The impact of hypovolemia and PEEP on recirculation in venovenous ECMO: an experimental porcine model.

BACKGROUND: Recirculation is a common problem in venovenous extracorporeal membrane oxygenation (VV ECMO) and may limit the effect of ECMO treatment due to less efficient blood oxygenation or unfavorable ECMO and ventilator settings. The impact of hypovolemia and positive end expiratory pressure (PEEP) on recirculation is unclear and poorly described in guidelines, despite clinical importance. The aim of this study was to investigate how hypovolemia, autotransfusion and PEEP affect recirculation in comparison to ECMO cannula distance and circuit flow. METHODS: In anesthetized and mechanically ventilated pigs (n = 6) on VV ECMO, we measured recirculation fraction (RF), changes in recirculation fraction (∆RF), hemodynamics and ECMO circuit pressures during alterations in PEEP (5 cmH2O vs 15 cmH2O), ECMO flow (3.5 L/min vs 5.0 L/min), cannula distance (10-14 cm vs 20-26 cm intravascular distance), hypovolemia (1000 mL blood loss) and autotransfusion (1000 mL blood transfusion). RESULTS: Recirculation increased during hypovolemia (median ∆RF 43%), high PEEP (∆RF 28% and 12% with long and short cannula distance, respectively), high ECMO flow (∆RF 49% and 28% with long and short cannula distance, respectively) and with short cannula distance (∆RF 16%). Recirculation decreased after autotransfusion (∆RF - 45%). CONCLUSIONS: In the present animal study, hypovolemia, PEEP and autotransfusion were important determinants of recirculation. The alterations were comparable to other well-known factors, such as ECMO circuit flow and intravascular cannula distance. Interestingly, hypovolemia increased recirculation without significant change in ECMO drainage pressure, whereas high PEEP increased recirculation with less negative ECMO drainage pressure. Autotransfusion decreased recirculation. The findings are interesting for clinical studies.

Extracorporeal driveline vibrations to detect left ventricular assist device thrombosis - A porcine model study.

BACKGROUND: Pump thrombosis (PT) and related adverse complications contributed to the HeartWare Ventricular Assist Device (HVAD) market withdrawal. Many patients still receive lifelong support, with deficient PT surveillance based on pump power trends. Analysis of pump vibrations is better for detecting PT. Here, we investigated the feasibility of an extracorporeal accelerometer to detect PT from pump vibrations propagated out on the driveline. METHODS: In a porcine HVAD model (n = 6), an accelerometer was attached to the pump as a reference and another to the driveline for comparisons of signals. In total, 59 thrombi were injected into the heart to induce PT, followed by intermittent thrombus washout maneuvers. Signals were compared visually in spectrograms and quantitatively in third harmonic saliences (S3H) by correlation analysis. Receiver operating characteristic curves expressed the method's outcome in sensitivity vs specificity, with the overall diagnostic performance in the area under the curve (AUC) score. RESULTS: Five experiments had good driveline signal strength, with clear spectrographic relationships between the 2 accelerometers. Third harmonic driveline vibrations were visible 20 vs 30 times in the reference. The comparison in S3H showed a strong correlation and yielded an AUC of 0.85. Notably, S3H proved robust regarding noise and false PT detections. CONCLUSIONS: An extracorporeal accelerometer on the driveline can be a readily available method for accurate HVAD PT detection before an accelerometer integration with left ventricular assist device is feasible.

Detection of inflow obstruction in left ventricular assist devices by accelerometer: A porcine model study.

BACKGROUND: Left ventricular assist devices (LVAD) provide circulatory blood pump support for severe heart failure patients. Pump inflow obstructions may lead to stroke and pump malfunction. We aimed to verify in vivo that gradual inflow obstructions, representing prepump thrombosis, are detectable by a pump-attached accelerometer, where the routine use of pump power (PLVAD) is deficient. METHOD: In a porcine model (n = 8), balloon-tipped catheters obstructed HVAD inflow conduits by 34% to 94% in 5 levels. Afterload increases and speed alterations were conducted as controls. We computed nonharmonic amplitudes (NHA) of pump vibrations captured by the accelerometer for the analysis. Changes in NHA and PLVAD were tested by a pairwise nonparametric statistical test. Detection sensitivities and specificities were investigated by receiver operating characteristics with areas under the curves (AUC). RESULTS: NHA remained marginally affected during control interventions, unlike PLVAD. NHA elevated during obstructions within 52-83%, while mass pendulation was most pronounced. Meanwhile, PLVAD changed far less. Increased pump speeds tended to amplify the NHA elevations. The corresponding AUC was 0.85-1.00 for NHA and 0.35-0.73 for PLVAD. CONCLUSION: Elevated NHA provides a reliable indication of subclinical gradual inflow obstructions. The accelerometer can potentially supplement PLVAD for earlier warnings and localization of pump.

Detection of inflow obstruction in left ventricular assist devices by accelerometer: An in vitro study.

Inflow obstruction in left ventricular assist devices (LVAD) may lead to embolic stroke and pump malfunction. We investigated if an accelerometer detected graded LVAD inflow obstructions. Detection performances were compared to the current continuous surveillance routine based on the pump power consumption (PLVAD). In ten mock circuit experiments, four different-sized pendulating balloons obstructed HVAD™ inflow conduits cross-section areas by 14%-75%. Nonharmonic amplitudes (NHA) of continuous signals from a triaxial accelerometer attached to the LVAD were compared against single-point PLVAD values, using load and speed alterations as control interventions. We analyzed the NHA band power with a pairwise nonparametric statistical test. The detection performances were analyzed by receiver operating characteristics with areas under the curves (AUC). The NHA remained unaffected during load alterations. In contrast, NHA increased significantly from the 27% obstruction level (AUC≥0.82), an effect amplified by increased pump speed. PLVAD did not change significantly below the maximal 75% obstruction level (AUC≤0.36). In conclusion, NHA detected the inflow obstructions much better than PLVAD. The technique may provide a future monitoring modality of any pendulating obstructive inflow pathology.

Automatic Detection of Aortic Valve Events Using Deep Neural Networks on Cardiac Signals From Epicardially Placed Accelerometer.

BACKGROUND: Miniaturized accelerometers incorporated in pacing leads attached to the myocardium, are used to monitor cardiac function. For this purpose functional indices must be extracted from the acceleration signal. A method that automatically detects the time of aortic valve opening (AVO) and aortic valve closure (AVC) will be helpful for such extraction. We tested if deep learning can be used to detect these valve events from epicardially attached accelerometers, using high fidelity pressure measurements to establish ground truth for these valve events. METHOD: A deep neural network consisting of a CNN, an RNN, and a multi-head attention module was trained and tested on 130 recordings from 19 canines and 159 recordings from 27 porcines covering different interventions. Due to limited data, nested cross-validation was used to assess the accuracy of the method. RESULT: The correct detection rates were 98.9% and 97.1% for AVO and AVC in canines and 98.2% and 96.7% in porcines when defining a correct detection as a prediction closer than 40 ms to the ground truth. The incorrect detection rates were 0.7% and 2.3% for AVO and AVC in canines and 1.1% and 2.3% in porcines. The mean absolute error between correct detections and their ground truth was 8.4 ms and 7.2 ms for AVO and AVC in canines, and 8.9 ms and 10.1 ms in porcines. CONCLUSION: Deep neural networks can be used on signals from epicardially attached accelerometers for robust and accurate detection of the opening and closing of the aortic valve.

Myocardial electrophysiological and mechanical changes caused by moderate hypothermia-A clinical study.

Moderate hypothermia has been used to improve outcomes in comatose out-of-hospital cardiac arrest survivors during the past two decades, although the effects remain controversial. We have recently shown in an experimental study that myocardial electrophysiological and mechanical relationships were altered during moderate hypothermia. Electromechanical window positivity increased, and electrical dispersion of repolarization decreased, both of which are changes associated with decreased arrhythmogenicity in clinical conditions. Mechanical dispersion, a parameter also linked to arrhythmic risk, remained unaltered. Whether corresponding electrophysiological and mechanical changes occur in humans during moderate hypothermia, has not been previously explored. Twenty patients with normal left ventricular function were included. Measurements were obtained at 36 and 32°C prior to ascending aortic repair while on partial cardiopulmonary bypass and at 36°C after repair. Registrations were performed in the presence of both spontaneous and comparable paced heart rate during standardized loading conditions. The following electrical and mechanical parameters were explored: (1) Electromechanical window, measured as time difference between mechanical and electrical systole, (2) dispersion of repolarization from ECG T-wave, and (3) mechanical dispersion, measured as segmental variation in time to peak echocardiographic strain. At moderate hypothermia, mechanical systolic prolongation (425 ± 43-588 ± 67 ms, p < 0.001) exceeded electrical systolic prolongation (397 ± 49-497 ± 79 ms, p < 0.001), whereby, electromechanical window positivity increased (29 ± 30-86 ± 50 ms, p < 0.001). Dispersion of repolarization and mechanical dispersion remained unchanged. Corresponding electrophysiological and mechanical relationships were present at comparable paced heart rates. After rewarming, the increased electromechanical window was reversed in the presence of both spontaneous and paced heart rates. Moderate hypothermia increased electromechanical window positivity, while dispersion of repolarization and mechanical dispersion remained unchanged. This impact of hypothermia may be clinically relevant for selected groups of patients after cardiac arrest.

Left Ventricular Function Changes Induced by Moderate Hypothermia Are Rapidly Reversed After Rewarming-A Clinical Study.

OBJECTIVES: Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts. DESIGN: Prospective clinical study, from June 2015 to May 2018. SETTING: Cardiothoracic surgery operation room, Oslo University Hospital. PATIENTS: Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included. INTERVENTIONS: Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions. MEASUREMENTS AND MAIN RESULTS: Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored. CONCLUSIONS: In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming.

Open chest and pericardium facilitate transpulmonary passage of venous air emboli.

BACKGROUND: Transpulmonary passage of air emboli can lead to fatal brain- and myocardial infarctions. We studied whether pigs with open chest and pericardium had a greater transpulmonary passage of venous air emboli than pigs with closed thorax. METHODS: We allocated pigs with verified closed foramen ovale to venous air infusion with either open chest with sternotomy and opening of the pleura and pericardium (n = 8) or closed thorax (n = 16). All pigs received a five-hour intravenous infusion of ambient air, starting at 4-6 mL/kg/h and increased by 2 mL/kg/h each hour. We assessed transpulmonary air passage by transesophageal M-mode echocardiography and present the results as median with inter-quartile range (IQR). RESULTS: Transpulmonary air passage occurred in all pigs with open chest and pericardium and in nine pigs with closed thorax (56%). Compared to pigs with closed thorax, pigs with open chest and pericardium had a shorter to air passage (10 minutes (5-16) vs. 120 minutes (44-212), P < .0001), a smaller volume of infused air at the time of transpulmonary passage (12 mL (10-23) vs.170 mL (107-494), P < .0001), shorter time to death (122 minutes (48-185) vs 263 minutes (248-300, P = .0005) and a smaller volume of infused air at the time of death (264 mL (53-466) vs 727 mL (564-968), P = .001). In pigs with open chest and, infused air and time to death correlated strongly (r = 0.95, P = .001). CONCLUSION: Open chest and pericardium facilitated the transpulmonary passage of intravenously infused air in pigs.

Left Ventricular Function During Epinephrine Stimulation and Hypothermia: Effects at Spontaneous and Paced Heart Rates in a Porcine Model.

Postcardiac arrest patients treated with hypothermia, frequently require vasopressors and inotropic medication. The aim of this experimental study was to investigate the effect of epinephrine on left ventricular (LV) function during hypothermia. In an open-chest porcine model, seven animals were equipped with LV micromanometer and epicardial ultrasound transducers to provide LV pressure, Tau, and wall thickness and thickening velocities in systole (S') and early diastole (e'). Arterial, central venous, and pulmonal artery pressures were recorded. Cardiac output (CO) was measured by transit-time flow probe on the ascending aorta. Hypothermia was induced using a cooling catheter through the femoral vein. Pacemaker leads were attached to the right atrium for pacing. LV volumes were obtained by two-dimensional echocardiography. Measurements were made at normothermia (38°C) and hypothermia (33°C), without and with epinephrine infusion (0.03 µg/kg/min), at spontaneous and paced heart rates (HRs) 120 and 140 beats/min. Hypothermia reduced LV stroke volume (SV). Epinephrine during hypothermia increased the SV with reduced end-systolic volumes. LV dP/dtmax and wall-thickening velocity increased. During normothermia, epinephrine increased CO mainly due to accelerated HR, but during hypothermia, the increased CO resulted from augmented SV and, to a lesser degree, elevated HR. The incomplete relaxation and shortened diastolic filling time and the following reduction in SV seen in hypothermic animals, was repealed by epinephrine. The CO remained elevated also due to a shortened systolic duration, which gave time for complete relaxation during higher HRs. Epinephrine infusion improved systolic and diastolic function during hypothermia, and thereby reversed the effects induced by hypothermia considerably. Epinephrine augmented CO at hypothermia through increases in both SV and HR, in contrast to a mainly HR-dependent effect during normothermia. Systolic duration was shortened, which gave sufficient diastolic duration for complete relaxation. This allowed diastolic filling and maintained CO at elevated HRs.

Continuous Estimation of Acute Changes in Preload Using Epicardially Attached Accelerometers.

OBJECTIVE: A miniaturized accelerometer can be incorporated in temporary pacemaker leads which are routinely attached to the epicardium during cardiac surgery and provide continuous monitoring of cardiac motion during and following surgery. We tested if such a sensor could be used to assess volume status, which is essential in hemodynamically unstable patients. METHODS: An accelerometer was attached to the epicardium of 9 pigs and recordings performed during baseline, fluid loading, and phlebotomy in a closed chest condition. Alterations in left ventricular (LV) preload alter myocardial tension which affects the frequency of myocardial acceleration associated with the first heart sound ( fS1). The accuracy of fS1 as an estimate of preload was evaluated using sonomicrometry measured end-diastolic volume (EDV[Formula: see text]). Standard clinical estimates of global end-diastolic volume using pulse index continuous cardiac output (PiCCO) measurements (GEDV[Formula: see text]) and pulmonary artery occlusion pressure (PAOP) were obtained for comparison. The diagnostic accuracy of identifying fluid responsiveness was analyzed for fS1, stroke volume variation (SVV[Formula: see text]), pulse pressure variation (PPV[Formula: see text]), GEDV[Formula: see text], and PAOP. RESULTS: Changes in fS1 correlated well to changes in EDV[Formula: see text] ( r2=0.81, 95%CI: [0.68, 0.89]), as did GEDV[Formula: see text] ( r2=0.59, 95%CI: [0.36, 0.76]) and PAOP ( r2=0.36, 95%CI: [0.01, 0.73]). The diagnostic accuracy [95%CI] in identifying fluid responsiveness was 0.79 [0.66, 0.94] for fS1, 0.72 [0.57, 0.86] for SVV[Formula: see text], and 0.63 (0.44, 0.82) for PAOP. CONCLUSION: An epicardially placed accelerometer can assess changes in preload in real-time. SIGNIFICANCE: This novel method can facilitate continuous monitoring of the volemic status in open-heart surgery patients and help guiding fluid resuscitation.

Changes in left ventricular electromechanical relations during targeted hypothermia.

BACKGROUND: Targeted hypothermia, as used after cardiac arrest, increases electrical and mechanical systolic duration. Differences in duration of electrical and mechanical systole are correlated to ventricular arrhythmias. The electromechanical window (EMW) becomes negative when the electrical systole outlasts the mechanical systole. Prolonged electrical systole corresponds to prolonged QT interval, and is associated with increased dispersion of repolarization and mechanical dispersion. These three factors predispose for arrhythmias. The electromechanical relations during targeted hypothermia are unknown. We wanted to explore the electromechanical relations during hypothermia at 33 °C. We hypothesized that targeted hypothermia would increase electrical and mechanical systolic duration without more profound EMW negativity, nor an increase in dispersion of repolarization and mechanical dispersion. METHODS: In a porcine model (n = 14), we registered electrocardiogram (ECG) and echocardiographic recordings during 38 °C and 33 °C, at spontaneous and atrial paced heart rate 100 beats/min. EMW was calculated by subtracting electrical systole; QT interval, from the corresponding mechanical systole; QRS onset to aortic valve closure. Dispersion of repolarization was measured as time from peak to end of the ECG T wave. Mechanical dispersion was calculated by strain echocardiography as standard deviation of time to peak strain. RESULTS: Electrical systole increased during hypothermia at spontaneous heart rate (p < 0.001) and heart rate 100 beats/min (p = 0.005). Mechanical systolic duration was prolonged and outlasted electrical systole independently of heart rate (p < 0.001). EMW changed from negative to positive value (- 20 ± 19 to 27 ± 34 ms, p = 0.001). The positivity was even more pronounced at heart rate 100 beats/min (- 25 ± 26 to 41 ± 18 ms, p < 0.001). Dispersion of repolarization decreased (p = 0.027 and p = 0.003), while mechanical dispersion did not differ (p = 0.078 and p = 0.297). CONCLUSION: Targeted hypothermia increased electrical and mechanical systolic duration, the electromechanical window became positive, dispersion of repolarization was slightly reduced and mechanical dispersion was unchanged. These alterations may have clinical importance. Further clinical studies are required to clarify whether corresponding electromechanical alterations are accommodating in humans.

Automatic detection of valve events by epicardial accelerometer allows estimation of the left ventricular pressure trace and pressure-displacement loop area.

Measurements of the left ventricular (LV) pressure trace are rarely performed despite high clinical interest. We estimated the LV pressure trace for an individual heart by scaling the isovolumic, ejection and filling phases of a normalized, averaged LV pressure trace to the time-points of opening and closing of the aortic and mitral valves detected in the individual heart. We developed a signal processing algorithm that automatically detected the time-points of these valve events from the motion signal of a miniaturized accelerometer attached to the heart surface. Furthermore, the pressure trace was used in combination with measured displacement from the accelerometer to calculate the pressure-displacement loop area. The method was tested on data from 34 animals during different interventions. The accuracy of the accelerometer-detected valve events was very good with a median difference of 2 ms compared to valve events defined from hemodynamic reference recordings acquired simultaneously with the accelerometer. The average correlation coefficient between the estimated and measured LV pressure traces was r = 0.98. Finally, the LV pressure-displacement loop areas calculated using the estimated and measured pressure traces showed very good correlation (r = 0.98). Hence, the pressure-displacement loop area can be assessed solely from accelerometer recordings with very good accuracy.

Esmolol for cardioprotection during resuscitation with adrenaline in an ischaemic porcine cardiac arrest model.

BACKGROUND: The effectiveness of adrenaline during resuscitation continues to be debated despite being recommended in international guidelines. There is evidence that the ß-adrenergic receptor (AR) effects of adrenaline are harmful due to increased myocardial oxygen consumption, post-defibrillation ventricular arrhythmias and increased severity of post-arrest myocardial dysfunction. Esmolol may counteract these unfavourable ß-AR effects and thus preserve post-arrest myocardial function. We evaluated whether a single dose of esmolol administered prior to adrenaline preserves post-arrest cardiac output among successfully resuscitated animals in a novel, ischaemic cardiac arrest porcine model. METHODS: Myocardial infarction was induced in 20 anaesthetized pigs by inflating a percutaneous coronary intervention (PCI) balloon in the circumflex artery 15 min prior to induction of ventricular fibrillation. After 10 min of untreated VF, resuscitation with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated and the animals were randomized to receive an injection of either 1 mg/kg esmolol or 9 mg/ml NaCl, prior to adrenaline. Investigators were blinded to allocation. Successful defibrillation was followed by a 1-h high-flow VA-ECMO before weaning and an additional 1-h stabilization period. The PCI-balloon was deflated 40 min after inflation. Cardiac function pre- and post-arrest (including cardiac output) was assessed by magnetic resonance imaging (MRI) and invasive pressure measurements. Myocardial injury was estimated with MRI, triphenyl tetrazolium chloride (TTC) staining and serum concentrations of cardiac troponin T. RESULTS: Only seven esmolol and five placebo-treated pigs were successfully resuscitated and available for post-arrest measurements (p = 0.7). MRI revealed severe but similar reductions in post-arrest cardiac function with cardiac output 3.5 (3.3, 3.7) and 3.3 (3.2, 3.9) l/min for esmolol and control (placebo) groups, respectively (p = 0.7). The control group had larger left ventricular end-systolic and end-diastolic ventricular volumes compared to the esmolol group (75 (65, 100) vs. 62 (53, 70) ml, p = 0.03 and 103 (86, 124) vs. 87 (72, 91) ml, p = 0.03 for control and esmolol groups, respectively). There were no other significant differences in MRI characteristics, myocardial infarct size or other haemodynamic measurements between the two groups. CONCLUSIONS: We observed similar post-arrest cardiac output with and without a single dose of esmolol prior to adrenaline administration during low-flow VA-ECMO in an ischaemic cardiac arrest pig model.

Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model.

INTRODUCTION: Right ventricular (RV) myocardial dysfunction is a common feature in septic shock. It can worsen outcome, but the etiology is poorly understood. Pulmonary artery hypertension (PAH) plays a part in the pathogenesis of the right heart dysfunction in sepsis but its importance is unknown. In pigs, PAH in sepsis is substantial and the translational value of porcine sepsis models therefore questioned. We hypothesized that porcine sepsis causes a myocardial inflammatory response which leads to myocardial dysfunction independent of PAH. MATERIALS AND METHODS: Sepsis was induced by Escherichia coli-infusion in 10 pigs resulting in PAH and increased right ventricular pressure (RVP). The same degree of RVP was achieved by external pulmonary artery banding (PAB) in a consecutive series of 6 animals. RESULTS: Sepsis, but not PAB, led to increase in endothelial damage marker PAI-1 and cytokines TNF and IL-6 (all p<0.05) in plasma. In myocardium, TNF and IL-6 were significantly elevated in sepsis, TNF in both ventricles and IL-6 mostly in RV, while IL-1ß, IL-18 and C5a were significantly higher in RV compared to LV after PAB (all p<0.05). Myocardial mRNA levels of IL-1ß, IL-6, IL-18, IP-10, E-selectin and PAI-1 were significantly elevated in RV and LV during sepsis compared to PAB, while Caspase-1 was decreased in septic compared to PAB animals (all p<0.05). Cathepsin L activity was increased in RV by PAB, while sepsis inhibited this response. Escherichia coli-induced sepsis caused myocardial inflammation independent of PAH. CONCLUSION: Prominent PAH should therefore not exclude porcine sepsis models to further our understanding of human sepsis.

Dynamic gravity compensation does not increase detection of myocardial ischemia in combined accelerometer and gyro sensor measurements.

Previous studies have shown that miniaturised accelerometers can be used to monitor cardiac function and automatically detect ischemic events. However, accelerometers cannot differentiate between acceleration due to motion and acceleration due to gravity. Gravity filtering is essential for accurate integration of acceleration to yield velocity and displacement. Heart motion is cyclic and mean acceleration over time is zero. Thus, static gravity filtering is performed by subtracting mean acceleration. However, the heart rotates during the cycle, the gravity component is therefore not constant, resulting in overestimation of motion by static filtering. Accurate motion can be calculated using dynamic gravity filtering by a combined gyro and accelerometer. In an animal model, we investigated whether increased accuracy using dynamic filtering, compared to using static filtering, would enhance the ability to detect ischemia. Additionally, we investigated how well the gyro alone could detect ischemia based on the heart's rotation. Dynamic filtering tended towards lower sensitivity and specificity, using receiver operating characteristics analysis, for ischemia-detection compared to static filtering (area under the curve (AUC): 0.83 vs 0.93, p = 0.125). The time-varying gravity component indirectly reflects the heart's rotation. Hence, static filtering has the advantage of indirectly including rotation, which alone demonstrated excellent sensitivity to ischemia (AUC = 0.98).

Can we ablate liver lesions close to large portal and hepatic veins with MR-guided HIFU? An experimental study in a porcine model.

OBJECTIVES: Invasive treatment of tumors adjacent to large hepatic vessels is a continuous clinical challenge. The primary aim of this study was to examine the feasibility of ablating liver tissue adjacent to large hepatic and portal veins with magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU). The secondary aim was to compare sonication data for ablations performed adjacent to hepatic veins (HV) versus portal veins (PV). MATERIALS AND METHODS: MRgHIFU ablations were performed in six male land swine under general anesthesia. Ablation cells of either 4 or 8 mm diameter were planned in clusters (two/animal) adjacent either to HV (n = 6) or to PV (n = 6), with diameter ≥ 5 mm. Ablations were made using 200 W and 1.2 MHz. Post-procedure evaluation was made on contrast-enhanced MRI (T1w CE-MRI), histopathology, and ablation data from the HIFU system. RESULTS: A total of 153 ablations in 81 cells and 12 clusters were performed. There were visible lesions with non-perfused volumes in all animals on T1w CE-MRI images. Histopathology showed hemorrhage and necrosis in all 12 clusters, with a median shortest distance to vessel wall of 0.4 mm (range 0-2.7 mm). Edema and endothelial swelling were observed without vessel wall rupture. In 8-mm ablations (n = 125), heat sink was detected more often for HV (43%) than for PV (19%; p = 0.04). CONCLUSIONS: Ablations yielding coagulative necrosis of liver tissue can be performed adjacent to large hepatic vessels while keeping the vessel walls intact. This indicates that perivascular tumor ablation in the liver is feasible using MRgHIFU. KEY POINTS: • High-intensity focused ultrasound ablation is a non-invasive treatment modality that can be used for treatment of liver tumors. • This study shows that ablations of liver tissue can be performed adjacent to large hepatic vessels in an experimental setting. • Liver tumors close to large vessels can potentially be treated using this modality.

Single-centre first experience with transapical transcatheter mitral valve replacement with an apical tether: factors influencing screening outcomes.

OBJECTIVES: Transcatheter mitral valve replacement has recently been introduced as an alternative treatment option for severe mitral regurgitation. We present our single-centre first experience with screening and implantation outcomes. METHODS: Twenty-five patients with mitral regurgitation grades 3 and 4 were screened based on study inclusion/exclusion criteria, echocardiography and computed tomography imaging. All patients were evaluated by the centre's Heart Team, followed by the Tendyne's internal screening process. Patients who failed the screening criteria were considered for alternative treatments. RESULTS: Of the 25 patients screened for transcatheter mitral valve replacement, 14 patients failed screening and 11 patients passed. The patients who failed screening were more often older, were women and were smaller in stature than those who passed screening. The main reason for patients to fail screening changed during the study from large annular dimensions to a small predicted neo-left ventricular outflow tract. Eight of the 11 patients who passed screening were treated using the Tendyne device, and 3 patients required alternate treatments due to urgency including 1 MitraClip procedure and 2 surgical repairs. Of the 14 patients who failed the screening, 5 patients had open surgery (4 patients received mitral valve repair and 1 mitral valve replacement). All 8 patients who underwent the Tendyne procedure were successfully treated without mortality during the observation time. CONCLUSIONS: Transcatheter mitral valve replacement is an effective and safe treatment for well-selected patients with symptomatic mitral regurgitation. For patients who fail the screening process, the MitraClip procedure or open surgical valve repair are feasible.

Monitoring cardiac function by accelerometer - detecting start systole from the acceleration signal makes additional ECG recordings for R-peak detection redundant.

A miniaturized accelerometer attached to the heart has been used for monitoring functional parameters such as early systolic velocity and displacement. Currently, processing of the accelerometer signal for derival of these functional parameters depends on determining start systole by detecting the ECG R-peaks. This study proposes an alternative method using only the accelerometer signal to detect start systole, making additional ECG recordings for this purpose redundant. A signal processing method for automatic detection of start systole by accelerometer alone was developed and compared with detected R-peaks in 15 pigs during 5 different interventions showing a difference of 30 ± 17 ms. Furthermore, the derived early systolic velocity and displacement using only accelerometer measurements correlated well (r2=0.91 and 0.82, respectively) with minor differences compared to the current method using ECG R-peaks as time reference. The results show that an accelerometer can be used to monitor cardiac function without the need to measure ECG which can simplify the monitoring system.

Reduced inflammatory response by transcatheter, as compared to surgical aortic valve replacement.

OBJECTIVES: The inflammatory response to on-pump cardiac surgery is well known. Systemic inflammatory response syndrome after transcatheter valve implantation (TAVI) has been reported. The objective of this study was to study the inflammatory response during TAVI, and compare with the response during surgical aortic valve replacement. METHODS: Eighteen patients undergoing transcatheter implantation, either by a transfemoral (n = 9) or transaortal (n = 9) approach were compared with eighteen patients admitted for surgical replacement. Blood samples per- and postoperatively were analysed for C3bc, terminal complement complex, myeloperoxidase, macrophage inflammatory protein-1ß, monocyte chemo-attractant peptide-1, eotaxin, IL-6 and troponin-T. All markers were measured at defined time points and the areas under the curve were compared. RESULTS: Activation of complement, granulocytes, monocytes and eosinophils were significantly lower in the transcatheter group as compared to the surgical group (<0.01). There was no difference in generation of troponin T and IL-6. A small difference in complement activation was observed between the transfemoral and transaortal placement of TAVI. There was no significant difference in clinical outcomes between the TAVI and surgical groups. DISCUSSION: Activation and release of inflammatory markers was significantly less during with TAVI as compared to SAVR, particularly for markers associated with extracorporeal circulation. TAVI and SAVR generated the same degree of IL-6 and troponin T, indicating that the burden on the myocardial tissue was the same. Clinical Trials: Gov ID: NCT03074838 Unique protocol ID: 2012/7919.

Urinary Kinetics of Heroin Metabolites in Pigs Shortly After Intake.

In previous experimental studies on heroin metabolites excretion in urine, the first sample was often collected a few hours after intake. In forensic cases, it is sometimes questioned if a positive urine result is expected e.g., 30 min after intake. The aim of this study was to investigate urinary excretion of heroin metabolites (morphine, 6-monoacetylmorphine (6-MAM) and morphine-3-glucuronide (M3G)) every 30 min until 330 min after injection of a 20 mg heroin dose in six pigs. Samples were analyzed using a previously published, fully validated liquid chromatography-tandem mass spectrometry method. All metabolites were detected after 30 min in all pigs. The time to maximum concentration (Tmax) median (range) for 6-MAM and morphine was 30 min (first sample) (30-120), and 90 min (30-330) for M3G. In four of the six pigs, the Tmax of 6-MAM and morphine was reached within 30 min. All analytes were still detectable at the end of study. This study showed that positive results in urine are expected to be seen shortly after use of heroin in pigs. Detection times were longer than previously indicated, especially for 6-MAM, but previous studies used lower doses. As the physiology of these animals resembles that of the humans, transferability to man is expected.