Title: Correlation between nonalcoholic fatty liver disease and left ventricular diastolic
dysfunction in non-obese adults: a cross-sectional study
Version: 2 Date: 17 Oct 2022
Reviewer's report:
In the study, Cong et al. “Correlation between nonalcoholic fatty liver disease and early left
ventricular diastolic dysfunction in non-obese adults: a cross-sectional study”, the authors
compared several echocardiographic parameters of the left ventricular structure and function
measured in non-obese NAFLD inpatients and non-obese inpatients (control group). The
main goal was to investigate whether non-obese NAFLD is an independent risk factor for
early left ventricular diastolic dysfunction (LVDD). All parts of the manuscript are concise,
well written, and accompanied with effective tables. While the study is interesting, several
methodological concerns, in particular how LVDD was defined, may require the re-evaluation
of study conclusion or providing additional measurements and data analysis.
Major concerns:
1.
Since this study aimed to assess the impact of non-obese NAFLD on (early) LVDD, it is
surprising that the authors used such unsatisfactory limited set of echocardiographic metrics
to evaluate LV diastolic function. Authors considered LVDD as E/A<1. This is too simplistic.
Echocardiographic community (including publications cited by the authors, e.g. refs 32 and 33)
applies a combination of echo metrics for LVDD diagnostics and LVDD grading, while metrics
should also be adjusted to age (e.g., E/A, e’).
It is well known that E/A typically decreases with age. By consensus, E/A<0.8 is considered
low in older population, and along with E<50 cm/s and/or low e’ (age adjusted), early LVDD
(grade I) could be concluded (especially if there are some abnormalities in other metrics like
LA volume, e’, E/e’, TR velocity, DT, IVRT...).
Without complex evaluation, the authors can only discuss the changes in transmitral flow or its
worsening in NAFLD, which may suggest LVDD (but not LVDD itself).
Among other additional factors, E/A is affected by heart rate (Galderisi et al. Impact of
heart rate and PR interval on Doppler indexes of left ventricular diastolic filling in an
elderly cohort (the Framingham Heart Study). Am J Cardiol. 1993 72(15):1183-7. doi:
10.1016/0002-9149(93)90991-k. PMID: 8237811), preload conditions and blood pressure
variability (Shin et al. Relation of blood pressure variability to left ventricular function
and arterial stiffness in hypertensive patients. Singapore Med J. 2019 Aug;60(8):427-431.
doi: 10.11622/smedj.2019030; Choong CY, Herrmann HC, Weyman AE, Fifer MA. Preload
dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am
Coll Cardiol. 1987 Oct;10(4):800-8. doi: 10.1016/s0735-1097(87)80273-5. PMID: 2958532.).
It would be desirable if the authors disclose the prevalence of those with E/A<0.8 in 2 groups.
Would this recategorization affect the main conclusion of the study? The data on heart rate,
systolic and diastolic blood pressure, and their relation to E/A would be also important to
provide.
2.
The authors measured the significant decrease of LVEDD in non-obese NAFLD patients
and linked this with LVDD. This is a very unexpected finding for ‘early LVDD’.
The difference in LVEDD size or LVEDV was not typically reported even at much
higher LVDD stage (e.g., Ohtani et al., European Heart Journal (2012) 33, 1742–1749.
doi:10.1093/eurheartj/ehs135.;  Weber et al, (J Am Coll Cardiol 2013;61:1874–83).  http://
dx.doi.org/10.1016/j.jacc.2013.02.013.; Kasner et al, Circulation. 2007;116:637-647. DOI:
10.1161/CIRCULATIONAHA.106.661983. ;   ). While the early filling may somewhat delay,
the end diastolic volume does not necessary decrease.
On the other hand, the higher heart rate may be associated with smaller LVEDV and stoke
volume. In addition, some medications (e.g., diuretics) may cause LV load decrease associated
with smaller LVEDV. In this respect, it would be beneficial if authors disclose the patient’s
medications.
3.
Authors state that the study subjects were hospital inpatients. It would be desirable if the reasons
of hospitalizations are described in the methods.
4.
NAFLD may be associated with increased risk of CAD. Despite the exclusion of all patients
with known heart disease by the authors, there is a concern that NAFLD patients could have
a larger prevalence of asymptomatic CAD, which itself is associated with LVDD and LVDD
echocardiographic features.
5.
Due to previously shown impact of DM on LVDD, it might be beneficial if authors also add
DM in the model despite it did not reach P<0.05 in the univariate test.
Title: Correlation between nonalcoholic fatty liver disease and left ventricular diastolic
dysfunction in non-obese adults: a cross-sectional study
Version: 2 Date: 17 Oct 2022
Reviewer's report:
In the study, Cong et al. “Correlation between nonalcoholic fatty liver disease and early left
ventricular diastolic dysfunction in non-obese adults: a cross-sectional study”, the authors
compared several echocardiographic parameters of the left ventricular structure and function
measured in non-obese NAFLD inpatients and non-obese inpatients (control group). The
main goal was to investigate whether non-obese NAFLD is an independent risk factor for
early left ventricular diastolic dysfunction (LVDD). All parts of the manuscript are concise,
well written, and accompanied with effective tables. While the study is interesting, several
methodological concerns, in particular how LVDD was defined, may require the re-evaluation
of study conclusion or providing additional measurements and data analysis.
Major concerns:
1.
Since this study aimed to assess the impact of non-obese NAFLD on (early) LVDD, it is
surprising that the authors used such unsatisfactory limited set of echocardiographic metrics
to evaluate LV diastolic function. Authors considered LVDD as E/A<1. This is too simplistic.
Echocardiographic community (including publications cited by the authors, e.g. refs 32 and 33)
applies a combination of echo metrics for LVDD diagnostics and LVDD grading, while metrics
should also be adjusted to age (e.g., E/A, e’).
It is well known that E/A typically decreases with age. By consensus, E/A<0.8 is considered
low in older population, and along with E<50 cm/s and/or low e’ (age adjusted), early LVDD
(grade I) could be concluded (especially if there are some abnormalities in other metrics like
LA volume, e’, E/e’, TR velocity, DT, IVRT...).
Without complex evaluation, the authors can only discuss the changes in transmitral flow or its
worsening in NAFLD, which may suggest LVDD (but not LVDD itself).
Among other additional factors, E/A is affected by heart rate (Galderisi et al. Impact of
heart rate and PR interval on Doppler indexes of left ventricular diastolic filling in an
elderly cohort (the Framingham Heart Study). Am J Cardiol. 1993 72(15):1183-7. doi:
10.1016/0002-9149(93)90991-k. PMID: 8237811), preload conditions and blood pressure
variability (Shin et al. Relation of blood pressure variability to left ventricular function
and arterial stiffness in hypertensive patients. Singapore Med J. 2019 Aug;60(8):427-431.
doi: 10.11622/smedj.2019030; Choong CY, Herrmann HC, Weyman AE, Fifer MA. Preload
dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am
Coll Cardiol. 1987 Oct;10(4):800-8. doi: 10.1016/s0735-1097(87)80273-5. PMID: 2958532.).
It would be desirable if the authors disclose the prevalence of those with E/A<0.8 in 2 groups.
Would this recategorization affect the main conclusion of the study? The data on heart rate,
systolic and diastolic blood pressure, and their relation to E/A would be also important to
provide.
2.
The authors measured the significant decrease of LVEDD in non-obese NAFLD patients
and linked this with LVDD. This is a very unexpected finding for ‘early LVDD’.
The difference in LVEDD size or LVEDV was not typically reported even at much
higher LVDD stage (e.g., Ohtani et al., European Heart Journal (2012) 33, 1742–1749.
doi:10.1093/eurheartj/ehs135.;  Weber et al, (J Am Coll Cardiol 2013;61:1874–83).  http://
dx.doi.org/10.1016/j.jacc.2013.02.013.; Kasner et al, Circulation. 2007;116:637-647. DOI:
10.1161/CIRCULATIONAHA.106.661983. ;   ). While the early filling may somewhat delay,
the end diastolic volume does not necessary decrease.
On the other hand, the higher heart rate may be associated with smaller LVEDV and stoke
volume. In addition, some medications (e.g., diuretics) may cause LV load decrease associated
with smaller LVEDV. In this respect, it would be beneficial if authors disclose the patient’s
medications.
3.
Authors state that the study subjects were hospital inpatients. It would be desirable if the reasons
of hospitalizations are described in the methods.
4.
NAFLD may be associated with increased risk of CAD. Despite the exclusion of all patients
with known heart disease by the authors, there is a concern that NAFLD patients could have
a larger prevalence of asymptomatic CAD, which itself is associated with LVDD and LVDD
echocardiographic features.
5.
Due to previously shown impact of DM on LVDD, it might be beneficial if authors also add
DM in the model despite it did not reach P<0.05 in the univariate test.
Please review this paper.
user
Title: Correlation between nonalcoholic fatty liver disease and left ventricular diastolic
dysfunction in non-obese adults: a cross-sectional study
Version: 2 Date: 17 Oct 2022
Reviewer's report:
In the study, Cong et al. “Correlation between nonalcoholic fatty liver disease and early left
ventricular diastolic dysfunction in non-obese adults: a cross-sectional study”, the authors
compared several echocardiographic parameters of the left ventricular structure and function
measured in non-obese NAFLD inpatients and non-obese inpatients (control group). The
main goal was to investigate whether non-obese NAFLD is an independent risk factor for
early left ventricular diastolic dysfunction (LVDD). All parts of the manuscript are concise,
well written, and accompanied with effective tables. While the study is interesting, several
methodological concerns, in particular how LVDD was defined, may require the re-evaluation
of study conclusion or providing additional measurements and data analysis.
Major concerns:
1.
Since this study aimed to assess the impact of non-obese NAFLD on (early) LVDD, it is
surprising that the authors used such unsatisfactory limited set of echocardiographic metrics
to evaluate LV diastolic function. Authors considered LVDD as E/A<1. This is too simplistic.
Echocardiographic community (including publications cited by the authors, e.g. refs 32 and 33)
applies a combination of echo metrics for LVDD diagnostics and LVDD grading, while metrics
should also be adjusted to age (e.g., E/A, e’).
It is well known that E/A typically decreases with age. By consensus, E/A<0.8 is considered
low in older population, and along with E<50 cm/s and/or low e’ (age adjusted), early LVDD
(grade I) could be concluded (especially if there are some abnormalities in other metrics like
LA volume, e’, E/e’, TR velocity, DT, IVRT...).
Without complex evaluation, the authors can only discuss the changes in transmitral flow or its
worsening in NAFLD, which may suggest LVDD (but not LVDD itself).
Among other additional factors, E/A is affected by heart rate (Galderisi et al. Impact of
heart rate and PR interval on Doppler indexes of left ventricular diastolic filling in an
elderly cohort (the Framingham Heart Study). Am J Cardiol. 1993 72(15):1183-7. doi:
10.1016/0002-9149(93)90991-k. PMID: 8237811), preload conditions and blood pressure
variability (Shin et al. Relation of blood pressure variability to left ventricular function
and arterial stiffness in hypertensive patients. Singapore Med J. 2019 Aug;60(8):427-431.
doi: 10.11622/smedj.2019030; Choong CY, Herrmann HC, Weyman AE, Fifer MA. Preload
dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am
Coll Cardiol. 1987 Oct;10(4):800-8. doi: 10.1016/s0735-1097(87)80273-5. PMID: 2958532.).
It would be desirable if the authors disclose the prevalence of those with E/A<0.8 in 2 groups.
Would this recategorization affect the main conclusion of the study? The data on heart rate,
systolic and diastolic blood pressure, and their relation to E/A would be also important to
provide.
2.
The authors measured the significant decrease of LVEDD in non-obese NAFLD patients
and linked this with LVDD. This is a very unexpected finding for ‘early LVDD’.
The difference in LVEDD size or LVEDV was not typically reported even at much
higher LVDD stage (e.g., Ohtani et al., European Heart Journal (2012) 33, 1742–1749.
doi:10.1093/eurheartj/ehs135.;  Weber et al, (J Am Coll Cardiol 2013;61:1874–83).  http://
dx.doi.org/10.1016/j.jacc.2013.02.013.; Kasner et al, Circulation. 2007;116:637-647. DOI:
10.1161/CIRCULATIONAHA.106.661983. ;   ). While the early filling may somewhat delay,
the end diastolic volume does not necessary decrease.
On the other hand, the higher heart rate may be associated with smaller LVEDV and stoke
volume. In addition, some medications (e.g., diuretics) may cause LV load decrease associated
with smaller LVEDV. In this respect, it would be beneficial if authors disclose the patient’s
medications.
3.
Authors state that the study subjects were hospital inpatients. It would be desirable if the reasons
of hospitalizations are described in the methods.
4.
NAFLD may be associated with increased risk of CAD. Despite the exclusion of all patients
with known heart disease by the authors, there is a concern that NAFLD patients could have
a larger prevalence of asymptomatic CAD, which itself is associated with LVDD and LVDD
echocardiographic features.
5.
Due to previously shown impact of DM on LVDD, it might be beneficial if authors also add
DM in the model despite it did not reach P<0.05 in the univariate test.
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