- Email: [email protected]
Sustained Improvements toVentricular Function Due to Asymptomatic Diaphragmatic Stimulation
S120 Journal of Cardiac Failure Vol. 23 No. 8S August 2017
Surgery/Transplantation/Devices 335 Animal Instrumentation Model of Diaphragmatic Stimulation Effects on Cardiovascular Function Peter Bauer1, Jay Snell1, Tim Wheeler1, Ed Chinchoy1, Mike Mirro2; 1Viscardia, Beaverton, Oregon; 2Indiana University, Fort Wayne, Indiana Introduction: Diaphragmatic Stimulation (DS) is a novel heart failure therapy concept under investigation. Diaphragmatic contractions have been previously shown to alter systolic and diastolic function, venous filling and compliance, and arterial resistance. By electrically stimulating the diaphragm to modulate intrathoracic pressures (ITP), mechanical forces are directly applied to all the organs and vessels within the thoracic cavity including the atria, ventricles, and major vessels. No standard animal instrumentation model exists to study diaphragmatic stimulation as a treatment for heart failure, so a series of experiments were undertaken to identify the most sensitive parameters to ITP modulation using standard cardiovascular hemodynamic parameters. The results will be used to optimize diaphragmatic stimulation effects in an animal heart failure model and human clinical studies. Hypothesis: DS therapy appropriately timed to the cardiac cycle alters hemodynamics. Methods: Sixteen mongrel swine were anesthetized using isoflourane and ventilated. A sutureless, bipolar sensing/ pacing lead was affixed to the left inferior diaphragm via laparoscopy. Milllar pressure catheters were positioned in a variety of locations including the right atrium, right ventricle, left ventricle and aorta. Cardiac output was determined using a thermodilution bolus or continuously via catheter thermistors. ITP was measured using a Millar pressure catheter via the Murphy procedure. Volume overload status was achieved using a 3L intravenous saline venous introduction. Hemodynamic measurements were made at baseline and with diaphragmatic pacing output timing varied relative to sensed R waves. Results: Intrathoracic pressure changes of up to 20% of ITP changes due to respiration were observed when stimulation was applied synchronously upon end diastole. Modifications of early and late LV diastolic filling were reflected in LV pressure traces with cardiac output increases of up to 25% and 10% in LV max dP/dt, with more pronounced effects observed in the volume overload model. Changes in right atrial and right ventricular pressure morphologies occurred contemporaneous to ITP pulsatile alterations suggesting increased venous return. Conclusions: Diaphragmatic stimulation appropriately timed to the cardiac cycle affected hemodynamic waveform morphologies in all chambers instrumented, with changes to cardiac output predominantly through modulation of intrathoracic pressure.
336 Sustained Improvements toVentricular Function Due to Asymptomatic Diaphragmatic Stimulation Remo Beeler1, Andreas Schoenenberger2, Michel Zuber1, Peter Bauer3, Susanne Erne4, Reinhard Schlaepfer4, Paul Erne5; 1University Heart Center, Zurich, Switzerland; 2 Inselpital, Bern, Switzerland; 3Viscardia, Beaverton, Oregon; 4Luzerner Kantonsspital, Luzern, Switzerland; 5Basel University Hospital, Basel, Switzerland Introduction: Asymptomatic Diaphragmatic Stimulation (ADS) for modulating intrathoracic pressures to augment cardiovascular hemodynamics is a novel heart failure therapy concept under investigation. The Epiphrenic II pilot previously demonstrated ADS improved cardiac hemodynamics after 3 weeks in moderate heart failure patients with reduced ejection fraction, incremental to CRT. Hypothesis: Cardiac hemodynamic improvements from continuous ADS therapy can be sustained for one year. Methods: CRT was applied using clinically standard programming of simultaneous biventricular pacing with AV delays optimized to maximize LV filling. ADS was provided via a separate electrode surgically affixed to the diaphragm. ADS stimulation outputs were determined by using a clinical assessment of the minimum output required to evoke a palpable yet asymptomatic diaphragmatic response. Therapy was synchronized to left ventricular activation for each cardiac cycle. Echocardiographic parameters were collected and analyzed offline in a blinded manner by an independent investigator. Upon completion of the randomized protocol for the study, patients were unblinded and provided the elective option to continue with CRT or CRT+ADS on a chronic continual basis and invited for a routine follow-up examination after one year. Results: All the 24 patients which completed the formal protocol elected to maintain CRT+ADS therapy and all were alive at their 1 year follow-up date. Five refused the follow-up examination and one had moved away, resulting in overall 18 patients one of which had ADS off due to non-ADS related device issues, producing 17 paired data sets with adjudicated continual CRT+ADS. Four patients had prior respiratory diseases known to affect diaphragmatic function (3 with COPD, 1 lung resection) and analyzed in a separate subgroup. Conclusions: In all patients, CRT+ADS was preferred over CRT alone without noticeable adverse events related to diaphragmatic function. In patients without respiratory diseases, ADS provided sustained incremental improvements to cardiac function versus CRT alone. Although the sample size is limited, these promising results warrant further chronic studies of ADS as a heart failure treatment including the use of a control group versus an ADS-only therapy arm, and for greater durations of time, to properly quantify the isolated effects of ADS.
337 Stability of AsymptomaticDiaphragmatic Stimulation Thresholds after 1 Year: Results of the Epiphrenic IIPilot Remo Beeler1, Andreas Schoenenberger2, Michel Zuber1, Peter Bauer3, Susanne Erne4, Reinhard Schlaepfer4, Paul Erne5; 1University Heart Center, Zurich, Switzerland; 2 Inselpital, Bern, Switzerland; 3Viscardia, Beaverton, Oregon; 4Luzerner Kantonsspital, Luzern, Switzerland; 5Basel University Hospital, Basel, Switzerland Introduction: Asymptomatic Diaphragmatic Stimulation (ADS) is a heart failure therapy concept under investigation. Within a range of voltages, electrical stimulation of the diaphragm synchronized to the cardiac cycle alters cardiovascular hemodynamics including venous return and preload by modulating diaphragmatic movement and intrathoracic pressure. The Epiphrenic II pilot utilized a cross-over design to investigate the chronic effects of continuous ADS on cardiac function, including changes to the minimum pacing output required to asymptomatically capture the diaphragm. Hypothesis: Within one year diaphragmatic pacing voltage and pulse width would not change significantly. Methods: In the Epiphrenic II pilot, post CABG patients received CRT devices branched to provide ADS via an epicardial electrode surgically fixated to the left diaphragm. ADS stimulation outputs were determined by using a clinical assessment of the minimum output required to evoke a palpable subcostal yet asymptomatic diaphragmatic response. Therapy was synchronized to left ventricular activation for each cardiac cycle. Upon completion of the formal study protocol at 9 weeks post-implant, patients were provided the option to continue with ADS and CRT, and were invited for a routine follow-up examination at one year post implant. Results: All 24 patients receiving ADS at baseline were alive at their 1 year follow-up, but five refused the follow-up examination and one had relocated. Eighteen patients agreed to perform a one year follow-up, of which one had diaphragmatic pacing off due to nonADS related device issues, resulting in 17 paired data sets. Diaphragmatic pacing voltage and pulse width at 1 year were compared to those at 9 weeks post-implant. Capture thresholds were not significantly different between 9 weeks and 1 year (2.8 ± 0.8 vs 2.9 ± 0.9 V, paired t-test, P = .8), nor was pulse width significantly different (0.5 ± 0.3 vs 0.6 ± 0.3 msec, paired t-test, P = .1). Conclusions: This limited patient set suggests that asymptomatic diaphragmatic threshold values are stable during constant electrical stimulation, providing credence to the hypothesis the diaphragm can be continuously paced for over one year with no changes to stimulation output, which is a minimum requisite for ADS to reliably augment cardiac function chronically.
338 Gender Differences in the Risk of Stroke after Mechanical Circulatory Support Vanessa Blumer, Rodrigo Mendirichaga, Jorge Monge, Gabriel A. Hernandez, Sandra Chaparro; Univ. of Miami / Jackson Memorial Hospital, Miami, Florida Introduction: Mechanical circulatory support (MCS) devices have extended survival and improved quality of life for select patients with advanced heart failure. There have been concerns regarding the incidence of stroke after MCS, and some studies have suggested that female gender is a risk factor for the development of neurological complications. Methods: Using the Healthcare Cost and Utilization Project National Inpatient Sample database we identified patients requiring MCS implantation in United States hospitals from 2010–2014. Ischemic and hemorrhagic strokes were identified by previously validated coding algorithms. Multivariate logistic regression models were
Surgery/Transplantation/Devices 335 Animal Instrumentation Model of Diaphragmatic Stimulation Effects on Cardiovascular Function Peter Bauer1, Jay Snell1, Tim Wheeler1, Ed Chinchoy1, Mike Mirro2; 1Viscardia, Beaverton, Oregon; 2Indiana University, Fort Wayne, Indiana Introduction: Diaphragmatic Stimulation (DS) is a novel heart failure therapy concept under investigation. Diaphragmatic contractions have been previously shown to alter systolic and diastolic function, venous filling and compliance, and arterial resistance. By electrically stimulating the diaphragm to modulate intrathoracic pressures (ITP), mechanical forces are directly applied to all the organs and vessels within the thoracic cavity including the atria, ventricles, and major vessels. No standard animal instrumentation model exists to study diaphragmatic stimulation as a treatment for heart failure, so a series of experiments were undertaken to identify the most sensitive parameters to ITP modulation using standard cardiovascular hemodynamic parameters. The results will be used to optimize diaphragmatic stimulation effects in an animal heart failure model and human clinical studies. Hypothesis: DS therapy appropriately timed to the cardiac cycle alters hemodynamics. Methods: Sixteen mongrel swine were anesthetized using isoflourane and ventilated. A sutureless, bipolar sensing/ pacing lead was affixed to the left inferior diaphragm via laparoscopy. Milllar pressure catheters were positioned in a variety of locations including the right atrium, right ventricle, left ventricle and aorta. Cardiac output was determined using a thermodilution bolus or continuously via catheter thermistors. ITP was measured using a Millar pressure catheter via the Murphy procedure. Volume overload status was achieved using a 3L intravenous saline venous introduction. Hemodynamic measurements were made at baseline and with diaphragmatic pacing output timing varied relative to sensed R waves. Results: Intrathoracic pressure changes of up to 20% of ITP changes due to respiration were observed when stimulation was applied synchronously upon end diastole. Modifications of early and late LV diastolic filling were reflected in LV pressure traces with cardiac output increases of up to 25% and 10% in LV max dP/dt, with more pronounced effects observed in the volume overload model. Changes in right atrial and right ventricular pressure morphologies occurred contemporaneous to ITP pulsatile alterations suggesting increased venous return. Conclusions: Diaphragmatic stimulation appropriately timed to the cardiac cycle affected hemodynamic waveform morphologies in all chambers instrumented, with changes to cardiac output predominantly through modulation of intrathoracic pressure.
336 Sustained Improvements toVentricular Function Due to Asymptomatic Diaphragmatic Stimulation Remo Beeler1, Andreas Schoenenberger2, Michel Zuber1, Peter Bauer3, Susanne Erne4, Reinhard Schlaepfer4, Paul Erne5; 1University Heart Center, Zurich, Switzerland; 2 Inselpital, Bern, Switzerland; 3Viscardia, Beaverton, Oregon; 4Luzerner Kantonsspital, Luzern, Switzerland; 5Basel University Hospital, Basel, Switzerland Introduction: Asymptomatic Diaphragmatic Stimulation (ADS) for modulating intrathoracic pressures to augment cardiovascular hemodynamics is a novel heart failure therapy concept under investigation. The Epiphrenic II pilot previously demonstrated ADS improved cardiac hemodynamics after 3 weeks in moderate heart failure patients with reduced ejection fraction, incremental to CRT. Hypothesis: Cardiac hemodynamic improvements from continuous ADS therapy can be sustained for one year. Methods: CRT was applied using clinically standard programming of simultaneous biventricular pacing with AV delays optimized to maximize LV filling. ADS was provided via a separate electrode surgically affixed to the diaphragm. ADS stimulation outputs were determined by using a clinical assessment of the minimum output required to evoke a palpable yet asymptomatic diaphragmatic response. Therapy was synchronized to left ventricular activation for each cardiac cycle. Echocardiographic parameters were collected and analyzed offline in a blinded manner by an independent investigator. Upon completion of the randomized protocol for the study, patients were unblinded and provided the elective option to continue with CRT or CRT+ADS on a chronic continual basis and invited for a routine follow-up examination after one year. Results: All the 24 patients which completed the formal protocol elected to maintain CRT+ADS therapy and all were alive at their 1 year follow-up date. Five refused the follow-up examination and one had moved away, resulting in overall 18 patients one of which had ADS off due to non-ADS related device issues, producing 17 paired data sets with adjudicated continual CRT+ADS. Four patients had prior respiratory diseases known to affect diaphragmatic function (3 with COPD, 1 lung resection) and analyzed in a separate subgroup. Conclusions: In all patients, CRT+ADS was preferred over CRT alone without noticeable adverse events related to diaphragmatic function. In patients without respiratory diseases, ADS provided sustained incremental improvements to cardiac function versus CRT alone. Although the sample size is limited, these promising results warrant further chronic studies of ADS as a heart failure treatment including the use of a control group versus an ADS-only therapy arm, and for greater durations of time, to properly quantify the isolated effects of ADS.
337 Stability of AsymptomaticDiaphragmatic Stimulation Thresholds after 1 Year: Results of the Epiphrenic IIPilot Remo Beeler1, Andreas Schoenenberger2, Michel Zuber1, Peter Bauer3, Susanne Erne4, Reinhard Schlaepfer4, Paul Erne5; 1University Heart Center, Zurich, Switzerland; 2 Inselpital, Bern, Switzerland; 3Viscardia, Beaverton, Oregon; 4Luzerner Kantonsspital, Luzern, Switzerland; 5Basel University Hospital, Basel, Switzerland Introduction: Asymptomatic Diaphragmatic Stimulation (ADS) is a heart failure therapy concept under investigation. Within a range of voltages, electrical stimulation of the diaphragm synchronized to the cardiac cycle alters cardiovascular hemodynamics including venous return and preload by modulating diaphragmatic movement and intrathoracic pressure. The Epiphrenic II pilot utilized a cross-over design to investigate the chronic effects of continuous ADS on cardiac function, including changes to the minimum pacing output required to asymptomatically capture the diaphragm. Hypothesis: Within one year diaphragmatic pacing voltage and pulse width would not change significantly. Methods: In the Epiphrenic II pilot, post CABG patients received CRT devices branched to provide ADS via an epicardial electrode surgically fixated to the left diaphragm. ADS stimulation outputs were determined by using a clinical assessment of the minimum output required to evoke a palpable subcostal yet asymptomatic diaphragmatic response. Therapy was synchronized to left ventricular activation for each cardiac cycle. Upon completion of the formal study protocol at 9 weeks post-implant, patients were provided the option to continue with ADS and CRT, and were invited for a routine follow-up examination at one year post implant. Results: All 24 patients receiving ADS at baseline were alive at their 1 year follow-up, but five refused the follow-up examination and one had relocated. Eighteen patients agreed to perform a one year follow-up, of which one had diaphragmatic pacing off due to nonADS related device issues, resulting in 17 paired data sets. Diaphragmatic pacing voltage and pulse width at 1 year were compared to those at 9 weeks post-implant. Capture thresholds were not significantly different between 9 weeks and 1 year (2.8 ± 0.8 vs 2.9 ± 0.9 V, paired t-test, P = .8), nor was pulse width significantly different (0.5 ± 0.3 vs 0.6 ± 0.3 msec, paired t-test, P = .1). Conclusions: This limited patient set suggests that asymptomatic diaphragmatic threshold values are stable during constant electrical stimulation, providing credence to the hypothesis the diaphragm can be continuously paced for over one year with no changes to stimulation output, which is a minimum requisite for ADS to reliably augment cardiac function chronically.
338 Gender Differences in the Risk of Stroke after Mechanical Circulatory Support Vanessa Blumer, Rodrigo Mendirichaga, Jorge Monge, Gabriel A. Hernandez, Sandra Chaparro; Univ. of Miami / Jackson Memorial Hospital, Miami, Florida Introduction: Mechanical circulatory support (MCS) devices have extended survival and improved quality of life for select patients with advanced heart failure. There have been concerns regarding the incidence of stroke after MCS, and some studies have suggested that female gender is a risk factor for the development of neurological complications. Methods: Using the Healthcare Cost and Utilization Project National Inpatient Sample database we identified patients requiring MCS implantation in United States hospitals from 2010–2014. Ischemic and hemorrhagic strokes were identified by previously validated coding algorithms. Multivariate logistic regression models were