Modelling and Simulation of the Combined Use of IABP and Impella as a Rescue Procedure in Cardiogenic Shock: An Alternative for Non-Transplant Centres?

The treatment of critically ill patients remains an evolving and controversial issue. Mechanical circulatory support through a percutaneous approach for the management of cardiogenic shock has taken place in recent years. The combined use of IABP and the Impella 2.5 device may have a role to play for this group of patients. A simulation approach may help with a quantitative assessment of the achievable degree of assistance. In this paper, we analyse the interaction between the Impella 2.5 pump applied as the LVAD and IABP using the numerical simulator of the cardiovascular system developed in our laboratory. Starting with pathological conditions reproduced using research data, the simulations were performed by setting different rotational speeds for the LVAD and driving the IABP in full mode (1:1) or partial mode (1:2, 1:3 and 1:4). The effects induced by drug administration during the assistance were also simulated. The haemodynamic parameters under investigation were aa follows: mean aortic pressure, systolic and diastolic aortic pressure, mean pulmonary arterial pressure, mean left and right atrial pressure, cardiac output, cardiac index, left and right ventricular end-systolic volume, left ventricular end-diastolic volume and mean coronary blood flow. The energetic variables considered in this study were as follows: left and right ventricular external work and left and right atrial pressure-volume area. The outcome of our simulations shows that the combined use of IABP and Impella 2.5 achieves adequate support in the acute phase of cardiogenic shock compared to each standalone device. This would allow further stabilisation and transfer to a transplant centre should the escalation of treatment be required.

IABP versus Impella Support in Cardiogenic Shock: "In Silico" Study.

Cardiogenic shock (CS) is part of a clinical syndrome consisting of acute left ventricular failure causing severe hypotension leading to inadequate organ and tissue perfusion. The most commonly used devices to support patients affected by CS are Intra-Aortic Balloon Pump (IABP), Impella 2.5 pump and Extracorporeal Membrane Oxygenation. The aim of this study is the comparison between Impella and IABP using CARDIOSIM© software simulator of the cardiovascular system. The results of the simulations included baseline conditions from a virtual patient in CS followed by IABP assistance in synchronised mode with different driving and vacuum pressures. Subsequently, the same baseline conditions were supported by the Impella 2.5 with different rotational speeds. The percentage variation with respect to baseline conditions was calculated for haemodynamic and energetic variables during IABP and Impella assistance. The Impella pump driven with a rotational speed of 50,000 rpm increased the total flow by 4.36% with a reduction in left ventricular end-diastolic volume (LVEDV) by ≅15% to ≅30%. A reduction in left ventricular end systolic volume (LVESV) by ≅10% to ≅18% (≅12% to ≅33%) was observed with IABP (Impella) assistance. The simulation outcome suggests that assistance with the Impella device leads to higher reduction in LVESV, LVEDV, left ventricular external work and left atrial pressure-volume loop area compared to IABP support.

Evaluation of Different Cannulation Strategies for Aortic Arch Surgery Using a Cardiovascular Numerical Simulator.

Aortic disease has a significant impact on quality of life. The involvement of the aortic arch requires the preservation of blood supply to the brain during surgery. Deep hypothermic circulatory arrest is an established technique for this purpose, although neurological injury remains high. Additional techniques have been used to reduce risk, although controversy still remains. A three-way cannulation approach, including both carotid arteries and the femoral artery or the ascending aorta, has been used successfully for aortic arch replacement and redo procedures. We developed circuits of the circulation to simulate blood flow during this type of cannulation set up. The CARDIOSIM© cardiovascular simulation platform was used to analyse the effect on haemodynamic and energetic parameters and the benefit derived in terms of organ perfusion pressure and flow. Our simulation approach based on lumped-parameter modelling, pressure-volume analysis and modified time-varying elastance provides a theoretical background to a three-way cannulation strategy for aortic arch surgery with correlation to the observed clinical practice.

CARDIOSIM©: The First Italian Software Platform for Simulation of the Cardiovascular System and Mechanical Circulatory and Ventilatory Support.

This review is devoted to presenting the history of the CARDIOSIM© software simulator platform, which was developed in Italy to simulate the human cardiovascular and respiratory systems. The first version of CARDIOSIM© was developed at the Institute of Biomedical Technologies of the National Research Council in Rome. The first platform version published in 1991 ran on a PC with a disk operating system (MS-DOS) and was developed using the Turbo Basic language. The latest version runs on PC with Microsoft Windows 10 operating system; it is implemented in Visual Basic and C++ languages. The platform has a modular structure consisting of seven different general sections, which can be assembled to reproduce the most important pathophysiological conditions. One or more zero-dimensional (0-D) modules have been implemented in the platform for each section. The different modules can be assembled to reproduce part or the whole circulation according to Starling's law of the heart. Different mechanical ventilatory and circulatory devices have been implemented in the platform, including thoracic artificial lungs, ECMO, IABPs, pulsatile and continuous right and left ventricular assist devices, biventricular pacemakers and biventricular assist devices. CARDIOSIM© is used in clinical and educational environments.

Telehealth: A winning weapon to face the COVID-19 outbreak for patients with pulmonary arterial hypertension.

BACKGROUND: COVID-19 pandemic severely affected national health systems, altering the modality and the type of care of patients with acute and chronic diseases. To minimize the risk of exposure to SARS-CoV2 for patients and health professionals, face-to-face visits were cancelled or postponed and the use of telemedicine was strongly encouraged. This reorganization involved especially patients with rare diseases needing periodic comprehensive assessment, such as pulmonary arterial hypertension (PAH). MAIN BODY: The paper reports a proposal of strategy adopted for patients followed at our PAH center in Rome, where patients management was diversified based on clinical risk according to the European Society of Cardiology/European Respiratory Society PH guidelines-derived score and the REVEAL 2.0 score. A close monitoring and support of these patients were made possible by policy changes reducing barriers to telehealth access and promoting the use of telemedicine. Synchronous/asynchronous modalities and remote monitoring were used to collect and transfer medical data in order to guide physicians in therapeutic-decision making. Conversely, the use of implantable monitors providing hemodynamic information and echocardiography-mobile devices wirelessly connecting was limited by the poor experience existing in this setting. Large surveys and clinical trials are welcome to test the potential benefit of the optimal balance between traditional PAH management and telemedicine opportunities. CONCLUSION: Italy was found unprepared to manage the dramatic effects caused by COVID-19 on healthcare systems. In this emergency situation telemedicine represented a promising tool especially in rare diseases as PAH, but was limited by its scattered availability and legal and ethical issues. Cohesive partnership of health care providers with regional public health officials is needed to prioritize PAH patients for telemedicine by dedicated tools.

Ventricular and Atrial Pressure-Volume Loops: Analysis of the Effects Induced by Right Centrifugal Pump Assistance.

The main indications for right ventricular assist device (RVAD) support are right heart failure after implantation of a left ventricular assist device (LVAD) or early graft failure following heart transplantation. We sought to study the effects induced by different RVAD connections when right ventricular elastance (EesRIGHT) was modified using numerical simulations based on atrial and ventricular pressure-volume analysis. We considered the effects induced by continuous-flow RVAD support on left/right ventricular/atrial loops when EesRIGHT changed from 0.3 to 0.8 mmHg/mL during in-series or parallel pump connection. Pump rotational speed was also addressed. Parallel RVAD support at 4000 rpm with EesRIGHT = 0.3 mmHg/mL generated percentage changes up to 60% for left ventricular pressure-volume area and external work; up to 20% for left ventricular ESV and up to 25% for left ventricular EDV; up to 50% change in left atrial pressure-volume area (PVLAL-A) and only a 3% change in right atrial pressure-volume area (PVLAR-A). Percentage variation was lower when EesRIGHT = 0.8 mmHg/mL. Early recognition of right ventricular failure followed by aggressive treatment is desirable, so as to achieve a more favourable outcome. RVAD support remains an option for advanced right ventricular failure, although the onset of major adverse events may preclude its use.

ECG evaluation in 11 949 Italian teenagers: results of screening in secondary school.

AIM: There is lack of evidence regarding the screening role of ECG for sudden cardiac death (SCD) prevention. Our aim was to evaluate the prevalence of ECG abnormalities among teenagers according to sport participation and competitive status. METHODS: Eleven thousand nine hundred and forty-nine Italian pupils from 179 secondary schools (13-19 years) were consecutively enrolled. ECG abnormalities were divided into minor and major. Medical history, clinical examination and sport activity information were acquired. Further evaluations were suggested in case of major ECG abnormalities. Follow-up was performed at 2 years. RESULTS: N = 1945 (16%) pupils had ECG abnormalities. Major ECG abnormalities were detected in 13% of the cohort, minor in 34%. ECG abnormalities were more common in nonathletes compared with athletes. A diagnosis of cardiac disease was reached in 25 (1.6%) of the pupils with major ECG abnormalities. CONCLUSION: ECG abnormalities are common among young populations and more prevalent in nonathletes. Among pupils with major ECG abnormalities 1.6% had a cardiac disease diagnosis. Our results are in line with the data supporting ECG screening in the general young population.

ECMO Assistance during Mechanical Ventilation: Effects Induced on Energetic and Haemodynamic Variables.

BACKGROUND AND OBJECTIVE: Simulation in cardiovascular medicine may help clinicians understand the important events occurring during mechanical ventilation and circulatory support. During the COVID-19 pandemic, a significant number of patients have required hospital admission to tertiary referral centres for concomitant mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Nevertheless, the management of ventilated patients on circulatory support can be quite challenging. Therefore, we sought to review the management of these patients based on the analysis of haemodynamic and energetic parameters using numerical simulations generated by a software package named CARDIOSIM©. METHODS: New modules of the systemic circulation and ECMO were implemented in CARDIOSIM© platform. This is a modular software simulator of the cardiovascular system used in research, clinical and e-learning environment. The new structure of the developed modules is based on the concept of lumped (0-D) numerical modelling. Different ECMO configurations have been connected to the cardiovascular network to reproduce Veno-Arterial (VA) and Veno-Venous (VV) ECMO assistance. The advantages and limitations of different ECMO cannulation strategies have been considered. We have used literature data to validate the effects of a combined ventilation and ECMO support strategy. RESULTS: The results have shown that our simulations reproduced the typical effects induced during mechanical ventilation and ECMO assistance. We focused our attention on ECMO with triple cannulation such as Veno-Ventricular-Arterial (VV-A) and Veno-Atrial-Arterial (VA-A) configurations to improve the hemodynamic and energetic conditions of a virtual patient. Simulations of VV-A and VA-A assistance with and without mechanical ventilation have generated specific effects on cardiac output, coupling of arterial and ventricular elastance for both ventricles, mean pulmonary pressure, external work and pressure volume area. CONCLUSION: The new modules of the systemic circulation and ECMO support allowed the study of the effects induced by concomitant mechanical ventilation and circulatory support. Based on our clinical experience during the COVID-19 pandemic, numerical simulations may help clinicians with data analysis and treatment optimisation of patients requiring both mechanical ventilation and circulatory support.

Computational Simulator Models and Invasive Hemodynamic Monitoring as Tools for Precision Medicine in Pulmonary Arterial Hypertension.

Precision medicine, providing the right therapeutic strategy for the right patient, could revolutionize management and prognosis of patients affected by cardiovascular diseases. Big data and artificial intelligence are pivotal for the realization of this ambitious design. In the setting of pulmonary arterial hypertension (PAH), the use of computational models and data derived from ambulatory implantable hemodynamic monitors could provide useful information for tailored treatment, as requested by precision medicine.

In silico study of airway/lung mechanics in normal human breathing.

The airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance. The model could be used in the study of the interaction between respiratory and cardiovascular systems in pathophysiological conditions.

Intra-aortic balloon counterpulsation timing: A new numerical model for programming and training in the clinical environment.

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 model 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 PIABP generator and resistances. PIABP 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 simulations 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 the simulation of 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.

How can LVAD support influence ventricular energetics parameters in advanced heart failure patients? A retrospective study.

BACKGROUND AND OBJECTIVE: Here we present a retrospective analysis of six heart failure patients previously discussed at a multidisciplinary team meeting. Only three out of six patients underwent LVAD insertion as the most appropriate management option. METHODS: We sought to reproduce the baseline conditions of these patients on hospital admission using our cardiovascular software simulator (CARDIOSIM©). Subsequently, we simulated the effects of LVAD support and drug administration on left and right ventricular energetics parameters. LVAD assistance was delivered by CARDIOSIM© based on the module reproducing the behaviour of the Berlin Heart INCOR pump. RESULTS: The results of our simulations were in agreement with the multidisciplinary team meeting outcome. The analysis of ventricular energetics parameters based on external work and pressure volume area confirmed LVAD support as a beneficial therapeutic option for the three patients considered eligible for this type of treatment. The effects induced by LVAD support and drugs administration showed specific patterns between the two groups of patients. CONCLUSION: A quantitative approach with the ability to predict outcome during patient's assessment may well be an aid and not a substitute for clinical decision-making.

Non-Ionizing Radiation for Cardiac Human Amniotic Mesenchymal Stromal Cell Commitment: A Physical Strategy in Regenerative Medicine.

Cell therapy is an innovative strategy for tissue repair, since adult stem cells could have limited regenerative ability as in the case of myocardial damage. This leads to a local contractile dysfunction due to scar formation. For these reasons, refining strategy approaches for "in vitro" stem cell commitment, preparatory to the "in vivo" stem cell differentiation, is imperative. In this work, we isolated and characterized at molecular and cellular level, human Amniotic Mesenchymal Stromal Cells (hAMSCs) and exposed them to a physical Extremely Low Frequency Electromagnetic Field (ELF-EMF) stimulus and to a chemical Nitric Oxide treatment. Physically exposed cells showed a decrease of cell proliferation and no change in metabolic activity, cell vitality and apoptotic rate. An increase in the mRNA expression of cardiac and angiogenic differentiation markers, confirmed at the translational level, was also highlighted in exposed cells. Our data, for the first time, provide evidence that physical ELF-EMF stimulus (7 Hz, 2.5 µT), similarly to the chemical treatment, is able to trigger hAMSC cardiac commitment. More importantly, we also observed that only the physical stimulus is able to induce both types of commitments contemporarily (cardiac and angiogenic), suggesting its potential use to obtain a better regenerative response in cell-therapy protocols.

Simulation as a preoperative planning approach in advanced heart failure patients. A retrospective clinical analysis.

BACKGROUND: Modelling and simulation may become clinically applicable tools for detailed evaluation of the cardiovascular system and clinical decision-making to guide therapeutic intervention. Models based on pressure-volume relationship and zero-dimensional representation of the cardiovascular system may be a suitable choice given their simplicity and versatility. This approach has great potential for application in heart failure where the impact of left ventricular assist devices has played a significant role as a bridge to transplant and more recently as a long-term solution for non eligible candidates. RESULTS: We sought to investigate the value of simulation in the context of three heart failure patients with a view to predict or guide further management. CARDIOSIM© was the software used for this purpose. The study was based on retrospective analysis of haemodynamic data previously discussed at a multidisciplinary meeting. The outcome of the simulations addressed the value of a more quantitative approach in the clinical decision process. CONCLUSIONS: Although previous experience, co-morbidities and the risk of potentially fatal complications play a role in clinical decision-making, patient-specific modelling may become a daily approach for selection and optimisation of device-based treatment for heart failure patients. Willingness to adopt this integrated approach may be the key to further progress.

Screening high school students in Italy for sudden cardiac death prevention by using a telecardiology device: a retrospective observational study.

BACKGROUND: In 2010, an Italian project was launched aimed at using a telecardiology device in order to perform early diagnosis of young students at risk of sudden cardiac death. METHODS: Our retrospective observational study was conducted on a population of 13,016 students, aged between 16 and 19 years, in different Italian regions. It consisted of analysis of data recorded during a telecardiology pilot study. The recorded data were electrocardiograms and data concerning lifestyle habits and family history of cardiovascular diseases. In total, 14 alterations in the electrocardiogram signal have been considered in this study. Some of these alterations are as follows: ventricular ectopic beats, atrioventricular block, Brugada-like electrocardiogram pattern, left anterior/posterior fascicular block, left/right ventricular hypertrophy, long/short QT interval, left atrial enlargement, right atrial enlargement, short PQ interval, and ventricular pre-excitation Wolff-Parkinson-White syndrome. On the basis of the collected data, we implemented this retrospective observational study. RESULTS: The analysed data showed that 13.60% of students had a family history for cardiovascular diseases, 22.43% reported smoking habits, 26.23% reported alcohol consumption, and 7.24% reported abuse of drugs. A total of 24% of students had at least one of the 14 electrocardiogram pathological alterations considered in our study and 32% had electrocardiogram values within the normal range. CONCLUSIONS: This retrospective observational study analysed data registered during our telecardiology activity. This activity permitted to maximise data collection and minimise the costs for collecting such data. This activity of screening is being continued and in the next few years it will allow us to have a greater mass of data.

Interactive simulator for e-Learning environments: a teaching software for health care professionals.

There is an established tradition of cardiovascular simulation tools, but the application of this kind of technology in the e-Learning arena is a novel approach. This paper presents an e-Learning environment aimed at teaching the interaction of cardiovascular and lung systems to health-care professionals. Heart-lung interaction must be analyzed while assisting patients with severe respiratory problems or with heart failure in intensive care unit. Such patients can be assisted by mechanical ventilatory assistance or by thoracic artificial lung."In silico" cardiovascular simulator was experimented during a training course given to graduate students of the School of Specialization in Cardiology at 'Sapienza' University in Rome.The training course employed CARDIOSIM©: a numerical simulator of the cardiovascular system. Such simulator is able to reproduce pathophysiological conditions of patients affected by cardiovascular and/or lung disease. In order to study the interactions among the cardiovascular system, the natural lung and the thoracic artificial lung (TAL), the numerical model of this device has been implemented. After having reproduced a patient's pathological condition, TAL model was applied in parallel and hybrid model during the training course.Results obtained during the training course show that TAL parallel assistance reduces right ventricular end systolic (diastolic) volume, but increases left ventricular end systolic (diastolic) volume. The percentage changes induced by hybrid TAL assistance on haemodynamic variables are lower than those produced by parallel assistance. Only in the case of the mean pulmonary arterial pressure, there is a percentage reduction which, in case of hybrid assistance, is greater (about 40%) than in case of parallel assistance (20-30%).At the end of the course, a short questionnaire was submitted to students in order to assess the quality of the course. The feedback obtained was positive, showing good results with respect to the degree of students' learning and the ease of use of the software simulator.

Mechanical ventilation and thoracic artificial lung assistance during mechanical circulatory support with PUCA pump: in silico study.

Patients assisted with left ventricular assist device (LVAD) may require prolonged mechanical ventilatory assistance secondary to postoperative respiratory failure. The goal of this work is the study of the interdependent effects LVAD like pulsatile catheter (PUCA) pump and mechanical ventilatory support or thoracic artificial lung (TAL), by the hemodynamic point of view, using a numerical simulator of the human cardiovascular system. In the simulator, different circulatory sections are described using lumped parameter models. Lumped parameter models have been designed to describe the hydrodynamic behavior of both PUCA pump and thoracic artificial lung. Ventricular behavior atrial and septum functions were reproduced using variable elastance model. Starting from simulated pathological conditions we studied the effects produced on some hemodynamic variables by simultaneous PUCA pump, thoracic artificial lung or mechanical ventilation assistance. Thoracic artificial lung was applied in parallel or in hybrid mode. The effects of mechanical ventilation have been simulated by changing mean intrathoracic pressure value from -4 mmHg to +5 mmHg. The hemodynamic variables observed during the simulations, in different assisted conditions, were: left and right ventricular end systolic (diastolic) volume, systolic/diastolic aortic pressure, mean pulmonary arterial pressure, left and right mean atrial pressure, mean systemic venous pressure and the total blood flow. Results show that the application of PUCA (without mechanical ventilatory assistance) increases the total blood flow, reduces the left ventricular end systolic volume and increases the diastolic aortic pressure. Parallel TAL assistance increases the right ventricular end diastolic (systolic) volume reduction both when PUCA is switched "ON" and both when PUCA is switched "OFF". By switching "OFF" the PUCA pump, it seems that parallel thoracic artificial lung assistance produces a greater cardiac output (respect to hybrid TAL assistance). Results concerning PUCA and TAL interaction produced by simulations cannot be compared with "in vivo" results since they are not presented in literature. But results concerning the effects produced by LVAD and mechanical ventilation have a trend consistent with those presented in literature.

Effects of amlodipine and adenosine on coronary haemodynamics: in vivo study and numerical simulation.

Amlodipine (AMLO) is a calcium channel blocker with vasodilating properties, in which the specific effects on the coronary circulation are not fully known. Coronary flow velocity-pressure (F/P) curves were obtained at rest and during administration of AMLO (10 mg to 20 mg iv) or adenosine (ADO, 1 mg ic) in 10 normal subjects (six women, age 48 ± 14 years). F/P curves were reproduced in a numerical simulator of systemic and coronary circulations (CARDIOSIM(©)) by adjustment of coronary resistance ( > or < 100 µm diameter vessels) and extravascular resistance applied to smaller vessels at endocardial (ENDO), middle and epicardial (EPI) myocardial layers. Best matching of in silico to in vivo curves was achieved by trial and error approach. ADO induced 170% and 250% increase in coronary flow velocity CFV and F/P diastolic slope as compared to 80% and 25-30% increase induced by AMLO, respectively. In the cardiovascular model, AMLO effects were predicted by progressive reduction of>100 µm vessels resistance from EPI to ENDO. ADO effects were mimicked by reducing resistance of both>100 µm and < 100 µm vessels, progressively from EPI to ENDO in the latter. Additional reduction in extravascular resistance avoided to impose a transmural gradient of vasodilating effect for both drugs. Numerical simulation predicts vasodilating effects of AMLO mainly on larger arteries and of ADO on both>and < 100 µm vessels. In vivo F/P loops could be completely reproduced in silico by adding extravascular resistance reduction for both drugs. Numerical simulator is useful tool for exploring the coronary effects of cardioactive drugs.

In silico study of the haemodynamic effects induced by mechanical ventilation and biventricular pacemaker.

In silico modeling of the cardiovascular system (CVS) can help both in understanding pharmacological or pathophysiological process and in providing information which could not be obtained by means of traditional clinical research methods due to practical or ethical reasons. In this work the numerical CVS was used to study the effect of interaction between mechanical ventilation and biventricular pacemaker by haemodynamic and energetic point of view. Starting from literature data on patients with intra and/or inter-ventricular activation time delay and treated using biventricular pacemaker, we used in silico simulator to analyse the effects induced by mechanical ventilatory assistance (MVA). After reproducing baseline and CRT conditions, the MVA was simulated changing the mean intrathoracic pressure value. Results show that simultaneous application of CRT and MVA yields a reduction of cardiac output, left ventricular end-diastolic and end-systolic volume when positive mean intrathoracic pressure is applied. In the same conditions, when MVA is applied, left ventricular ejection fraction, mean left (right) atrial and pulmonary arterial pressure increase.

Interaction between the septum and the left (right) ventricular free wall in order to evaluate the effects on coronary blood flow: numerical simulation.

Mathematical modelling of the cardiovascular system (CVS) can help in understanding the complex interactions between both the ventricles and the septum. By describing the behaviour of the left (right) ventricular free wall, atria and septum using the variable elastance models, it is possible to reproduce their interactions. By relating the mechanical properties of both atria and both ventricles to the electrocardiogram (ECG) signal, it is possible to analyse the effects produced by different ECG delay on haemodynamic parameters. In the cardiovascular field, the incorrect interactions between septum and both ventricular free walls are based on many pathological conditions, i.e. symptomatic heart failure resulting from systolic dysfunction, ischemic dilated cardiomyopathy, and so on. The possible corrections that can be induced on the QRS complex duration in the ECG signal (i.e. cardiac resynchronisation therapy, CRT) can produce benefits improving the clinical status of the patient. The aim of this work was to evaluate, using our numerical simulator of the CVS, the effects induced on coronary blood flow (CBF) and aortic pressure using different ECG times, intra-ventricular and inter-ventricular delays. The results were obtained by reproducing the circulatory baseline and CRT conditions of seven patients described in literature. Haemodynamic simulated results are in accordance with literature data. Also the controversial results on CBF, in presence of CRT, are consistent with those described in the literature.