AJP-Heart and Circulatory Physiology Podcasts American Physiological Society

Heart failure with preserved ejection fraction (HFpEF) is, in many ways, a fascinating tale of modern cardiovascular medicine that, according to lead author Dr. Joshua Hare (University of Miami Miller School of Medicine), has taught cardiovascular researchers and clinicians a lot of humility. Understanding HFpEF in a variety of animal models has led to a paradigm shift away from heart failure linked to low ejection fraction. In this episode Associate Editor Dr. Jonathan Kirk (Loyola University Chicago Stritch School of Medicine) interviews Dr. Hare along with expert Dr. Julie McMullen (Baker Heart and Diabetes Institute, Melbourne, Australia) about the latest study by Kanashiro-Takeuchi et al. The Hare Lab was originally attracted to a cardiometabolic model of HFpEF pioneered by Dr. Joseph Hill, because in a large proportion of human patients, HFpEF is due to metabolic syndrome, which is a combination of obesity, diabetes, and hypertension. Armed with the ability to create this cardiometabolic HFpEF model, Hare and co-authors decided to test growth hormone-releasing hormone-agonist using a powerhouse of methods to determine if exercise intolerance could be improved. Kanashiro-Takeuchi et al. found that diastolic function and exercise performance improved, and myocyte hypertrophy and fibrosis were restored. Essentially all of the features of cardiometabolic HFpEF responded to treatment with GHRH-agonist. The authors did not see a reduction in blood pressure or weight, indicating a direct myocardial effect. In a wide-ranging discussion that touches on skeletal muscle, aging, sarcomeric proteins, and the technical complexities of running titin gels and PV loops, our experts explain why HFpEF is such a challenging syndrome to treat and why this translational research is so important. Listen now.
 
Rosemeire M. Kanashiro-Takeuchi, Lauro M. Takeuchi, Raul A. Dulce, Katarzyna Kazmierczak, Wayne Balkan, Renzhi Cai, Wei Sha, Andrew V. Schally, Joshua M. Hare Efficacy of a Growth Hormone-Releasing Hormone Agonist in a Murine Model of Cardiometabolic Heart Failure with Preserved Ejection Fraction Am J Physiol Heart Circ Physiol, published April 25, 2023. DOI: 10.1152/ajpheart.00601.2022.

“You cannot make good predictions for patients until you understand the physiology,” stated Dr. Kristian Becker (Icahn School of Medicine at Mount Sinai). Becker and co-authors demonstrated for the first time echocardiographic evidence of a transition in the left ventricular vortex patterns of the heart from the newborn period to the adult period. Listen as Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews Dr. Becker and expert Dr. Ann Chiao (Oklahoma Medical Research Foundation) about how the authors used vector flow mapping to identify changes in cardiovascular efficiency, which were marked by increased energy loss during infancy. In this Rapid Report, which was published in the Call for Papers on the Impact of Aging in the Cardiovascular System, Becker and co-authors found that one early diastolic vortex in newborns transitions to two early diastolic vortices by 2 years of age. Vector flow mapping is an echocardiographic technique that combines doppler ultrasound and blood speckle tracking to follow the direction and velocity of blood in the heart. As a bridge between cardiac MRI and traditional ultrasound, vector flow mapping gives researchers and pediatric cardiologists an understanding of how blood is flowing in the heart and whether heart defects or cardiomyopathies affect blood flow. Given that the heart is a master adapter—it grows from about the size of a walnut at birth to the size of a peach in adulthood—mapping energy loss when the heart is transitioning in size and shape with age is critically important to clinicians. The authors want to take their research from bench to bedside, and back to the bench, for a complete understanding of the heart. Listen now to find out more.
 
Kristian C. Becker, Jennifer Cohen, Jon D. Nyce, Jen Lie Yau, Santosh C. Uppu, Partho P Sangupta, and Shubhika Srivastava Age Related Changes in Left Ventricular Vortex and Energy Loss Patterns: From Newborns to Adults Am J Physiol Heart Circ Physiol, published March 10, 2023. DOI: 10.1152/ajpheart.00002.2023

While anxiety disorders are the most common mental health issue in the United States and are known to increase the risk of hypertension and cardiovascular disease, the links between anxiety, muscle sympathetic nerve activity and blood pressure have not been interrogated to date. Listen as host Dr. Megan Wenner (University of Delaware) interviews author Dr. Jeremy Bigalke (Montana State University) and expert Dr. Jody Greaney (The University of Texas at Arlington) about the latest research by Bigalke et al. Leveraging a large dataset of 88 young adults, the authors examined the relationship between anxiety, blood pressure and resting muscle sympathetic nerve activity using seated blood pressure measurements and the Spielberger State/Trait Anxiety Inventory, which denotes an individual’s propensity for anxiousness along a spectrum. After controlling for several key characteristics including age and sex, Bigalke and collaborators determined that there was a modest relationship between anxiety symptom severity and resting sympathetic outflow in young otherwise healthy adults. Do these changes in sympathetic regulation of blood pressure indicate a significantly increased long-term risk for cardiovascular comorbidities later in life? Our experts discuss this work in the context of the dramatic increase in patients diagnosed with anxiety and associated mental health disorders during the COVID pandemic, and delve into the consideration of sex as a biological variable in the prevalence of anxiety diagnoses among women compared with men. Why are multi-center collaborations critical to the future of research linking subjective psychological characteristics to physiological outcomes? Listen and find out.
 
Jeremy A. Bigalke, John J. Durocher, Ian M. Greenlund, Manda Keller-Ross, and Jason R. Carter Blood pressure and muscle sympathetic nerve activity are associated with trait anxiety in humans Am J Physiol Heart Circ Physiol, published February 17, 2023. DOI: 10.1152/ajpheart.00026.2023

What effects do COVID symptomology and time since diagnosis have on cardiac autonomic function? Listen as Guest Editor Dr. Tiago Peçanha (Manchester Metropolitan University) interviews first author Dr. Rachel Skow (The University of Texas at Arlington) and expert Dr. Chris Minson (University of Oregon) about the research by Skow et al, aimed at better understanding the mechanisms underlying increased cardiovascular risk associated with COVID infection. Skow and co-authors set out to study the cardiovascular health of young adults diagnosed during the early variants of COVID-19 compared to those who had never had COVID. The authors measured resting cardiac baroreflex sensitivity and heart rate variability in order to determine whether having COVID impacted these measures of cardiac autonomic function. Their results were very encouraging: Skow et al. did not show an impact of COVID-19 on cardiac baroreflex sensitivity nor heart rate variability. The authors also studied the impact of symptomology by stratifying their study participants with COVID into different groups – comparing those with persistent symptoms at the time of their assessment to those who did not have persistent symptoms. The authors found no difference between these groups on markers of cardiac autonomic function. However, when Skow and co-authors analyzed their COVID participant group according to date of diagnosis, the authors found better cardiac autonomic function in participants who were studied after a longer time since diagnosis had elapsed, indicating a potential transient effect on cardiac autonomic function in these otherwise healthy young adults. Listen as we discuss the need to study more subjects overall, particularly more diverse patient populations especially in terms of age and co-morbidities, in order to better understand the time course of cardiovascular and autonomic dysregulation during and after COVID.
 
Rachel J. Skow, Nicole A. Garza, Damsara Nandadeva, Brandi Y. Stephens, Alexis N. Wright, Ann-Katrin Grotle, Benjamin E. Young and Paul J. Fadel Impact of COVID-19 on cardiac autonomic function in healthy young adults: potential role of symptomatology and time since diagnosis Am J Physiol Heart Circ Physiol, published November 21, 2022. DOI: 10.1152/ajpheart.00520.2022

What happens when your hypothesis is…wrong? Listen as host Dr. Dan Tyrrell (University of Michigan Medical School) interviews lead author Dr. Julie Freed (Medical College of Wisconsin) and content expert Dr. Chi Fung Lee (Oklahoma Medical Research Foundation) about the new Rapid Report by SenthilKumar et al., which investigated the function of estradiol on human microvessels. In contrast to their hypothesis, Freed and co-authors found that exogenous estradiol treatment of arterioles isolated from both young and older women promoted endothelial dysfunction. In addition, the authors found that estradiol treatment of microvessels isolated from men led to endothelial and smooth muscle dysfunction. The timing of this article is key, given the new AJP-Heart and Circ requirements launched in January 2023 for considering sex as a biological variable. Freed and collaborators originally hypothesized that estrogen may activate the enzyme sphingosine kinase, and therefore mediate cardioprotective effects in the vasculature. However, that was not the case. Freed summed up their surprising results: “There is something going on here. Do we have all the answers yet? No. But we’re going to figure this out.” Listen as we discuss the complexities of human tissue banking, and the grit and flexibility necessary for all researchers to follow the science where it leads.
 
Gopika SenthilKumar, Boran Katunaric, Henry Bordas-Murphy, Micaela Young, Erin L. Doren, Mary E. Schulz, Michael E. Widlansky, and Julie K. Freed 17β-Estradiol Promotes Sex-Specific Dysfunction in Isolated Human Arterioles Am J Physiol Heart Circ Physiol, published January 6, 2023. DOI: 10.1152/ajpheart.00708.2022

Is inflammation the driving force for diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF)? In this episode, Deputy Editor Dr. Zamaneh Kassiri (University of Alberta) interviews author Dr. Thassio Mesquita (Cedars-Sinai Medical Center) and expert Dr. Darryl Davis (University of Ottawa Heart Institute) about the research by de Couto et al. Using a Dahl salt-sensitive rat model of HFpEF, the authors delivered cardiosphere-derived cells (CDCs) via intracoronary injection into the microcirculation. After 2 weeks of treatment with CDCs, the hypertensive rats showed improved endothelial-dependent vasodilation, reduced oxidative stress, restored expression of endothelial nitric oxide synthase, and reduced inflammation. Overall, the authors found that CDCs made significant improvements in the cardiovascular health of hypertensive rats with HFpEF. What is the therapeutic potential of cardiosphere-derived cells for treating heart failure with preserved ejection fraction (HFpEF)? Listen and learn more.
 
Geoffrey de Couto, Thassio Mesquita, Xiaokang Wu, Alex Rajewski, Feng Huang, Akbarshakh Akhmerov, Na Na, Di Wu, Yizhou Wang, Liang Li, My Tran, Peter Kilfoil, Eugenio Cingolani, and Eduardo Marbán Cell therapy attenuates endothelial dysfunction in hypertensive rats with heart failure and preserved ejection fraction Am J Physiol Heart Circ Physiol, published October 17, 2022. DOI: 10.1152/ajpheart.00287.2022