Left Atrial Remodeling Related to Disproportionately Low B-Type Natriuretic Peptide in Acute Heart Failure Patients with Atrial Fibrillation

The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n = 899) were divided into groups with (n = 382) or without AF (n = 507) and subdivided into disproportionately low BNP (LB) (≤200 pg/ml), medium BNP (200 to 600 pg/ml) and high BNP (≥600 pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p = 0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis. The diagnostic performance of B-type natriuretic peptide (BNP) for acute heart failure (HF) is impaired in patients with atrial fibrillation (AF). Increased AF burden in HF is associated with left atrial (LA) remodeling. Recent studies have revealed that LA remodeling may affect LV filling. We hypothesized that LA remodeling affects BNP secretion in acute HF conditions. The study investigated the clinical impact of LA remodeling on admission BNP levels in acute HF patients with and without AF. Consecutive acute HF hospitalized patients (n = 899) were divided into groups with (n = 382) or without AF (n = 507) and subdivided into disproportionately low BNP (LB) (≤200 pg/ml), medium BNP (200 to 600 pg/ml) and high BNP (≥600 pg/ml) subgroups. The AF group had a higher proportion of patients with LB than the non-AF group (23.6% vs 16.6%, p = 0.009). BNP levels in both groups were positively correlated with LV end-diastolic volume and negatively correlated with LV ejection fraction in both groups. In contrast, BNP was positively correlated with LA volume index in the non-AF group, but negatively correlated in the AF group. The survival rates were significantly higher in the LB group than in the other groups in non-AF. Conversely, there were no significant differences across all groups in AF patients. In conclusion, in patients with acute HF and AF, disproportionately low BNP levels are associated with LA structural remodeling and poor prognosis. B-type natriuretic peptide (BNP) is mainly secreted by myocytes in the left ventricle (LV) in response to volume and pressure overload. BNP is the most studied biomarker reflecting congestion and prognosis in patients with acute heart failure (HF).1Maisel AS Krishnaswamy P Nowak RM McCord J Hollander JE Duc P Omland T Storrow AB Abraham WT Wu AHB Clopton P Steg PG Westheim A Knudsen CW Perez A Kazanegra R Herrmann HC McCullough PA Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.N Engl J Med. 2002; 347: 161-167Crossref PubMed Scopus (2869) Google Scholar Moreover the levels of BNP are believed to increase protectively under HF condition, given the cardioprotective roles of NP in regulating cardiovascular homeostasis and intravascular volume.2Nishikimi T Maeda N Matsuoka H. The role of natriuretic peptides in cardioprotection.Cardiovasc Res. 2006; 69: 318-328Crossref PubMed Scopus (415) Google Scholar However, the BNP concentration known to be disproportionately low (relative BNP deficiency) in some patients with constrictive pericarditis and obesity despite acute HF conditions.3Sakane K Kanzaki Y Tsuda K Maeda D Sohmiya K Hoshiga M. Disproportionately low BNP levels in patients of acute heart failure with preserved vs. reduced ejection fraction.Int J Cardiol. 2021; 327: 105-110Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 4Mueller C McDonald K de Boer RA Maisel A Cleland JGF Kozhuharov N Coats AJS Metra M Mebazaa A Ruschitzka F Lainscak M Filippatos G Seferovic PM Meijers WC Bayes-Genis A Mueller T Richards M Januzzi Jr, JL Heart Failure Association of the European Society of CardiologyHeart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations.Eur J Heart Fail. 2019; 21: 715-731Crossref PubMed Scopus (399) Google Scholar, 5Spodick DH. Low atrial natriuretic factor levels and absent pulmonary edema in pericardial compression of the heart.Am J Cardiol. 1989; 63: 1271-1272Abstract Full Text PDF PubMed Scopus (23) Google Scholar In patients with atrial fibrillation (AF), the diagnostic performance of BNP for acute HF is impaired. BNP levels are also independently influenced by both AF and HF conditions, hence it is difficulat to determine which BNP level can be used for the diagnosis of one condition in the presence of the other.6Kelly JP Mentz RJ Mebazaa A Voors AA Butler J Roessig L Fiuzat M Zannad F Pitt B O'Connor CM Lam CSP Patient selection in heart failure with preserved ejection fraction clinical trials.J Am Coll Cardiol. 2015; 65: 1668-1682Crossref PubMed Scopus (107) Google Scholar An increased AF burden in HF is associated with left atrial (LA) remodeling.7Reddy YNV Obokata M Verbrugge FH Lin G Borlaug BA. Atrial dysfunction in patients with heart failure with preserved ejection fraction and atrial fibrillation.J Am Coll Cardiol. 2020; 76: 1051-1064Crossref PubMed Scopus (161) Google Scholar Recent studies revealed that LA remodeling may affect LV filling.8Borlaug BA Reddy YNV. The role of the pericardium in heart failure: implications for pathophysiology and treatment.JACC Heart Fail. 2019; 7: 574-585Crossref PubMed Scopus (96) Google Scholar We hypothesized that LA remodeling affects BNP secretion under acute HF conditions. The study investigated the clinical impact of LA remodeling upon admission BNP levels in patients of acute HF with and without AF. This study was a retrospective observational study of a small-single center. All study procedures were performed by the ethical standards of the Institutional and National Research Committee and the Declaration of Helsinki and its later amendments or comparable ethical standards. The Ethics Review Board of Osaka Medical and Pharmaceutical University approved this retrospective study and waived the requirement for informed consent (approval number 2194). Among the 1,016 patients who required immediate treatment for acute HF or acute exacerbation of chronic HF at Osaka Medical and Pharmaceutical University Hospital between January 2015 and December 2020, a total of 889 consecutive patients were included in the study. HF was diagnosed by well-trained cardiologists based on the Framingham criteria or the universal definition of HF.9Bozkurt B Coats AJS Tsutsui H Abdelhamid CM Adamopoulos S Albert N Anker SD Atherton J Böhm M Butler J Drazner MH Michael Felker G Filippatos G Fiuzat M Fonarow GC Gomez-Mesa JE Heidenreich P Imamura T Jankowska EA Januzzi J Khazanie P Kinugawa K Lam CSP Matsue Y Metra M Ohtani T Francesco Piepoli M Ponikowski P Rosano GMC Sakata Y Seferović P Starling RC Teerlink JR Vardeny O Yamamoto K Yancy C Zhang J Zieroth S Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.Eur J Heart Fail. 2021; 23: 352-380Crossref PubMed Scopus (470) Google Scholar Moreover, an expert HF team confirmed the diagnosis. Patients with complete atrioventricular block, unrepaired cyanotic congenital heart disease, acute coronary syndrome requiring emergent revascularization or mechanical circulatory support, acute myocarditis, chronic renal failure requiring dialysis, or incomplete data were excluded. We categorized the patients according to their baseline heart rhythm on hospital admission into the with AF (n = 382) or without AF (non-AF, n = 507) groups. The groups were then subdivided into the disproportionately low BNP (LB), medium BNP (MB), and high BNP (HB) subgroups with BNP cut-off levels of 200 and 600 pg/ml (Figure 1), or into the LA volume index (LAVI) using cut-off LAVI values of 40, 80, 120, and 160 ml/m2 in each group respectively. 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BNP levels were positively correlated with LAVI values in the non-AF group, but negatively correlated in the AF group. BNP levels were for HF and in the non-AF group but in the AF group. studies have that BNP levels are in patients with AF in the of M S Mueller C Nowak R Ponikowski P M C Wu Clopton P Filippatos L LB K R O Anker SD Maisel Atrial fibrillation the diagnostic performance of natriuretic peptides in from the Study in Heart Heart Fail. PubMed Scopus (107) Google Scholar Conversely, the diagnostic performance of BNP is impaired by AF in the presence of M S Mueller C Nowak R Ponikowski P M C Wu Clopton P Filippatos L LB K R O Anker SD Maisel Atrial fibrillation the diagnostic performance of natriuretic peptides in from the Study in Heart Heart Fail. PubMed Scopus (107) Google Scholar the BNP for acute HF in patients without AF were to with AF, the was but a in to was to an increase in the M S Mueller C Nowak R Ponikowski P M C Wu Clopton P Filippatos L LB K R O Anker SD Maisel Atrial fibrillation the diagnostic performance of natriuretic peptides in from the Study in Heart Heart Fail. PubMed Scopus (107) Google Scholar clinical have used higher BNP cut-off values to patients with AF than without AF to Jr, Butler J A Felker Fiuzat M O'Connor C SD M Januzzi Jr, JL peptides criteria in clinical a heart failure Heart Fail. 2020; PubMed Scopus Google R Abraham WT A K JL K M SD L and and Investigators. of natriuretic peptide levels in heart failure patients with and without atrial Heart Fail. PubMed Scopus Google Scholar the clinical in acute HF patients with disproportionately low BNP levels and AF to of BNP levels and the LAVI have to LV M of left using and in patients with of left atrial left atrial ejection fraction and the in of pulmonary and at atrial Am Coll Cardiol. PubMed Scopus Google Scholar in the AF the between LA remodeling and BNP with a significant in patients with acute HF and AF. were in the the BNP was mainly in the and of its secretion may be by Drazner B-type natriuretic peptide in cardiovascular Full Text Full Text PDF PubMed Scopus Google Scholar BNP was in patients with constrictive pericarditis despite the presence of of the of by the and DH. Low atrial natriuretic factor levels and absent pulmonary edema in pericardial compression of the heart.Am J Cardiol. 1989; 63: 1271-1272Abstract Full Text PDF PubMed Scopus (23) Google D D The of in Am Coll Cardiol. PubMed Scopus Google Scholar Moreover, patients with obesity have BNP than without obesity despite higher K Kanzaki Y Tsuda K Maeda D Sohmiya K Hoshiga M. Disproportionately low BNP levels in patients of acute heart failure with preserved vs. reduced ejection fraction.Int J Cardiol. 2021; 327: 105-110Abstract Full Text Full Text PDF PubMed Scopus (14) Google K M B-type natriuretic peptide and B-type natriuretic peptide are in obesity despite higher left Heart 2006; PubMed Scopus Google M Reddy YNV Borlaug BA. the of a of heart failure with preserved ejection PubMed Scopus Google Scholar a of increased in pericardial BA Reddy YNV. The role of the pericardium in heart failure: implications for pathophysiology and treatment.JACC Heart Fail. 2019; 7: 574-585Crossref PubMed Scopus (96) Google M Reddy YNV Borlaug BA. the of a of heart failure with preserved ejection PubMed Scopus Google Scholar The are with the between and BNP levels in the study Recent studies have revealed that an increase in pericardial from pericardial but also from heart volume ventricle or BA Reddy YNV. The role of the pericardium in heart failure: implications for pathophysiology and treatment.JACC Heart Fail. 2019; 7: 574-585Crossref PubMed Scopus (96) Google Scholar Moreover, LA to to of the LV in L BA atrial and and left Am Coll Cardiol. 2019; PubMed Scopus Google Scholar The of LA is associated with LV in LA remodeling be associated with in LV the of atrioventricular and pericardial in reduced secretion of NP from the The of the heart mainly in the in patients with JP L B Atrial secretion of B-type natriuretic Heart 2006; PubMed Scopus Google de de The of the Full Text Full Text PDF PubMed Scopus Google Scholar studies have that LAVI of LV are positively correlated with BNP levels in patients without AF but with chronic B A Atrial a in atrial Res. 76: PubMed Scopus Google Scholar However, the studies included patients with chronic HF with LA remodeling LAVI to with study. atrial remodeling may to reduced secretion of NP deficiency) from atrial F B Butler J J G J D H. left atrial failure in heart J Heart Fail. PubMed Scopus Google Scholar the between the BNP level and LAVI be in patients without AF with LA and the in with AF with LA in the study (Figure We that LA remodeling to pericardial and atrial in BNP of impaired and atrial secretion of BNP despite high LV B A Atrial a in atrial Res. 76: PubMed Scopus Google S M. Atrial remodeling and atrial and Am Coll Cardiol. 63: PubMed Scopus Google Scholar BNP is believed to increase protectively under of given the cardioprotective roles of NP in regulating cardiovascular homeostasis and intravascular volume.2Nishikimi T Maeda N Matsuoka H. The role of natriuretic peptides in cardioprotection.Cardiovasc Res. 2006; 69: 318-328Crossref PubMed Scopus (415) Google Scholar it that BNP HF of the to BNP despite high LV biomarker Not in heart failure with preserved ejection Heart PubMed Scopus Google Scholar BNP to increased increased and increased in LA remodeling (Figure studies that BNP levels are associated with the of in AF patients without Y M K Y M H H K H M S M. of natriuretic peptide levels in atrial fibrillation without heart 2021; PubMed Scopus Google Scholar In contrast, a of the of with to on and in Heart Failure and The to in Patients with Heart Failure have revealed that BNP levels have in AF patients with HF and BNP levels R Abraham WT A K JL K M SD L and and Investigators. of natriuretic peptide levels in heart failure patients with and without atrial Heart Fail. PubMed Scopus Google Scholar However, patients with AF and low BNP pg/ml) levels had a significantly higher than without R Abraham WT A K JL K M SD L and and Investigators. of natriuretic peptide levels in heart failure patients with and without atrial Heart Fail. PubMed Scopus Google Scholar We that the presence of LB was to a prognosis in the non-AF group, but in the AF group, in with the of a R Abraham WT A K JL K M SD L and and Investigators. of natriuretic peptide levels in heart failure patients with and without atrial Heart Fail. PubMed Scopus Google Scholar in the high LAVI values were associated with a poor prognosis in patients with and without AF. The data on the between BNP levels and LAVI in the AF group the that the presence of LB was an of poor prognosis. clinical for the use of BNP to HF diagnosis and HF or Januzzi Jr, JL LA K Butler J Fonarow GC J A Yancy CW Writing to the for of heart failure to heart failure with reduced ejection a report of the of Cardiology Am Coll Cardiol. 2021; PubMed Scopus Google Scholar The diagnosis of HF in the of AF is AF is associated with in the and BNP levels that HF D Lam Voors AA M. Heart failure with preserved ejection fraction and atrial Am Coll Cardiol. PubMed Scopus Google Scholar that LB in patients with AF was to higher LAVI values and poor prognosis into a higher BNP cut-off was in most clinical HF for the of patients with AF. Patients with disproportionately low BNP levels and high LAVI values be to of HF diagnosis and its study in the of patients with acute HF and AF. using a BNP concentration may be for patients with LA remodeling and BNP in acute HF conditions. that BNP levels significantly and HF treatment in all the LB group. However, using an BNP concentration may be for patients with acute HF and BNP study some this was a retrospective observational study of a small-single with a the study the between LA remodeling and BNP to its retrospective However, that BNP be a or of atrial remodeling. studies may be required to the on LA remodeling and BNP HF was diagnosed by well-trained cardiologists based on the universal definition of HF B Coats AJS Tsutsui H Abdelhamid CM Adamopoulos S Albert N Anker SD Atherton J Böhm M Butler J Drazner MH Michael Felker G Filippatos G Fiuzat M Fonarow GC Gomez-Mesa JE Heidenreich P Imamura T Jankowska EA Januzzi J Khazanie P Kinugawa K Lam CSP Matsue Y Metra M Ohtani T Francesco Piepoli M Ponikowski P Rosano GMC Sakata Y Seferović P Starling RC Teerlink JR Vardeny O Yamamoto K Yancy C Zhang J Zieroth S Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.Eur J Heart Fail. 2021; 23: 352-380Crossref PubMed Scopus (470) Google Scholar and confirmed by an expert HF However, despite diagnostic criteria are for HF diagnosis. the of the AF group was based on the to at hospital and some patients in the non-AF group may have an AF or the the LA remodeling was a the of the atrial and volume are for its S C C L G atrial remodeling in heart failure: the role of index J PubMed Scopus Google Scholar We that LA remodeling in patients with AF was associated with disproportionately low BNP levels and poor which be in clinical be in patients with acute HF and AF to the of HF diagnosis and prognosis. is to the that LA remodeling affects and BNP