Implantable cardioverter defibrillator treatment in patients with hypertrophic cardiomyopathy
Author: Magnusson, Peter
Date: 2020-11-06
Location: J3:04 Torsten N Wiesel, entrance Eugeniavägen 3, Karolinska University Hospital Solna
Time: 09.00
Department: Inst för medicin, Solna / Dept of Medicine, Solna
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Thesis (4.425Mb)
Abstract
Background: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease with various clinical manifestations, including sudden cardiac death, which can be prevented by an implantable cardioverter defibrillator (ICD).
Aims: The general aim of this thesis was to elucidate different aspects of ICD treatment in patients with HCM. This includes the use of ICDs among HCM patients with focus on risk stratification for ventricular arrhythmias, mortality, and cause of death; assessment of health-related quality of life; qualitative aspects of living with an ICD; and characterization using positron emission tomography (PET) to explore risk markers for sudden death.
Methods: The Swedish Pacemaker and ICD Registry was retrieved to identify eligible patients. Data from the National Patient Registers, the Cause of Death Register, Statistics Sweden, and medical records were used. Health-related quality of life was assessed using SF-36. Interviews were analyzed by hermeneutics and latent content analysis. PET and echocardiography were performed.
Results and Conclusions: In Paper Ⅰ, the nationwide cohort of unselected HCM patients with ICDs was based on established risk factors for sudden cardiac death at the time. ICDs effectively terminated potentially life-threatening ventricular arrhythmias in HCM. The cumulative incidences of first appropriate ICD therapy at 1 year, 3 years, and 5 years were 8%, 15%, and 21%, respectively. Left ventricular ejection fraction less than 50% and atrial fibrillation were strong predictors of appropriate ICD therapy. In Paper Ⅱ, among HCM patients with ICDs, the main cause of death is deterioration of systolic function leading to end-stage heart failure. The risk of sudden cardiac death was almost eliminated. Still, there was an increased risk of death (standardized mortality ratio 3.4) compared to the Swedish general population matched for age, sex, and calendaric time. In Paper Ⅲ, generic health-related quality of life, both mental and physical components, was lower in HCM patients with ICDs than in Swedish age- and sex-matched population norms. Systolic heart failure and atrial fibrillation are determinants of low health-related quality of life, especially physical functioning. In Paper Ⅳ, based on qualitative interpretation, HCM patients with ICDs perceive poor health due to limiting dyspnea but accept the change in lifestyle. They feel grateful for their device, which gives them hope during the life course despite necessary restrictions and adaptation, even after experiencing inappropriate shocks. The knowledge about the disease and device therapy varies substantially and the support from the health care providers is generally constrained to technical issues rather than an attempt at a holistic approach. In Paper Ⅴ, HCM patients with ICDs represent advanced disease manifestation determined as decreased myocardial blood flow at stress, altered oxidative metabolism, and sympathetic denervation using the tracers 15O-water, 11C-acetate, and 11C-HED during PET exams. The endocardium/epicardium myocardial blood flow gradient at adenosine stress is lower in HCM patients with nonsustained ventricular tachycardia, which provides a potential marker for risk stratification of sudden cardiac death.
Aims: The general aim of this thesis was to elucidate different aspects of ICD treatment in patients with HCM. This includes the use of ICDs among HCM patients with focus on risk stratification for ventricular arrhythmias, mortality, and cause of death; assessment of health-related quality of life; qualitative aspects of living with an ICD; and characterization using positron emission tomography (PET) to explore risk markers for sudden death.
Methods: The Swedish Pacemaker and ICD Registry was retrieved to identify eligible patients. Data from the National Patient Registers, the Cause of Death Register, Statistics Sweden, and medical records were used. Health-related quality of life was assessed using SF-36. Interviews were analyzed by hermeneutics and latent content analysis. PET and echocardiography were performed.
Results and Conclusions: In Paper Ⅰ, the nationwide cohort of unselected HCM patients with ICDs was based on established risk factors for sudden cardiac death at the time. ICDs effectively terminated potentially life-threatening ventricular arrhythmias in HCM. The cumulative incidences of first appropriate ICD therapy at 1 year, 3 years, and 5 years were 8%, 15%, and 21%, respectively. Left ventricular ejection fraction less than 50% and atrial fibrillation were strong predictors of appropriate ICD therapy. In Paper Ⅱ, among HCM patients with ICDs, the main cause of death is deterioration of systolic function leading to end-stage heart failure. The risk of sudden cardiac death was almost eliminated. Still, there was an increased risk of death (standardized mortality ratio 3.4) compared to the Swedish general population matched for age, sex, and calendaric time. In Paper Ⅲ, generic health-related quality of life, both mental and physical components, was lower in HCM patients with ICDs than in Swedish age- and sex-matched population norms. Systolic heart failure and atrial fibrillation are determinants of low health-related quality of life, especially physical functioning. In Paper Ⅳ, based on qualitative interpretation, HCM patients with ICDs perceive poor health due to limiting dyspnea but accept the change in lifestyle. They feel grateful for their device, which gives them hope during the life course despite necessary restrictions and adaptation, even after experiencing inappropriate shocks. The knowledge about the disease and device therapy varies substantially and the support from the health care providers is generally constrained to technical issues rather than an attempt at a holistic approach. In Paper Ⅴ, HCM patients with ICDs represent advanced disease manifestation determined as decreased myocardial blood flow at stress, altered oxidative metabolism, and sympathetic denervation using the tracers 15O-water, 11C-acetate, and 11C-HED during PET exams. The endocardium/epicardium myocardial blood flow gradient at adenosine stress is lower in HCM patients with nonsustained ventricular tachycardia, which provides a potential marker for risk stratification of sudden cardiac death.
List of papers:
I. Magnusson P, Gadler F, Liv P, Mörner S. Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy. Pacing Clin Electrophysiology. 2016 March;39(3):291-301.
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II. Magnusson P, Gadler F, Liv P, Mörner S. Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden. J Cardiovascular Med (Hagerstown). 2016 July;17(7):478-484.
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III. Magnusson P, Mörner S, Gadler F, Karlsson J. Health-related quality of life in hypertrophic cardiomyopathy patients with implantable defibrillators. Health Qual Life Outcomes. 2016 April 14;14:62.
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IV. Magnusson P, Jonsson J, Mörner S, Fredriksson L. Living with hypertrophic cardiomyopathy and an implantable defibrillator. BMC Cardiovascular Disorders. 2017;17:121.
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V. Magnusson P, Nordström J, Harms J. H, Lubberink M, Gadler F, Sörensen J, Mörner S. Positron emission tomography (15O-water, 11C-acetate, 11C-HED) risk markers and nonsustained ventricular tachycardia in hypertrophic cardiomyopathy. IJC Heart and Vasculature. 2019 December 20;26:100452.
Fulltext (DOI)
Pubmed
View record in Web of Science®
I. Magnusson P, Gadler F, Liv P, Mörner S. Risk Markers and Appropriate Implantable Defibrillator Therapy in Hypertrophic Cardiomyopathy. Pacing Clin Electrophysiology. 2016 March;39(3):291-301.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Magnusson P, Gadler F, Liv P, Mörner S. Causes of death and mortality in hypertrophic cardiomyopathy patients with implantable defibrillators in Sweden. J Cardiovascular Med (Hagerstown). 2016 July;17(7):478-484.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Magnusson P, Mörner S, Gadler F, Karlsson J. Health-related quality of life in hypertrophic cardiomyopathy patients with implantable defibrillators. Health Qual Life Outcomes. 2016 April 14;14:62.
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Magnusson P, Jonsson J, Mörner S, Fredriksson L. Living with hypertrophic cardiomyopathy and an implantable defibrillator. BMC Cardiovascular Disorders. 2017;17:121.
Fulltext (DOI)
Pubmed
View record in Web of Science®
V. Magnusson P, Nordström J, Harms J. H, Lubberink M, Gadler F, Sörensen J, Mörner S. Positron emission tomography (15O-water, 11C-acetate, 11C-HED) risk markers and nonsustained ventricular tachycardia in hypertrophic cardiomyopathy. IJC Heart and Vasculature. 2019 December 20;26:100452.
Fulltext (DOI)
Pubmed
View record in Web of Science®
Institution: Karolinska Institutet
Supervisor: Mörner, Stellan
Co-supervisor: Gadler, Fredrik
Issue date: 2020-09-17
Rights:
Publication year: 2020
ISBN: 978-91-7831-873-5
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