Publications by authors named "Peter M van de Ven"

205 Publications

Impact of percutaneous coronary intervention of chronic total occlusions on absolute perfusion in remote myocardium.

EuroIntervention 2021 Dec 6. Epub 2021 Dec 6.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Background: Revascularisation of a chronic total coronary occlusion (CTO) impacts the coronary physiology of the remote myocardial territory.

Aims: This study aimed to evaluate the intrinsic effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium.

Methods: A total of 164 patients who underwent serial [O]HO positron emission tomography (PET) perfusion imaging at baseline and three months after successful single-vessel CTO PCI were included to evaluate changes in hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in remote myocardium supplied by both non-target coronary arteries.

Results: Perfusion indices in CTO and remote myocardium showed a positive correlation before (resting MBF: r=0.84, hMBF: r=0.75, and CFR: r=0.77, p<0.01 for all) and after (resting MBF: r=0.87, hMBF: r=0.87, and CFR: r=0.81, p<0.01 for all) CTO PCI. Absolute increases in hMBF and CFR were observed in remote myocardium following CTO revascularisation (from 2.29±0.67 to 2.48±0.75 mL・min・g and from 2.48±0.76 to 2.74±0.85, respectively, p<0.01 for both). Improvements in remote myocardial perfusion were largest in patients with a higher increase in hMBF (β 0.58, 95% CI: 0.48-0.67, p<0.01) and CFR (β 0.54, 95% CI: 0.44-0.64, p<0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics.

Conclusions: CTO revascularisation resulted in an increase in remote myocardial perfusion. Furthermore, the quantitative improvement in hMBF and CFR in the CTO territory was independently associated with the absolute perfusion increase in remote myocardial regions. As such, CTO PCI may have a favourable physiologic impact beyond the intended treated myocardium.
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http://dx.doi.org/10.4244/EIJ-D-21-00702DOI Listing
December 2021

Ablation Index-guided point-by-point ablation versus Grid annotation-guided dragging for pulmonary vein isolation: A randomized controlled trial.

J Cardiovasc Electrophysiol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.

Introduction: Radiofrequency (RF) atrial fibrillation (AF) ablation using a catheter dragging technique may shorten procedural duration and improve durability of pulmonary vein isolation (PVI) by creating uninterrupted linear ablation lesions. We compared a novel AF ablation approach guided by Grid annotation allowing for "drag lesions" with a standard point-by-point ablation approach in a single-center randomized study.

Methods: Eighty-eight paroxysmal or persistent AF patients were randomized 1:1 to undergo RF-PVI with either a catheter dragging ablation technique guided by Grid annotation or point-by-point ablation guided by Ablation Index (AI) annotation. In the Grid annotation arm, ablation was visualized using 1 mm³ grid points coloring red after meeting predefined stability and contact force criteria. In the AI annotation arm, ablation lesions were created in a point-by-point fashion with AI target values set at 380 and 500 for posterior/inferior and anterior/roof segments, respectively. Patients were followed up for 12 months after PVI using ECGs, 24-h Holter monitoring and a mobile-based one-lead ECG device.

Results: Procedure time was not different between the two randomization arms (Grid annotation 71 ± 19 min, AI annotation 72 ± 26 min, p = .765). RF time was significantly longer in the Grid annotation arm compared with the AI annotation arm (49 ± 8 min vs. 37 ± 8 min, respectively, p < .001). Atrial tachyarrhythmia recurrence was documented in 10 patients (23%) in the Grid annotation arm compared with 19 patients (42%) in the AI annotation arm with time to recurrence not reaching statistical significance (p = .074).

Conclusions: This study shows that a Grid annotation-guided dragging approach provides an alternative to point-by-point RF-PVI using AI annotation.
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http://dx.doi.org/10.1111/jce.15294DOI Listing
November 2021

Surgical learning curve in reverse shoulder arthroplasty for proximal humerus fractures.

JSES Int 2021 Nov 9;5(6):1034-1041. Epub 2021 Oct 9.

Department of Trauma Surgery, Zaandam Medical Center, Zaandam, the Netherlands.

Background: Fracture reverse shoulder arthroplasty (fRSA) in geriatric, complex dislocated proximal humerus fractures is becoming the standard treatment next to conservative treatment. fRSA is a multifaceted, reasonably challenging procedure of which functional outcomes and complication rates are likely to depend on the experience of the surgeon. The goal of this study was to determine whether there is a learning curve for fRSA.

Methods: All patients with a dislocated multipart proximal humerus fracture that were treated with an fRSA between 2013 and 2019 in a specialized institution were included. The functional outcomes (Constant Shoulder Score, Oxford Shoulder Score, and range of motion), complications, and operation time of fRSA were assessed with linear regression plots and cumulative summation analysis to establish whether a learning curve was present.

Results: In this cohort study, 50 patients were included. They had a mean age of 77.1 years and were treated with an fRSA by one trauma surgeon. Learning curves were distinguished for functional outcomes, complications, and operation time based on learning targets for daily activity and the mean complications and operation time. Results indicated that an optimal treatment is achieved after performing 20 fRSAs.

Conclusion: The results show that functional outcomes of PHFs treated with an fRSA improve with surgical experience. Also, outcomes are getting less variable after about 20 procedures. Surgeons starting this procedure should be aware of the learning curve and, therefore, should consider guidance from an experienced surgeon to swiftly optimize functional outcomes and prevent unnecessary complications.
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http://dx.doi.org/10.1016/j.jseint.2021.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569002PMC
November 2021

Hospitalized COVID-19 Patients Were Five Times More Likely to Suffer From Total Sleep Deprivation Compared to Non-COVID-19 Patients; an Observational Comparative Study.

Front Neurosci 2021 5;15:680932. Epub 2021 Oct 5.

Section General Internal Medicine Unit Acute Medicine, Department of Internal Medicine, Amsterdam Public Health research institute, Amsterdam University Medical Center, location VU University Medical Center, Amsterdam, Netherlands.

Sleeping disorders are a common complaint in patients who suffer from an acute COVID-19 infection. Nonetheless, little is known about the severity of sleep disturbances in hospitalized COVID-19 patients, and whether these are caused by disease related symptoms, hospitalization, or the SARS-CoV-2 virus itself. Therefore, the aim of this study was to compare the quality and quantity of sleep in hospitalized patients with and without COVID-19, and to determine the main reasons for sleep disruption. This was an observational comparative study conducted between October 1, 2020 and February 1, 2021 at the pulmonary ward of an academic hospital in the Netherlands. This ward contained both COVID-19-positive and -negative tested patients. The sleep quality was assessed using the PROMIS-Sleep Disturbance Short Form and sleep quantity using the Consensus Sleep Diary. Patient-reported sleep disturbing factors were summarized. A total of 79 COVID-19 patients (mean age 63.0, male 59.5%) and 50 non-COVID-19 patients (mean age 59.5, male 54.0%) participated in this study. A significantly larger proportion of patients with COVID-19 reported not to have slept at all (19% vs. 4% of non-COVID-19 patients, ). The Sleep quality (PROMIS total score) and quantity (Total Sleep Time) did not significantly differ between both groups ((median PROMIS total score COVID-19; 26 [IQR 17-35], non-COVID-19; 23 [IQR 18-29], , (Mean Total Sleep Time COVID-19; 5 h 5 min, non-COVID-19 mean; 5 h 32 min, )). The most frequently reported disturbing factors by COVID-19 patients were; 'dyspnea', 'concerns about the disease', 'anxiety' and 'noises of other patients, medical staff and medical devices'. This study showed that both patients with and without an acute COVID-19 infection experienced poor quality and quantity of sleep at the hospital. Although the mean scores did not significantly differ between groups, total sleep deprivation was reported five times more often by COVID-19 patients. With one in five COVID-19 patients reporting a complete absence of night sleep, poor sleep seems to be a serious problem. Sleep improving interventions should focus on physical and psychological comfort and noise reduction in the hospital environment.
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http://dx.doi.org/10.3389/fnins.2021.680932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525610PMC
October 2021

Optimising personal continuity for older patients in general practice: a study protocol for a cluster randomised stepped wedge pragmatic trial.

BMC Fam Pract 2021 10 20;22(1):207. Epub 2021 Oct 20.

Department of General Practice, Amsterdam University Medical Centre, location VU University Medical Centre, van der Boechorststraat 7, 1081, BT, Amsterdam, the Netherlands.

Background: Continuity of care, in particular personal continuity, is a core principle of general practice and is associated with many benefits such as a better patient-provider relationship and lower mortality. However, personal continuity is under pressure due to changes in society and healthcare. This affects older patients more than younger patients. As the number of older patients will double the coming decades, an intervention to optimise personal continuity for this group is highly warranted.

Methods: Following the UK Medical Research Council framework for complex Interventions, we will develop and evaluate an intervention to optimise personal continuity for older patients in general practice. In phase 0, we will perform a literature study to provide the theoretical basis for the intervention. In phase I we will define the components of the intervention by performing surveys and focus groups among patients, general practitioners, practice assistants and practice nurses, concluded by a Delphi study among members of our group. In phase II, we will test and finalise the intervention with input from a pilot study in two general practices. In phase III, we will perform a stepped wedge cluster randomised pragmatic trial. The primary outcome measure is continuity of care from the patients' perspective, measured by the Nijmegen Continuity Questionnaire. Secondary outcome measures are level of implementation, barriers and facilitators for implementation, acceptability and feasibility of the intervention. In phase IV, we will establish the conditions for large-scale implementation.

Discussion: This is the first study to investigate an intervention for improving personal continuity for older patients in general practice. If proven effective, our intervention will enable General practitioners to improve the quality of care for their increasing population of older patients. The pragmatic design of the study will enable evaluation in real-life conditions, facilitating future implementation.

Trial Registration Number: Netherlands Trial Register, trial NL8132 . Registered 2 November 2019.
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http://dx.doi.org/10.1186/s12875-021-01511-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526277PMC
October 2021

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

Crit Care Med 2021 Sep 22. Epub 2021 Sep 22.

Department of Cardiology, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Cardiology, Amphia Hospital, Breda, The Netherlands. Department of Intensive Care Medicine, Amphia Hospital, Breda, The Netherlands. Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands. Department of Intensive Care Medicine, Rijnstate Hospital, Arnhem, The Netherlands. Department of Cardiology, HAGA Hospital, Den Haag, The Netherlands. Department of Intensive Care Medicine, HAGA Hospital, Den Haag, The Netherlands. Department of Cardiology, Maasstad Hospital, Rotterdam, The Netherlands. Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maasstad Hospital, Rotterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Maastricht University Medical Center, University Maastricht, Maastricht, The Netherlands. Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. Department of Intensive Care Medicine, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Medisch Spectrum Twente, Enschede, The Netherlands. Department of Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. Department of Cardiology, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Intensive Care Medicine, Amsterdam University Medical Center, location AMC, Amsterdam, The Netherlands. Department of Cardiology, OLVG, Amsterdam, The Netherlands. Department of Intensive Care Medicine, OLVG, Amsterdam, The Netherlands. Department of Cardiology, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Intensive Care Medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands. Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. Department of Cardiology, Scheper Hospital, Emmen, The Netherlands. Department of Cardiology, Haaglanden Medical Center, Den Haag, The Netherlands. Department of Cardiology, Isala Hospital, Zwolle, The Netherlands. Department of Cardiology, Tergooi Hospital, Blaricum, The Netherlands. Department of Cardiology, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands. Department of Epidemiology and Data Science, Amsterdam University Medical Center, location VUmc, Amsterdam, The Netherlands.

Objectives: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.

Design: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.

Setting: Nineteen hospitals in The Netherlands.

Patients: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.

Interventions: None.

Measurements And Main Results: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.

Conclusions: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.
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http://dx.doi.org/10.1097/CCM.0000000000005271DOI Listing
September 2021

Comparing the sensitivities of two screening tests in nonblinded randomized paired screen-positive trials with differential screening uptake.

Stat Med 2021 Oct 10. Epub 2021 Oct 10.

Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Before a new screening test can be used in routine screening, its performance needs to be compared to the standard screening test. This comparison is generally done in population screening trials with a screen-positive design where participants undergo one or both screening tests after which disease verification takes place for those positive on at least one screening test. We consider the randomized paired screen-positive design of Alonzo and Kittelson where participants are randomized to receive one of the two screening tests and only participants with a positive screening test subsequently receive the other screening test followed by disease verification. The tests are usually offered in an unblinded fashion in which case the screening uptake may differ between arms, in particular when one test is more burdensome than the other. When uptake is associated with disease, the estimator for the relative sensitivity derived by Alonzo and Kittelson may be biased and the type I error of the associated statistical test is no longer guaranteed to be controlled. We present methods for comparing sensitivities of screening tests in randomized paired screen-positive trials that are robust to differential screening uptake. In a simulation study, we show that our methods adequately control the type I error when screening uptake is associated with disease. We apply the developed methods to data from the IMPROVE trial, a nonblinded cervical cancer screening trial comparing the accuracy of HPV testing on self-collected versus provider-collected samples. In this trial, screening uptake was higher among participants randomized to self-collection.
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http://dx.doi.org/10.1002/sim.9215DOI Listing
October 2021

Comparison of the predictive value of ten risk scores for outcomes of atrial fibrillation patients undergoing radiofrequency pulmonary vein isolation.

Int J Cardiol 2021 Dec 20;344:103-110. Epub 2021 Sep 20.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands. Electronic address:

Background: A significant number of patients experience recurrent atrial fibrillation (AF) after ablation. Various risk scores have been described that may predict outcomes after AF ablation. In this study, we aimed to compare ten previously described risk scores with regard to their predictive value for post-ablation AF recurrence and procedural complications.

Methods: A total of 482 AF patients (63% paroxysmal AF, 66% male, mean age 62 ± 9 years) undergoing initial radiofrequency pulmonary vein isolation (PVI) were included in the present analysis. Prior to ablation, all patients underwent both transthoracic echocardiography (TTE) and either cardiac CT imaging or CMR imaging. The following risk scores were calculated for each patient: APPLE, ATLAS, BASE-AF, CAAP-AF, CHADS, CHADS-VASc, DR-FLASH, HATCH, LAGO and MB-LATER.

Results: Median follow-up was 16 (12-31) months. AF recurrence after a 90-day blanking period was observed in 199 patients (41%), occurring after a median of 183 (124-360) days. AF recurrence was less frequent in paroxysmal AF patients compared to non-paroxysmal AF patients (34% vs. 54%, p < 0.001). Overall periprocedural complication rate was 6%. All scores, except the HATCH score, demonstrated statistically significant but poor predictive value for recurrent AF after ablation (area under curve [AUC] 0.553-0.669). CHADS-VASc and CAAP-AF were the only risk scores with predictive value for procedural complications (AUC 0.616, p = 0.043; AUC 0.615, p = 0.044; respectively).

Conclusions: Currently available risk scores perform poorly in predicting outcomes after AF ablation. These data suggest that the utility of these scores for clinical decision-making is limited.
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http://dx.doi.org/10.1016/j.ijcard.2021.09.029DOI Listing
December 2021

Residual Quantitative Flow Ratio to Estimate Post-Percutaneous Coronary Intervention Fractional Flow Reserve.

J Interv Cardiol 2021 31;2021:4339451. Epub 2021 Aug 31.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Objectives: Quantitative flow ratio (QFR) computes fractional flow reserve (FFR) based on invasive coronary angiography (ICA). Residual QFR estimates post-percutaneous coronary intervention (PCI) FFR. This study sought to assess the relationship of residual QFR with post-PCI FFR.

Methods: Residual QFR analysis, using pre-PCI ICA, was attempted in 159 vessels with post-PCI FFR. QFR lesion location was matched with the PCI location to simulate the performed intervention and allow computation of residual QFR. A post-PCI FFR < 0.90 was used to define a suboptimal PCI result.

Results: Residual QFR computation was successful in 128 (81%) vessels. Median residual QFR was higher than post-PCI FFR (0.96 Q1-Q3: 0.91-0.99 vs. 0.91 Q1-Q3: 0.86-0.96, < 0.001). A significant correlation and agreement were observed between residual QFR and post-PCI FFR ( = 0.56 and intraclass correlation coefficient = 0.47, < 0.001 for both). Following PCI, an FFR < 0.90 was observed in 54 (42%) vessels. Specificity, positive predictive value, sensitivity, and negative predictive value of residual QFR for assessment of the PCI result were 96% (95% confidence interval (CI): 87-99%), 89% (95% CI: 72-96%), 44% (95% CI: 31-59%), and 70% (95% CI: 65-75%), respectively. Residual QFR had an accuracy of 74% (95% CI: 66-82%) and an area under the receiver operating characteristic curve of 0.79 (95% CI: 0.71-0.86).

Conclusions: A significant correlation and agreement between residual QFR and post-PCI FFR were observed. Residual QFR ≥ 0.90 did not necessarily commensurate with a satisfactory PCI (post-PCI FFR ≥ 0.90). In contrast, residual QFR exhibited a high specificity for prediction of a suboptimal PCI result.
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http://dx.doi.org/10.1155/2021/4339451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426071PMC
November 2021

Functional recovery after percutaneous revascularization of coronary chronic total occlusions: insights from cardiac magnetic resonance tissue tracking.

Int J Cardiovasc Imaging 2021 Oct 2;37(10):3057-3068. Epub 2021 Aug 2.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit, ZH 5F003, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

To evaluate the effect of percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) on left ventricular (LV) strain assessed using cardiac magnetic resonance (CMR) tissue tracking. In 150 patients with a CTO, longitudinal (LS), radial (RS) and circumferential shortening (CS) were determined using CMR tissue tracking before and 3 months after successful PCI. In patients with impaired LV strain at baseline, global LS (10.9 ± 2.4% vs 11.6 ± 2.8%; P = 0.006), CS (11.3 ± 2.9% vs 12.0 ± 3.5%; P = 0.002) and RS (15.8 ± 4.9% vs 17.4 ± 6.6%; P = 0.001) improved after revascularization of the CTO, albeit to a small, clinically irrelevant, extent. Strain improvement was inversely related to the extent of scar, even after correcting for baseline strain (B =  - 0.05; P = 0.008 for GLS, B =  - 0.06; P = 0.016 for GCS, B =  - 0.13; P = 0.017 for GRS). In the vascular territory of the CTO, dysfunctional segments showed minor improvement in both CS (10.8 [6.9 to 13.3] % vs 11.9 [8.1 to 15.0] %; P < 0.001) and RS (14.2 [8.4 to 18.7] % vs 16.0 [9.9 to 21.8] %; P < 0.001) after PCI. Percutaneous revascularization of CTOs does not lead to a clinically relevant improvement of LV function, even in the subgroup of patients and segments most likely to benefit from revascularization (i.e. LV dysfunction at baseline and no or limited myocardial scar).
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http://dx.doi.org/10.1007/s10554-021-02355-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494704PMC
October 2021

Viability and functional recovery after chronic total occlusion percutaneous coronary intervention.

Catheter Cardiovasc Interv 2021 11 30;98(5):E668-E676. Epub 2021 Jul 30.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Objectives: This study evaluated myocardial viability as well as global and regional functional recovery after successful chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) using sequential quantitative cardiac magnetic resonance (CMR) imaging.

Background: The patient benefits of CTO PCI are being questioned.

Methods: In a single high-volume CTO PCI center patients were prospectively scheduled for CMR at baseline and 3 months after successful CTO PCI between 2013 and 2018. Segmental wall thickening (SWT) and percentage late gadolinium enhancement (LGE) were quantitatively measured per segment. Viability was defined as dysfunctional myocardium (<2.84 mm SWT) with no or limited scar (≤50% LGE).

Results: A total of 132 patients were included. Improvement of left ventricular ejection fraction was modest after CTO PCI (from 48.1 ± 11.8 to 49.5 ± 12.1%, p < 0.01). CTO segments with viability (N = 216, [31%]) demonstrated a significantly higher increase in SWT (0.80 ± 1.39 mm) compared to CTO segments with pre-procedural preserved function (N = 456 [65%], 0.07 ± 1.43 mm, p < 0.01) or extensive scar (LGE >50%, N = 26 [4%], -0.08 ± 1.09 mm, p < 0.01). Patients with ≥2 CTO segments viability showed more SWT increase in the CTO territory compared to patients with 0-1 segment viability (0.49 ± 0.93 vs. 0.12 ± 0.98 mm, p = 0.03).

Conclusions: Detection of dysfunctional myocardial segments without extensive scar (≤50% LGE) as a marker for viability on CMR aids in identifying patients with significant regional functional recovery after CTO PCI.
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http://dx.doi.org/10.1002/ccd.29888DOI Listing
November 2021

The important role of cisplatin in the treatment of HPV-positive oropharyngeal cancer assessed by real-world data analysis.

Oral Oncol 2021 10 23;121:105454. Epub 2021 Jul 23.

Amsterdam UMC, Vrije Universiteit Amsterdam, Otolaryngology / Head and Neck Surgery, Cancer Center Amsterdam, the Netherlands.

Objectives: The prognostic advantage of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) resulted in the initiation of treatment de-intensification studies. Two randomized controlled trials (RCTs) reported inferior survival of HPV-positive OPSCC treated with radiotherapy plus cetuximab compared to standard of care radiotherapy plus cisplatin. In this study we investigated whether the important role of cisplatin in the treatment of HPV-positive OPSCCs would also emerge from causal inference analyses of real-world data.

Material And Methods: A retrospective cohort of 263 advanced-stage OPSCC-patients from 5 European clinics was studied, treated with radiotherapy (RT) alone or cisplatin-based chemoradiotherapy (CRT) based on standard clinical indications. Causal inference was applied to adjust for treatment assignment, thereby simulating a randomized setting. Average treatment effect of concurrent cisplatin on overall survival (OS) probability was estimated using Bayesian Additive Regression Trees (BART) and Bayesian logistic regression.

Results: Significantly better survival probabilities were found for HPV-positive OPSCC treated with CRT compared to RT alone (3-year OS probability 0.961 versus 0.798, p = 0.008).

Conclusion: This study using causal inference of retrospective patient data confirms the important role of cisplatin in the treatment of HPV-positive OPSCC. Causal inference analyses of real-world data complements the evidence from the published RCTs.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105454DOI Listing
October 2021

Segment Length in Cine Strain Analysis Predicts Cardiac Resynchronization Therapy Outcome Beyond Current Guidelines.

Circ Cardiovasc Imaging 2021 07 20;14(7):e012350. Epub 2021 Jul 20.

Department of Cardiology, and Amsterdam Cardiovascular Sciences (ACS) (A.Z., C.V., P.S.B., A.C.v.R., C.P.A., R.N.), Amsterdam University Medical Center, location VU Medical Center, Amsterdam, The Netherlands.

Background: Patients with a class I recommendation for cardiac resynchronization therapy (CRT) are likely to benefit, but the effect of CRT in class II patients is more heterogeneous and additional selection parameters are needed in this group. The recently validated segment length in cine strain analysis of the septum (SLICE-ESS) measurement on cardiac magnetic resonance cine imaging predicts left ventricular functional recovery after CRT but its prognostic value is unknown. This study sought to evaluate the prognostic value of SLICE-ESS for clinical outcome after CRT.

Methods: Two hundred eighteen patients with a left bundle branch block or intraventricular conduction delay and a class I or class II indication for CRT who underwent preimplantation cardiovascular magnetic resonance examination were enrolled. SLICE-ESS was manually measured on standard cardiovascular magnetic resonance cine imaging. The primary combined end point was all-cause mortality, left ventricular assist device, or heart transplantation. Secondary end points were (1) appropriate implantable cardioverter defibrillator therapy and (2) heart failure hospitalization.

Results: Two-thirds (65%) of patients had a positive SLICE-ESS ≥0.9% (ie, systolic septal stretching). During a median follow-up of 3.8 years, 66 (30%) patients reached the primary end point. Patients with positive SLICE-ESS were at lower risk to reach the primary end point (hazard ratio 0.36; <0.001) and heart failure hospitalization (hazard ratio 0.41; =0.019), but not for implantable cardioverter defibrillator therapy (hazard ratio, 0.66; =0.272). Clinical outcome of class II patients with a positive ESS was similar to those of class I patients (hazard ratio, 1.38 [95% CI, 0.66-2.88]; =0.396).

Conclusions: Strain assessment of the septum (SLICE-ESS) provides a prognostic measure for clinical outcome after CRT. Detection of a positive SLICE-ESS in patients with a class II indication predicts improved CRT outcome similar to those with a class I indication whereas SLICE-ESS negative patients have poor prognosis after CRT implantation.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.012350DOI Listing
July 2021

Ischemic Burden Reduction and Long-Term Clinical Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention.

JACC Cardiovasc Interv 2021 07;14(13):1407-1418

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address:

Objectives: The authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief.

Background: The clinical benefit of CTO PCI is questioned.

Methods: In a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [O]HO positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min · g) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction.

Results: After a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus <3 segment PD reduction (p < 0.01; risk-adjusted p = 0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11 ml · min · g) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min · g (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min · g were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04).

Conclusions: Patients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.
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http://dx.doi.org/10.1016/j.jcin.2021.04.044DOI Listing
July 2021

Left ventricular function, strain, and infarct characteristics in patients with transient ST-segment elevation myocardial infarction compared to ST-segment and non-ST-segment elevation myocardial infarctions.

Eur Heart J Cardiovasc Imaging 2021 Jul 1. Epub 2021 Jul 1.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Aims: This study aims to explore cardiovascular magnetic resonance (CMR)-derived left ventricular (LV) function, strain, and infarct size characteristics in patients with transient ST-segment elevation myocardial infarction (TSTEMI) compared to patients with ST-segment and non-ST-segment elevation myocardial infarctions (STEMI and NSTEMI, respectively).

Methods And Results: In total, 407 patients were enrolled in this multicentre observational prospective cohort study. All patients underwent CMR examination 2-8 days after the index event. CMR cine imaging was performed for functional assessment and late gadolinium enhancement to determine infarct size and identify microvascular obstruction (MVO). TSTEMI patients demonstrated the highest LV ejection fraction and the most preserved global LV strain (longitudinal, circumferential, and radial) across the three groups (overall P ≤ 0.001). The CMR-defined infarction was less frequently observed in TSTEMI than in STEMI patients [77 (65%) vs. 124 (98%), P < 0.001] but was comparable with NSTEMI patients [77 (65%) vs. 66 (70%), P = 0.44]. A remarkably smaller infarct size was seen in TSTEMI compared to STEMI patients [1.4 g (0.0-3.9) vs. 13.5 g (5.3-26.8), P < 0.001], whereas infarct size was not significantly different from that in NSTEMI patients [1.4 g (0.0-3.9) vs. 2.1 g (0.0-8.6), P = 0.06]. Whilst the presence of MVO was less frequent in TSTEMI compared to STEMI patients [5 (4%) vs. 53 (31%), P < 0.001], no significant difference was seen compared to NSTEMI patients [5 (4%) vs. 5 (5%), P = 0.72].

Conclusion: TSTEMI yielded favourable cardiac LV function, strain, and infarct-related scar mass compared to STEMI and NSTEMI. LV function and infarct characteristics of TSTEMI tend to be more similar to NSTEMI than STEMI.
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http://dx.doi.org/10.1093/ehjci/jeab114DOI Listing
July 2021

Sex-specific differences in outcome and risk stratification of ventricular arrhythmias in implantable cardioverter defibrillator patients.

ESC Heart Fail 2021 10 29;8(5):3726-3736. Epub 2021 Jun 29.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.

Aims: Risk stratification models of sudden cardiac death (SCD) are based on the assumption that risk factors of SCD affect risk to a similar extent in both sexes. The aim of the study is to evaluate differences in clinical outcomes between sexes and evaluate whether risk factors associated with appropriate device therapy (ADT) differ between men and women.

Methods And Results: We performed a cohort study of implantable cardioverter defibrillator (ICD) patients referred for primary or secondary prevention of SCD between 2009 and 2018. Multivariable Cox regression models for prediction of ADT were constructed for men and women separately. Of 2300 included patients, 571 (25%) were women. Median follow-up was 4.6 (inter-quartile range: 4.4-4.9) years. Time to ADT was shorter for men compared with women [hazard ratio (HR) 1.71, P < 0.001], as was time to mortality (HR 1.37, P = 0.003). In women, only secondary prevention ICD therapy (HR 1.82, P < 0.01) was associated with ADT, whereas higher age (HR 1.20, P < 0.001), absence of left bundle branch block (HR 0.72, P = 0.01), and secondary prevention therapy (HR 1.80, P < 0.001) were independently associated with ADT in men. None of the observed parameters showed a distinctive sex-specific pattern in ADT.

Conclusions: Male ICD patients were at higher risk of ADT and death compared with female ICD patients, irrespective of an ischaemic or non-ischaemic underlying cardiomyopathy. Our study highlights the importance to stratify outcomes of ICD trials by sex, as study results differ between men and women. However, none of the available clinical parameters showed a clear sex-specific relation to ventricular arrhythmias. As a consequence, sex-specific risk stratification models of SCD using commonly available clinical parameters could not be derived.
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http://dx.doi.org/10.1002/ehf2.13444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497372PMC
October 2021

External Validation and Addition of Prostate-specific Membrane Antigen Positron Emission Tomography to the Most Frequently Used Nomograms for the Prediction of Pelvic Lymph-node Metastases: an International Multicenter Study.

Eur Urol 2021 08 21;80(2):234-242. Epub 2021 May 21.

Department of Urology, Prostate Cancer Network Netherlands, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands; Department of Urology, Prostate Cancer Network Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET).

Objective: To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa.

Design, Setting, And Participants: All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included.

Outcome Measurements And Statistical Analysis: Performance of the three nomograms was assessed using the receiver operating characteristic curve-derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed.

Results And Limitations: Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64-0.77), 0.71 (95% CI: 0.65-0.77), and 0.76 (95% CI: 0.71-0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70-0.82), 0.77 (95% CI: 0.72-0.83), and 0.82 (95% CI: 0.76-0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits.

Conclusions: The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram.

Patient Summary: Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.
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http://dx.doi.org/10.1016/j.eururo.2021.05.006DOI Listing
August 2021

Transient ST-elevation myocardial infarction versus persistent ST-elevation myocardial infarction. An appraisal of patient characteristics and functional outcome.

Int J Cardiol 2021 08 15;336:22-28. Epub 2021 May 15.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081HV Amsterdam, the Netherlands; Department of Cardiology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525GA Nijmegen, the Netherlands. Electronic address:

Background: Up to 24% of patients presenting with ST-elevation myocardial infarction (STEMI) show resolution of ST-elevation and symptoms before revascularization. The mechanisms of spontaneous reperfusion are unclear. Given the more favorable outcome of transient STEMI, it is important to obtain further insights in differential aspects.

Methods: We compared 251 patients who presented with transient STEMI (n = 141) or persistent STEMI (n = 110). Clinical angiographic and laboratory data were collected at admission and in subset of patients additional index hemostatic data and at steady-state follow-up. Cardiac magnetic resonance imaging (CMR) was performed at 2-8 days to assess myocardial injury.

Results: Transient STEMI patients had more cardiovascular risk factors than STEMI patients, including more arterial disease and higher cholesterol values. Transient STEMI patients showed angiographically more often no intracoronary thrombus (41.1% vs. 2.7%, P < 0.001) and less often a high thrombus burden (9.2% vs. 40.0%, P < 0.001). CMR revealed microvascular obstruction less frequently (4.2% vs. 34.6%, P < 0.001) and smaller infarct size [1.4%; interquartile range (IQR), 0.0-3.7% vs. 8.8%; IQR, 3.9-17.1% of the left ventricle, P < 0.001] with a better preserved left ventricular ejection fraction (57.8 ± 6.7% vs. 52.5 ± 7.6%, P < 0.001). At steady state, fibrinolysis was higher in transient STEMI, as demonstrated with a reduced clot lysis time (89 ± 20% vs. 99 ± 25%, P = 0.03).

Conclusions: Transient STEMI is a syndrome with less angiographic thrombus burden and spontaneous infarct artery reperfusion, resulting in less myocardial injury than STEMI. The presence of a more effective fibrinolysis in transient STEMI patients may explain these differences and might provide clues for future treatment of STEMI.
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http://dx.doi.org/10.1016/j.ijcard.2021.05.018DOI Listing
August 2021

Comparison between cardiac magnetic resonance stress T1 mapping and [15O]H2O positron emission tomography in patients with suspected obstructive coronary artery disease.

Eur Heart J Cardiovasc Imaging 2021 May 13. Epub 2021 May 13.

Department of Cardiology, Amsterdam University Medical Centers, Vrije Universiteit, De Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands.

Aims: To compare cardiac magnetic resonance (CMR) measurement of T1 reactivity (ΔT1) with [15O]H2O positron emission tomography (PET) measurements of quantitative myocardial perfusion.

Methods And Results: Forty-three patients with suspected obstructed coronary artery disease underwent [15O]H2O PET and CMR at 1.5-T, including rest and adenosine stress T1 mapping (ShMOLLI) and late gadolinium enhancement to rule out presence of scar tissue. ΔT1 was determined for the three main vascular territories and compared with [15O]H2O PET-derived regional stress myocardial blood flow (MBF) and myocardial flow reserve (MFR). ΔT1 showed a significant but poor correlation with stress MBF (R2 = 0.04, P = 0.03) and MFR (R2 = 0.07, P = 0.004). Vascular territories with impaired stress MBF (i.e. ≤2.30 mL/min/g) demonstrated attenuated ΔT1 compared with vascular territories with preserved stress MBF (2.9 ± 2.2% vs. 4.1 ± 2.2%, P = 0.008). In contrast, ΔT1 did not differ between vascular territories with impaired (i.e. <2.50) and preserved MFR (3.2 ± 2.6% vs. 4.0 ± 2.1%, P = 0.25). Receiver operating curve analysis of ΔT1 resulted in an area under the curve of 0.66 [95% confidence interval (CI): 0.57-0.75, P = 0.009] for diagnosing impaired stress MBF and 0.62 (95% CI: 0.53-0.71, P = 0.07) for diagnosing impaired MFR.

Conclusions: CMR stress T1 mapping has poor agreement with [15O]H2O PET measurements of absolute myocardial perfusion. Stress T1 and ΔT1 are lower in vascular territories with reduced stress MBF but have poor accuracy for detecting impaired myocardial perfusion.
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http://dx.doi.org/10.1093/ehjci/jeab073DOI Listing
May 2021

Assessing COVID-19 pneumonia-Clinical extension and risk with point-of-care ultrasound: A multicenter, prospective, observational study.

J Am Coll Emerg Physicians Open 2021 Jun 1;2(3):e12429. Epub 2021 May 1.

Section Acute Internal Medicine, Department of Internal Medicine Radboud University Medical Center Nijmegen The Netherlands.

Background: Assessing the extent of lung involvement is important for the triage and care of COVID-19 pneumonia. We sought to determine the utility of point-of-care ultrasound (POCUS) for characterizing lung involvement and, thereby, clinical risk determination in COVID-19 pneumonia.

Methods: This multicenter, prospective, observational study included patients with COVID-19 who received 12-zone lung ultrasound and chest computed tomography (CT) scanning in the emergency department (ED). We defined lung disease severity using the lung ultrasound score (LUS) and chest CT severity score (CTSS). We assessed the association between the LUS and poor outcome (ICU admission or 30-day all-cause mortality). We also assessed the association between the LUS and hospital length of stay. We examined the ability of the LUS to differentiate between disease severity groups. Lastly, we estimated the correlation between the LUS and CTSS and the interrater agreement for the LUS. We handled missing data by multiple imputation with chained equations and predictive mean matching.

Results: We included 114 patients treated between March 19, 2020, and May 4, 2020. An LUS ≥12 was associated with a poor outcome within 30 days (hazard ratio [HR], 5.59; 95% confidence interval [CI], 1.26-24.80; = 0.02). Admission duration was shorter in patients with an LUS <12 (adjusted HR, 2.24; 95% CI, 1.47-3.40; < 0.001). Mean LUS differed between disease severity groups: no admission, 6.3 (standard deviation [SD], 4.4); hospital/ward, 13.1 (SD, 6.4); and ICU, 18.0 (SD, 5.0). The LUS was able to discriminate between ED discharge and hospital admission excellently, with an area under the curve of 0.83 (95% CI, 0.75-0.91). Interrater agreement for the LUS was strong: κ = 0.88 (95% CI, 0.77-0.95). Correlation between the LUS and CTSS was strong: κ = 0.60 (95% CI, 0.48-0.71).

Conclusions: We showed that baseline lung ultrasound - is associated with poor outcomes, admission duration, and disease severity. The LUS also correlates well with CTSS. Point-of-care lung ultrasound may aid the risk stratification and triage of patients with COVID-19 at the ED.
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http://dx.doi.org/10.1002/emp2.12429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087918PMC
June 2021

Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques, Plaque Volume, and Ischemia.

JACC Cardiovasc Imaging 2021 08 3;14(8):1598-1610. Epub 2021 May 3.

Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address:

Objectives: This study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)-derived plaque volume and positron emission tomography (PET) determined ischemia.

Background: Inflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD).

Methods: A total of 539 patients who underwent CCTA and [O]HO PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables.

Results: During a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm, CPV >110 mm, NCPV >85 mm, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011).

Conclusions: Parameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.
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http://dx.doi.org/10.1016/j.jcmg.2021.02.026DOI Listing
August 2021

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

Resuscitation 2021 07 28;164:93-100. Epub 2021 Apr 28.

Department of Intensive care medicine, Noord West Ziekenhuisgroep, Alkmaar, The Netherlands.

Background: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown.

Methods: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography.

Results: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32).

Conclusion: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy.

Clinical Trial Registration: Netherlands Trial Register number, NTR4973.
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http://dx.doi.org/10.1016/j.resuscitation.2021.04.020DOI Listing
July 2021

Coronary Collateral Flow Index Is Correlated With the Palmar Collateral Flow Index: Indicating Systemic Collateral Coherence in Individual Patients-Brief Report.

Arterioscler Thromb Vasc Biol 2021 05 18;41(5):1830-1836. Epub 2021 Mar 18.

Department of Cardiology (M.R.H., M.F.J., S.P.S., W.J.S., M.A.H.v.L., A.N., P.K., N.v.R.), Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.316092DOI Listing
May 2021

Changes in Respiratory Muscle Thickness during Mechanical Ventilation: Focus on Expiratory Muscles.

Anesthesiology 2021 05;134(5):748-759

Background: The lateral abdominal wall muscles are recruited with active expiration, as may occur with high breathing effort, inspiratory muscle weakness, or pulmonary hyperinflation. The effects of critical illness and mechanical ventilation on these muscles are unknown. This study aimed to assess the reproducibility of expiratory muscle (i.e., lateral abdominal wall muscles and rectus abdominis muscle) ultrasound and the impact of tidal volume on expiratory muscle thickness, to evaluate changes in expiratory muscle thickness during mechanical ventilation, and to compare this to changes in diaphragm thickness.

Methods: Two raters assessed the interrater and intrarater reproducibility of expiratory muscle ultrasound (n = 30) and the effect of delivered tidal volume on expiratory muscle thickness (n = 10). Changes in the thickness of the expiratory muscles and the diaphragm were assessed in 77 patients with at least two serial ultrasound measurements in the first week of mechanical ventilation.

Results: The reproducibility of the measurements was excellent (interrater intraclass correlation coefficient: 0.994 [95% CI, 0.987 to 0.997]; intrarater intraclass correlation coefficient: 0.992 [95% CI, 0.957 to 0.998]). Expiratory muscle thickness decreased by 3.0 ± 1.7% (mean ± SD) with tidal volumes of 481 ± 64 ml (P < 0.001). The thickness of the expiratory muscles remained stable in 51 of 77 (66%), decreased in 17 of 77 (22%), and increased in 9 of 77 (12%) patients. Reduced thickness resulted from loss of muscular tissue, whereas increased thickness mainly resulted from increased interparietal fasciae thickness. Changes in thickness of the expiratory muscles were not associated with changes in the thickness of the diaphragm (R2 = 0.013; P = 0.332).

Conclusions: Thickness measurement of the expiratory muscles by ultrasound has excellent reproducibility. Changes in the thickness of the expiratory muscles occurred in 34% of patients and were unrelated to changes in diaphragm thickness. Increased expiratory muscle thickness resulted from increased thickness of the fasciae.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003736DOI Listing
May 2021

Characteristics and prognostic value of right ventricular (dys)function in patients with non-ischaemic dilated cardiomyopathy assessed with cardiac magnetic resonance imaging.

ESC Heart Fail 2021 04 9;8(2):1055-1063. Epub 2021 Feb 9.

Department of Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.

Aims: In non-ischaemic dilated cardiomyopathy (DCM), concomitant right ventricular (RV) dysfunction is frequently observed. This study sought to determine the correlation of RV dysfunction with several cardiac magnetic resonance (CMR) imaging characteristics in patients with DCM, and the prognostic value of RV dysfunction on all-cause mortality and ventricular arrhythmias (VA) was evaluated.

Methods And Results: Consecutive patients with DCM and left ventricular (LV) dysfunction (ejection fraction < 50%) on CMR were included retrospectively. Left atrial (LA), LV, and RV volumes and function were quantified. RV systolic dysfunction was defined as RVEF<45%. The presence and pattern of late gadolinium enhancement (LGE) on CMR were assessed visually. Septal midwall LGE was defined as midmyocardial stripe-like or patchy hyperenhancement in the septal segments, and the extent was quantified using the full width at half maximum method. Primary endpoint was a composite of all-cause mortality and VA, including resuscitated cardiac arrest, sustained VA, and appropriate implantable cardioverter defibrillator therapy. Secondary endpoints were time to all-cause mortality alone and time to VA alone. A total of 216 DCM patients were included (42% female, age 58 ± 14 years). Mean RVEF was 46 ± 12%, and RV dysfunction was present in 38%. RVEF was moderately correlated with LA dilation (LA minimal volume ρ = -0.38, P < 0.001) and strongly correlated with LA and LV dysfunction (LA emptying fraction r = 0.58, P < 0.001 and LVEF ρ = 0.52, P < 0.001). Septal midwall LGE was more often observed in patients with RV dysfunction compared with patients with preserved RV function (respectively 40% vs. 26%, P = 0.04). No correlation was found between RVEF and the extent of septal midwall LGE (ρ = -0.12, P = 0.34). During a median follow-up of 2.2 years [IQR 1.6-2.8], 30 patients experienced the primary endpoint. RV dysfunction was significantly associated with shorter time to the composite primary endpoint (HR 3.19 [95% CI 1.49-6.84], P < 0.01) and to the secondary endpoint of VA alone (HR 6.48 [95% CI 1.83-22.98], P < 0.01). There was a trend towards increased mortality when RV dysfunction was present (HR 2.54 [95% CI 0.99-6.57], P = 0.05).

Conclusions: Right ventricular dysfunction was predominantly observed in patients with DCM with advanced heart failure and pronounced myocardial remodelling, defined as increased LV and LA dilation and dysfunction and the presence of septal midwall LGE on CMR. During follow-up, RV dysfunction was associated with shorter time to all-cause mortality and ventricular arrhythmic events.
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http://dx.doi.org/10.1002/ehf2.13072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006611PMC
April 2021

Systematic Review of N-of-1 Studies in Rare Genetic Neurodevelopmental Disorders: The Power of 1.

Neurology 2021 03 27;96(11):529-540. Epub 2021 Jan 27.

's Heeren Loo (A.R.M.), Amersfoort, the Netherlands, and Amsterdam UMC (A.R.M.), Pediatric Metabolic Diseases, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands; Pediatric Metabolic Diseases (M.M.G.B), Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics (P.M.v.d.V.), Amsterdam UMC, Amsterdam, the Netherlands; Department of Health Evidence, Biostatistics (K.C.B.R.), Radboud University Medical Center, Radboud University, Nijmegen, the Netherlands; Department of Clinical Genetics (M.C.C.), Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands; Pediatric Metabolic Diseases (C.D.M.v.K.), Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands, and Department of Pediatrics (C.D.M.v.K.), Radboud University Medical Center, Radboud Centre for Mitochondrial Medicine, Nijmegen, the Netherlands; Pediatric Metabolic Diseases (F.A.W.), Amsterdam UMC, Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands; Medical Library (J.G.D.), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; 's Heeren Loo (E.B.), Amersfoort, the Netherlands, and Department of Psychiatry and Neuropsychology (E.B.), Maastricht University, Maastricht, the Netherlands, University Health Network (E.B.), The Dalglish Family 22q Clinic, Toronto, Ontario, Canada; and 's Heeren Loo (A.M.v.E.), Amersfoort, the Netherlands, Amsterdam UMC (A.M.v.E.), Emma Children's Hospital, University of Amsterdam, Amsterdam, the Netherlands, and Erasmus Medical Center (A.M.v.E.), ENCORE, Rotterdam, the Netherlands.

Objective: To improve the use of N-of-1 studies in rare genetic neurodevelopmental disorders, we systematically reviewed the literature and formulated recommendations for future studies.

Methods: The systematic review protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42020154720). EMBASE and MEDLINE were searched for relevant studies. Information was recorded on types of interventions, outcome measures, validity, strengths, and limitations using standard reporting guidelines and critical appraisal tools. Qualitative and descriptive analyses were performed.

Results: Twelve studies met the N-of-1 inclusion criteria, including both single trials and series. Interventions were mainly directed to neuropsychiatric manifestations. Main strengths were the use of personalized and clinically relevant outcomes in most studies. Generalizability was compromised due to limited use of validated and generalizable outcome measures.

Conclusion: N-of-1 studies are sporadically reported in rare genetic neurodevelopmental disorders. Properly executed N-of-1 studies may provide a powerful alternative to larger randomized controlled trials in rare disorders and a much needed bridge between practice and science. We provide recommendations for future N-of-1 studies in rare genetic neurodevelopmental disorders, ultimately optimizing evidence-based and personalized care.
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http://dx.doi.org/10.1212/WNL.0000000000011597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032375PMC
March 2021

Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome.

J Clin Endocrinol Metab 2021 03;106(3):e1084-e1095

Department of Reproductive Medicine, Amsterdam UMC, Vrije Universiteit, HV Amsterdam, the Netherlands.

Context: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated.

Objective: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood.

Design And Setting: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997.

Participants And Interventions: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study.

Results: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) μg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 μg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value.

Conclusions: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice.
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http://dx.doi.org/10.1210/clinem/dgaa949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947839PMC
March 2021

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.

Data Brief 2020 Dec 12;33:106521. Epub 2020 Nov 12.

Department of Intensive care medicine, Maastricht University Medical Center, University Maastricht, Maastricht, the Netherlands.

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.
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http://dx.doi.org/10.1016/j.dib.2020.106521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691722PMC
December 2020

Chest CT in COVID-19 at the ED: Validation of the COVID-19 Reporting and Data System (CO-RADS) and CT Severity Score: A Prospective, Multicenter, Observational Study.

Chest 2021 03 30;159(3):1126-1135. Epub 2020 Nov 30.

Section General & Acute Internal Medicine, Department of Internal Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands. Electronic address:

Background: CT is thought to play a key role in coronavirus disease 2019 (COVID-19) diagnostic workup. The possibility of comparing data across different settings depends on the systematic and reproducible manner in which the scans are analyzed and reported. The COVID-19 Reporting and Data System (CO-RADS) and the corresponding CT severity score (CTSS) introduced by the Radiological Society of the Netherlands (NVvR) attempt to do so. However, this system has not been externally validated.

Research Question: We aimed to prospectively validate the CO-RADS as a COVID-19 diagnostic tool at the ED and to evaluate whether the CTSS is associated with prognosis.

Study Design And Methods: We conducted a prospective, observational study in two tertiary centers in The Netherlands, between March 19 and May 28, 2020. We consecutively included 741 adult patients at the ED with suspected COVID-19, who received a chest CT and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR (PCR). Diagnostic accuracy measures were calculated for CO-RADS, using PCR as reference. Logistic regression was performed for CTSS in relation to hospital admission, ICU admission, and 30-day mortality.

Results: Seven hundred forty-one patients were included. We found an area under the curve (AUC) of 0.91 (CI, 0.89-0.94) for CO-RADS using PCR as reference. The optimal CO-RADS cutoff was 4, with a sensitivity of 89.4% (CI, 84.7-93.0) and specificity of 87.2% (CI, 83.9-89.9). We found a significant association between CTSS and hospital admission, ICU admission, and 30-day mortality; adjusted ORs per point increase in CTSS were 1.19 (CI, 1.09-1.28), 1.23 (1.15-1.32), 1.14 (1.07-1.22), respectively. Intraclass correlation coefficients for CO-RADS and CTSS were 0.94 (0.91-0.96) and 0.82 (0.70-0.90).

Interpretation: Our findings support the use of CO-RADS and CTSS in triage, diagnosis, and management decisions for patients presenting with possible COVID-19 at the ED.
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http://dx.doi.org/10.1016/j.chest.2020.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704067PMC
March 2021

Bayesian adaptive decision-theoretic designs for multi-arm multi-stage clinical trials.

Stat Methods Med Res 2021 03 26;30(3):717-730. Epub 2020 Nov 26.

Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.

Multi-arm multi-stage clinical trials in which more than two drugs are simultaneously investigated provide gains over separate single- or two-arm trials. In this paper we propose a generic Bayesian adaptive decision-theoretic design for multi-arm multi-stage clinical trials with () arms. The basic idea is that after each stage a decision about continuation of the trial and accrual of patients for an additional stage is made on the basis of the expected reduction in loss. For this purpose, we define a loss function that incorporates the patient accrual costs as well as costs associated with an incorrect decision at the end of the trial. An attractive feature of our loss function is that its estimation is computationally undemanding, also when >2. We evaluate the frequentist operating characteristics for settings with a binary outcome and multiple experimental arms. We consider both the situation with and without a control arm. In a simulation study, we show that our design increases the probability of making a correct decision at the end of the trial as compared to nonadaptive designs and adaptive two-stage designs.
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http://dx.doi.org/10.1177/0962280220973697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008394PMC
March 2021
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