ORIGINAL ARTICLE – ADULT CARDIAC
Interactive CardioVascular and Thoracic Surgery 21 (2015) 573–582 doi:10.1093/icvts/ivv191 Advance Access publication 8 August 2015
Cite this article as: Grymyr O-JHN, Nguyen A-TT, Tjulkins F, Espinoza A, Remme EW, Skulstad H et al. Continuous monitoring of cardiac function by 3-dimensional accelerometers in a closed-chest pig model. Interact CardioVasc Thorac Surg 2015;21:573–82.
Ole-Johannes H.N. Grymyra,b,*, Anh-Tuan T. Nguyenc, Fjodors Tjulkinsc, Andreas Espinozaa,d, Espen W. Remmea,e, Helge Skulstadf, Erik Fossea,b, Kristin Imenesc and Per S. Halvorsena,d a b c d e f
The Intervention Centre, Oslo University Hospital, Oslo, Norway Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Department of Micro and Nano Systems Technology, Buskerud and Vestfold University College, Kongsberg, Norway Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway K.G. Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway Department of Cardiology, Oslo University Hospital, Oslo, Norway
* Corresponding author. The Intervention Centre, Rikshospitalet, Oslo University Hospital, 0027 Oslo, Norway. Tel: +47-23070100; fax: +47-23070110; e-mail:
[email protected] (O.-J.H.N. Grymyr). Received 18 February 2015; received in revised form 1 June 2015; accepted 15 June 2015
Abstract OBJECTIVES: Cardiac wall motions reflect systolic and diastolic function. We have previously demonstrated the ability of a miniaturized three-axis (3D) accelerometer to monitor left ventricular function in experimental models and in patients. The main aim of this study was to investigate the clinical utility of the method for monitoring the left and right ventricular function during changes in global and regional cardiac function in a postoperative closed-chest situation. METHODS: In 13 closed-chest pigs, miniaturized 3D accelerometers were placed on the left ventricle in the apical and basal regions and in the basal region of the right ventricle. An epicardial 3D motion vector was calculated from the acceleration signals in each heart region. Peak systolic velocity along this 3D vector (3D Vsys) was compared with the positive time derivative of the left and right ventricular pressure and with cardiac index during changes in global LV function (unloading, fluid loading, esmolol, dobutamine) and with ultrasound during regional left ventricular dysfunction (3-min occlusion of the left anterior descending coronary artery). RESULTS: Significant and typical changes in accelerometer 3D Vsys were seen in all heart regions during changes in global cardiac function. 3D Vsys reflected the left and right ventricular contractility via significant correlations with the positive time derivative of the left and right ventricular pressure, r = 0.86 and r = 0.72, and with cardiac index r = 0.82 and r = 0.73 (all P < 0.001), respectively. The miniaturized accelerometers also detected regional dysfunction, but showed reduced ability to localize ischaemia as the 3D Vsys in all heart regions showed similar reductions during coronary artery occlusion. CONCLUSIONS: Miniaturized 3D accelerometers placed on the heart can assess global and regional function in a closed-chest model. The technique may be used for continuous postoperative monitoring after cardiac surgery. Keywords: Left ventricular function • Right ventricular function • Cardiac monitoring • Motion sensor
INTRODUCTION Accelerometers are motion sensors which, when attached to the heart, can provide detailed information on heart wall motion and cardiac function [1]. We have previously demonstrated the capability of this method to quantify and monitor global and regional left ventricular function in experimental studies and in patients scheduled for off-pump coronary artery bypass grafting [2, 3]. Our goal is to use a combined miniaturized accelerometer and † Presented at the Annual Techno-College Meeting at the 26th Annual Meeting of the European Association for Cardio-Thoracic Surgery, Barcelona, Spain, 27 October 2012.
temporary pacemaker lead to improve postoperative monitoring of cardiac surgery patients. Such a sensor would permit continuous monitoring of ventricular function after cardiac surgery, enabling early detection of complications and treatment guidance. However, our previous studies on the accelerometer have all been performed under open-chest conditions and with a large prototype [1–4]. Sternotomy and pericardiotomy affect cardiac motion and contraction [5, 6]. The findings from these studies therefore require validation under closed-chest conditions. Furthermore, in these earlier studies, the sensor was sutured onto the epicardial surface; evaluation of a subepicardial attachment is now required as this approach would facilitate insertion and postoperative removal of the sensor.
© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
ORIGINAL ARTICLE
Continuous monitoring of cardiac function by 3-dimensional accelerometers in a closed-chest pig model†
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A new miniaturized three-axis (3D) accelerometer has been developed for postoperative testing [7]. The small size of the sensor also allows subepicardial positioning. The main aim of this study was to test the performance of the accelerometer in a postoperative closed-chest situation. We also aimed to investigate the effects of chest closure on the accelerometer measurements and to examine whether subepicardial positioning of the sensor would increase the reliability of the method in monitoring cardiac function. Our hypotheses were (i) that chest closure would reduce the amplitude of the acceleration signals, (ii) that under closed-chest conditions, the accelerometer would be able to monitor changes in global left and right ventricular function induced by pharmacological interventions, and detect regional myocardial ischaemia during temporary coronary artery occlusion and (iii) that subepicardial positioning of the sensor would increase signal quality.
METHODS Animal preparation Thirteen Norwegian Landrace pigs of either sex (44 ± 4 kg) were used. The study protocol was approved by the Norwegian Animal Research Authority. Anaesthesia was induced by intravenous pentobarbital 2–3 mg/kg and morphine 0.5–1.0 mg/kg until tracheotomy was completed. General anaesthesia was continued with inhaled isoflurane (1.0–1.5%) and morphine infusion (0.15–0.2 mg/kg/h). Mechanical ventilation was performed by a LeonPlus anaesthesia machine (Heinen + Löwestein, Germany), with inspired oxygen fraction 0.35 and tidal volume/ventilation rate adjusted to keep arterial PCO2 5.5 kPa. Ringer’s acetate was given at the rate of 10–15 ml/ kg/h to keep a diuresis above 1 ml/kg/h. No blood transfusions were given. A PiCCO catheter (Pulsion, Munich, Germany) was inserted into the left femoral artery. The right carotid artery and the right
internal jugular vein were exposed. The right jugular vein was cannulated with an 8 French introducer and a pulmonary artery catheter (Edwards Lifesciences Corporation, Irvine, CA, USA) inserted. The right carotid artery was cannulated using an 8 French introducer to allow insertion of a micromanometer (MPC-500, Millar Instruments, TX, USA) into the left ventricle. A median sternotomy was performed, and the pericardium opened. A second micromanometer was inserted directly into the right ventricular cavity and secured with a suture. A snare was placed around the left anterior descending artery (LAD) distal to the second diagonal branch, and left open. Four silicon encapsulated 3D accelerometers (CMA3000-A, Murata Electronics Oy, Vantaa, Finland) with dimensions of 2.8 × 3 × 10 mm were attached to the heart (Fig. 1A). Three of them were sutured to the epicardium by stitches (Prolene 6-0): one in the left ventricular apical region, supplied by the LAD, the second in the left ventricular basal region, supplied by the circumflex coronary artery and the third to the right ventricular basal region. A fourth accelerometer was placed subepicardially 1–1.5 cm lateral to the epicardial sensor in the left ventricular apical region by use of Seldinger’s technique through a 9 French introducer. The sensor was positioned 2 mm subepicardially. Two miniaturized single-element ultrasonic 10-MHz transducers (Imasonic SA, Besancon, France) with a diameter of 3 mm were attached with three stiches (Prolene 6-0) in the left ventricular apical region and right ventricular basal region (Fig. 1A), and used as the reference method for detection of ischaemia [8]. The chest was closed with two layers of sutures (Monofilament Nylon 2-0), and the pig was placed in the dorsal supine position.
Experimental protocol The pig was allowed to rest for 30 min after surgery before baseline measurements were undertaken under open-chest conditions.
Figure 1: (A) Schematic illustration showing sensor placements and instrumentation in the heart. Four 3D accelerometers and two miniaturized ultrasonic transducers were used. Accelerometer #4 was positioned subepicardially. Pressure catheters were positioned in the LV and RV, and in the pulmonary artery. A snare was placed around the left anterior descending coronary artery distally to the second diagonal branch. (B) A 3D displacement loop showing an accelerometer’s trajectory during one cardiac cycle in the LV apical region. The loop started and stopped at ECG R-peak. The farthest part of the loop corresponded to end systole and during baseline a reference vector is drawn from ECG R-peak to this point in the loop. Velocity was calculated along this reference vector. The first 150 ms from ECG R-peak are marked in blue, and peak systolic velocity is measured within this interval (3D Vsys). The diastolic early (e0 ) and atrial (a0 ) velocities are also indicated. LV: left ventricle; RV: right ventricle; ECG: electrocardiogram.
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Pressures and haemodynamic measures The electrocardiogram (ECG) and hydrostatic pressures were monitored using a Siemens SC 9000XL monitor (Siemens AG, Erlangen, Germany). Mean arterial pressure and central venous pressure were recorded via the introducers in the carotid artery and the jugular vein. From the micromanometer in the ventricles, peak systolic pressure of the left and right ventricle and end-diastolic pressure were measured, and positive and negative time derivatives (dP/ dtmax and dP/dtmin) calculated. Systole was defined from start of R-peak on ECG to left ventricular dP/dtmin. The pulmonary artery catheter was used for registrations of mean pulmonary artery pressure. Cardiac index was calculated by transthoracic thermodilution with PiCCO. PiCCO was chosen because it offered continuous monitoring of cardiac index during the LAD occlusions. Stroke volume index and systemic vascular resistance index were calculated from the PiCCO measurements and pulmonary vascular resistance index from the pulmonary artery catheter measurements.
Accelerometer The acceleration signals were collected by an NI USB 6009 AD converter (National Instruments, Inc., Austin, TX, USA), using the LabVIEW software (National Instruments, Inc.) and a high-pass filter used to reduce effects of gravity and breathing motion on the signals. Data from the accelerometers were obtained over a 10-s period at all time points, ensuring that all heartbeats in at least one ventilation cycle were included. Synchronous and continuous sampling of accelerometer signals, ECG and pressures (sample rate 500/s) allowed measurement of heart motions in different phases within the cardiac cycle. A customized Matlab algorithm (MathWorks, Natick, MA, USA) was used to automatically calculate the accelerometer variables. Mathematical time integration of the acceleration signals was performed to obtain the corresponding epicardial velocities and displacements, which could be presented in three dimensions (3D) simultaneously. Based on 3D displacement loops, a 3D motion vector in the main contraction direction was calculated during baseline, and used as a reference vector (Fig. 1B). The effects of the interventions on displacement and velocity were calculated along this 3D vector, in the form of relative changes from baseline [9]. As the greatest changes in cardiac function revealed by epicardially attached accelerometers
are seen in early systole, the peak systolic velocity within a 150-ms time interval after ECG R-peak (3D Vsys) was automatically measured and used as the accelerometer indicator of left ventricular systolic function (Fig. 1B). All accelerometer 3D Vsys measurements were calculated automatically.
Ultrasound Both transoesophageal and transthoracic ultrasound recordings are difficult to perform in the closed-chest pig due to a different orientation of the heart within the chest compared with humans. We therefore used two miniaturized ultrasonic transducers, which produced high-quality M-mode images of the ventricular walls. Ultrasonic transducers are sensitive markers for regional ischaemia, but are less able to detect changes in global cardiac function [10]. The ultrasonic transducers were therefore used to confirm ischaemia during LAD occlusion. The pictures were sampled by a 14-bit digitizer board (NI-PCI 5122, National Instruments, Inc.) [8], and were analysed using the LabView 8.2 software (National Instruments, Inc.). End-diastolic and end-systolic wall thickness was recorded, and the transmural systolic displacement calculated by subtracting end-diastolic from end-systolic wall thickness. Systolic displacement was used as a reference for the detection of ischaemia.
Statistical analysis Based on the results of previous experiments, sample size was calculated assuming a mean difference in response to accelerometer 3D Vsys of 2.0 cm/s (δ), standard deviation (SD) of 2.0 cm/s (σ) and α of 0.05. The null hypothesis could be rejected with probability ( power) of 0.80 by using 10 animals. Parametric statistical methods were used (data showed normal distribution for each intervention), and data are presented as mean ± SD unless otherwise indicated. Paired sample t-tests were used for repeated measurements with Bonferroni correction. Baseline values were obtained before each intervention. No differences were found between haemodynamic baseline values under closed-chest conditions, so the first baseline was used for comparison with the subsequent interventions. Receiver-operating characteristic (ROC) curves were constructed to determine sensitivity, specificity and cut-off values for detection of ischaemia by the accelerometer. The Pearson correlation coefficient was used for the correlation analyses. The Bland Altman method was used to compare the measurements from the subepicardial and epicardial fixated accelerometers. P < 0.05 was considered significant. Statistical analysis was performed by SPSS (Version 20, SPSS, Inc., IL, USA).
RESULTS Two pigs were excluded due to cardiac arrest during the surgical preparation. One pig had heart failure after LAD occlusion under closed-chest conditions and measurements from the last intervention were not obtained. In one pig, the accelerometers in the left apical region were placed outside the LAD supply area (verified with the ultrasonic transducer) and data were omitted from these sensors during LAD occlusion. Two ultrasound sensors malfunctioned, resulting in missing data from the right ventricle in one pig and the left ventricle during LAD occlusion in another pig.
ORIGINAL ARTICLE
Thereafter, the chest was closed and new measurements were performed after 30 min. Under closed-chest conditions, measurements were made during reduced or increased preload and contractility, and also during ischaemia. Preload was reduced by applying a positive end-expiratory pressure (PEEP) of 10 cmH2O on the ventilator and increased by fluid infusion of 500 ml Ringer’s acetate. Myocardial contractility was enhanced by an infusion of dobutamine (10 µg/kg/min) and decreased by an infusion of esmolol (range 10–37 mg/kg/h) to achieve changes in mean arterial blood pressure of at least 30% relative to baseline values. Ischaemia was induced by occluding LAD for 3 min. A resting period of at least 30 min between each intervention was used to ensure stable haemodynamic baseline values. Finally, the chest was reopened, and a second LAD occlusion performed after 30 min. Regional dysfunction during the occlusion of LAD was verified through reduced systolic wall motion revealed by the ultrasonic transducers in the left ventricular apical region.
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Table 1: Haemodynamic parameters during the experiment Baselines
Heart rate (beats/s) Mean arterial pressure (mmHg) Central venous pressure (mmHg) Cardiac index (l/min/m2) Systemic vascular resistance index (dynes s/cm5/m2) Pulmonary vascular resistance index (dynes s/cm5/m2) Stroke volume index (ml/beat/m2) LV peak systolic pressure (mmHg) LV end-diastolic pressure (mmHg) LV dP/dtmax (mmHg/s) LV dP/dtmin (mmHg/s) RV peak systolic pressure (mmHg) RV end-diastolic pressure (mmHg) RV dP/dtmax (mmHg/s) RV dP/dtmin (mmHg/s) LV end-diastolic wall thickness (mm) LV end-systolic wall thickness (mm) LV systolic displacement (mm) RV end-diastolic wall thickness (mm) RV end-systolic wall thickness (mm) RV systolic displacement (mm)
89 ± 12 61 ± 9 7±3 4.8 ± 0.7 863 ± 89 125 ± 87 54 ± 5 86 ± 11 13 ± 4 1379 ± 303 −1525 ± 442 30 ± 3 10 ± 3 510 ± 96 −471 ± 105 9.5 ± 1.6 12.9 ± 2.5 3.4 ± 1.1 4.9 ± 1.5 6.6 ± 2.5 1.8 ± 1.3
Global interventions in closed chest Closed chest †
PEEP
Fluid a
97 ± 11 62 ± 9 9 ± 2† 5.1 ± 1.0 840 ± 108 194 ± 80† 53 ± 10
93 ± 10 51 ± 10a 11 ± 3a 3.6 ± 0.8a 1038 ± 100a 196 ± 115 39 ± 7†a
87 ± 6 14 ± 4 1357 ± 285 −1681 ± 751 35 ± 3† 12 ± 3† 570 ± 82* −623 ± 178†
75 ± 9†a 15 ± 3 1127 ± 369† −1283 ± 514†a 32 ± 3†a 12 ± 3 439 ± 77†a −547 ± 301 10.3 ± 2.5* 13.8 ± 3.0* 3.5 ± 1.2 5.0 ± 1.1 6.1 ± 1.8 1.2 ± 0.7
9.4 ± 1.6* 12.9 ± 2.3 3.5 ± 1.1 4.9 ± 1.3 6.0 ± 1.8* 1.1 ± 0.6
Values from open-chest conditions are marked in bold. Data presented as mean ± SD. Paired sample t-test. LV: left ventricle. RV: right ventricle; PEEP: positive end-expiratory pressure. Panel of baselines: comparison of baselines open versus closed: *P < 0.05, †P < 0.01. Panel of global interventions: comparison to baseline closed: *P < 0.05, †P < 0.01. Panel of LAD occlusion: comparison to respective baseline: ‡P < 0.05, $P < 0.01. a P < 0.05 after Bonferroni correction for multiple comparisons.
95 ± 10 64 ± 7 12 ± 3†a 5.2 ± 1.0 899 ± 228 177 ± 82 56 ± 12*
LAD occlusions Dobutamine †a
Esmolol
Closed chest
150 ± 19 68 ± 5 7 ± 3†a 8.9 ± 0.8†a 521 ± 67†a 124 ± 46† 60 ± 9†a
102 ± 6 51 ± 4†a 11 ± 2†a 4.1 ± 0.7†a 819 ± 131 223 ± 95 40 ± 7†a
101 ± 9 44 ± 8$a 11 ± 2$a 4.0 ± 1.5‡ 739 ± 120‡ 159 ± 102 40 ± 15$a
85 ± 5 20 ± 3†a 1337 ± 287 −1418 ± 554* 40 ± 5†a 17 ± 3†a 555 ± 75 −703 ± 301
122 ± 23†a 13 ± 3 4820 ± 1226†a −2680 ± 769†a 47 ± 6†a 8 ± 3†a 1964 ± 718†a −1170 ± 444†a
75 ± 6†a 17 ± 4 907 ± 152†a −975 ± 190†a 35 ± 4 15 ± 4†a 439 ± 72†a −541 ± 151†a
67 ± 13$a 20 ± 4$a 940 ± 207$a −904 ± 219$a 34 ± 5 17 ± 4$a 481 ± 84$a −495 ± 107‡
9.7 ± 2.1 13.6 ± 3.1 3.8 ± 1.3 4.7 ± 1.3 5.8 ± 1.8 1.2 ± 0.6
9.8 ± 2.2 17.2 ± 2.7†a 7.3 ± 1.6†a 5.4 ± 1.7* 8.7 ± 3.0†a 3.3 ± 1.7†a
9.8 ± 1.7 12.1 ± 2.2 2.3 ± 1.0†a 4.6 ± 1.2 5.5 ± 1.5 0.9 ± 0.4
9.5 ± 1.5 10.4 ± 2.0$a 1.0 ± 1.1$a 5.2 ± 1.3 6.2 ± 1.6 1.0 ± 1.0
Open chest 106 ± 8$a 50 ± 4$a 10 ± 3$a 4.7 ± 0.9 708 ± 89‡ 159 ± 93 45 ± 11$a 73 ± 8‡ 17 ± 4 1032 ± 84$ −1133 ± 235 32 ± 7 14 ± 4$a 486 ± 136 −647 ± 352 8.6 ± 1.8 10.2 ± 2.3* 1.6 ± 1.0$a 4.8 ± 1.3 6.2 ± 2.1 1.4 ± 0.8
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Open chest
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Effects of chest closure Chest closure increased heart rate, central venous pressure, pulmonary vascular resistance index, right ventricular peak and end-diastolic pressures in addition to dP/dtmax (Table 1). The right ventricular end-systolic wall thickness was reduced. Thus, chest closure mainly affected right ventricular filling and contraction. Chest closure significantly reduced 3D Vsys only in the left apical region (Fig. 2).
Interventions in the closed-chest situation Interventions affecting global cardiac function. Significant haemodynamic changes were observed during interventions targeting global cardiac function (Table 1). Interventions with PEEP and esmolol produced a reduction in the left and right ventricular systolic function. The magnitude of changes in haemodynamic variables for these two interventions was similar, with the exception of the left and right ventricular dP/dtmax and dP/dtmin, which were affected to a greater degree by esmolol. In addition, a significant decrease in left ventricular systolic displacement, revealed by the ultrasonic transducers, was only observed with esmolol. Dobutamine infusion increased heart rate and the left and right ventricular contractility when assessed by the ultrasonic transducers, peak systolic pressures and dP/dtmax. Furthermore, there were increases in cardiac index and stroke volume index, whereas the right ventricular end-diastolic- and central venous pressures were reduced. Fluid loading significantly increased central venous pressure, the left and right end-diastolic pressures and stroke volume index. The right ventricular dP/dtmin also changed significantly. Significant changes were seen in accelerometer 3D Vsys in all sensor locations during the interventions affecting global cardiac
function (Figs 3 and 4). Unloading with PEEP reduced 3D Vsys in all accelerometer sensors, whereas during fluid loading there were decreases in 3D Vsys for the sensors placed on the right ventricle and the apical region of the left ventricle, but an increase in 3D Vsys for the sensor placed on the basal region of the left ventricle. Similar changes were observed for all sensors during infusions with dobutamine and esmolol. The infusion with dobutamine increased the accelerometer 3D Vsys for all sensor locations, whereas the opposite was observed during the esmolol infusion.
Interventions affecting regional cardiac function. Occlusion of the LAD was verified by the miniaturized ultrasonic transducer in the left ventricular apical region with a significant reduction in systolic displacement in both open- and closed-chest situations (Table 1). No changes were seen with the ultrasonic transducer placed on the right ventricle. The LAD occlusion also had systemic haemodynamic effects in both open- and closed-chest situations, but the greatest changes during this intervention were seen when the chest was closed (Table 1). Under these conditions, LAD occlusion led to significant reductions in cardiac index, stroke volume index, mean arterial pressure, central venous pressure, left ventricular pressure and dP/dtmax in both ventricles. The left and right ventricular end-diastolic pressures increased. A marked reduction in accelerometer 3D Vsys was observed in all accelerometer sensors during the LAD occlusion in both open and closed-chest situations (Fig. 5). However, an increase in the post-systolic velocity, a sensitive marker of myocardial ischaemia [11, 12], was most prominent in the 3D velocity signal for the accelerometer placed in the left ventricular apical region and was observed only during the LAD occlusion and not during the interventions affecting global cardiac function (Fig. 3). Using the ROC analysis, the epicardial sensor in the apical region demonstrated an area under the curve of 0.84 (P < 0.001) with a sensitivity of 78% and a specificity of 73%, with a cut-off value of 0.8 cm/s to discriminate regional ischaemia from changes in global cardiac function. During closed-chest interventions, the accelerometer 3D Vsys on the right ventricle correlated significantly with the right ventricular dP/dtmax (r = 0.72, P < 0.001) and cardiac index (r = 0.73, P < 0.001). For the accelerometer sensors in the apical and basal regions of the left ventricle, the correlations with left ventricular dP/dtmax were r = 0.77 (P < 0.001) and r = 0.63 (P < 0.001), and with cardiac index r = 0.74 (P < 0.001) and r = 0.69 (P < 0.001), respectively.
Epicardial versus subepicardial positioning of the accelerometer
Figure 2: Accelerometer peak systolic velocities (3D Vsys) with open and closed chest. Data reported as mean ± SD and analysed by paired sample t-tests. *P < 0.05, †P < 0.01. LV: left ventricle; RV: right ventricle; SD: standard deviation.
In the left ventricular apical region, the subepicardial sensor tracked similar changes in global and regional left ventricular function to the sensor placed epicardially (Fig. 6A). The subepicardial accelerometer signal displayed less variation during the ventilation cycle, especially after chest closure (Fig. 6B). The correlation between the epicardial and subepicardial 3D Vsys was 0.91 (P < 0.001). The 3D Vsys of the two sensors was almost equal during the interventions, with a mean difference of 0.93 cm/s and limits of agreements of −3.87 to 5.73 cm/s. The subepicardial 3D Vsys demonstrated an even better correlation with the left ventricular dP/dtmax and cardiac index, r = 0.86 and r = 0.82, respectively (both P < 0.001). ROC analysis for the subepicardial 3D Vsys demonstrated a sensitivity/specificity of 78%/83% with area under the curve of 0.81 (P = 0.003) using a cut-off value of 2.8 cm/s to discriminate regional myocardial ischaemia. In summary, the
ORIGINAL ARTICLE
Our dataset consists of data from 11 pigs, which remained circulatory stable during the experiment with minor changes in haemodynamic baseline values and no significant changes in serum lactate concentration or haemoglobin values throughout the experiment, 1.2 ± 0.3 to 1.0 ± 0.3 mmol/l and 8.2 ± 0.6 to 7.4 ± 0.5 g/dl, respectively.
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Figure 3: Representative accelerometer 3D velocity traces in the LV apical and basal regions and the RV basal region during alterations of global cardiac function and occlusion of the LAD. Peak systolic velocity (3D Vsys) within 150 ms after ECG R-peak (blue interval) is marked with arrows. LV: left ventricular; RV: right ventricular; LAD: left descending coronary artery; PEEP: positive end-expiratory pressure.
subepicardial sensor showed less signal variability, correlated better with global haemodynamic measurements and had similar ability to detect ischaemia compared with the epicardial sensor.
DISCUSSION Our main finding was that the accelerometer 3D Vsys made it possible to track changes in both global and regional cardiac function during pharmacological interventions and temporary coronary artery occlusion in a closed-chest situation. These results imply that the sensor can be used as a continuous postoperative monitoring modality in cardiac surgery patients for the guidance of treatment and the detection of complications. Subepicardial placement of the sensor allows it to be removed in a similar manner to temporary pacemaker wires.
Effects of chest closure The miniaturized version of the accelerometers used in this study allowed investigation of the effects of chest closure on the accelerometer signals. The main effect of this intervention was a marked decrease in 3D Vsys in the left ventricular apical region. In the openchest situation, loss of pericardial pressure causes the apex to move more freely [5, 6]. Chest closure may therefore stabilize the apex of the left ventricle. Furthermore, when the pig is placed in a dorsal position as in our study, the apex of the left ventricle is pointing upwards. In this situation, apical systolic motion is affected by translational motion in addition to regional myocardial contraction. This is supported by the fact that systolic displacement as revealed by the ultrasonic transducer did not change after chest closure (Table 1) and also that no changes in accelerometer velocities were observed in other heart regions. In further support of the argument that the
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main effect of chest closure is mechanical stabilization of the apex, minor haemodynamic changes were also detected during this intervention. Our findings on chest closure will need to be verified in patients as humans have a different orientation of the heart within the chest.
Figure 4: Accelerometer peak systolic velocities (3D Vsys) in the left and right ventricle (LV and RV) under closed-chest conditions during interventions affecting global cardiac function. Data reported as mean ± SD and analysed by paired sample t tests. *P < 0.05, †P < 0.01. BP < 0.05 after Bonferroni correction for multiple comparisons. LV: left ventricular; RV: right ventricular; PEEP: positive end-expiratory pressure.
The current study confirmed our previous findings under closedchest conditions [1–3, 9, 13]. Significant changes were observed for the accelerometer velocities in both the left and right ventricles during the interventions affecting global and regional cardiac function in our closed-chest model. Importantly, the accelerometer measurements obtained from both ventricles correlated significantly with dP/dtmax and cardiac index during the interventions affecting global function. These results demonstrate that the accelerometer can be used for monitoring global cardiac function also after cardiac surgery. This is important, as there is no existing standard monitoring modality that can assess both the left and right ventricular function continuous in real time. Compared with haemodynamics and ST-segment monitoring, the accelerometer is superior in detection
Figure 5: Accelerometer peak systolic velocities (3D Vsys) in the LV and RV during occlusion of the LAD under open- and closed-chest conditions. The horizontal blue lines indicate the mean values. Data analysed by paired sample t-tests. †P < 0.01. BP < 0.05 after Bonferroni correction for multiple comparisons. LV: left ventricular; RV: right ventricular; LAD: left anterior descending coronary artery.
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Performance of the accelerometer under closed-chest conditions
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Figure 6: (A) Accelerometer peak systolic velocity (3D Vsys) for the subepicardial accelerometer in the LV apical region during interventions targeting global and regional cardiac function under closed-chest conditions. Data reported as mean ± SD and analysed by paired sample t-tests. *P < 0.05, †P < 0.01. BP < 0.05 after Bonferroni correction for multiple comparisons. (B) Representative accelerometer 3D velocity traces from subepicardial and epicardial accelerometers in the LV apical region. The dashed line marks the variation in 3D Vsys during two ventilation cycles. LV: left ventricular; RV: right ventricular; LAD: left descending coronary artery; PEEP: positive end-expiratory pressure.
of regional ischaemia [3, 13]. Echocardiography is unsuitable for continuous real-time assessment of cardiac function in the postoperative phase as the examination is performed intermittently, usually after deterioration of the patient’s condition. Furthermore, the method is resource demanding, since a cardiologist is often required to do the examination and interpreting the results. The accelerometer has an advantage as it provides a real-time and continuous output, which can be processed and displayed by an automated beat-to-beat analysis. Still, the accelerometer must be considered a supplementary rather than competing modality to echocardiography. The sensor intends to be placed like ordinary pacemaker lead during surgery and removal postoperatively when there is no need for further monitoring. Thus, the technique is currently limited to patients undergoing open-heart surgery. In the present study, regional ischaemia was induced by a temporary occlusion of the LAD and characterized by substantial reductions in accelerometer systolic velocities in all measured heart regions. This was evident in both open- and closed-chest conditions. In contrast to the accelerometer measurements, systolic displacement as revealed by the ultrasonic transducer was decreased only in the left ventricular apical region during LAD occlusion. This demonstrated that accelerometer velocities in the non-ischaemic regions were influenced by a considerable tethering effect from the remote ischaemic left ventricular apical region.
This finding is in line with our previous studies [1, 9], but has not been verified before under closed-chest conditions and in the right ventricle. In the pig, collaterals from the LAD supply 30% of the right ventricle, and mainly the apical region [14]. Occlusion of the LAD resulted in biventricular apical ischaemia in our model and was visually observed as cyanosis. Thus, it is likely that the decrease in right ventricular accelerometer 3D Vsys during LAD occlusion was due to an effect of tethering from a dysfunctional apical right ventricular segment. LAD occlusion induced biventricular pump failure with decreases in peak systolic pressures, dP/dtmax, stroke volume index and an increase in end-diastolic pressures. It is therefore probable that this also contributed to the decrease in accelerometer 3D Vsys observed during LAD occlusion. Taken together, these results indicate that it is difficult to localize an ischaemic heart region by use of accelerometers. Still, this may not be a disadvantage, as it means that few sensors are needed to detect the presence of ischaemia, irrespective of which region is affected. The clinical implications of these findings would be that if a substantial decrease in accelerometer 3D Vsys occurs in a circulatory stable patient, this should trigger further investigations by echocardiography in order to precisely localize which heart region is affected. In a haemodynamic compromised patient, treatment should be aimed at optimizing the circulation to exclude global myocardial hypoperfusion due to a low perfusion pressure. In this way, the
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Epicardial versus subepicardial positioning of the accelerometer After chest closure, an increased variability of the epicardial accelerometer signal due to breathing was observed compared with the signals from the sensor placed subepicardially (Fig. 6B). A temporary cessation of ventilation almost abolished this variability (data not shown). This indicates that epicardial accelerometer measurements in the left ventricular apical region were most affected by mechanical compression and decompression by the surrounding lung tissue. Furthermore, data from the subepicardial sensor correlated better with global haemodynamic measurements. Nevertheless, the epicardial accelerometer demonstrated a robust ability to track changes in global and regional left ventricular function. This was achievable by use of our automatic signal processing, which averaged peak systolic velocities over several heart beats [2, 9]. The measured absolute values and significance level at each intervention were similar between the sensors. These results imply that the accelerometer does not need to be placed within the myocardium to be reliable in monitoring the left ventricular function after cardiac surgery.
Clinical implications The method may be used to evaluate the effects of treatment and to detect complications during and after cardiac surgery. Complex cardiac surgery is being performed in ever older and sicker patients [15–17]. Many of them have severe biventricular failure where continuous monitoring of the left and right ventricular function by the accelerometer can be beneficial. The accelerometers may prove to be a useful monitoring modality in patients treated with a left ventricular assist device and in patients undergoing heart transplants. The results of this study indicate that this method may have the potential to improve clinical outcomes in these high-risk patients. With the accelerometer, a precise and continuous quantification of the left and right ventricular function is possible for days by the automatic analysis of epicardial systolic velocities. The accelerometer velocities can be processed and displayed in real-time on an external monitor and, if deviations from normal activity are detected, an alarm can be triggered. Subepicardial positioning of the accelerometer is preferable for clinical use as the sensor has to be removed, just like ordinary pacemaker leads, before the patient leaves the hospital. A prototype of the next generation of cardiac accelerometers with pacing functionality and outer dimensions of 2 mm in diameter has recently been tested. The sensor is inserted in the same way as temporary pacemaker wires. Further experimental and clinical studies will be performed to test the clinical utility of this new multifunctional accelerometer. The technique may also be useful in heart failure patients not needing open-heart surgery. In the future, we envision a miniaturized wireless combined accelerometer and pacemaker sensor may be implanted by endoscopy through a mini-thoracotomy. After hospital discharge, such a permanent sensor may give continuous information on arrhythmias, ventricular performance and occurrence of ischaemic events during daily living activities. This offers promise for better diagnosis, earlier treatment of complications and improved guidance of interventions in such patients.
Limitations The interventions affecting global and regional cardiac function were not performed in a randomized order as we experienced a prolonged depressive effect of esmolol in our pilot experiments. Furthermore, coronary artery occlusion in the pig carries a risk of ventricular fibrillation and loss of the animal. The optimal study design would have been to perform all interventions on global and regional function under both open and closed conditions. This would, however, have extended the experiment substantially with the risk of circulatory instability in the pig. Moreover, the performance of the sensor has previously been documented thoroughly under open-chest conditions [1–3, 9, 13]. The miniaturized ultrasonic transducer allows a precise quantification of regional ischaemia [10, 18], but the system allows only two sensors to be used at the same time. No ultrasonic transducer was placed in the left ventricular basal region and, therefore, we cannot exclude the possibility that this region was ischaemic during LAD occlusion. It is still likely that tethering from an ischaemic apical region was the main cause of the observed reduction in 3D Vsys in this region, as myocardial strain has been found to be unaltered in this region during LAD occlusion in similar experimental models [1, 9]. Bleeding and laceration of the ventricular wall is a feared complication of temporary pacemaker use. This did not occur with the accelerometers used in our study. Risk assessment is required by means of a greater number of implantations of our latest prototype.
CONCLUSIONS Miniaturized 3D accelerometers placed on the heart enabled a precise real-time quantification of global left and right ventricular function in a closed-chest model. Under these conditions, regional left ventricular dysfunction was detected with high sensitivity and specificity. However, sensor measurements in remote nonischaemic regions were also affected due to tethering effects, so the information provided by the sensor has limited regional specificity. This may be an advantage, as it means that few sensors will be required to detect the presence of ischaemia. Our results imply that the sensor can be used as a postoperative monitoring modality for continuous monitoring of the left and right ventricular function in cardiac surgery patients in order to guide medical treatment and detect complications.
ACKNOWLEDGEMENTS We thank Are Hugo Pripp for statistical review of the study and the staff at The Intervention Centre for excellent assistance during the experiments. The research was carried out at The Intervention Centre at Oslo University Hospital. The idea of using accelerometers in monitoring ventricular function won the ‘Techno College Innovation Award’ at the European Association for Cardio-Thoracic Surgery (EACTS) conference in Barcelona 2012 (Heart failure devices, 27 October at 14.15), but none of the results in the current manuscript were presented.
Funding Ole-Johannes H.N. Grymyr was the recipient of a clinical research fellowship from the Faculty of Medicine, University of Oslo, Norway.
ORIGINAL ARTICLE
accelerometer allows a dynamic approach in monitoring the patient and in the guidance of treatment.
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Conflict of interest: Andreas Espinoza, Erik Fosse and Per S. Halvorsen are patent holders of the accelerometer technology for assessment of cardiac function and, together with Espen W. Remme, shareholders in Cardiaccs AS. Anh-Tuan T. Nguyen is an employee of Cardiaccs AS.
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