The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assess... more The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assessment technique. In order to develop a fast and label-free immunosensor for C-reactive protein (CRP), a risk factor for this condition, anti-CRP antibodies were physically adsorbed to the hydrogen (H)-terminated surface of nanocrystalline diamond (NCD). An Enzyme-Linked ImmunoSorbent Assay (ELISA) reference technique showed that this was a suitable substrate for antibody-antigen recognition reactions. Electrochemical Impedance Spectroscopy (EIS) was used to electronically detect CRP recognition. The specificity of the immunosensor was demonstrated by incubation with CRP and plasminogen as reference molecule. A different impedance behavior was observed in real-time after CRP addition as compared to plasminogen addition: the impedance increased only during CRP incubation. Fitting the data showed that this corresponded with a decrease in capacitance of the molecular layer due to its increased thickness by specific CRP recognition. Sensitivity experiments in real-time showed a clear discrimination between 1 M, 100 nM, and 10 nM of CRP after 10 min at 100 Hz. Since, 10 nM of CRP was still clearly distinguishable from buffer solution, our CRP-directed immunosensor prototype reaches a sensitivity that is within the physiologically relevant concentration range of this biomarker in healthy controls and CVD patients. Moreover, this prototype displayed real-time discriminating power between spiked and unspiked serum, and thus also shows its applicability in this biological matrix.
Journal of the American College of Cardiology, 2015
Background: Beta-blockers reduce mortality and readmissions in heart failure with reduced ejectio... more Background: Beta-blockers reduce mortality and readmissions in heart failure with reduced ejection fraction (HFrEF), which might be explained by resting heart rate (HR) reduction.
Detection of intermittent atrial fibrillation (AF) is done using a 24-h Holter. Holter recordings... more Detection of intermittent atrial fibrillation (AF) is done using a 24-h Holter. Holter recordings are powerful but lack the comfort and have limited recording times resulting in under diagnosing of intermittent AF. Within this work we evaluated and compared a novel miniaturized three-channel ECG monitoring patch versus a 24-h Holter system. Both patients with a chronic AF rhythm (n=5) as well as patients with an AF rhythm that underwent electrical reconversion (n = 5) were equipped with both a 24-h Holter and ECG patch. Alignment of raw data of both ECG systems allowed cross-correlation analysis. Overall good correlations of up to 85% were obtained. RR-interval analysis of both systems resulted in very high correlations of 99% and higher. AF analysis showed correct identification of AF on both ECG systems. The performance of our ECG patch matches that of the 24-h Holter and could provide a suitable tool for long-term monitoring applications.
To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection ... more To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). In this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and cardiac index <2.5 L/min.m(2) , received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65-75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin-angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP <25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase >3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037). Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support.
ABSTRACT AimsTo study pulmonary vascular response patterns to exercise in heart failure with redu... more ABSTRACT AimsTo study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH).Methods and resultsIn this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) >15 mmHg, and cardiac index <2.5 L/min.m2, received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65–75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin–angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP <25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase >3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037).Conclusions Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support.
Echocardiography is increasingly important in the guidance and follow-up of percutaneous transcat... more Echocardiography is increasingly important in the guidance and follow-up of percutaneous transcatheter device closures. It was recently shown that the Amplatzer left atrial appendage occluder frequently presents as a figure-of-eight artifact due to interaction of device mesh and ultrasound waves. It remains unknown whether this can be translated to other types of disc occluders. Furthermore, the morphology of this figure-of-eight artifact appears to be different in the transesophageal and transthoracic image of the same device. The aim of this study was to evaluate the echocardiographic appearance of different types of disc occluders, and to clarify differences in morphology of the figure-of-eight artifact. A mathematical model of an epitrochoid curve was used for numerical simulation of disc occluder appearance at various imaging depths. In addition, an in vitro setup was used for echocardiographic analysis of different types of disc occluders at adjustable imaging depth and position. Mathematically, decreasing the imaging depth resulted in a more asymmetric figure-of-eight, i.e. with small upper part and wide lower part. In vitro results were in close agreement with the mathematical results. In addition, in vitro a figure-of-eight artifact was obtained in all different types of disc occluder devices. Different types of percutaneous disc occluders all present as a figure-of-eight artifact on echocardiography when imaged from a coronal imaging position. The morphology of the artifact depends on the imaging depth, with a more asymmetric figure-of-eight morphology at smaller probe-to-device distance. This clarifies the differences observed between transesophageal and transthoracic imaging.
The European journal of general practice, Jan 9, 2015
Background: Most patients presenting chest complaints in primary care are referred to secondary c... more Background: Most patients presenting chest complaints in primary care are referred to secondary care facilities, whereas only a few are diagnosed with acute coronary syndrome (ACS). Objectives: The aim is to determine the optimal cut-off value for a point-of-care heart-type fatty acid binding protein (H-FABP) test in patients presenting to the emergency department and to evaluate a possible future role of H-FABP in safely ruling out ACS in primary care. Methods: Serial plasma H-FABP (index test) and high sensitivity troponin T (hs-cTnT) (reference test) were determined in patients with any new-onset chest complaint. In a receiver operating characteristic (ROC) curve, the optimal cut-off value of H-FABP for ACS was determined. Predictive values of H-FABP for ACS were calculated. Results: For 202 consecutive patients (prevalence ACS 59%), the ROC curve based on the results of the first H-FABP was equal to the ROC curve of hs-cTnT (AUC 0.79 versus 0.80). Using a cut-off value of 4.0 ng...
Probe DNA, consisting of a 36-mer fragment was covalently immobilized on nanocrystalline chemical... more Probe DNA, consisting of a 36-mer fragment was covalently immobilized on nanocrystalline chemical vapour deposition (CVD) diamond electrodes and hybridized with a 29-mer target DNA. In this paper, we report on the label-free real-time electronic monitoring of DNA denaturation upon exposure to NaOH at different flow rates and molarities, using electrochemical impedance spectroscopy as readout technology. The impedance response was separated into a denaturation time constant and a medium exchange time constant by means of a double exponential fit. It was observed that the denaturation time is dependent on the flow rate as well as on the molarity of the NaOH. Surprisingly, it was observed that at low molarities (0.05 M) the DNA does not fully denature at low flow rates. Only after flushing the flow cell a second time with 0.05 M NaOH, complete denaturation was achieved. Confocal images were obtained and plotted in 3D graphs to confirm the results. This paper provides a systematic overview of measured denaturation times for different flow rates and at different molarities of NaOH. Optimization of these parameters can be a valuable asset in the field of mutation analysis.
This paper focuses on the characterization of the ZnO/poly(3hexylthiophene) (P3HT) interfaces in ... more This paper focuses on the characterization of the ZnO/poly(3hexylthiophene) (P3HT) interfaces in nanostructured hybrid solar cells, aiming to elucidate the relationship between thermal treatment, local morphology, and device performance. An equivalent impedimetric model for the device is proposed, allowing us to extract information about the ZnO/P3HT interface morphology and its impact on the photovoltaic properties by comparing devices with and without nanopatterning. It is found that the influence of thermal treatment on performance lies solely in the interface, resulting from a different interfacial morphology of P3HT depending on which crystal direction of ZnO is present.
The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assess... more The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assessment technique. In order to develop a fast and label-free immunosensor for C-reactive protein (CRP), a risk factor for this condition, anti-CRP antibodies were physically adsorbed to the hydrogen (H)-terminated surface of nanocrystalline diamond (NCD). An Enzyme-Linked ImmunoSorbent Assay (ELISA) reference technique showed that this was a suitable substrate for antibody–antigen recognition reactions. Electrochemical Impedance Spectroscopy (EIS) was used to electronically detect CRP recognition. The specificity of the immunosensor was demonstrated by incubation with CRP and plasminogen as reference molecule. A different impedance behavior was observed in real-time after CRP addition as compared to plasminogen addition: the impedance increased only during CRP incubation. Fitting the data showed that this corresponded with a decrease in capacitance of the molecular layer due to its increase...
Journal of the American College of Cardiology, 2014
background: Restrictive mitral valve annuloplasty (RMA) is the surgical treatment of choice for s... more background: Restrictive mitral valve annuloplasty (RMA) is the surgical treatment of choice for severe functional mitral regurgitation, yet postoperative mitral stenosis remains debated. The aim of this study was to evaluate the evolution of the mean transmitral gradient and effective mitral valve area (MVA) during exercise in RMA patients compared with fixed prosthetic orifices. methods: Consecutive RMA patients (n=39) underwent a symptom-limited bicycle exercise test with stepwise Doppler echocardiography. At each stage of exercise transmitral flow rate, mean transmitral gradient and effective MVA were assessed.
2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2015
A new technique to monitor the fluid status of congestive heart failure (CHF) patients in the hos... more A new technique to monitor the fluid status of congestive heart failure (CHF) patients in the hospital is proposed and verified in a clinical trial with 8 patients. A wearable Bio-impedance (BioZ) sensor allows a continuous localized measurement which can be complement clinical tools in the hospital. Thanks to the multi-parametric approach and correlation analysis with clinical reference, BioZ is successfully shown as a promising parameter for continuous and wearable CHF patient monitoring application.
Physica Status Solidi (A) Applications and Materials
A new impedance spectroscopy unit is developed, fully customized to become a vital part of label ... more A new impedance spectroscopy unit is developed, fully customized to become a vital part of label free biosensor arrays with possible applications in DNA and protein sensing. Test measurements are conducted to explore the accuracy and specificity of the system, both under electronic lab conditions as well as under wet cell conditions with synthetic-diamond based sensor electrodes. The impedance of seven resistors was monitored for 17 h and a maximum error <0.02% was found. Furthermore, the impedance of PBS at different concentrations was monitored for 60 min per concentration and a different impedance for each concentration was detected. The impedance is also monitored for NaOH, PBS and nuclease free water at different temperatures with a total duration of 60 min per fluid. Systematically different impedances for each temperature per fluid were found and the temperature coefficients were determined. All test measurements lead to results well within specification.
Physica Status Solidi (A) Applications and Materials
The study of protein adsorption on solid surfaces is interesting for theoretical and practical bi... more The study of protein adsorption on solid surfaces is interesting for theoretical and practical bio-analytical sensing applications. In this work we combine electrochemical impedance spectroscopy, enzyme linked immunosorbent assay, and fluorescence microscopy with thin boron doped nanocrystalline diamond films to address and study the adsorption behavior of globular proteins (antibodies) on hydrophobic and hydrophilic diamond surfaces. A powerful combination of time resolved impedance spectroscopy and data modeling with equivalent circuits allow a detailed insight in the protein behavior at an interface. It is found that hydrogenated diamond is greatly favorable for impedimetric read-out but causes slight conformational loss of the protein structure and therefore also its biological activity. The oxidized surface allows faster adsorption and a high biological activity but results in smaller impedimetric response.
Our aim was to test if intra-thoracic impedance (ITI) measurements would improve short-term clini... more Our aim was to test if intra-thoracic impedance (ITI) measurements would improve short-term clinical outcome (i.e. all-cause mortality and heart failure hospitalizations) in patients with cardiac resynchronization therapy (CRT) who were followed in a telemonitoring program with structural biofeedback. Methods: CRT patients (n=200; age= 70 +/-14y) were included in a telemonitoring program at Ziekenhuis Oost-Limburg Genk, which comprised daily transmissions through a wireless system installed at their homes. All patients were followed for potential lead/device problems, episodes of anti-tachycardia pacing, device shocks, occurrence of arrhytmias, a decline in biventricular pacing percentage and/or a sudden drop in physical activity. Patients with missed transmissions were contacted by phone. Devices with ITI measurement ability were implanted in 108 patients. Those provided extra alerts when pre-specified ITI tresholds were crossed during at least 7 days. Heart failure nurses checked ...
Journal of the American College of Cardiology, Jan 3, 2015
The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptom... more The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptoms. Most HF hospitalizations are related to sodium (Na(+)) and fluid retention resulting from neurohumoral up-regulation. Recent insights suggest that Na(+) is not distributed in the body solely as a free cation, but that it is also bound to large interstitial glycosaminoglycan (GAG) networks in different tissues, which have an important regulatory function. In HF, high Na(+) intake and neurohumoral alterations disrupt GAG structure, leading to loss of the interstitial buffer capacity and disproportionate interstitial fluid accumulation. Moreover, a diminished endothelial GAG network (the endothelial glycocalyx) results in increased vascular resistance and disturbed endothelial nitric oxide production. New imaging modalities can help evaluate interstitial Na(+) and endothelial glycocalyx integrity. Furthermore, several therapies have been proven to stabilize interstitial GAG networks. Hen...
The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assess... more The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assessment technique. In order to develop a fast and label-free immunosensor for C-reactive protein (CRP), a risk factor for this condition, anti-CRP antibodies were physically adsorbed to the hydrogen (H)-terminated surface of nanocrystalline diamond (NCD). An Enzyme-Linked ImmunoSorbent Assay (ELISA) reference technique showed that this was a suitable substrate for antibody-antigen recognition reactions. Electrochemical Impedance Spectroscopy (EIS) was used to electronically detect CRP recognition. The specificity of the immunosensor was demonstrated by incubation with CRP and plasminogen as reference molecule. A different impedance behavior was observed in real-time after CRP addition as compared to plasminogen addition: the impedance increased only during CRP incubation. Fitting the data showed that this corresponded with a decrease in capacitance of the molecular layer due to its increased thickness by specific CRP recognition. Sensitivity experiments in real-time showed a clear discrimination between 1 M, 100 nM, and 10 nM of CRP after 10 min at 100 Hz. Since, 10 nM of CRP was still clearly distinguishable from buffer solution, our CRP-directed immunosensor prototype reaches a sensitivity that is within the physiologically relevant concentration range of this biomarker in healthy controls and CVD patients. Moreover, this prototype displayed real-time discriminating power between spiked and unspiked serum, and thus also shows its applicability in this biological matrix.
Journal of the American College of Cardiology, 2015
Background: Beta-blockers reduce mortality and readmissions in heart failure with reduced ejectio... more Background: Beta-blockers reduce mortality and readmissions in heart failure with reduced ejection fraction (HFrEF), which might be explained by resting heart rate (HR) reduction.
Detection of intermittent atrial fibrillation (AF) is done using a 24-h Holter. Holter recordings... more Detection of intermittent atrial fibrillation (AF) is done using a 24-h Holter. Holter recordings are powerful but lack the comfort and have limited recording times resulting in under diagnosing of intermittent AF. Within this work we evaluated and compared a novel miniaturized three-channel ECG monitoring patch versus a 24-h Holter system. Both patients with a chronic AF rhythm (n=5) as well as patients with an AF rhythm that underwent electrical reconversion (n = 5) were equipped with both a 24-h Holter and ECG patch. Alignment of raw data of both ECG systems allowed cross-correlation analysis. Overall good correlations of up to 85% were obtained. RR-interval analysis of both systems resulted in very high correlations of 99% and higher. AF analysis showed correct identification of AF on both ECG systems. The performance of our ECG patch matches that of the 24-h Holter and could provide a suitable tool for long-term monitoring applications.
To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection ... more To study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH). In this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;15 mmHg, and cardiac index &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;2.5 L/min.m(2) , received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65-75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin-angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037). Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support.
ABSTRACT AimsTo study pulmonary vascular response patterns to exercise in heart failure with redu... more ABSTRACT AimsTo study pulmonary vascular response patterns to exercise in heart failure with reduced ejection fraction (HFrEF) and pulmonary hypertension (PH).Methods and resultsIn this prospective single-centre cohort study, consecutive symptomatic HFrEF patients (n = 40) with mean pulmonary arterial pressure (MPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) &gt;15 mmHg, and cardiac index &lt;2.5 L/min.m2, received protocol-driven titrated sodium nitroprusside (SNP) and diuretics to reach mean arterial blood pressure 65–75 mmHg and PAWP ≤15 mmHg. Patients performed symptom-limited supine bicycle testing under continued SNP administration. Afterwards, SNP was gradually withdrawn, renin–angiotensin system blockers uptitrated, and hydralazine added to maintain haemodynamic targets. Subsequently, bicycle testing was repeated. Patients presented with pulmonary vascular resistance (PVR) = 3.8 ± 1.4 Wood Units at rest, decreasing to 2.9 ± 0.9 Wood Units after decongestion, with PH was completely reversed (MPAP &lt;25 mmHg) in 22%. From rest to maximal exercise, the cardiac index did not change significantly (P = 0.334 under SNP; P-value = 0.552 under oral therapy). A dynamic exercise-induced PVR increase &gt;3.5 Wood Units was noted in 19 patients (48%) under oral therapy vs. five (13%) under SNP. Such exercise-induced PVR increase was associated with a 33% relative decrease in right ventricular stroke work index (P = 0.037).Conclusions Even after thorough decongestion and under continuous afterload reduction, PH secondary to HFrEF is completely reversible in only a minority of patients. Others demonstrate an exercise-induced PVR increase, associated with impaired right ventricular stroke work, which might be ameliorated by nitric oxide donor support.
Echocardiography is increasingly important in the guidance and follow-up of percutaneous transcat... more Echocardiography is increasingly important in the guidance and follow-up of percutaneous transcatheter device closures. It was recently shown that the Amplatzer left atrial appendage occluder frequently presents as a figure-of-eight artifact due to interaction of device mesh and ultrasound waves. It remains unknown whether this can be translated to other types of disc occluders. Furthermore, the morphology of this figure-of-eight artifact appears to be different in the transesophageal and transthoracic image of the same device. The aim of this study was to evaluate the echocardiographic appearance of different types of disc occluders, and to clarify differences in morphology of the figure-of-eight artifact. A mathematical model of an epitrochoid curve was used for numerical simulation of disc occluder appearance at various imaging depths. In addition, an in vitro setup was used for echocardiographic analysis of different types of disc occluders at adjustable imaging depth and position. Mathematically, decreasing the imaging depth resulted in a more asymmetric figure-of-eight, i.e. with small upper part and wide lower part. In vitro results were in close agreement with the mathematical results. In addition, in vitro a figure-of-eight artifact was obtained in all different types of disc occluder devices. Different types of percutaneous disc occluders all present as a figure-of-eight artifact on echocardiography when imaged from a coronal imaging position. The morphology of the artifact depends on the imaging depth, with a more asymmetric figure-of-eight morphology at smaller probe-to-device distance. This clarifies the differences observed between transesophageal and transthoracic imaging.
The European journal of general practice, Jan 9, 2015
Background: Most patients presenting chest complaints in primary care are referred to secondary c... more Background: Most patients presenting chest complaints in primary care are referred to secondary care facilities, whereas only a few are diagnosed with acute coronary syndrome (ACS). Objectives: The aim is to determine the optimal cut-off value for a point-of-care heart-type fatty acid binding protein (H-FABP) test in patients presenting to the emergency department and to evaluate a possible future role of H-FABP in safely ruling out ACS in primary care. Methods: Serial plasma H-FABP (index test) and high sensitivity troponin T (hs-cTnT) (reference test) were determined in patients with any new-onset chest complaint. In a receiver operating characteristic (ROC) curve, the optimal cut-off value of H-FABP for ACS was determined. Predictive values of H-FABP for ACS were calculated. Results: For 202 consecutive patients (prevalence ACS 59%), the ROC curve based on the results of the first H-FABP was equal to the ROC curve of hs-cTnT (AUC 0.79 versus 0.80). Using a cut-off value of 4.0 ng...
Probe DNA, consisting of a 36-mer fragment was covalently immobilized on nanocrystalline chemical... more Probe DNA, consisting of a 36-mer fragment was covalently immobilized on nanocrystalline chemical vapour deposition (CVD) diamond electrodes and hybridized with a 29-mer target DNA. In this paper, we report on the label-free real-time electronic monitoring of DNA denaturation upon exposure to NaOH at different flow rates and molarities, using electrochemical impedance spectroscopy as readout technology. The impedance response was separated into a denaturation time constant and a medium exchange time constant by means of a double exponential fit. It was observed that the denaturation time is dependent on the flow rate as well as on the molarity of the NaOH. Surprisingly, it was observed that at low molarities (0.05 M) the DNA does not fully denature at low flow rates. Only after flushing the flow cell a second time with 0.05 M NaOH, complete denaturation was achieved. Confocal images were obtained and plotted in 3D graphs to confirm the results. This paper provides a systematic overview of measured denaturation times for different flow rates and at different molarities of NaOH. Optimization of these parameters can be a valuable asset in the field of mutation analysis.
This paper focuses on the characterization of the ZnO/poly(3hexylthiophene) (P3HT) interfaces in ... more This paper focuses on the characterization of the ZnO/poly(3hexylthiophene) (P3HT) interfaces in nanostructured hybrid solar cells, aiming to elucidate the relationship between thermal treatment, local morphology, and device performance. An equivalent impedimetric model for the device is proposed, allowing us to extract information about the ZnO/P3HT interface morphology and its impact on the photovoltaic properties by comparing devices with and without nanopatterning. It is found that the influence of thermal treatment on performance lies solely in the interface, resulting from a different interfacial morphology of P3HT depending on which crystal direction of ZnO is present.
The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assess... more The high prevalence of cardiovascular diseases (CVD) demands a reliable and sensitive risk assessment technique. In order to develop a fast and label-free immunosensor for C-reactive protein (CRP), a risk factor for this condition, anti-CRP antibodies were physically adsorbed to the hydrogen (H)-terminated surface of nanocrystalline diamond (NCD). An Enzyme-Linked ImmunoSorbent Assay (ELISA) reference technique showed that this was a suitable substrate for antibody–antigen recognition reactions. Electrochemical Impedance Spectroscopy (EIS) was used to electronically detect CRP recognition. The specificity of the immunosensor was demonstrated by incubation with CRP and plasminogen as reference molecule. A different impedance behavior was observed in real-time after CRP addition as compared to plasminogen addition: the impedance increased only during CRP incubation. Fitting the data showed that this corresponded with a decrease in capacitance of the molecular layer due to its increase...
Journal of the American College of Cardiology, 2014
background: Restrictive mitral valve annuloplasty (RMA) is the surgical treatment of choice for s... more background: Restrictive mitral valve annuloplasty (RMA) is the surgical treatment of choice for severe functional mitral regurgitation, yet postoperative mitral stenosis remains debated. The aim of this study was to evaluate the evolution of the mean transmitral gradient and effective mitral valve area (MVA) during exercise in RMA patients compared with fixed prosthetic orifices. methods: Consecutive RMA patients (n=39) underwent a symptom-limited bicycle exercise test with stepwise Doppler echocardiography. At each stage of exercise transmitral flow rate, mean transmitral gradient and effective MVA were assessed.
2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), 2015
A new technique to monitor the fluid status of congestive heart failure (CHF) patients in the hos... more A new technique to monitor the fluid status of congestive heart failure (CHF) patients in the hospital is proposed and verified in a clinical trial with 8 patients. A wearable Bio-impedance (BioZ) sensor allows a continuous localized measurement which can be complement clinical tools in the hospital. Thanks to the multi-parametric approach and correlation analysis with clinical reference, BioZ is successfully shown as a promising parameter for continuous and wearable CHF patient monitoring application.
Physica Status Solidi (A) Applications and Materials
A new impedance spectroscopy unit is developed, fully customized to become a vital part of label ... more A new impedance spectroscopy unit is developed, fully customized to become a vital part of label free biosensor arrays with possible applications in DNA and protein sensing. Test measurements are conducted to explore the accuracy and specificity of the system, both under electronic lab conditions as well as under wet cell conditions with synthetic-diamond based sensor electrodes. The impedance of seven resistors was monitored for 17 h and a maximum error <0.02% was found. Furthermore, the impedance of PBS at different concentrations was monitored for 60 min per concentration and a different impedance for each concentration was detected. The impedance is also monitored for NaOH, PBS and nuclease free water at different temperatures with a total duration of 60 min per fluid. Systematically different impedances for each temperature per fluid were found and the temperature coefficients were determined. All test measurements lead to results well within specification.
Physica Status Solidi (A) Applications and Materials
The study of protein adsorption on solid surfaces is interesting for theoretical and practical bi... more The study of protein adsorption on solid surfaces is interesting for theoretical and practical bio-analytical sensing applications. In this work we combine electrochemical impedance spectroscopy, enzyme linked immunosorbent assay, and fluorescence microscopy with thin boron doped nanocrystalline diamond films to address and study the adsorption behavior of globular proteins (antibodies) on hydrophobic and hydrophilic diamond surfaces. A powerful combination of time resolved impedance spectroscopy and data modeling with equivalent circuits allow a detailed insight in the protein behavior at an interface. It is found that hydrogenated diamond is greatly favorable for impedimetric read-out but causes slight conformational loss of the protein structure and therefore also its biological activity. The oxidized surface allows faster adsorption and a high biological activity but results in smaller impedimetric response.
Our aim was to test if intra-thoracic impedance (ITI) measurements would improve short-term clini... more Our aim was to test if intra-thoracic impedance (ITI) measurements would improve short-term clinical outcome (i.e. all-cause mortality and heart failure hospitalizations) in patients with cardiac resynchronization therapy (CRT) who were followed in a telemonitoring program with structural biofeedback. Methods: CRT patients (n=200; age= 70 +/-14y) were included in a telemonitoring program at Ziekenhuis Oost-Limburg Genk, which comprised daily transmissions through a wireless system installed at their homes. All patients were followed for potential lead/device problems, episodes of anti-tachycardia pacing, device shocks, occurrence of arrhytmias, a decline in biventricular pacing percentage and/or a sudden drop in physical activity. Patients with missed transmissions were contacted by phone. Devices with ITI measurement ability were implanted in 108 patients. Those provided extra alerts when pre-specified ITI tresholds were crossed during at least 7 days. Heart failure nurses checked ...
Journal of the American College of Cardiology, Jan 3, 2015
The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptom... more The current understanding of heart failure (HF) does not fully explain the spectrum of HF symptoms. Most HF hospitalizations are related to sodium (Na(+)) and fluid retention resulting from neurohumoral up-regulation. Recent insights suggest that Na(+) is not distributed in the body solely as a free cation, but that it is also bound to large interstitial glycosaminoglycan (GAG) networks in different tissues, which have an important regulatory function. In HF, high Na(+) intake and neurohumoral alterations disrupt GAG structure, leading to loss of the interstitial buffer capacity and disproportionate interstitial fluid accumulation. Moreover, a diminished endothelial GAG network (the endothelial glycocalyx) results in increased vascular resistance and disturbed endothelial nitric oxide production. New imaging modalities can help evaluate interstitial Na(+) and endothelial glycocalyx integrity. Furthermore, several therapies have been proven to stabilize interstitial GAG networks. Hen...
In this article, we report on the electronic monitoring of DNA denaturation by NaOH using electro... more In this article, we report on the electronic monitoring of DNA denaturation by NaOH using electrochemical impedance spectroscopy in combination with fluorescence imaging as a reference technique. The probe DNA consisting of a 36-mer fragment was covalently immobilized on nanocrystalline-diamond electrodes and hybridized with different types of 29-mer target DNA (complementary, single-nucleotide defects at two different positions, and a non-complementary random sequence). The mathematical separation of the impedimetric signals into the time constant for NaOH exposure and the intrinsic denaturation-time constants gives clear evidence that the denaturation times reflect the intrinsic stability of the DNA duplexes. The intrinsic time constants correlate with calculated DNA-melting temperatures. The impedimetric method requires minimal instrumentation, is label-free and fast with a typical time scale of minutes and is highly reproducible. The sensor electrodes can be used repetitively. These elements suggest that the monitoring of chemically induced denaturation at room temperature is an interesting approach to measure DNA duplex stability as an alternative to thermal denaturation at elevated temperatures, used in DNA-melting experiments and single nucleotide polymorphism (SNP) analysis.
In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation... more In this article, we report on the heat-transfer resistance at interfaces as a novel, denaturation-based method to detect single-nucleotide polymorphisms in DNA. We observed that a molecular brush of double-stranded DNA grafted onto synthetic diamond surfaces does not notably affect the heattransfer resistance at the solid-to-liquid interface. In contrast to this, molecular brushes of singlestranded DNA cause, surprisingly, a substantially higher heat-transfer resistance and behave like a thermally insulating layer. This effect can be utilized to identify ds-DNA melting temperatures via the switching from low-to high heat-transfer resistance. The melting temperatures identified with this method for different DNA duplexes (29 base pairs without and with built-in mutations) correlate nicely with data calculated by modeling. The method is fast, label-free (without the need for fluorescent or radioactive markers), allows for repetitive measurements, and can also be extended toward array formats. Reference measurements by confocal fluorescence microscopy and impedance spectroscopy confirm that the switching of heat-transfer resistance upon denaturation is indeed related to the thermal on-chip denaturation of DNA.
The quest for a good natural user interface (NUI) between healthcare provider and technology is e... more The quest for a good natural user interface (NUI) between healthcare provider and technology is extremely important and will determine by enlarge its acceptance in clinical practice. Combining human gestures and voice commands may provide an interesting solution for human interaction with high tech clinical equipment. As proof of concept we focused on the setting of the cardiac catheterization laboratory where many interactions are required in reviewing the fluoroscopic cine-recordings. The new Kinect from Windows was used to develop a protocol allowing real-time interaction between the interventional cardiologist and the imaging software of the fluoroscopic image viewer. These interactions were based on single arm gestures to limit interference with invasive procedures. In situations where the cardiologist is unable to free up his hand, voice commands could be activated to execute the required actions. This natural user interface platform improved the efficiency in the catheterizat...
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Papers by Lars Grieten