and was a better predictor of these episodes than global longitudinal strain or late gadolinium enhancement. Mechanical dispersion may be a useful marker of arrhythmogenic potential in HCM patients. We evaluated conventional and novel ECG parameters in the whole cohort of mutation carriers. An abnormal ECG was present in 97% of G+/LVH+ and 86% of G+/LVH- subjects. The combination criteria of RV1RV3 + Q waves and septal remodeling identified G+/LVH- subjects with a 64% sensitivity and 97% specificity. The proposed novel ECG criteria may increase the efficacy of using electrocardiography in identification of G+/LVH- subjects. A group of 46 HCM patients was assessed with a 24h ambulatory ECG with comprehensive repolarization analysis and these findings were compared with imaging findings. Rate adapted QTe interval was prolonged in HCM patients. Maximal wall thickness was associated with longer maximal QTe and median T wave peak to T wave end interval. HCM patients with late gadolinium enhancement had a steeper QTe/RR slope compared to HCM patients without LGE and control subjects. The presence of LGE may independently affect the repolarization dynamics in HCM. The metabolome of carriers of the MYBPC3-Q1061X mutation was investigated with comprehensive laboratory assays. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction.

KW - Cardiomyopathy, Hypertrophic

KW - +diagnostic imaging

KW - +genetics

KW - +metabolism

KW - Myocardium

KW - Hypertrophy

KW - Hypertrophy, Left Ventricular

KW - Carrier Proteins

KW - Heterozygote

KW - Death, Sudden, Cardiac

KW - Gadolinium

KW - Echocardiography

KW - 3121 Internal medicine

M3 - Doctoral Thesis

SN - 978-951-51-4683-0

T3 - Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis

PB - Helsingin yliopisto

CY - Helsinki

ER -

Jalanko M. Alterations in myocardial function and electrocardiology in hypertrophic cardiomyopathy. Helsinki : Helsingin yliopisto, 2018. 90 p. (Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis; 78/2018).