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1.
Neth Heart J ; 32(6): 228-237, 2024 Jun.
Article En | MEDLINE | ID: mdl-38776039

This paper presents an overview of the development of an integrated patient-centred cardiac care registry spanning the initial 5 years (September 2017 to December 2022). The Netherlands Heart Registration facilitates registration committees in which mandated cardiologists and cardiothoracic surgeons structurally evaluate quality of care using real-world data. With consistent attendance rates exceeding 60%, a valuable network is supported. Over time, the completeness level of the registry has increased. Presently, four out of six quality registries show over 95% completeness in variables that are part of the quality policies of cardiology and cardiothoracic surgery societies. Notably, 93% of the centres voluntarily report outcomes related to open heart surgery and (trans)catheter interventions publicly. Moreover, outcomes after implantable cardioverter-defibrillator and pacemaker procedures are transparently reported by 26 centres. Multiple innovation projects have been initiated by the committees, signalling a shift from publishing outcomes transparently to collaborative efforts in sharing healthcare processes and investigating improvement initiatives. The next steps will focus on the entire pathway of cardiac care for a specific medical condition instead of focusing solely on the outcomes of the procedures. This redirection of focus to a comprehensive assessment of the patient pathway in cardiac care ultimately aims to optimise outcomes for all patients.

2.
Neth Heart J ; 32(3): 118-124, 2024 Mar.
Article En | MEDLINE | ID: mdl-37823980

BACKGROUND: To date, claims data have not been used to study outcome differences between low and high socioeconomic status (SES) patients surviving ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in the Netherlands. AIM: To evaluate STEMI and NSTEMI care among patients with low and high SES in the referral area of three Dutch percutaneous coronary intervention (PCI) centres, using claims data as a source. METHODS: STEMI and NSTEMI patients treated in 2015-2017 were included. Patients' SES scores were collected based on their postal code via an open access government database. In patients with low (SES1) and high (SES4) status, revascularisation strategies and secondary prevention medication were compared. RESULTS: A total of 2065 SES1 patients (age 68 ± 13 years, 58% NSTEMI) and 1639 SES4 patients (age 68 ± 13 years, 63% NSTEMI) were included. PCI use was lower in SES1 compared to SES4 in both STEMI (80% vs 84%, p < 0.012) and NSTEMI (42% vs 48%, p < 0.002) patients. Coronary artery bypass grafting was performed more often in SES1 than in SES4 in both STEMI (7% vs 4%, p = NS) and NSTEMI (11% vs 7%, p < 0.001) patients. Optimal medical therapy use in STEMI patients was higher in SES1 compared to SES4 (52% vs 46%, p = 0.01) but comparable among NSTEMI patients (39% vs 40%, p = NS). One-year mortality was comparable in SES1 and SES4 patients following STEMI (14% vs 16%, p = NS) and NSTEMI (10% vs 11%, p = NS). CONCLUSION: Combined analysis of claims data and area-specific socioeconomic statistics can provide unique insight into how to improve myocardial infarction care for low and high SES patients.

3.
Ned Tijdschr Geneeskd ; 1672023 07 05.
Article Nl | MEDLINE | ID: mdl-37493329

Bacterial endocarditis is associated with high morbidity and mortality and requires a long hospitalization due to long-term intravenous antimicrobial therapy. It is possible to partially treat selected and stable patients at home. We present 3 patients partially treated at home with intravenous antibiotics for proven complicated endocarditis. Patient A presented with a septic shock and mitral valve endocarditis. Patient B presented with an ICD lead endocarditis and patient C presented with an mitral valve endocarditis. All 3 patients had a complicated endocarditis and presented with extensive embolic dissemination. Following the initial complicated clinical course, the patients were discharged for antibiotic home treatment after clinical improvement. Subsequent treatment was successful and reduced their hospital stay with more than 14 days. Thanks to transmural cooperation with the home-care colleagues, we can safely provide antibiotic care at home so that stabilized endocarditis patients can be treated in their own habitat.


Anti-Infective Agents , Endocarditis, Bacterial , Endocarditis , Humans , Outpatients , Endocarditis, Bacterial/drug therapy , Endocarditis/drug therapy , Endocarditis/complications , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use
4.
Eur Heart J Acute Cardiovasc Care ; 12(7): 451-461, 2023 Jul 07.
Article En | MEDLINE | ID: mdl-37096818

AIMS: Evidence regarding the role of serial measurements of biomarkers for risk assessment in post-acute coronary syndrome (ACS) patients is limited. The aim was to explore the prognostic value of four, serially measured biomarkers in a large, real-world cohort of post-ACS patients. METHODS AND RESULTS: BIOMArCS is a prospective, multi-centre, observational study in 844 post-ACS patients in whom 12 218 blood samples (median 17 per patient) were obtained during 1-year follow-up. The longitudinal patterns of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and growth differentiation factor 15 (GDF-15) were analysed in relation to the primary endpoint (PE) of cardiovascular mortality and recurrent ACS using multivariable joint models. Median age was 63 years, 78% were men and the PE was reached by 45 patients. The average biomarker levels were systematically higher in PE compared with PE-free patients. After adjustment for 6-month post-discharge Global Registry of Acute Coronary Events score, 1 standard deviation increase in log[hs-cTnT] was associated with a 61% increased risk of the PE [hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.02-2.44, P = 0.045], while for log[GDF-15] this was 81% (HR 1.81, 95% CI 1.28-2.70, P = 0.001). These associations remained significant after multivariable adjustment, while NT-proBNP and hs-CRP were not. Furthermore, GDF-15 level showed an increasing trend prior to the PE (Structured Graphical Abstract). CONCLUSION: Longitudinally measured hs-cTnT and GDF-15 concentrations provide prognostic value in the risk assessment of clinically stabilized patients post-ACS. CLINICAL TRIAL REGISTRATION: The Netherlands Trial Register. Currently available at URL https://trialsearch.who.int/; Unique Identifiers: NTR1698 and NTR1106.


Acute Coronary Syndrome , C-Reactive Protein , Male , Humans , Middle Aged , Female , C-Reactive Protein/metabolism , Natriuretic Peptide, Brain , Troponin T , Growth Differentiation Factor 15 , Prospective Studies , Aftercare , Patient Discharge , Biomarkers , Risk Assessment/methods , Prognosis , Peptide Fragments
5.
Neth Heart J ; 31(10): 390-398, 2023 Oct.
Article En | MEDLINE | ID: mdl-36995641

BACKGROUND: Infective endocarditis is a severe and potentially lethal cardiac disease. Recognition of the clinical features of endocarditis, such as distant embolisation, and adequate treatment should be initiated promptly given the grim perspective of upcoming virulent pathogens. METHODS: We report on our registry-based experience with outcomes of consecutive patients with infective endocarditis with distant embolisation. We aimed to describe the patient characteristics of infective endocarditis complicated by distant organ embolisation and the safety aspects of continuing endocarditis treatment at home in these patients. RESULTS: From November 2018 through April 2022, 157 consecutive patients were diagnosed with infective endocarditis. Of them, 38 patients (24%) experienced distant embolisation, either in the cerebrum (n = 18), a visceral organ (n = 5), the lungs (n = 7) or the myocardium (n = 8). Pathogens identified in blood cultures were predominantly streptococcal variants (43%), with only one culture-negative endocarditis case. Of the 18 patients with cerebral embolisation, 12 had neurological complaints and most often discrete abnormal findings on neurological examination. Six of the 8 cardiac embolism patients experienced chest pain before admission. Visceral organ and pulmonary embolism occurred silently. Of the 38 patients with distant embolisation, 17 could be discharged earlier by providing antibiotic treatment at home without complications. CONCLUSION: This registry-based single-centre experience showed an incidence of distant embolisation in daily care of 24%. Cerebral and coronary embolisation provoked symptoms, while visceral emboli remained silent. Pulmonary emboli may present with inflammatory signs. Distant embolisation was not in itself a contra-indication for outpatient endocarditis@home treatment.

6.
Int J Cardiol ; 364: 77-84, 2022 10 01.
Article En | MEDLINE | ID: mdl-35714717

BACKGROUND: This study aimed to identify heart failure (HF) subphenotypes using 92 repeatedly measured circulating proteins in 250 patients with heart failure with reduced ejection fraction, and to investigate their clinical characteristics and prognosis. METHODS: Clinical data and blood samples were collected tri-monthly until the primary endpoint (PEP) or censoring occurred, with a maximum of 11 visits. The Olink Cardiovascular III panel was measured in baseline samples and the last two samples before the PEP (in 66 PEP cases), or the last sample before censoring (in 184 PEP-free patients). The PEP comprised cardiovascular death, heart transplantation, Left Ventricular Assist Device implantation, and hospitalization for HF. Cluster analysis was performed on individual biomarker trajectories to identify subphenotypes. Then biomarker profiles and clinical characteristics were investigated, and survival analysis was conducted. RESULTS: Clustering revealed three clinically diverse subphenotypes. Cluster 3 was older, with a longer duration of, and more advanced HF, and most comorbidities. Cluster 2 showed increasing levels over time of most biomarkers. In cluster 3, there were elevated baseline levels and increasing levels over time of 16 remaining biomarkers. Median follow-up was 2.2 (1.4-2.5) years. Cluster 3 had a significantly poorer prognosis compared to cluster 1 (adjusted event-free survival time ratio 0.25 (95%CI:0.12-0.50), p < 0.001). Repeated measurements clusters showed incremental prognostic value compared to clusters using single measurements, or clinical characteristics only. CONCLUSIONS: Clustering based on repeated biomarker measurements revealed three clinically diverse subphenotypes, of which one has a significantly worse prognosis, therefore contributing to improved (individualized) prognostication.


Heart Failure , Heart Transplantation , Ventricular Dysfunction, Left , Biomarkers , Humans , Prognosis , Stroke Volume , Ventricular Function, Left
7.
Ann Intensive Care ; 12(1): 12, 2022 Feb 11.
Article En | MEDLINE | ID: mdl-35147784

BACKGROUND: Acute kidney injury (AKI) is a frequent complication in cardiac arrest survivors and associated with adverse outcome. It remains unclear whether the incidence of AKI increases after the post-cardiac arrest contrast administration for coronary angiography and whether this depends on timing of angiography. Aim of this study was to investigate whether early angiography is associated with increased development of AKI compared to deferred angiography in out-of-hospital cardiac arrest (OHCA) survivors. METHODS: In this retrospective multicenter cohort study, we investigated whether early angiography (within 2 h) after OHCA was non-inferior to deferred angiography regarding the development of AKI. We used an absolute difference of 5% as the non-inferiority margin. Primary non-inferiority analysis was done by calculating the risk difference with its 90% confidence interval (CI) using a generalized linear model for a binary outcome. As a sensitivity analysis, we repeated the primary analysis using propensity score matching. A multivariable model was built to identify predictors of acute kidney injury. RESULTS: A total of 2375 patients were included from 2009 until 2018, of which 1148 patients were treated with early coronary angiography and 1227 patients with delayed or no angiography. In the early angiography group 18.5% of patients developed AKI after OHCA and 24.1% in the deferred angiography group. Risk difference was - 3.7% with 90% CI ranging from - 6.7 to - 0.7%, indicating non-inferiority of early angiography. The sensitivity analysis using propensity score matching showed accordant results, but no longer non-inferiority of early angiography. The factors time to return of spontaneous circulation (odds ratio [OR] 1.12, 95% CI 1.06-1.19, p < 0.001), the (not) use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 0.20, 95% CI 0.04-0.91, p = 0.04) and baseline creatinine (OR 1.05, 95% CI 1.03-1.07, p < 0.001) were found to be independently associated with the development of AKI. CONCLUSIONS: Although AKI occurred in approximately 20% of OHCA patients, we found that early angiography was not associated with a higher AKI incidence than a deferred angiography strategy. The present results implicate that it is safe to perform early coronary angiography with respect to the risk of developing AKI after OHCA.

9.
J Am Heart Assoc ; 10(1): e017393, 2021 01 05.
Article En | MEDLINE | ID: mdl-33325242

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P<0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; P<0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (rspearman=0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.


Acute Coronary Syndrome , Aftercare , Biological Variation, Population/physiology , Troponin I , Troponin T , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/therapy , Aftercare/methods , Aftercare/statistics & numerical data , Biomarkers/blood , Biomarkers/metabolism , Female , Hospitalization/statistics & numerical data , Humans , Kinetics , Longitudinal Studies , Male , Middle Aged , Netherlands/epidemiology , Precision Medicine/methods , Troponin I/blood , Troponin I/metabolism , Troponin T/blood , Troponin T/metabolism
10.
Can J Cardiol ; 36(10): 1587-1591, 2020 10.
Article En | MEDLINE | ID: mdl-32827637

In this prospective cohort study of 250 stable heart failure patients with trimonthly blood sampling, we investigated associations of 17 repeatedly measured cytokines and cytokine receptors with clinical outcome during a median follow-up of 2.2 (25th-75th percentile, 1.4-2.5) years. Sixty-six patients reached the primary end point (composite of cardiovascular mortality, heart failure hospitalization, heart transplantation, left ventricular assist device implantation). Repeatedly measured levels of 8 biomarkers correlated with clinical outcomes independent of clinical characteristics. Rates of change over time (slopes of biomarker evolutions) remained independently associated with outcome for 15 biomarkers. Thus, temporal patterns of cytokines and cytokine receptors, in particular tumour necrosis factor ligand superfamily member 13B and interleukin-1 receptor type 1, might contribute to personalized risk assessment.


Assisted Circulation , B-Cell Activating Factor/blood , Heart Failure , Interleukin-1/blood , Outcome Assessment, Health Care , Receptors, Interleukin-1/blood , Assisted Circulation/instrumentation , Assisted Circulation/methods , Assisted Circulation/statistics & numerical data , Biomarkers/blood , Cohort Studies , Cytokines/blood , Female , Heart Failure/blood , Heart Failure/mortality , Heart Failure/therapy , Heart Transplantation/methods , Heart Transplantation/statistics & numerical data , Heart-Assist Devices , Humans , Male , Middle Aged , Netherlands/epidemiology , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Prospective Studies , Receptors, Cytokine/blood , Risk Assessment/methods
11.
Nucl Med Commun ; 41(8): 783-789, 2020 Aug.
Article En | MEDLINE | ID: mdl-32427699

AIM: Evaluation of major adverse cardiovascular events (MACE) in women referred for NH3-PET/CT in relation to scan outcome and pharmacological stress ECG (PxECG) results. PATIENTS AND METHODS: Six hundred twenty-four women, referred for NH3-PET/CT between 2012 and 2016, were included. Demographic data and MACE during follow-up (407 ± 207 days) were retrieved from electronic patient charts. NH3-PET/CT was scored as either normal or abnormal. PxECG was scored as negative, non-diagnostic or positive. PxECG was compared with NH3-PET/CT and related to MACE. RESULTS: The NH3-PET/CT was normal in 482/624 (77%) and abnormal in 142/624 (23%). PxECG was negative in 234/624 (38%), non-diagnostic in 365/624 (58%) and positive in 25/624 (4%). NH3-PET/CT was normal in 87, 71 and 72% with normal, nondiagnostic and positive PxECG, respectively. 41/624(7%) experienced a MACE, 38 with abnormal NH3-PET/CT versus three with normal NH3-PET/CT (P < 0.001). MACE occurred in 5/234 (0.9%), 31/365 (8%) and 5/25 (20%) with normal, non-diagnostic and positive PxECG, respectively (P < 0.001). No MACEs were seen in 204 with both normal PxECG and NH3-PET/CT versus 5/30(17%) with normal PxECG but abnormal NH3-PET/. No MACE occurred in 3/260(1%) with non-diagnostic PxECG and normal NH3-PET/CT versus 28/105(27%) with non-diagnostic PxECG and abnormal NH3-PET/CT. 0/18 with positive PxECG and normal NH3-PET/CT showed MACE versus 5/7(71%) with a positive PxECG and abnormal NH3-PET/CT. CONCLUSION: Normal NH3-PET/CT is most prevalent in women with normal PxECG. The occurrence of MACE during follow-up is more frequently related to an abnormal NH3-PET/CT than to PxECG. Furthermore, in women with positive PxECG but normal NH3-PET/CT no MACE are to be expected.


Ammonia , Cardiovascular Diseases/complications , Chest Pain/complications , Chest Pain/diagnostic imaging , Electrocardiography , Positron Emission Tomography Computed Tomography , Stress, Physiological , Aged , Chest Pain/physiopathology , Female , Follow-Up Studies , Humans , Nitrogen Radioisotopes , Risk Assessment
12.
Clin Chem Lab Med ; 58(12): 2099-2106, 2020 11 26.
Article En | MEDLINE | ID: mdl-32383686

Objectives Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients.


Acute Coronary Syndrome/metabolism , Acute Coronary Syndrome/blood , Adult , Aged , Biomarkers/blood , C-Reactive Protein/analysis , Coronary Artery Disease/blood , Female , Humans , Interleukin-1 Receptor-Like 1 Protein/analysis , Interleukin-1 Receptor-Like 1 Protein/blood , Longitudinal Studies , Male , Middle Aged , Myocardial Infarction/blood , Natriuretic Peptide, Brain/analysis , Natriuretic Peptide, Brain/blood , Peptide Fragments/analysis , Peptide Fragments/blood , Prospective Studies , Risk Assessment , Risk Factors
13.
J Clin Med ; 9(1)2020 Jan 10.
Article En | MEDLINE | ID: mdl-31936828

Cardiovascular inflammation and vascular endothelial dysfunction are involved in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. We evaluated temporal patterns of 12 blood biomarkers of cell adhesion in patients with CHF. In 263 ambulant patients, serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (1.4-2.5) years. The primary endpoint (PE) was a composite of cardiovascular mortality, HF hospitalization, heart transplantation and implantation of a left ventricular assist device and was reached in 70 patients. We selected the baseline blood samples in all patients, the two samples closest to a PE, or, for event-free patients, the last sample available. In these 567 samples, associations between biomarkers and PE were investigated by joint modelling. The median age was 68 (59-76) years, with 72% men and 74% New York Heart Association class I-II. Repeatedly measured levels of Complement component C1q receptor (C1qR), Cadherin 5 (CDH5), Chitinase-3-like protein 1 (CHI3L1), Ephrin type-B receptor 4 (EPHB4), Intercellular adhesion molecule-2 (ICAM-2) and Junctional adhesion molecule A (JAM-A) were independently associated with the PE. Their rates of change also predicted clinical outcome. Level of CHI3L1 was numerically the strongest predictor with a hazard ratio (HR) (95% confidence interval) of 2.27 (1.66-3.16) per SD difference in level, followed by JAM-A (2.10, 1.42-3.23) and C1qR (1.90, 1.36-2.72), adjusted for clinical characteristics. In conclusion, temporal patterns of C1qR, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A are strongly and independently associated with clinical outcome in CHF patients.

14.
Data Brief ; 27: 104750, 2019 Dec.
Article En | MEDLINE | ID: mdl-31763405

The Biomarker Study to Identify the Acute Risk of a Coronary Syndrome (BIOMArCS) is a prospective, observational study that has been designed to study the evolution of blood biomarkers in post-acute coronary syndrome (ACS) patients. In our recently published study "Temporal evolution of Myeloperoxidase and Galectin 3 during 1 year after acute coronary syndrome admission" [1] in the American Heart Journal, we demonstrated that repeatedly measuring MPO and Galectin-3 does not aid to differentiate between patients with and without adverse cardiac events during 1-year follow-up. In this Data-In-Brief article, we present further details on data collections and data analysis. In addition, a detailed description of baseline characteristics and the distribution of blood sampling moments is provided. The BIOMArCS dataset contains clinical information and follow-up data on all enrolled 844 patients. These patients underwent a median of 17 (25th -75th percentile 12-20) repeated blood samples in the first year after the index ACS. Blood samples were stored at -80 °C within a median of 82 (25th-75th percentile 58-117) minutes after withdrawal. We collected whole blood, citrate plasma, EDTA plasma, serum and DNA. The dataset used for the analysis in the accompanying research paper has been made available online. We welcome collaborations for further use of our data, whether or not in combination with other biobanks.

15.
Thromb Haemost ; 119(12): 1947-1955, 2019 Dec.
Article En | MEDLINE | ID: mdl-31659734

OBJECTIVE: This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). METHODS: A median of 9 (interquartile range [IQR] 5-10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4-2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. RESULTS: Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28-3.45) for PAI-1, 1.91 (1.18-3.24) for uPA, and 3.96 (2.48-6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. CONCLUSION: Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.


Biomarkers/blood , Fibrinolysis , Heart Failure/blood , Aged , Aged, 80 and over , Chronic Disease , Death , Disease Progression , Female , Heart Failure/therapy , Heart Transplantation , Heart-Assist Devices , Humans , Longitudinal Studies , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Prognosis , Receptors, Urokinase Plasminogen Activator/blood , Time Factors , Tissue Plasminogen Activator/blood , Treatment Outcome , Urokinase-Type Plasminogen Activator/blood
16.
J Am Soc Echocardiogr ; 32(8): 1000-1009, 2019 08.
Article En | MEDLINE | ID: mdl-31230778

BACKGROUND: We aimed to compare the prognostic value of a single "baseline" echocardiogram with repeated echocardiography in stable chronic heart failure (CHF) patients. We hypothesized that repeated echocardiograms would contain incremental prognostic information. METHODS: In the prospective Bio-SHiFT study, we performed 332 echocardiograms in 106 patients during a median follow-up of 2.3 years. The endpoint comprised HF hospitalization, left ventricular (LV) assist device implantation, heart transplantation, and cardiovascular death. We compared hazard ratios (HRs; adjusted for N-terminal pro-brain natriuretic peptide) from Cox models for the first available measurement with HRs from joint models, which model individual trajectories based on the repeated measurements and link these to the time-to-event data. RESULTS: The mean age of the patients was 58.1 years; 78.3% were male, 12.6% had New York Heart Association class >II, all had reduced ejection fraction, and the most common HF etiologies were cardiomyopathies (51%) and ischemia (40%). The endpoint occurred in 25 patients. Both the single measurements and the temporal trajectories were significantly associated with the endpoint (adjusted HR Cox model [95% CI] vs adjusted HR joint model [95% CI]): LV ejection fraction, 1.47 (0.93-2.31) vs 1.77 (1.13-2.93); diastolic LV diameter, 1.64 (1.09-2.47) vs 1.68 (1.12-2.57); systolic LV diameter, 1.72 (1.10-2.69) vs 1.68 (1.13-2.63); systolic left atrial diameter, 1.88 (1.18-3.00) vs 2.60 (1.48-4.97); E/A ratio, 2.73 (1.42-5.26) vs 3.87 (1.75-10.13); and E/e' ratio, 2.30 (1.38-3.84) vs 2.99 (1.68-6.19). None of the trajectories from the investigated parameters showed worsening prior to events. CONCLUSIONS: Although single baseline or repeatedly measured echocardiographic parameters were associated with the endpoint, all parameters remained on average stable during the 2.3 years of follow-up in this largely minimally symptomatic CHF cohort. Thus, regular echocardiographic monitoring of systolic or diastolic LV function within this time frame does not carry incremental prognostic information over a single baseline measurement.


Echocardiography , Heart Failure/diagnostic imaging , Biomarkers/analysis , Chronic Disease , Female , Heart Failure/physiopathology , Humans , Male , Middle Aged , Netherlands , Prognosis , Prospective Studies , Retreatment
17.
Am Heart J ; 216: 143-146, 2019 10.
Article En | MEDLINE | ID: mdl-31053235

Prior studies reported that Myeloperoxidase and Galectin-3, which are biomarkers of coronary plaque vulnerability, are elevated in acute coronary syndrome (ACS) patients. We studied the temporal evolution of these biomarkers early after ACS admission and prior to a recurrent ACS event during 1 year follow-up.


Acute Coronary Syndrome/blood , Galectin 3/blood , Peroxidase/blood , Aged , Biomarkers/blood , Blood Proteins , Cohort Studies , Female , Follow-Up Studies , Galectins , Hospitalization , Humans , Male , Middle Aged , Netherlands , Time Factors
18.
Data Brief ; 21: 371-376, 2018 Dec.
Article En | MEDLINE | ID: mdl-30364643

The GRACE score is currently the most widely used model to assess patient prognosis after myocardial infarction (MI). We have demonstrated that the prognostic performance of the GRACE score can be improved by adding blood biomarkers measured routinely at hospital admission in our study recently published in the International Journal of Cardiology: "Addition of routinely measured blood biomarkers significantly improves GRACE risk stratification in patients with myocardial infarction". In this Data-in-Brief article we present additional original data from our dataset. This dataset consists of clinical and biomarker information and follow-up data of 2055 confirmed MI patients. In 143 of these patients the endpoint (all-cause mortality or reMI) occurred during six months follow-up. We describe the differences in baseline characteristics between ST-elevation MI (STEMI) patients and non-STEMI patients, differences in biomarker levels at admission between patients in whom the endpoint occurred and patients who remained endpoint-free, and associations of the biomarkers with the endpoint. Moreover, we show additional statistical results of analyses that compare the original GRACE-only model with our extended GRACE/biomarker model.

19.
EBioMedicine ; 36: 63-72, 2018 Oct.
Article En | MEDLINE | ID: mdl-30131305

Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386?days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively. Findings: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p=0.012; p=0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p=0.027) and percentage of plaque occupied by necrotic core (p=0.011), as well as lipid core burden index (p=0.024) in the worst 4 mm segment. Interpretation: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.


Coronary Artery Disease/blood , Immunoglobulin M/blood , Lipoproteins, LDL/immunology , Malondialdehyde/analogs & derivatives , Necrosis/blood , Aged , Atherosclerosis/blood , Biomarkers/blood , Female , Humans , Male , Malondialdehyde/immunology , Middle Aged , Prospective Studies
20.
J Womens Health (Larchmt) ; 27(4): 476-484, 2018 04.
Article En | MEDLINE | ID: mdl-29297745

AIM: The value of exercise electrocardiogram (ExECG) in symptomatic female patients with low to intermediate risk for significant coronary artery disease (CAD) has been under debate for many years, and nondiagnostic or even erroneous test results are frequently encountered. Cardiac-CT may be more appropriate to exclude CAD in women. This study compares the results of ExECGs with those of cardiac-CTs, performed within a time frame of 1 month in an all-comers female chest pain population. PATIENTS AND METHODS: Five hundred fifty-one consecutive female patients from a patient registry were included. ExECGs were negative in 324 (59%), positive in 14 (3%), and nondiagnostic in 213 (39%) patients. CAD was revealed by cardiac-CT in 57% of the women with negative ExECG. No signs of CAD were present on cardiac-CT in 64% of the women with a positive ExECG. Cardiac-CT showed presence of CAD in 268/551 (49%) patients, of whom 56/268 (21%) was diagnosed with ≥50% stenosis. The ExECG of the latter group was negative in 26 (46%), inconclusive in 29 (52%), and positive in 1 (2%). Considering ≥50% stenosis at cardiac-CT as the reference, sensitivity, specificity, PPV, and NPV of ExECG for the present population were 3.7%, 95.7%, 7.1%, and 91.7%, respectively. Similar diagnostic performance was calculated when considering ≥70% stenosis at cardiac-CT as the reference. CONCLUSION: ExECG failed to detect CAD in more than half of this cohort and in almost half of women with >50% stenosis at cardiac-CT. Importantly, no CAD was detected by cardiac-CT in 64% of women with a positive ExECG. ExECG is therefore questionable as a diagnostic strategy in women with low-to-intermediate risk of CAD, although prospective studies are warranted to determine whether replacing ExECG by cardiac-CT provides better prognoses.


Coronary Artery Disease/diagnosis , Echocardiography/methods , Electrocardiography/methods , Exercise Test/methods , Aged , Chest Pain/etiology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Sensitivity and Specificity
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