Development of a laboratory of excellence in the cardiovascular field.

Located in the Italian city of Latina, near Rome, the LABoEx certainly represents a one-of-its kind concentrate of know-how and advanced research in the field of Cardiovascular disease. Conceived during a meeting between cardiologists and bioengineers, LAboEx was created in reply to the shared needs for an in-depth understanding of the many variables and parameters of the cardiovascular system and of their interaction with mechanical assist devices (such as the oxygenator, the intra-aortic balloon pump, centrifugal pump, the ventricular assist device, the ventilatory assistance etc). The initial idea, brought forth by the bioengineers, was to develop a tool of diverse numerical models that could simulate the behaviour of the cardiovascular system in presence of different mechanical cardiac or ventilatory assist devices. The concept was then extended by the cardiologists who suggested to extend its application in predicting, starting from few cardiovascular variables (measured non invasively), the trend, or better, the behaviour of those variables that cannot be directly measured on the patient. The successive step was use numerical models ad hoc for patents affected by specific pathologies, hence providing the physician a tool for deciding the most appropriate strategies for the patient. From there, the group developed the idea of orienting the cardiovascular numerical models also towards other applications, such as a commercial device that monitors the correct functioning of a 24-hr blood pressure Holter. Indeed, the laboratory of the Institute of Clinical Physiology of the Italian National Research Council (C.N.R.) has already started working towards the realization of a software tool (CARDIOSIM?) aimed at simulating the behaviour of the cardiovascular system. This modular software was developed by Italian researchers together with colleagues from the Institute of Biocybernetics and Biomedical Engineering, IBIBPAN Warsaw, Poland, of the Iwate Prefectural University in Japan, the Biomedical Engineering and Cardiothoracic Surgery of the University Medical Center Groningen in Holland, and the N.I.H in the USA. The software implements on a PC platform a family of lumped parameter circulatory models designed to be used in clinical, research, and educational applications. The family of the circulatory models represents the circulation at the level of large vessels and allows to evaluate the global effects of external disturbances (pathologies, therapies, mechanical assistance, special environments or surgery) on the circulatory system. The software tool simulates different mechanical heart assist devices, like left and right Ventricular Assist Device (VAD) and Intraaortic Balloon Pumping (IABP): both pulsatile and continuous flow VAD can be used inside the tool. Also the mechanical ventilatory assistance is implemented

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 ECG signal it is possible to analyze 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 on the 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 Resynchronization Therapy - CRT), can produce benefits improving 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

Modelli numerici per la stima di parametri non direttamente misurabili: Simulazione e Telecardiologia

Numerical models of the cardiovascular system are a good way to represent the interaction between the heart and circulatory system and to play their pathophysiological phenomena of a patient. These models, created as research tools have evolved to use in a clinical and educational field..

ENERGETIC VENTRICULAR BALANCE DURING CARDIAC RESYNCHRONIZATION THERAPY: NUMERICAL SIMULATION

Cardiac Resynchronization Therapy (CRT), realised using biventricular pacemaker is used to treat patients with in systolic heart failure (HF) and with prolonged QRS. The goal of CRT is to eliminate or reduce the electromechanical dyssynchrony processes often responsible of cardiac remodelling. The aim of this work is to study the effects of CRT on the energetic left ventricular variables as external work, the pressure-volume area and the potential energy. In order to study the effects produced by CRT on energetic left ventricular balance it was used the numerical model of the cardiovascular system (CARDIOSIM?), able to reproduce the effects induced by biventricular pacemaker (BPM). Starting from literature data, the haemodynamic conditions of a group of patients, representative of the most common disease etiologies of heart failure, were simulated before and after CRT treatment. The trend of the energetic left ventricular variables was studied for each patient in order to evaluate the effects produced by the CRT. The obtained results shown that the software simulator can predict the dynamics of energetic left ventricular balance in patients affected by HF and treated with cardiac resynchronization therapy

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

ENERGETIC VENTRICULAR BALANCE DURING CARDIAC RESYNCHRONIZATION THERAPY: NUMERICAL SIMULATION

Cardiac Resynchronization Therapy (CRT), realised using biventricular pacemaker is used to treat patients with in systolic heart failure (HF) and with prolonged QRS. The goal of CRT is to eliminate or reduce the electromechanical dyssynchrony processes often responsible of cardiac remodelling. The aim of this work is to study the effects of CRT on the energetic left ventricular variables as external work, the pressure-volume area and the potential energy. In order to study the effects produced by CRT on energetic left ventricular balance it was used the numerical model of the cardiovascular system (CARDIOSIM?), able to reproduce the effects induced by biventricular pacemaker (BPM). Starting from literature data, the haemodynamic conditions of a group of patients, representative of the most common disease etiologies of heart failure, were simulated before and after CRT treatment. The trend of the energetic left ventricular variables was studied for each patient in order to evaluate the effects produced by the CRT. The obtained results shown that the software simulator can predict the dynamics of energetic left ventricular balance in patients affected by HF and treated with cardiac resynchronization therap

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

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 out- come. 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

La Telecardiologia

Telemedicine is a form of real-time sharing of patient information, so that the contribution of more health workers at the same time can ensure a higher level of care, reducing hospitalization costs and transport . This work is the fruit of a "handful" of traders, who for some time dealing with this issue and are often made promoters of cultural and scientific experiences to sensitize decision makers to bring up a new Health how to manage the patient...

MODELLI DI SISTEMI BIOLOGICI

The use of analytical methods and in particular the study of biological systems using mathematical models is relatively recent, although the first attempts at quantitative analysis of biological systems have had since the nineteenth century: the first models of pressure-volume relationship in the major arteries , windkessel model, date precisely the end of this century. The late use of such an approach, compared to other branches of science such as physics and engineering typically is due not only to the objective complexity of the systems in question, the suspicion that the use of such methods has to long time at many schools met biological. On the one hand it was thought that the necessary simplification and schematization behind the writing of a mathematical model could lead to a distortion of reality, on the other hand, believed that the living reality was too complex and to be described on the basis of well physical laws, as with the inert matter, such approach is too mechanistic and therefore not suitable for biological reality. E \u27on the other hand should be noted that, despite these concerns contained some truth, whatever the cognitive process of schematization and implies that they may still be acceptable, whereas the ability to interpret reality in a quantitative model that can provide in comparison to pure description that can be derived from experimental data. On the other hand, although difficult to refute the biological reality that is substantially different and more complex of inert matter, it is true that some aspects of the two companies are essentially treated the same way