Image-Based Modelling of Cardiac Mechanics

The main objective of this study was to model the left ventricle (LV) based on 2D echocardiography imaging technique to assess the cardiac mechanics for group of patients affected by heart failure. A prospective study has been made at Ibn Al-Bitar center for cardiac surgery, for 13 patients with heart failure (HF), 9 patients were males (69%) and 4 females (31%). The mean age was 54±7 years. Those patients were supposed to undergo a CRT-D (Cardiac Resynchronization Therapy Defibrillator) implant as they didn’t respond to drug therapy. Before CRT-D implantation, 2D echocardiography was performed for all the patients, to model the left ventricle and to measure indices that were used to evaluate cardiac mechanics which are LV pressure, wall stresses, global longitudinal strain, and cardiac output. After 3-months of follow-up, 2D echocardiography was re-assessed and the left ventricular mechanics has been re-measured. Post CRT-D implantation, significant improvement in the cardiac mechanics was observed in 54% of the patients which were called responders (patients that respond to CRT-D device) and the other patients were called non-responders. It has been seen that, the circumferential wall stresses were decreased in responder’s group while increased or remain unchanged in non-responders. Global longitudinal strain for the responder’s group were increased while remain unchanged in the non-responders. So, patients were divided into responders and non-responders, based on improvement of the cardiac mechanics after 3-moths of follow up. It has been concluded that the modelling of the left ventricle based on images obtained from 2D echocardiography imaging techniques, was an important computational tool that was used to enhance understanding and support the evaluation, surgical guidance and treatment management of basic biophysics underlying cardiac mechanics.

Electro-energetics of Biventricular, Septal and Conduction System Pacing

Abnormal electrical activation of the ventricles creates abnormalities in cardiac mechanics. Local contraction patterns, as reflected by strain, are not only out of phase, but also show opposing length changes in early and late activated regions. Consequently, the efficiency of cardiac pump function (the amount of stroke work generated by a unit of oxygen consumed), is approximately 30% lower in dyssynchronous than in synchronous hearts. Maintaining good cardiac efficiency appears important for long-term outcomes. Biventricular, left ventricular septal, His bundle and left bundle branch pacing may minimise the amount of pacing-induced dyssynchrony and efficiency loss when compared to conventional right ventricular pacing. An extensive animal study indicates maintenance of mechanical synchrony and efficiency during left ventricular septal pacing and data from a few clinical studies support the idea that this is also the case for left bundle branch pacing and His bundle pacing. This review discusses electro-mechanics and mechano-energetics under the various paced conditions and provides suggestions for future research.

In silico identification of potential calcium dynamics and sarcomere targets for recovering left ventricular function in rat heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a complex disease associated with multiple co-morbidities, where impaired cardiac mechanics are often the end effect. At the cellular level, cardiac mechanics can be pharmacologically manipulated by altering calcium signalling and the sarcomere. However, the link between cellular level modulations and whole organ pump function is incompletely understood. Our goal is to develop and use a multi-scale computational cardiac mechanics model of the obese ZSF1 HFpEF rat to identify important biomechanical mechanisms that underpin impaired cardiac function and to predict how whole-heart mechanical function can be recovered through altering cellular calcium dynamics and/or cellular contraction. The rat heart was modelled using a 3D biventricular biomechanics model. Biomechanics were described by 16 parameters, corresponding to intracellular calcium transient, sarcomere dynamics, cardiac tissue and hemodynamics properties. The model simulated left ventricular (LV) pressure-volume loops that were described by 14 scalar features. We trained a Gaussian process emulator to map the 16 input parameters to each of the 14 outputs. A global sensitivity analysis was performed, and identified calcium dynamics and thin and thick filament kinetics as key determinants of the organ scale pump function. We employed Bayesian history matching to build a model of the ZSF1 rat heart. Next, we recovered the LV function, described by ejection fraction, peak pressure, maximum rate of pressure rise and isovolumetric relaxation time constant. We found that by manipulating calcium, thin and thick filament properties we can recover 34%, 28% and 24% of the LV function in the ZSF1 rat heart, respectively, and 39% if we manipulate all of them together. We demonstrated how a combination of biophysically based models and their derived emulators can be used to identify potential pharmacological targets. We predicted that cardiac function can be best recovered in ZSF1 rats by desensitising the myofilament and reducing the affinity to intracellular calcium concentration and overall prolonging the sarcomere staying in the active force generating state.

EXPRESS: Murine models of sickle cell disease and beta-thalassemia demonstrate pulmonary hypertension with distinctive features.

Sickle cell anemia (SCA) and β-thalassemia intermedia are very different genetically determined hemoglobinopathies predisposing to pulmonary hypertension (PH). The etiologies responsible for the associated development of PH in both diseases are multi-factorial with extensive mechanistic contributors described. Both SCA and β-thalassemia intermedia present with intra and extravascular hemolysis, and because SCA and β-thalassemia intermedia share features of extravascular hemolysis, macrophage iron excess and anemia we sought to characterize the common features of the PH phenotype, cardiac mechanics, and function as well as lung and right ventricular metabolism. Within the concept of iron, we have defined a unique pulmonary vascular iron accumulation in lungs of SCA PH patients at autopsy. This observation is unlike findings in idiopathic or other forms of pulmonary arterial hypertension. In this study we hypothesized that a common pathophysiology would characterize the PH phenotype in SCA and β-thalassemia intermedia murine models, but because unlike SCA, β-thalassemia is also a disease of dyserythropoiesis, with increased iron absorption and cellular iron extrusion mediated by high erythroferrone and low hepcidin levels as well as dysregulated iron transport due transferrin saturation, there may be differences as well. Herein we describe common and divergent features of PH in aged Berk-ss (SCA) and Hbbth/3+ (intermediate β-thalassemia) mice and suggest translational utility as proof-of-concept models to study PH therapeutics specific to genetic anemias.

Efficient Ventricular Parameter Estimation Using AI-Surrogate Models

The onset and progression of pathological heart conditions, such as cardiomyopathy or heart failure, affect its mechanical behaviour due to the remodelling of the myocardial tissues to preserve its functional response. Identification of the constitutive properties of heart tissues could provide useful biomarkers to diagnose and assess the progression of disease. We have previously demonstrated the utility of efficient AI-surrogate models to simulate passive cardiac mechanics. Here, we propose the use of this surrogate model for the identification of myocardial mechanical properties and intra-ventricular pressure by solving an inverse problem with two novel AI-based approaches. Our analysis concluded that: (i) both approaches were robust toward Gaussian noise when the ventricle data for multiple loading conditions were combined; and (ii) estimates of one and two parameters could be obtained in less than 9 and 18 s, respectively. The proposed technique yields a viable option for the translation of cardiac mechanics simulations and biophysical parameter identification methods into the clinic to improve the diagnosis and treatment of heart pathologies. In addition, the proposed estimation techniques are general and can be straightforwardly translated to other applications involving different anatomical structures.

Cardiac mechanics as predictors of left ventricular reverse remodelling in patients with dilated non-ischemic cardiomyopathy

Background and purpose The appearance of left ventricular reverse remodelling (LVRR) is associated with a better prognosis in patients with dilated non-ischemic cardiomyopathy (DCM). Our aim was to identify cardiac imaging parameters, including speckle tracking by transthoracic echocardiography (TTE) and feature tracking by CMR, associated with LVRR in a prospective cohort of patients with DCM. Methods From 2014 to 2021, 182 patients with DCM and left ventricle ejection fraction (LVEF) <40% were prospectively evaluated in our hospital. LVRR was defined as an increase in LVEF ≥10 points or absolute LVEF ≥50%, associated with a reduction in left ventricular end- diastolic diameter ≥10%. Patients underwent multimodality imaging evaluation including CMR with a 1.5 Tesla scanner, and TTE. Cardiac mechanics, including global longitudinal strain (GLS), strain rate (SR) and mechanical dispersion (MD) were measured. Results Median age of our cohort was 62.3 (14.4) years, and 67.7% were male. Most patients (>90%) were treated with beta-blockers or RASS blockers, and 67% with mineralocorticoid receptor antagonists. 30% had cardiac resynchronization therapy (CRT) and 37% had ICD as primary prevention. Mean LVEF was 31.3%. During a mean follow-up period of 35.9 (35.4) months, 38.3% of patients had LVRR. Age and gender distribution were similar in both groups. Regarding cardiovascular risk factors and pharmacological treatment, no differences were found between patients with and without LVRR. Baseline CRT therapy was not associated with LVRR (22.6% vs 34.7%; p=0.249). However, there was a trend towards higher LVRR in those who received CRT during follow-up 18.8% vs 0%; p=0.069). Patients who experienced LVRR had lower basal LVEF (23.4% vs 29%; p<0.008), as well as poorer RV function, including lower RVEF (40.5% vs 51%; p=0.006) and lower TAPSE (16 mm vs 19 mm; p=0.021). Regarding cardiac mechanics, those patients with lower GLS (−9% vs −12%; p=0.001), and higher MD (73 mm vs 55 mm; p=0,050) had LVRR more frequently during follow-up. The presence of a left bundle branch block (LBBB) contraction pattern by strain was associated with higher rate of LVRR (83.3% vs 30.4%; p=0.011). The burden of fibrosis measured by LGE with CMR was not associated with LVRR (14% vs 12%; p=NS). Patients with LVRR had a lower cardiovascular mortality (3.3 vs 14.3%; p=0.117), lower mortality due to heart failure (0% vs 12.2%; p=0.046), less heart failure hospitalizations (20% vs 46.9%; p=0.016), and a lower incidence of ventricular tachyarrhythmias (3.3% vs 18.4%; p=0.051). Conclusions LVRR in patients with DCM receiving optimized medical therapy is associated with a better prognosis. Imaging parameters, including a lower basal LVEF, RVEF, GLS and higher MD, as well as LBBB echo pattern, were associated with a higher frequency of LVRR, and might help to identify patients who could benefit from CRT/and may be helpful to stratify patients's risk. FUNDunding Acknowledgement Type of funding sources: None.