This thesis was scanned from the print manuscript for digital preservation and is copyright the a... more This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.
American Journal of Cardiovascular Drugs, Jul 25, 2020
Legrand et al. [1] report on predictors for the development of a reduced left ventricular ejectio... more Legrand et al. [1] report on predictors for the development of a reduced left ventricular ejection fraction (LVEF) in Friedreich ataxia (FRDA) based on 12/115 subjects who developed an LVEF ≤ 50% during 13 ± 6 years of echocardiographic follow-up [1]. Longer length of the shorter GAA repeat expansion in the FXN gene was one predictor, with > 800 categorized as high risk. Left ventricular end-diastolic diameter (LVEDD) and septal wall thickness (SWT) assessed 5 years prior to the diagnosis of a reduced LVEF were also reported to be predictors of a deterioration in LVEF independently of GAA repeats, and an LVEDD ≥ 52.6 mm and SWT ≥ 13.3 mm were both categorized as high risk. However, while the early prediction of a reduced LVEF in FRDA may be a justifiable aim, I have a number of concerns regarding the validity of the conclusions of this study with regard to the echocardiographic predictors. First, echocardiographic measurement reproducibility of < 1 mm is not possible, therefore cut-offs including fractions of 1 mm (52.6 and 13.3 mm) cannot be meaningful at an individual level. Second, in healthy adults, both LVEDD and SWT can vary over a large range, with a large part of this variability in LVEDD related to body size, whereas SWT is affected independently by body size, sex, and age [2]. There is also evidence in FRDA that while smaller than in healthy subjects, LVEDD is independently determined by body size, and while larger than in healthy subjects, SWT is also higher in males [3]. Therefore, identification of measurements of LVEDD and SWT that have not been adjusted for either body size or sex as predictors of a reduced LVEF must be questionable and, at the very least, would appear to require an attempt at a justification in the discussion. An additional implication of the recognized importance of sex effects on wall thickness for both healthy and FRDA subjects is that Henry’s nomogram (in which there is no adjustment for sex) is an anachronism from a time when the effects of sex were not understood and should be abandoned as a means of diagnosing hypertrophy in FRDA. Finally, it is stated that the model including LVEDD and SWT was able to predict an LVEF ≤ 50% 5 years prior to its development. However, echocardiography was not performed yearly in this study, with the mean time between visits approximately 2 years, and it is not made clear in the text whether the 5 years refers to a median of 5 years, a mean of 5 years, or a cut-off of ≥ 5 years, with the last option providing a genuine early prediction. If it is in fact a median or mean of 5 years then this should have been made clearer in both the abstract and the manuscript. Furthermore, it has not been specifically explained how the 5-year timing was applied to the subjects with a preserved ejection fraction, presumably 5 years prior to their most recent study.
TO THE EDITOR: The report by Mangion et al draws attention to a serious risk in the environment. ... more TO THE EDITOR: The report by Mangion et al draws attention to a serious risk in the environment. The general public has been increasingly protected against the risk of harm from domestic products by a combination of legal liability actions and government regulation. Thus, the continuing availability to the general public of hydrofluoric acid (HF) in concentrations that are hazardous is something of an anachronism. While we applaud Mangion and colleagues for raising the issue of HF burns, we feel that their article is deficient in failing to mention a number of important points. ■ Topical calcium gluconate has been shown to be more effective in treating HF burns if the preparation contains dimethyl sulfoxide (DMSO).2
This thesis was scanned from the print manuscript for digital preservation and is copyright the a... more This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.
American Journal of Cardiovascular Drugs, Jul 25, 2020
Legrand et al. [1] report on predictors for the development of a reduced left ventricular ejectio... more Legrand et al. [1] report on predictors for the development of a reduced left ventricular ejection fraction (LVEF) in Friedreich ataxia (FRDA) based on 12/115 subjects who developed an LVEF ≤ 50% during 13 ± 6 years of echocardiographic follow-up [1]. Longer length of the shorter GAA repeat expansion in the FXN gene was one predictor, with > 800 categorized as high risk. Left ventricular end-diastolic diameter (LVEDD) and septal wall thickness (SWT) assessed 5 years prior to the diagnosis of a reduced LVEF were also reported to be predictors of a deterioration in LVEF independently of GAA repeats, and an LVEDD ≥ 52.6 mm and SWT ≥ 13.3 mm were both categorized as high risk. However, while the early prediction of a reduced LVEF in FRDA may be a justifiable aim, I have a number of concerns regarding the validity of the conclusions of this study with regard to the echocardiographic predictors. First, echocardiographic measurement reproducibility of < 1 mm is not possible, therefore cut-offs including fractions of 1 mm (52.6 and 13.3 mm) cannot be meaningful at an individual level. Second, in healthy adults, both LVEDD and SWT can vary over a large range, with a large part of this variability in LVEDD related to body size, whereas SWT is affected independently by body size, sex, and age [2]. There is also evidence in FRDA that while smaller than in healthy subjects, LVEDD is independently determined by body size, and while larger than in healthy subjects, SWT is also higher in males [3]. Therefore, identification of measurements of LVEDD and SWT that have not been adjusted for either body size or sex as predictors of a reduced LVEF must be questionable and, at the very least, would appear to require an attempt at a justification in the discussion. An additional implication of the recognized importance of sex effects on wall thickness for both healthy and FRDA subjects is that Henry’s nomogram (in which there is no adjustment for sex) is an anachronism from a time when the effects of sex were not understood and should be abandoned as a means of diagnosing hypertrophy in FRDA. Finally, it is stated that the model including LVEDD and SWT was able to predict an LVEF ≤ 50% 5 years prior to its development. However, echocardiography was not performed yearly in this study, with the mean time between visits approximately 2 years, and it is not made clear in the text whether the 5 years refers to a median of 5 years, a mean of 5 years, or a cut-off of ≥ 5 years, with the last option providing a genuine early prediction. If it is in fact a median or mean of 5 years then this should have been made clearer in both the abstract and the manuscript. Furthermore, it has not been specifically explained how the 5-year timing was applied to the subjects with a preserved ejection fraction, presumably 5 years prior to their most recent study.
TO THE EDITOR: The report by Mangion et al draws attention to a serious risk in the environment. ... more TO THE EDITOR: The report by Mangion et al draws attention to a serious risk in the environment. The general public has been increasingly protected against the risk of harm from domestic products by a combination of legal liability actions and government regulation. Thus, the continuing availability to the general public of hydrofluoric acid (HF) in concentrations that are hazardous is something of an anachronism. While we applaud Mangion and colleagues for raising the issue of HF burns, we feel that their article is deficient in failing to mention a number of important points. ■ Topical calcium gluconate has been shown to be more effective in treating HF burns if the preparation contains dimethyl sulfoxide (DMSO).2
Uploads
Papers