Improving Understanding of Long-Term Cardiac Functional Remodelling via Cross-Sectional Analysis of Polyaffine Motion Parameters

International audienceChanges in cardiac motion dynamics occur as a direct result of alterations in structure, hemodynamics, and electrical activation. Abnormal ventricular motion compromises long-term sustainability of heart function. While motion abnormalities are reasonably well documented and have been identified for many conditions, the remodelling process that occurs as a condition progresses is not well understood. Thanks to the recent development of a method to quantify full ventricular motion (as opposed to 1D abstractions of the motion) with few comparable parameters, population-based statistical analysis is possible. A method for describing functional remodelling is proposed by performing statistical cross-sectional analysis of spatio-temporally aligned subject-specific polyaffine motion parameters. The proposed method is applied to pathological and control datasets to compare functional remodelling occurring as a process of disease as opposed to a process of ageing

Myocardial fibrosis in repaired tetralogy of Fallot; Predicting ventricular arrhythmia and sudden cardiac death

We are faced with new challenges in the growing population of adult survivors with repaired tetralogy of Fallot (rTOF). The risk of premature death persists and drives eager pursuit for the accurate identification of patients at high-risk of malignant ventricular tachycardia (VT) and sudden cardiac death (SCD). It is previously known that inducible VT predicts mortality in rTOF patients. We show that the burden of right ventricular (RV) late gadolinium enhancement (LGE) defined fibrosis > 25cm3 quantified by high-sensitivity 3D LGE can predict inducible VT as a proxy endpoint for mortality. Patients with minimal RV LGE < 10cm3 were extremely unlikely to have inducible VT suggesting those with minimal RVLGE avoid an invasive study. In a prospective study of 550 rTOF patients, a high-risk subgroup of patients with a 4.4% annualised risk of death and 3.7% annualised risk of life-threatening VT/SCD were identified. RVLGE was a strong predictor of outcome. We demonstrated how RVLGE can be integrated with other independent predictors into weighted risk scores ready for clinical use. Diffuse fibrosis defined by RV T1 shows promise as a subtle biomarker of adverse remodelling. An imbalance in the expression of fibrosis biomarkers suggests that a state of high-collagen turnover exists and correlates with adverse remodelling. In conclusion, myocardial fibrosis plays a central role in predicting death and malignant VT in rTOF. This work identifies biomarkers to help risk stratify and enable more personalised and targeted care in the life-long follow up of adult rTOF patients.Open Acces

Improved outcome prediction in tetralogy of Fallot

Successful advances in cardiac surgery have led to a paradigm shift in the management of an expanding population of repaired tetralogy of Fallot (rTOF) patients. However, late morbidity and mortality have not been abolished, with patients vulnerable to arrhythmia and sudden death. Outcome prediction remains challenging, mandating the identification of novel sensitive and specific non-invasive biomarkers. Cardiac fibrosis in rTOF has been shown to correlate to adverse clinical features, and therefore merits further study, particularly with regards to interstitial fibrosis. Cardiac remodelling following surgical pulmonary valve replacement in patients with rTOF was investigated. Structural reverse remodelling was observed to occur immediately after surgery, followed by gradual biological remodelling. A proactive surgical approach before right ventricular (RV) end-systolic indexed volumes exceed 82ml/m2 confers optimal postoperative RV normalisation. Novel cardiovascular magnetic resonance T1 mapping techniques were developed and tested to improve identification of RV interstitial cardiac fibrosis in rTOF. Multi-echo imaging to separate fat from myocardium, combined with blood signal suppression is promising as a feasible method in saturation-recovery T1 mapping, but requires further technical study prior to clinical application and validation. The genomic signatures of the pathological RV in rTOF were investigated by next generation RNA sequencing. Differential gene expression was evident, and potential molecular determinants of fibrotic and restrictive phenotypes were ascertained. Ubiquitin C may have important functional implications as a ‘network hub’ gene in rTOF. Finally, the longitudinal predictive role of neurohormone expression in patients with rTOF was examined. Neurohormonal activation was confirmed in rTOF, with serum brain natriuretic peptide being prognostic for mortality and sustained arrhythmias during extended follow-up. In conclusion, this work reflects the complex interplay of candidate biomarkers in influencing clinical outcomes. Myocardial fibrosis in rTOF remains a key diagnostic and therapeutic target for improving risk stratification and ameliorating morbidity in the lifelong care of these individuals.Open Acces

When Cardiac Biophysics Meets Groupwise Statistics: Complementary Modelling Approaches for Patient-Specific Medicine

This habilitation manuscript contains research on biophysical and statistical modeling of the heart, as well as interactions between these two approaches

When Cardiac Biophysics Meets Groupwise Statistics: Complementary Modelling Approaches for Patient-Specific Medicine

This habilitation manuscript contains research on biophysical and statistical modeling of the heart, as well as interactions between these two approaches

Functional cardiovascular assessment in congenital heart disease

Adequate and serial functional cardiovascular assessment is important in patients with congenital heart disease because many show disruption of normal myocardial geometry, which may or may not be accompanied with hemodynamic overload. We now know, that even after so-called “corrective surgery”, total cure is only seldomly achieved. The presence of residual cardiac abnormalities may lead to malignant myocardial remodeling, which eventually may result in heart failure

Video Kinematic Evaluation: new insights on the cardiac mechanical function

The cardiac mechanical function plays a critical role in governing and regulating its performance under both normal and pathological conditions. The left ventricle has historically received more attention in both congenital and acquired heart diseases and was considered as the mainstay of normal hemodynamics. However, over the past few decades, there has been increasing recognition of the pivotal role of the right ventricle in determining functional performance status and prognosis in multiple conditions. Nonetheless, the ventricles should not be considered separately as they share the septum, are encircled with common myocardial fibers and are surrounded by the pericardium. Thus, changes in the filling of one ventricle may alter the mechanical function of its counterpart. This ventricular interdependence remains even after the removal of the pericardium because of constrictive pericarditis or during open chest surgery. Interestingly, during open chest surgery, only the right ventricle mechanical activity is visually checked by the surgeon and cardiologist due to the absence of an intraoperative imaging technique able to evaluate its complex function. Noteworthy, most of the imaging techniques available to clinicians are established for the assessment of the left ventricle, with the ejection fraction being the most used parameter. However, this value is a measure of global systolic function which comes short in identifying regional myocardial impairment and the mechanical contraction. Therefore, new approaches are needed to deeply investigate the mechanics of both ventricles and correctly assess the cardiac mechanical performance. In this thesis, I studied the mechanical function of the left ventricle through different modalities of cardiac magnetic resonance and employed an innovative imaging technique for the assessment of the right ventricle mechanical function during open chest surgery