Naomi Chesler

• Professor (Full) at University of California, Irvine

Autologous vascular grafts, the only clinically approved option for small-diameter (<6 mm) revascularizations, require invasive harvesting and have limited availability and variable quality. To address these challenges, we develop a 3-mm-diameter artery graft by using arterial endothelial cells (AECs) derived from pluripotent stem cells (PSCs). Aft...

In addition to activation of muscle contraction by Ca ²⁺ , recent studies suggest that Ca ²⁺ also affects muscle passive mechanical properties. The goal of this study was to determine if Ca ²⁺ regulates the stiffness of cardiac muscle, independent of active contraction. The mechanical response to stretch for mouse demembranated cardiac trabeculae w...

Patient-specific modeling is a valuable tool in cardiovascular disease research, offering insights beyond what current clinical equipment can measure. Given the limitations of available clinical data, models that incorporate uncertainty can provide clinicians with better guidance for tailored treatments. However, such modeling must align with clini...

Ventricular catheterization with a pressure-volume (PV) catheter is the gold-standard method for assessing in vivo cardiac function in animal studies, providing valuable “load-independent” indices of systolic and diastolic heart performance. PV studies are commonly performed to elucidate mechanistic insights into cardiovascular disease using surgic...

Background: Highly precise definition of high-risk features associated with HFpEF may guide targeted treatments and inform biological studies. The aim of this two-step study is to 1) define a high risk HFpEF cluster with unsupervised machine learning approach using cardiac magnetic resonance (CMR), 2) define novel pulmonary vascular mechanics at re...

Background and Purpose Thrombectomy in distal, medium vessels is a topic of increasing interest. To date, there are few in vitro studies focused on performance of ≤5F catheters in medium vessels. The purpose of this study is to compare the performance of the 3F, 4F, and 5F MIVI Neuroscience Q Catheters versus Penumbra 3F, 4F, and MicroVention Sofia...

Introduction Thrombectomy in distal, medium vessels is a topic of increasing interest. To date there are few in vitro studies focused on performance of ≤ 5F catheters in medium vessels Aim of Study The purpose of this study is to compare the performance of the 3F, 4F, and 5F MIVI Neuroscience Q Catheters versus Penumbra 3F, 4F, and MicroVention So...

Introduction Passive leg raise (PLR) is a simple, dynamic maneuver that has been used to increase preload to the heart. We hypothesize that PLR may offer a new and efficient office-based tool for assessing blood pressure (BP) control in older adults. Methods One hundred and three veterans (≥60 years old) without known cardiovascular disease and va...

Pulmonary hypertension (PH) is a debilitating disease that alters the structure and function of both the proximal and distal pulmonary vasculature. This alters pressure-flow relationships in the pulmonary arterial and venous trees, though there is a critical knowledge gap in the relationships between proximal and distal hemodynamics in disease. Mul...

Background and Purpose Thrombectomy in distal, medium vessels is a topic of increasing interest. To date there are few in vitro studies focused on performance of ≤ 5F catheters in medium vessels. The purpose of this study is to compare the performance of the 3F, 4F, and 5F MIVI Neuroscience Q Catheters versus Penumbra 3F, 4F, and MicroVention Sofia...

Pulmonary artery stenosis (PAS) often presents in children with congenital heart disease, altering blood flow and pressure during critical periods of growth and development. Variability in stenosis onset, duration, and severity result in variable growth and remodeling of the pulmonary vasculature. Computational fluid dynamics (CFD) models enable in...

Computational, or in-silico, models are an effective, non-invasive tool for investigating cardiovascular function. These models can be used in the analysis of experimental and clinical data to identify possible mechanisms of (ab)normal cardiovascular physiology. Recent advances in computing power and data management have led to innovative and compl...

While cardiac output reserve with exercise predicts outcomes in cardiac and pulmonary vascular disease, precise quantification of exercise cardiac output requires invasive cardiopulmonary testing (iCPET). To improve the accuracy of cardiac output reserve estimation with transthoracic echocardiography (TTE), this prospective study aims to define cha...

Microvascular disease is a contributor to persistent pulmonary hypertension in those with chronic thromboembolic pulmonary hypertension (CTEPH). The heterogenous nature of the micro and macrovascular defects motivates the use of personalized computational models, which can predict flow dynamics within multiple generations of the arterial tree and i...

A major barrier to the impact of genomic diagnosis in patients with congenital malformations is the lack of understanding regarding how sequence variants contribute to disease pathogenesis and whether this information could be used to generate patient-specific therapies. Congenital diaphragmatic hernia (CDH) is among the most common and severe of a...

Pulmonary hypertension is a cardiovascular disorder manifested by elevated mean arterial blood pressure (>20 mmHg) together with vessel wall stiffening and thickening due to alterations in collagen, elastin, and smooth muscle cells. Hypoxia‐induced (type 3) pulmonary hypertension can be studied in animals exposed to a low oxygen environment for pro...

Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstructs flow and increases pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the small pulmonary arteries due to CTEPH ar...

Computational hemodynamics models are becoming increasingly useful in the management and prognosis of complex, multiscale pathologies, including those attributed to the development of pulmonary vascular disease. However, diseases like pulmonary hypertension are heterogeneous, and affect both the proximal arteries and veins as well as the microcircu...

Computational hemodynamics models are becoming increasingly useful in the management and prognosis of complex, multiscale pathologies, including those attributed to the development of pulmonary vascular disease. However, diseases like pulmonary hypertension are heterogeneous, and affect both the proximal arteries and veins as well as the microcircu...

Introduction: The left (LV) and right (RV) ventricles are linked biologically, hemodynamically, and mechanically, a phenomenon known as ventricular interdependence. While LV function has long been known to impact RV function, the reverse is increasingly being realized to have clinical importance. Investigating ventricular interdependence clinically...

Introduction Thrombectomy in distal, medium vessels is becoming a topic of increasing interest. To date, most benchtop comparisons of aspiration catheters have focused on larger catheters utilized in proximal occlusions and there are no in vitro studies focused on 3, 4, & 5F catheters performance. Aim of Study The purpose of this study is to compa...

Chronic thromboembolic pulmonary hypertension (CTEPH) develops due to the accumulation of blood clots in the lung vasculature that obstruct flow and increase pressure. The mechanobiological factors that drive progression of CTEPH are not understood, in part because mechanical and hemodynamic changes in the pulmonary vasculature due to CTEPH are not...

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interac...

Introduction: The left (LV) and right (RV) ventricles are intrinsically linked directly via shared myofiber and an interventricular septum and indirectly via a closed loop hemodynamic circuit [1], a phenomenon known as ventricular interdependence. While this interdependence has been investigated for over a century [1], the individual contributions...

The American Institute for Medical and Biological Engineering (AIMBE) hosted a virtual symposium titled “Diversifying Paths to Academic Leadership” on January 27 and 28, 2022. The symposium sought to educate the community on the opportunities for and impact of leadership by biomedical engineering faculty, to encourage and invite women faculty, espe...

Combined pre-/postcapillary pulmonary hypertension (Cpc-PH), a complication of left heart failure, is associated with higher mortality rates than isolated postcapillary pulmonary hypertension alone. Currently, knowledge gaps persist on the mechanisms responsible for the progression of isolated postcapillary pulmonary hypertension (Ipc-PH) to Cpc-PH...

Computational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interac...

Chronic stimulation of cardiac a1A-adrenergic receptors (a1A-ARs) improves symptoms in multiple preclinical models of heart failure. However, the translational significance remains unclear. This study tested the effects of chronic a1A-AR stimulation on human engineered heart tissue (EHT). EHTs were created from thin slices of decellularized pig myo...

Background: Exercise-induced changes in arterial function could contribute to a hypertensive response to exercise (HRE) in older individuals. We performed the present analysis to define the acute arterial stiffness response to exercise in ambulatory older adults. Methods: Thirty-nine Veterans (>60 years old), without known cardiovascular disease...

Background Right ventricular (RV) dilation has been used to predict adverse outcomes in acute pulmonary conditions. It has been used to categorize the severity of novel coronavirus infection (COVID-19) infection. Our study aimed to use chest CT-angiogram (CTA) to assess if increased RV dilation, quantified as an increased RV:LV (left ventricle) rat...

Objectives: In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and...

In-vivo studies of pulmonary vascular disease and pulmonary hypertension (PH) have provided key insight into the progression of right ventricular (RV) dysfunction. Additional in-silico experiments using multiscale computational models have provided further details into biventricular mechanics and hemodynamic function in the presence of PH, yet few...

Hiring practices in academia have critically limited the entry of individuals from historically excluded groups (e.g., people who identify as Black/African American, Hispanic/Latino, American Indian/Alaskan Native, LGBTQ+, people with disabilities) into our biomedical engineering faculty. Excluding such individuals has hindered our profession’s res...

For heart failure (HF) patients, myocardial ATP level can be reduced to one half of that observed in healthy controls. This marked reduction (from ≈ 8 mM in healthy controls to as low as 3-4 mM in HF) has been suggested to contribute to impaired myocardial contraction, and to the decreased pump function characteristic of heart failure. However, in...

Hiring practices in academia have critically limited the entry of individuals from historically excluded groups into our biomedical engineering faculty. Excluding diverse individuals has hindered our profession’s research impact and ability to equitably educate our students. With many departments committed to “do better,” we now need to embrace a n...

Purpose: To measure native T1 values, a marker of diffuse fibrosis, by using cardiac MRI (CMR) in young adults born prematurely. Materials and methods: This secondary analysis of a prospective cohort study included young adults born moderately to extremely preterm and age-matched, term-born participants. CMR was performed with a 3.0-T imager tha...

Deep phenotyping of pulmonary hypertension (PH) with multimodal diagnostic exercise interventions can lead to early focused therapeutic interventions. In this study, we report methods to simultaneously assess pulmonary impedance, differential biventricular myocardial strain, and right ventricular: pulmonary arterial (RV:PA) uncoupling during exerci...

Background: Among subjects with exercise intolerance and suspected early-stage pulmonary hypertension (PH), early identification of pulmonary vascular disease (PVD) with noninvasive methods is essential for prompt PH management. Hypothesis: Rest gas exchange parameters (minute ventilation to carbon dioxide production ratio: VE /VCO2 and end-tida...

In-vivo studies of pulmonary hypertension (PH) have provided key insight into the progression of the disease and right ventricular (RV) dysfunction. Additional in-silico experiments using multiscale computational models have provided further details into biventricular mechanics and hemodynamic function in the presence of PH, yet few have assessed w...

Pulmonary artery (PA) pressure increases during lung growth after unilateral pneumonectomy (PNX). Mechanosensitive transcriptional co-activator, yes-associated protein (YAP1), in endothelial cells (ECs) is necessary for angiogenesis during post-PNX lung growth. We investigate whether increases in PA pressure following PNX control-angiogenesis throu...

Pulmonary hypertension is a cardiovascular disorder manifested by elevated arterial blood pressure together with vessel wall stiffening and thickening due to alterations in collagen, elastin and smooth muscle cells. Hypoxia-induced (type 3) pulmonary hypertension can be studied in animals exposed to a low oxygen environment for prolonged time perio...

Patients with pulmonary arterial hypertension (PAH) exhibit cardiac metabolic remodeling, which precedes right ventricular (RV) dysfunction and subsequent heart failure. In this proof-of-concept study of two PAH patients, we demonstrate RV glucose dependency that is unmasked by exercise using a novel in-bore PET/MRI metabolic stress test. This arti...

With severe right ventricular (RV) pressure overload, women demonstrate better clinical outcomes compared to men. The mechanoenergetic mechanisms underlying this protective effect, and their dependence on female endogenous sex hormones, remain unknown. To investigate these mechanisms and their impact on RV systolic and diastolic functional adaptati...

Isolated post-capillary pulmonary hypertension (Ipc-PH) occurs due to left heart failure, which contributes to 1 out of every 9 deaths in the United States. In some patients, through unknown mechanisms, Ipc-PH transitions to combined pre-/post-capillary PH (Cpc-PH) and is associated with a dramatic increase in mortality. Altered mechanical forces a...

Pulmonary vascular distensibility (α) is a marker of the ability of the pulmonary vasculature to dilate in response to increases in cardiac output, which protects the right ventricle from excessive increases in afterload. α measured with exercise predicts clinical outcomes in pulmonary hypertension (PH) and heart failure. In this study, we aim to d...

Introduction: In this study, we report novel methods to investigate impact of pulmonary arterial (PA) afterload with impedance and ventricular interdependency with myocardial strain on right ventricular (RV) reserve with exercise and RV:PA coupling. Hypothesis: In pre-capillary pulmonary hypertension (PH), RV is conditioned to a higher contractilit...

Introduction: Combined pre- and post-capillary pulmonary hypertension (Cpc-PH) is the most severe form of PH-LHF. While the impact of elevated left atrial and consequently elevated pulmonary venous (PV) pressure on Cpc-PH progression is well studied, little is known about how compromised PV flow secondary to LHF affects disease progression. To asse...

Introduction: Bronchopulmonary dysplasia (BPD) is the most common complication of premature birth. Whether right ventricular (RV) injury or chronically increased afterload are more responsible for long-term RV dysfunction in BPD is unknown. We aim to determine key drivers of RV dysfunction in BPD using both experimental data and a computational mod...

Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. Differentiating these closely coupled mechanisms is important to understanding vascular aging. MESA (Multi-Ethnic Study of Atherosclerosis) participants with B-mode carotid ultraso...

Pulmonary Hypertension (PH) is a challenging cardiopulmonary disease diagnosed when the mean pulmonary artery pressure (mPAP) is greater than 20 mmHg. Unfortunately, mPAP can only be measured through invasive right heart catheterization (RHC) motivating the development of novel non-invasive estimates. Pulmonary hypertension patients (n=7) and contr...

Introduction: Aging stiffens arteries, increasing cardiovascular disease (CVD) risk. Elastic arteries stiffen via two main mechanisms: 1) acute load dependent stiffening from higher blood pressure (BP), and 2) structural stiffening such as collagen accumulation. AHA’s arterial stiffness scientific statement highlights differentiating structural vs...

The efficacy of neurovascular thrombectomy depends on several fluid dynamic and material property considerations. Only an entirely impermeable clot that completely obstructs the tip of a thrombectomy device will be governed in its removal by force (of suction) divided by area (of the catheter lumen). However, nearly all blood clots are both porous...

Background Premature birth is associated with lower levels of cardiorespiratory fitness (CRF) but the underlying mechanisms responsible remain unclear. This study assessed whether differences in cardiac morphology or function mediate differences in CRF among adolescents and young adults born preterm. Methods Adolescents and young adults born moder...

Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Ins...

A 48-year-old woman who had been receiving long-term interferon-β for 8 years for multiple sclerosis developed drug-induced World Health Organization group I pulmonary arterial hypertension. Triple therapy for pulmonary arterial hypertension and suspension of interferon-β led to improvement from a high-risk to low-risk state and improvement in exer...

Individuals born very premature have an increased cardiometabolic and heart failure risk. While the structural differences of the preterm heart are now well-described, metabolic insights into the physiologic mechanisms underpinning this risk are needed. Here, we used dynamic fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance i...

Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular function in adults born preterm. Adults b...

Isolated post-capillary pulmonary hypertension (Ipc-PH) occurs due to left heart failure, which contributes to 1 out of every 9 deaths in the United States. In some patients, through unknown mechanisms, Ipc-PH transitions to combined pre-/post-capillary PH (Cpc-PH), diagnosed by an increase in pulmonary vascular resistance and associated with a dra...

PurposeOur study aimed to use chest CT-angiogram (CTA) to assess if right ventricular (RV) dilation, quantified as an increased RV:LV (left ventricle) ratio, is associated with adverse outcomes in the novel coronavirus (COVID-19) infection.Methods We reviewed clinical, laboratory, and chest CTA findings in COVID-19 patients (n=100), and two control...

Our nationwide network of BME women faculty collectively argue that racial funding disparity by the National Institutes of Health (NIH) remains the most insidious barrier to success of Black faculty in our profession. We thus refocus attention on this critical barrier and suggest solutions on how it can be dismantled.

Women with pulmonary arterial hypertension (PAH) exhibit better right ventricular (RV) function and survival than men; however, the underlying mechanisms are unknown. We hypothesized that 17β-estradiol (E2), through estrogen receptor α (ERα), attenuates PAH-induced RV failure (RVF) by up-regulating the pro-contractile and pro-survival peptide apeli...

Introduction: Post-capillary pulmonary hypertension (PH) is diagnosed with rest hemodynamics and requires management of left heart disease. However, in subclinical PH and mixed PH (mixed pre- and post-capillary), it is imperative to identify a predominant post-capillary phenotype with exercise (aka. Pulmonary venous hypertension). Hypothesis: In su...

Sickle cell disease (SCD) is a hereditary blood disorder affecting millions of people in which red blood cells become sickled and lyse easily driven by polymerization of hemoglobin. Chronically, SCD causes anemia and biventricular dysfunction. GBT440 is an experimental treatment for SCD that prevents hemoglobin polymerization. We hypothesized that...

While women are more susceptible to pulmonary arterial hypertension (PAH) than men, their right ventricular (RV) function is better preserved. Estrogen receptor alpha (ERα) has been identified as a likely mediator for estrogen protection in the RV. However, the role of ERα in preserving RV function and remodeling during pressure overload remains po...

Background Hemolysis in sickle cell disease (SCD) releases cell free hemoglobin, which scavenges nitric oxide (NO), leading to pulmonary vascular vasoconstriction, increased pulmonary vascular resistance (PVR), and the development of PH. However, PVR is only one component of right ventricular (RV) afterload. Whether sickled red blood cells increase...

Importance Premature birth is associated with substantially higher lifetime risk for cardiovascular disease, including arrhythmia, ischemic disease, and heart failure, although the underlying mechanisms are poorly understood. Objective To characterize cardiac structure and function in adolescents and young adults born preterm using cardiac magneti...

High-altitude pulmonary edema (HAPE), a reversible form of capillary leak, is a common consequence of rapid ascension to high-altitude and a major cause of death related to high-altitude exposure. Individuals with a prior history of HAPE are more susceptible to future episodes, but the underlying risk factors remain uncertain. Previous studies have...

Computational fluid dynamics (CFD) models are emerging tools for assisting in diagnostic assessment of cardiovascular disease. Recent advances in image segmentation have made subject-specific modelling of the cardiovascular system a feasible task, which is particularly important in the case of pulmonary hypertension, requiring a combination of inva...

Engineering teaching assessment at the college-level should provide: 1) data to assess the quality of instruction provided by an instructor; 2) instructors with actionable information on how their instruction may be improved; and 3) evidence of effective instruction for tenure and promotion purposes. Many institutions rely primarily on student eval...

Background: Pulmonary hypertension causes pulmonary artery (PA) stiffening, which overloads the right ventricle (RV). Since symptoms of pulmonary hypertension (PH) are exacerbated by exercise, exercise-induced PA stiffening is relevant to cardiopulmonary status. Here, we sought to demonstrate the feasibility of using magnetic resonance imaging (MRI...

Right ventricular failure (RVF) is a common cause of death in patients suffering from pulmonary arterial hypertension (PAH). The current treatment for PAH only moderately improves symptoms, and RVF ultimately occurs. Therefore, it is necessary to develop new treatment strategies to protect against right ventricle (RV) maladaptation despite PAH prog...

Left heart failure (LHF) is the most common cause of pulmonary hypertension, which confers an increase in morbidity and mortality in this context. Pulmonary vascular resistance has prognostic value in LHF, but otherwise the mechanical consequences of LHF for the pulmonary vasculature and right ventricle (RV) remain unknown. We sought to investigate...

To accelerate the development of an inclusive culture in biomedical engineering (BME), we must accept complexity, seek to understand our own privilege, speak out about diversity, learn the difference between intent and impact, accept our mistakes, and learn how to engage in difficult conversations. In turn, we will be rewarded by the ideas, designs...