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In 2015, the Texas Heart Institute (THI) was again ranked among the nation’s top heart centers. This represents the 25th consecutive year of top rankings for THI as a heart center by U.S. News & World Report’s annual guide to “America’s Best Hospitals.”
As THI embarks on its 54th year, it has new and unparalleled capabilities and opportunities in an alliance that does not exist anywhere else in the region. THI and Catholic Health Initiatives (CHI) have finalized a partnership that will make THI stronger, and with the continued generosity of its donors, enable it to do even more to reduce the significant toll of cardiovascular disease.
Adult Stem Cell Research and Therapy 2015
Adult Stem Cell Therapy offers hope to the almost 6 million Americans who have congestive heart failure, a progressive form of cardiovascular disease that is usually a consequence of injury to the heart that impairs its pumping ability. Approximately two-thirds of patients with severe heart failure will die within 5 years after diagnosis. Stem cells are “generic” cells that can regenerate themselves and promote repair of damaged tissue. In stem cell therapy today, stem cells are typically removed from another part of the patient’s own body—usually bone marrow, blood, or adipose tissue. The cells are then transplanted into the heart where they can lead to the repair of heart muscle cells and growth of new blood vessels.
In 2012, THI’s Stem Cell Center was selected, after a nationwide competition, to be a member of the prestigious Cardiovascular Cell Therapy Research Network (CCTRN), which is funded by the National Institutes of Health (NIH). THI, one of the original 5 clinical sites in the nation, was awarded a 7-year extension and $5.7 million in additional funding (CCTRN II). Proposed in this second phase was the investigation of novel cell combinations to treat heart failure and novel clinical stem cell research in patients with intermittent claudication, a condition caused by atherosclerotic disease in one or both legs that results in cramping leg pain that occurs during exercise. The potential of stem cell therapy to treat this condition has not been studied thoroughly before. In 2015, it was the recruitment effort of the THI Stem Cell Center and the entire CCTRN that led to fulfilling target enrollment in the intermittent claudication stem cell trial named PACE. In-person patient follow-up will be completed in the first quarter of 2016. Analysis of the data will follow. Additionally, a novel heart failure research trial using cell combination therapy was developed by the collaborative efforts of the CCTRN stem cell research centers. Because the vast experience of the THI Stem Cell Center, this site was one of only 4 sites selected to participate in the “lead-in” phase of this study. THI also continues to expand its recruitment efforts within its referral network of physicians and hospitals throughout Houston and continues to work to expand this network throughout Texas. Also funded by CCTRN II, the Nursing Skills Core Training Program at THI inducted its third trainee in 2015. This program is designed to train nurses in the specialized field of stem cell research.
Under the direction of Dr. James T. Willerson, THI President, and Dr. Emerson Perin, Director of Clinical Research for Cardiovascular Medicine and Medical Director of the Stem Cell Center, clinical trials sponsored by the CCTRN and other corporate benefactors were designed to improve outcomes for patients with chronic ischemic and nonischemic heart disease, left ventricular dysfunction and heart failure, and peripheral vascular disease. In these pioneering studies, THI investigators examined novel stem cell types and critical therapeutic protocol factors, including cell doses and routes of delivery, to improve the therapeutic outcomes of stem cell therapy. THI’s Stem Cell Center currently has 7 U.S. Food and Drug Administration (FDA)-approved adult clinical stem cell trials that are providing treatment for patients with heart and vascular diseases.
In addition to researching stem cell therapy, the Stem Cell Center continues to participate in a clinical device trial for heart failure treatment. This involves implanting a percutaneous device that walls off part of the left ventricle to reduce left ventricular volume. The device may improve blood flow and reduce the severity of symptoms in patients currently being treated with conventional drug therapy or who have advanced heart failure necessitating the use of a heart assist device.
In 2013-2014, the Stem Cell Center participated in a phase II clinical gene therapy trial of hepatocyte growth factor in patients with chronic limb ischemia, showing that this therapy helped heal lower extremity ulceration caused by peripheral vascular disease. In 2015, the report of this trial was accepted for publication in Gene Therapy. International collaboration is ongoing and includes planning and development of a phase III trial for wound healing.
The Stem Cell Center is also active in preclinical research. In August 2013, Dr. Perin was named THI’s 2013 Robert McNair Scholar, an honor designed to recognize and support the work of outstanding scientists and physicians. This is a 5-year award, and in 2014 it supported innovative preclinical research focused on combining early detection and treatment of aortic aneurysms with stem cell therapy to reduce the risk of aneurysm rupture. In addition, the Stem Cell Center preclinical team collaborated with the Texas A&M Institute for Preclinical Studies (TIPS) in a trial of stem cells for treating chemotherapy-induced congestive heart failure.
Currently, the Stem Cell Center is engaged in groundbreaking research in collaboration with Rice University to develop nanoparticle treatments that limit damage from heart attacks.
Stem Cell Engineering
Under the direction of Dr. Robert J. Schwartz, researchers in the Stem Cell Engineering Laboratory are focused on developing methods that will allow them to obtain human skin cells and stem cells from fat tissue and convert them into heart muscle cells (cardiomyocytes).
The researchers are working to identify the optimal cell types for regenerative therapy and thus overcome the technical and ethical issues involved with the use of embryonic stem cells. In keeping with THI's mission to reconstitute a human heart, the researchers plan to grow the cells they “engineer” on artificial biomatrices. The stem cell patches that result will be used to help repair and regenerate injured hearts.
Dr. Schwartz and his team were the first to show the conversion of human adipogenic mesenchymal stem cells (hADMSCs) into advanced mature cardiac myocytes. Two transcription factors, ETS2 and MESP1, were sufficient to convert hADMSCs into cardiac progenitor cells. The team created a novel maturation paradigm by culturing in a Synthecon slow turning bioreactor, which generated 3D cardio-spheroids that enhanced the maturation of converted cardiac myocytes by the coordinate induction of calcium handling ion channels and pumps.
In addition, Dr. Schwartz and his team are the first to show that hADMSCs can convert into pacemaker and Purkinje cells that produce currents necessary for normal cardiac electrical activity. Electrical activity in the heart can become abnormal when scar tissue blocks electrical conductivity between myocytes, resulting in cardiac arrhythmias. Replacement therapy with Purkinje conduction cells and myocytes will be an important step in treating these cardiac arrhythmias by replacing scar tissue with functional cardiac tissue. Thus, there is a growing hope that the conversion of hADMSCs into highly mature myocytes and conduction cells might be used to regenerate and repair damaged hearts.
Regenerative Medicine Research
Under the direction of Dr. Doris A. Taylor, Regenerative Medicine Research (RMR) continues to advance cardiovascular disease research and accelerate its translation into leading-edge patient care. Overall, 2015 was a year of significant RMR accomplishments and successes in research, education, and service to the CHI/Baylor, THI, TMC, and Houston communities.
Focal areas of research include building a human heart in the laboratory, creating a human cardiac patch from extracellular matrix, and developing new personalized cell-based treatments for heart disease. In the US, 22 people die daily on the heart-transplant waiting list. Currently in Texas alone there are 13,300 patients waiting for transplants. Dr. Taylor’s “build a heart” program has successfully expanded its extracellular matrix (ECM) production from small animals into large animals, developed new tissue-engineering strategies, and completed cardiac patch studies—necessary steps toward a first-in-human test.
In 2015, the Center for Cell and Organ Biotechnology (CCOB), a THI-Texas A&M University (TAMU) partnership directed by Dr. Taylor, convened its second annual CCOB Scientific Symposium, bringing together scientists from both institutions who are committed to forging inter-institutional research and commercialization initiatives in regenerative medicine. The CCOB also established a Taylor research lab at TAMU and launched the CCOB Innovation Kitchen, a training ground for students interested in regenerative medicine research. Dr. Richard Dixon, Director of the Wafic Said Molecular Cardiology Research Laboratories at THI, presented at the 2015 Texas A&M University OTC Investment Showcase on behalf of CCOB. Dr. Dixon is also chair of the CCOB’s External Commercialization Advisory Board (ECAG), and along with Dr. Taylor, held the first face-to-face ECAG meeting at Texas Heart Institute.
Dr. Taylor also directs the Biorepository and Sample Profiling Core (BRSPC) laboratory at THI. The laboratory receives, processes, and stores thousands of blood, bone marrow, and tissue samples collected from patients enrolled in clinical studies. In August 2015, the BRSPC became the first biorepository in Texas (1 of only 24 nationwide) to receive accreditation by the College of American Pathologists, the benchmark for excellence in biospecimen management. The BRSPC serves as the Biorepository Core for the National Heart, Lung, and Blood Institute’s Cardiovascular Cell Therapy Research Network (CCTRN, a network of physicians and scientists committed to improving stem cell therapies for heart disease) and the Cardiothoracic Surgical Trials Network (CTSN). THI has provided biobanking and cell profiling for both CCTRN and CTSN, as well as for other companies and institutions seeking the core lab’s services.
Dr. Taylor’s Regenerative Medicine Research (RMR) group was fully committed to research education and service in 2015. At the nationwide Biomedical Engineering Society’s 2015 Annual Meeting in Tampa, Florida, RMR scientists and clinicians presented posters on topics including “Optimization of Re-Endothelialization of Acellular Rabbit Whole-Heart Scaffold” and “Construction of CABG Graft Using Decellularization and Recellularization Techniques.” At the American Heart Association in Orlando, FL, the group presented “Cell Therapy and Extracellular Matrix: A Dual Treatment for Cardiac Disease” and “Identification of Cardiovascular Risk Factors Associated with Bone Marrow Cell Subsets in Patients with STEMI: A Biorepository Evaluation from the CCTRN TIME and Late TIME Clinical Trials.” The group published 3 papers and 7 abstracts describing their research and submitted several American Heart Association and National Science Foundation proposals for funding. Dr. Taylor and the RMR team successfully recruited 3 graduate students from TAMU to her group in 2015, provided summer internships for 17 students, taught in multiple STEM courses (including a course for DeBakey High School teachers), and hosted 2 University of Kentucky co-op undergrads working for 6 months in the laboratory. The RMR hosted more than 130 visitors touring THI RMR Labs.
Dr. Taylor continues to serve on prestigious scientific steering committees, including the Board of Directors for the Alliance for Regenerative Medicine, the outreach committee for the American Association of Gene and Cell Therapy, and the standards committee (writing the guidelines) for the American Association of Blood Banks. She also served on the Executive Committee for the 2nd Annual Medical World Americas Conference and Exposition. That organization recognized Dr. Taylor this year for her service on numerous ad hoc advisory panels for the NIH and the FDA. She also serves on multiple international scientific think tanks, is a jury member for the Institute de France Lefoulon-Delalande Grand Prix (an international scientific prize awarded yearly), and makes frequent appearances as an expert on stem cell therapy and regenerative medicine in the media and the scientific arena. Through her collaborative efforts with institutions both in the TMC and abroad, Dr. Taylor hopes to bring together ideas from across the globe to create ground-breaking treatments that will benefit the citizens of Houston and the world, and to solidify THI’s role as a leader in molecular cell genetics and regenerative medicine.
To that end, Dr. Taylor served as invited speaker for numerous national or international meetings this year, including:
Brazilian Cell Therapy Association, Búzios, Brazil
CCTRN Research Coordinator & Steering Committee Meeting, NIH, Washington, DC
Medical World Americas Conference and Expo, Houston, Texas
27th Annual Scientific Symposium of Transcatheter Cardiovascular Therapeutics, San Francisco, California
2015 Women in Science & Entrepreneurship Conference, St. Louis, Missouri
National Policy and Science Summit on Women’s Cardiovascular Health, Washington, DC
American Heart Association, Orlando, Florida
World Stem Cell Summit, Atlanta, Georgia
Chief of Naval Operations Strategic Studies Group, Newport, Rhode Island
In recognition of her scientific achievements since graduating from Mississippi University for Women, Dr. Taylor was awarded an honorary doctorate in 2015, the university’s highest honor, when she spoke at the May commencement exercises in Columbus, Mississippi. The event’s press release recognized Dr. Taylor as a pioneer in cardiovascular cell therapy research, further noting that “She and her team are internationally renowned for their research on ‘whole organ decellularization,’ in which they have demonstrated that they can remove the existing cells from hearts of laboratory animals, and even humans, to leave a framework for building new organs. The hope is that this research is an early step toward being able to grow a fully functional human heart in the laboratory, which if it can be achieved would revolutionize the field of organ transplantation.”
The Cardiomyocyte Renewal Laboratory (CRL), directed by Dr. James Martin, is focused on understanding how genetic signaling pathways influence adult heart muscle homeostasis and regeneration.
In 2015, Dr. Martin and his group strengthened their work in elucidating the genetic pathways that inhibit cardiac repair in the adult mammalian heart. They identified several genes that are turned on in the adult heart after a heart attack that may be therapeutically targeted to enhance adult heart repair. They have constructed and successfully tested small molecules designed to treat heart muscle damage that occurs after a heart attack.
The CRL researchers also characterized the genetic pathways that are active in cardiac arrhythmia states, such as atrial fibrillation, the most common sustained arrhythmia in humans. By obtaining an in-depth understanding of these pathways, they can develop ways to treat atrial fibrillation. They have already identified promising therapeutic targets for suppressing susceptibility to atrial fibrillation.
The CRL researchers have established a direct link between the genes that regulate cardiac regeneration and Duchenne muscular dystrophy–associated cardiomyopathy, the progressive weakening of the heart muscle caused by a genetic mutation. Dr. Martin and the CRL team will use insights from these studies to identify therapeutic options that will promote normal heart function and regenerative capabilities in patients with muscular dystrophy.
The CRL team is developing novel cardiac therapies, such as the use of gene-editing technology, to restore the function of mutated genes that cause genetic cardiovascular disorders.
Wafic Said Molecular Cardiology Research
Researchers in the Wafic Said Molecular Cardiology Research Laboratories, directed by Dr. Richard Dixon, strengthened their innovative work in adult stem cell therapeutic mechanisms and in stem cell and gene therapies for treating pulmonary arterial hypertension and peripheral arterial disease.
Dr. Dixon established extensive collaborations both inside and outside THI that allowed his team to make several important discoveries in 2015. He collaborated with Dr. Taylor to enhance tissue regeneration by developing a small-molecule “stem cell glue” that can be used to more effectively target stem cells to the site of injury in damaged tissues. This joint effort revealed that this compound could also enhance the efficacy of immune checkpoint modulators to make those novel therapies more effective. Dr. Dixon also established collaborations with Dr. Robert Schwartz, Director of Stem Cell Engineering at THI, and Dr. James Martin, Director of the Cardiomyocyte Renewal Laboratory at THI, to form a core group of researchers who can rapidly bring cardiac stem cell therapies to clinical trials. The stem cell glue is being used in these collaborative programs. Dr. Dixon’s group also developed a novel gene therapy that causes mesenchymal stem cells to express the vasoactive substance prostacyclin. When tested in animals with peripheral arterial disease, stem cells treated with this gene therapy were better able to engraft to damaged tissues while simultaneously stimulating endogenous stem cells to repair these tissues much faster than untreated cells could. We believe these therapies will soon be ready for clinical testing.
Dr. Dixon and his team have developed noninvasive molecular imaging systems for visualizing vulnerable plaques—atherosclerotic plaques that are likely to rupture and cause a heart attack. The researchers are working with the molecular modeling department at UT Austin to create computer models of vulnerable plaque development. This program has advanced rapidly into animal testing, and the team hopes to be able to bring this technology into the clinic soon. This program was recently awarded $250,000 from the Fondren Foundation in support of this work. The team and the UT Austin group also received a $250,000 joint philanthropic grant.
Dr. Dixon established a collaboration with Dr. Jeffrey Hartgerink of the chemistry department at Rice University to develop and test synthetic peptides with angiogenic properties. The peptides were found to significantly enhance healing in animal models of peripheral arterial disease. This research is being further expanded to investigate the use of synthetic peptides in animal models with experimentally-caused heart attacks. These compounds continue to yield remarkably efficacious patches when used to treat a variety of animal tissue injuries.
Dr. Edward Yeh (a 2008-2013 THI McNair Scholar) and his team continued to advance 3 critical and interrelated areas of cardiovascular research: 1) how therapy with certain stem cells work mechanistically to repair damaged hearts, 2) how modification of potassium channels control seizures and sudden cardiac death, and 3) how turbulent flow accelerates atherosclerosis through Sentrin/SUMO-specific protease 2. In an article published this year in the Journal of Clinical Investigation Dr. Yeh’s team revealed aspects of the process by which disturbances in blood flow alter the behavior of cells that line blood vessels, making the vessels prone to atherosclerosis. This could lead to the development of better treatments for preventing atherosclerotic disease.
THI scientists have shown that aged human stem cells and murine stem cells lose their ability to promote regeneration in injured hearts and blood vessels. THI stem cell biologists collaborated to identify genes that are involved in regenerating heart muscle and preventing the cellular deterioration associated with aging. They demonstrated that blood flow could be increased by treating aged cells in mice with 2 genes that act together to enhance cardiovascular regeneration and restore the aged cells to their youthful capacity. We believe these cells may be effective for “regenerative” therapy in aged patients with injured hearts, and studies are planned to test this hypothesis.
The State of Texas committed $2.5 million in each year of the September 2013-August 2015 biennium for the Texas Heart Institute’s Adult Stem Cell Research Program under the direction of Dr. Willerson. These research activities are continuing, and additional funding of $500,000 over 4 years from the Fondren Foundation was obtained to support Drs. Dixon and Martin in their adult stem cell efforts.
Cardiovascular Surgical Research
Surgeons and cardiologists in THI’s Center for Cardiac Support continued their leadership in the use of left ventricular assist devices (LVADs) for support of patients with severe heart failure.
In 2014, 77 patients received LVADs under the direction of Drs. O. H. Frazier, William E. Cohn, and Steven K. Singh. Dr. Frazier has now implanted more than 1,000 assist devices in patients with severe heart failure. The HeartWare LVAD is the most recent to receive FDA approval as a bridge to transplantation, thus providing an additional option for patients requiring LVAD support. Destination therapy studies of the HeartWare LVAD for patients who are not approved for heart transplantation are still ongoing. Of note, Dr. Frazier and his team were instrumental in the development of the HeartWare device. In fact, every cardiac assist device currently in clinical use world-wide was either developed by or received initial developmental support from Dr. Frazier at THI. Over 200 patients with assist devices are actively followed up at St. Luke’s and in the Heart & Lung Treatment Center.
Dr. Frazier’s team is continuing to develop and test new heart assist devices, including the HeartMate III, which uses a magnet to suspend its single moving part (an impeller). Clinical trials of the HeartMate III have already begun. In addition, cardiologist Dr. Reynolds Delgado is continuing his work on a new minimally invasive assist device that is wrapped around the aorta rather than being attached directly to the ventricle. Called the C-Pulse System, this device can be implanted through a small chest incision and is intended for patients with moderate-to-severe heart failure. THI researchers are also participating in the NIH Pediatric Circulatory Support program, whose goal is to develop an assist device for infants and children in collaboration with Jarvik Heart, Inc.
Dr. Frazier and Dr. Cohn continue to lead the development and evaluation of 2 total artificial hearts (TAHs). The current device is a dual-pump, continuous-flow TAH, which has received over $7 million in cumulative funding from the NIH and other sources. This work has given researchers valuable insights into the effects of continuous (nonpulsatile) flow on mammalian physiology. Continuous flow is the current standard for mechanical support devices. The second TAH was developed under the directorship of Dr. Daniel Timms. He was recruited to THI along with his outstanding team of engineers. Dr. Timms’ innovative TAH is small, lightweight, and designed for total heart replacement. Because it contains only a single moving part it promises to be durable and less susceptible to wear than the pulsatile heart replacement devices in current use. Currently, this TAH is being refined and tested with the use of 3-dimensional printing in our cardiovascular research lab in preparation for possible human trials in the near future. It has worked well in animal studies.
Under the direction of Dr. Cohn, THI’s Center for Technology Innovation made advances in several promising technologies, including a miniature heart assist device the size of a pencil eraser, which targets heart failure at a relatively early stage. Like a pacemaker, the mini-pump is inserted intravenously. The simplicity of the procedure should decrease the risks associated with implantation and shorten the recovery period. This pump may also be useful for children with debilitating heart failure. Another of the Center’s projects involves a novel treatment for mitral regurgitation that does not require a large chest incision or cardiopulmonary bypass. The first two patients were recently implanted with the device by Dr. Cohn in Kuala Lumpur, with very encouraging results. Moreover, a novel catheter-based technology for creating arteriovenous fistulas to allow patients with renal failure to receive safer dialysis has been developed in the Center and has now been used in over 150 patients in Canada and Europe. TVA Medical, the company that was founded by the Center, is now seeking US FDA approval of the technology. Lastly, The Center continues to work closely with BiVACOR Inc. to develop the world’s first practical mechanical replacement for the failing human heart, and success has never been closer.
THI’s Adult Cardiac Surgery Department, under the direction of Dr. Joseph Coselli, continues to perform innovative clinical studies for severe, life-threatening heart conditions.
The aorta is the major artery that transports blood from the left ventricle to the rest of the body, and aortic rupture caused by “ballooning” (aneurysm) or tearing (dissection) of the aortic wall results in more than 10,000 deaths annually in the United States. Early diagnosis is critical for some types of dissections, which, if left untreated, kill 33 to 50 percent of patients within 24 to 48 hours. As a tertiary-care center, THI routinely receives critically ill patients via Life Flight on a 24-hour basis to undergo emergent operative treatment. Dr. Coselli’s team is continuing to collaborate with researchers from Shriners Hospital for Children in Portland, Oregon, the Oregon Health & Science University in Portland, and Baylor College of Medicine to evaluate a blood test that may help diagnose these dissections early.
Dr. Coselli continues to perform a high volume of challenging aortic operations. In May 2015, Dr. Coselli shared the outcomes of 3309 thoracoabdominal aortic aneurysm (TAAA) repair procedures at the annual meeting of the American Association for Thoracic Surgery to mark the beginning of his presidential term.
Dr. Coselli and others continue to participate in novel clinical trials. The CoreValve trial involves replacing a stenotic aortic valve with a specially designed prosthetic valve delivered through a catheter system. The aortic valve is replaced without the need for traditional open heart surgery. The CoreValve has recently been approved by the FDA for use in very high-risk patients who otherwise would not be candidates for aortic valve replacement, and the device is currently being evaluated in patients at lesser risk. The TRANSFORM clinical trial aims to evaluate the use of “rapid deployment” prosthetic valves that incorporate features of transcatheter valves and traditional open repair. Inserted by a minimally invasive open approach (ie, a mini-sternotomy), the replacement aortic valve quickly springs into place and does not require laborious suturing, which greatly reduces time in the operating room and may help patients fare better after repair.
In addition to providing histopathologic support for THI colleagues from other departments, the Cardiovascular Pathology Laboratory is involved in several research projects. Our investigators are Ibrahim Aboshady, MD, L. Maximilian Buja, MD, Ana Segura, MD, and Deborah Vela, MD.
THI pathologists have an ongoing interest in the study of patients with end-stage heart failure and continuous-flow mechanical support, with an emphasis on identifying those whose disease has improved enough to allow device explantation. This research includes studies of cardiac remodeling and the effects of continuous flow on human physiology. Other special topics include sarcoidosis-related cardiomyopathy and doxorubicin (Adriamycin)-induced heart failure.
THI pathologists, along with colleagues at the Department of Cardiothoracic and Vascular Surgery of the McGovern Medical School at the University of Texas Health Science Center at Houston and the Clinical Research Division of the 59th Medical Wing at Joint Base San Antonio-Lackland, San Antonio, Texas, have completed work on the second phase of the project of locally developing a triple-antimicrobial-bonded aortic graft for preventing and treating perioperative graft infections. This work was recently published in the Journal of Vascular Surgery. Currently, the investigators are preparing for the third phase of the project, which includes completing the animal studies for the maximal protective period (4 months) and, in parallel, conducting a prospective clinical trial in collaboration with the military group. This work was presented at the 2015 Annual Meeting of the United States and Canadian Academy of Pathology.
Findings from our study of the unusual complications of using different vascular prostheses have been accepted for presentation at the upcoming meeting of the United States and Canadian Academy of Pathology.
We have continued our collaboration with MD Anderson Cancer Center's Division of Diagnostic Imaging, performing additional experimental work in the third phase of a project intended to assess the maximal capabilities of a new flat-panel computed tomography (CT) technology, images from which will be compared with those produced by MRI.
In 2015, THI pathologists continued their collaborative, grant-funded work in atherosclerosis imaging research. These projects focus on enhancing the diagnostic capabilities of certain imaging modalities (optical coherence tomography and combined intravascular ultrasound and photoacoustic imaging) and involve collaboration with research groups at UT at San Antonio and Austin. Another ongoing focus of research is the development and application of approaches to document the localization and effects of stem cells and other biological agents in the heart.
Investigators in the Electrophysiology Research Laboratory, under the direction of Dr. Jie Cheng, continue to focus on understanding how various types of abnormal heart rhythms develop.
Dr. Cheng’s group recently identified a novel mechanism that contributes to atrial fibrillation, the most common sustained cardiac arrhythmia. This mechanism involves a neuronal transmitter called vasoactive intestinal polypeptide (VIP). Dr. Cheng and his team described how a receptor gene of VIP is expressed abnormally in the atria of patients with heart failure. The researchers hypothesize that increased abnormal VIP receptor expression parallels the progression of heart failure and correlates with arrhythmogenic ion-channel dysfunction in response to VIP. In an animal model, they plan to study how these abnormal receptors alter the response of heart tissue to VIP. They hope to develop a specific inhibitor against abnormal receptors that would affect diseased tissue, but have little effect on normal heart tissue. They have applied for a grant to test their hypotheses.
The researchers have identified the mechanism by which B-type natriuretic peptide promotes arrhythmias. This peptide is secreted from the heart’s pumping chambers as heart failure develops and worsens. The group’s initial findings brought attention to this common peptide, which is not only a marker for assessing heart failure, but also a target for preventing and treating the disease.
Dr. Cheng and his team have found a way to prevent the anti-tumor drug, doxorubicin from depleting human cardiac stem cells. Doxorubicin is one of the most effective anti-tumor agents, but it can be toxic to heart muscle. THI researchers have shown that a drug called iloprost, used to treat pulmonary hypertension, can protect the heart against the toxic effects of doxorubicin. They hope this drug will be approved for use in cancer patients undergoing doxorubicin therapy.
The researchers have also been conducting extensive screening studies to identify genetic mutations that may put people at risk for arrhythmias and other cardiovascular disorders. These studies hold promise for developing personalized therapies tailored for individual patients.
Electrophysiology Clinical Research & Innovations
Dr. Mehdi Razavi directs the Electrophysiology Clinical Research & Innovations (ECRI) program at THI. His goal is to develop an infrastructure for translational and clinical cardiac arrhythmia research and innovation that will establish THI as a nationally and internationally recognized leader in the field of cardiac arrhythmias.
Most recently, Dr. Razavi and his collaborator Professor Matteo Pasquali (chair of the Department of Chemistry at Rice University, where Dr. Razavi is also an adjunct professor of Bioengineering) have won the American Heart Association's prestigious Collaborative Research Award. Only 4 groups are selected to receive this award each year from among nearly 200 applicants nationwide. The Award is to support Drs. Razavi and Pasquali's groundbreaking research, which has shown that carbon fibers can be used to effectively treat diseased electrical conduction in heart tissue. This diseased conduction leads to ventricular arrhythmias, which are the leading cause of sudden death in the United States.
In clinical studies, the ECRI researchers are identifying how symptoms begin in patients who have asymptomatic arrhythmias, specifically atrial fibrillation, which can cause blood clots to form in the left atrium and result in a stroke. Dr. Razavi is involved in a clinical trial that is investigating a novel, catheter-based way to tie off the part of the left atrium that is responsible for such strokes. He is also evaluating a new 3D analysis and mapping system to detect the sources of arrhythmias and, thus, identify targets for catheter ablation.
In animal studies, Dr. Razavi and his team are analyzing the effects of different treatment options on cardiac arrhythmias. For example, they are studying a new catheter that can be used to predict the occurrence of cardiac perforation, a potential complication of arrhythmia ablation procedures. The investigators are also collaborating with Rice University on several projects that will integrate the Rice professors’ engineering knowledge with the Razavi team’s medical knowledge to develop new device-related treatments for cardiac arrhythmias.
Other Research Projects
THI-affiliated physicians were among the first in the nation to begin implanting bioresorbable stents in place of metal stents as scaffolds to open blocked coronary arteries. Designed to disappear within 6 months to 2 years, these stents may prevent the inflammatory reaction that develops over time with metal stents. This method may also allow more complete coverage of blocked arteries in patients with more advanced disease.
A minimally invasive option for aortic valve replacement is a procedure in which a catheter is inserted into an artery in the groin and advanced into valve position. A balloon at the end of the catheter, with a replacement valve folded around it, delivers the new valve to take the place of the old one. Among THI physicians involved in this type of treatment are Drs. Ali Mortazavi, Neil Strickman, Zvonimir Krajcer, Ross Reul, David Ott, Guilherme Silva, David Fish, and Jose Diez.
The treatment of structural heart disease, which includes any cardiac abnormality that interrupts normal blood flow, is a new subspecialty that has emerged over the last decade. Under the direction of Dr. Guilherme V. Silva, members of THI’s Structural Heart Disease Program are working to develop new transcatheter therapies for treating a variety of conditions, including congenital defects, without open heart surgery.
The TEXGEN Program, led by Drs. Willerson, Eric Boerwinkle, and A. J. Marian continued to focus on delineating genetic factors and early markers that can identify individuals at risk for cardiovascular disease before clinical signs develop. In 2014, the TEXGEN group identified several novel genetic markers and other risk factors (eg, low vitamin D levels) associated with human heart failure. The researchers also secured federal funding for continuing these studies.
Dr. Mohammad Madjid and his team continued their groundbreaking research concerning the link between influenza and heart disease. This group has proven the importance of influenza vaccines and antiviral medications for preventing heart attacks linked to the flu virus. Their research is reflected by new national guidelines emphasizing how important it is for high-risk populations to get influenza vaccinations. Dr. Madjid has been invited to lead task forces for the Centers for Disease Control and Prevention, the American Heart Association, and the American College of Cardiology. The program is currently expanding to include the study of different inflammatory biomarkers (blood proteins) measured in several thousand subjects; these biomarkers could be used to identify patients with a particularly high risk of cardiovascular events. In addition, Dr. Madjid, in collaboration with Dr. Mehdi Razavi, has invented and developed a thermal mapping catheter that can be used in electrophysiologic studies to detect and treat the source of arrhythmias. The catheter is currently under study in animal models at THI.
During 2015, THI’s Continuing Medical Education (CME) website featured 24 online courses with CME credits. There were more than 215,000 page views, 179,000 visitors, and 823 online CME certificates awarded.
THI accredited 9 live CME symposia, 23 regularly scheduled series, and 3 ending materials in the THI Journal.
The Scientific Publications section edited 533 manuscripts and other materials that documented the important basic science and clinical research being done at THI; 277 manuscripts were published in scientific journals, and 80 more were accepted and are pending publication.
The THI Journal continues to be published 6 times annually and includes articles about discoveries and advancements in cardiovascular medicine. The journal is available online at thij.org to cardiologists and cardiovascular surgeons worldwide. The Journal has begun charging a modest processing fee for case reports and Images in Cardiovascular Medicine papers. Past issues of the scientific bulletin Heart Watch are available in English and Spanish on the THI website.
In 2015, THI’s Library and Learning Resource Center was accessed nearly 19,000 times. Reference and computer support was provided to more than 2,000 persons. More than 200 mediated literature searches were performed, and more than 30 classes were offered to assist physicians and students in preparation of their research.
Community Outreach & Education
Under the medical direction of cardiologists Dr. Paolo Angelini and Dr. James T. Willerson, THI’s Center for Coronary Artery Anomalies (CCAA) is performing an ongoing, large-scale study aimed at preventing sudden cardiac death (SCD) in young children. In the United States alone, 1 or 2 children per week succumb to SCD. These children were born with high-risk heart defects that are hard to detect and may not cause symptoms until tragedy strikes. Focusing on prevention, the CCAA has developed a novel screening protocol based on magnetic resonance imaging (MRI) and designed to detect most of these high-risk heart defects. Through studies of a general population of several thousand children, this protocol has demonstrated unprecedented accuracy, as well as offering a higher level of protection than do currently recommended practices (history and physical exam by a general practitioner). The simple and noninvasive study takes about 30 minutes and includes electrocardiography and MRI of the heart in a mobile imaging unit. With the cooperation of the Houston Independent School District and parents in the greater Houston area, the Center has screened, free of charge, almost 5,000 middle-school and high-school students—not just athletes—as part of this scientific study for the prevention of SCD. The mobile imaging unit and the study itself have been funded by a generous donation from the Kinder Foundation’s Outreach Program and other donors.
THI’s Center for Women’s Heart & Vascular Health (WHC), under the direction of cardiologist Dr. Stephanie Coulter, continues to focus on heart disease in women by addressing the significant gender gaps that exist in cardiovascular medicine, educating women and the physicians who care for them, and investigating the causes of excess cardiac risk in minority populations. The mission of the WHC is to reduce the devastating impact of heart and vascular disease on women through a coordinated program of education, research, treatment, and prevention strategies.
The Center is conducting unique research to identify and explain heart and vascular disease and health trends among women through the Houston Heart Reach for Women project. The screening is voluntary, requires consent, and is performed at no cost to the participants. Since the Center’s inception in 2010, more than 1,400 individuals have participated in screenings at 28 health fair and clinic events. The WHC also collaborates with established community service organizations to provide screening in underserved and underinsured communities. Through this program, the WHC has developed a cost-effective outreach model that can be implemented across the community for both men and women. These screenings are also an opportunity to share educational resources developed at THI, such as “Ask a Texas Heart Doctor” and the Project Heart K-6 online curriculum. During American Heart Month, the WHC hosted the first ever Girl Scouts Experience Day at the Texas Heart Institute, extending the successful Cool-E merit badge pilot program aimed at helping young girls adopt healthy habits at an early age. Over 50 fourth and fifth graders also completed requirements for their Staying Fit badge. Parents and chaperones were given a tour of THI while the girls participated in hands-on activities. To date, over 225 Girl Scouts have earned a Cool-E merit badge.
The WHC supported THI's educational charter in multiple ways, including developing and conducting the Annual Symposium on Risk, Diagnosis, and Treatment of Cardiovascular Disease in Women. Now in its 6th year, the symposium awards continuing education credits to nurses as well as doctors. Dr. Coulter and other members of the WHC Speakers Bureau (composed of volunteers from the THI Professional Staff) participated in meetings and events throughout the community, including breakfast clubs, alumni meetings, and community center activities, reaching hundreds of women across the Houston area and over 3,200 women since the WHC was founded. The WHC also hosted 10 Women Heart Houston support group events in 2015. Women Heart Houston provides peer-to-peer patient support and education for women with heart and vascular disease. It is the Texas Medical Center’s only support group for such women.
Through the THI website, women worldwide can access current, comprehensive educational materials, online assessment tools, “Know Your Numbers” information, e-newsletters, health news, and facts about other heart topics. These valuable resources empower women to take ownership of their cardiovascular health and live a heart-healthy lifestyle. To date, the WHC has published 38 bilingual newsletter editions of “Straight Talk from Stephanie.” These succinct messages from Dr. Coulter address topics related to women and heart disease and aim to separate fact from fiction. The WHC uses social media outlets such as Facebook, Twitter, and Pinterest to promote activities in the community and share Dr. Coulter’s monthly newsletter.
The THI website, www.texasheart.org, had more than 6 million unique visitors during 2015. Seventy-five percent of them visited the Heart Information Center (HIC), which features a reference library of 176 lay-oriented topics on the prevention, diagnosis, and treatment of cardiovascular disease in both English and Spanish. New topics are being developed, and existing ones are reviewed and updated annually with assistance from our Professional Staff. The HIC also features educational programs designed specifically for women (The Center for Women’s Heart and Vascular Health) and for children (Project Heart).
In the past year, more than 580,000 visitors used the services of 41 THI staff cardiologists, surgeons, and experts in pathology, nuclear medicine, pharmacology, and nutrition via “Ask a Texas Heart Institute Doctor,” which provided answers to approximately 650 new questions. Since September 1, 2008, this program has answered nearly 7,000 questions from 92 countries worldwide and all 50 US states.
THI’s Research Compliance Programs maintain and foster the highest standards of quality for research conducted by dedicated professional and research staff affiliated with the Texas Heart Institute. The goals of the program are to ensure safety, quality, and strict adherence to applicable local and federal guidelines. Compliance Program personnel help investigators and research staff learn about and adhere to regulations, prepare timely reports, and maintain timely and accurate data. The program’s effectiveness is measured by metrics related to compliance with regulations.
From January 1 through December 31, 2015, THI was awarded 16 new research grants and contracts totaling $9.5 million in funding over the life of the projects.