Session: 20-17-01: Rising Stars of Mechanical Engineering

Paper Number: 173189

Hemodynamic Mechanisms of Heart-Aorta-Brain Coupling 

Heart failure (HF), a condition in which the heart fails to circulate enough blood or does so only at the expense of elevated filling pressure, has reached epidemic levels. Addressing this challenge requires more advanced prevention and diagnostic strategies, beginning with a deeper understanding of the hemodynamic mechanisms underlying heart-aorta-brain (HAB) interactions. Abnormal aortic wave dynamics can impair myocardial function by reducing coronary blood flow and increasing left ventricular (LV) pulsatile workload, leading to LV hypertrophy and ultimately HF. The two main HF subtypes, HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), differ in pathophysiology, etiology, and treatment. Over the past three decades, the incidence of HFpEF has increased relative to HFrEF and now accounts for roughly half of all HF cases, with a higher prevalence in women. Currently, there is no proven therapy to reduce morbidity or mortality in HFpEF, and clinical evidence suggests that its contributing hemodynamic mechanisms are more heterogeneous than in HFrEF. This underscores the need for a more comprehensive understanding of the fluid dynamic principles governing LV-aortic interactions and the mechanisms driving abnormal aortic wave dynamics in HFpEF.

Aortic biomechanics also play a critical role in brain health. Dementia, often caused by a combination of neurodegenerative and vascular insults, presents a major public health burden, especially given the lack of effective treatments. Abnormal aortic wave dynamics can impact the brain by reducing cerebral perfusion and increasing transmission of harmful pulsatile energy. The brain's high resting blood flow and low vascular resistance make it particularly vulnerable to this type of hemodynamic condition, especially in the presence of aging and hypertension. Clinical studies have linked impaired cerebral blood flow to lacunes, microinfarcts, white matter hyperintensities (WMH), and degradation of white and gray matter integrity. Increased pulsatility has been associated with microbleeds and enlarged Virchow-Robin spaces. The Dallas Heart Study identified aortic arch stiffness as the strongest predictor of WMH volume after age, with additional impact from elevated blood pressure. Although the underlying mechanisms are not yet fully understood, it is widely accepted that aortic stiffening leads to the impairment of arterial wave dynamics and increased transmission of damaging pulsatile energy to the brain. The Reykjavik Study further demonstrated that elevated flow pulsatility is associated with microvascular damage and cognitive decline in memory, processing speed, and executive function. These findings highlight the central role of aortic wave dynamics in aorta-brain hemodynamic coupling and suggest that targeting wave reflections may be a viable strategy for protecting brain function. Additionally, individuals with HF show greater cognitive impairment than age-matched controls without HF, and HF has been proposed as a risk factor for Alzheimer’s disease. Reduced cerebral blood flow in HF may contribute to neurovascular dysfunction and impaired clearance of amyloid beta. However, previous studies have not adequately addressed the complex hemodynamic interactions among the LV, aorta, and brain.

This project is based on the hypothesis that wave dynamics in the aorta dominate the pulsatile hemodynamics of the heart, the brain, and their nonlinear interactions. It aims to uncover the systems-level impact of aortic hemodynamics on HAB coupling by integrating physiology and physics through experimental, analytical, and clinical approaches. A better understanding of these interactions may lead to new strategies for diagnosis, monitoring, treatment, and disease management. Such insights could improve preventive medicine, reduce the burden of HF and dementia, and enhance both survival and quality of life. The project may also contribute to a paradigm shift in viewing organs as dynamically interconnected fluid systems at both macroscopic and microscopic levels. These findings have the potential to inform the development of novel diagnostic tools for HF-related brain injury and support the design of targeted pharmacological and interventional therapies to restore optimal HAB coupling. Ultimately, this research could enable the development of low-cost, easy-to-use, accessible, and noninvasive technologies to transform cardiovascular and neurological care.

Presenting Author: Niema Pahlevan University of Southern California

Presenting Author Biography: Dr. Pahlevan is an Associate Professor of Aerospace and Mechanical Engineering at the Viterbi School of Engineering and an Associate Professor of Medicine in the Division of Cardiovascular Medicine at the Keck School of Medicine at the University of Southern California (USC). Dr. Pahlevan received his B.S. in Mechanical Engineering from the University of Tehran, M.S. in Mechanical Engineering from California State University, Northridge, and Ph.D. in Bioengineering from the California Institute of Technology (Caltech) in 2013. He completed his postdoctoral training in hemodynamics and cardiovascular imaging at Caltech and Huntington Medical Research Institutes (HMRI) as a Boswell fellow. He is the recipient of both the NSF CAREER Award and the American Heart Association’s Career Development Award. In 2022, he received the Junior Research Award from USC's Viterbi School of Engineering. He is an Executive Editorial Board Member of Physiological Measurement and an Academic Editor at PLOS ONE. He also serves on the Editorial Board of Scientific Reports (Nature). In 2022, he was appointed the Gordon S. Marshall Early Career Chair in Engineering. He was honored as a Fellow of the American Heart Association (FAHA) in 2024 and named a Senior Member of the National Academy of Inventors (NAI) in 2025. Dr. Pahlevan is the author of more than 100 peer-reviewed publications and holds 11 issued U.S. patents with 5 additional U.S. patent applications.

Authors:

Niema Pahlevan University of Southern California