Cardiac growth is the natural capability of the heart to change size in response to changes in blood flow demand of the growing body. Cardiac diseases can trigger the same process leading to an abnormal type of growth. Prediction of cardiac growth would be clinically valuable, but so far published models on cardiac growth differ with respect to the stimulus-effect relation and constraints used for maximum growth. In this study, we use a zero-dimensional, multiscale model of the left ventricle to evaluate cardiac growth in response to three valve diseases, aortic and mitral regurgitation along with aortic stenosis. We investigate how different combinations of stress-and strain-based stimuli affect growth in terms of cavity volume and wall volume and hemodynamic performance. All of our simulations are able to reach a converged state without any growth constraint, with the most promising results obtained while considering at least one stress-based stimulus. With this study, we demonstrate how a simple model of left ventricular mechanics can be used to have a first evaluation on a designed growth law.

Cardiac growth is an important mechanism for the human body to respond to changes in blood flow demand. Being able to predict the development of chronic growth is clinically relevant, but so far models to predict growth have not reached consensus on the stimulus–effect relation. In a previously published study, we modeled cardiac and hemodynamic function through a lumped parameter approach. We evaluated cardiac growth in response to valve disease using various stimulus–effect relations and observed an unphysiological decline pump function. Here we extend that model with a model of hemodynamic feedback that maintains mean arterial pressure and cardiac output through adaptation of peripheral resistance and circulatory unstressed volume. With the combined model, we obtain stable growth and restoration of pump function for most growth laws. We conclude that a mixed combination of stress and strain stimuli to drive cardiac growth is most promising since it (1) reproduces clinical observations on cardiac growth well, (2) requires only a small, clinically realistic adaptation of the properties of the circulatory system and (3) is robust in the sense that results were fairly insensitive to the exact choice of the chosen mechanics loading measure. This finding may be used to guide the choice of growth laws in more complex finite element models of cardiac growth, suitable for predicting the response to spatially varying changes in tissue load. Eventually, the current model may form a basis for a tool to predict patient-specific growth in response to spatially homogeneous changes in tissue load, since it is computationally inexpensive.

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Funding Acknowledgements Type of funding sources: None. Background/introduction Optimisation of cardiac resynchronisation therapy (CRT) response still represents a significant challenge to cardiac electrophysiology. In this regard, perhaps the area of greatest uncertainty revolves around optimal left ventricular lead (LVL) position and in particular whether this should be directed at areas of latest electrical or mechanical activation given the equivocal evidence on their precise relationship in heart failure (HF) patients. Furthermore, while echocardiography has demonstrated that LVL aimed at regions of greatest mechanical delay maximises CRT response, cardiac magnetic resonance (CMR) with its greater spatial resolution and tissue definition is yet to demonstrate a role in doing so. Purpose To retrospectively evaluate concordance between latest electrical and CMR-determined mechanical activation in a CRT population and its relationship with reverse remodeling. Methods This is a retrospective single center analysis of 104 CRT patients. All patients had CMR and echocardiography performed before implantation. During implantation, coronary sinus angiogram was performed and electrical delay (QLV time with RV-LV time greater than 80 ms) was mapped on all veins suitable for lead implantation and LVL was positioned in the region of latest electrical activation programming LVL cathode accordingly. LVL cathode position was thus assumed to represent the region of latest electrical delay. A post-hoc analysis was then conducted by means of CART-Tech® software providing radial strain and scar maps on a 36-segment anatomical model. Patients were then stratified based on concordance between LVL cathode position (using 3D heart models superimposed on 2D angiography images) and most mechanically delayed segments (either the three most delayed segments or adjacent ones) or non concordance (one or more segments between LVL cathode and three most mechanically delayed segments). Data from patient follow-up was collected with echocardiography at least 3 months after implant date. CRT response was expressed as reduction in end-systolic volume (ESV) greater than 15%. Results A preliminary analysis of the first 30 patients of our cohort was conducted. Electromechanical concordance and non-concordance were present in 24 and 6 patients, respectively. Baseline patient characteristics including demographics, comorbidities, HF aetiology, ECG and echocardiography features were comparable between groups except for scar burden, which was higher in the non-concordance group. Response to CRT was 80% in the concordant vs. 20% in the non-concordant group. Conclusions While a confounding effect of scar burden cannot be excluded, these preliminary data suggest that electromechanical concordance in LVL cathode placement may represent a predictor of optimal CRT response. The full scope of this study will be fully appreciated in the coming month on completion of analysis of the entire patient cohort.

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