Cardiac and Vascular Research
Cardiovascular disease remains the primary cause of death worldwide and impacts patient quality of life on every level. In the Michael E. DeBakey Department of Surgery, colleagues are working closely together to take all the exciting advances in cardiovascular science and translate them into real benefit for patients with cardiovascular disease. In addition to translating research from “bench to bedside,” our surgeon-scientists are uniquely situated to meet clinical challenges with a “bedside to bench” approach. They are able to combine a first-hand view of patient disease and surgical problems with access to the exceptional research infrastructure and expertise found within Baylor’s scientific community to solve those problems.
Our academic mission is to conduct research in order to treat our patients with the most up to date, life-saving treatments. High quality clinical trials conducted throughout Baylor’s affiliated institutions offer patients with cardiovascular disease treatments that are often not available elsewhere. A growing portfolio of clinical and translational research efforts in the division includes more than 30 clinical studies in areas ranging from genetics and molecular biology to new surgical techniques and technologies.
Aortic aneurysms and dissections are common, interrelated cardiovascular diseases that cause nearly 10,000 deaths in the United States each year. Currently, there are no medications that effectively prevent or treat these diseases. To develop such treatments, there is a need to better understand how disease starts and progresses in the aortic wall.
Under the supervision of Dr. Scott A. LeMaire, director of research for the Division and Vice Chair for Research in the Department, and Dr. Ying H. Shen, the research team within the Aortic Disease Research Laboratory maintains one of the world’s most extensive and well-cataloged aortic tissue banks. This core resource facilitates investigations into the causes and progression of aortic disease pursued by our researchers, as well as researchers from other academic institutions. Lab members employ a wide range of standard and advanced techniques, including tissue analysis, cell-based experiments, mouse models of aortic disease, and single-cell transcriptome analysis to understand how different types of cells in the aortic wall respond to stress and how these responses differ in men and women.
Detrimental effects of ciprofloxacin on the aortic wall
Despite concerns raised by population-based cohort studies, the U.S. FDA previously determined that there was not sufficient evidence to issue a warning that the use of fluoroquinolone antibiotics increases the risk of aortic aneurysm, dissection, and rupture. To address the gap in evidence, Drs. LeMaire and Shen conducted experiments to test the hypothesis that ciprofloxacin impairs aortic homeostasis and renders the aortic wall susceptible to stress-induced development of aortic aneurysm and dissection. In an established mouse model of aortic disease, they found that ciprofloxacin significantly increased susceptibility to challenge-induced aortic dissection and rupture compared to controls. They also found that ciprofloxacin decreased lysyl oxidase expression and activity, increased matrix metalloproteinase levels and activity, and increased elastic fiber fragmentation and cell injury. These findings, reported in JAMA Surgery, supported concerns over the use of the class of fluoroquinolones antibiotics for patients at high risk for aortic aneurysm and dissection. Soon after this publication, official protective warnings were issued by the European Medicines Agency and US FDA.
Molecular and cellular signatures provide new possibilities for prevention and treatment
The Aortic Disease Research Laboratory is now working to further identify the mechanisms that drive aortic degeneration. Within the high-volume clinical aortopathy program at Baylor, these scientists are taking advantage of advances in single-cell analysis technologies to explore the molecular and cellular signatures in the aortic wall that are uniquely associated with the risk factors and conditions of aortic disease. Their recent Circulation publication reported that cytosolic DNA and abnormal activation of the cytosolic DNA sensing adaptor stimulator of interferon genes (STING) play a critical role in vascular inflammation and destruction; pharmacological agents inhibiting these genes have been shown to partially prevent aortic aneurysm and dissection.
Valve Sparing Approach for Aortic Root Repair
Under the leadership of Dr. Joseph S. Coselli, the division is active in evaluating the outcomes of both standard and emerging surgical techniques for aortic repair. While the traditional approach toward repair of an aortic root aneurysm involves replacing it with a composite valve graft, an alternate approach—valve-sparing aortic root replacement—has increasingly become more widely used. The valve-sparing approach maintains the superior hemodynamics of the native aortic valve and replaces the surrounding aneurysmal aorta with graft material. An important advantage of valve-sparing repair is the avoidance of long-term anticoagulant therapy, which necessitates an often intolerable change in lifestyle. For the past 15 years, Dr. Coselli has led the international prospective registry study, Aortic Valve Operative Outcomes in Marfan Patients (AVOMP), to compare the durability of valve-sparing operations vs. traditional valve-replacing operations in patients with Marfan syndrome.
New Technologies for Aortic Repair
Dr. Coselli also leads the division’s participation in several clinical trials focused on new devices that may improve surgeons’ ability to treat complex aortic and valvular disease. A few examples of active trials include:
ARISE: Evaluation of the GORE Ascending Stent Graft in the Treatment of DeBakey Type I/II Aortic Dissection. The purpose of this study is to assess the feasibility of using the GORE TAG Thoracic Branch Endoprosthesis (TBE) to treat DeBakey Type I/II aortic dissection.
RelayBranch: A Prospective, Multicenter, Non-Blinded, Non-Randomized Early Feasibility Study of the RelayBranch Thoracic Stent-Graft System in Subjects with Thoracic Aortic Pathologies Requiring Treatment Proximal to the Origin of the Innominate Artery
The study is planned as an initial investigation in using the device for aortic arch and proximal descending thoracic aortic aneurysms, penetrating atherosclerotic ulcers, intramural hematoma, and uncomplicated chronic DeBakey Type III aortic dissection.
TAMBE: Evaluation of the Gore EXCLUDER Thoracoabdominal Branch Endoprosthesis in the Treatment of Thoracoabdominal and Pararenal Aortic Aneurysms
The primary objective of this study is to determine whether the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis (TAMBE Device) is safe and effective in the treatment of thoracoabdominal and pararenal aortic aneurysms.
Heart Valve Disease
Less Invasive Surgeries Make Treatment Possible for More Patients
Mitral valve regurgitation affects an estimated 4 million people in the US. In this condition, the mitral valve leaflets don’t close properly and allow blood to flow backward, which can lead to heart failure. Conventional treatment requires a highly invasive open-heart surgery with prolonged recovery times. Now, a transcatheter mitral valve repair offers a minimally invasive option with an average hospital stay of 2-3 days. In the APOLLO Trial: Transcatheter Mitral Valve Replacement with the Medtronic Intrepid TMVR System in Patients with Severe Symptomatic Mitral Regurgitation led by Dr. Coselli and cardiologist Dr. Guilherme Silva, the safety and efficacy of this system is being evaluated.
Cardiothoracic Surgical Trials Network
Baylor College of Medicine was selected as a Core Clinical Center (CCC) for the NIH/NHLBI-funded Cardiothoracic Surgical Trials Network (CTSN). Led by our chair Dr. Todd K. Rosengart and Dr. Ravi Ghanta, the Michael E. DeBakey Department of Surgery at Baylor College of Medicine is one of 30 highly experienced cardiothoracic surgical centers participating in the CTSN Tricuspid Repair Trial entitled “Evaluating the Benefit of Concurrent Tricuspid Valve Repair during Mitral Surgery.” In addition, BCM has been selected as a trial site for the CTSN “Anticoagulation for New-Onset Post-Operative Atrial Fibrillation after CABG (CTSN PACES Trial),” which seeks to compare anti-coagulation strategies after the development of atrial fibrillation in patients who undergo coronary artery bypass surgery. Both of these trials address fundamental questions in the surgical management of ischemic and valvular heart disease, building on the legacy of innovation in cardiovascular surgery at the BCM.
Ischemic Heart Disease and Heart Failure
Laboratory for Cardiac Regeneration
Heart failure, often caused by myocardial infarction which creates scar tissue within the heart, remains a leading cause of death and decreased quality of life for millions of patients, and traditional treatments have reached the limits of their effectiveness. Researchers in the Laboratory for Cardiac Regeneration, led by department chair Dr. Todd K. Rosengart, are studying whether cells can be reprogrammed to improve cardiac remodeling and function after myocardial infarction. By converting scar tissue into new contractile cells, cellular reprogramming can reduce fibrosis and restore cardiac function. Although this process has been established in rodent models, the next step is to develop pro-plasticity strategies that will work in human cells. The novelty of this work is reflected in the three US patent applications filed by Dr. Rosengart’s lab regarding these discoveries. Some of the exciting research questions they are striving to answer include:
- Whether inadequate expression of reprogramming genes limits transdifferentiation efficiency, which can be optimized by genomic activation strategies.
- Determining the anti-fibrotic mechanisms of reprogramming therapy, particularly those mediated by the transcription factor Gata4
- Whether epigenetic modulation can increase the susceptibility of human cardiac fibroblasts to cellular reprogramming in a clinically relevant fashion
- Exploring the effects of immune modulation on cardiac remodeling after myocardial infarction via local delivery of paracrine factors
Answering these important research questions will redirect efforts in the novel field of cardiac cellular reprogramming and help elucidate a new clinical strategy for treating heart failure.
A New Artificial Heart on the Horizon
Professors in the Division of Cardiothoracic Transplantation & Circulatory Support, Dr. O.H. Frazier and Dr. William E. Cohn, are the leaders of a team of cardiac surgeons and engineers who received a $2.8 million federal grant from the NIH to develop a new smaller, less costly, pulseless artificial heart device that could perform the functions of both left and right ventricles. Drs. Frazier and Cohn collaborate with physician-scientists, engineers, and biologists from Texas Heart Institute, the University of Houston, and Rice University to develop a control system that mimics the heart’s response to the body’s physiological conditions.
The Division of Congenital Heart Surgery focuses specifically on congenital heart surgical outcomes and quality, pediatric heart and lung transplantation, mechanical circulatory support, neurodevelopmental protection, minimally invasive repair of congenital heart defects, aortic reconstruction, surgical repair of congenital coronary anomalies, and, in collaboration with Rice University, pediatric bioengineering. This research takes place at Texas Children’s Hospital, which is ranked #1 in the nation for pediatric cardiology and heart surgery by U.S. News & World Report.
Strong local, national, and global networks and collaborations, such as the Pediatric Heart Network funded by the National Heart, Lung and Blood Institute, are a critical component of congenital heart disease research, bringing together adequate numbers of patients with uncommon, dissimilar forms of disease for meaningful research. Dr. Christopher Caldarone, chief of Congenital Heart Surgery has been at the forefront of many of these collaborative efforts. Helping to create and maintain an important resource for this research, faculty in the Division of Congenital Heart Surgery contribute to the Heart Center Tissue Bank (HCTB), which has collected nearly 4000+ specimens including peripheral blood, urine and cardiac tissues obtained from patients undergoing cardiac surgeries for congenital or acquired heart defects. These specimens are available not only for local researchers but shared through registries around the world.
Dr. Iki Adachi, associate professor of surgery, has continued leading research for ventricular assist device (VAD) use in children, which began with Baylor’s instrumental role in the pivotal 17-center Berlin Heart Study. He conducts research in pediatric myocardial recovery and mechanical assist devices to understand the factors that impact either a bridge to transplant or bridge to recovery, and is now the lead investigator for the Pump for Kids, Infants, and Neonates (PumpKIN) study funded by the National Heart, Lung, and Blood Institute, evaluating the Jarvik Infant 2015 that he helped develop. This device is the size of an AA battery and contains a control system that can change the rate of blood flow as a child grows.
The Pediatric Cardiac Bioengineering Laboratory within the Division of Congenital Heart Surgery is a joint effort between Baylor College of Medicine, Texas Children’s Hospital, and Rice University, and seeks to solve critical congenital heart issues through new technology. Dr. Sundeep Keswani, director of surgical research at Texas Children’s and associate professor of Surgery at Baylor, in collaboration with Dr. Jane Grande-Allen of Rice University’s Department of Bioengineering, is investigating the influences of biophysical cues such as stress, strain, shear, substrate stiffness, and electrical stimulation on the development and maturation of heart cells and tissues.
Congenital diaphragmatic hernia, which often causes significant cardiovascular complications, is also a focus of research within the department. This defect of the fetal diaphragmatic muscle allows abdominal organs to crowd the lungs and prevents them from developing fully, while often causing cardiac problems as well. Researchers within the division are also exploring new ways to target the tissue architectures contributing to the pulmonary hypertension in order to treat this condition more effectively.
Peripheral Vascular Disease
New Device for Chronic Limb-Threatening Ischemia
Patients endure severe vascular disease or ischemia when the arterial system cannot deliver blood due to a blockage. In the leg, this can cause unrelenting pain, a troublesome wound, or even gangrene, in a condition known as critical limb ischemia (CLI). These patients may not be candidates for balloons, stents or bypass surgery and, therefore, often have no alternative but to face a leg amputation. In addition to decreased personal independence and physical complications, amputation carries a 25% risk for mortality within 6 months.
In one of the most dramatic advances in peripheral vascular disease, a new treatment option developed by LimFlow, Inc., is under investigation in the PROMISE II study being conducted by Dr. Joseph Mills, professor and chief of Vascular Surgery and medical director of the Diabetic Foot and Wound Care Center at Baylor St. Luke’s Medical Center, and Dr. Miguel Montero, associate professor. Bypassing blocked arteries in the leg and foot, the LimbFlo device creates an artificial arteriovenous fistula in the below-the-knee vasculature to create a clear channel from the open artery above the blockage to an open vein, so that blood can flow down to the lower leg and foot and enable wound healing.
Innovative Treatment for Diabetic Foot Ulcers with PulseFlow
Caused by peripheral neuropathy and ischemia, diabetic foot ulceration is an all too common and preventable complication of diabetes, which requires amputation in 20% of cases. These patients often present with lower extremity edema and venous insufficiency, but because of the associated peripheral arterial disease, clinicians are reluctant to apply compressive dressings. A novel treatment has been developed that addresses these competing concerns. Dr. Bijan Najafi, professor and director of clinical research in the Division of Vascular Surgery and Endovascular Therapy and director the Interdisciplinary Consortium for Advance Motion Performance (iCAMP), is principal investigator of an interventional study to determine whether a novel low voltage, battery powered medical boot, PulseFlow DF, developed in collaboration with the Diabetic Boot Company, Ltd. UK, can help improve lower extremity perfusion, while holding the foot and lower leg in a position that reduces shear and friction forces and provides a reduction in plantar pressure to improve balance and gait. This timely intervention has been shown to heal wounds, allowing diabetic patients to maintain their mobility and independence.
Determining appropriate transfusion triggers in vascular surgery
Dr. Panagiotis Kougias, associate professor in the Division of Vascular Surgery and Endovascular Therapy, is the national PI on a 17-million dollar trial titled “TOP Trial: Transfusion Triggers After Operations in High Cardiac Risk Patients,” funded by the VA Office of Research and Development, Cooperative Studies Program (CSP). The goal of the TOP Trial is to determine whether a liberal transfusion strategy (transfusion trigger at hemoglobin level < 10 gm/dl) in Veterans with high cardiac risk who undergo major vascular and general surgery operations is associated with decreased risk of adverse postoperative outcomes compared to a restrictive transfusion strategy (transfusion trigger at hemoglobin level < 7 gm/dl). This trial has enrolled over 3000 participants and will continue through 2022.
NIH T32 Research Training Program in Cardiovascular Surgery
Our NIH-funded T32 training program aims to increase the pool of MDs and PhDs who enter cardiovascular surgical research careers, and provide our trainees with the skills necessary to be successful and productive in cardiovascular research. Learn about our T32 training program in cardiovascular surgery research.