Publications by authors named "Rutger J Hassink"

32 Publications

Sarcoma of the Heart Treated with Stereotactic MR-Guided Online Adaptive Radiation Therapy.

Case Rep Oncol 2021 Jan-Apr;14(1):453-458. Epub 2021 Mar 12.

Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

We present the first case in the literature of a patient with a histology-proven intimal sarcoma of the heart, recurrent after surgery, treated with stereotactic MR-guided online adaptive radiation therapy on an MR-Linac machine. The treatment was feasible and well tolerated. The CT scan 6 months after the last treatment showed stable disease.
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http://dx.doi.org/10.1159/000513623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983626PMC
March 2021

Familial Evaluation in Idiopathic Ventricular Fibrillation: Diagnostic Yield and Significance of J Wave Syndromes.

Circ Arrhythm Electrophysiol 2021 Mar 7;14(3):e009089. Epub 2021 Feb 7.

Cardiovascular Clinical Academic Group, Molecular & Clinical Sciences Rsrch Inst, St. George's, University of London and St. George's University Hospitals NHS Foundation Trust, London, United Kingdom (B.E., C.S., E.R.B.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCEP.120.009089DOI Listing
March 2021

Discovering and Visualizing Disease-Specific Electrocardiogram Features Using Deep Learning: Proof-of-Concept in Phospholamban Gene Mutation Carriers.

Circ Arrhythm Electrophysiol 2021 Feb 5;14(2):e009056. Epub 2021 Jan 5.

Department of Cardiology, University Medical Center Utrecht, the Netherlands (R.R.v.d.L., K.T., M.N.B., J.F.v.d.H., M.J.C., R.J.H., P.v.d.H., P.A.D., F.W.A., R.v.E.).

Background: ECG interpretation requires expertise and is mostly based on physician recognition of specific patterns, which may be challenging in rare cardiac diseases. Deep neural networks (DNNs) can discover complex features in ECGs and may facilitate the detection of novel features which possibly play a pathophysiological role in relatively unknown diseases. Using a cohort of PLN (phospholamban) p.Arg14del mutation carriers, we aimed to investigate whether a novel DNN-based approach can identify established ECG features, but moreover, we aimed to expand our knowledge on novel ECG features in these patients.

Methods: A DNN was developed on 12-lead median beat ECGs of 69 patients and 1380 matched controls and independently evaluated on 17 patients and 340 controls. Differentiating features were visualized using Guided Gradient Class Activation Mapping++. Novel ECG features were tested for their diagnostic value by adding them to a logistic regression model including established ECG features.

Results: The DNN showed excellent discriminatory performance with a c-statistic of 0.95 (95% CI, 0.91-0.99) and sensitivity and specificity of 0.82 and 0.93, respectively. Visualizations revealed established ECG features (low QRS voltages and T-wave inversions), specified these features (eg, R- and T-wave attenuation in V2/V3) and identified novel PLN-specific ECG features (eg, increased PR-duration). The logistic regression baseline model improved significantly when augmented with the identified features (<0.001).

Conclusions: A DNN-based feature detection approach was able to discover and visualize disease-specific ECG features in PLN mutation carriers and revealed yet unidentified features. This novel approach may help advance diagnostic capabilities in daily practice.
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http://dx.doi.org/10.1161/CIRCEP.120.009056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892204PMC
February 2021

Big Data and Artificial Intelligence: Opportunities and Threats in Electrophysiology.

Arrhythm Electrophysiol Rev 2020 Nov;9(3):146-154

Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

The combination of big data and artificial intelligence (AI) is having an increasing impact on the field of electrophysiology. Algorithms are created to improve the automated diagnosis of clinical ECGs or ambulatory rhythm devices. Furthermore, the use of AI during invasive electrophysiological studies or combining several diagnostic modalities into AI algorithms to aid diagnostics are being investigated. However, the clinical performance and applicability of created algorithms are yet unknown. In this narrative review, opportunities and threats of AI in the field of electrophysiology are described, mainly focusing on ECGs. Current opportunities are discussed with their potential clinical benefits as well as the challenges. Challenges in data acquisition, model performance, (external) validity, clinical implementation, algorithm interpretation as well as the ethical aspects of AI research are discussed. This article aims to guide clinicians in the evaluation of new AI applications for electrophysiology before their clinical implementation.
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http://dx.doi.org/10.15420/aer.2020.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675143PMC
November 2020

Complications in pulmonary vein isolation in the Netherlands Heart Registration differ with sex and ablation technique.

Europace 2021 Feb;23(2):216-225

Department of Cardiology and Cardiac Surgery, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands.

Aims : Pulmonary vein isolation (PVI) has become a cornerstone of the invasive treatment of atrial fibrillation. Severe complications are reported in 1-3% of patients. This study aims to compare complications and follow-up outcome of PVI in patients with atrial fibrillation.

Methods And Results : The data were extracted from the Netherlands Heart Registration. Procedural and follow-up outcomes in patients treated with conventional radiofrequency (C-RF), multielectrode phased RF (Ph-RF), or cryoballoon (CB) ablation from 2012 to 2017 were compared. Subgroup analysis was performed to identify variables associated with complications and repeat ablations. In total, 13 823 patients (69% male) were included. The reported complication incidence was 3.6%. Patients treated with C-RF developed more cardiac tamponades (C-RF 0.8% vs. Ph-RF 0.3% vs. CB 0.3%, P ≤ 0.001) and vascular complications (C-RF 1.7% vs. Ph-RF 1.2% vs. CB 1.3%, P ≤ 0.001). Ph-RF was associated with fewer bleeding complications (C-RF: 1.0% vs. Ph-RF: 0.4% vs. CB: 0.7%, P = 0.020). Phrenic nerve palsy mainly occurred in patients treated with CB (C-RF: 0.1% vs. Ph-RF: 0.2% vs. CB: 1.5%, P ≤ 0.001). In total, 18.4% of patients were referred for repeat ablation within 1 year. Female sex, age, and CHA2DS2-VASc were independent risk factors for cardiac tamponade and bleeding complications, with an adjusted OR for female patients of 2.97 (95% CI 1.98-4.45) and 2.02 (95% CI 1.03-4.00) respectively.

Conclusion : The reported complication rate during PVI was low. Patients treated with C-RF ablation were more likely to develop cardiac tamponades and vascular complications. Female sex was associated with more cardiac tamponade and bleeding complications.
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http://dx.doi.org/10.1093/europace/euaa255DOI Listing
February 2021

Follow-up after hemodynamically not tolerated ventricular tachycardia in patients with midrange reduced to normal ejection fraction: A retrospective single-centre case series.

Eur J Clin Invest 2021 Jan 7;51(1):e13359. Epub 2020 Aug 7.

Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands.

Introduction: The benefit of implantable cardioverter-defibrillator (ICD) implantation in patients with hemodynamically not tolerated ventricular tachycardia (VT) and midrange reduced to normal ejection fraction (LVEF >35%) is currently unclear. The purpose of this study was to investigate follow-up after hemodynamically not tolerated VT in patients with LVEF >35%. In addition, we aimed to find possible predictive factors to identify who will benefit from ICD implantation.

Methods: In a retrospective single-centre case series, all patients with hemodynamically not tolerated VT and LVEF >35% that underwent electrophysiological study (EPS) and/or radiofrequency VT ablation were included.

Results: Forty-two patients (5 women, median age 68 years) with hemodynamically not tolerated VT and LVEF >35% underwent EPS. VT ablation was performed in thirty-one patients, which was considered successful in twenty-three patients. Nineteen patients had an ICD at discharge while 23 patients were discharged without an ICD. The severity of hemodynamic compromise, LVEF and ablation success played an important role in the decision-making for ICD implantation. Six patients (14.3%) had recurrence of VT, all hemodynamically tolerated.

Conclusions: In this small case series, patients with hemodynamically not tolerated VT and LVEF >35% had a relatively low recurrence rate and all recurrences were nonfatal. Based on our results, we hypothesize that the severity of hemodynamic compromise, LVEF and ablation success might modify the risk for VA recurrence. A prospective study to determine the prognostic value of these factors in patients with hemodynamically not tolerated VT and LVEF >35% is necessary.
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http://dx.doi.org/10.1111/eci.13359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757240PMC
January 2021

[Sudden death in the young: the importance of autopsy and DNA testing].

Ned Tijdschr Geneeskd 2020 05 20;164. Epub 2020 May 20.

UMC Utrecht, afd. Cardiologie, Utrecht.

When a young person suddenly dies, there is a real chance that this was caused by genetic heart disease. Autopsy plays an important role in determining the cause of death, but the autopsy rate in the Netherlands is relatively low. Practical problems and a lack of information on autopsy play a role. It is important to inform the family on the importance of autopsy and DNA testing. If the family refuses autopsy, consent can be given for removal of material for DNA testing. If no autopsy and no DNA test were done, cardiological screening of family members remains highly recommended. New guidelines and procedures for diagnostics after sudden death are very important. For that reason, we developed a step-by-step plan to support healthcare providers. Early detection of genetic heart disease may prevent sudden death of family members, for example, by using preventive medication or internal defibrillators (ICD).
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May 2020

Automatic Triage of 12-Lead ECGs Using Deep Convolutional Neural Networks.

J Am Heart Assoc 2020 05 14;9(10):e015138. Epub 2020 May 14.

Department of Cardiology University Medical Center Utrecht Utrecht The Netherlands.

BACKGROUND The correct interpretation of the ECG is pivotal for the accurate diagnosis of many cardiac abnormalities, and conventional computerized interpretation has not been able to reach physician-level accuracy in detecting (acute) cardiac abnormalities. This study aims to develop and validate a deep neural network for comprehensive automated ECG triage in daily practice. METHODS AND RESULTS We developed a 37-layer convolutional residual deep neural network on a data set of free-text physician-annotated 12-lead ECGs. The deep neural network was trained on a data set with 336.835 recordings from 142.040 patients and validated on an independent validation data set (n=984), annotated by a panel of 5 cardiologists electrophysiologists. The 12-lead ECGs were acquired in all noncardiology departments of the University Medical Center Utrecht. The algorithm learned to classify these ECGs into the following 4 triage categories: normal, abnormal not acute, subacute, and acute. Discriminative performance is presented with overall and category-specific concordance statistics, polytomous discrimination indexes, sensitivities, specificities, and positive and negative predictive values. The patients in the validation data set had a mean age of 60.4 years and 54.3% were men. The deep neural network showed excellent overall discrimination with an overall concordance statistic of 0.93 (95% CI, 0.92-0.95) and a polytomous discriminatory index of 0.83 (95% CI, 0.79-0.87). CONCLUSIONS This study demonstrates that an end-to-end deep neural network can be accurately trained on unstructured free-text physician annotations and used to consistently triage 12-lead ECGs. When further fine-tuned with other clinical outcomes and externally validated in clinical practice, the demonstrated deep learning-based ECG interpretation can potentially improve time to treatment and decrease healthcare burden.
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http://dx.doi.org/10.1161/JAHA.119.015138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660886PMC
May 2020

Incidence and predictors of implantable cardioverter-defibrillator therapy and its complications in idiopathic ventricular fibrillation patients.

Europace 2019 Oct;21(10):1519-1526

Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Aims: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest. Implantable cardioverter-defibrillator (ICD) implantation is currently the only treatment option. Limited data are available on the prevalence and complications of ICD therapy in these patients. We sought to investigate ICD therapy and its complications in patients with IVF.

Methods And Results: Patients were selected from a national registry of IVF patients. Patients in whom no underlying diagnosis was found during follow-up were eligible for inclusion. Recurrence of ventricular arrhythmia (VA) was derived from medical and ICD records, electrogram records of ICD therapies were used to differentiate between appropriate or inappropriate interventions. Independent predictors for appropriate ICD shock were calculated using cox regression. In 217 IVF patients, recurrence of sustained VAs occurred in 66 patients (30%) during a median follow-up period of 6.1 years. Ten patients died (4.6%). Thirty-eight patients (17.5%) experienced inappropriate ICD therapy, and 32 patients (14.7%) had device-related complications. Symptoms before cardiac arrest [hazard ratio (HR): 2.51, 95% confidence interval (CI): 1.48-4.24], signs of conduction disease (HR: 2.27, 95% CI: 1.15-4.47), and carrier of the DPP6 risk haplotype (HR: 3.24, 1.70-6.17) were identified as independent predictors of appropriate shock occurrence.

Conclusion: Implantable cardioverter-defibrillator therapy is an effective treatment in IVF, treating recurrences of potentially lethal VAs in approximately one-third of patients during long-term follow-up. However, device-related complications and inappropriate shocks were also frequent. We found significant predictors for appropriate ICD therapy. This may imply that these patients require additional management to prevent recurrent events.
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http://dx.doi.org/10.1093/europace/euz151DOI Listing
October 2019

Incidence of Pulmonary Vein Stenosis After Radiofrequency Catheter Ablation of Atrial Fibrillation.

JACC Clin Electrophysiol 2017 06 26;3(6):589-598. Epub 2017 Apr 26.

Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.

Objectives: This study aimed to determine incidence of pulmonary vein stenosis (PVS) and evaluate PVS-related symptoms.

Background: The real-life incidence of PVS after radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) is unknown.

Methods: All patients who underwent RFCA of AF from 2005 to 2016 with routine pre- and post-ablation screening by magnetic resonance imaging or computed tomography were included. Primary ablation strategy was PV antrum isolation alone in all patients. PVS, defined as a significant reduction in the superoinferior or anteroposterior PV diameter, was classified as mild (30% to 50%), moderate (50% to 70%), or severe (>70%).

Results: Sufficient quality imaging of the PV anatomy before ablation and during follow-up (mean 6 ± 4 months) was performed in 976 patients (76.4% men, 59.1% paroxysmal AF). Of these patients, 306 (31.4%) showed mild stenosis, 42 (4.3%) revealed moderate stenosis, and 7 (0.7%) had a severe stenosis in at least 1 PV. Incidence of PVS fluctuated over the past decade. All severe PVS cases were likely caused by ablations being performed inside the PVs. Only 1 (0.1%) patient reported PVS-related symptoms of severe dyspnea during follow-up. Computed tomography revealed a subtotal occlusion of the left inferior PV and a severe stenosis of the left superior PV, requiring stenting.

Conclusions: Although mild PVS was frequently observed after RFCA in this large cohort, incidence of severe PVS was <1% and incidence of symptomatic PVS necessitating intervention was negligible. Based on these findings, it seems appropriate to only screen for PVS in patients with suggestive symptoms.
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http://dx.doi.org/10.1016/j.jacep.2017.02.003DOI Listing
June 2017

The Effects of β-Adrenergic Blockade on the Degrading Effects of Eye Movements on Negative Autobiographical Memories.

Biol Psychiatry 2017 Oct 28;82(8):587-593. Epub 2017 Mar 28.

Department of Clinical Psychology, Utrecht University, the Netherlands.

Background: Eye movement desensitization and reprocessing (EMDR) is an effective treatment for posttraumatic stress disorder. During EMDR, patients make horizontal eye movements (EMs) while simultaneously recalling a traumatic memory, which renders the memory less vivid and emotional when it is later recalled again. Recalling highly emotional autobiographical memories enhances noradrenergic neurotransmission. Noradrenaline (NA) strengthens memory (re)consolidation. However, memories become less vivid after recall+EMs. Therefore, NA might either play no significant role or serve to strengthen memories that are degraded by EMs. The present study was designed to test the latter hypothesis. We predicted that blocking NA would abolish the memory degrading effects of EMs.

Methods: Fifty-six healthy participants selected three negative autobiographical memories. One was then recalled while making EMs, one was recalled without EMs, and one was not recalled. Vividness and emotionality of the memories as well as heart rate and skin conductance level during memory retrieval were measured before, directly after, and 24 hours after the EM task. Before the task, participants received a placebo or the noradrenergic β-receptor blocker propranolol (40 mg).

Results: There were no effects of EMs on memory emotionality or psychophysiological measures in the propranolol and placebo groups. However, in the placebo group, but not in the propranolol group, memory vividness significantly decreased from pretest to posttest and follow-up after recall+EMs relative to the control conditions.

Conclusions: Blocking NA abolished the effects of EMs on the vividness of emotional memories, indicating that NA is crucial for EMDR effectiveness and possibly strengthens the reconsolidation of the degraded memory.
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http://dx.doi.org/10.1016/j.biopsych.2017.03.012DOI Listing
October 2017

Impaired Mental Health-Related Quality of Life in Patients with Idiopathic Ventricular Fibrillation.

Pacing Clin Electrophysiol 2017 May 23;40(5):578-584. Epub 2017 Mar 23.

Department of Cardiology, University Medical Centre, Utrecht, The Netherlands.

Background: Idiopathic ventricular fibrillation (iVF) is diagnosed in cardiac arrest survivors without an identifiable cause. Data regarding the health-related quality of life (HRQoL) in iVF patients are lacking. The purpose of this study was to investigate the HRQoL of iVF patients and to compare it to patients with an implantable cardioverter defibrillator (ICD) diagnosed with an underlying disease and healthy subjects.

Methods: In 61 iVF patients with an ICD (iVF-ICD) and 59 ICD patients with a diagnosis (diagnosis-ICD), HRQoL was assessed using the 12-item Short-Form Health Survey (SF-12), the EuroQoL-5 dimensions (EQ-5D), the 9-item Patient Health Questionnaire, and the ICD Patient Concerns (ICDC) Questionnaire. In addition, 860 healthy subjects completed the SF-12.

Results: IVF-ICD showed similar SF-12 physical summary scores compared with diagnosis-ICD patients (50.8 [interquartile range (IQR) = 42.1-53.9] vs 54.1 [IQR = 46.5-58.3]; P = 0.080) and healthy subjects (51.8 [IQR = 45.9-54.1]; P = 0.691). The mental summary score was impaired in iVF-ICD patients compared with diagnosis-ICD patients (45.9 [IQR = 40.7-49.4] vs 54.6 [IQR = 46.0-57.9]; P < 0.001) and healthy subjects (47.7 [IQR = 43.0-50.4]; P = 0.027). Scores on all five EQ-5D domains were similar between iVF-ICD patients and diagnosis-ICD patients, as well as symptoms of severe depression (19% vs 12%; P = 0.101). ICD concerns were similar between iVF-ICD and diagnosis-ICD patients (ICDC-scores 2 vs 2; P = 0.494).

Conclusions: Data suggest that there is a reduced mental HRQoL in patients with iVF compared to other cardiac arrest survivors. Screening and treatment of psychological distress should therefore be considered in iVF patients.
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http://dx.doi.org/10.1111/pace.13034DOI Listing
May 2017

Next-generation sequencing of a large gene panel in patients initially diagnosed with idiopathic ventricular fibrillation.

Heart Rhythm 2017 07 11;14(7):1035-1040. Epub 2017 Jan 11.

Department of Cardiology, University Medical Centre, Utrecht, The Netherlands; Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, The Netherlands.

Background: Idiopathic ventricular fibrillation (IVF) is a rare primary cardiac arrhythmia syndrome that is diagnosed in a resuscitated cardiac arrest victim, with documented ventricular fibrillation, in whom no underlying cause is identified after comprehensive clinical evaluation. In some patients, causative genetic mutations are detected that facilitate patient treatment and follow-up. The feasibility of next-generation sequencing (NGS) has increased with its greater availability and decreasing costs.

Objective: The aim of this study was to assess the diagnostic yield of NGS in patients with IVF.

Methods: A total of 33 patients initially diagnosed with IVF were included (mean age 53 ± 15 years; 14(42%) men). In all included patients, NGS of 33 genes and the DPP6 haplotype revealed no pathogenic mutations. Genetic screening comprised NGS of a panel of 179 additional genes. Variants with a minor allele frequency of <0.05% were assessed for pathogenicity by using existing mutation databases and in silico predictive algorithms.

Results: In 1 of 33 patients, a likely pathogenic mutation was detected. The added yield of genetic testing with NGS of 179 additional genes is 3% in patients with IVF. In 15% of patients, 1 or multiple variants of uncertain clinical significance were detected.

Conclusion: The added yield of genetic screening of extended NGS panels in patients initially diagnosed with IVF is minimal. Routine analysis of large diagnostic NGS panels is therefore not recommended.
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http://dx.doi.org/10.1016/j.hrthm.2017.01.010DOI Listing
July 2017

Long-Term Outcome of Patients Initially Diagnosed With Idiopathic Ventricular Fibrillation: A Descriptive Study.

Circ Arrhythm Electrophysiol 2016 10;9(10)

From the Departments of Cardiology (M.V., J.F.v.d.H., P.A.D., P.L., R.J.H.) and Clinical Genetics (J.J.v.d.S.), University Medical Centre, Utrecht, The Netherlands; Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, The Netherlands (M.V., R.J.H.); and Department of Clinical and Experimental Cardiology, Heart Centre, AMC, Amsterdam, The Netherlands (A.A.W.).

Background: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest. Limited data are available on the long-term outcome of IVF patients.

Methods And Results: In this retrospective cohort study, 107 consecutive patients with an initial diagnosis of IVF were analyzed (age at index event 40.4 years, 60% male). Missing diagnostic data were acquired during follow-up, including genetic testing, to exclude underlying disease. A specific diagnosis was revealed in 22 of 107 patients (21%) during a median follow-up of 10.2 years. Mortality rate was 9% in IVF patients (8/85). Appropriate implantable cardioverter-defibrillator therapy was delivered in 23 patients (29%) of 78 IVF patients with an implantable cardioverter-defibrillator, with a median of 3 appropriate shocks per patient.

Conclusions: One fifth of the patients initially diagnosed with IVF reveal a specific diagnosis during long-term follow-up. Additional diagnostic testing, including genetic testing, contributes to the detection of specific diseases. The recurrence rate of ventricular arrhythmias in IVF patients is high. Our data show the importance of thorough follow-up and reassessment of diagnosis in IVF patients.
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http://dx.doi.org/10.1161/CIRCEP.116.004258DOI Listing
October 2016

Time matters: adenosine testing immediately after pulmonary vein isolation does not substitute a waiting period.

Europace 2017 Jul;19(7):1140-1145

Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.

Aims: Adenosine testing can reveal dormant pulmonary vein (PV) conduction after PV antrum isolation (PVAI). However, the optimal timing for adenosine administration is unknown. We hypothesized that adenosine testing immediately after PVAI reliably reveals PV reconnection and thereby eliminates the need for an observation period.

Methods And Results: Fifty patients underwent PVAI. Immediately after isolation of a PV pair, adenosine was administered. Both PV pairs were separately tested. If adenosine restored PV conduction, PVs were re-isolated. During a ≥30 min observation period after immediate adenosine-guided isolation, spontaneous reconnection was assessed and reconnected PVs were re-isolated. After the observation period, adenosine testing was repeated. Immediate adenosine testing revealed dormant conduction in 10.4% of the left PVs and 16.3% of the right PVs. All PVs were successfully re-isolated. During a mean observation period of 36 ± 10 min, spontaneous reconnection occurred in 8.2% of the left and 16.3% of the right PVs. None of these PVs had shown reconnection during immediate testing. Late adenosine testing revealed dormant conduction in 12.5% of the left and 16.3% of the right PVs. In patients without reconnection during immediate adenosine testing, 14.6% of the left PVs and 30.6% of the right PVs showed either spontaneous reconnection or restored PV conduction during late adenosine testing.

Conclusion: Adenosine testing immediately after PVAI does not reliably exclude later spontaneous or adenosine-induced PV reconnection. Adenosine testing should be performed after an appropriate observation period to reduce risk of PV reconnection.
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http://dx.doi.org/10.1093/europace/euw173DOI Listing
July 2017

A patient with early repolarization syndrome and concurrent Brugada syndrome: Demonstration of a different pathophysiology?

Int J Cardiol 2016 Nov 5;223:58-60. Epub 2016 Aug 5.

Department of Cardiology, University Medical Centre, Utrecht, the Netherlands; Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, the Netherlands.

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http://dx.doi.org/10.1016/j.ijcard.2016.08.072DOI Listing
November 2016

Idiopathic Ventricular Fibrillation: The Struggle for Definition, Diagnosis, and Follow-Up.

Circ Arrhythm Electrophysiol 2016 May;9(5)

From the Department of Cardiology, University Medical Center, Utrecht, The Netherlands (M.V., J.F.v.d.H., P.A.D., P.L., R.J.H.); Department of Internal Medicine and Cardiology, Bergman Clinics, Bilthoven, The Netherlands (M.V., R.J.H.); and Department of Clinical and Experimental Cardiology, Heart Centre, AMC, Amsterdam, The Netherlands (A.A.W.).

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http://dx.doi.org/10.1161/CIRCEP.115.003817DOI Listing
May 2016

Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation: a single-centre cohort study.

Europace 2016 Sep 2;18(9):1335-42. Epub 2016 Feb 2.

Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, The Netherlands

Aims: Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence.

Methods And Results: A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 ± 23 and 55 ± 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% (n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% (n = 297). Additional substrate modification (n = 70) increased success to 62.5% (n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration.

Conclusion: Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success.
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http://dx.doi.org/10.1093/europace/euv439DOI Listing
September 2016

Fever-induced atrial flutter associated with SCN5A mutation--a first report on successful catheter ablation in a very young child.

Int J Cardiol 2014 Feb 7;171(2):e31-4. Epub 2013 Dec 7.

University Medical Center Utrecht, Department of Cardiology, Utrecht, The Netherlands.

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http://dx.doi.org/10.1016/j.ijcard.2013.11.121DOI Listing
February 2014

A rare and difficult diagnosis: a ruptured sinus of valsalva aneurysm.

J Am Coll Cardiol 2010 Mar;55(9):921

Department of Cardiology, University Medical Center, Utrecht, the Netherlands.

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http://dx.doi.org/10.1016/j.jacc.2009.04.107DOI Listing
March 2010

Cell-cycle-based strategies to drive myocardial repair.

Pediatr Cardiol 2009 Jul 2;30(5):710-5. Epub 2009 Apr 2.

The Riley Heart Research Center, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 West Walnut Street, R4 Building Room W376, Indianapolis, IN 46202-5225, USA.

Cardiomyocytes exhibit robust proliferative activity during development. After birth, cardiomyocyte proliferation is markedly reduced. Consequently, regenerative growth in the postnatal heart via cardiomyocyte proliferation (and, by inference, proliferation of stem-cell-derived cardiomyocytes) is limited and often insufficient to affect repair following injury. Here, we review studies wherein cardiomyocyte cell cycle proliferation was induced via targeted expression of cyclin D2 in postnatal hearts. Cyclin D2 expression resulted in a greater than 500-fold increase in cell cycle activity in transgenic mice as compared to their nontransgenic siblings. Induced cell cycle activity resulted in infarct regression and concomitant improvement in cardiac hemodynamics following coronary artery occlusion. These studies support the notion that cell-cycle-based strategies can be exploited to drive myocardial repair following injury.
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http://dx.doi.org/10.1007/s00246-009-9408-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2691809PMC
July 2009

Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction.

Cardiovasc Res 2008 Apr 12;78(1):18-25. Epub 2007 Dec 12.

Department of Cardiology, University Medical Center, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Aims: Cardiomyocyte loss is a major contributor to the decreased cardiac function observed in diseased hearts. Previous studies have shown that cardiomyocyte-restricted cyclin D2 expression resulted in sustained cell cycle activity following myocardial injury in transgenic (MHC-cycD2) mice. Here, we investigated the effects of this cell cycle activation on cardiac function following myocardial infarction (MI).

Methods And Results: MI was induced in transgenic and non-transgenic mice by left coronary artery occlusion. At 7, 60, and 180 days after MI, left ventricular pressure-volume measurements were recorded and histological analysis was performed. MI had a similar adverse effect on cardiac function in transgenic and non-transgenic mice at 7 days post-injury. No improvement in cardiac function was observed in non-transgenic mice at 60 and 180 days post-MI. In contrast, the transgenic animals exhibited a progressive and marked increase in cardiac function at subsequent time points. Improved cardiac function in the transgenic mice at 60 and 180 days post-MI correlated positively with the presence of newly formed myocardial tissue which was not apparent at 7 days post-MI. Intracellular calcium transient imaging indicated that cardiomyocytes present in the newly formed myocardium participated in a functional syncytium with the remote myocardium.

Conclusion: These findings indicate that cardiomyocyte cell cycle activation leads to improvement of cardiac function and morphology following MI and may represent an important clinical strategy to promote myocardial regeneration.
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http://dx.doi.org/10.1093/cvr/cvm101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653079PMC
April 2008

Patterning the heart, a template for human cardiomyocyte development.

Dev Dyn 2006 Jul;235(7):1994-2002

Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht, The Netherlands.

Although in mice, the dynamics of gene expression during heart development is well characterized, information on humans is scarce due to the limited availability of material. Here, we analyzed the transcriptional distribution of Mlc-2a, Mlc-1v, Mlc-2v, and atrial natriuretic factor (ANF) in human embryonic hearts between 7 and 18 weeks of gestation and in healthy and hypertrophic adult hearts by in situ hybridization and compared expression with that in mice. Strikingly, Mlc-2a, Mlc-1v, and ANF, which are essentially chamber-restricted in mice by mid-gestation, showed a broader distribution in humans. On the other hand, Mlc-2v may prove to be an adequate ventricular marker in humans in contrast to mouse. This study emphasizes the importance of careful comparative human-animal analyses during embryonic development and adulthood, as avoiding erroneous extrapolations may be critical to develop new and successful myocardial replacement therapies.
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http://dx.doi.org/10.1002/dvdy.20830DOI Listing
July 2006

Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures.

Stem Cells 2005 Jun-Jul;23(6):772-80

Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.

Human embryonic stem cells (hESCs) can differentiate into cardiomyocytes, but the efficiency of this process is low. We routinely induce cardiomyocyte differentiation of the HES-2 cell line by coculture with a visceral endoderm-like cell line, END-2, in the presence of 20% fetal calf serum (FCS). In this study, we demonstrate a striking inverse relationship between cardiomyocyte differentiation and the concentration of FCS during HES-2-END-2 coculture. The number of beating areas in the cocultures was increased 24-fold in the absence of FCS compared with the presence of 20% FCS. An additional 40% increase in the number of beating areas was observed when ascorbic acid was added to serum-free cocultures. The increase in serum-free cocultures was accompanied by increased mRNA and protein expression of cardiac markers and of Isl1, a marker of cardiac progenitor cells. The number of beating areas increased up to 12 days after initiation of coculture of HES-2 with END-2 cells. However, the number of alpha-actinin-positive cardiomyocytes per beating area did not differ significantly between serum-free cocultures (503 +/- 179; mean +/- standard error of the mean) and 20% FCS cocultures (312 +/- 227). The stimulating effect of serum-free coculture on cardiomyocyte differentiation was observed not only in HES-2 but also in the HES-3 and HES-4 cell lines. To produce sufficient cardiomyocytes for cell replacement therapy in the future, upscaling cardiomyocyte formation from hESCs is essential. The present data provide a step in this direction and represent an improved in vitro model, without interfering factors in serum, for testing other factors that might promote cardiomyocyte differentiation.
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http://dx.doi.org/10.1634/stemcells.2004-0184DOI Listing
September 2005

The role of stem cells in cardiac regeneration.

J Cell Mol Med 2005 Jan-Mar;9(1):25-36

Laboratory of Experimental Cardiology, Department of Cardiology, Heart Lung Center, Utrecht, The Netherlands.

After myocardial infarction, injured cardiomyocytes are replaced by fibrotic tissue promoting the development of heart failure. Cell transplantation has emerged as a potential therapy and stem cells may be an important and powerful cellular source. Embryonic stem cells can differentiate into true cardiomyocytes, making them in principle an unlimited source of transplantable cells for cardiac repair, although immunological and ethical constraints exist. Somatic stem cells are an attractive option to explore for transplantation as they are autologous, but their differentiation potential is more restricted than embryonic stem cells. Currently, the major sources of somatic cells used for basic research and in clinical trials originate from the bone marrow. The differentiation capacity of different populations of bone marrow-derived stem cells into cardiomyocytes has been studied intensively. The results are rather confusing and difficult to compare, since different isolation and identification methods have been used to determine the cell population studied. To date, only mesenchymal stem cells seem to form cardiomyocytes, and only a small percentage of this population will do so in vitro or in vivo. A newly identified cell population isolated from cardiac tissue, called cardiac progenitor cells, holds great potential for cardiac regeneration. Here we discuss the potential of the different cell populations and their usefulness in stem cell based therapy to repair the damaged heart.
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http://dx.doi.org/10.1111/j.1582-4934.2005.tb00334.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6741329PMC
April 2005

Images in clinical medicine. Backscatter from lead.

N Engl J Med 2004 Nov;351(19):e17

University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.

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http://dx.doi.org/10.1056/ENEJMicm030057DOI Listing
November 2004

Human stem cells shape the future of cardiac regeneration research.

Int J Cardiol 2004 Jun;95 Suppl 1:S20-2

Department of Cardio-Thoracic Surgery, Heart Lung Center, Utrecht, The Netherlands.

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http://dx.doi.org/10.1016/s0167-5273(04)90006-xDOI Listing
June 2004

Stem cell therapy for ischemic heart disease.

Trends Mol Med 2003 Oct;9(10):436-41

University Medical Center, Heart Lung Center, Dept of Cardio-Thoracic Surgery, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Recent experimental and clinical observations have suggested that cell transplantation could be of therapeutic value for the treatment of heart disease. This approach was based on the idea that transplanted donor cardiomyocytes would integrate with the host myocardium and thereby directly contribute to cardiac function. Surprisingly, the observation that non-cardiomyogenic cells could also improve cardiac function indicates that functional integration of donor cells might not be required to achieve a beneficial effect. More recently, several observations have suggested the presence of a greater than anticipated developmental repertoire in adult-derived stem cells, which, if further validated, would offer unprecedented opportunities for the restoration of cardiac function in diseased hearts. Here, we discuss current issues regarding the potential use of stem cell transplantation for the treatment of ischemic heart disease.
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http://dx.doi.org/10.1016/j.molmed.2003.08.002DOI Listing
October 2003