Since 2004, the Stanford Cardiovascular Institute (CVI) has driven basic and translational research to address cardiovascular diseases by identifying and developing novel therapeutic interventions. The unique organizational structure of the CVI facilitates the funding and coordination of partnerships between scientists, engineers, educators, and physicians. 

“The transformative advances in knowledge and novel approaches to cardiovascular disease therapy that our members and collaborators have achieved are a testament to their willingness and ability to innovate,” says Joseph C. Wu, MD, PhD, director of the Stanford CVI and president of the American Heart Association (AHA) starting July 2023. “I am equally proud of our efforts to support research that advances equity and inclusion efforts across health care.”

The following represent five areas of active research being undertaken by physician-investigators from Stanford Medicine CVI, and research led by Stanford Medicine and supported by AHA to promote interventions for improved cardiovascular health.   

Stem Cell Therapy to Treat or Prevent Heart Failure (HF)

Ischemic heart disease accounts for around 60% of HF, and patients with chronic HF have a poor prognosis (5-year survival rate: <60%), primarily due to irreversibly impaired left-ventricular function.

Some therapies that use cardiomyocytes generated from human embryonic stem cells (hESC-CMs) have shown significant promise. Mechanistically, injected hESC-CMs can either

• Release paracrine factors that engage host cells in repairing the myocardium
• Directly engraft in the myocardium to improve cardiac function

However, clinical trials to assess the safety and efficacy of such applications remain necessary.

Dr. Wu is the principal investigator for a phase I clinical trial called Pilot Study of Human Embryonic Stem Cell-Derived Cardiomyocytes in PaTients with ChrOnic Ischemic Left VentRicular Dysfunction Secondary to Myocardial Infarction (HECTOR). The study aims to determine hESC-CM safety and efficacy, as well identify the recommended dose for the phase II trial. This represents the first in-human evaluation of hESC-CMs for treating HF and preventing progression to HF in patients with chronic ischemic cardiomyopathy.

Learn more about the HECTOR trial. 

Expanding the Diversity of Clinical Trials Related to Cardiovascular Health

Although clinical trials are required to determine the feasibility of specific treatments, many trials fail to include suitable cohorts of minorities and other vulnerable populations. This subsequently hinders an understanding of treatment effectiveness within these populations.

Eldrin Lewis, MD, MPH, division chief of Cardiovascular Medicine, is leading the Diversity and Inclusion in CardioVascular Trials Through Enrollment and Education Resulting in Sustainable Equity (DIVERSE) Network Center. This is a joint partnership between Stanford University, Morehouse School of Medicine, and participating communities focused on improving diversity in clinical research. Their goals are as follows:

• Meet diverse groups and partner with them to overcome long-established barriers to their participation in clinical trials
• Advance diversity in clinical trials in order to enhance health equity
• Create an open access Clinical Trials Toolkit to collate and disseminate evidence-based strategies for removing barriers to participation in clinical trials
• Develop a network of sites to connect institutions, organizations, and clinicians serving diverse populations with clinical trial sponsors and stakeholders
• Train and develop clinical trial leaders to adopt and improve these approaches for future generations

The DIVERSE Network Center is a core component for the American Heart Association (AHA) Strategically-Focused Research Network (SFRN) on the Science of Diversity in Clinical Trials.

Learn more about the DIVERSE Network Center and the AHA SFRNs.

Utilizing Technology to Manage Hypertension

Approximately 50% of people in the United States are unable to control their high blood pressure with medication, resulting in annual healthcare costs of around $22.4 billion.

Additionally, high blood pressure is a major risk factor for heart attack, stroke, and HF, with underrepresented populations particularly affected. The prevalence of hypertension among Black men and women aged ≥20 years in the United States is among the highest in the world. Moreover, underemployed and undertreated gig economy workers may present a particular challenge for chronic disease management.

Paul Wang, MD, director of the Stanford Cardiac Arrhythmia Service, is leading a study (Technology-Enabled Management of Hypertension in Underrepresented Communities and in the Gig Economy) that employs a digital hypertension application on a smartphone to help patients manage their blood pressure.

The app will do the following:

• Remind patients to check their blood pressure
• Alert doctors when patients need to change their medication

Use of the app will also facilitate straightforward data analysis to determine whether those using the app on a regular basis demonstrate greater decreases in blood pressure relative to those that check their blood pressure monthly. Furthermore, the study locations will include Camden, NJ (48% Hispanic or Latino and 41% Black population), as well as Uber drivers in order achieve ethnic, racial, socioeconomic, and generational diversity.

Use of this simple, non-invasive method can potentially improve the cardiovascular and overall health of large numbers of people and enable doctors to apply timely changes in patient care.

Learn more about this study.

A Digital Toolkit for Managing the Treatment of HF

HF is a major cause of morbidity, mortality, disability, and health care costs. Although existing medication regimens can successfully treat HF, appropriate dosing and administration are critical. Failure to meet treatment guidelines is generally a consequence of either:

• Incorrect medication dosing
• Inadequate management of complex medication regimens

The Get with the Guidelines-Heart Failure program developed by the AHA successfully helps physicians and patients adhere to a care plan in hospital settings; however, the program ends upon discharge from the hospital.

Alexander Sandhu, MD, MS, co-director of the Stanford Heart Health Technology Center and instructor of cardiovascular medicine, is developing a digital toolkit that will aid in the care of patients after hospital discharge. The tool will help patients better understand heart failure and encourage an active partnership in managing their heart. This is intended to help care teams better optimize the effective medications used to treat heart failure. Following development, Dr. Sandhu’s Stanford Medicine team and collaborators at other AHA health technology research centers will test the effectiveness of the toolkit.

Learn more about this study.

The Role of Genetics in Mediating Cardiotoxicity Related to Cancer Therapy 

Despite significant advances in the effectiveness of cancer therapies, evidence suggests that therapy-related cardiotoxicity remains a possibility in certain patients. Notably, data suggest that Black patients may be more vulnerable to these outcomes relative to white patients, although the underlying factors and mechanisms for this difference in susceptibility remain unknown.

To investigate the potential mechanisms associated with these outcomes, Nazish Sayed, MD, PhD, assistant professor in the division of vascular surgery in the department of surgery and Stanford CVI, is performing in vitro experiments to identify possible genetic determinants of risk.

The study will recruit 50 breast cancer patients (25 white and 25 Black) and 50 prostate cancer patients (same profile), with each of these cohorts including patients with and without heart complications. Using a method developed by Dr. Sayed’s lab, patient-derived stem cells will be collected and differentiated into vascular cells (endothelial and smooth muscle cells) and cardiomyocytes, followed by exposure of these cells to treatments specific for each respective cancer.

Analyses of the post-treatment outcomes will offer insight into phenotypic changes in the vascular cells suggestive of a genetic component involved in therapy-related cardiotoxicity. This information will benefit patients by allowing care teams to better screen, prevent, and treat heart complications according to racial background.                

Learn more about this study.

Expanding Access to Care and Cardiovascular Disease Prevention

As a nationally recognized leader in cardiovascular care, Stanford Health Care specializes in preventing, diagnosing, and treating all types of heart disease and vascular disorders. These projects highlight the sustained commitment of the Stanford CVI to drive innovation and increase access to outstanding medical services and treatments for everyone.

Learn more about the Stanford CVI and the spectrum of cardiovascular care offered by Stanford Health Care.