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• W4291677410 abstract "HomeCirculationVol. 146, No. 6Longitudinal Evolution of Cardiac Dysfunction in Heart Failure and Preserved Ejection Fraction With Normal Natriuretic Peptide Levels Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLongitudinal Evolution of Cardiac Dysfunction in Heart Failure and Preserved Ejection Fraction With Normal Natriuretic Peptide Levels Hidemi Sorimachi, Frederik H. Verbrugge, Kazunori Omote, Massar Omar, Masaru Obokata, Yogesh N.V. Reddy, Zi Ye, Hector I. Michelena and Barry A. Borlaug Hidemi SorimachiHidemi Sorimachi Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author , Frederik H. VerbruggeFrederik H. Verbrugge https://orcid.org/0000-0003-0599-9290 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Centre for Cardiovascular Diseases, University Hospital Brussels, Jette, Belgium (F.H.V.). Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Belgium (F.H.V.). Search for more papers by this author , Kazunori OmoteKazunori Omote Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author , Massar OmarMassar Omar https://orcid.org/0000-0002-9634-3889 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author , Masaru ObokataMasaru Obokata https://orcid.org/0000-0002-5473-0688 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author , Yogesh N.V. ReddyYogesh N.V. Reddy Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author , Zi YeZi Ye Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author , Hector I. MichelenaHector I. Michelena https://orcid.org/0000-0002-2341-5247 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author and Barry A. BorlaugBarry A. Borlaug Correspondence to: Barry A. Borlaug, MD, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905. Email E-mail Address: [email protected] https://orcid.org/0000-0001-9375-0596 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (H.S., F.H.V., K.O., M. Omar, M. Obokata, Y.N.V.R., Z.Y., H.I.M., B.A.B.). Search for more papers by this author Originally published8 Aug 2022https://doi.org/10.1161/CIRCULATIONAHA.121.058592Circulation. 2022;146:500–502Heart failure with preserved left ventricular (LV) ejection fraction (HFpEF) is a heterogeneous syndrome caused by abnormalities in cardiac function at rest or with exercise.1 It was originally believed that all patients with HF displayed elevated plasma natriuretic peptide (NP) levels, but it is now well known that a sizeable proportion of patients have normal NP levels.2,3 Although individuals with HFpEF and normal NP levels experience lower event rates than those with elevated NP, they still display increased risk compared with patients with normal NP and normal hemodynamics.3 It is unclear whether patients with HFpEF and normal NP represent a fundamentally different phenotype or are simply identified at an earlier stage of disease progression.4 To explore this question, we evaluated longitudinal changes in cardiac function in patients with HFpEF on the basis of the presence or absence of elevated NP levels.The data that support the findings of this study are available from the corresponding author on reasonable request. Patients with invasively verified HFpEF (rest or exercise pulmonary capillary wedge pressure ≥15 or ≥25 mm Hg, respectively) and healthy controls underwent echocardiographic evaluations >1 year apart. Plasma N-terminal pro-brain natriuretic peptide levels were measured at examination 1. Patients with HFpEF were classified as those with normal NP (N-terminal pro-brain natriuretic peptide <125 mg/dL, nNP-HFpEF) or high NP (N-terminal pro-brain natriuretic peptide ≥125 mg/dL, hNP-HFpEF). Sensitivity analyses were performed in subcohorts frequency matched by age, sex, and body mass index (60 controls, 55 nNP-HFpEF, and 66 hNP-HFpEF). The Mayo Clinic Institutional Review Board approved the study protocol and all subjects provided consent for data use.Cardiac function was assessed by myocardial deformation analyses from 2-dimensional images using commercially available software (Image Arena, TomTec Imaging Systems). Left ventricular global longitudinal strain (LVGLS) was measured using 2-dimensional speckle tracking, determined as the average of the 2 apical views (4- and 2-chamber views). The myocardial reservoir function of the left atrium (LA) was evaluated by the LA strain peak during LA relaxation. Right ventricular free wall strain (RVFWS) was obtained by the value of peak longitudinal systolic strain from the free wall of the right ventricle (RV). LV systolic dysfunction was defined by LVGLS <16%, LA dysfunction was LA reservoir strain <26%, and RV systolic dysfunction was RVFWS <20%. Between-group differences were first compared by 1-way ANOVA or χ2 test. The Tukey honestly significant-difference test was then used to compare individual groups. Paired within-group differences between examination 1 and examination 2 were assessed using the McNemar test or paired t-test. A 2-sided P value of <0.05 was considered statistically significant. All data were analyzed using JMP14.0 (SAS Institute Inc).The sample includes 287 patients: 66 with nNP-HFpEF, 136 hNP-HFpEF, and 85 health controls. Compared with patients with hNP-HFpEF, patients with nNP-HFpEF were a decade younger (61±11 versus 71±10 years, P<0.001), with higher body mass index (34.9±7.7 versus 31.8±6.9 kg/m2, P<0.001) and lower prevalence of atrial fibrillation (9% versus 59%, P<0.001). There were no differences in prevalence of hypertension (88% versus 95%, P=0.09) or diabetes (23% versus 27%, P=0.5). At examination 1, LVGLS, LA reservoir strain, and RVFWS were higher in nNP-HFpEF than in hNP-HFpEF (Figure). LA reservoir strain was lower in nNP-HFpEF than in healthy controls, but there were no statistically significant differences in LVGLS or RVFWS between nNP-HFpEF and controls at examination 1.Download figureDownload PowerPointFigure. Longitudinal changes in cardiac structure and function in controls, normal NP HFpEF, and high NP HFpEF. Left ventricular (LV) global longitudinal strain (LVGLS; A), left atrial (LA) reservoir strain (B), and right ventricular (RV) free wall strain (RVFWS; C) deteriorated at the same velocity in HFpEF with normal and high levels of NT-proBNP. D and E, The prevalence of LV and LA dysfunction increased only in HFpEF with normal and high levels of NT-proBNP over the duration of follow-up. F, The prevalence of RV systolic function was to be increased only in HFpEF with high NT-proBNP but did not in HFpEF with normal NT-proBNP and controls. HFpEF indicates heart failure with preserved ejection fraction; hNP, high natriuretic peptide; LA, left atrial; nNP, normal natriuretic peptide; and NT-proBNP, N-terminal pro-brain natriuretic peptide. *P<0.05 vs control at examination 1; †P<0.05 vs HFpEF with normal NT-proBNP HFpEF at examination 1.The median time between examinations 1 and 2 was 3.1 (interquartile range, 2.1–5.1) years, with no difference between groups (P=0.7). In both nNP-HFpEF and hNP-HFpEF, LVGLS, LA reservoir strain, and RVFWS deteriorated over time (Figure). The prevalence of LV and LA dysfunction increased in nNP-HFpEF. It is noteworthy that there were no differences in the rate of change between nNP-HFpEF and hNP-HFpEF for LVGLS (–0.6%/y versus –0.6%/y, P=1.0), LA reservoir strain (–1.2%/y versus –0.6%/y, P=0.4), or RVFWS (–1.0%/y versus –1.1%/y, P=0.9). Crucially, and in contrast to both HFpEF groups, there was no change in biventricular or LA function in controls over the same time interval (Figure). All group differences in longitudinal changes in cardiac function were similar in age-, sex-, and body mass index–matched sensitivity analysis.We have previously shown in longitudinal studies that deterioration in RV function over time is a marker of progression to advanced HFpEF.5 Here, we show for the first time that progression in biventricular and atrial dysfunction over time is similar in patients with HFpEF and normal NP levels to what is observed in patients with HFpEF with elevated NP levels, who are on average a decade older. These data collectively suggest that normal NP-HFpEF is more representative of an earlier stage of HFpEF rather than a fundamentally different phenotype. Because cardiac dysfunction in patients with HFpEF and normal NP is less advanced compared with elevated NP, this cohort may be more responsive to therapeutic intervention to improve clinical outcomes, even as they are often excluded from trials because of normal NP levels.Article InformationAcknowledgmentsThe authors thank the staff of the Earl Wood Catheterization Laboratory and the patients who agreed to participate in research, allowing for this study to be completed.Sources of FundingDr Borlaug is supported by R01 HL128526 and U01 HL160226 from the National Institutes of Health, and W81XWH2210245, from the US Department of Defense. Dr Verbrugge is supported by a Fellowship of the Belgian American Educational Foundation (B.A.E.F.) and by the Special Research Fund (BOF) of Hasselt University (BOF19PD04).Nonstandard Abbreviations and AcronymsHFpEFheart failure with preserved ejection fractionhNPhigh natriuretic peptideLAleft atriumLVleft ventricleLVGLSleft ventricular global longitudinal strainnNPnormal natriuretic peptideNPnatriuretic peptideRVright ventricularRVFWSright ventricular free wall strainDisclosures Dr Borlaug has received research grants from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics, along with consulting fees from Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations. Dr Borlaug is named inventor on an issued patent (US Patent no. 10 307 179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page 502.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Barry A. Borlaug, MD, Mayo Clinic and Foundation, 200 First St SW, Rochester, MN 55905. Email Borlaug.Barry@mayo.eduReferences1. Borlaug BA. Evaluation and management of heart failure with preserved ejection fraction.Nat Rev Cardiol. 2020; 17:559–573. doi: 10.1038/s41569-020-0363-2CrossrefMedlineGoogle Scholar2. Shah SJ. BNP: biomarker not perfect in heart failure with preserved ejection fraction.Eur Heart J. 2022; 43:1952–1954. doi: 10.1093/eurheartj/ehac121CrossrefMedlineGoogle Scholar3. Verbrugge FH, Omote K, Reddy YNV, Sorimachi H, Obokata M, Borlaug BA. Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality.Eur Heart J. 2022; 43:1941–1951. doi: 10.1093/eurheartj/ehab911CrossrefMedlineGoogle Scholar4. Senni M, Caravita S, Paulus WJ. Do existing definitions identify subgroup phenotypes or reflect the natural history of heart failure with preserved ejection fraction?.Circulation. 2019; 140:366–369. doi: 10.1161/CIRCULATIONAHA.119.041657LinkGoogle Scholar5. Obokata M, Reddy YNV, Melenovsky V, Pislaru S, Borlaug BA. Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction.Eur Heart J. 2019; 40:689–697. doi: 10.1093/eurheartj/ehy809CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Gard E, Beale A, Telles F, Silvestry F, Hanff T, Hummel S, Litwin S, Petrie M, Shah S, Borlaug B, Burkhoff D, Komtebedde J, Kaye D and Nanayakkara S (2023) Left atrial enlargement is associated with pulmonary vascular disease in heart failure with preserved ejection fraction, European Journal of Heart Failure, 10.1002/ejhf.2805 Dal Canto E, Scheffer M, Kortekaas K, Driessen-Waaijer A, Paulus W and van Heerebeek L (2023) Natriuretic Peptide Levels and Stages of Left Ventricular Dysfunction in Heart Failure with Preserved Ejection Fraction, Biomedicines, 10.3390/biomedicines11030867, 11:3, (867) Omote K, Hsu S and Borlaug B (2022) Hemodynamic Assessment in Heart Failure with Preserved Ejection Fraction, Cardiology Clinics, 10.1016/j.ccl.2022.06.010, 40:4, (459-472), Online publication date: 1-Nov-2022. August 9, 2022Vol 146, Issue 6 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.121.058592PMID: 35939545 Originally publishedAugust 8, 2022 Keywordsnatriuretic peptidesheart atriapro-brain natriuretic peptideheart failure, diastolicPDF download Advertisement SubjectsHeart Failure" @default.
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