Pankaj Arora, M.D.Pankaj Arora, M.D., director of the Cardiovascular Clinical and Translational Research Program and associate professor in the Department of Medicine, is the latest winner of the Heersink School of Medicine’s Featured Discovery. This initiative celebrates important research from Heersink faculty members.  

Arora's study, "Association of transthyretin val122Ile variant with incident heart failure among Black individuals," was recently published in the Journal of the American Medical Association. 

The study, led by Arora and Vibhu Parcha, M.D., instructor fellow in the Department of Medicine, found that a genetic variation in the Transthyretin gene (TTR V122I) is relatively more common among individuals of Black/African American ancestry (3 out every 100 individuals), and it increases their risk of developing heart failure and having fatal outcomes like deaths due to heart failure, cardiovascular diseases, and all-causes.

“Within the last few years, multiple lines of treatment are now available for patients with transthyretin cardiac amyloidosis, and carriers of the TTR V122I genetic variation can now avail these treatments to prevent the progression of the disease,” said Arora.

Genetic variation in the gene encoding transthyretin protein causes an abnormal folding. This result leads to its accumulation in the heart, leading to its decreased function, a condition called transthyretin cardiac amyloidosis. 

With treatments available, the team recognized a need to identify at-risk individuals more effectively before serious issues develop.

This study exemplifies how advances in genomic medicine can help alleviate health disparities by breaking down a significant barrier to heart health for underrepresented communities with potentially fatal and treatable medical conditions.

Read more from UAB News about their work.   

The Heersink School of Medicine communications staff sat down with Drs. Pankaj Arora and Vibhu Parcha to gain insights about the research of this study, UAB, and the science community.   

Q: What compelled you to pursue this research? 

Arora: There is a growing recognition of transthyretin cardiac amyloidosis among cardiovascular healthcare providers. We and our colleagues across the nation have noted that patients with cardiac amyloidosis include a disproportionately higher number of Black/African American individuals. With the recent availability of FDA-approved treatment for transthyretin cardiac amyloidosis, we wanted to see if the growing recognition of broad inclusivity and advances in genomic medicine can be used to identify individuals at risk of heart failure and death. We wanted to assess if carriers of TTR V122I variants seen more commonly among Black/African American individuals predispose them to develop heart failure and die more frequently compared with those without the genetic variation. The overall goal was to utilize the advances of genomic medicine to directly address health inequities in heart failure, specifically related to transthyretin cardiac amyloidosis. Our vision has been to develop UAB as a center of excellence for precision cardiovascular medicine by encompassing the latest advances in precision medicine including whole-genome sequencing, artificial intelligence and machine learning, multi-omics biomarkers, and targeted individualized therapeutics to improve clinical outcomes, especially among the socioeconomically disadvantaged communities. We were motivated to pursue this investigation at UAB and establish it as a clinical and translational research powerhouse for precision cardiovascular medicine.

Vibhu Parcha, M.D.Q: What was your most unexpected finding?

Parcha: We found that even after accounting for the clinical status, social determinants of health, and demographics, Black/African American individuals carrying the TTR V122I variant had a two-fold higher risk of developing heart failure and ~40% higher risk of dying. 

Q: How do you feel your research will impact the science community?

Arora: Our study is an example of how genomic medicine can help identify individuals having a higher genetic predisposition to developing heart failure. Appropriate diagnostic imaging and testing combined with genetic screening may allow for early detection of Black/African American individuals carrying the TTR V122I variant at a higher risk of heart failure and death. I serve as the director of the UAB Cardiogenomics Clinic, and we regularly assess patients with inherited heart diseases. The TTR gene was previously not included in the panel of genes that are assessed for any secondary findings since there was insufficient evidence supporting its inclusion. In light of the current study, the American College of Medical Genetics and Genomics has now updated its recommendations to include the TTR gene in the panel of genes to be assessed for secondary findings during any genetic test.

Q: What is your research’s relevance to human disease?

Arora: It identifies that a genetic variation seen more commonly among individuals of African ancestry predisposes the carriers to a higher risk of heart failure and death. The findings support the greater inclusion of historically marginalized racial and ethnic groups in cardiovascular genetic and genomic research. This study has led to multiple lines of further investigations assessing the role of diet, exercise, and other lifestyle measures in preventing the disease progression among carriers of the pathogenic TTR V122I genetic variant.  The results of the study have led to the design of new and innovative investigations of genotype-guided physiological and mechanistic clinical studies which will be unraveling novel mechanistic insights into the TTR amyloid disease pathophysiology.

Parcha: Understanding the clinical and social implications of this study’s findings has contributed to the growing recognition of the potential of genomic medicine to overcome longstanding health inequities. It has been a humbling experience to understand that clinical and translational research has the potential to impact the lives of millions of people globally.

Q: When did you know you had an important discovery?

Arora: We realized this was an especially important finding when we noted that in our study TTR V122I genetic variant carriers were at a higher risk of heart failure and death even when accounting for clinical status, social determinants of health, and demographics. We realized that with new FDA-approved therapeutics now available for the disease, these findings will have implications for an estimated 1.4 million Black/African American individuals carrying this genetic variation.

Q: How has being at UAB and living in Birmingham affected your research?

Arora: I first came to UAB two decades ago in 2001 as a medical student. My early formative experience in clinical and translational research at UAB allowed me to pursue a career as a physician-scientist. UAB’s research environment has been focused on utilizing a unique blend of public health and precision medicine as exemplified by the current investigation. UAB has a rich experience in cultivating a collaborative research atmosphere that supports multi-disciplinary research teams across the campus and beyond. The current study was envisioned, led, and completed by clinical and translational research experts at UAB. It is a testament to UAB’s growing international presence in the domains of precision cardiovascular medicine.

Parcha: Working on this project has been an exhilarating experience. The most exciting part of working on this translational project was inter-disciplinary mentorship from internationally renowned experts in cardiovascular genomics (Dr. Pankaj Arora, Dr. Marguerite R. Irvin), heart failure (Dr. Parag Goyal), cardiac amyloidosis (Dr. Mathew Maurer), epidemiology (Dr. Emily D. Levitan), and health disparities (Dr. Suzanne E. Judd). UAB allows us to pursue multi-disciplinary investigations with ease, facilitating and fostering a collaborative work atmosphere leading to a conducive milieu of experience and innovation necessary to lead projects like this. Research leaders and clinical experts from diverse backgrounds are always available. The collaborative and supportive work atmosphere at UAB facilitates the execution of complex and nuanced projects like the current one.