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2. Identifying plasma proteomic signatures from health to heart failure, across the ejection fraction spectrum

Author

Andrzejczyk, Karolina, Abou Kamar, Sabrina, van Ommen, Anne-Mar, Canto, Elisa Dal, Petersen, Teun B., Valstar, Gideon, Akkerhuis, K. Martijn, Cramer, Maarten Jan, Umans, Victor, Rutten, Frans H., Teske, Arco, Boersma, Eric, Menken, Roxana, van Dalen, Bas M., Hofstra, Leonard, Verhaar, Marianne, Brugts, Jasper, Asselbergs, Folkert, den Ruijter, Hester, and Kardys, Isabella

Published
2024
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6. Diagnostic Value of Aortic Valve Calcification Levels in the Assessment of Low-Gradient Aortic Stenosis

Author

Adrichem, Rik, Hokken, Thijmen W., Bouwmeester, Sjoerd, Abdelkarim, Ola, Vogel, Birgit, Blusztein, David I., Veulemans, Verena, Kuneman, Jurrien H., Geleijnse, Marcel L., Verhemel, Sarah, Van den Dorpel, Mark M.P., Kardys, Isabella, Tonino, Pim A.L., Chang, Su Min, Faza, Nadeen N., Jou, Stephanie, Ueyama, Hiroki A., Bartkowiak, Joanna, Zeus, Tobias, Bax, Jeroen J., Bertrand, Philippe B., Hahn, Rebecca T., Kodali, Susheel K., Lerakis, Stamatios, Mehran, Roxana, Little, Stephen H., Houthuizen, Patrick, and Van Mieghem, Nicolas M.

Published
2024
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8. Trajectories of cardiac troponin in the decades before cardiovascular death: a longitudinal cohort study

Author

Kimenai, Dorien M., Anand, Atul, de Bakker, Marie, Shipley, Martin, Fujisawa, Takeshi, Lyngbakken, Magnus N., Hveem, Kristian, Omland, Torbjørn, Valencia-Hernández, Carlos A., Lindbohm, Joni V., Kivimaki, Mika, Singh-Manoux, Archana, Strachan, Fiona E., Shah, Anoop S. V., Kardys, Isabella, Boersma, Eric, Brunner, Eric J., and Mills, Nicholas L.

Published
2023
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11. Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

Author

Vanmaele, Alexander, Bouwens, Elke, Hoeks, Sanne E, Kindt, Alida, Lamont, Lieke, Fioole, Bram, Moelker, Adriaan, ten Raa, Sander, Hussain, Burhan, Oliveira-Pinto, José, Ijpma, Arne S, van Lier, Felix, Akkerhuis, K. Martijn, Majoor-Krakauer, Danielle F, Hankemeier, Thomas, de Rijke, Yolanda, Verhagen, Hence JM, Boersma, Eric, and Kardys, Isabella

Published
2024
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18. Vessel fractional flow reserve-based non-culprit lesion reclassification in patients with ST-segment elevation myocardial infarction: Impact on treatment strategy and clinical outcome (FAST STEMI I study)

Author

Groenland, Frederik T.W., Huang, Jager, Scoccia, Alessandra, Neleman, Tara, Ziedses Des Plantes, Annemieke C., Nuis, Rutger-Jan, den Dekker, Wijnand K., Wilschut, Jeroen M., Diletti, Roberto, Kardys, Isabella, Van Mieghem, Nicolas M., and Daemen, Joost

Published
2023
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19. Impact of membranous septum length on pacemaker need with different transcatheter aortic valve replacement systems: The INTERSECT registry

Author

Hokken, Thijmen W., Muhemin, Mohammed, Okuno, Taishi, Veulemans, Verena, Lopes, Bernardo B., Beneduce, Alessandro, Vittorio, Romano, Ooms, Joris F., Adrichem, Rik, Neleman, Tara, Kardys, Isabella, Daemen, Joost, Chieffo, Alaide, Montorfano, Matteo, Cavalcante, Joao, Zeus, Tobias, Pilgrim, Thomas, Toggweiler, Stefan, and Van Mieghem, Nicolas M.

Published
2022
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22. The prognostic value of angiography-based vessel fractional flow reserve after percutaneous coronary intervention: The FAST Outcome study

Author

Neleman, Tara, Scoccia, Alessandra, Masdjedi, Kaneshka, Tomaniak, Mariusz, Ligthart, Jurgen M.R., Witberg, Karen T., Vermaire, Alise, Wolff, Quinten, Visser, Leon, Cummins, Paul, Kardys, Isabella, Wilschut, Jeroen, Diletti, Roberto, Den Dekker, Wijnand K., Zijlstra, Felix, Van Mieghem, Nicolas M., and Daemen, Joost

Published
2022
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25. Proteomic biomarkers related to obesity in heart failure with reduced ejection fraction and their associations with outcome.

Author

Petersen, Teun B., Suthahar, Navin, Asselbergs, Folkert W., de Bakker, Marie, Akkerhuis, K. Martijn, Constantinescu, Alina A., van Ramshorst, Jan, Katsikis, Peter D., van der Spek, Peter J., Umans, Victor A., de Boer, Rudolf A., Boersma, Eric, Rizopoulos, Dimitris, and Kardys, Isabella

Subjects
PEPTIDES, NEURON development, HEART transplantation, CELL adhesion, HEART failure, HEART assist devices
Abstract

Objective: Heart failure (HF) pathophysiology in patients with obesity may be distinct. To study these features, we identified obesity‐related biomarkers from 4210 circulating proteins in patients with HF with reduced ejection fraction (HFrEF) and examined associations of these proteins with HF prognosis and biological mechanisms. Methods: In 373 patients with trimonthly blood sampling during a median follow‐up of 2.1 (25th–75th percentile: 1.1–2.6) years, we applied an aptamer‐based multiplex approach measuring 4210 proteins in baseline samples and the last two samples before study end. Associations between obesity (BMI > 30 kg/m2) and baseline protein levels were analyzed. Subsequently, associations of serially measured obesity‐related proteins with biological mechanisms and the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, left ventricular assist device implantation, and heart transplantation) were examined. Results: Obesity was identified in 26% (96/373) of patients. A total of 30% (112/373) experienced a PEP (with obesity: 26% [25/96] vs. without obesity: 31% [87/277]). A total of 141/4210 proteins were linked to obesity, reflecting mechanisms of neuron projection development, cell adhesion, and muscle cell migration. A total of 50/141 proteins were associated with the PEP, of which 12 proteins related to atherosclerosis or hypertrophy provided prognostic information beyond clinical characteristics, N‐terminal pro‐B‐type natriuretic peptide, and high‐sensitivity troponin T. Conclusions: Patients with HFrEF and obesity show distinct proteomic profiles compared to patients with HFrEF without obesity. Obesity‐related proteins are independently associated with HF outcome. These proteins carry potential to improve management of obesity‐related HF and could be leads for future research. [ABSTRACT FROM AUTHOR]

Published
2024
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39. Sex‐specific cardiovascular protein levels and their link with clinical outcome in heart failure.

Author

de Bakker, Marie, Loncq de Jong, Mylène, Petersen, Teun, de Lange, Iris, Akkerhuis, K. Martijn, Umans, Victor A., Rizopoulos, Dimitris, Boersma, Eric, Brugts, Jasper J., and Kardys, Isabella

Subjects
HEART assist devices, FATTY acid-binding proteins, HEART failure, MATRIX metalloproteinases, TREFOIL factors, HEART transplantation
Abstract

Aims: This study aims to provide insight into sex‐specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. Methods and results: In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow‐up: 26 [17–30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex‐based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67 years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid‐binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction: 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase‐3, interleukin 1 receptor‐like 1, and myoglobin were higher in men (Pinteraction: <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction = 0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P = 0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P = 0.347]. Conclusions: Although multiple cardiovascular‐related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF. [ABSTRACT FROM AUTHOR]

Published
2024
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40. The different risk of new‐onset, chronic, worsening, and advanced heart failure: A systematic review and meta‐regression analysis.

Author

Shakoor, Abdul, Abou Kamar, Sabrina, Malgie, Jishnu, Kardys, Isabella, Schaap, Jeroen, de Boer, Rudolf A., van Mieghem, Nicolas M., van der Boon, Robert M.A., and Brugts, Jasper J.

Subjects
HEART failure, PROGNOSIS, MORTALITY, DEATH rate, SCIENTIFIC observation, CONFIDENCE intervals
Abstract

Aims: Heart failure (HF) is a chronic and progressive syndrome associated with a poor prognosis. While it may seem intuitive that the risk of adverse outcomes varies across the different stages of HF, an overview of these risks is lacking. This study aims to determine the risk of all‐cause mortality and HF hospitalizations associated with new‐onset HF, chronic HF (CHF), worsening HF (WHF), and advanced HF. Methods and results: We performed a systematic review of observational studies from 2012 to 2022 using five different databases. The primary outcomes were 30‐day and 1‐year all‐cause mortality, as well as 1‐year HF hospitalization. Studies were pooled using random effects meta‐analysis, and mixed‐effects meta‐regression was used to compare the different HF groups. Among the 15 759 studies screened, 66 were included representing 862 046 HF patients. Pooled 30‐day mortality rates did not reveal a significant distinction between hospital‐admitted patients, with rates of 10.13% for new‐onset HF and 8.11% for WHF (p = 0.10). However, the 1‐year mortality risk differed and increased stepwise from CHF to advanced HF, with a rate of 8.47% (95% confidence interval [CI] 7.24–9.89) for CHF, 21.15% (95% CI 17.78–24.95) for new‐onset HF, 26.84% (95% CI 23.74–30.19) for WHF, and 29.74% (95% CI 24.15–36.10) for advanced HF. Readmission rates for HF at 1 year followed a similar trend. Conclusions: Our meta‐analysis of observational studies confirms the different risk for adverse outcomes across the distinct HF stages. Moreover, it emphasizes the negative prognostic value of WHF as the first progressive stage from CHF towards advanced HF. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Genetics, Clinical Features, and Long-Term Outcome of Noncompaction Cardiomyopathy

Author

van Waning, Jaap I., Caliskan, Kadir, Hoedemaekers, Yvonne M., van Spaendonck-Zwarts, Karin Y., Baas, Annette F., Boekholdt, S. Matthijs, van Melle, Joost P., Teske, Arco J., Asselbergs, Folkert W., Backx, Ad P.C.M., du Marchie Sarvaas, Gideon J., Dalinghaus, Michiel, Breur, Johannes M.P.J., Linschoten, Marijke P.M., Verlooij, Laura A., Kardys, Isabella, Dooijes, Dennis, Lekanne Deprez, Ronald H., IJpma, Arne S., van den Berg, Maarten P., Hofstra, Robert M.W., van Slegtenhorst, Marjon A., Jongbloed, Jan D.H., and Majoor-Krakauer, Danielle

Published
2018
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46. Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

Author

Chin, Jie Fen, Aga, Yaar S., Abou Kamar, S., Kroon, D., Snelder, Sanne M., van de Poll, Sweder W.E., Kardys, Isabella, Brugts, Jasper J., de Boer, Rudolf A., and van Dalen, Bas M.

Subjects
HEART failure, HEART diseases, GLOBAL longitudinal strain, ADIPOSE tissues, BODY mass index, OBESITY
Abstract

Aim: Epicardial adipose tissue (EAT) plays a role in obesity‐related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. The aim of this study was to determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. Methods and results: Subjects with body mass index ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT‐1 (EAT <3.8 mm), 63 in EAT‐2 (EAT 3.8–5.4 mm), and 61 in EAT‐3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT‐3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one‐unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β coefficient −0.404, p = 0.002), and a decrease in LASct (%) (β coefficient −0.544, p = 0.027). Furthermore, EAT‐3 independently predicted cardiac dysfunction as defined by a GLS <18% (odds ratio 2.8, p = 0.013) and LASct <14% (odds ratio 2.5, p = 0.045). Conclusions: Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease. [ABSTRACT FROM AUTHOR]

Published
2023
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47. Serum uric acid is related to liver and kidney disease and 12-year mortality risk after myocardial infarction.

Author

Heerkens, Luc, van Westing, Anniek C., Voortman, Trudy, Kardys, Isabella, Boersma, Eric, and Geleijnse, Johanna M.

Subjects
URIC acid, KIDNEY diseases, NON-alcoholic fatty liver disease, MYOCARDIAL infarction, LIVER diseases
Abstract

Objective: To study the associations of non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), and serum uric acid (SUA) in patients with post-myocardial infarction (MI) patients, and the relationship of SUA with 12-year mortality risk. Methods: We included 3,396 patients (60-80 years old, 78% men) of the Alpha Omega Cohort. Multivariable prevalence ratios (PRs) were obtained for the association of NAFLD [fatty liver index (FLI), ≥77 (women) and ≥79 (men)] with CKD [estimated glomerular filtration rate (eGFR), <60 mL/min per 1.73 m²]. We calculated sensitivity and specificity of SUA to detect the (combined) presence and absence of NAFLD and CKD. Cause-specific mortality was monitored from enrolment (2002-2006) through December 2018. Hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality in SUA categories were obtained from multivariable Cox models. Results: Median baseline FLI was 67 (men, 68; women, 64), and mean ± SD eGFR was 81 ± 20 mL/min per 1.73 m² (17% with CKD). Sex-specific FLI was associated with higher CKD prevalence (PRtertile3 vs. tertile1, 1.94; 95% confidence interval: 1.57, 2.39). Baseline SUA was 0.36 ± 0.09 mmol/L. With increasing SUA concentrations, specificity for the presence of NAFLD, CKD, or both increased, and sensitivity decreased. During 12 (interquartile range, 9-14) years of follow-up, 1,592 patients died (713 from CVD). HRs ranged from 1.08 (0.88, 1.32) for SUA ≤0.25 mmol/L to 2.13 (1.75, 2.60) for SUA >0.50 mmol/L vs. SUA >0.30-0.35 mmol/L for all-cause mortality. For CVD mortality, HRs ranged from 1.05 (0.77, 1.44) to 2.43 (1.83, 3.25). Conclusions: NAFLD and CKD were strongly associated, which was reflected by higher SUA concentrations. SUA was a strong predictor of 12-year mortality risk after MI. [ABSTRACT FROM AUTHOR]

Published
2023
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48. Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm.

Author

Bouwens, Elke, Vanmaele, Alexander, Hoeks, Sanne E, Verhagen, Hence JM, Fioole, Bram, Moelker, Adriaan, ten Raa, Sander, Hussain, Burhan, Oliveira-Pinto, José, Bastos Gonçalves, Frederico, Ijpma, Arne S, Hoefer, Imo E, van Lier, Felix, Akkerhuis, K Martijn, Majoor-Krakauer, Danielle F, Boersma, Eric, and Kardys, Isabella

Subjects
ABDOMINAL aortic aneurysms, ENDOVASCULAR aneurysm repair, ENDOVASCULAR surgery, CARDIOVASCULAR diseases, BIOMARKERS
Abstract

Background: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. Methods: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Results: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of −0.092 (−0.148, −0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: −0.128 (−0.212, −0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). Conclusion: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD. ClinicalTrials.gov Identifier: NCT03703947. [ABSTRACT FROM AUTHOR]

Published
2023
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