Heart Failure (HF) and Atrial Fibrillation (AF) are both associated with impairment of cardiac mechanical function. To assist ventricular contractility in HF, left ventricular assist devices (LVADs) have been developed and demonstrated able to reduce mortality in patients awaiting transplantation, but enormous disadvantages largely limit their long-term use. In parallel, promising devices to mechanically assist atrial contractile function have been successfully tested in large animals but never reached the clinical use. Our revolutionary idea to solve these clinical challenges is to exploit smart materials to support or restore the cardiac mechanical function. Among smart materials, liquid crystalline elastomers (LCEs) are able to respond to external stimuli in a reversible manner to generate movement or tension. The REPAIR consortium has recently developed a novel LCE-based artificial muscle that under external light stimulation is able to enhance cardiac muscle contraction. These results pave the way for the development of a novel generation of cardiac assist devices. We will first develop a mechanical performant and energetically efficient LCE material that, integrated with light sources (µLED array), will result in fundamental biomimetic contractile units to be structured in a suturable, remote controlled contractile tissue. The LCE-µLEDs contractile tissue will be exploited to develop a new generation of cardiac assist devices (e.g. ventriculoplasty patches, aortic rings for diastolic counterpulsation and epicardial bundles for atrial contraction assistance) and test the effects of their acute implantation in large mammals (open-chest sacrifice experiments) and human explanted hearts. Among LCE-device features: they will be self-contracting, low weight, associated with low thromboembolic risk, and most importantly, they will rely on a control unit that can modulate the exerted force providing the fist “tunable” cardiac assist device ever developed.

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease (prevalence 1:200 - 1:500), manifested by thickening of cardiac walls, increasing risks of arrhythmia, and sudden cardiac death. HCM affects all ages - it is the leading cause of death among young athletes. Comorbidities due to gene mutations include altered vascular control, and, caused by HCM, ischemia, stroke, dementia, or psychological and social difficulties. Multiple causal mutations and variations in cellular processes lead to highly diverse phenotypes and disease progression. However, HCM is still diagnosed as one single disease, leading to suboptimal care. SMASH-HCM will develop a digital-twin platform to dramatically improve HCM stratification and disease management, both for clinicians and patients. Multilevel and multiorgan dynamic biophysical and data-driven models are integrated in a three-level deep phenotyping approach designed for fast uptake into the clinical workflow. SMASH-HCM unites 8 research partners, 3 hospitals, 3 SMEs, and a global health-technology corporation in collaboration with patients to advance the state of the art in human digital-twins: including in-vitro tools, in-silico from molecular to systemic level models, structured and unstructured data analysis, explainable artificial intelligence - all integrated into a decision support solution for both healthcare professionals and patients. SMASH-HCM delivers new insights into HCM, improved patient care and guidance, validated preclinical tools, and above all, a first HCM stratification and management strategy, validated in a pilot clinical trial, and tested with end users. Thus providing a cost efficient and effective solution for this complex disease. SMASH-HCM develops a strategy towards fast regulatory approval. In reaching its goals, SMASH-HCM serves as a basis for future digital-twin platforms for other cardiac diseases integrating models and data from various scales and sources.

INSIDE-HEART brings together universities, companies and hospitals from countries (Italy, Finland, France, Israel, Netherlands, Spain, and Sweden) with the main scope of establishing a multi-disciplinary network to tackle the design and the early-phase validation of digital biomarkers, specifically targeting the diagnosis of supraventricular arrhythmias (SVAs) and their associated potential for adverse risk assessment, via the joint combination of signal processing, artificial intelligence and non-clinical devices. This will be achieved by performing excellent research through a unique doctoral training “without walls” among field-expert academic, industrial and clinical entities. The composite nature of the INSIDE-HEART network ensures a highly qualified training and research infrastructure for the specific goal, which aims to generate a new profile of researcher with multi-sectoral expertise able to fill the existing gap, i.e., the absence of digital biomarkers for SVAs reliably estimated with non-clinical devices, taking into account basic research, clinical needs and business interests. Research and training are designed to consider relevant aspects such as public concern of private data management, gender and ethics related to SVAs, all according to Responsible Research & Innovation principles and Open Science practices. All activities in INSIDE-HEART are designed to pursue innovation in three domains: i) Educational domain – by implementing a new multi-sectoral paradigm of PhD training to shape modern professional researchers with cross-competencies in the field, and able to accelerate the translation from basic science to market and clinics; ii) Basic science domain - by producing new knowledge about digital biomarkers by means of a multi-sectoral approach to explore the complex aspects related to SVAs; and iii) Technological domain – by developing new data-driven and model-based methodologies to compute digital biomarkers and support the clinical decision.

Early identification of individuals at risk for CVD allows early intervention to halt or reverse the pathological process. This is the driver of Medtronic and partners to develop a mobile, low-cost, non-invasive, point-of-care screening device for CVD. Assessment of arterial stiffness by measurement of the aortic pulse wave velocity (aPWV) is included in the latest ESC/ESH guidelines for CVD risk prediction. Besides aPWV, early identification of arterial stenosis and cardiac contraction abnormalities can be used to improve CVD risk classification. However, no tools are available today to screen a large population at primary care on these parameters, and individuals that are considered to be at low or moderate risk are too often undiagnosed. The objective of CARDIS is to investigate and demonstrate the concept of a mobile, low-cost device based on a silicon photonics integrated laser Doppler vibrometer and validate the concept for the screening of arterial stiffness, detection of stenosis and heart failure. We will: •Investigate, design and fabricate the optical subsystems and components: silicon photonics chip with integrated Ge-detectors, micro-optics, micro-optical laser bench, optical package •Integrate the subsystems and build a multi-array laser interferometer system •Develop a process flow scalable to high volumes for all sub-systems and their integration steps •Investigate and develop the biomechanical model to translate optical signals related to skin-level vibrations into underlying CVD physiological events •Validate the system in a clinical setting Photonics integration is needed to enable a device that is mobile (small size, small weight, robust (no moving parts), low cost (high volume scalable process flow) and allows fast screening (laser array). The partners commit to protect IP whenever possible, disseminate results via open access and, if target specs are met, commercially exploit and transfer the technology to create social and economic impact.