ABSTRACT Polydimethylsiloxane (PDMS) is a widely used polymer for medical implants due to its exc... more ABSTRACT Polydimethylsiloxane (PDMS) is a widely used polymer for medical implants due to its excellent physical properties, low cost and ease of fabrication. However, in some applications the hydrophobic nature of the material remains an issue. To increase PDMS hydrophillicity, a variety of surface treatments based on plasma discharge have been proposed. In this study, we investigated the effect of water-vapor based plasma on PDMS surfaces. Surface topography was analyzed by means of atomic force microscopy (AFM) while surface chemistry was obtained by Fourier transform infrared spectroscopy (FTIR). To analyze the stability of the treatment, surface wettability was assessed over a period of seven months by contact angle measurement. Furthermore, using primary human fibroblasts,in vitro cell growth and morphology was investigated. It was found that plasma treament produced long-term stable hydrophillic surfaces (contact angle between 70° to 80°). This property was correlated with hydroxylation of the surface and was accompanied by a slight increase in RMS roughness. Concomitantly, there was a significant increase in the number of cells growing on the plasma-treated surfaces, which was linked with a more spread cellular morphology. The results presented here suggest that water-vapor plasma treatment may be useful to enhance cell adhesion on PDMS implants.
Neuromodulation : journal of the International Neuromodulation Society, Jan 14, 2018
As the left vagus nerve (LVN) mediates a baroreflex blood pressure (BP) decrease, LVN stimulation... more As the left vagus nerve (LVN) mediates a baroreflex blood pressure (BP) decrease, LVN stimulation (LVNS) could be a therapy for hypertension. Moreover, LVNS could elegantly be adjusted to the patient's actual BP and physical activity by using the neural information about BP and respiration extractable from LVN. However, unselective LVNS will trigger undesirable side-effects and therefore we here investigated the feasibility of using an intraneural electrode for extracting BP and respiration markers from the LVN and for selective LVNS. Experiments were performed on six anesthetized pigs from which the BP was recorded using arterial catheters and the respiratory cycles by recording the airway pressure. An electrode comprising four tripolar channels was inserted longitudinally in the LVN of the animals to extract BP and respiration markers from the LVN and for selective LVNS. BP-related and respiratory-related neural profiles (BPnPs and RnPs, respectively) were derived from at leas...
Diagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. A... more Diagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. Acoustic analysis of transcutaneous heart sounds of cardiac movement and intracoronary turbulence due to obstructive coronary disease could potentially change this. The aim of this study was thus to test the diagnostic accuracy of a new portable acoustic device for detection of CAD. We included 1675 patients consecutively with low to intermediate likelihood of CAD who had been referred for cardiac CT angiography. If significant obstruction was suspected in any coronary segment, patients were referred to invasive angiography and fractional flow reserve (FFR) assessment. Heart sound analysis was performed in all patients. A predefined acoustic CAD-score algorithm was evaluated; subsequently, we developed and validated an updated CAD-score algorithm that included both acoustic features and clinical risk factors. Low risk is indicated by a CAD-score value ≤20. Haemodynamically significant CAD...
Neuromodulation: Technology at the Neural Interface
Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in... more Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings. The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms. The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (Rvalues between 0.85 and 0.99). The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems.
Because of ambiguous reports in the literature, we aimed to investigate the association between P... more Because of ambiguous reports in the literature, we aimed to investigate the association between PR interval and the risk of all-cause and cardiovascular death, heart failure, and pacemaker implantation, allowing for a nonlinear relationship. We included 293,111 individuals, corresponding to one-third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram recorded in a general practitioner's core facility from 2001-2011. Data on drug use, comorbidities, and outcomes were collected from Danish registries. We divided the population into 7 groups based on the population PR interval distribution. Cox models were used, with reference to a PR interval between 152 and 161 ms (40th to < 60th percentile). During follow-up, we identified 34,783 deaths from all causes, 9867 cardiovascular deaths, 9526 cases of incident heart failure, and 1805 pacemaker implantations. A short PR interval (< 125 ms; hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.08-1.41; P = 0.001) as well as a long PR interval (> 200 ms; HR, 1.23; 95% CI, 1.14-1.32; P < 0.001) was associated with an increased risk of cardiovascular death after multivariable adjustment. A long PR interval conferred an increased risk of heart failure (> 200 ms; HR, 1.31; 95% CI, 1.22-1.42; P < 0.001). An increasing PR interval conferred an increased risk of pacemaker implantation, in a dose-response manner, with the highest risk associated with a PR interval > 200 ms (HR, 3.49; 95% CI, 2.96-4.11; P < 0.001). PR interval was significantly associated with the risk of the adverse outcomes investigated. The nonlinear relationships, in combination with relatively weak associations, could contribute to previously reported conflicting results on the subject.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, Jan 13, 2017
To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones. The... more To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones. The present retrospective study took place in an anechoic chamber facility at Aalborg University, Aalborg, Denmark, in 2012, and included pregnant participants aged 18-40 years with a singleton pregnancy at 32-36 weeks and a parity of 0-2. Abdominal Doppler ultrasonography was performed bilaterally on the uterine arteries. Subsequently, in the same positions, sound recordings were performed with microphones. The derived raw sound signal was separated into two frequency ranges, and characterized accordingly. The mean pregnancy length among 25 participants was 33.6 ± 2.0 weeks. The pulsatility index of the uterine artery was 0.67 ± 0.24. All 50 recordings displayed the first and second maternal heart sounds (frequency 25-100 Hz), and in 17 of 50 recordings, maternal vascular murmurs (frequency 200-800 Hz) were present. The average pulse wave velocity between the maternal aortic valve and the ...
Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, Jan 27, 2016
Recently, numerous models and techniques have been developed for analyzing and extracting feature... more Recently, numerous models and techniques have been developed for analyzing and extracting features from the T wave which could be used as biomarkers for drug-induced abnormalities. The majority of these techniques and algorithms use features that determine readily apparent characteristics of the T wave, such as duration, area, amplitude, and slopes. In the present work the T wave was down-sampled to a minimal rate, such that a good reconstruction was still possible. The entire T wave was then used as a feature vector to assess drug-induced repolarization effects. The ability of the samples or combinations of samples obtained from the minimal T-wave representation to correctly classify a group of subjects before and after receiving d,l-sotalol 160 mg and 320 mg was evaluated using a linear discriminant analysis (LDA). The results showed that a combination of eight samples from the minimal T-wave representation can be used to identify normal from abnormal repolarization significantly ...
Ictal tachycardia (IT) is common and may pave the way towards cardiac conditions with high risk p... more Ictal tachycardia (IT) is common and may pave the way towards cardiac conditions with high risk potential. However, the mechanisms of IT remain obscure and therefore difficult to control. For example, whereas IT is associated with a sympathetic surge, it is unclear why the IT effects are not opposed by baroreflex cardiac inhibition during seizures. As the vagus nerves (VN) are main mediators for such baroreflexes, this study was performed to investigate the VN activity in IT. The present experiments were performed in ten pigs where IT seizures were induced by controlled infusion of pentylenetetrazole. The electrocorticogram was recorded using a cranial electrode, the electrocardiogram (ECG) using surface electrodes and the blood pressure (BP) using a catheter inserted in the right carotid artery. The VN activity was recorded from both nerves using cuff electrodes and further analyzed in correlation with the cortical seizures and the associated heart rate (HR), BP and HR variability ...
Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fib... more Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fibres. For example, nerve fibres are usually assumed to be perfectly straight. Such idealizations can cause discrepancies between theoretical predictions and experimental results. One well-known discrepancy is that the currently used models predict (contradictory to experimental findings) that an activation of nerve fibres is not possible with a pure transverse electric field. This situation occurs when a magnetic coil is placed symmetrically above a straight nerve fibre for magnetic nerve stimulation, or when an anode and a cathode are placed equidistantly on a line perpendicular to the fibre in the case of electrical stimulation. It is shown that this discrepancy does not occur if the physiological undulation of peripheral nerve fibres is included in the models. Even for small undulation amplitudes (e.g. 0.02 mm), it is possible to activate the fibre in these positions. For physiological undulations, as found in the literature, and favourable (off-centre) positions, the typical reduction of the thresholds is in a range between one and five, compared with perfectly straight fibres.
Heart rate (HR) at rest is a well-known marker of cardiovascular morbidity and mortality. Results... more Heart rate (HR) at rest is a well-known marker of cardiovascular morbidity and mortality. Results on the association between HR and incident atrial fibrillation (AF) have, however, been conflicting. Using digital electrocardiograms from 281,451 primary care patients, we aimed to describe the association between HR at rest and the hazards of incident AF. Secondary end points were death from all causes and pacemaker implantation. Data on drug use, co-morbidity, and outcomes were collected from nationwide administrative health care registries. During a median follow-up time of 8.4 years, 15,666 subjects were observed to develop AF, of which 1,631 were lone AF. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.16 (95% CI 1.06 to 1.27) for AF compared with the reference group (66 to 72 beats/min). From 72 beats/min and upward, the hazard ratio of AF increased in a dose-response manner, reaching an adjusted hazard ratio of 1.36 (95% CI 1.26 to 1.46) for HR between 95 and 120 beats/min. Both for low and high HR, the associations were accentuated for the outcome lone AF (adjusted hazard ratios of 1.48, 95% CI 1.19 to 1.84 and 1.84, 95% CI 1.47 to 2.30 for HR between 30 to 51 and 95 to 120 beats/min, respectively). For death from all causes, the hazard increased almost linearly with increasing HR. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.80 (95% CI 1.46 to 2.21) for pacemaker implantation. In conclusion, a U-shaped association was found between HR at rest and incident AF, and this association was strongest for the outcome lone AF.
Journal of Cardiovascular Electrophysiology, Dec 13, 2013
Phrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activat... more Phrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activation characteristics of the heart and phrenic nerve are different with higher chronaxie for the heart. Therefore, longer pulse durations could be beneficial in preventing phrenic nerve stimulation during CRT due to a decreased threshold for the heart compared with the phrenic nerve. We investigated if long pulse durations decreased left ventricular (LV) thresholds relatively to phrenic nerve thresholds in humans. Eleven patients, with indication for CRT and phrenic nerve stimulation at the intended pacing site, underwent determination of thresholds for the heart and phrenic nerve at different pulse durations (0.3-2.9 milliseconds). The resulting strength duration curves were analyzed by determining chronaxie and rheobase. Comparisons for those parameters were made between the heart and phrenic nerve, and between the models of Weiss and Lapicque as well. In 9 of 11 cases, the thresholds decreased faster for the LV than for the phrenic nerve with increasing pulse duration. In 3 cases, the thresholds changed from unfavorable for LV stimulation to more than a factor 2 in favor of the LV. The greatest change occurred for pulse durations up to 1.5 milliseconds. The chronaxie of the heart was significantly higher than the chronaxie of the phrenic nerve (0.47 milliseconds vs. 0.22 milliseconds [P = 0.029, Lapicque] and 0.79 milliseconds vs. 0.27 milliseconds [P = 0.033, Weiss]). Long pulse durations lead to a decreased threshold of the heart relatively to the phrenic nerve and may prevent stimulation of the phrenic nerve in a clinical setting.
ABSTRACT Polydimethylsiloxane (PDMS) is a widely used polymer for medical implants due to its exc... more ABSTRACT Polydimethylsiloxane (PDMS) is a widely used polymer for medical implants due to its excellent physical properties, low cost and ease of fabrication. However, in some applications the hydrophobic nature of the material remains an issue. To increase PDMS hydrophillicity, a variety of surface treatments based on plasma discharge have been proposed. In this study, we investigated the effect of water-vapor based plasma on PDMS surfaces. Surface topography was analyzed by means of atomic force microscopy (AFM) while surface chemistry was obtained by Fourier transform infrared spectroscopy (FTIR). To analyze the stability of the treatment, surface wettability was assessed over a period of seven months by contact angle measurement. Furthermore, using primary human fibroblasts,in vitro cell growth and morphology was investigated. It was found that plasma treament produced long-term stable hydrophillic surfaces (contact angle between 70° to 80°). This property was correlated with hydroxylation of the surface and was accompanied by a slight increase in RMS roughness. Concomitantly, there was a significant increase in the number of cells growing on the plasma-treated surfaces, which was linked with a more spread cellular morphology. The results presented here suggest that water-vapor plasma treatment may be useful to enhance cell adhesion on PDMS implants.
Neuromodulation : journal of the International Neuromodulation Society, Jan 14, 2018
As the left vagus nerve (LVN) mediates a baroreflex blood pressure (BP) decrease, LVN stimulation... more As the left vagus nerve (LVN) mediates a baroreflex blood pressure (BP) decrease, LVN stimulation (LVNS) could be a therapy for hypertension. Moreover, LVNS could elegantly be adjusted to the patient's actual BP and physical activity by using the neural information about BP and respiration extractable from LVN. However, unselective LVNS will trigger undesirable side-effects and therefore we here investigated the feasibility of using an intraneural electrode for extracting BP and respiration markers from the LVN and for selective LVNS. Experiments were performed on six anesthetized pigs from which the BP was recorded using arterial catheters and the respiratory cycles by recording the airway pressure. An electrode comprising four tripolar channels was inserted longitudinally in the LVN of the animals to extract BP and respiration markers from the LVN and for selective LVNS. BP-related and respiratory-related neural profiles (BPnPs and RnPs, respectively) were derived from at leas...
Diagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. A... more Diagnosing coronary artery disease (CAD) continues to require substantial healthcare resources. Acoustic analysis of transcutaneous heart sounds of cardiac movement and intracoronary turbulence due to obstructive coronary disease could potentially change this. The aim of this study was thus to test the diagnostic accuracy of a new portable acoustic device for detection of CAD. We included 1675 patients consecutively with low to intermediate likelihood of CAD who had been referred for cardiac CT angiography. If significant obstruction was suspected in any coronary segment, patients were referred to invasive angiography and fractional flow reserve (FFR) assessment. Heart sound analysis was performed in all patients. A predefined acoustic CAD-score algorithm was evaluated; subsequently, we developed and validated an updated CAD-score algorithm that included both acoustic features and clinical risk factors. Low risk is indicated by a CAD-score value ≤20. Haemodynamically significant CAD...
Neuromodulation: Technology at the Neural Interface
Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in... more Left vagus nerve (LVN) stimulation (LVNS) has been tested for lowering the blood pressure (BP) in patients with resistant hypertension (RH). Whereas, closed-loop LVNS (CL-LVNS) driven by a BP marker may be superior to open-loop LVNS, there are situations (e.g., exercising) when hypertension is normal. Therefore, an ideal anti-RH CL-LVNS system requires a variable to avoid stimulation in such conditions, for example, a respiratory marker ideally extracted from the LVN. As the LVN conducts respiratory signals, this study aimed to investigate if such signals can be recorded using implantable means and if a marker to monitor respiration could be derived from such recordings. The experiments were performed in 14 anesthetized pigs. Five pigs were subjected to changes of the respiratory frequency and nine to changes of the respiratory volume. The LVN electroneurogram (VENG) was recorded using two cuff electrodes and the respiratory cycles (RC) using a pressure transducer. To separate the afferent and efferent VENGs, vagotomy was performed between the cuffs in the first group of pigs. The VENG was squared to derive respiration-related neural profiles (RnPs) and their correlation with the RCs was investigated in regard to timing and magnitude parameters derived from the two waveforms. The RnPs were morphologically similar with the RCs and the average RnPs represented accurate copies of the average RCs. Consequently, the lung inflation/deflation RC and RnP components had the same duration, the respiratory frequency changes affected in the same way both waveforms and the RnP amplitude increased linearly with the lung inflation in all tested pigs (Rvalues between 0.85 and 0.99). The RnPs comprise information regarding the timing and magnitude of the respiratory parameters. As those LVN profiles were derived using implantable means, this study indicates that the RnPs could serve as respiratory markers in implantable systems.
Because of ambiguous reports in the literature, we aimed to investigate the association between P... more Because of ambiguous reports in the literature, we aimed to investigate the association between PR interval and the risk of all-cause and cardiovascular death, heart failure, and pacemaker implantation, allowing for a nonlinear relationship. We included 293,111 individuals, corresponding to one-third of the population in the greater region of Copenhagen. These individuals had a digital electrocardiogram recorded in a general practitioner's core facility from 2001-2011. Data on drug use, comorbidities, and outcomes were collected from Danish registries. We divided the population into 7 groups based on the population PR interval distribution. Cox models were used, with reference to a PR interval between 152 and 161 ms (40th to < 60th percentile). During follow-up, we identified 34,783 deaths from all causes, 9867 cardiovascular deaths, 9526 cases of incident heart failure, and 1805 pacemaker implantations. A short PR interval (< 125 ms; hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.08-1.41; P = 0.001) as well as a long PR interval (> 200 ms; HR, 1.23; 95% CI, 1.14-1.32; P < 0.001) was associated with an increased risk of cardiovascular death after multivariable adjustment. A long PR interval conferred an increased risk of heart failure (> 200 ms; HR, 1.31; 95% CI, 1.22-1.42; P < 0.001). An increasing PR interval conferred an increased risk of pacemaker implantation, in a dose-response manner, with the highest risk associated with a PR interval > 200 ms (HR, 3.49; 95% CI, 2.96-4.11; P < 0.001). PR interval was significantly associated with the risk of the adverse outcomes investigated. The nonlinear relationships, in combination with relatively weak associations, could contribute to previously reported conflicting results on the subject.
International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, Jan 13, 2017
To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones. The... more To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones. The present retrospective study took place in an anechoic chamber facility at Aalborg University, Aalborg, Denmark, in 2012, and included pregnant participants aged 18-40 years with a singleton pregnancy at 32-36 weeks and a parity of 0-2. Abdominal Doppler ultrasonography was performed bilaterally on the uterine arteries. Subsequently, in the same positions, sound recordings were performed with microphones. The derived raw sound signal was separated into two frequency ranges, and characterized accordingly. The mean pregnancy length among 25 participants was 33.6 ± 2.0 weeks. The pulsatility index of the uterine artery was 0.67 ± 0.24. All 50 recordings displayed the first and second maternal heart sounds (frequency 25-100 Hz), and in 17 of 50 recordings, maternal vascular murmurs (frequency 200-800 Hz) were present. The average pulse wave velocity between the maternal aortic valve and the ...
Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc, Jan 27, 2016
Recently, numerous models and techniques have been developed for analyzing and extracting feature... more Recently, numerous models and techniques have been developed for analyzing and extracting features from the T wave which could be used as biomarkers for drug-induced abnormalities. The majority of these techniques and algorithms use features that determine readily apparent characteristics of the T wave, such as duration, area, amplitude, and slopes. In the present work the T wave was down-sampled to a minimal rate, such that a good reconstruction was still possible. The entire T wave was then used as a feature vector to assess drug-induced repolarization effects. The ability of the samples or combinations of samples obtained from the minimal T-wave representation to correctly classify a group of subjects before and after receiving d,l-sotalol 160 mg and 320 mg was evaluated using a linear discriminant analysis (LDA). The results showed that a combination of eight samples from the minimal T-wave representation can be used to identify normal from abnormal repolarization significantly ...
Ictal tachycardia (IT) is common and may pave the way towards cardiac conditions with high risk p... more Ictal tachycardia (IT) is common and may pave the way towards cardiac conditions with high risk potential. However, the mechanisms of IT remain obscure and therefore difficult to control. For example, whereas IT is associated with a sympathetic surge, it is unclear why the IT effects are not opposed by baroreflex cardiac inhibition during seizures. As the vagus nerves (VN) are main mediators for such baroreflexes, this study was performed to investigate the VN activity in IT. The present experiments were performed in ten pigs where IT seizures were induced by controlled infusion of pentylenetetrazole. The electrocorticogram was recorded using a cranial electrode, the electrocardiogram (ECG) using surface electrodes and the blood pressure (BP) using a catheter inserted in the right carotid artery. The VN activity was recorded from both nerves using cuff electrodes and further analyzed in correlation with the cortical seizures and the associated heart rate (HR), BP and HR variability ...
Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fib... more Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fibres. For example, nerve fibres are usually assumed to be perfectly straight. Such idealizations can cause discrepancies between theoretical predictions and experimental results. One well-known discrepancy is that the currently used models predict (contradictory to experimental findings) that an activation of nerve fibres is not possible with a pure transverse electric field. This situation occurs when a magnetic coil is placed symmetrically above a straight nerve fibre for magnetic nerve stimulation, or when an anode and a cathode are placed equidistantly on a line perpendicular to the fibre in the case of electrical stimulation. It is shown that this discrepancy does not occur if the physiological undulation of peripheral nerve fibres is included in the models. Even for small undulation amplitudes (e.g. 0.02 mm), it is possible to activate the fibre in these positions. For physiological undulations, as found in the literature, and favourable (off-centre) positions, the typical reduction of the thresholds is in a range between one and five, compared with perfectly straight fibres.
Heart rate (HR) at rest is a well-known marker of cardiovascular morbidity and mortality. Results... more Heart rate (HR) at rest is a well-known marker of cardiovascular morbidity and mortality. Results on the association between HR and incident atrial fibrillation (AF) have, however, been conflicting. Using digital electrocardiograms from 281,451 primary care patients, we aimed to describe the association between HR at rest and the hazards of incident AF. Secondary end points were death from all causes and pacemaker implantation. Data on drug use, co-morbidity, and outcomes were collected from nationwide administrative health care registries. During a median follow-up time of 8.4 years, 15,666 subjects were observed to develop AF, of which 1,631 were lone AF. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.16 (95% CI 1.06 to 1.27) for AF compared with the reference group (66 to 72 beats/min). From 72 beats/min and upward, the hazard ratio of AF increased in a dose-response manner, reaching an adjusted hazard ratio of 1.36 (95% CI 1.26 to 1.46) for HR between 95 and 120 beats/min. Both for low and high HR, the associations were accentuated for the outcome lone AF (adjusted hazard ratios of 1.48, 95% CI 1.19 to 1.84 and 1.84, 95% CI 1.47 to 2.30 for HR between 30 to 51 and 95 to 120 beats/min, respectively). For death from all causes, the hazard increased almost linearly with increasing HR. A HR at rest from 30 to 51 beats/min was associated with an adjusted hazard ratio of 1.80 (95% CI 1.46 to 2.21) for pacemaker implantation. In conclusion, a U-shaped association was found between HR at rest and incident AF, and this association was strongest for the outcome lone AF.
Journal of Cardiovascular Electrophysiology, Dec 13, 2013
Phrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activat... more Phrenic nerve stimulation is a major obstacle in cardiac resynchronization therapy (CRT). Activation characteristics of the heart and phrenic nerve are different with higher chronaxie for the heart. Therefore, longer pulse durations could be beneficial in preventing phrenic nerve stimulation during CRT due to a decreased threshold for the heart compared with the phrenic nerve. We investigated if long pulse durations decreased left ventricular (LV) thresholds relatively to phrenic nerve thresholds in humans. Eleven patients, with indication for CRT and phrenic nerve stimulation at the intended pacing site, underwent determination of thresholds for the heart and phrenic nerve at different pulse durations (0.3-2.9 milliseconds). The resulting strength duration curves were analyzed by determining chronaxie and rheobase. Comparisons for those parameters were made between the heart and phrenic nerve, and between the models of Weiss and Lapicque as well. In 9 of 11 cases, the thresholds decreased faster for the LV than for the phrenic nerve with increasing pulse duration. In 3 cases, the thresholds changed from unfavorable for LV stimulation to more than a factor 2 in favor of the LV. The greatest change occurred for pulse durations up to 1.5 milliseconds. The chronaxie of the heart was significantly higher than the chronaxie of the phrenic nerve (0.47 milliseconds vs. 0.22 milliseconds [P = 0.029, Lapicque] and 0.79 milliseconds vs. 0.27 milliseconds [P = 0.033, Weiss]). Long pulse durations lead to a decreased threshold of the heart relatively to the phrenic nerve and may prevent stimulation of the phrenic nerve in a clinical setting.
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Papers by Johannes Struijk