Topic 4.4. Management strategies for heart failure
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
Topic Contents
4.4 Management strategies for heart failure
4.4.1 Pharmacologic treatment of heart failure with reduced left ventricular ejection fraction
4.4.2 Lifestyle factors and cautions to aid in management of heart failure
4.4.3 Device therapy and heart transplantation for heart failure
4.4.4 Fluid and operative management of individuals with and without heart failure
Disclaimer / Intended Use / Funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.
4.4 Management strategies for heart failure
Roger E. Peverill, Kimberly Y. Lin, Francoise Pousset, Aarti Patel and Konstantinos Savvatis
There is currently no evidence to support any cardiac treatment for individuals with FRDA with normal LV ejection fraction and without cardiac symptoms or signs. A number of studies have investigated the effects of idebenone on LV wall thickness and/or LV mass but most of these studies have been small and the findings have not been consistent (2). Furthermore, a reduction of wall thickness or LV mass cannot be assumed to be a beneficial outcome of treatment in FRDA.
Spontaneous onset of HF symptoms is rarely seen in individuals with FRDA with increased LV wall thickness in the setting of a normal LVEF and normal sinus rhythm, and so regular HF medication therapy is unlikely to be indicated in such individuals. However, individuals with FRDA with such patterns of LV remodeling are more likely to develop symptoms and signs of acute HF in circumstances of stress, such as surgery and serious infections, particularly when accompanied by changes in intravascular volume. Careful fluid management to avoid depletion or overload is recommended in such situations and diuretic therapy could be required if symptoms or signs develop due to fluid overload.
4.4.1 Pharmacologic treatment of heart failure with reduced left ventricular ejection fraction
Adults
There are no RCT data regarding the treatment of either asymptomatic people with FRDA with reduced LVEF or of individuals with FRDA and with HF associated with reduced LVEF (HFREF). However, in the absence of any evidence for any FRDA disease-specific harmful effects of standard HF treatments it is reasonable to use standard HF guidelines as a guide to therapy in FRDA, recognizing that there could be differences in the pathophysiology of FRDA heart disease. The fundamentals of medication management for symptomatic HFREF are provided in the 2013 ACCF/AHA guideline for the management of HF (79) and in the 2017 ACC/AHA/HFSA update on the 2013 ACCF/AHA guideline (85).
Children
There are no RCTs investigating the treatment of reduced LVEF with or without HF in children with FRDA. Neither is there even much data available from trials in children with HF due to a cardiomyopathy with reduced LVEF and causes other than FRDA. This is due in part to the difficulty of performing RCTs in children given the low prevalence of pediatric HFREF. Treatment of HFREF in children has been based on the results from adult studies.
4.4.2 Lifestyle factors and cautions to aid in management of heart failure
Lack of physical activity, poor diet, excessive consumption of salt and fluids and being overweight can exacerbate HF. Exercise-based rehabilitation can lead to reductions in hospitalizations for HF and improved quality of life and does not increase mortality in people with stable HF. Individuals who are requiring diuretics should generally be on a fluid restriction of less than 2L/day and more strict fluid restrictions may be necessary depending on the severity of the HF, the sodium level and the required doses of diuretics.
4.4.3 Device therapy and heart transplantation for heart failure
Prolongation of the QRS interval occurs in a proportion of people with advanced HF and has been associated with ventricular electromechanical delay (“dyssynchrony”) (83). QRS duration, dyssynchrony of contraction, and left bundle branch block (LBBB) in particular, have been identified as predictors of worsening HF, SCD, and total mortality. Modification of ventricular electromechanical delay with multisite ventricular pacing (biventricular pacing and cardiac resynchronization therapy (CRT)) can improve ventricular systolic function, ameliorate functional mitral regurgitation, and, in some individuals, induce favorable remodeling with reduction of cardiac chamber dimensions. Individuals with FRDA can develop HF due to severe systolic LV systolic dysfunction and can have a LBBB so CRT should be considered in such circumstances. There is a single case report of the successful use of a ventricular assist device in a patient with FRDA and heart failure due reduced LVEF (86).
Guidelines for CRT in patients with severe systolic HF are included in the 2013 ACCF/AHA guideline for the management of HF (79).
Transplantation of the heart in FRDA is not common but has been reported (87-91). Individuals with FRDA appear to do well after transplantation.
4.4.4 Fluid and operative management of individuals with and without heart failure
The increased thickness of the left ventricle in FRDA results in a reduction in coronary flow reserve and less tolerance to tachycardia. The reduced size of the LV cavity in FRDA means a greater reliance on heart rate to maintain cardiac output and a reduction in stroke volume reserve. Hearts of individuals with FRDA will therefore have less tolerance for changes in hemodynamics such as bradycardia, tachycardia, low blood pressure, and increases or decreases in LV filling. Careful monitoring of fluid balance is essential in individuals with FRDA undergoing stressful events, such as scoliosis surgery or hydration therapy in the emergency room setting. In addition, rapid access to advanced technologies for supporting cardiac output following major surgery, such as dialysis and left ventricular assist devices, may be required.
Although significant advances have been made in understanding the molecular biology of FRDA, there remain substantial and fundamental gaps in our understanding of the clinical disease and natural history of FRDA. Furthermore, there are no RCTs of the treatment or prevention of arrhythmias or the treatment of HF and no trials showing any benefit of treatment to delay the onset of or prevent the development of left ventricular dysfunction in FRDA.
Heart failure medication/devices (preserved left ventricular ejection fraction)
QUESTION: Should heart failure medication and/or devices vs. no medication and/or devices be used for individuals with Friedreich ataxia and a preserved left ventricular ejection fraction (i.e. >55%)?
[sg_popup id=”587″ event=”click”]
[/sg_popup]STRENGTH OF RECOMMENDATION: ↓
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We do not suggest using heart failure medication and/or devices for individuals with Friedreich ataxia with a preserved left ventricular ejection fraction.
JUSTIFICATION: There is no evidence that the use of medication and/or devices has any benefit in reducing the occurrence of cardiac dysfunction in individuals with Friedreich ataxia with preserved ejection fraction and there are risks of side effects and over-medication if such treatments are used.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia and a preserved left ventricular ejection fraction (i.e. >55%).
Evidence to Recommendation Table PDFHeart failure medication (reduced ejection fraction)
QUESTION: Should heart failure medication versus no medication be used for individuals with reduced ejection fraction with Friedreich ataxia?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↑
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: We conditionally recommend treating individuals with Friedreich ataxia with a reduced left ventricular ejection fraction with medications according to current American Heart Association/American College of Cardiology heart failure guidelines (2013 & 2017 update).
JUSTIFICATION: Medical treatment of an individual with Friedreich ataxia with reduced ejection fraction should include those with a LVEF <50%, but could also be considered for those with a significant downward trend in ejection fraction over time. This is based on current recommendations of the AHA/ACC (79, 85) for treatment of heart failure as there is no evidence to suggest that individuals with Friedreich ataxia should be treated differently to other people with heart failure and reduced ejection fraction.
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia and a reduced ejection fraction, and as indicated in the justification above.
Evidence to Recommendation Table PDFAdvanced heart failure treatments (reduced left ventricular ejection fraction)
QUESTION: Should advanced heart failure treatments (e.g., biventricular pacemaker, internal cardioverter-defibrillator, left ventricular assist device, heart transplantation) versus supportive care be used for individuals with Friedreich ataxia in the advanced stages of heart failure due to a reduced left ventricular ejection fraction?
[sg_popup id=”587″ event=”click”][/sg_popup]STRENGTH OF RECOMMENDATION: ↑
[sg_popup id=”658″ event=”click”][/sg_popup]LEVEL OF EVIDENCE: ⨁◯◯◯
RECOMMENDATION: Advanced heart failure therapies such as a left ventricular assist device, implantable cardioverter-defibrillator, biventricular pacemaker and heart transplantation should be considered for individuals with Friedreich ataxia and heart failure due to a reduced left ventricular ejection fraction, based on consideration of both their cardiac and overall health status.
JUSTIFICATION: Based on the current evidence, advanced heart failure therapies should be considered based on individual circumstances. A diagnosis of Friedreich ataxia alone should not preclude such consideration. Evidence from case reports indicates positive outcomes (86-91).
SUBGROUP CONSIDERATION: This recommendation is for individuals with Friedreich ataxia with a reduced left ventricular ejection fraction (i.e. <55%).
Evidence to Recommendation Table PDFIn adults with Friedreich ataxia and a reduction in left ventricular ejection fraction there is a case for treating according to standard heart failure guidelines.
In individuals with Friedreich ataxia and symptomatic heart failure there is a case for treating according to standard heart failure guidelines.
Women with Friedreich ataxia and a reduction in left ventricular ejection fraction should be advised that pregnancy could result in cardiac decompensation and a greater maternal and fetal risk.
Treatment options such as an ICD and heart transplantation are not contraindicated in Friedreich ataxia, but the appropriateness of such therapy requires careful consideration of the individual’s functional status and their prognosis from non-cardiac morbidities.
Lay summary of clinical recommendations for heart failure in Friedreich ataxia
Why these recommendations?
Heart failure is a condition where your heart function is impaired and it can result in loss of exercise tolerance, breathlessness and leg swelling. Heart failure can also result in abnormal heart rhythms.
These recommendations did not find that any specific heart failure medication or devices had evidence of benefit in individuals with Friedreich ataxia with a normal left ventricular ejection fraction (a commonly used measure of the percentage of blood pumped by the left ventricle with each heart beat). On the other hand, if an individual has a reduced left ventricular ejection fraction, we suggest that treatment should follow the same guidelines as for individuals with a reduced left ventricular ejection fraction who do not have Friedreich ataxia.
In the case of advanced heart failure, and after considering both the heart and general health of the individual concerned, we suggest that devices that can help to maintain heart output or heart transplantation could be considered.
What does this mean for you as a person living with Friedreich ataxia or caring for someone living with Friedreich ataxia?
It may be important for you to speak with your healthcare professional about Friedreich ataxia and heart failure and what it means for you.
Who are these recommendations specifically for?
These recommendations are for individuals with Friedreich ataxia who have been diagnosed with heart failure.
Associate Professor, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Aarti Patel, MD
Associate Professor of Medicine, University of South Florida, Tampa, Florida, USA
Email: apatel15@usf.edu
Roger E. Peverill, MBBS, PhD
Cardiologist, MonashHeart, Monash Health, Clayton, Victoria, Australia
Email: roger.peverill@monash.edu
Francoise Pousset, MD
Sorbonne Université, Cardiology Department, AP-HP, Pitié-Salpêtrière University Hospital, Paris, France
Email: f.pousset@aphp.fr
Konstantinos Savvatis, MD, PhD
Consultant Cardiologist, St. Bartholomew’s Hospital, Barts Health NHS Trust, London, UK
Email: k.savvatis@ucl.ac.uk
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These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
This chapter of the Clinical Management Guidelines for Friedreich Ataxia and the recommendations and best practice statements contained herein were endorsed by the authors and the Friedreich Ataxia Guidelines Panel in 2022.
It is our expectation that going forward individual topics can be updated in real-time in response to new evidence versus a re-evaluation and update of all topics simultaneously.