Publications by authors named "Pieter A F M Doevendans"

50 Publications

Clinical Course Long After Atrial Switch: A Novel Risk Score for Major Clinical Events.

J Am Heart Assoc 2021 Feb 22;10(5):e018565. Epub 2021 Feb 22.

Department of Clinical and Experimental Cardiology Heart Center Amsterdam Cardiovascular SciencesAmsterdam University Medical CenterUniversity of Amsterdam the Netherlands.

Background Patients with transposition of the great arteries corrected by an atrial switch operation experience major clinical events during adulthood, mainly heart failure (HF) and arrhythmias, but data on the emerging risks remain scarce. We assessed the risk for events during the clinical course in adulthood, and provided a novel risk score for event-free survival. Methods and Results This multicenter study observed 167 patients with transposition of the great arteries corrected by an atrial switch operation (61% Mustard procedure; age, 28 [interquartile range, 24-36] years) for 13 (interquartile range, 9-16) years, during which 16 (10%) patients died, 33 (20%) had HF events, defined as HF hospitalizations, heart transplantation, ventricular assist device implantation, or HF-related death, and 15 (9%) had symptomatic ventricular arrhythmias. Five-year risk of mortality, first HF event, and first ventricular arrhythmia increased from 1% each at age 25 years, to 6% (95% CI, 4%-9%), 23% (95% CI, 17%-28%), and 5% (95% CI, 2%-8%), respectively, at age 50 years. Predictors for event-free survival were examined to construct a prediction model using bootstrapping techniques. A prediction model combining age >30 years, prior ventricular arrhythmia, age >1 year at repair, moderate or greater right ventricular dysfunction, severe tricuspid regurgitation, and mild or greater left ventricular dysfunction discriminated well between patients at low (<5%), intermediate (5%-20%), and high (>20%) 5-year risk (optimism-corrected C-statistic, 0.86 [95% CI, 0.82-0.90]). Observed 5- and 10-year event-free survival rates in low-risk patients were 100% and 97%, respectively, compared with only 31% and 8%, respectively, in high-risk patients. Conclusions The clinical course of patients undergoing atrial switch increasingly consists of major clinical events, especially HF. A novel risk score stratifying patients as low, intermediate, and high risk for event-free survival provides information on absolute individual risks, which may support decisions for pharmacological and interventional management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.018565DOI Listing
February 2021

Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocytes.

STAR Protoc 2021 Mar 9;2(1):100334. Epub 2021 Feb 9.

Utrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, Department of Cardiology, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands.

Since the discovery of human induced pluripotent stem cells (hiPSCs), numerous strategies have been established to efficiently derive cardiomyocytes from hiPSCs (hiPSC-CMs). Here, we describe a cost-effective strategy for the subsequent massive expansion (>250-fold) of high-purity hiPSC-CMs relying on two aspects: removal of cell-cell contacts and small-molecule inhibition with CHIR99021. The protocol maintains CM functionality, allows cryopreservation, and the cells can be used in downstream assays such as disease modeling, drug and toxicity screening, and cell therapy. For complete details on the use and execution of this protocol, please refer to Buikema (2020).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xpro.2021.100334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881265PMC
March 2021

Efficacy of multi-electrode linear irreversible electroporation.

Europace 2021 Mar;23(3):464-468

Department of Cardiology, Isala Hospital, Heart Centre, Dr Van Heesweg 2, 8025 AB Zwolle, The Netherlands.

Aims: We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model.

Methods And Results: The study was performed in six pigs (weight 60-75 kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1-3.6] and 5.5 mm (IQR 4.6-6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7-4.8) and 5.4 mm (IQR 5.0-6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications.

Conclusion: Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euaa280DOI Listing
March 2021

Impact of baseline cigarette smoking status on clinical outcome after transcatheter aortic valve replacement.

Catheter Cardiovasc Interv 2019 Nov 22;94(6):795-805. Epub 2019 Mar 22.

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

Objectives: To explore the prevalence of smoking, and its association with clinical and mortality outcome among patients undergoing transcatheter aortic valve replacement (TAVR).

Background: Less data exist regarding the effect of baseline smoking status on clinical and mortality outcome among patients undergoing TAVR.

Methods: Consecutive patients who underwent TAVR at two high volume Dutch centers were included. Smoking status was prospectively questioned by a structured interview at admission. Primary endpoint was 1-year all-cause mortality after TAVR.

Results: A total of 913 consecutive patients (80.1 ± 7.6 years; logistic EuroSCORE: 16.5 ± 9.9%) who underwent TAVR for severe aortic valve stenosis were included. There were 47% (n = 432) males, and 57% (n = 522) never-smokers, and 35% (n = 317) prior-smokers, and 8% (n = 74) current-smokers. Smokers (i.e., prior-smokers or current-smokers) were younger compared to never-smokers (78.9 ± 7.9 and 76.4 ± 8.0 vs. 81.3 ± 7.1, P < 0.000, respectively). Median follow-up time was 365 (interquartile range [IQR]: 280-365) days. Overall, prior-smoking was not associated with all-cause mortality at 1-year following TAVR (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.55-1.23). After stratification according to sex, male prior-smokers showed better 1-year survival after TAVR than male never-smokers (12% vs. 20%; P = 0.018, respectively, HR 0.52, 95% CI 0.29-0.89), while this reversed effect was not observed among female prior-smokers versus female never-smokers after TAVR (HR 1.70, 95% CI 0.95-3.05).

Conclusions: Overall, baseline prior-smokers had similar 1-year mortality outcome after TAVR compared with baseline never-smokers. However, there was a reversed association between baseline prior-smoking status and 1-year mortality after TAVR among males, which could partially be explained due to the favorable baseline characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.28175DOI Listing
November 2019

Ex Vivo Pilot Study of Cardiac Magnetic Resonance Velocity Mapping for Quantification of Aortic Regurgitation in a Porcine Model in the Presence of a Transcatheter Heart Valve.

J Cardiovasc Transl Res 2019 08 15;12(4):310-320. Epub 2019 Mar 15.

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

Accuracy of aortic regurgitation (AR) quantification by magnetic resonance (MR) imaging in the presence of a transcatheter heart valve (THV) remains to be established. We evaluated the accuracy of cardiac MR velocity mapping for quantification of antegrade flow (AF) and retrograde flow (RF) across a THV and the optimal slice position to use in cardiac MR imaging. In a systematic and fully controlled laboratory ex vivo setting, two THVs (Edwards SAPIEN XT, Medtronic CoreValve) were tested in a porcine model (n = 1) under steady flow conditions. Results showed a high level of accuracy and precision. For both THVs, AF was best measured at left ventricular outflow tract level, and RF at ascending aorta level. At these levels, MR had an excellent repeatability (ICC > 0.99), with a tendency to overestimate (4.6 ± 2.4% to 9.4 ± 7.0%). Quantification of AR by MR velocity mapping in the presence of a THV was accurate, precise, and repeatable in this pilot study, when corrected for the systematic error and when the best MR slice position was used. Confirmation of these results in future clinical studies would be a step forward in increasing the accuracy of the assessment of paravalvular AR severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12265-019-09878-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708050PMC
August 2019

Postoperative Delirium in Individuals Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

J Am Geriatr Soc 2018 12 8;66(12):2417-2424. Epub 2018 Oct 8.

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

Objectives: To evaluate the incidence of in-hospital postoperative delirium (IHPOD) after transcatheter aortic valve replacement (TAVR).

Design: Systematic review and meta-analysis.

Setting: Elective procedures PARTICIPANTS: Individuals undergoing TAVR.

Measurements: A literature search was conducted in PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials (up to December 2017). All observational studies reporting the incidence of IHPOD after TAVR (sample size > 25) were included in our meta-analysis. The reported incidence rates were weighted to obtain a pooled estimate rate with 95% confidence interval (CI).

Results: Of 96 potentially relevant articles, 31 with a total of 32,389 individuals who underwent TAVR were included in the meta-analysis. The crude incidence of IHPOD after TAVR ranged from 0% to 44.6% in included studies, with a pooled estimate rate of 8.1% (95% CI=6.7-9.4%); heterogeneity was high (Q = 449; I = 93%; p  < .001). The pooled estimate rate of IHPOD was 7.2% (95% CI=5.4-9.1%) after transfemoral (TF) TAVR and 21.4% (95% CI=10.3-32.5%) after non-TF TAVR.

Conclusion: Delirium occurs frequently after TAVR and is more common after non-TF than TF procedures. Recommendations are made with the aim of standardizing future research to reduce heterogeneity between studies on this important healthcare problem. J Am Geriatr Soc 66:2417-2424, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.15600DOI Listing
December 2018

Anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS), fractional flow reserve- and intravascular ultrasound-guided management in adult patients.

Catheter Cardiovasc Interv 2018 07 9;92(1):68-75. Epub 2018 Mar 9.

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

Objectives: To describe the use of fractional flow reserve (FFR) and intravascular ultrasound (IVUS) in the evaluation of patients with anomalous coronary arteries originating from the opposite sinus of Valsalva (ACAOS).

Background: ACAOS of the right and left coronary are rare, but may lead to symptoms and impose a risk for sudden cardiac death, depending on several anatomical features. Assessment and risk estimation is challenging in (nonathlete) adults, especially if they present without symptoms or with atypical complaints.

Methods: The team retrospectively studied 30 consecutive patients with ACAOS with interarterial course, who received IVUS- and FFR-guided treatment at our institution between October 2010 and September 2017.

Results: FFR was abnormal in only seven patients. IVUS showed the typical slit-like anatomy of the orifice in 23 patients. Based on FFR and/or IVUS results, in conjunction with the clinical presentation, clinical decision was made. A decision for intervention was made if at least two out of three entities were abnormal. Intervention implied unroofing of the coronary artery (n = 10) or coronary artery bypass grafting (n = 1). In all other patients a conservative strategy was followed. No adverse events occurred in the total population after a median of 37 (0-62) months of follow-up.

Conclusions: Conservative treatment may be justifiable in adult patients with ACAOS in the presence of normal FFR and nonsuspicious symptoms, despite the presence of an interarterial course and/or slitlike orifice on IVUS. We recommend the use of FFR and IVUS in the standard work-up for adult patients with ACAOS and propose the use of a flowchart to aid in decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ccd.27578DOI Listing
July 2018

Evaluation of Cognitive Function Following Transcatheter Aortic Valve Replacement.

Heart Lung Circ 2018 Dec 20;27(12):1454-1461. Epub 2017 Oct 20.

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

Background: Transcatheter aortic valve replacement (TAVR) is associated with procedural-related neurological events and acute cognitive decline. However, data on the effect of TAVR on mid-term cognitive outcome are scarce. Therefore, we aimed to assess the impact of TAVR on mid-term cognitive outcome using different neurocognitive test batteries.

Methods: Patients with severe aortic valve stenosis scheduled for TAVR were enrolled. Cognitive assessment was performed at baseline and 4 months post-TAVR using an eight-word verbal-learning test ("Immediate Recall Memory Test" [IRMT], "Delayed Recall Memory Test" [DRMT], "Recognition of Verbal Information Test" [RVIT]), global cognitive function ("Mini Mental State Examination" [MMSE]), and executive function ("Trail Making Test" [TMT], "Clock-Drawing Test" [CDT]).

Results: A total of 30 patients (age: 81±6years, logistic EuroSCORE: 19±10%) completed the follow-up cognitive assessments. Postoperatively, 17% (n=5) developed delirium, 13% (n=4) received permanent pacemaker, and there were no cerebrovascular events. Mean hospital duration time was 5±2 days. Patients (n=22) who did not complete the follow-up cognitive assessments had comparable baseline, procedural and hospital outcome. At follow-up there was a significant improvement in IRMT (27±5 vs. 30±4, p=0.016), with a trend toward improved DRMT (4±2 vs. 5±2, p=0.079). Moreover, patients with lower baseline MMSE and IRMT improved significantly during the follow-up.

Conclusions: Transcatheter aortic valve replacement was associated with an improved IRMT during follow-up. Both MMSE and IRMT were significantly improved among those with lower baseline scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hlc.2017.10.006DOI Listing
December 2018

Sudden Death Due to Coronary Artery Lesions Long-term After the Arterial Switch Operation: A Systematic Review.

Can J Cardiol 2017 09 8;33(9):1180-1187. Epub 2017 Apr 8.

Pediatric Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Background: The arterial switch operation (ASO) is the preferred procedure for children with dextrotransposition of the great arteries or Taussig-Bing anomaly. Short- as well as long-term outcome of ASO are excellent, but coronary artery stenoses are reported as a common long-term complication. It has been hypothesized that these might result in sudden cardiac death late after ASO.

Methods: A systematic search of PubMed and EMBASE was conducted to evaluate sudden cardiac death because of coronary complications late after ASO. Data on patients surviving ≥ 5 years post-ASO were collected from selected studies, corrected for duplicate data, and analyzed.

Results: After duplicate data correction 52 studies remained for data analysis. Among the 8798 survivors with follow-up, 27 patients died ≥ 5 years post-ASO (0.3%). Of these patients, 10 were known with relevant residual lesions. Five late deaths were sudden, possibly from a cardiac cause. None of the late sudden deaths were confirmed to be coronary-related.

Conclusions: Sudden cardiac death in asymptomatic patients as a result of coronary artery stenosis or occlusion is extremely rare, with 5 possible cases and no proven cases of coronary artery-related sudden cardiac death in 8798 patients with 66,450 patient follow-up years. Therefore, routine coronary imaging of asymptomatic, single-stage ASO patients is not justified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjca.2017.02.017DOI Listing
September 2017

The concept of triple wavefront fusion during biventricular pacing: Using the EGM to produce the best acute hemodynamic improvement in CRT.

Pacing Clin Electrophysiol 2017 Jul 16;40(7):873-882. Epub 2017 Jun 16.

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

Background: Previous reports suggest that biventricular pacing (BiVp) fused with intrinsic conduction (BiVp-fusion, triple wavefront fusion) is associated with improved resynchronization compared to pure-BiVp in cardiac resynchronization therapy (CRT). This study aimed to assess the association between acute hemodynamic benefit of CRT and signs of BiVp-fusion by using a novel electrogram (EGM)-based method.

Methods: In 17 patients undergoing CRT implantation, 28 combinations of atrioventricular (AV) and interventricular (VV) delays were applied while invasively measuring acute hemodynamic response based on maximum rate of left ventricular (LV) pressure rise (LV dP/dt ) to assess optimal BiVp settings. BiVp-fusion was noted if farfield signal (caused by first intrinsic ventricular depolarization) was seen prior to right ventricular (RV) pacing (RVp) artifact on integrated bipolar RV EGM, or QRS morphology changed compared to pure-BiVp (short AV-delay) as seen on electrocardiogram (ECG).

Results: Mean optimal RVp timing was at 98 ± 17% of intrinsic right atrial (RA)-RV (interval from right atrial pace or sense to RV farfield signal) interval, while preactivating the LV at 50 ± 11% of RA-RV (interval from right atrial pace or sense to RV sense interval) interval. BiVp-fusion was noted in 16 of 17 (94%) patients on ECG during optimal BiVp. Eight of these patients showed intrinsic farfield signal prior to RVp artifact on RV EGM. In the remaining eight, the RVp was paced just within the RA-RV interval with a mean of 25 ± 14 ms prior to the onset; therefore, the intrinsic farfield was masked.

Conclusion: Optimal hemodynamic BiVp facilitates triple wavefront fusion, by pacing the RV around the onset of intrinsic farfield signal on RV EGM, while preactivating the LV. Aiming at BiVp-fusion could be a target for noninvasive EGM-based CRT device setting optimization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pace.13118DOI Listing
July 2017

Additional Candidate Genes for Human Atherosclerotic Disease Identified Through Annotation Based on Chromatin Organization.

Circ Cardiovasc Genet 2017 Apr;10(2)

Background: As genome-wide association efforts, such as CARDIoGRAM and METASTROKE, are ongoing to reveal susceptibility loci for their underlying disease-atherosclerotic disease-identification of candidate genes explaining the associations of these loci has proven the main challenge. Many disease susceptibility loci colocalize with DNA regulatory elements, which influence gene expression through chromatin interactions. Therefore, the target genes of these regulatory elements can be considered candidate genes. Applying these biological principles, we used an alternative approach to annotate susceptibility loci and identify candidate genes for human atherosclerotic disease based on circular chromosome conformation capture followed by sequencing.

Methods And Results: In human monocytes and coronary endothelial cells, we generated 63 chromatin interaction data sets for 37 active DNA regulatory elements that colocalize with known susceptibility loci for coronary artery disease (CARDIoGRAMplusC4D) and large artery stroke (METASTROKE). By circular chromosome conformation capture followed by sequencing, we identified a physical 3-dimensional interaction with 326 candidate genes expressed in at least 1 of these cell types, of which 294 have not been reported before. We highlight 16 genes based on expression quantitative trait loci.

Conclusions: Our findings provide additional candidate-gene annotation for 37 disease susceptibility loci for human atherosclerotic disease that are of potential interest to better understand the complex pathophysiology of cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCGENETICS.116.001664DOI Listing
April 2017

Identifying Coronary Artery Disease in Asymptomatic Middle-Aged Sportsmen: The Additional Value of Pulse Wave Velocity.

PLoS One 2015 6;10(7):e0131895. Epub 2015 Jul 6.

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

Background: Cardiovascular screening may benefit middle-aged sportsmen, as coronary artery disease (CAD) is the main cause of exercise-related sudden cardiac death. Arterial stiffness, as measured by pulse wave velocity (PWV), may help identify sportsmen with subclinical CAD. We examined the additional value of PWV measurements to traditional CAD risk factors for identifying CAD.

Methods: From the Measuring Athlete's Risk of Cardiovascular events (MARC) cohort of asymptomatic, middle-aged sportsmen who underwent low-dose Cardiac CT (CCT) after routine sports medical examination (SME), 193 consecutive sportsmen (aged 55 ± 6.6 years) were included with additional PWV measurements before CCT. Sensitivity, specificity and predictive values of PWV values (>8.3 and >7.5 m/s) assessed by Arteriograph were used to identify CAD (coronary artery calcium scoring ≥ 100 Agatston Units or coronary CT angiography luminal stenosis ≥ 50%) and to assess the additional diagnostic value of PWV to established cardiovascular risk factors.

Results: Forty-seven sportsmen (24%) had CAD on CCT. They were older (58.9 vs. 53.8 years, p<0.001), had more hypertension (17 vs. 4%, p=0.003), higher cholesterol levels (5.7 vs. 5.4 mmol/l) p=0.048), and more often were (ever) smokers (55 vs. 34%, p=0.008). Mean PWV was higher in those with CAD (8.9 vs. 8.0 m/s, p=0.017). For PWV >8.3m/s respectively >7.5 m/s sensitivity to detect CAD on CT was 43% and 74%, specificity 69% and 45%, positive predictive value 31% and 30%, and negative predictive value 79% and 84%. Adding PWV to traditional risk factor models did not change the area under the curve (from 0.78 (95% CI = 0.709-0.848)) to AUC 0.78 (95% CI 0.710-0.848, p = 0.99)) for prediction of CAD on CCT.

Conclusions: Limited additional value was found for PWV on top of established risk factors to identify CAD. PWV might still have a role to identify CAD in middle-aged sportsmen if risk factors such as cholesterol are unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131895PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493032PMC
April 2016

Characterization of exercise limitations by evaluating individual cardiac output patterns: a prospective cohort study in patients with chronic heart failure.

BMC Cardiovasc Disord 2015 Jun 23;15:57. Epub 2015 Jun 23.

Department of Cardiology, Máxima Medical Centre, De Run 4600, P.O. Box 7777, Veldhoven, 5500 MB, The Netherlands.

Background: Patients with chronic heart failure (CHF) suffer from exercise intolerance due to impaired central hemodynamics and subsequent alterations in peripheral skeletal muscle function and structure. The relative contribution of central versus peripheral factors in the reduced exercise capacity is still subject of debate. The main purpose was to investigate heterogeneity in the nature of exercise intolerance by evaluating individual cardiac output (Q) patterns. The secondary purpose was to evaluate whether patient and disease characteristics were associated with a central hemodynamic exercise limitation.

Methods: Sixty-four stable CHF patients performed a symptom limited incremental exercise test with respiratory gas analysis and simultaneous assessment of Q, using a radial artery pulse contour analysis method. A central hemodynamic exercise limitation was defined as a plateau or decline in Q from 90 to 100 % of exercise duration.

Results: Data from 61 patients were analyzed. A central hemodynamic exercise limitation was observed in 21 patients (34 %). In these patients, a higher occurrence of a plateau/decrease in oxygen uptake (VO2) (52 % vs 23 %, p = 0.02), stroke volume (SV) (100 % vs. 75 %, p = 0.01) and chronotropic incompetence (31 % vs. 2.5 %, p = 0.01) was observed, while presence of a left bundle branch block (LBBB) occurred significantly less (19 % vs 48 %, p = 0.03) There was no difference in disease characteristics such as etiology, duration, NYHA class, mitral regurgitation or ischemia.

Conclusions: The study revealed considerable heterogeneity in the nature of exercise limitations between moderately impaired CHF patients. In one third of the study population a plateau or decrease in Q towards peak exercise was demonstrated, which is indicative of a central hemodynamic exercise limitation. A central hemodynamic exercise limitation was associated with an impairment to augment stroke volume and heart rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-015-0057-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476170PMC
June 2015

Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction.

Biomaterials 2015 Aug 28;61:339-48. Epub 2015 May 28.

Dept. of Cardiology, DH&L, University Medical Center Utrecht, Utrecht, The Netherlands; Interuniversity Cardiology Institute of the Netherlands (ICIN), Utrecht, The Netherlands. Electronic address:

Cardiac cell therapy suffers from limitations related to poor engraftment and significant cell death after transplantation. In this regard, ex vivo tissue engineering is a tool that has been demonstrated to increase cell retention and survival. The aim of our study was to evaluate the therapeutic potential of a 3D-printed patch composed of human cardiac-derived progenitor cells (hCMPCs) in a hyaluronic acid/gelatin (HA/gel) based matrix. hCMPCs were printed in the HA/gel matrix (30 × 10(6) cells/ml) to form a biocomplex made of six perpendicularly printed layers with a surface of 2 × 2 cm and thickness of 400 μm, in which they retained their viability, proliferation and differentiation capability. The printed biocomplex was transplanted in a mouse model of myocardial infarction (MI). The application of the patch led to a significant reduction in adverse remodeling and preservation of cardiac performance as was shown by both MRI and histology. Furthermore, the matrix supported the long-term in vivo survival and engraftment of hCMPCs, which exhibited a temporal increase in cardiac and vascular differentiation markers over the course of the 4 week follow-up period. Overall, we developed an effective and translational approach to enhance hCMPC delivery and action in the heart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2015.05.005DOI Listing
August 2015

Low vulnerability of the right phrenic nerve to electroporation ablation.

Heart Rhythm 2015 Aug 18;12(8):1838-44. Epub 2015 May 18.

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

Background: Circular electroporation ablation is a novel ablation modality for electrical pulmonary vein isolation. With a single 200-J application, deep circular myocardial lesions can be created. However, the acute and chronic effects of this energy source on phrenic nerve (PN) function are unknown.

Objective: The purpose of this study was to analyze nerve vulnerability to electroporation ablation in a porcine model.

Methods: In 20 animals (60-75 kg), the course of the right PN was pace-mapped inside the superior caval vein (SCV). Thereafter, a single 200-J circular electroporation ablation was performed via a multipolar circular catheter in firm contact with the inner SCV wall.

Results: In 19 of 20 animals, the PN could be captured along an estimated 6-8 cm trajectory above the right atrial contour. Directly after the application, the PN could be captured above the ablation level in 17 of 19 animals and after maximally 30 minutes in all animals. Fifteen animals were restudied after 3-13 weeks, and PN functionality was unaffected in all. Histological analysis in 5 animals in which the application had been delivered in the muscular sleeve just above the right atrium showed a transmural circular lesion. However, no lesion was found in the other animals in which the application had been delivered in the fibrous section more cranial in the SCV.

Conclusions: Electroporation ablation at an energy level that may create deep myocardial lesions may spare the targeted right PN. These animal data suggest that electroporation may be a safe ablation modality near the right PN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrthm.2015.05.012DOI Listing
August 2015

Pulmonary vein stenosis after catheter ablation: electroporation versus radiofrequency.

Circ Arrhythm Electrophysiol 2014 Aug 23;7(4):734-8. Epub 2014 Jun 23.

From the Departments of Cardiology (V.J.H.M.v.D., K.G.E.J.N., H.v.W., B.C.d.P., P.A.F.M.D., F.H.M.W.) and Pathology (A.V.), University Medical Center, Utrecht, The Netherlands; and Department of Rhythmology, Alfried Krupp Hospital, Essen, Germany (K.G.E.J.N.).

Background: Radiofrequency ablation inside pulmonary vein (PV) ostia can cause PV stenosis. A novel alternative method of ablation is irreversible electroporation, but the long-term response of PVs to electroporation ablation is unknown.

Methods And Results: In ten 6-month-old pigs (60-75 kg), the response of PVs to circular electroporation and radiofrequency ablation was compared. Ten consecutive, nonarcing, electroporation applications of 200 J were delivered 5 to 10 mm inside 1 of the 2 main PVs, using a custom-deflectable, 18-mm circular decapolar catheter. Inside the other PV, circular radiofrequency ablation was performed using 30 W radiofrequency applications via an irrigated 4-mm ablation catheter. PV angiograms were made before ablation, immediately after ablation, and after 3-month survival. PV diameters and heart size were measured. With electroporation ablation, PV ostial diameter decreased 11±10% directly after ablation, but had increased 19±11% after 3 months. With radiofrequency ablation, PV ostial diameter decreased 23±15% directly after ablation and remained 7±17% smaller after 3 months compared with preablation diameter despite a 21±7% increase in heart size during aging from 6 to 9 months.

Conclusions: In this porcine model, multiple circumferential 200-J electroporation applications inside the PV ostia do not affect PV diameter at 3-month follow-up. Radiofrequency ablation inside PV ostia causes considerable PV stenosis directly after ablation, which persists after 3 months.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.113.001111DOI Listing
August 2014

The impact of susceptibility loci for coronary artery disease on other vascular domains and recurrence risk.

Eur Heart J 2013 Oct 4;34(37):2896-904. Epub 2013 Jul 4.

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

Aims: Genome-wide association studies (GWAS) have identified many genetic loci related to coronary artery disease (CAD) and myocardial infarction (MI). However, the extent to which these loci are related to other vascular diseases is not clear. The aim of this study is to investigate the cumulative effects of risk alleles associated with CAD/MI on ischaemic stroke (IS), abdominal aortic aneurysm (AAA), and peripheral artery disease (PAD).

Methods And Results: We calculated a multi-locus genetic risk score (GRS) in 8446 participants of the SMART (Second Manifestations of ARTerial disease) study based on the lead single-nucleotide polymorphisms (SNPs) at 30 CAD/MI loci, and tested this GRS for cross-sectional association with CAD/MI, IS, AAA and PAD, adjusting for age and sex. We also investigated whether this GRS was associated with recurrent vascular events using Cox regression, adjusting for age, sex, body mass index, type 2 diabetes, low-density lipoprotein-cholesterol, smoking, and hypertension. We found that the GRS was significantly associated with CAD (P = 1.31 × 10(-9)), IS (P = 0.030), and PAD (P = 6.93 × 10(-04)), but not with AAA (P = 0.057). The lead SNP at the 9p21 locus (rs4977574) was associated with all four vascular diseases (P < 4 × 10(-3)), illustrating the functional pleiotropy of this locus. The GRS was associated with recurrent risk of MI (P = 0.026), with a hazard ratio of 1.13 (95% CI 1.00-1.28) for individuals in the top quartile of the GRS distribution (n = 30 recurrent events) compared with those in the bottom quartile (n = 8 recurrent events). Finally, we found a significant positive relationship between the GRS and the number of vascular events (P = 3.26 × 10(-05)).

Conclusions: These findings suggest that CAD/MI-associated risk alleles play an aetiological role in different types of atherosclerotic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/eht222DOI Listing
October 2013

Atherosclerotic renal artery stenosis is prevalent in cardiorenal patients but not associated with left ventricular function and myocardial fibrosis as assessed by cardiac magnetic resonance imaging.

BMC Cardiovasc Disord 2012 Sep 18;12:76. Epub 2012 Sep 18.

Department of Cardiology, UMC Utrecht, The Netherlands.

Background: Atherosclerotic renal artery stenosis (ARAS) is common in cardiovascular diseases and associated with hypertension, renal dysfunction and/or heart failure. There is a paucity of data about the prevalence and the role of ARAS in the pathophysiology of combined chronic heart failure (CHF) and chronic kidney disease (CKD). We investigated the prevalence in patients with combined CHF/CKD and its association with renal function, cardiac dysfunction and the presence and extent of myocardial fibrosis.

Methods: The EPOCARES study (ClinTrialsNCT00356733) investigates the role of erythropoietin in anaemic patients with combined CHF/CKD. Eligible subjects underwent combined cardiac magnetic resonance imaging (cMRI), including late gadolinium enhancement, with magnetic resonance angiography of the renal arteries (MRA).

Results: MR study was performed in 37 patients (median age 74 years, eGFR 37.4 ± 15.6 ml/min, left ventricular ejection fraction (LVEF) 43.3 ± 11.2%), of which 21 (56.8%) had ARAS (defined as stenosis >50%). Of these 21 subjects, 8 (21.6%) had more severe ARAS >70% and 8 (21.6%) had a bilateral ARAS >50% (or previous bilateral PTA). There were no differences in age, NT-proBNP levels and medication profile between patients with ARAS versus those without. Renal function declined with the severity of ARAS (p = 0.03), although this was not significantly different between patients with ARAS versus those without. Diabetes mellitus was more prevalent in patients without ARAS (56.3%) against those with ARAS (23.8%) (p = 0.04). The presence and extent of late gadolinium enhancement, depicting myocardial fibrosis, did not differ (p = 0.80), nor did end diastolic volume (p = 0.60), left ventricular mass index (p = 0.11) or LVEF (p = 0.15). Neither was there a difference in the presence of an ischemic pattern of late enhancement in patients with ARAS versus those without.

Conclusions: ARAS is prevalent in combined CHF/CKD and its severity is associated with a decline in renal function. However, its presence does not correlate with a worse LVEF, a higher left ventricular mass or with the presence and extent of myocardial fibrosis. Further research is required for the role of ARAS in the pathophysiology of combined chronic heart and renal failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1471-2261-12-76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3470969PMC
September 2012

23Na chemical shift imaging and Gd enhancement of myocardial edema.

Int J Cardiovasc Imaging 2013 Feb 12;29(2):343-54. Epub 2012 Jul 12.

Laboratory of Experimental Cardiology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands.

Myocardial edema can arise in several disease states. MRI contrast agent can accumulate in edematous tissue, which complicates differential diagnosis with contrast-enhanced (CE)-MRI and might lead to overestimation of infarct size. Sodium Chemical Shift Imaging ((23)Na-CSI) may provide an alternative for edema imaging. We have developed a non-infarct, isolated rat heart model with two levels of edema, which was studied with (23)Na-CSI and CE-MRI. In edematous, but viable tissue the extracellular sodium (Na (e) (+)) signal is hypothesized to increase, but not the intracellular sodium (Na (i) (+)) signal. Isolated hearts were perfused at 60 (n = 6) and 140 mmHg (n = 5). Dimethyl methylphosphonate (DMMP) and phenylphosphonate (PPA) were used to follow edema formation by (31)P-MR Spectroscopy. In separate groups, Thulium(III)1,4,7,10 tetraazacyclododecane-N,N',N″,N'''-tetra(methylenephosphonate) (TmDOTP(5-)) and Gadovist were used for (23)Na-CSI (n = 8) and CE-MRI (n = 6), respectively. PPA normalized signal intensity (SI) was higher at 140 versus 60 mmHg, with a ratio of 1.27 ± 0.12 (p < 0.05). The (DMMP-PPA)/dry weight ratio, as a marker of intracellular volume, remained unchanged. The mid-heart cross sectional area (CSA) of the left ventricle (LV) was significantly increased at 140 mmHg. In addition, at 140 mmHg, the LV Na (e) (+) SI increased with a 140 mmHg/60 mmHg ratio of 1.24 ± 0.18 (p < 0.05). Na (i) (+) SI remained essentially unchanged. With CE-MRI, a subendocardially enhanced CSA was identified, increasing from 0.20 ± 0.02 cm(2) at 60 mmHg to 0.31 ± 0.02 cm(2) at 140 mmHg (p < 0.05). Edema shows up in both CE-MRI and Na (e) (+) . High perfusion pressure causes more edema subendocardially than subepicardially. (23)Na-CSI is an attractive alternative for imaging of edema and is a promising tool to discriminate between edema, acute and chronic MI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10554-012-0093-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560947PMC
February 2013

Relation between abdominal obesity, insulin resistance and left ventricular hypertrophy diagnosed by electrocardiogram and magnetic resonance imaging in hypertensive patients.

Am J Cardiol 2012 Jul 5;110(2):227-33. Epub 2012 Apr 5.

Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass (LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted β = -0.02, 95% confidence interval -0.02 to -0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (β = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2012.03.016DOI Listing
July 2012

Long-term outcome of cardiac pacing in octogenarians and nonagenarians.

Europace 2012 Apr 23;14(4):502-8. Epub 2011 Oct 23.

Department of Cardiology, UMC Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.

Aims: The number of patients >80 years receiving pacemakers (PMs) is increasing. Little is known about survival and complications in this specific subgroup. We aim to determine predictors of long-term survival.

Methods And Results: Pacemaker-related complications and death occurring in patients receiving a first PM for conventional bradycardia indications were systematically documented (the FollowPace registry). This report describes 481 patients ≥80 years during a mean follow-up of 5.8 (SD 1.2) years. Within 2 months 54 PM complications occurred in 47 patients (9.8%). During follow-up, 35 adverse PM events were reported in 33 patients (6.9%). Complication rates in patients ≥80 years were comparable with those for patients <80 years. Survival rates were 86, 75, and 49% after 1, 2, and 5 years, respectively, and were comparable with survival for age- and sex-matched controls from the general Dutch population. Most patients died of non-cardiac causes. Age at the time of implantation, male gender, the presence of congestive heart failure, coronary pathology, and diabetes mellitus were independent predictors of all-cause mortality.

Conclusion: This large study of long-term cardiac pacing for bradycardia in octogenarians and nonagenarians showed a cumulative 5-year survival of ~50%, which compares with that of age- and sex-matched controls. These data suggest a beneficial impact of bradycardia pacing, restoring life expectancy to previous levels. The occurrence of PM complications during long-term follow-up is not infrequent with 18.1% of patients experiencing a PM-related complication during a mean of 5.8 years follow-up. The complication rate was not higher than in younger PM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/eur329DOI Listing
April 2012

A genome-wide association study identifies a region at chromosome 12 as a potential susceptibility locus for restenosis after percutaneous coronary intervention.

Hum Mol Genet 2011 Dec 30;20(23):4748-57. Epub 2011 Aug 30.

Department of Human Genetics, Leiden University Medical Center, Leiden 2300RC, The Netherlands.

Percutaneous coronary intervention (PCI) has become an effective therapy to treat obstructive coronary artery diseases (CAD). However, one of the major drawbacks of PCI is the occurrence of restenosis in 5-25% of all initially treated patients. Restenosis is defined as the re-narrowing of the lumen of the blood vessel, resulting in renewed symptoms and the need for repeated intervention. To identify genetic variants that are associated with restenosis, a genome-wide association study (GWAS) was conducted in 295 patients who developed restenosis (cases) and 571 who did not (controls) from the GENetic Determinants of Restenosis (GENDER) study. Analysis of ~550 000 single nucleotide polymorphisms (SNPs) in GENDER was followed by a replication phase in three independent case-control populations (533 cases and 3067 controls). A potential susceptibility locus for restenosis at chromosome 12, including rs10861032 (P(combined) = 1.11 × 10(-7)) and rs9804922 (P(combined) = 1.45 × 10(-6)), was identified in the GWAS and replication phase. In addition, both SNPs were also associated with coronary events (rs10861032, P(additive) = 0.005; rs9804922, P(additive) = 0.023) in a trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER) and all-cause mortality in PROSPER (rs10861032, P(additive) = 0.007; rs9804922, P(additive) = 0.013) and GENDER (rs10861032, P(additive) = 0.005; rs9804922, P(additive) = 0.023). Further analysis suggests that this locus could be involved in regulatory functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddr389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209827PMC
December 2011

Determinants of red cell distribution width (RDW) in cardiorenal patients: RDW is not related to erythropoietin resistance.

J Card Fail 2011 Aug 28;17(8):626-33. Epub 2011 May 28.

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

Background: Studies have shown that red cell distribution width (RDW) is related to outcome in chronic heart failure (CHF). The pathophysiological process is unknown. We studied the relationship between RDW and erythropoietin (EPO) resistance, and related factors such as erythropoietic activity, functional iron availability and hepcidin.

Methods And Results: In the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome (EPOCARES) study, which investigates the role of EPO in 54 iron-supplemented anemic patients with CHF and chronic kidney disease (CKD) (n = 35 treated with 50 IU/kg/wk Epopoetin beta, n = 19 control), RDW was not associated with EPO resistance. We defined EPO resistance by EPO levels (r = 0.12, P = .42), the observed/predicted log EPO ratio (r = 0.12, P = .42), the increase in reticulocytes after 2 weeks of EPO treatment (r = -0.18, P = .31), and the increase of hemoglobin after 6 months of EPO treatment (r = 0.26, P = .35). However, RDW was negatively correlated with functional iron availability (reticulocyte hemoglobin content, r = -0.48, P < .001, and transferrin saturation, r = -0.39, P = .005) and positively with erythropoietic activity (soluble transferrin receptor, r = 0.48, P < .001, immature reticulocyte fraction, r = 0.36, P = .01) and positively with interleukin-6 (r = 0.48, P < .001). No correlation existed between hepcidin-25 and RDW.

Conclusions: EPO resistance was not associated with RDW. RDW was associated with functional iron availability, erythropoietic activity, and interleukin-6 in anemic patients with CHF and CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2011.04.009DOI Listing
August 2011

Factor VII Activating Protease Polymorphism (G534E) Is Associated with Increased Risk for Stroke and Mortality.

Stroke Res Treat 2011 30;2011:424759. Epub 2011 Jun 30.

Department of Cardiology, Leiden University Medical Center, C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

Introduction. The FSAP-Marburg I polymorphism (1704G > A), which reduces FSAP activity, is associated with late complications of carotid stenosis in humans. Therefore, this study examines the influence of the Marburg I polymorphism and the closely linked Marburg II polymorphism (1280G > C) on various cardiovascular outcomes in two large independent study populations. Methods. The two Marburg polymorphisms in the HABP2 gene encoding FSAP were genotyped in a large population of elderly patients at risk for vascular disease (the PROSPER-study, n = 5804) and in a study population treated with a percutaneous coronary intervention (the GENDER-study, n = 3104). Results. In the PROSPER study, the Marburg I polymorphism was associated with an increased risk of clinical stroke (HR: 1.60, 95% CI: 1.13-2.28) and all-cause mortality (HR: 1.33, 95% CI: 1.04-1.71). In the GENDER study carriers of this variant seemed at lower risk of developing restenosis (HR: 0.59, 95% CI: 0.34-1.01). The Marburg II polymorphism showed similar but weaker results. Conclusion. The increase in stroke risk in Marburg I carriers could be due to differential effects on smooth muscle cells and on matrix metalloproteinases, thereby influencing plaque stability. The possible protective effect on restenosis could be the result of reduced activation of zymogens, which are involved in hemostasis and matrix remodeling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4061/2011/424759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140705PMC
November 2011

Toll-like receptor 2 and 4 stimulation elicits an enhanced inflammatory response in human obese patients with atherosclerosis.

Clin Sci (Lond) 2011 Sep;121(5):205-14

Experimental Laboratory Cardiology, Department of Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

The innate immune response elicited by activation of TLRs (Toll-like receptors) plays an important role in the pathogenesis of atherosclerosis. We hypothesized that cardiovascular risk factors are associated with the activation status of the innate immune system. We therefore assessed the responsiveness of TLRs on circulating cells in two groups of patients with established atherosclerosis and related this to the presence of cardiovascular risk factors. TNF (tumour necrosis factor)-α release induced by TLR2 and TLR4 activation was measured in patients with established coronary [PCI (percutaneous coronary intervention) study, n=78] or carotid artery disease [CEA (carotid endarterectomy) study, n=104], by stimulating whole blood samples with lipopolysaccharide (TLR4 ligand) and Pam3CSK4 [tripalmitoylcysteinylseryl-(lysyl)4; TLR2 ligand]. As an early activation marker, CD11b expression was measured by flow cytometry on CD14+ cells. Obesity was the 'only' risk factor that correlated with the TLR response. In both studies, obese patients had significantly higher TNF-α levels after stimulation of TLR2 compared with non-obese patients [16.9 (7.7-49.4) compared with 7.5 (1.5-19.2) pg/ml (P=0.008) in coronary artery disease and 14.6 (8.1-28.4) compared with 9.5 (6.1-15.7) pg/ml (P=0.015) in carotid artery disease; values are medians (interquartile range)]. Similar results were obtained following TLR4 stimulation. The enhanced inflammatory state in obese patients was also confirmed by a significant increased expression of the activation marker CD11b on circulating monocytes. In conclusion, obesity is associated with an enhanced TLR response in patients suffering from established atherosclerotic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/CS20100601DOI Listing
September 2011

Cardiogenetic screening of first-degree relatives after sudden cardiac death in the young: a population-based approach.

Europace 2011 May 11;13(5):716-22. Epub 2011 Jan 11.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.

Aims: To investigate the yield of cardiogenetic screening of relatives of young sudden cardiac death (SCD) and sudden unexplained death (SUD) victims in a population-based setting.

Methods And Results: A population-based study was carried out between 2000 and 2006. Records of the hospital, death declaration certificates, and resuscitation records were reviewed for SCD and SUD cases (1-40 years). Information on autopsy results and cardiogenetic screening of the victims' first-degree relatives was collected. Relatives were invited for additional cardiogenetic screening when this had not yet been performed. The search led to 16 cases of SCD/SUD and 4 cases of aborted SCD/SUD. Causes of SCD/SUD were myocardial infarction (n = 3), arrhythmogenic right ventricular cardiomyopathy (ARVC) (n = 2), long-QT syndrome (n = 1), hypertrophic cardiomyopathy (n = 2), left ventricular hypertrophy due to aortic stenosis (n = 1), and unknown cause of death (n = 7). Causes of aborted SCD/SUD were myocardial infarction (n = 2), idiopatic ventricular fibrillation (n = 1), and the Brugada syndrome (n = 1). The cardiogenetic screening of 37 relatives of 12 victims led to a diagnosis of Brugada syndrome in 3 relatives and the suspicion of ARVC in 2 relatives. The yield of screening of these relatives was 14% (95% confidence interval: 3-25%).

Conclusion: In the usual care, relatives of (aborted) SCD and SUD victims are often not referred for cardiogenetic screening. Screening is often not performed according to a systematic approach, and the detection rate of inherited diseases in relatives of (aborted) SCD and SUD victims in a population-based setting, although substantial, is lower than expected based on previous studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/europace/euq460DOI Listing
May 2011

Genetic variation in PCAF, a key mediator in epigenetics, is associated with reduced vascular morbidity and mortality: evidence for a new concept from three independent prospective studies.

Heart 2011 Jan 8;97(2):143-50. Epub 2010 Nov 8.

Department of Cardiology, Leiden University Medical Center, RC Leiden, The Netherlands.

Aims: This study was designed to investigate the counterbalancing influence of genetic variation in the promoter of the gene encoding P300/CBP associated factor (PCAF), a lysine acetyltransferase (KAT), on coronary heart disease (CHD) and mortality.

Methods And Results: The association of genetic variation in the PCAF-gene with CHD, restenosis and mortality was investigated in three large cohorts. The results were combined to examine overall effects on CHD mortality and on restenosis risk. Compared with the homozygous -2481G allele in the PCAF promoter, a significant reduction in CHD mortality risk with the homozygous -2481C PCAF promoter allele was observed. A combined risk reduction for CHD death for the three studies was 21% (15-26%; p=8.1×10(-4)). In elderly patients (>58 years) the effects were stronger. Furthermore, this PCAF allele was significantly associated with all-cause mortality (p=0.001). Functional analysis showed that nuclear factors interact in vitro with the oligonucleotides encompassing the -2481G/C polymorphism and that this interaction might be influenced by this polymorphism in the PCAF promoter. Moreover, modulation of PCAF gene expression was detectable upon cuff-placement in an animal model of reactive stenosis.

Conclusion: We showed in three large prospective studies that the -2481C allele in the PCAF promoter is associated with a significant survival advantage in elderly patients. Our observations promote the concept that epigenetic processes are under genetic control and that, other than environment, variation in genes encoding KATs may also determine susceptibility to CHD outcomes and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/hrt.2010.199927DOI Listing
January 2011

Chest pain in the emergency room: a multicenter validation of the HEART Score.

Crit Pathw Cardiol 2010 Sep;9(3):164-9

Department of Cardiology, Universitair Medisch Centrum, Utrecht, Nieuwegein, The Netherlands.

Objective: Decision-making in chest pain patients is hampered by poor diagnostic power of patient's history, electrocardiogram, age, risk factors, and troponin. Each of these findings may be qualified with 0, 1, or 2 points. Together they compose the HEART score. We tested the hypothesis that the HEART score predicts major adverse cardiac events.

Design: Retrospective multicenter analysis in patients presenting at the cardiology emergency room.

Setting: Patient inclusion between January 1 and March 31, 2006.

Patients: A total of 2161 patients were admitted, of which 910 patients (42%) presented with chest pain. Analysis was performed in 880 cases (96.7%).

Main Outcome Measures: The primary endpoint was a composite of acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery and death, within 6 weeks after presentation, together called major adverse cardiac events.

Results: A total of 158 patients (17.95%) reached the primary endpoint. Ninety-two patients had an acute myocardial infarction (10.45%), 82 a percutaneous coronary intervention (9.32%), 36 a coronary artery bypass graft (4.09%), and 13 died (1.48%). Of 303 patients with HEART score 0 to 3, three (0.99%) had an endpoint. In 413 patients with HEART score 4 to 6, 48 cases (11.6%) reached an endpoint. In case of a HEART score of 7 to 10, an endpoint was reached in 107/164 cases (65.2%).

Conclusions: The HEART score helps in making accurate diagnostic and therapeutic decisions without the use of radiation or invasive procedures. The HEART score is an easy, quick, and reliable predictor of outcome in chest pain patients and can be used for triage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HPC.0b013e3181ec36d8DOI Listing
September 2010

Echocardiographic screening results in patients with tuberous sclerosis complex.

Tex Heart Inst J 2010 ;37(3):280-3

Department of Radiology, Atrium Medical Center, 6419 PC Heerlen, The Netherlands.

We sought to examine the frequency of abnormal echocardiographic findings in patients with tuberous sclerosis complex. In a retrospective cohort study, we included all patients with known tuberous sclerosis complex who had been sent to our cardiology department for echocardiographic screening from 1995 through August 2003 (n=56). Two research scientists independently reviewed the reports of the echocardiographic screening examinations for abnormal findings. We used descriptive statistics, the Mann-Whitney U test, and the chi(2) test. The mean age of patients included in the study was 35 years (range, 12-73 yr); 23 patients were male. Abnormal findings were seen in 22 patients (39%). The most common abnormal findings were focal areas of increased intramyocardial echogenicity, which were seen in 16 patients (29%). The clinical consequence of this finding is still unknown. We conclude that echocardiographic abnormalities are common in patients with tuberous sclerosis complex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2879195PMC
September 2010