CUSTOM-AF

Pulmonary Hypertension (PH), particularly Pulmonary Arterial Hypertension (PAH), presents a fatal complication in chronic diseases, affecting 1 in 50,000 individuals, predominantly at a young age and more often in females. The underlying genetic link involves mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, disrupting BMP signaling. The PHAEDRA-IMPACT consortium aims to understand PH and PAH. The Research The research focuses on understanding PAH through the transforming growth factor-β (TGFβ) signaling pathway, particularly influenced by mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene, prevalent in heritable and some non-hereditary PAH cases. The PHAEDRA initiative identified compounds that modulate the TGFβ/BMP balance, showing efficacy in restoring endothelial function and reversing pulmonary vascular remodeling in preclinical models, though not curing PAH, making early detection crucial. PHAEDRA has identified biomarkers for timely diagnosis and personalized treatment. PHAEDRA-IMPACT will enhance early detection using non-invasive risk assessments, imaging, and biomarker profiling to detect pre-capillary PH. Precision medicine will guide tailored therapies based on advanced imaging and biomarker analyses, addressing disease progression variability among predisposed individuals. Additionally, patient-derived induced pluripotent stem (iPS) cells will be used in 3D culture models of lung and heart tissues to uncover PAH mechanisms and identify therapeutic targets. This comprehensive approach aims to advance our understanding of PAH pathogenesis, accelerate drug development, and enable personalized treatment and preventive strategies for individuals at risk or affected by PH. Origin This consortium was funded through the Impulse Grant program by the Dutch Heart Foundation.

Heart failure poses a large burden on patients and healthcare, largely because heart failure patients have low fitness and require frequent hospitalisation for close monitoring. In CardiacCare@Home, researchers work together with patients, doctors, industry, and others to develop technology for home-based monitoring of cardiac function and rehabilitation. This approach facilitates early detection of worsening of cardiac function, which allows doctors to rapidly alter treatment and prevent hospitalisation. Moreover, home-based rehabilitation will improve patients’ fitness levels. Technological innovations will facilitate a new care path that improves patients’ quality of life and lower socio-economic costs, and lower burden for hospital staff. The research CardiacCare@Home has the following aims: To integrate a feasible, easy-to-use monitoring + biomarker system within the home environment of patients with HF, that is validated against gold standard measures, and to identify parameters suitable for integrated, frequent patient evaluation to improve and personalise treatment. To design an inclusive transmural home-based cardiac rehabilitation programme, personalised to patient (and caregivers) and disease characteristics, tailored to the needs and preferences and co-created with relevant end-users using a combination of user-friendly sensors and an eHealth platform. To develop a data analytics and decision support system to be incorporated in a novel eHealth platform to (i) enable effective monitoring of vital signs for the personalised, early detection of clinical deterioration, and (ii) facilitate personalised behaviour change to improve participation in rehabilitation. Co-develop an integrated, AI-driven, home-based monitoring and/or home-based rehabilitation program in patients with chronic HF after hospital admission due to decompensated HF, and assess its effects on quality of life, functional capacity and re-hospitalisation (WP3). To assess the impact, including cost-effectiveness and budget impact, of the home-based monitoring and/or rehabilitation CardiacCare@Home-intervention compared to current care from the perspective of patients with HF, healthcare providers, health insurance companies, and society. The origin Heart failure is linked to poor hospital recovery, low functional capacity, and high risk of hospital re-admission. CardiacCare@Home aims to develop and adopt innovative technology for home-based monitoring and cardiac telerehabilitation to improve quality of life, reduce admission and lower healthcare costs. This project was funded by the NWO perspective TTW. This public-private program stimulates the development of innovative technologies that may impact economy and society.