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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

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.

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 p = 0.005). Mechanical systolic duration was prolonged and outlasted electrical systole independently of heart rate (p p = 0.001). The positivity was even more pronounced at heart rate 100 beats/min (− 25 ± 26 to 41 ± 18 ms, p 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.

BackgroundTargeted temperature management is recommended after cardiac arrest, but the beneficial effects are controversial. The recently published TTM2 study reports that arrhythmias causing hemodynamic compromise are more common during moderate hypothermia. The causation is not explored. Experimentally, moderate hypothermia attenuates electromechanical relations with pro-arrhythmic impact. Mechanical systole outlasts the electrical systole to a greater extent giving increased electromechanical window positivity, and dispersion of electrical and mechanical activity are unaltered. In this prospective clinical study, we explored the effect of moderate hypothermia on electromechanical relations in un-insulted left ventricles. We hypothesized that during moderate hypothermia, prolongation of systolic duration would exceed electrical duration without dispersed electrical- or mechanical activity. Methods20 patients with normal left ventricular function, undergoing surgery on the ascending aorta and connected to cardiopulmonary bypass, were included. Measurements were obtained at 36 °C and 32 °C prior to aortic-repair, and at 36 °C after repair at spontaneous and paced heart rate 90 bpm. Comparable loading conditions were ensured and cardiopulmonary bypass was reduced to 20% of estimated maximum during the measurements. Global cardiac function was measured invasively and with echocardiography. Electromechanical window, dispersion of repolarization by ECG and mechanical dispersion by echocardiography, were calculated. ResultsAt moderate hypothermia (32°C), mechanical systolic prolongation exceeded electrical prolongation so that electromechanical window increased (29 ± 30 to 86 ± 50 ms, p ConclusionModerate hypothermia increased electromechanical window positivity. Dispersion of repolarisation, mechanical dispersion, and myocardial function were unchanged. Moderate hypothermia did not induce adverse electromechanical changes in the left ventricle during standardized conditions, but rather an attenuation of pro-arrhythmic electromechanical relations.

We have recently demonstrated that accelerometer-based pump thrombosis and thromboembolic events detection is feasible in vitro. This article focuses on detection of these conditions in vivo. In an open-chest porcine model (n = 7), an accelerometer was attached to the pump casing of an implanted HeartWare HVAD. Pump vibration was analyzed by Fast Fourier Transform of the accelerometer signals, and the spectrogram third harmonic amplitude quantified and compared with pump power. Interventions included injection of thrombi into the left atrium (sized 0.3-0.4 ml, total n = 35) and control interventions; pump speed change, graft obstruction, and saline bolus injections (total n = 47). Graft flow to cardiac output ratio was used to estimate the expected number of thrombi passing through the pump. Sensitivity/specificity was assessed by receiver operating characteristic curve. Graft flow to cardiac output ratio averaged 66%. Twenty-six of 35 (74%) thrombi caused notable accelerometer signal change. Accelerometer third harmonic amplitude was significantly increased in thromboembolic interventions compared with control interventions, 64.5 (interquartile range [IQR]: 18.8-107.1) and 5.45 (IQR: 4.2-6.6), respectively (p0.01). The corresponding difference in pump power was 3 W (IQR: 2.9-3.3) and 2.8 W (IQR: 2.4-2.9), respectively (p0.01). Sensitivity/specificity of the accelerometer and pump power to detect thromboembolic events was 0.74/1.00 (area under the curve [AUC]: 0.956) and 0.40/1.00 (AUC: 0.759), respectively. Persistent high third harmonic amplitude was evident at end of all experiments, and pump thrombosis was confirmed by visual inspection. The findings demonstrate that accelerometer-based detection of thromboembolic events and pump thrombosis is feasible in vivo and that the method is superior to detection based on pump power.

Cardiac disease is a leading cause of death worldwide. Disturbance in the conduction system of the heart may trigger or aggravate heart dysfunction, affecting the efficiency of the heart, and lead to heart failure or cardiac arrest. Patients may require implantable cardiac rhythm management devices (ICRMDs) to maintain or restore the heart rhythm. ICRMDs have undergone important improvements, yet limitations still exist, presenting important technological challenges. Most ICRMDs consist of a subcutaneous control unit and intracardiac electrodes. The leads, which connect the electrodes to the control unit, are usually placed transvenously through the subclavian veins. Various locations inside the heart are used for placement of electrodes, depending on the specific condition. Some of the limitations to effective pacemaker therapy are associated with placement and location of the leads. Various approaches have been developed to overcome these challenges, such as multi-site pacing and leadless solutions. This paper aims to review the state of the art for the selection of placement sites for pacemakers, implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy devices (CRT) devices and discuss potential technological advancements to improve the results of ICRMD-therapy including development av leadless technology.

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.

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.

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 ( $f_{S1}$ ). The accuracy of $f_{S1}$ as an estimate of preload was evaluated using sonomicrometry measured end-diastolic volume (EDV $_{\text{SONO}}$ ). Standard clinical estimates of global end-diastolic volume using pulse index continuous cardiac output (PiCCO) measurements (GEDV $_{\text{PiCCO}}$ ) and pulmonary artery occlusion pressure (PAOP) were obtained for comparison. The diagnostic accuracy of identifying fluid responsiveness was analyzed for $f_{S1}$ , stroke volume variation (SVV $_{\text{PiCCO}}$ ), pulse pressure variation (PPV $_{\text{PiCCO}}$ ), GEDV $_{\text{PiCCO}}$ , and PAOP. Results: Changes in $f_{S1}$ correlated well to changes in EDV $_{\text{SONO}}$ ( $r^2=0.81$ , 95%CI: [0.68, 0.89]), as did GEDV $_{\text{PiCCO}}$ ( $r^2=0.59$ , 95%CI: [0.36, 0.76]) and PAOP ( $r^2=0.36$ , 95%CI: [0.01, 0.73]). The diagnostic accuracy [95%CI] in identifying fluid responsiveness was 0.79 [0.66, 0.94] for $f_{S1}$ , 0.72 [0.57, 0.86] for SVV $_{\text{PiCCO}}$ , 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.

Therapeutic hypothermia is an established treatment in patients resuscitated from cardiac arrest. It is usually well-tolerated circulatory, but hypothermia negatively effects myocardial contraction and relaxation velocities and increases diastolic filling restrictions. A significant proportion of resuscitated patients are treated with long-acting beta-receptor blocking agents' prearrest, but the combined effects of hypothermia and beta-blockade on left ventricle (LV) function are not previously investigated. We hypothesized that beta1-adrenergic receptor blockade (esmolol infusion) exacerbates the negative effects of hypothermia on active myocardial motions, affecting both systolic and diastolic LV function. A pig (n = 10) study was performed to evaluate the myocardial effects of esmolol during hypothermia (33°C) and during normothermia, at spontaneous and pacing-increased heart rates (HRs). LV function was assessed by a LV pressure transducer, an epicardial ultrasonic transducer (wall thickness, wall thi...

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.

Purpose We aimed to study the safety and feasibility of low-dose dobutamine stress echocardiography in a symptomatic high gradient aortic stenosis population scheduled for transfemoral transcatheter aortic valve implantation (TAVI) and to quantify left ventricular (LV) flow reserve. Methods Fifty patients underwent dobutamine stress echocardiography with 5 minutes increments of 5 μg/kg/min up to 20 μg/kg/min until the heart rate increased ≥20 beats/min from baseline or exceeded 100 beats/min. Other criteria for discontinuing the infusion were major adverse events: ventricular arrhythmia, persistent supraventricular arrhythmia, pulmonary edema, chest pain with significant ST-changes, or minor events: ST-changes, drop in systolic blood pressure >30 mmHg, mild chest pain, and/or dyspnea. LV flow reserve was defined as an increase in stroke volume ≥20% during the test. Results Of 50 patients, 45 completed the test according to protocol. No patient had major adverse event. Five patients experienced minor side effects: mild chest pain/dyspnea in three, self-terminating atrial flutter in one, and decrease in blood pressure in one. Significant LV flow reserve was observed in 20 patients (40%). Conclusion Low-dose dobutamine stress test appeared safe and feasible patients with high gradient aortic stenosis, and showed LV flow reserve in a minority of them.

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.

Background The effectiveness of adrenaline during resuscitation continues to be debated despite being recommended in international guidelines. There is evidence that the β-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 β-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.

Introduction Hypothermia is therapeutically used after cardiac arrest. The moderate hypothermia alters cardiac function, with reduced heart rate (HR), prolonged systolic duration and increased QT interval. The risk of arrhythmia increases with prolonged QT-interval, but clinical studies have not been able to demonstrate an increase of arrhythmic events during moderate hypothermia. The mechanism of this is not thoroughly described, but the concurrent increase in mechanical systolic duration may play a part of the explanation. Purpose QT prolongation and increased electromechanical window (EMW) negativity; the duration of left ventricle mechanical systole relatively to the duration of the electrical systole, are associated with arrhythmia. We hypothesized that moderate hypothermia would increase ECG intervals and systolic duration without an increase in EMW negativity. Methods In an open-chest porcine model (n=10), 2D echocardiography measurements and Doppler recordings were performed with concurrent 3-lead ECG registrations during normothermia (38°C) and moderate hypothermia (33°C) at spontaneous HR. Diastolic and systolic durations were assessed by valve opening to valve closure and Doppler assessed ejection time (ET). Isovolumetric contraction time (IVCT) and EMW, were measured. Systolic function was assessed by ejection fraction (EF), stroke volume (SV) and systolic velocity (s'). Results are presented as means ± SD. Two-sided T-test was used for comparison and P-value Results Moderate hypothermia reduced HR from 91±9 to 82±7 beats/min (p Conclusion Moderate hypothermia increased the QTc-interval but the mechanical systolic duration was even more prolongated. The EMW became positive demonstrating that the mechanical systole outlasted the electrical systole. As less EMW negativity is considered to be protective regarding arrhythmia, these findings may explain why arrhythmia is not frequently occurring during moderate hypothermia. Acknowledgement/Funding None

Machine learning is widely used on stored data, recently it is developed to model real time streams. Applying machine learning on medical streams might lead to a breakthrough on emergency and critical care through online predictions. Modeling real time streams implies limitations to the current state-of-the-art of machine learning and requires different learning paradigm. In this paper, we investigate and evaluate two different machine learning paradigms for real time predictions of medical streams. Both the hierarchical temporal memory (HTM) and long short-term memory (LSTM) are employed. The performance assessment using both algorithms is provided in terms of the root mean square error (RMS) and mean absolute percentage error (MAPE). HTM is found advantageous as it provides efficient unsupervised predictions compared to the semi-supervised learning supported by LSTM in terms of the error measures. © 2019 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other works.

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).

A miniaturized accelerometer fixed to the heart can be used for monitoring of cardiac function. However, an accelerometer cannot differentiate between acceleration caused by motion and acceleration due to gravity. The accuracy of motion measurements is therefore dependent on how well the gravity component can be estimated and filtered from the measured signal. In this study we propose a new method for estimating the gravity, based on strapdown inertial navigation, using a combined accelerometer and gyro. The gyro was used to estimate the orientation of the gravity field and thereby remove it. We compared this method with two previously proposed gravity filtering methods in three experimental models using: (1) in silico computer simulated heart motion; (2) robot mimicked heart motion; and (3) in vivo measured motion on the heart in an animal model. The new method correlated excellently with the reference (r 2 > 0.93) and had a deviation from reference peak systolic displacement (6.3 ± 3.9 mm) below 0.2 ± 0.5 mm for the robot experiment model. The new method performed significantly better than the two previously proposed methods (p

OBJECTIVES Transcatheter aortic valve implantation improves survival in patients with severe aortic stenosis who are ineligible for surgical valve replacement; however, not all patients benefit from the procedure. We endeavoured to identify these patients using intraoperative echocardiography and hypothesized that intraoperative left ventricular function in response to the acute afterload reduction during the procedure was related to long-term outcomes. METHODS We prospectively included 64 patients who were scheduled for transcatheter aortic valve implantation and divided them into responders and non-responders based on their left ventricular intraoperative responses to the acute afterload reduction after valve deployment. Responders were defined by increases of ≥20% in left ventricular longitudinal peak systolic velocities determined by tissue Doppler echocardiography. All patients were assessed for the following outcomes at 12 months: cardiac mortality, adverse cardiac events, quality of life, New York Heart Association class, N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiography. RESULTS Thirty-five patients (55%) were classified as responders and 29 patients (45%) as non-responders. Compared with responders, non-responders had higher risks of death (28 vs 9%, respectively, P = 0.04) and cardiac events (66 vs 26%, respectively, P < 0.01) during the 12-month follow-up. Significant long-term improvements in quality of life, NT-proBNP and left ventricular function were observed only in the responders. Preoperative risk stratification, intraoperative handling, aortic gradient and valve area were similar between groups. CONCLUSIONS Intraoperative assessment of left ventricular function by tissue Doppler echocardiography predicted long-term outcomes after transcatheter aortic valve implantation. Our results suggest that a preoperative test of myocardial contractile reserve might improve risk stratification and patient selection prior to the procedure.

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

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 (r 2 =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.

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.

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). 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. 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). 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. • 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.

OBJECTIVES Left ventricular function is expected to improve after transcatheter aortic valve implantation due to the acute reduction in afterload, but does not occur in all patients. We hypothesized that the immediate intraoperative response in systolic left ventricular longitudinal motion during the procedure could be a predictor of short-term outcome. METHODS Sixty-four patients treated with transcatheter aortic valve implantation for severe aortic stenosis were included. Transoesophageal 4- and 2-chamber echocardiograms were obtained immediately prior to and ∼15 min after valve implantation. Patients were defined as responders if their average left ventricular longitudinal peak systolic velocity increased by ≥20% from the preimplantation value and was related to the 3-month outcome. RESULTS Thirty-five patients were classified as responders, with an increase in the intraoperative longitudinal peak systolic velocity from an average of 2.2 ± 0.8 to 3.1 ± 1.1 cm/s (P < 0.001); the velocity was unchanged in the remaining 29 patients, who averaged 2.4 ± 1.1 cm/s. There were significantly fewer adverse cardiac events in the responder group at the 3-month follow-up (20 vs 45%, P = 0.03) and the New York Heart Association class was significantly better in the responders compared with non-responders. Responders had a significant reduction in N-terminal probrain natriuretic peptide levels [243 (113-361) vs 163 (64-273), P = 0.004] at the 3-month follow-up, whereas non-responders did not [469 (130-858) vs 289 (157-921), P = 0.48]. CONCLUSIONS An immediate improvement in the longitudinal peak systolic velocity during the transcatheter aortic valve implantation procedure predicted a better short-term outcome and may be useful in identifying patients who are at risk of a less favourable outcome after transcatheter aortic valve implantation.

Early detection of cardiac complications after heart surgery is a crucial demand in clinical surveillance facilities. The use of accelerometer devices fixated to the heart has been demonstrated as a promising method for the detection of myocardial ischemia with high sensitivity and specificity. One of the most important challenges in developing heart implantable accelerometer devices is to minimize any tissue trauma. In this study, a new approach in making a heart muscle implantable accelerometer sensor is described. An overall diameter of 2 mm is achieved by encapsulating a miniaturized three-axis MEMS accelerometer (similar to the BMA355) from Bosch Sensortec GmbH, Germany. The design of the sensor features a simple implantation procedure, which aims to be similar to the medical procedure of temporary pacing wire attachment. The device remained in place in the heart muscle without the need for additional attachment or fixation. The essential clinical requirements for implantable devices, especially heart implantable sensors, are also taken into account in this study. Additional safety enhancement is realized by adding a galvanic isolator, which ensures electrical safety.

Ultra wideband (UWB) radio technology for wireless implants has gained significant attention. UWB enables the fabrication of faster and smaller transceivers with ultra low power consumption, which may be integrated into more sophisticated implantable biomedical sensors and actuators. Nevertheless, the large path loss suffered by UWB signals propagating through inhomogeneous layers of biological tissues is a major hindering factor. For the optimal design of implantable transceivers, the accurate characterization of the UWB radio propagation in living biological tissues is indispensable. Channel measurements in phantoms and numerical simulations with digital anatomical models provide good initial insight into the expected path loss in complex propagation media like the human body, but they often fail to capture the effects of blood circulation, respiration, and temperature gradients of a living subject. Therefore, we performed UWB channel measurements within 1-6 GHz on two living porcine subjects because of the anatomical resemblance with an average human torso. We present for the first time a path loss model derived from these invivo measurements, which includes the frequency-dependent attenuation. The use of multiple on-body receiving antennas to combat the high propagation losses in implant radio channels was also investigated. This is the authors accepted and refereed manuscript to the article. (c) 2015 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.

Sensitive methods for the early detection of myocardial dysfunction are still needed, as ischemia is a leading cause of decreased ventricular function during and after heart surgery. The aim of this study was to test the hypothesis that low-grade ischemia could be detected quantitatively by a miniaturized epicardial ultrasound transducer (Ø = 3 mm), allowing continuous monitoring.In 10 pigs, transducers were positioned in the left anterior descending and circumflex coronary artery areas. Left ventricular pressure was obtained by a micromanometer. The left internal mammary artery was grafted to the left anterior descending coronary artery, which was occluded proximal to the anastomosis. Left internal mammary artery flow was stepwise reduced by 25%, 50%, and 75% for 18 min each. From the transducers, M-mode traces were obtained, allowing continuous tissue velocity traces and displacement measurements. Regional work was assessed as left ventricular pressure-displacement loop area. Tissue lactate measured from intramyocardial microdialysis was used as reference method to detect ischemia.All steps of coronary flow reduction demonstrated reduced peak systolic velocity (P.05) and regional work (P.01).The decreases in peak systolic velocity and regional work were closely related to the degree of ischemia, demonstrated by their correlations with lactate (R = -0.74, P.01, and R = -0.64, P.01, respectively). The circumflex coronary artery area was not affected by any of the interventions.The epicardially attached miniaturized ultrasound transducer allowed the precise detection of different levels of coronary flow reduction. The results also showed a quantitative and linear relationship among coronary flow, ischemia, and myocardial function. Thus, the ultrasound transducer has the potential to improve the monitoring of myocardial ischemia and to detect graft failure during and after heart surgery.

This is the pre-print version of an article published by Taylor & Francis in Scandinavian Cardiovascular Journal on 12 December 2017, available online: http://www.tandfonline.com/10.1080/14017431.2017.1416157. 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-1β, 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 (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.

OBJECTIVES: Miniaturized accelerometers attached to the epicardium have been shown to provide useful clinical information. However, attachment of such a sensor has been cumbersome due to requirement of aligning the three sensor axes with the cardiac coordinate axes, limiting clinical utility. We propose a new method to process the three-dimensional (3D) accelerometer signal that does not require such alignment. METHODS: In 20 open-chest pigs, miniaturized 3D accelerometers were fixated on the epicardium in apical and basal regions of left ventricle. Accelerations in circumferential, longitudinal and radial directions were measured and a 3D velocity vector was calculated. Systolic velocity along the 3D vector and velocities in circumferential, longitudinal and radial directions were compared with the positive time derivate of left ventricular pressure during changes in global left ventricular function (epinephrine, esmolol and fluid loading) and to strain echocardiography during left anterior descending artery occlusion. RESULTS: Distinct changes in all accelerometer velocities were observed during alterations on global and regional left ventricular function. Accelerometer 3D and circumferential systolic velocities in apical region best reflected left ventricular function during interventions on global function by correlating significantly with the positive time derivate of left ventricular pressure, r = 0.83 and r = 0.86, respectively. The accelerometer 3D velocity also demonstrated equally good capacity as circumferential velocity in discriminating coronary occlusion from interventions on global left ventricular function with sensitivity/specificity of 0.90/0.83 and 0.90/0.86, respectively. CONCLUSIONS: Accelerometer 3D systolic velocity showed very good correspondence to changes in global and regional left ventricular function. Our results demonstrate that by the use of the accelerometer 3D motion vector, no alignment of the sensor with the cardiac coordinate axes was required. This increases potential clinical applicability of the accelerometer in cardiac surgery.

Hepatic biomarkers are often not assessed routinely after cardiac surgery. Alanine aminotransferase (ALT) has become the primary biomarker of any type of liver injury. Our purpose was to study the prognostic value of serum ALT in early and late mortality.Patients subjected to any type of cardiac operation from January 1999 through December 2010 were studied. According to postoperative maximum ALT level, four groups were created: group 1 = ALT ≤ 50 U/L (n = 8,669), group 2 = ALT 50 to 150 U/L (n = 3,055), group 3 = ALT 151 to 500 U/L (n = 248), and group 4 = ALT 500 U/L (n = 50). Cox multivariate modeling was used for survival analysis.Patients in groups 3 and 4 had increased 30-day mortality (hazard ratio [HR] = 8.07 [4.15-15.69], p 0.001 and HR = 19.07 [9.88-36.80], p 0.001, respectively). Late mortality was increased for group 4 after final adjustments (HR = 1.87 [1.18-2.95], p = 0.007).Elevated postoperative ALT level (above 150 U/L) is closely associated with early mortality after cardiac surgery. ALT level above 500 U/L implies a substantial liver dysfunction with a considerable negative association on both early and late survival.

The aim of this study was to investigate experimental conditions for efficient and controlled in vivo liver tissue ablation by magnetic resonance (MR)-guided high-intensity focused ultrasound (HIFU) in a swine model, with the ultimate goal of improving clinical treatment outcome. Histological changes were examined both acutely (four animals) and 1 wk after treatment (five animals). Effects of acoustic power and multiple sonication cycles were investigated. There was good correlation between target size and observed ablation size by thermal dose calculation, post-procedural MR imaging and histopathology, when temperature at the focal point was kept below 90°C. Structural histopathology investigations revealed tissue thermal fixation in ablated regions. In the presence of cavitation, mechanical tissue destruction occurred, resulting in an ablation larger than the target. Complete extra-corporeal MR-guided HIFU ablation in the liver is feasible using high acoustic power. Nearby large vessels were preserved, which makes MR-guided HIFU promising for the ablation of liver tumors adjacent to large veins.