Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the ‘digital twin’ of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively.

Background-The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomeregene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P<0.0001), including in subgroup comparisons of HCM subjects without evidence of late gadolinium enhancement, as well as of hypertensive patients LV wall thickness of >15 mm (P<0.0001). Compared with controls, native T1 was significantly higher in G+P− subjects (P<0.0001) and 65% of G+P− subjects had a native T1 value >2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions-Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects. (Figure 1). Methods and Results-Patients with diagnoses of HCM or hypertension 8-12Although T1 mapping supports detection of diffuse myocardial disease, late gadolinium enhancement (LGE) helps with visualizing regional changes, such as replacement fibrosis in phenotypically subexpressed HCM gene carriers (G+P− subjects) and overt HCM disease. In compensated LVH because of hypertension-that is before extensive structural and metabolic remodeling with cavity dilatation and functional impairment (eccentric remodeling)-findings reflect physiological adaptations with an increased cellular size because of addition of new, but functional myofibrilles in-parallel and in-series, enabling the ventricle to generate greater forces and to outweigh the increased wall stress. 11,[13][14][15][16][17] Interstitial fibrosis and the expansion of extracellular space in hypertension herald decompensation with eccentric remodeling and heart failure. [12][13][14][15][18][19][20][21][22] In this study, we investigated the ability of CMR to discern hypertrophic phenotypes based on detection of diffuse myocardial disease and regional fibrosis by myocardial T1 mapping and LGE, respectively, first, in overt LVH, and second, in phenotypically subexpressed HCM gene carriers. MethodsConsecutive subjects en...

This paper presents a new registration algorithm, called Temporal Diffeomorphic Free Form Deformation (TDFFD), and its application to motion and strain quantification from a sequence of 3D ultrasound (US) images. The originality of our approach resides in enforcing time consistency by representing the 4D velocity field as the sum of continuous spatiotemporal B-Spline kernels. The spatiotemporal displacement field is then recovered through forward Eulerian integration of the non-stationary velocity field. The strain tensor is computed locally using the spatial derivatives of the reconstructed displacement field. The energy functional considered in this paper weighs two terms: the image similarity and a regularization term. The image similarity metric is the sum of squared differences between the intensities of each frame and a reference one. Any frame in the sequence can be chosen as reference. The regularization term is based on the incompressibility of myocardial tissue. TDFFD was compared to pairwise 3D FFD and 3D+t FFD, both on displacement and velocity fields, on a set of synthetic 3D US images with different noise levels. TDFFD showed increased robustness to noise compared to these two state-of-the-art algorithms. TDFFD also proved to be more resistant to a reduced temporal resolution when decimating this synthetic sequence. Finally, this synthetic dataset was used to determine optimal settings of the TDFFD algorithm. Subsequently, TDFFD was applied to a database of cardiac 3D US images of the left ventricle acquired from 9 healthy volunteers and 13 patients treated by Cardiac Resynchronization Therapy (CRT). On healthy cases, uniform strain patterns were observed over all myocardial segments, as physiologically expected. On all CRT patients, the improvement in synchrony of regional longitudinal strain correlated with CRT clinical outcome as quantified by the reduction of end-systolic left ventricular volume at follow-up (6 and 12 months), showing the potential of the proposed algorithm for the assessment of CRT.