Precision medicine in human heart modeling

Abstract

Precision medicine is a new frontier in healthcare that uses scientific methods to customize medical treatment to the individual genes, anatomy, physiology, and lifestyle of each person. In cardiovascular health, precision medicine has emerged as a promising paradigm to enable cost-effective solutions that improve quality of life and reduce mortality rates. However, the exact role in precision medicine for human heart modeling has not yet been fully explored. Here, we discuss the challenges and opportunities for personalized human heart simulations, from diagnosis to device design, treatment planning, and prognosis. With a view toward personalization, we map out the history of anatomic, physical, and constitutive human heart models throughout the past three decades. We illustrate recent human heart modeling in electrophysiology, cardiac mechanics, and fluid dynamics and highlight clinically relevant applications of these models for drug development, pacing lead failure, heart failure, ventricular assist devices, edge-to-edge repair, and annuloplasty. With a view toward translational medicine, we provide a clinical perspective on virtual imaging trials and a regulatory perspective on medical device innovation. We show that precision medicine in human heart modeling does not necessarily require a fully personalized, high-resolution whole heart model with an entire personalized medical history. Instead, we advocate for creating personalized models out of population-based libraries with geometric, biological, physical, and clinical information by morphing between clinical data and medical histories from cohorts of patients using machine learning. We anticipate that this perspective will shape the path toward introducing human heart simulations into precision medicine with the ultimate goals to facilitate clinical decision making, guide treatment planning, and accelerate device design.

Sex Differences in Drug-Induced Arrhythmogenesis

“…Prior to this, a critical and logical next step would be to validate our method using our own independent experiments with human adult cardiomyocytes, and ideally, healthy human volunteers. Ultimately, with a view toward precision cardiology, this sex-specific approach forms an important initial step toward identifying the optimal course of care for each individual patient based on personalized block-concentration characteristics and personalized cardiac heart models (Trayanova, 2018 ; Peirlinck et al, 2021 ; Rodero et al, 2021 ).…”

“…To model the multiscale cardiac electrophysiological behavior across the male and female heart, respectively, we discretize the governing Equations (1)–(4) in space using finite elements (Goktepe and Kuhl, 2009 ) and in time using finite differences (Sahli Costabal et al, 2018a ). Temporally, we utilize an explicit time integration scheme for both the reaction-diffusion equation (Equation 1) and the Purkinje and cardiomyocyte (Equations 3 and 4) ionic models, with a fixed time step size Δ t = 0.005 ms. Spatially, we use a full three-dimensional representation of the human ventricles, created from magnetic resonance images of a healthy, 21-year old, 50th percentile U.S. male (Baillargeon et al, 2014 ; Zygote Media Group Inc., 2014 ; Peirlinck et al, 2021 ). We infer the female geometry as a 90% isometric scaling of the male geometry, following the reported average female to male adult left ventricular mass ratio of 72% (de Simone et al, 1995 ).…”

Computationally efficient model of myocardial electromechanics for multiscale simulations

“…A number of models with detailed descriptions of various ion currents, AP generation, and propagation have been suggested [1][2][3][4][5][6]. Mechano-electrical and mechano-calcium feedbacks causing changes in the time course of AP and Ca 2+ transients and the twitch amplitude were also taken into account by some detailed electromechanical models in 0D simulations [10,14,30,60].…”

“…The modelling approach is particularly important because apart from direct excitation-contraction coupling, there are mechano-electrical and mechano-calcium feedbacks that make the system particularly complex for experimental studying. Detailed electrophysiological models of human ventricular or atrial cardiomyocytes and their clinical applications were reviewed recently [1,2]. Some of these cell-level models [3][4][5][6] reproduce accurately the time-courses of various ionic currents, Ca 2+ transients, and the dependency of the AP duration and amplitude on the stimulation frequency.…”

“…Some of these cell-level models [3][4][5][6] reproduce accurately the time-courses of various ionic currents, Ca 2+ transients, and the dependency of the AP duration and amplitude on the stimulation frequency. Such models allowed their authors to simulate various arrhythmias in the human heart and their drug or surgical treatment [1,2,7,8]. One can combine electrophysiological models with a description of myocardial mechanics including both passive elastic and active Ca 2+ -dependent stress.…”