Publications by authors named "Eric Boersma"

595 Publications

Effect of routine preoperative screening for aortic calcifications using noncontrast computed tomography on stroke rate in cardiac surgery: the randomized controlled CRICKET study.

Eur Radiol 2021 Nov 16. Epub 2021 Nov 16.

Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, PO BOX 2040, ND-547, 3000-CA, Rotterdam, The Netherlands.

Objectives: To evaluate if routine screening for aortic calcification using unenhanced CT lowers the risk of stroke and alters the surgical approach in patients undergoing general cardiac surgery compared with standard of care (SoC).

Methods: In this prospective, multicenter, randomized controlled trial, adult patients scheduled for cardiac surgery from September 2014 to October 2019 were randomized 1:1 into two groups: SoC alone, including chest radiography, vs. SoC plus preoperative noncontrast CT. The primary endpoint was in-hospital perioperative stroke. Secondary endpoints were preoperative change of the surgical approach, in-hospital mortality, and postoperative delirium. The trial was halted halfway for expected futility, as the conditional power analysis showed a chance < 1% of finding the hypothesized effect.

Results: A total of 862 patients were evaluated (SoC-group: 433 patients (66 ± 11 years; 74.1% male) vs. SoC + CT-group: 429 patients (66 ± 10 years; 69.9% male)). The perioperative stroke rate (SoC + CT: 2.1%, 9/429 vs. SoC: 1.2%, 5/433, p = 0.27) and rate of changed surgical approach (SoC + CT: 4.0% (17/429) vs. SoC: 2.8% (12/433, p = 0.35) did not differ between groups. In-hospital mortality and postoperative delirium were comparable between groups. In the SoC + CT group, aortic calcification was observed on CT in the ascending aorta in 28% (108/380) and in the aortic arch in 70% (265/379).

Conclusions: Preoperative noncontrast CT in cardiac surgery candidates did not influence the surgical approach nor the incidence of perioperative stroke compared with standard of care. Aortic calcification is a frequent finding on the CT scan in these patients but results in major surgical alterations to prevent stroke in only few patients.

Key Points: • Aortic calcification is a frequent finding on noncontrast computed tomography prior to cardiac surgery. • Routine use of noncontrast computed tomography does not often lead to a change of the surgical approach, when compared to standard of care. • No effect was observed on perioperative stroke after cardiac surgery when using routine noncontrast computed tomography screening on top of standard of care.
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http://dx.doi.org/10.1007/s00330-021-08360-4DOI Listing
November 2021

2D-echocardiography vs cardiac MRI strain: a prospective cohort study in patients with HER2-positive breast cancer undergoing trastuzumab.

Cardiovasc Ultrasound 2021 Nov 9;19(1):35. Epub 2021 Nov 9.

Department of Cardiology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.

Background: We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer.

Methods: HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF < 45% and/or absolute decline > 10% during trastuzumab.

Results: Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson's r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11-2.93; p = 0.016; explained variance 0.34).

Conclusions: Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.
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http://dx.doi.org/10.1186/s12947-021-00266-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576921PMC
November 2021

Prediction of long-term hospitalisation and all-cause mortality in patients with chronic heart failure on Dutch claims data: a machine learning approach.

BMC Med Inform Decis Mak 2021 11 1;21(1):303. Epub 2021 Nov 1.

Department of Cardiology, Thorax Centre, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.

Background: Accurately predicting which patients with chronic heart failure (CHF) are particularly vulnerable for adverse outcomes is of crucial importance to support clinical decision making. The goal of the current study was to examine the predictive value on long term heart failure (HF) hospitalisation and all-cause mortality in CHF patients, by exploring and exploiting machine learning (ML) and traditional statistical techniques on a Dutch health insurance claims database.

Methods: Our study population consisted of 25,776 patients with a CHF diagnosis code between 2012 and 2014 and one year and three years follow-up HF hospitalisation (1446 and 3220 patients respectively) and all-cause mortality (2434 and 7882 patients respectively) were measured from 2015 to 2018. The area under the receiver operating characteristic (ROC) curve (AUC) was calculated after modelling the data using Logistic Regression, Random Forest, Elastic Net regression and Neural Networks.

Results: AUC rates ranged from 0.710 to 0.732 for 1-year HF hospitalisation, 0.705-0.733 for 3-years HF hospitalisation, 0.765-0.787 for 1-year mortality and 0.764-0.791 for 3-years mortality. Elastic Net performed best for all endpoints. Differences between techniques were small and only statistically significant between Elastic Net and Logistic Regression compared with Random Forest for 3-years HF hospitalisation.

Conclusion: In this study based on a health insurance claims database we found clear predictive value for predicting long-term HF hospitalisation and mortality of CHF patients by using ML techniques compared to traditional statistics.
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http://dx.doi.org/10.1186/s12911-021-01657-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561992PMC
November 2021

Vessel fractional flow reserve (vFFR) for the assessment of stenosis severity: the FAST II study.

EuroIntervention 2021 Oct 14. Epub 2021 Oct 14.

Department of Cardiology, Erasmus Medical Center, Rotterdam, the Netherlands.

Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is superior to angiography-guided PCI. The clinical uptake of FFR has been limited, however, by the need to advance a wire in the coronary artery, the additional time required and the need for hyperaemic agents which can cause patient discomfort. FFR derived from routine coronary angiography eliminates these issues.

Aims: The aim of this study was to assess the diagnostic performance and accuracy of three-dimensional quantitative coronary angiography (3D-QCA)-based vessel FFR (vFFR) compared to pressure wire-based FFR (≤0.80).

Methods: The FAST II (Fast Assessment of STenosis severity) study was a prospective observational multicentre study designed to evaluate the diagnostic accuracy of vFFR compared to the reference standard (pressure wire-based FFR ≤0.80). A total of 334 patients from six centres were enrolled. Both site-determined and blinded independent core lab vFFR measurements were compared to FFR.

Results: The core lab vFFR was 0.83±0.09 and pressure wire-based FFR 0.83±0.08. A good correlation was found between core lab vFFR and pressure wire-based FFR (R=0.74; p<0.001; mean bias 0.0029±0.0642). vFFR had an excellent diagnostic accuracy in identifying lesions with an invasive wire-based FFR ≤0.80 (AUC 0.93; 95% CI: 0.90-0.96; p<0.001). Positive predictive value, negative predictive value, diagnostic accuracy, sensitivity and specificity of vFFR were 90%, 90%, 90%, 81% and 95%, respectively.

Conclusions: 3D-QCA-based vFFR has excellent diagnostic performance to detect FFR ≤0.80. The study was registered on clinicaltrials.gov under identifier NCT03791320.
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http://dx.doi.org/10.4244/EIJ-D-21-00471DOI Listing
October 2021

The genomics of heart failure: design and rationale of the HERMES consortium.

ESC Heart Fail 2021 Sep 3. Epub 2021 Sep 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.

Methods And Results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 under an additive genetic model.

Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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http://dx.doi.org/10.1002/ehf2.13517DOI Listing
September 2021

Systematic review with meta-analysis: effect of inflammatory bowel disease therapy on lipid levels.

Aliment Pharmacol Ther 2021 10 28;54(8):999-1012. Epub 2021 Aug 28.

Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, the Netherlands.

Background: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes.

Aim: To precisely assess the effect of different IBD drug classes on lipid profiles METHODS: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (≤10 weeks) and maintenance (>10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models.

Results: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI ] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI +0.42 to +0.79), but not after anti-TNFα treatment (-0.11 mmol/L, CI -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes.

Conclusions: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNFα agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.
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http://dx.doi.org/10.1111/apt.16580DOI Listing
October 2021

Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR.

N Engl J Med 2021 Aug 28. Epub 2021 Aug 28.

From the Department of Cardiology, Erasmus University Medical Center, Thoraxcenter, Rotterdam, the Netherlands (N.M.V.M., E.B.); Daiichi Sankyo, Basking Ridge, NJ (M.U., J.J., A.D., C.C.); the Department of Internal Medicine II, Division of Cardiology, Vienna General Hospital, Medical University, Vienna (C.H., I.L.); the Department of Internal Medicine, St. Johannes Hospital, Dortmund (H.M.), the Department of Internal Medicine I, University Hospital Würzburg, Würzburg (P.N.), the Department of Internal Medicine-Cardiology, Heart Center Leipzig at University of Leipzig, Leipzig (H.T.), Bremer Institute for Heart and Circulation Research at Klinikum Links der Weser, Bremen (R.H.), the Department of Cardiology, Asklepios Klinik St. Georg, Hamburg (F.M.), Daiichi Sankyo Europe, Munich (P.L., H.L.), the Department of Neurology, Alfried Krupp Krankenhaus, Essen (R.V.), and the Department of Neurology, University Hospital Heidelberg, Heidelberg (R.V.) - all in Germany; Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New York (R. Mehran, G.D.D.); the Department of Cardiology, Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela (D.L.-O.), the Cardiovascular Institute, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (L.N.-F.), the Department of Cardiology, University Hospital La Paz (R. Moreno), and the Department of Cardiology, University Hospital Ramon y Cajal (J.L.Z.), Madrid - all in Spain; the Department of Cardiology, Washington Adventist Hospital, Takoma Park, MD (F.S.); the Department of Cardiology, Toyohashi Heart Center, Toyohashi (M.Y.), the Department of Cardiology, Teikyo University School of Medicine (Y.W.), and the Department of Cardiology, Keio University School of Medicine (K.H.), Tokyo, and the Division of Cardiology and Catheterization Laboratories, Shonan Kamakura General Hospital, Kamakura (S.S.) - all in Japan; the Department of Cardiology, Jessa Hospital, Hasselt, Belgium (P.V.); Quebec Heart and Lung Institute, Laval University, Quebec, QC, Canada (J.R.-C.); the Division of Cardiovascular Medicine, University Hospital of Strasbourg, Strasbourg, France (P.O.); the Division of Cardiology, Policlinico Hospital, University of Catania, Catania, Italy (P.C.); the Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, South Korea (H.-S.K.); the Department of Cardiology, University of Bern, Bern (T.P.), and Cardiocentro Ticino Institute and Department of Biomedical Sciences, University of Italian Switzerland, Lugano (M.V.) - both in Switzerland; the Department of Cardiology, University Hospital of Wales, Cardiff (R.A.), and the Division of Brain Sciences, Imperial College London, London (R.V.) - both in the United Kingdom; the Cardiology Section, University of Oklahoma Health Sciences Center, Oklahoma City (U.B.); and National and Kapodistrian University of Athens, School of Medicine, Athens (G.D.D.).

Background: The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.

Methods: We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding.

Results: A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11).

Conclusions: In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).
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http://dx.doi.org/10.1056/NEJMoa2111016DOI Listing
August 2021

Determinants of quality of life in acute heart failure patients with and without comorbidities: a prospective, observational study.

Eur J Cardiovasc Nurs 2021 Aug 15. Epub 2021 Aug 15.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, Rotterdam 3015 GD, the Netherlands.

Aims: The relation between non-cardiac comorbidities and health-related quality of life (HRQoL) in patients with heart failure (HF) has been studied to a limited extent. To investigate the HRQoL and their determinants among HF patients with and without comorbidities.

Methods And Results: TRIUMPH (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure) is a Dutch prospective, multicentre study enrolling 496 acute HF patients between 2009 and 2014. We included 334 patients who had completed the HRQoL questionnaires at baseline. The HRQoL was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) en EuroQuality-of-life five Dimensions (EQ-5D). Comorbidity was defined as having a history of at least one of the following comorbidities: chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and/or cerebrovascular accident. Patients with comorbidity (n = 205, 61%) had lower scores on the physical limitation scale and clinical summary score of the KCCQ (P = 0.03 and P = 0.01, respectively). Female sex, COPD, previous HF, increasing body mass index (BMI), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), high systolic blood pressure, and the presence of anxiety and/or depression negatively influenced the HRQoL among HF patients with comorbidity. Besides anxiety and depression, we hardly found any other determinant of HRQoL in patients without comorbidity.

Conclusion: Heart failure patients without comorbidity had better HRQoL than patients with comorbidity. Sex, previous HF, BMI, COPD, systolic blood pressure, NT-proBNP levels, and also anxiety and depression were determinants of HRQoL in patients with comorbidity. In those without comorbidity, apart from anxiety and depression, no further determinants of HRQoL were found.
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http://dx.doi.org/10.1093/eurjcn/zvab061DOI Listing
August 2021

ABC-SPH risk score for in-hospital mortality in COVID-19 patients: development, external validation and comparison with other available scores.

Int J Infect Dis 2021 Sep 24;110:281-308. Epub 2021 Jul 24.

Hospital Eduardo de Menezes. Belo Horizonte. Brazil. Electronic address:

Objectives: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones.

Methods: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients.

Results: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO/FiO ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/).

Conclusions: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.
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http://dx.doi.org/10.1016/j.ijid.2021.07.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302820PMC
September 2021

Heart failure and promotion of physical activity before and after cardiac rehabilitation (HF-aPProACH): a study protocol.

ESC Heart Fail 2021 10 16;8(5):3621-3627. Epub 2021 Jul 16.

Department of Cardiology, Thorax Centre, Erasmus MC, Erasmus University Medical Centre Rotterdam, Rotterdam, The Netherlands.

Aims: Lifestyle changes, such as increasing physical activity (PA), are a cornerstone of treatment of patients with chronic heart failure (HF). However, improving PA in HF patients is challenging, and low participation rates for cardiac rehabilitation (CR) as well as relapse to low PA levels after CR are major issues. We designed a randomized controlled trial to investigate if PA monitoring with motivational feedback before and after centre-based CR in HF patients with reduced ejection fraction (HFrEF) will lead to a clinically meaningful increase in physical fitness.

Methods And Results: A randomized controlled trial will be conducted in a sample of 180 HFrEF patients (New York Heart Association Class II/III) who are referred to 12-week standard CR. Patients will be randomized (2:1) to (1) standard of care (SoC) plus wearing a PA monitoring device (Fitbit Charge 3) with personalized step goals, feedback and motivation or (2) SoC only. The intervention lasts ±7 months: 4-5 weeks before CR, 12 weeks during CR and 12 weeks after CR. Measurements will take place at three time points. The primary endpoint is the change in the distance in 6-min walking test (6MWT) over the entire study period. Other endpoints include step count, grip strength, quality of life and all-cause mortality or hospitalization.

Conclusions: HF-aPProACH will provide novel information on the effectiveness of remote PA stimulation and feedback before, during and after standard CR using a commercially available device to improve physical fitness in HFrEF patients.
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http://dx.doi.org/10.1002/ehf2.13505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497333PMC
October 2021

Physical Activity and Sedentary Behavior in Cardiac Rehabilitation: Does Body Mass Index Matter?

Phys Ther 2021 09;101(9)

Department of Rehabilitation Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.

Objective: The purpose of this study was to investigate the relationship between body mass index (BMI) class and physical activity and sedentary behavior in patients with acute coronary syndrome (ACS) during cardiac rehabilitation (CR).

Methods: This study was a secondary analysis of the OPTICARE trial. Physical activity and sedentary behavior were measured in participants with ACS (n = 359) using actigraphy at baseline, directly after completion of a multidisciplinary 12-week exercise-based CR program and 9 months thereafter. Outcome measures were step count and duration of time (percentage of wear time) spent in light physical activity, moderate-to-vigorous physical activity, and sedentary behavior. Participants were classified as normal weight (BMI = 18.5-24.99 kg/m2; n = 82), overweight (BMI = 25.0-29.99 kg/m2; n = 182), or obese (BMI ≥ 30.0 kg/m2; n = 95). Linear mixed-effects models were applied to study the relationship between BMI class and physical activity and sedentary behavior.

Results: At the start of CR, compared with participants with normal weight, participants with obesity made on average 1.11 steps fewer per minute (952 steps/d), spent 2.9% (25 min/d) less time in light physical activity, and spent 3.31% (28 min/d) more time in sedentary behavior. Participants of all BMI classes improved their physical activity and sedentary behavior levels similarly during CR, and these improvements were maintained after completion of CR.

Conclusion: Participants with ACS who had obesity started CR with a less favorable physical activity and sedentary behavior profile than that of participants with normal weight. Because all BMI classes showed similar improvement during CR, this deficit was preserved.

Impact: This study indicates that reconsideration of the CR program in the Netherlands for patients with ACS and obesity is warranted, and development of more inclusive interventions for specific populations is needed. A new program for people with obesity should include added counseling on increasing physical activity and preventing sedentary behavior to facilitate weight loss and reduce mortality risk.

Lay Summary: People with ACS who have obesity are less active and sit more than individuals with normal weight, both during and after CR. This study suggests that CR needs to be changed to help individuals increase their physical activity to help them lose weight and reduce their risk of death.
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http://dx.doi.org/10.1093/ptj/pzab142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459883PMC
September 2021

The effect of age on blood pressure response by 4-week treatment perindopril: A pooled sex-specific analysis of the EUROPA, PROGRESS, and ADVANCE trials.

Clin Transl Sci 2021 11 21;14(6):2193-2199. Epub 2021 Jun 21.

Department of Internal Medicine, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.

Previous studies showed that postmenopausal women are more likely to have poorly controlled hypertension than men of the same age. Whether this is caused by inadequate treatment or poor response to antihypertensive agents remains unknown. The aim of this study is to analyze treatment response to the most potent renin angiotensin aldosterone system (RAAS) inhibitor perindopril in different age categories in women and men. Individual patient data were used from the combined European Trial on Reduction of Cardiac Events With Perindopril (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), and Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trials, which include patients with vascular disease (n = 29,463). We studied the relative and absolute changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) during a 4-week run-in phase in which all patients were treated with the perindopril-based treatment in different age categories. In total, 8366 women and 21,097 men were included in the analysis. Women greater than 65 years of age showed a significantly smaller blood pressure reduction after perindopril treatment (2.8 mmHg [95% confidence interval {CI} = 0.1-5.5] less reduction compared to women ≤45 years, p = 0.039). In men, the SBP reduction after perindopril in patients greater than 55-65 and greater than 65 years was lower compared to the age category less than or equal to 45 years (adjusted mean difference >55-65: 2.8 mmHg [95% CI = 1.8-3.7], p < 0.001, >65: 3.7 mmHg [95% CI = 2.7-4.7], p < 0.001). A trend of less blood pressure reduction was seen with ageing in both men and women (p < 0.001). To conclude, we observed that in both women and men the perindopril leads to less SBP reduction with increasing age, whereas the DBP reduction increases with age. More research is needed to determine whether it would be beneficial to use age-adjusted perindopril dosages.
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http://dx.doi.org/10.1111/cts.13076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604217PMC
November 2021

Relative conditional survival analysis provides additional insights into the prognosis of heart failure patients.

Eur J Prev Cardiol 2021 Feb 1. Epub 2021 Feb 1.

Department of Cardiology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1093/eurjpc/zwab003DOI Listing
February 2021

The legacy of HOPE-3.

Eur Heart J 2021 08;42(31):3008-3010

Erasmus MC, Department of Cardiology, Rotterdam, The Netherlands.

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http://dx.doi.org/10.1093/eurheartj/ehab208DOI Listing
August 2021

Left ventricular remodelling and prognosis after discharge in new-onset acute heart failure with reduced ejection fraction.

ESC Heart Fail 2021 08 2;8(4):2679-2689. Epub 2021 May 2.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, Room Rg4, PO Box 2040, Rotterdam, 3015 GD, The Netherlands.

Aims: This study aimed to investigate the left ventricular (LV) remodelling and long-term prognosis of patients with new-onset acute heart failure (HF) with reduced ejection fraction who were pharmacologically managed and survived until hospital discharge. We compared patients with ischaemic and non-ischaemic aetiology.

Methods And Results: This cohort study consisted of 111 patients admitted with new-onset acute HF in the period 2008-2016 [62% non-ischaemic aetiology, 48% supported by inotropes, vasopressors, or short-term mechanical circulatory devices, and left ventricular ejection fraction (LVEF) at discharge 28% (interquartile range 22-34)]. LV dimensions, LVEF, and mitral valve regurgitation were used as markers for LV remodelling during up to 3 years of follow-up. Both patients with non-ischaemic and ischaemic HF had significant improvement in LVEF (P < 0.001 and P = 0.004, respectively) with significant higher improvement in those with non-ischaemic HF (17% vs. 6%, P < 0.001). Patients with non-ischaemic HF had reduction in LV end-diastolic and end-systolic diameters (6 and 10 mm, both P < 0.001), but this was not found in those with ischaemic HF [+3 mm (P = 0.09) and +2 mm (P = 0.07), respectively]. During a median follow-up of 4.6 years, 98 patients (88%) did not reach the composite endpoint of LV assist device implantation, heart transplantation, or all-cause mortality, with no difference between with ischaemic and non-ischaemic HF [hazard ratio 0.69 (95% confidence interval 0.19-2.45)].

Conclusions: Patients with new-onset acute HF with reduced ejection fraction discharged on optimal medical treatment have a good prognosis. We observed a considerable LV remodelling with improvement in LV function and dimensions, starting already at 6 months in patients with non-ischaemic HF but not in their ischaemic counterparts.
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http://dx.doi.org/10.1002/ehf2.13299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318456PMC
August 2021

Influence of renal insufficiency pre-heart transplantation on malignancy risk post-heart transplantation.

ESC Heart Fail 2021 06 28;8(3):2172-2182. Epub 2021 Mar 28.

Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Aims: Recent reports demonstrated that patients with heart failure (HF) might have an increased risk to develop malignancies. This is also seen in patients with chronic kidney disease (CKD). Immunosuppression in heart transplantation (HT) recipients additionally increases the risk of malignancies. The aim of this study was to determine the relation between HF duration and CKD pre-HT and the risk of malignancy development post-HT.

Methods And Results: We included all adult HT recipients transplanted between January 2000 and November 2017 in our centre. Patients were excluded if they died or were retransplanted within 3 months post-HT. Clinical characteristics were retrospectively collected. Sixty out of 250 patients (24%) developed a malignancy after a median of 66 months [interquartile range 33-108] post-HT. In multivariable Cox regression analysis, HF duration was not a risk factor for all malignancies or solid organ malignancies post-HT [hazard ratio (HR) 1.033 (0.974-1.096), P = 0.281 and HR 1.036 (0.958-1.120), P = 0.376, respectively]. Age [HR 1.051 (1.016-1.086), P = 0.004] and CKD pre-HT [HR 2.173 (1.236-3.822), P = 0.007] were independent risk factors for all malignancies. CKD pre-HT [HR 2.542 (1.142-5.661), P = 0.022] increased the risk for solid organ malignancies. Exclusion of patients with durable mechanical circulatory support in the analysis did not alter the significance of these risk factors.

Conclusions: Duration of HF pre-HT was not associated with malignancy risk post-HT. CKD was an independent risk factor for malignancies post-HT. More studies are needed to investigate this association.
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http://dx.doi.org/10.1002/ehf2.13309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120392PMC
June 2021

Personalized screening intervals for kidney function in patients with chronic heart failure: a modeling study.

J Nephrol 2021 10 18;34(5):1421-1427. Epub 2021 Mar 18.

Department of Cardiology, Erasmus MC University Medical Center, Room Na-316, 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.

Background: High mortality and rehospitalization rates demonstrate that improving risk assessment in heart failure patients remains challenging. Individual temporal evolution of kidney biomarkers is associated with poor clinical outcome in these patients and hence may carry the potential to move towards a personalized screening approach.

Methods: In 263 chronic heart failure patients included in the prospective Bio-SHiFT cohort study, glomerular and tubular biomarker measurements were serially obtained according to a pre-scheduled, fixed trimonthly scheme. The primary endpoint (PE) comprised cardiac death, cardiac transplantation, left ventricular assist device implantation or heart failure hospitalization. Personalized scheduling of glomerular and tubular biomarker measurements was compared to fixed scheduling in individual patients by means of a simulation study, based on clinical characteristics of the Bio-SHiFT study. For this purpose, repeated biomarker measurements and the PE were jointly modeled. For personalized scheduling, using this fitted joint model, we determined the optimal time point of the next measurement based on the patient's individual risk profile as estimated by the joint model and the maximum information gain on the patient's prognosis. We compared the schedule's capability of enabling timely intervention before the occurrence of the PE and number of measurements needed.

Results: As compared to a pre-defined trimonthly scheduling approach, personalized scheduling of glomerular and tubular biomarker measurements showed similar performance with regard to prognostication, but required a median of 0.4-2.7 fewer measurements per year.

Conclusion: Personalized scheduling is expected to reduce the number of patient visits and healthcare costs. Thus, it may contribute to efficient monitoring of chronic heart failure patients and could provide novel opportunities for timely adaptation of treatment.
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http://dx.doi.org/10.1007/s40620-021-01014-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494722PMC
October 2021

Association between Clinical Frailty Scale score and hospital mortality in adult patients with COVID-19 (COMET): an international, multicentre, retrospective, observational cohort study.

Lancet Healthy Longev 2021 Mar 9;2(3):e163-e170. Epub 2021 Feb 9.

Department of Geriatrics, Amphia Hospital, Breda, Netherlands.

Background: During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe.

Methods: This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS), mildly frail (CFS), or frail (CFS). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities).

Findings: Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55-77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS CFS odds ratio [OR] 2·71 [95% CI 2·04-3·60], p<0·0001 and CFS CFS OR 1·54 [1·16-2·06], p=0·0030; age ≥65 years: CFS CFS OR 2·90 [2·12-3·97], p<0·0001 and CFS CFS OR 1·64 [1·20-2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS CFS OR 2·22 [1·08-4·57], p=0·030; CFS CFS OR 1·08 [0·48-2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS CFS OR 1·54 [1·21-1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS CFS OR 0·71 [0·55-0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS CFS OR 2·96 [1·98-4·43], p<0·0001), whereas mildly frail patients had no significant difference in incidence compared with fit patients (CFS CFS OR 0·93 [0·63-1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS CFS OR 1·27 [0·92-1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS CFS OR 0·66 [0·47-0·93], p=0·018).

Interpretation: The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution.

Funding: LOEY Foundation.
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http://dx.doi.org/10.1016/S2666-7568(21)00006-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906710PMC
March 2021

Associations Between Blood Biomarkers, Cardiac Function, and Adverse Outcome in a Young Fontan Cohort.

J Am Heart Assoc 2021 02 24;10(5):e015022. Epub 2021 Feb 24.

Division of Pediatric Cardiology Department of Pediatrics Erasmus University Medical Center Rotterdam The Netherlands.

Background Patients who have undergone the Fontan procedure are at high risk of circulatory failure. In an exploratory analysis we aimed to determine the prognostic value of blood biomarkers in a young cohort who have undergone the Fontan procedure. Methods and Results In multicenter prospective studies patients who have undergone the Fontan procedure underwent blood sampling, cardiopulmonary exercise testing, and stress cardiac magnetic resonance imaging. Several biomarkers including NT-proBNP (N-terminal pro-B-type natriuretic peptide), GDF-15 (growth differentiation factor 15), Gal-3 (galectin-3), ST2 (suppression of tumorigenicity 2), DLK-1 (protein delta homolog 1), FABP-4 (fatty acid-binding protein 4), IGFBP-1 (insulin-like growth factor-binding protein 1), IGFBP-7, MMP-2 (matrix metalloproteinase 2), and vWF (von Willebrand factor) were assessed in blood at 9.6 (7.1-12.1) years after Fontan completion. After this baseline study measurement, follow-up information was collected on the incidence of adverse cardiac events, including cardiac death, out of hospital cardiac arrest, heart transplantation (listing), cardiac reintervention (severe events), hospitalization, and cardioversion/ablation for arrhythmias was collected and the relation with blood biomarkers was assessed by Cox proportional hazard analyses. The correlation between biomarkers and other clinical parameters was evaluated. We included 133 patients who have undergone the Fontan procedure, median age 13.2 (25th, 75th percentile 10.4-15.9) years, median age at Fontan 3.2 (2.5-3.9) years. After a median follow-up of 6.2 (4.9-6.9) years, 36 (27.1%) patients experienced an event of whom 13 (9.8%) had a severe event. NT-proBNP was associated with (all) events during follow-up and remained predictive after correction for age, sex, and dominant ventricle (hazard ratio, 1.89; CI, 1.32-2.68). The severe event-free survival was better in patients with low levels of GDF-15 (=0.005) and vWF (=0.008) and high levels of DLK-1 (=0.041). There was a positive correlation (β=0.33, =0.003) between DLK-1 and stress cardiac magnetic resonance imaging functional reserve. Conclusions NT-proBNP, GDF-15, vWF, DLK-1, ST-2 FABP-4, and IGFBP-7 levels relate to long-term outcome in young patients who have undergone the Fontan procedure.
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http://dx.doi.org/10.1161/JAHA.119.015022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174257PMC
February 2021

The Prognostic Value of a Validated and Automated Intravascular Ultrasound-Derived Calcium Score.

J Cardiovasc Transl Res 2021 10 23;14(5):992-1000. Epub 2021 Feb 23.

Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands.

Background: Coronary calcification has been linked to cardiovascular events. We developed and validated an algorithm to automatically quantify coronary calcifications on intravascular ultrasound (IVUS). We aimed to assess the prognostic value of an IVUS-calcium score (ICS) on patient-oriented composite endpoint (POCE).

Methods: We included patients that underwent coronary angiography plus pre-procedural IVUS imaging. The ICS was calculated per patient. The primary endpoint was a composite of all-cause mortality, stroke, myocardial infarction, and revascularization (POCE).

Results: In a cohort of 408 patients, median ICS was 85. Both an ICS ≥ 85 and a 100 unit increase in ICS increased the risk of POCE at 6-year follow-up (adjusted hazard ratio (aHR) 1.51, 95%CI 1.05-2.17, p value = 0.026, and aHR 1.21, 95%CI 1.04-1.41, p value = 0.014, respectively).

Conclusions: The ICS, calculated by a validated automated algorithm derived from routine IVUS pullbacks, was strongly associated with the long-term risk of POCE.
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http://dx.doi.org/10.1007/s12265-021-10103-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575752PMC
October 2021

Variability in lipid measurements can have major impact on treatment during secondary prevention.

Eur J Prev Cardiol 2020 Sep 30. Epub 2020 Sep 30.

Department of Cardiology, Erasmus MC, University Medical Center Rotterdam, Room Na317, RG-5, PO Box 2040, 3000 CA Rotterdam, the Netherlands.

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http://dx.doi.org/10.1093/eurjpc/zwaa004DOI Listing
September 2020

Associations of serially measured PCSK9, LDLR and MPO with clinical outcomes in heart failure.

Biomark Med 2021 03 16;15(4):247-255. Epub 2021 Feb 16.

Department of Cardiology, Erasmus MC, Rotterdam, The Netherlands.

To investigate the temporal evolution of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor (LDLR) and myeloperoxidase (MPO) in relation to clinical outcome in chronic heart failure (CHF). Trimonthly blood sampling was performed during a median follow-up of 2.2 (IQR 1.4-2.5) years in 263 CHF patients. Seventy patients reached the primary end point (PE) (cardiovascular death, heart transplantation, left ventricular assist device implantation or HF-hospitalization). MPO level was independently associated with the PE; the adjusted (for clinical factors) hazard ratio (aHR) per standard deviation difference in MPO was 1.71 (95% CI: 1.23-2.43) at any time during follow-up. PCSK9 level (HR: 1.45 [1.04-2.06]) and LDLR (HR: 0.66 [0.49-0.87]) were statistical significantly associated with the PE but only in unadjusted analyses. Slope of temporal MPO evolution (aHR: 1.34 [1.12-1.76] per 0.1 standard deviation/year difference in slope) and LDLR (aHR: 0.78 [0.61-0.90]) however, were associated with PE. Temporal patterns of MPO and LDLR are independently associated with clinical outcome in CHF, which illustrates the importance of assessing temporal evolutions. registered in ClinicalTrials.gov, number NCT01851538. https://clinicaltrials.gov/ct2/show/NCT01851538.
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http://dx.doi.org/10.2217/bmm-2020-0585DOI Listing
March 2021

Artificial Intelligence and Transcatheter Interventions for Structural Heart Disease: A glance at the (near) future.

Trends Cardiovasc Med 2021 Feb 10. Epub 2021 Feb 10.

Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address:

With innovations in therapeutic technologies and changes in population demographics, transcatheter interventions for structural heart disease have become the preferred treatment and will keep growing. Yet, a thorough clinical selection and efficient pathway from diagnosis to treatment and follow-up are mandatory. In this review we reflect on how artificial intelligence may help to improve patient selection, pre-procedural planning, procedure execution and follow-up so to establish efficient and high quality health care in an increasing number of patients.
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http://dx.doi.org/10.1016/j.tcm.2021.02.002DOI Listing
February 2021

Predicting outcome in children with dilated cardiomyopathy: the use of repeated measurements of risk factors for outcome.

ESC Heart Fail 2021 04 5;8(2):1472-1481. Epub 2021 Feb 5.

Department of Pediatric Cardiology, Erasmus MC, University Medical Center Rotterdam, Dr Molewaterplein 60, PO Box 2060, Rotterdam, 3000 CB, The Netherlands.

Aims: We aimed to determine whether in children with dilated cardiomyopathy repeated measurement of known risk factors for death or heart transplantation (HTx) during disease progression can identify children at the highest risk for adverse outcome.

Methods And Results: Of 137 children we included in a prospective cohort, 36 (26%) reached the study endpoint (SE: all-cause death or HTx), 15 (11%) died at a median of 0.09 years [inter-quartile range (IQR) 0.03-0.7] after diagnosis, and 21 (15%) underwent HTx at a median of 2.9 years [IQR 0.8-6.1] after diagnosis. Median follow-up was 2.1 years [IQR 0.8-4.3]. Twenty-three children recovered at a median of 0.6 years [IQR 0.5-1.4] after diagnosis, and 78 children had ongoing disease at the end of the study. Children who reached the SE could be distinguished from those who did not, based on the temporal evolution of four risk factors: stunting of length growth (-0.42 vs. -0.02 length Z-score per year, P < 0.001), less decrease in N-terminal pro-B-type natriuretic peptide (NT-proBNP) (-0.26 vs. -1.06 2log pg/mL/year, P < 0.01), no decrease in left ventricular internal diastolic dimension (LVIDd; 0.24 vs. -0.60 Boston Z-score per year, P < 0.01), and increase in New York University Pediatric Heart Failure Index (NYU PHFI; 0.49 vs. -1.16 per year, P < 0.001). When we compared children who reached the SE with those with ongoing disease (leaving out the children who recovered), we found similar results, although the effects were smaller. In univariate analysis, NT-proBNP, length Z-score, LVIDd Z-score, global longitudinal strain (%), NYU PHFI, and age >6 years at presentation (all P < 0.001) were predictive of adverse outcome. In multivariate analysis, NT-proBNP appeared the only independent predictor for adverse outcome, a two-fold higher NT-proBNP was associated with a 2.8 times higher risk of the SE (hazard ratio 2.78, 95% confidence interval 1.81-3.94, P < 0.001).

Conclusions: The evolution over time of NT-proBNP, LVIDd, length growth, and NYU PHFI identified a subgroup of children with dilated cardiomyopathy at high risk for adverse outcome. In this sample, with a limited number of endpoints, NT-proBNP was the strongest independent predictor for adverse outcome.
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http://dx.doi.org/10.1002/ehf2.13233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006605PMC
April 2021

No association between use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to hospital admission and clinical course of COVID-19 in the COvid MEdicaTion (COMET) study.

Br J Clin Pharmacol 2021 08 18;87(8):3301-3309. Epub 2021 Feb 18.

Hospital Pharmacy, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.

Since the outbreak of SARS-CoV-2, also known as COVID-19, conflicting theories have circulated on the influence of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID-19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID-19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID-19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.
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http://dx.doi.org/10.1111/bcp.14751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014637PMC
August 2021

A heart failure phenotype stratified model for predicting 1-year mortality in patients admitted with acute heart failure: results from an individual participant data meta-analysis of four prospective European cohorts.

BMC Med 2021 01 27;19(1):21. Epub 2021 Jan 27.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB, Groningen, the Netherlands.

Background: Prognostic models developed in general cohorts with a mixture of heart failure (HF) phenotypes, though more widely applicable, are also likely to yield larger prediction errors in settings where the HF phenotypes have substantially different baseline mortality rates or different predictor-outcome associations. This study sought to use individual participant data meta-analysis to develop an HF phenotype stratified model for predicting 1-year mortality in patients admitted with acute HF.

Methods: Four prospective European cohorts were used to develop an HF phenotype stratified model. Cox model with two rounds of backward elimination was used to derive the prognostic index. Weibull model was used to obtain the baseline hazard functions. The internal-external cross-validation (IECV) approach was used to evaluate the generalizability of the developed model in terms of discrimination and calibration.

Results: 3577 acute HF patients were included, of which 2368 were classified as having HF with reduced ejection fraction (EF) (HFrEF; EF < 40%), 588 as having HF with midrange EF (HFmrEF; EF 40-49%), and 621 as having HF with preserved EF (HFpEF; EF ≥ 50%). A total of 11 readily available variables built up the prognostic index. For four of these predictor variables, namely systolic blood pressure, serum creatinine, myocardial infarction, and diabetes, the effect differed across the three HF phenotypes. With a weighted IECV-adjusted AUC of 0.79 (0.74-0.83) for HFrEF, 0.74 (0.70-0.79) for HFmrEF, and 0.74 (0.71-0.77) for HFpEF, the model showed excellent discrimination. Moreover, there was a good agreement between the average observed and predicted 1-year mortality risks, especially after recalibration of the baseline mortality risks.

Conclusions: Our HF phenotype stratified model showed excellent generalizability across four European cohorts and may provide a useful tool in HF phenotype-specific clinical decision-making.
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http://dx.doi.org/10.1186/s12916-020-01894-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839199PMC
January 2021

Chronic kidney disease and the outcomes of fibrinolysis for ST-segment elevation myocardial infarction: A real-world study.

PLoS One 2021 19;16(1):e0245576. Epub 2021 Jan 19.

Peking University Clinical Research Institute, Peking University First Hospital, Beijing, China.

Background: In low-resource regions, fibrinolytic therapy is often the only option for ST-elevation myocardial infarction (STEMI) patients as primary percutaneous coronary intervention (PCI) is often not available and patients are hardly transferred to a medical center with PCI capacity within the first 120 minutes. Chronic kidney disease (CKD) is one of the most frequently encountered complications of STEMI. However, the evidence for the efficacy of fibrinolytic therapy in STEMI patients with CKD is still limited. The aim of this study is to test whether CKD modifies the association between fibrinolytic therapy and short-term major adverse cardiovascular events (MACEs) among patients with STEMI.

Methods And Findings: This is a real-world study analyzing the data from 9508 STEMI patients (mean age: 64.0±12.4 years; male: 70.1%) in the third phase of Clinical Pathways in Acute Coronary Syndromes program (CPACS-3), which is a large study of the management of acute coronary syndromes (ACS) in 101 county hospitals without PCI capacity in China. CKD was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1·73 m2 at the admission. The primary outcome is short-term MACEs, including all-cause death, recurrent myocardial infarction, or nonfatal stroke. Patients were recruited consecutively between October 2011 and November 2014. Out of them, 1282 patients (13.5%) were classified as having CKD. Compared with non-CKD patients, CKD patients were less likely to receive fibrinolytic therapy than non-CKD patients (26.4% vs. 38.9%, P<0.001), more likely to experience a failed fibrinolytic therapy (32.8% vs. 16.9%), and had a higher risk of short-term MACEs (19.7% vs. 5.6%). After full adjustment, use of fibrinolytic therapy was associated with a significantly lower risk of short-term MACEs in non-CKD patients (relative risk [RR] = 0.87, 95% confidence interval [CI]: 0.76-0.99), but not in CKD patients (P for interaction = 0.026). Further analysis stratified by the success of fibrinolysis showed that compared with patients who did not receive fibrinolytic therapy, patients with successful fibrinolysis had a lower risk of short-term MACEs that was similar between patients with (RR = 0.71, 95% CI: 0.55-0.82) and without CKD (RR = 0.67, 95% CI: 0.55-0.92), while patients with unsuccessful fibrinolysis had a similarly higher risk in CKD patients (RR = 1.25, 95% CI: 1.09-1.43) and non-CKD patients (RR = 1.30, 95% CI: 1.13-1.50).

Conclusions: CKD reduced the likelihood of successful fibrinolysis and increased the risk of short-term MACEs in patients with STEMI. Attention should be paid to how to improve the success rate of fibrinolytic therapy for STEMI patients with CKD.

Trial Registration: The CPACS-3 study was registered on www.clinicaltrials.gov (NCT01398228).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245576PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815111PMC
June 2021

Remote hemodynamic guidance before and after left ventricular assist device implantation: short-term results from the HEMO-VAD pilot study.

Future Cardiol 2021 Aug 7;17(5):885-898. Epub 2021 Jan 7.

Department of Cardiology, Thorax Center, Erasmus MC, University Medical Center Rotterdam, Rotterdam 3015GD, The Netherlands.

We aimed to assess the safety and feasibility of using CardioMEMS monitoring in patients before and after left ventricular assist device (LVAD) surgery. Ten patients accepted for elective LVAD surgery were included, received a CardioMEMS at baseline and were categorized based on mean pulmonary artery pressure (mPAP) ≤25 mmHg (n = 4) or mPAP >25 mmHg [n = 6]) before LVAD surgery. The combined end point of all-cause mortality, acute kidney injury and/or renal replacement therapy, and right ventricular failure occurred more often in patients with an mPAP >25 mmHg (83 vs 0%, p = 0.017). This pilot study demonstrates that combining CardioMEMS monitoring with LVAD therapy is safe and generates the hypothesis that patients with an mPAP >25 mmHg before LVAD surgery identify a very high-risk group for adverse clinical outcomes.
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http://dx.doi.org/10.2217/fca-2020-0182DOI Listing
August 2021

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

J Am Heart Assoc 2021 01 16;10(1):e017393. Epub 2020 Dec 16.

Erasmus MCUniversity Medical Center Rotterdam Rotterdam The Netherlands.

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; <0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; <0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (=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.
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http://dx.doi.org/10.1161/JAHA.120.017393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955490PMC
January 2021
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