key: cord-0820474-eh36uzwj authors: De Lazzari, Claudio; De Lazzari, Beatrice; Iacovoni, Attilio; Marconi, Silvia; Papa, Silvia; Capoccia, Massimo; Badagliacca, Roberto; Vizza, Carmine Dario title: Intra-Aortic Balloon Counterpulsation Timing: A New Numerical Model for Programming and Training in the Clinical Environment. date: 2020-05-15 journal: Comput Methods Programs Biomed DOI: 10.1016/j.cmpb.2020.105537 sha: 98d009462275e88cac36390c31ff4ca45dbb4eac doc_id: 820474 cord_uid: eh36uzwj BACKGROUND AND OBJECTIVE: : The intra-aortic balloon pump (IABP) is the most widely available device for short-term mechanical circulatory support, often used to wean off cardiopulmonary bypass or combined with extra-corporeal membrane oxygenation support or as a bridge to a left ventricular assist device. Although based on a relatively simple principle, its complex interaction with the cardiovascular system remains challenging and open to debate. The aim of this work was focused on the development of a new numerical model of IABP. METHODS: : The new module was implemented in CARDIOSIM©, which is a modular software simulator of the cardiovascular system used in research and e-learning environment. The IABP is inserted into the systemic bed divided in aortic, thoracic and two abdominal tracts modelled with resistances inertances and compliances. The effect induced by the balloon is reproduced in each tract of the aorta by the presence of compliances connected to P(IABP) generator and resistances. P(IABP) generator reproduces the balloon pressure with the option to change IABP timing.We have used literature data to validate the potential of this new numerical model. RESULTS: : The results have shown that our simulation reproduced the typical effects induced during IABP assistance. We have also simulated the effects induced by the device on the hemodynamic variables when the IABP ratio was set to 1:1, 1:2, 1:4 and 1:8. The outcome of these simulations is in accordance with literature data measured in the clinical environment. CONCLUSIONS: : The new IABP module is easy to manage and can be used as a training tool in a clinical setting. Although based on literature data, the outcome of the simulations is encouraging. Additional work is ongoing with a view to further validate its features. The configuration of CARDIOSIM© presented in this work allows to simulate the effects induced by mechanical ventilatory assistance. This facility may have significant importance in the management of patients affected by COVID-19 when they require mechanical circulatory support devices. The intra-aortic balloon pump (IABP) is a widely available in-series cardiac assist device. It consists of a double-lumen catheter with a polyurethane balloon attached at its distal end and a mobile pump console, which shuttles helium through the main lumen of the catheter. The tip of the catheter has a pressure sensor to monitor aortic blood pressure. The IABP is now inserted percutaneously through the femoral artery and positioned just below the origin of the left subclavian artery either under fluoroscopic guidance in the cath lab or under trans-oesophageal guidance in theatre. The IABP is based on the principle of counterpulsation, which aims to optimize the balance between myocardial oxygen supply and demand in terms of endocardial viability ratio (EVR) [1] , [2] . The functional relationship between stroke volume (SV), aortic mean diastolic pressure (MDP), tension time index (TTI), aortic end diastolic pressure (EDP), balloon inflation/deflation timing and heart rate is a key element for optimal pump control [1] , [2] . The physiological advantage of intra-aortic balloon counterpulsation is increased aortic diastolic blood pressure. Rapid inflation of the balloon at the beginning of diastole generates proximal and distal blood displacement, which is proportional to the volume of the balloon. Diastolic blood pressure augmentation increases the intrinsic windkessel effect leading to storage of extra potential energy in the aorta and conversion to kinetic energy following the elastic recoil of the vessel [3] . This event has the potential to increase coronary blood flow. Rapid deflation of the balloon in early systole leads to afterload reduction or, to be more precise, to reduction of impedance to ventricular ejection and cardiac work [4] , [5] . This is in accordance with a previous analytical model [5] . The ability to model the interactions between IABP and the cardiovascular system and how alterations of specific parameters such as timing can affect their coupling remains a key element for clinical application [6] , [7] . Simulations of combined VA-ECMO and IABP support show an increase in pulsatility and LV stroke volume between 5% and 10% due to afterload reduction although PCWP and left ventricular EDV are only marginally affected. Significant LV unloading is achieved during combined VA-ECMO and Impella support although aortic valve opening and improved diastolic coronary perfusion pressure are not observed in comparison with IABP [8] . Nevertheless, the pulse contour is higher and more similar to the physiological pattern during partial ECMO support where some degree of LV ejection is allowed [9] . The concomitant use of IABP and VA-ECMO shows reduced in-hospital mortality in patients with cardiogenic shock secondary to post-cardiotomy failure, ischaemic heart disease and myocarditis [10] [11] , which is in contrast with the outcome of the SHOCK II trial [12] , [13] , [14] . The study was designed as a multicentre, randomised, open-label trial. Between 2009 and 2012, 600 patients with cardiogenic shock following acute myocardial infarction and requiring early revascularisation were randomised to IABP versus control. Long-term follow-up (6.2 years) showed no difference in mortality, recurrent myocardial infarction, stroke, repeat revascularisation or hospital readmission for cardiac reasons between the two groups. Nevertheless, the use of IABP in cardiogenic shock remains the subject of significant debate and controversy. The electrical analogue of the cardiovascular system assembled inside the software simulator platform CARDIOSIM © is reported in Fig. 1 . The circuit consists of systemic and venous sections, coronary section and pulmonary arterial and venous sections. Each section is modelled by RLC electrical circuit based on 0-D numerical representation. The systemic venous section consists of a compliance (Cvs) and two variable resistances (Rvs1 and Rvs2); the pulmonary arterial section is modelled with a characteristic resistance (Rcp), a variable pulmonary arterial resistance (Rap), a compliance (Cap) and an inertance (Lap). Finally, the behavior of the pulmonary venous section is reproduced with a resistance (Rvp) and a compliance (Cvp). Pt is the mean intrathoracic pressure. The following CARDIOSIM © module was selected to simulate the heart activity. The behavior of the left and right native ventricles is reproduced by the time-varying elastance model. The same theory is used to model both left and right atria and the septum [15] - [19] . Ventricles, atria and septum activities are synchronized with the electrocardiographic (ECG) signal [19] . The described model allows inter-ventricular and intra-ventricular dyssynchrony to be simulated [19] - [21] . Figure 3 shows the waveform generator reproduced by the following equation: When the IABP is OFF, the network showed in Fig. 2 is solved by the equations: If the IABP is ON, the equations are: IABP I 2 TT IABP I 3 ABT 1 IABP AT I 1 TT AT AT IABP1 TT TT TT I 2 IABP2 ABT 1 where Plv is the left ventricular pressure. The resistance Rlo and the diode D1 model the mitral valve (Fig. 2) . The software simulator allows the IABP to be synchronized with either the ECG or the arterial waveform. The frequency of balloon-assisted beats can be set from the maintenance 1:1 ratio to a weaning 1:2 ratio (every other systole is assisted). Depending on the clinician's judgment, weaning modes of 1:4 or even 1:8 may be initiated if a more gradual approach is needed. In addition, IABP driving and vacuum pressures can be changed. The hemodynamic effects induced by the IABP may vary with assisting frequency and depend on balloon inflation/deflation timing. A range of settings T1-T7 is available in the software simulator. The IABP can be triggered to deflate during systole once the peak of the R wave is sensed. IABP inflation may be triggered to occur in the middle of the T wave, which corresponds to diastole. The simulator allows the setting of different delays. Changing IABP compliance and resistance allows the balloon volume to be modified. Patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) may require intra-aortic balloon counterpulsation as an adjunct to medical treatment [27] . For the purposes of our study, literature data [28] - [30] were used to reproduce the baseline conditions of CS patients and those following IABP assistance. The hemodynamic data used in this study have been listed in Table 1 . Figure 4a shows a screen output produced by CARDIOSIM © when patient's baseline conditions were reproduced using the data reported in Table 1 The numerical model for IABP assistance implemented in CARDIOSIM © produces an increase between 25% (ratio 1:1) and 10% (ratio1:8) in CO following activation. It is estimated that IABP assistance with 1:1 ratio in the presence of sinus rhythm can increase cardiac output up to 20-25% of its initial value according to the available literature data. We point out that in the transition from IABP setting with 1:1 ratio to that with 1:8 ratio, the parameters of the simulator were not changed. Systemic vascular resistance (SVR) decreases from 23% to 18% when IABP is activated. The assistance induces about 10% reduction in EDV (when the ratio is 1:1) and about 5% reduction in the mean value of EDV The peak diastolic blood pressure (PDP) increases by 30% when the IABP ratio is set to 1:1. The left ventricular arterial coupling (Ea/Eas) decreases by 32% (14%) when the assistance ratio is set to 1:1 (1:8). The mean coronary blood flow (MCBF) increases by 21% when the IABP ratio is set to 1:1 but it decreases by 8% when the ratio is set to 1:8. In this case, the MCBF is calculated over eight cardiac cycles where only one is assisted by IABP activation. The limitations of this work are related to the use of incomplete data from the available literature, which affects the accurate reproduction of a patient's cardiovascular conditions. Furthermore, we were unable to obtain data related to the trend of the hemodynamic variables during different IABP operating modes. We believe these data would be useful to further validate our model. Nevertheless, the cardiovascular network used in this work has been previously validated [15] [16] and has led to the successful evaluation of the trend of the hemodynamic variables during patient weaning off the device. We have also observed that the cardiovascular network outlined in Fig.1 aortic (pulmonary) valve to systemic (pulmonary) arterial section. The coronary network is modelled using RC elements as already described in [22] - [26] . Pt is the mean intrathoracic pressure. Table 1 . Mathematical Modelling of Optimal Intraaortic Balloon Pumping Control of Intraaortic Balloon Pumping: Theory and Guidelines for Clinical Applications Principles of intra-aortic balloon pump counterpulsation, Continuing Education in Anaesthesia Intraaortic Balloon Counterpulsation: A Review of Physiological Principles, Clinical Results and Device Safety The Intra-Aortic Balloon for Left Heart Assistance: An Analytic Model Modelling the Interaction Between the Intra-Aortic Balloon Pump and the Cardiovascular System: The Effect of Timing Does conventional intra-aortic balloon pump trigger timing produce optimal haemodynamic effects in vivo? Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study Computational analysis of aortic hemodynamics during total and partial extracorporeal membrane oxygenation and intra-aortic balloon pump support Effect of an intraaortic balloon pump with venoarterial extracorporeal membrane oxygenation on mortality of patients with cardiogenic shock: a systematic review and meta-analysis Concurrent initiation of intra-aortic balloon pumping with extracorporeal membrane oxygenation reduced in-hospital mortality in postcardiotomy cardiogenic shock Intraaortic Balloon Pump in cardiogenic shock II (IABP-SHOCK II) trial investigators. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial IABPSHOCK II Trial (Intraaortic Balloon Pump in Cardiogenic Shock II) Investigators. Intraaortic Balloon Pump in Cardiogenic Shock Complicating Acute Myocardial Infarction: Long-Term 6-Year Outcome of the Randomized IABP-SHOCK II Trial Simulation as a preoperative planning approach in advanced heart failure patients. A retrospective clinical analysis Decision-making in advanced heart failure patients requiring LVAD insertion: Can preoperative simulation become the way forward? A case study Load Independence of the Instantaneous Pressure-Volume Ratio of the Canine Left Ventricle and Effects of Epinephrine and Heart Rate on the Ratio Interactive simulator for e-Learning environments: a teaching software for health care professionals Interaction between the septum and the left (right) ventricular free wall in order to evaluate the effects on coronary blood flow: numerical simulation Cardiac contraction and the Pressure-Volume relationships Ventricular systolic interdependence: volume elastance model in isolated canine hearts CARDIOSIM © Website. Original website platform regarding the implementation of the cardiovascular software simulator CARDIOSIM © Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation Cardiac resynchronization therapy: could a numerical simulator be a useful tool in order to predict the response of the biventricular pacemaker synchronization Computer simulation of coronary flow waveforms during caval occlusion The influence of left ventricle assist device and ventilatory support on energy-related cardiovascular variables No long-term benefit of IABP in cardiogenic shock First-Line Support by Intra-Aortic Balloon Pump in Non-Ischaemic Cardiogenic Shock in the Era of Modern Ventricular Assist Devices Prophylactic Intra-Aortic Balloon Pump Before Ventricular Assist Device Implantation Reduces Perioperative Medical Expenses and Improves Postoperative Clinical Course in INTERMACS Profile 2 Patients Acute Hemodynamic Effects of Intra-aortic Balloon Counterpulsation Pumps in Advanced Heart Failure