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53. Proteomic diversity of high‐density lipoprotein explains its association with clinical outcome in patients with heart failure

Author

Emmens, Johanna Elisabeth, Jones, Donald J.L., Cao, Thong H., Chan, Daniel C.S., Romaine, Simon P.R., Quinn, Paulene A., Anker, Stefan D., Cleland, John G., Dickstein, Kenneth, Filippatos, Gerasimos, Hillege, Hans L., Lang, Chim C., Ponikowski, Piotr, Samani, Nilesh J., van Veldhuisen, Dirk J., Zannad, Faiz, Zwinderman, Aeilko H., Metra, Marco, de Boer, Rudolf A., Voors, Adriaan A., and Ng, Leong L.

Published
2018
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54. Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure.

Author

Markousis-Mavrogenis, George, Minich, Waldemar B, Al-Mubarak, Ali A, Anker, Stefan D, Cleland, John G F, Dickstein, Kenneth, Lang, Chim C, Ng, Leong L, Samani, Nilesh J, Zannad, Faiez, Metra, Marco, Seemann, Petra, Hoeg, Antonia, Lopez, Patricio, Veldhuisen, Dirk J van, Boer, Rudolf A de, Voors, Adriaan A, van der Meer, Peter, Schomburg, Lutz, and Bomer, Nils

Subjects
MUSCARINIC receptors, HEART failure patients, AUTOANTIBODIES, CHRONIC obstructive pulmonary disease, CHEMILUMINESCENCE immunoassay
Abstract

Aims The importance of autoantibodies (AABs) against adrenergic/muscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinical/prognostic associations of four AABs recognizing the M2-muscarinic receptor or the β1-, β2-, or β3-adrenergic receptor in a large and well-characterized cohort of patients with HF. Methods and results Serum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analysed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (P = 0.045). Seropositivity occurred more frequently only for anti-M2 AABs (P = 0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, and atrial fibrillation) and with medication use. Only anti-β1 AAB seropositivity was associated with the primary outcome [hazard ratio (95% confidence interval): 1.37 (1.04–1.81), P = 0.024] and HF rehospitalization [1.57 (1.13–2.19), P = 0.010] in univariable analyses but remained associated only with HF rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model [1.47 (1.05–2.07), P = 0.030]. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function. Conclusions AAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-β1 AABs were independently associated with HF rehospitalization. The exact clinical value of AABs remains to be elucidated. [ABSTRACT FROM AUTHOR]

Published
2023
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55. Using matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) profiling in order to predict clinical outcomes of patients with heart failure

Author

Cao, Thong Huy, Jones, Donald J. L., Quinn, Paulene A., Chan, Daniel Chu Siong, Hafid, Narayan, Parry, Helen M., Mohan, Mohapradeep, Sandhu, Jatinderpal K., Anker, Stefan D., Cleland, John G., Dickstein, Kenneth, Filippatos, Gerasimos, Hillege, Hans L., Metra, Marco, Ponikowski, Piotr, Samani, Nilesh J., Van Veldhuisen, Dirk J., Zannad, Faiez, Zwinderman, Aeilko H., Voors, Adriaan A., Lang, Chim C., and Ng, Leong L.

Published
2018
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57. Clinical implications of left atrial changes after optimization of medical therapy in patients with heart failure

Author

Inciardi, Riccardo M., primary, Pagnesi, Matteo, additional, Lombardi, Carlo M., additional, Anker, Stefan D., additional, Cleland, John G., additional, Dickstein, Kenneth, additional, Filippatos, Gerasimos S., additional, Lang, Chim C., additional, Ng, Leong L., additional, Pellicori, Pierpaolo, additional, Ponikowski, Piotr, additional, Samani, Nilesh J., additional, Zannad, Faiez, additional, van Veldhuisen, Dirk J., additional, Solomon, Scott D., additional, Voors, Adriaan A., additional, and Metra, Marco, additional

Published
2022
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58. Fibro‐inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial

Author

Brady, Emer M., primary, Gulsin, Gaurav S., additional, Mirkes, Evgeny M., additional, Parke, Kelly, additional, Kanagala, Prathap, additional, Ng, Leong L., additional, Graham‐Brown, Matthew P. M., additional, Athithan, Lavanya, additional, Henson, Joseph, additional, Redman, Emma, additional, Yang, Jang, additional, Zhao, Lei, additional, Argyridou, Stavroula, additional, Gray, Laura J., additional, Yates, Thomas, additional, Davies, Melanie J., additional, and McCann, Gerry P., additional

Published
2022
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59. Whole blood transcriptomic profiling identifies molecular pathways related to cardiovascular mortality in heart failure

Author

Nath, Mintu, primary, Romaine, Simon P.R., additional, Koekemoer, Andrea, additional, Hamby, Stephen, additional, Webb, Thomas R., additional, Nelson, Christopher P., additional, Castellanos‐Uribe, Marcos, additional, Papakonstantinou, Manolo, additional, Anker, Stefan D., additional, Lang, Chim C., additional, Metra, Marco, additional, Zannad, Faiez, additional, Filippatos, Gerasimos, additional, van Veldhuisen, Dirk J., additional, Cleland, John G., additional, Ng, Leong L., additional, May, Sean T., additional, Marelli‐Berg, Federica, additional, Voors, Adriaan A., additional, Timmons, James A., additional, and Samani, Nilesh J., additional

Published
2022
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61. Biomarker changes as surrogate endpoints in early-phase trials in heart failure with reduced ejection fraction

Author

Cardiovasculaire Epi Team 7B, Onderzoek Precision medicine, Savarese, Gianluigi, Uijl, Alicia, Ouwerkerk, Wouter, Tromp, Jasper, Anker, Stefan D, Dickstein, Kenneth, Hage, Camilla, Lam, Carolyn S P, Lang, Chim C, Metra, Marco, Ng, Leong L, Orsini, Nicola, Samani, Nilesh J, van Veldhuisen, Dirk J, Cleland, John G F, Voors, Adriaan A, Lund, Lars H, Cardiovasculaire Epi Team 7B, Onderzoek Precision medicine, Savarese, Gianluigi, Uijl, Alicia, Ouwerkerk, Wouter, Tromp, Jasper, Anker, Stefan D, Dickstein, Kenneth, Hage, Camilla, Lam, Carolyn S P, Lang, Chim C, Metra, Marco, Ng, Leong L, Orsini, Nicola, Samani, Nilesh J, van Veldhuisen, Dirk J, Cleland, John G F, Voors, Adriaan A, and Lund, Lars H

Published
2022

65. Clinical implications of low estimated protein intake in patients with heart failure

Author

Streng, Koen W., primary, Hillege, Hans L., additional, ter Maaten, Jozine M., additional, van Veldhuisen, Dirk J., additional, Dickstein, Kenneth, additional, Ng, Leong L., additional, Samani, Nilesh J., additional, Metra, Marco, additional, Ponikowski, Piotr, additional, Cleland, John G., additional, Anker, Stefan D., additional, Romaine, Simon P.R., additional, Damman, Kevin, additional, van der Meer, Peter, additional, Lang, Chim C., additional, and Voors, Adriaan A., additional

Published
2022
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66. Biomarker changes as surrogate endpoints in early‐phase trials in heart failure with reduced ejection fraction

Author

Savarese, Gianluigi, primary, Uijl, Alicia, additional, Ouwerkerk, Wouter, additional, Tromp, Jasper, additional, Anker, Stefan D., additional, Dickstein, Kenneth, additional, Hage, Camilla, additional, Lam, Carolyn S.P., additional, Lang, Chim C., additional, Metra, Marco, additional, Ng, Leong L., additional, Orsini, Nicola, additional, Samani, Nilesh J., additional, van Veldhuisen, Dirk J., additional, Cleland, John G.F., additional, Voors, Adriaan A., additional, and Lund, Lars H., additional

Published
2022
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67. Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

Author

Núñez, Julio, primary, Bayés-Genís, Antoni, additional, Revuelta-López, Elena, additional, Miñana, Gema, additional, Santas, Enrique, additional, ter Maaten, Jozine M., additional, de la Espriella, Rafael, additional, Carratalá, Arturo, additional, Lorenzo, Miguel, additional, Palau, Patricia, additional, Llàcer, Pau, additional, Valle, Alfonso, additional, Bodi, Vicent, additional, Núñez, Eduardo, additional, Lupón, Josep, additional, Lang, Chim, additional, Ng, Leong L., additional, Metra, Marco, additional, Sanchis, Juan, additional, and Voors, Adriaan A., additional

Published
2022
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68. Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure

Author

Emmens, Johanna E. de Borst, Martin H. Boorsma, Eva M. and Damman, Kevin Navis, Gerjan van Veldhuisen, Dirk J. and Dickstein, Kenneth Anker, Stefan D. Lang, Chim C. and Filippatos, Gerasimos Metra, Marco Samani, Nilesh J. and Ponikowski, Piotr Ng, Leong L. Voors, Adriaan A. ter Maaten, Jozine M.

Subjects
urogenital system, urologic and male genital diseases, female genital diseases and pregnancy complications
Abstract

Background and objectives The estimated glomerular filtration rate (eGFR) is a crucial parameter in heart failure. Much less is known about the importance of tubular function. We addressed the effect of tubular maximum phosphate reabsorption capacity (TmP/GFR), a parameter of proximal tubular function, in patients with heart failure.Design, setting, participants, & measurements We established TmP/GFR (Bijvoet formula) in 2085 patients with heart failure and studied its association with deterioration of kidney function (> 25% eGFR decrease from baseline) and plasma neutrophil gelatinase-associated lipocalin (NGAL) doubling (baseline to 9 months) using logistic regression analysis and clinical outcomes using Cox proportional hazards regression. Additionally, we evaluated the effect of sodium-glucose transport protein 2 (SGLT2) inhibition by empagliflozin on tubular maximum phosphate reabsorption capacity in 78 patients with acute heart failure using analysis of covariance.Results Low TmP/GFR (< 0.80 mmol/L) was observed in 1392 (67%) and 21 (27%) patients. Patients with lower TmP/GFR had more advanced heart failure, lower eGFR, and higher levels of tubular damage markers. The main determinant of lower TmP/GFR was higher fractional excretion of urea (P < 0.001). Lower TmP/GFR was independently associated with higher risk of plasma NGAL doubling (odds ratio, 2.20; 95% confidence interval, 1.05 to 4.66; P=0.04) but not with deterioration of kidney function. Lower TmP/GFR was associated with higher risk of all-cause mortality (hazard ratio, 2.80; 95% confidence interval, 1.37 to 5.73; P=0.005), heart failure hospitalization (hazard ratio, 2.29; 95% confidence interval, 1.08 to 4.88; P=0.03), and their combination (hazard ratio, 1.89; 95% confidence interval, 1.07 to 3.36; P=0.03) after multivariable adjustment. Empagliflozin significantly increased TmP/GFR compared with placebo after 1 day (P=0.004) but not after adjustment for eGFR change.Conclusions TmP/GFR, a measure of proximal tubular function, is frequently reduced in heart failure, especially in patients with more advanced heart failure. Lower TmP/GFR is furthermore associated with future risk of plasma NGAL doubling and worse clinical outcomes, independent of glomerular function.

Published
2022

69. Additional burden of iron deficiency in heart failure patients beyond the cardio‐renal anaemia syndrome: findings from the BIOSTAT‐CHF study

Author

Alnuwaysir, Ridha I.S., Grote Beverborg, Niels, Hoes, Martijn F., Markousis‐Mavrogenis, George, Gomez, Karla A., van der Wal, Haye H., Cleland, John G.F., Dickstein, Kenneth, Lang, Chim C., Ng, Leong L., Ponikowski, Piotr, Anker, Stefan D., van Veldhuisen, Dirk J., Voors, Adriaan A., and van der Meer, Peter

Abstract

Aims:\ud Whereas the combination of anaemia and chronic kidney disease (CKD) has been extensively studied in patients with heart failure (HF), the contribution of iron deficiency (ID) to this dysfunctional interplay is unknown. We aimed to assess clinical associates and pathophysiological pathways related to ID in this multimorbid syndrome.\ud \ud Methods and results:\ud We studied 2151 patients with HF from the BIOSTAT-CHF cohort. Patients were stratified based on ID (transferrin saturation

Published
2022

70. Midregion Prohormone Adrenomedullin and Prognosis in Patients Presenting With Acute Dyspnea: Results From the BACH (Biomarkers in Acute Heart Failure) Trial

Author

Maisel, Alan, Mueller, Christian, Nowak, Richard M., Peacock, W. Frank, Ponikowski, Piotr, Mockel, Martin, Hogan, Christopher, Wu, Alan H.B., Richards, Mark, Clopton, Paul, Filippatos, Gerasimos S., Di Somma, Salvatore, Anand, Inder, Ng, Leong L., Daniels, Lori B., Neath, Sean-Xavier, Christenson, Robert, Potocki, Mihael, McCord, James, Hartmann, Oliver, Morgenthaler, Nils G., and Anker, Stefan D.

Published
2011
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73. Assessment of Proximal Tubular Function by Tubular Maximum Phosphate Reabsorption Capacity in Heart Failure

Author

Emmens, Johanna E., primary, de Borst, Martin H., additional, Boorsma, Eva M., additional, Damman, Kevin, additional, Navis, Gerjan, additional, van Veldhuisen, Dirk J., additional, Dickstein, Kenneth, additional, Anker, Stefan D., additional, Lang, Chim C., additional, Filippatos, Gerasimos, additional, Metra, Marco, additional, Samani, Nilesh J., additional, Ponikowski, Piotr, additional, Ng, Leong L., additional, Voors, Adriaan A., additional, and ter Maaten, Jozine M., additional

Published
2022
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74. Determination ofN7‐glycidamide guanine adducts in human blood DNA following exposure to dietary acrylamide using liquid chromatography/tandem mass spectrometry

Author

Jones, Donald J. L., primary, Singh, Raj, additional, Emms, Victoria, additional, Farmer, Peter B., additional, Grant, Derryn, additional, Quinn, Paulene, additional, Maxwell, Colleen, additional, Mina, Antria, additional, Ng, Leong L., additional, Schumacher, Sandra, additional, and Britton, Robert G., additional

Published
2022
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75. Pathophysiological pathways related to high plasma growth differentiation factor 15 concentrations in patients with heart failure

Author

Ceelen, Daan, primary, Voors, Adriaan A., additional, Tromp, Jasper, additional, van Veldhuisen, Dirk J., additional, Dickstein, Kenneth, additional, de Boer, Rudolf A., additional, Lang, Chim C., additional, Anker, Stefan D., additional, Ng, Leong L., additional, Metra, Marco, additional, Ponikowski, Piotr, additional, and Figarska, Sylwia M., additional

Published
2022
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76. Additional burden of iron deficiency in heart failure patients beyond the cardio‐renal anaemia syndrome: findings from theBIOSTAT‐CHFstudy

Author

Alnuwaysir, Ridha I.S., primary, Grote Beverborg, Niels, additional, Hoes, Martijn F., additional, Markousis‐Mavrogenis, George, additional, Gomez, Karla A., additional, Wal, Haye H., additional, Cleland, John G.F., additional, Dickstein, Kenneth, additional, Lang, Chim C., additional, Ng, Leong L., additional, Ponikowski, Piotr, additional, Anker, Stefan D., additional, Veldhuisen, Dirk J., additional, Voors, Adriaan A., additional, and Meer, Peter, additional

Published
2021
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77. 128 Clinical impact of changes in mitral regurgitation severity after optimization of medical therapy in heart failure: insights from BIOSTAT-CHF

Author

Pagnesi, Matteo, primary, Adamo, Marianna, additional, Sama, Iziah E., additional, Anker, Stefan D., additional, Cleland, John G., additional, Dickstein, Kenneth, additional, Filippatos, Gerasimos S., additional, Inciardi, Riccardo M., additional, Lang, Chim C., additional, Lombardi, Carlo M., additional, Ng, Leong L., additional, Ponikowski, Piotr, additional, Samani, Nilesh J., additional, Zannad, Faiez, additional, Van Veldhuisen, Dirk J., additional, Voors, Adriaan A., additional, and Metra, Marco, additional

Published
2021
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82. Abstract 11702: Sex Differences in Diabetic Cardiomyopathy: Greater Reduction in Myocardial Perfusion Reserve in Women Than Men Driven by Increased Resting Perfusion

Author

Yeo, Jian L, primary, Gulsin, Gaurav S, additional, Brady, Emer M, additional, Athithan, Lavanya, additional, Arnold, Jayanth R, additional, Singh, Anvesha, additional, Henson, Joseph, additional, Redman, Emma, additional, Khunti, Kamlesh, additional, Yates, Thomas, additional, Ng, Leong L, additional, Davies, Melanie J, additional, and McCann, Gerry P, additional

Published
2021
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83. Pathophysiological pathways in patients with heart failure and atrial fibrillation

Author

Santema, Bernadet T, primary, Arita, Vicente Artola, additional, Sama, Iziah E, additional, Kloosterman, Mariëlle, additional, van den Berg, Maarten P, additional, Nienhuis, Hans L A, additional, Van Gelder, Isabelle C, additional, van der Meer, Peter, additional, Zannad, Faiez, additional, Metra, Marco, additional, Ter Maaten, Jozine M, additional, Cleland, John G, additional, Ng, Leong L, additional, Anker, Stefan D, additional, Lang, Chim C, additional, Samani, Nilesh J, additional, Dickstein, Kenneth, additional, Filippatos, Gerasimos, additional, van Veldhuisen, Dirk J, additional, Lam, Carolyn S P, additional, Rienstra, Michiel, additional, and Voors, Adriaan A, additional

Published
2021
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87. Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.

Author

Ibrahim, Wadah, Wilde, Michael J., Cordell, Rebecca L., Richardson, Matthew, Salman, Dahlia, Free, Robert C., Zhao, Bo, Singapuri, Amisha, Hargadon, Beverley, Gaillard, Erol A., Suzuki, Toru, Ng, Leong L., Coats, Tim, Thomas, Paul, Monks, Paul S., Brightling, Christopher E., Greening, Neil J., Siddiqui, Salman, Munton, Rachel, and Le Quesne, John

Subjects
CHRONIC obstructive pulmonary disease, DYSPNEA, NONINVASIVE diagnostic tests, VOLATILE organic compounds, ACUTE diseases, COMMUNITY-acquired pneumonia
Abstract

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analyzed exhaled breath samples from 277 participants presenting acute cardiorespiratory exacerbations and aged-matched healthy volunteers. Topological data analysis phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes (acute heart failure, acute asthma, acute chronic obstructive pulmonary disease, and community-acquired pneumonia). A multibiomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example, selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs. Take my breath(lessness) away: Breath analysis can be a useful noninvasive way to detect disease. Here, Ibrahim et al. studied the volatile organic compound (VOC) signatures associated with acute cardiorespiratory diseases in patients presenting breathlessness. Using two-dimensional gas chromatography and mass spectrometry, the authors found clusters of VOCs associated with acute heart failure, asthma, chronic obstructive pulmonary disease, and pneumonia. These breath biomarkers correlated with blood-based biomarkers. An acute disease VOC score based on a 101-biomarker panel was associated with 2-year all-cause mortality. This study demonstrates how breathomics can help diagnose disease and further our understanding of metabolic subgroups. [ABSTRACT FROM AUTHOR]

Published
2022
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88. Impact of mitral regurgitation in patients with worsening heart failure: insights from BIOSTAT‐CHF

Author

Pagnesi, Matteo, primary, Adamo, Marianna, additional, Sama, Iziah E., additional, Anker, Stefan D., additional, Cleland, John G., additional, Dickstein, Kenneth, additional, Filippatos, Gerasimos S., additional, Lang, Chim C., additional, Ng, Leong L., additional, Ponikowski, Piotr, additional, Ravera, Alice, additional, Samani, Nilesh J., additional, Zannad, Faiez, additional, Veldhuisen, Dirk J., additional, Voors, Adriaan A., additional, and Metra, Marco, additional

Published
2021
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89. Differences in biomarkers and molecular pathways according to age for patients with HFrEF

Author

Ferreira, Joao Pedro Ouwerkerk, Wouter Santema, Bernadet T. and van Veldhuisen, Dirk J. Lang, Chim C. Ng, Leong L. Anker, Stefan D. Dickstein, Kenneth Metra, Marco Cleland, John G. F. Nilesh, Samani J. Filippatos, Gerasimos Aboumsallem, Joseph-Pierre de Boer, Rudolf A. Figarska, Sylwia Sama, Iziah E. Voors, Adriaan A. Zannad, Faiez

Abstract

Aims Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. We aim to better understand the underlying pathophysiological processes associated with ageing in HFrEF potentially leading to targeted therapies in this vulnerable population. Methods and results From a panel of 363 cardiovascular biomarkers available in 1611 patients with HFrEF in the BIOSTAT-CHF index cohort and cross-validated in 823 patients in the BIOSTAT-CHF validation cohort, we tested which biomarkers were dysregulated in patients aged >75 vs.

Published
2021

90. Impact of mitral regurgitation in patients with worsening heart failure: insights from BIOSTAT-CHF

Author

Pagnesi, Matteo Adamo, Marianna Sama, Iziah E. Anker, Stefan D. Cleland, John G. Dickstein, Kenneth Filippatos, Gerasimos S. Lang, Chim C. Ng, Leong L. Ponikowski, Piotr Ravera, Alice Samani, Nilesh J. Zannad, Faiez van Veldhuisen, Dirk J. Voors, Adriaan A. Metra, Marco

Abstract

Aims Few data regarding the prevalence and prognostic impact of mitral regurgitation (MR) in patients with worsening chronic or new-onset acute heart failure (HF) are available. We investigated the role of MR in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Methods and results We performed a retrospective post-hoc analysis including patients from both the index and validation BIOSTAT-CHF cohorts with data regarding MR status. The primary endpoint was a composite of all-cause death or HF hospitalization. Among 4023 patients included, 1653 patients (41.1%) had moderate- severe MR. Compared to others, patients with moderate- severe MR were more likely to have atrial fibrillation and chronic kidney disease and had larger left ventricular (LV) dimensions, lower LV ejection fraction (LVEF), worse quality of life, and higher plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP). A primary outcome event occurred in 697 patients with, compared to 836 patients without, moderate- severe MR [Kaplan- Meier 2-year estimate: 42.2% vs. 35.3%; hazard ratio (HR) 1.28; 95% confidence interval (CI) 1.16- 1.41; log-rank P < 0.0001]. The association between MR and the primary endpoint remained significant after adjusting for baseline variables and the previously validated BIOSTAT-CHF risk score (adjusted HR 1.11; 95% CI 1.00- 1.23; P = 0.041). Subgroup analyses showed a numerically larger impact of MR on the primary endpoint in patients with lower LVEF, larger LV end-diastolic diameter, and higher plasma NT-proBNP. Conclusions Moderate- severe MR is common in patients with worsening chronic or new-onset acute HF and is strongly associated with outcome, independently of other features related to HF severity.

Published
2021

91. Pathophysiological pathways in patients with heart failure and atrial fibrillation

Author

Santema, Bernadet T. Arita, Vicente Artola Sama, Iziah E. Kloosterman, Mariëlle van den Berg, Maarten P. Nienhuis, Hans L. A. Van Gelder, Isabelle C. van der Meer, Peter Zannad, Faiez Metra, Marco Ter Maaten, Jozine M. Cleland, John G. Ng, Leong L. Anker, Stefan D. Lang, Chim C. Samani, Nilesh J. Dickstein, Kenneth Filippatos, Gerasimos van Veldhuisen, Dirk J. Lam, Carolyn S. P. Rienstra, Michiel Voors, Adriaan A.

Abstract

AIMS: Atrial fibrillation (AF) and heart failure (HF) are two growing epidemics that frequently co-exist. We aimed to gain insights into underlying pathophysiological pathways in HF patients with AF by comparing circulating biomarkers using pathway overrepresentation analyses. METHODS AND RESULTS: From a panel of 92 biomarkers from different pathophysiological domains available in 1,620 patients with HF, we first tested which biomarkers were dysregulated in patients with HF and AF (n = 648) compared with patients in sinus rhythm (n = 972). Secondly, pathway overrepresentation analyses were performed to identify biological pathways linked to higher plasma concentrations of biomarkers in patients who had HF and AF. Findings were validated in an independent HF cohort (n = 1,219, 38\% with AF). Patient with AF and HF were older, less often women, and less often had a history of coronary artery disease compared with those in sinus rhythm. In the index cohort, 24 biomarkers were upregulated in patients with AF and HF. In the validation cohort, 8 biomarkers were upregulated, which all overlapped with the 24 biomarkers found in the index cohort. The strongest up-regulated biomarkers in patients with AF were spondin-1 (fold change 1.18, p = 1.33x10-12), insulin-like growth factor-binding protein-1 (fold change 1.32, p = 1.08x10-8), and insulin-like growth factor-binding protein-7 (fold change 1.33, p = 1.35x10-18). Pathway overrepresentation analyses revealed that the presence of AF was associated with activation amyloid-beta metabolic processes, amyloid-beta formation, and amyloid precursor protein catabolic processes with a remarkable consistency observed in the validation cohort. CONCLUSION: In two independent cohorts of patients with HF, the presence of AF was associated with activation of three pathways related to amyloid-beta. These hypothesis-generating results warrant confirmation in future studies. TRANSLATIONAL PERSPECTIVE: Using an unbiased approach, we identified and validated dysregulation of three amyloid-beta related pathways in patients who had heart failure (HF) with concomitant atrial fibrillation (AF). Amyloid-beta depositions are a hallmark of Alzheimer's disease, but might also play a role in pathophysiological processes outside the central nervous system. Biopsy studies are needed to confirm the pathophysiological role of amyloid-beta in patients with AF and HF. Diagnostic and therapeutic implications should be investigated in the light of potential pathophysiological overlap between the three aging-related epidemics: Alzheimer's disease, AF and HF.

Published
2021

98. Neutrophil‐to‐lymphocyte ratio and outcomes in patients with new‐onset or worsening heart failure with reduced and preserved ejection fraction

Author

Curran, Fraser M., primary, Bhalraam, U, additional, Mohan, Mohapradeep, additional, Singh, Jagdeep S., additional, Anker, Stefan D., additional, Dickstein, Kenneth, additional, Doney, Alexander S., additional, Filippatos, Gerasimos, additional, George, Jacob, additional, Metra, Marco, additional, Ng, Leong L., additional, Palmer, Colin N., additional, Samani, Nilesh J., additional, van Veldhuisen, Dirk J., additional, Voors, Adriaan A., additional, Lang, Chim C., additional, and Mordi, Ify R., additional

Published
2021
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99. Perceived risk profile and treatment optimization in heart failure: an analysis from BIOlogy Study to TAilored Treatment in chronic heart failure

Author

Kobayashi, Masatake, primary, Voors, Adriaan A., additional, Ouwerkerk, Wouter, additional, Duarte, Kevin, additional, Girerd, Nicolas, additional, Rossignol, Patrick, additional, Metra, Marco, additional, Lang, Chim C., additional, Ng, Leong L., additional, Filippatos, Gerasimos, additional, Dickstein, Kenneth, additional, van Veldhuisen, Dirk J., additional, Zannad, Faiez, additional, and Ferreira, João Pedro, additional

Published
2021
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100. Impaired High‐Density Lipoprotein Function in Patients With Heart Failure

Author

Emmens, Johanna E., primary, Jia, Congzhuo, additional, Ng, Leong L., additional, van Veldhuisen, Dirk J., additional, Dickstein, Kenneth, additional, Anker, Stefan D., additional, Lang, Chim C., additional, Filippatos, Gerasimos, additional, Cleland, John G. F., additional, Metra, Marco, additional, Voors, Adriaan A., additional, de Boer, Rudolf A., additional, and Tietge, Uwe J. F., additional

Published
2021
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