The invention pertains to a prosthetic valve featuring a saddle-shaped annulus that synchronously transforms between concave and convex configurations, facilitating seamless opening and closure synchronized with cardiac cycles. Comprising leaflets and support elements, the valve mimics natural heart valve function, enabling effective blood flow regulation and offering versatile deployment options for cardiac and vascular applications.

This technology describes a prosthetic heart valve system designed to accommodate the growth of children.

Lipoxygenases (LOX) are enzymes that catalyze the peroxidation of certain fatty acids. The cell membrane is mostly made of lipids (which include fatty acids), and peroxidation can cause damage to the cell membrane. The human genome contains six functional LOX genes that encode for six LOX enzyme variants, or isozymes. The role that each LOX isozyme plays in health and disease varies greatly, spanning issues such as asthma, diabetes, and stroke. LOX enzymes are extremely difficult to target due to high hydrophobicity. Potential leads are often ineffective because they are either not readily soluble or not selective for a particular LOX enzyme.  Studies have implicated human epithelial 15-lipoxygenase-2 (h15-LOX-2, ALOX15B) in various diseases. h15-LOX-2 is highly expressed in atherosclerotic plaques and is linked to the progression of macrophages to foam cells, which are present in atherosclerotic plaques. h15-LOX-2 mRNA levels are also highly elevated in human macrophages isolated from carotid atherosclerotic lesions in symptomatic patients. Children with cystic fibrosis had reduced levels of h15-LOX-2, which affects the lipoxin A4 to leukotriene B4 ratio. Furthermore, the interactions of h15-LOX-2 and PEBP1 changes the substrate specificity of h15-LOX-2 from free polyunsaturated fatty acids (PUFA) to PUFA-phosphatidylethanolamines (PE), leading to the generation of hydroperoxyeicosatetraenoic acid (HpETE) esterified into PE (HpETE-PE). Accumulation of these hydroperoxyl membrane phospholipids has been shown to cause ferroptotic cell death, which implicates h15-LOX-2 in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases.  

A primary reason behind the lack of progress in heart therapeutics is the inability to use phenotypic human tissue-level approaches to discover novel therapies. In recent years, there have been significant advances in the development microphysiological systems (MPS), which recapitulate organ-level and even organism-level functions.   MPS are quickly becoming representative of the future of disease modeling and drug screening, therefore paving the way for complex in vitro models to dominate the preclinical drug discovery landscape. However, there has yet to be an effective LNP formulation for therapeutic mRNA delivery to the heart. Therefore, despite progress in this area, one of the remaining challenges is to develop a LNP formulation capable of diffusing within human cardiac muscle, transfecting cardiomyocytes, and escaping the endo-lysosome before degradation more efficiently than current strategies. UC Berkeley researchers and others have developed compositions and methods using lipid nanoparticles for delivery of a payload (e.g., messenger RNA (mRNA)) to the heart, for delivery of mRNA for transfection of cells and methods of treatment.

Lipoxygenases catalyze the peroxidation of fatty acids which contain bisallylic hydrogens between two cis double bonds, such as in linoleic acid (LA) and arachidonic acid (AA). Lipoxygenases are named according to their product specificity with AA as the substrate because AA is the precursor of many active lipid metabolites that are involved in a number of significant disease states. The human genome contains six functional human lipoxygenases (LOX) genes (ALOX5, ALOX12, ALOX12B, ALOX15, ALOX15B, eLOX3) encoding for six different human LOX isoforms (h5-LOX, h12S-LOX, h12R-LOX, h15-LOX-1, h15-LOX-2, eLOX3, respectively). The biological role in health and disease for each LOX isozyme varies dramatically, ranging from asthma to diabetes or stroke. The nomenclature of the LOX isozymes is loosely based on the carbon position (e.g., 5, 12, or 15) at which they oxidize arachidonic acid to form the corresponding hydroperoxyeicosatetraenoic acid (HpETE), which is reduced to the hydroxyeicosatetraenoic acid (HETE) by intracellular glutathione peroxidases. Lipoxygenase inhibitors are difficult to formulate due to challenges with solubility and other factors, therefore new formulations are needed.

Lipoxygenases form a large family of enzymes capable of oxidizing arachidonic acid and related polyunsaturated fatty acids. One such lipoxygenase, 12/15 LOX can oxidize both the C-12 and C-15 of arachidonic acid, forming 12- or 15-hydroperosyarachidonic acid (12- or 15-HPETE). Lipoxygenases and their metabolites have been implicated in many diseases. In particular 12/15-LOX (also known as 15-LOX-1, 15-LOX, or 15-LO-1 in humans and L-12-LoX, leukocyte-type 12-LO, or L-12-LO in mice) plays a role in atherogenesis, diabetes, Alzheimer's, newborn periventricular leukomalacia, breast cancer, and stroke. Whatever the name, the protein is encoded by the gene ALOX15 in both mice and humans. Lox inhibitors are difficult to develop due to the mouse and human homologs having different substrate and inhibitor specificities - 12/15 LOX produces predominantly 15-HETE in humans and 12-HETE in mice. So existing inhibitors are not selective for 12/15 LOX with regard to other LOX isoforms. In addition, many are strong antioxidants and therefore may result in off-target effects. 

Scientists at UC Irvine have developed a sensitive, customizable, and user-friendly sensor for (1) strain detection as a result of cellular movement, (2) micro-fluidic device pressure detection, and (3) real-time monitoring of valve statuses in microfluidic chips. This research tool will provide new insights regarding cellular biophysics.

Researchers at UC Irvine have developed a novel algorithm that more accurately filters raw blood pressure (BP) data collected from continuous non-invasive blood pressure sensors. The algorithm features improvements in eliminating baseline signal drift while maintaining signal integrity and BP estimation accuracy across significant hemodynamic changes.

Researchers at the University of California, Davis have developed an effective drug therapy, utilizing Soluble Epoxide Hydrolase (sEH) inhibitors, to prevent sudden death and treat the progression of myocardial dysfunction in patients with Arrhythmogenic Cardiomyopathy (“ACM”).

Cardiovascular disease is the leading cause of death both worldwide and in the United States, with associated costs in the U.S. reaching approximately $229 billion, each, in 2017 and 2018. Early detection, which can drastically reduce both rates of death and treatment costs, requires access to facilities and highly-trained physicians that can be difficult to access in rural areas and developing countries—despite their prevalence of cardiovascular disease. Computer-based models that use, e.g., PCG (phonocardiogram), EKG (electrocardiogram), or other cardiac data, are a promising route to bridge the gap in standard-of-care for these underserved areas. However, current algorithms are unable to account for demographic features, such as race, sex, or other characteristics, which are known to affect both the structure of the heart and presentation of heart disease. To address this problem, UC Berkeley researchers have developed a new, cloud-based system for collecting a patient's continuous cardiovascular data, monitoring for and detecting disease, and keeping a doctor informed about the cardiac health of the patient. The system sends an alarm when disease or heart attack are detected. To generate the most accurate diagnoses by taking into account demographic information, the system includes private and ethical dataset collection and model-training techniques.

Researchers at University of California, Irvine have developed a novel percutaneous heart valve delivery system for coordinated delivery, positioning, repositioning, and/or percutaneous retrieval of percutaneously implanted heart valves. This system enables optimal placement of the transcatheter heart valve and may thereby significantly reduce the risk of paravalvular aortic regurgitation, myocardial infarction, or ischemia related to improper positioning.

Researchers at University of California, Irvine have developed a novel distensible wire mesh that can be used in the heart surround sleeve component of a whole heart assist device. This wire mesh design enables the device to collapse and expand reversibly for a variety of uses, such as during the delivery process of the whole heart assist device as well as for allowing the device to contract and expand to physically pump the heart.

Researchers at UC Irvine have developed an assembly of components that work together as a system for first grabbing, and then securing the native mitral valve’s leaflet to a prosthesis via transcatheter means.

Currently available techniques used to measure velocimetry within chambers, such as heart chambers, are prone to error due to the inherent limitations of imaging and computational modalities. UC Irvine researchers have developed a novel method that significantly improves the accuracy of velocimetry techniques inside a chamber regardless of the modality.

Cardiovascular disease is among the leading causes of death for citizens in affluent nations, and the most significant cause of morbidity in those with cardiovascular disease is hypertension. Often called the “silent killer” because it has few clinical signs in its early stages, elevated blood pressure is often in an advanced stage before it is treated, leading to a substantially worse prognosis than if it had been detected earlier.In order to address this problem, researchers at UC Berkeley have developed a wearable device which continuously monitors diastolic blood pressure, transmitting data to a portable device such as a cell phone, where it can be stored and analyzed. The device utilizes piezoelectric transducers to perform the measurement, which allows the wearable device to remain small while containing a large number of sensors in order to reduce noise.

CO poisoning is the most common form of poisoning worldwide. In the United States alone, over 50,000 emergency department visits each year are attributed to CO exposure. Despite the prevalence of CO poisoning, there is no clinically-approved antidote available.Current best practices involve placing the afflicted subject in fresh air, delivering 100% O2, or administering superatmospheric levels of O2 in a hyperbaric chamber. These treatments all serve to clear CO from the body by displacing it from metalloproteins with O2. The typical half-life of COHb in the bloodstream is 5.3 h, but hyperbaric O2 (1.5-3 atm) can decrease this half-life to < 1 h.Unfortunately, these large chambers are generally located in tertiary care centers to which patients must be transported. Moreover, hospitals typically house only a few such chambers, which would be rapidly overwhelmed in the event of a mass exposure.Although there are no clinically approved antidotes to CO poisoning, two strategies have been described: the creation of molecules that enhance the rate of release of CO from carboxyhemoglobin (formed during CO poisoning) and the creation of molecules that bind CO more strongly than physiologically important proteins such as hemoglobin.  

See patent publication no. US20210128000A1. A network of electrodes configured to sense and/or pace the heart, wherein the network of electrodes are in contact with an epicardial surface of the heart, within a wrapping sleeve that assist the heart as a whole, wherein the network of electrodes sense the heart by quantifying intrinsic electrical activities of the heart, and wherein the network of electrodes pace the heart by inducing an electrical impulse to the heart to control its contractile activities. The network may be interfaced with a controller system, wherein the controller uses spatial and temporal electrical activities of the heart muscles to generate electrical impulse to synchronize the wrapping sleeve around the heart with the heart. Also disclosed is a system configured to construct space-time mapping of cardiac electrical activities and/or propagation, and sensing effects of a first assist event of a prior beat and controlling a second assist event.

Researchers at the University of California, Davis have developed a surgical device to facilitate vascular anastomosis procedures with enhanced ease and speed.

Researchers at the University of California, Davis have developed a potential drug target for cancer and inflammation by studying the binding of integrins to P-selectin.

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Researchers at the University of California, Davis have designed a motor drive unit that enables combined fluorescence lifetime imaging and optical coherence tomography of luminal structures.

UCI researchers have developed a novel transcatheter pulmonary valve (TPV) that addresses the current lack of options for children with progressive pulmonary valve regurgitation (PVR), which may lead to right ventricular (RV) dysfunction and failure. This TPV allows for implantation into patients of a younger age, preventing the progression of PVR and the RV issues that follow, and can also expand to accommodate the need for a larger pulmonary valve as the patient grows.

Researchers at UCI have developed a minimally invasive mechanism to help deliver and implant a cardiac assist device inside the body to help patients with heart failure.

Inventors at UCI have developed a method of monitoring ECG signals from wearable devices while using artificial intelligence to only select the signals that are relevant to disease for further evaluation.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a predominantly genetic-based heart disease characterized by right but also recently left ventricular dysfunction, fibrofatty replacement of the myocardium leading to fatal/severe ventricular arrhythmias leading to sudden cardiac death in young people and athletes. ARVC is responsible for 10% of sudden cardiac deaths in people ≥65 years of age and 24% in people ≤30 years of age. ARVC is thought to be a rare disease as it occurs in 1 in 1000-5000 people, although the prevalence may be higher as some patients are undiagnosed or misdiagnosed due to poor diagnostic markers. Growing evidence also reveals earlier onset since pediatric populations ranging from infants to children in their teens are also particularly vulnerable to ARVC, highlighting the critical need to identify and treat patients at an earlier stage of the disease. At present there are no effective treatments for ARVC nor has there been any randomized clinical trials conducted to examine treatment modalities, screening regimens, or medications specific for ARVC. As a result, treatment strategies for ARVC patients are directed at symptomatic relief of electrophysiological defects, based on clinical expertise, results of retrospective registry-based studies, and the results of studies on model systems. The current standard of care is the use of anti-arrhythmic drugs (sotalol, amniodarone and beta-blockers) that transition into more invasive actions, which include implantable cardioverter defibrillators and cardiac catheter ablation, if the patient becomes unresponsive or intolerant to anti-arrhythmic therapies. However, current therapeutic modalities have limited effectiveness in managing the disease, 40% of ARVC patients (a young heart disease) die within 10-11 years after initial diagnosis, highlighting the need for development of more effective therapies for patients with ARVC.