Structural Heart Disease Interventions: An Emerging Discipline in Cardiovascular Medicine

ABSTRACT: Within the past decade, we have witnessed the exponential growth of novel percutaneous transcatheter therapies for the treatment of valvular and congenital heart disorders among others. Consequently, a new field has emerged in the world of adult cardiovascular medicine known as “structural heart disease interventions.” We herein provide a contemporary review highlighting many of the important historical landmarks that have set the stage for the development of this new and exciting subspecialty, and introduce a comprehensive overview of the structured training and challenges that will be required to master this field. To our knowledge, our Structural Heart Disease fellowship constitutes one of the very first dedicated training programs in the United States. We believe our experience may be of value to other similar emerging programs across the country and the world. J INVASIVE CARDIOL 2009;21:478–482 A new field has emerged in the world of adult cardiovascular medicine. Over the past decades the exponential growth of novel percutaneous transcatheter therapies for the treatment of non-coronary cardiac diseases (or structural heart disease) has been overwhelming and worthy of focused attention, recognition and expertise training. This perspective highlights the important historical landmarks that have set the stage for the development of this new and exciting subspecialty, and introduces a comprehensive overview of the structured training we believe is required to master this field. Historical Evolution of Structural Heart Disease Interventions Conceptually, this new cardiovascular entity was first highlighted and presented by Dr. Martin Leon at the Transcatheter Cardiovascular Therapeutics meeting in 1999. However, the true origin of the field dates back to the early 1950s following the audacious interventional transcatheter journeys to the “remote” heart by brave interventionalists. As a result of these efforts, a better understanding and a series of important technical developments have evolved. The landmark procedure of Drs. Rubio Alvares and Limon Lason from the Instituto de Cardiologia de Mexico set the initial stage for the field’s future when, in 1952, they performed the first percutaneous attempt to relieve pulmonary valve stenosis using a ureteral catheter and a guitar string to slice the valve open.1,2 Their courageous expedition and contribution merit our most sincere acknowledgment as interventional pioneers. Several years later, in 1959, Drs. Cope and Ross described the first transseptal atrial puncture catheterization.3,4 This major technical advancement allows antegrade access to the left atrial chamber and represents today the backbone tool of every structural heart interventionalist. In 1966, Drs. William Rashkind and William Miller from the Children’s Hospital of Philadelphia, described the first case of atrial balloon septostomy to relief cyanosis in newborns with transposition of the great arteries.5 Soon after, in 1979, Dr. Semb et al employed similar transcatheter techniques to split the commissures of stenotic valves after rapidly withdrawing a balloon through the narrowed segment.6 However, widespread utilization of pulmonary valvuloplasty did not occur until the work of Dr. Jean Kan and her associates who, in 1982,7 adopted a technique similar to the one described by Dr. Andreas Gruentzig to relieve pulmonary valve obstruction by inflating a balloon to high pressure while positioned across the valve.8 Since then, pulmonary valvuloplasty has been considered the therapy of choice for adults, children and neonates with severe pulmonic stenosis.9 Dr. Kan’s contribution is best represented by the widespread applicability of this technique, which has now been expanded for use in other valvular pathologies. In the early 1980s, Dr. Zuhdi Lababidi et al pioneered comparable balloon techniques to treat children with aortic coarctation and infants with critical aortic stenosis.10–12 Balloon techniques have now been adopted by many interventional cardiologists worldwide and are commonly used to treat a variety of valvular heart conditions.13 For mitral valvular stenosis, the initial work of Dr. Kanji Inoue, who in 1984 introduced mitral balloon valvuloplasty as an open surgical procedure, set the stage for the first human percutaneous transseptal mitral balloon valvuloplasty (PMV) to be performed in India by Dr. James Lock.14 Soon thereafter, in 1985, Drs. Igor Palacios and Peter Block15 performed the first U.S. human PMV at Massachusetts General Hospital in Boston simultaneously with Dr. Raymond McKay at Beth Israel Hospital in Boston.16 This technique has largely replaced surgical mitral valvulotomy and is considered today’s treatment of choice for most patients with rheumatic mitral stenosis, with durable results.17 Unfortunately, the results of valvuloplasty have not been as encouraging for patients with degenerative calcific aortic valvular stenosis due to the high incidence of early restenosis and poor long-term survival.18 Dr. Alain Cribier (from the Charles Nicole University Hospital in Rouen, France), in September 1985, became the first to perform percutaneous aortic balloon valvuloplasty in adult patients with calcific degenerative aortic stenosis.19 Fortunately, his perseverance has led to a major resurgence of interest in transcatheter aortic valve therapies. In April 2002, Dr. Cribier became the first physician to perform a human percutaneous aortic valve implantation mounted on a balloon-expandable stent.20 This procedure was performed in a critically ill 57-year-old male with severe aortic stenosis, cardiogenic shock and multiple comorbidities, who was deemed unsuitable for conventional valve surgery. The success of this case has triggered a cascade of new emerging transcatheter therapies in valvular heart disease. Registry data on high-risk surgical candidates with critical aortic stenosis have subsequently been reported with very encouraging initial results. The PARTNER trial (Placement of AoRTic TraNscathetER Valve Trial), a randomized clinical trial comparing transcatheter balloon-expandable aortic valve replacement versus traditional aortic valve surgery and medical therapy is currently in progress, and will serve to better ascertain the role of this novel therapy in the treatment paradigm of aortic stenosis. Further developments are currently being explored with other implantable valve models. Among them is the promising self-expandable stented CoreValve ReValving™ system (CoreValve, Inc., Irvine, California) , which is widely used in Europe and offers comparable results. We can anticipate that the results of these extraordinary catheter-based interventions will only improve with the passage of time. Similar percutaneous valve replacement strategies have evolved for pulmonary and right ventricular outflow tract disorders. In fact, with the turn of the century in the year 2000, Dr. Phillip Bonhoeffer reported the very first human percutaneous valve implantation. His pioneering work represents yet another revolutionary milestone for the interventionalist and a major contribution and advancement to the field’s growth.21 Regurgitant valvular lesions have become another major target for transcatheter therapies. Mitral regurgitation (MR) is the most common type of valvular insufficiency in the United States and affects millions of people worldwide. It is primarily a mechanical disorder that requires mechanical intervention. Unfortunately, many patients with MR are left untreated despite current surgical options and are managed conservatively with palliative medical therapy. The complex mechanical derangements of MR explain why percutaneous mitral valve strategies have evolved less rapidly. However, by understanding these anatomical and technical limitations, interventionalists have taken advantage of the emerging supportive integrated technologies such as cardiac magnetic resonance imaging, cardiac computed tomography, laparoscopy and transesophageal and intracardiac ultrasonography. Novel percutaneous devices are presently being developed to target organic and functional mitral insufficiency. Many are currently being evaluated in animal models, while a few others are being explored in humans including the MitraClip system (Evalve, Inc., Menlo Park, California), the MitraLife (ev3, Inc., Plymouth, Minnesota), the Monarc (Edwards Lifesciences, Irvine, California), the Carillon Mitral Contour system (Cardiac Dimensions®, Inc., Kirkland, Washington), the percutaneous septal-sinus synching device (Ample Medical, Foster City, California), and the iCoapsys™ (Myocor, Inc., Minneapolis, Minnesota).22–28 Early pivotal trials will soon determine their efficacy and therapeutic role. Drs. John Webb from Vancouver, Canada, and Ted Feldman from Evanston Northwestern Hospital in Chicago, Illinois, deserve historical recognition for their important contributions to these mitral valve therapies. As the field of interventional structural heart disease continues to expand and define itself, many other unique transcatheter applications have emerged. Among them are percutaneous therapies for prosthetic paravalvular regurgitation, arterial-venous fistulae, prosthetic vascular disorders, left atrial appendage occlusion, septal ablations in obstructive idiopathic hypertrophic cardiomyopathy, balloon pericardiotomy for chronic effusions, intra- and extracardiac communications including atrial septal defects, patent foramen ovale, ventricular septal defects, and patent ductus arteriosus, pulmonary vein and arterial stenosis, aortic coarctation and mechanical ventricular assist devices, among others. This simplified list largely summarizes the armamentarium and extent of percutaneous non-valvular structural heart disease therapies that are currently available and have flourished over the past two decades. Another major component of this field includes catheter-based interventions for the treatment of adult patients with complex congenital heart disease. Until recently, congenital heart disease pertained largely to the pediatric population. Today, congenital heart disease is more prevalent in adults than in children, and it is expected to continue to rise. Understanding the anatomical, mechanical and physiological variants of this increasing population of patients is therefore imperative and fundamental to the practicing structural heart disease interventionalist. We must therefore acknowledge the major contributions made by the renowned pediatric interventionalists who have forged this exciting pathway, including Drs. Charles E. Mullins from the Children’s Hospital of Houston, James Lock from the Children’s Hospital in Boston, Carlos Ruiz from the University of Loma Linda California and Lenox Hill Hospital and Ziyad Hijazi from the Boston Floating Hospital and now Rush University in Chicago. Last, but not least, we must acknowledge the major ground-breaking contribution of Dr. Kurt Amplatz, an innovative pioneer of interventional radiology and pediatric cardiology who created the Amplatzer device, which has truly revolutionized and simplified transcatheter closure of intracardiac communications. Prior to the Amplatzer Septal Occluder, very few interventional cardiologists would dare to close an atrial septal defect (ASD) due to the complexity of the available devices. Since the introduction of the Amplatzer technology, most ASD closures have become a routine affair. Furthermore, Dr. Amplatz has invented many other devices that are currently used in a wide variety of applications (patent foramen ovale, patent ductus arteriosus, ventricular septal defects, vascular plugs and the more recent left atrial appendage cardiac plug). It is noteworthy that with the rapid rise of technically advanced interventional procedures a 1-year accredited interventional cardiology fellowship program is unlikely to provide sufficient training, exposure to and mastery of complex percutaneous techniques. We strongly believe that, as is now practiced in the subspecialty of peripheral vascular disease, an additional interventional training year focused solely on structural and adult congenital heart disease is necessary. The complex nature of these procedures requires focused expertise and training, and should probably be limited to high-volume centers with highly trained personnel. The increasing population of adult congenital heart disease patients has produced the need for these programs. This specific subgroup of adult patients has traditionally remained in the care of pediatric cardiologists and interventionalists and needs to transition to expert adult congenital specialists. Structural Heart Disease Training in 2009 To address these concerns, we have established a dedicated fellowship program in Interventional Structural and Congenital Heart Disease, effective July 1, 2008. This is a 1-year advanced interventional program that functions as an integral component of the subspecialty programs in cardiology, interventional cardiology and the categorical residency program in internal medicine. The program has been specifically developed to offer proficiency training for adult congenital and structural heart disease interventions. Candidates must be highly qualified physicians with a prior minimum of 12 months’ experience in interventional cardiology. The trainee is expected to master knowledge of the indications, techniques and risks involved in structural heart disease practice. He or she is expected to develop the judgment and experience necessary to select patients and function as an independent operator for patients with a wide variety of structural heart diseases, including adults with complex congenital heart defects. At our institution, we perform approximately 7,000 percutaneous cardiac and vascular diagnostic and interventional procedures annually. Of these, over 2,000 involve coronary interventions, approximately 900 peripheral vascular disease procedures and 300 structural and congenital heart disease procedures. The figure below demonstrates how the volume of structural heart disease interventions has nearly doubled over the last 8 years, not including the emerging valve therapies that are becoming available for many patients. With the increasing adult congenital heart disease population that numbers over 1 million in the U.S., the participation of interventional cardiac laboratories will steadily rise. Thus, the expert management of adult congenital heart disease has become essential to many major academic centers. We expect that similar emerging programs will be unique in providing the necessary training and expertise. The anticipated number of structural heart interventions performed by each trainee at our institution will be approximately > 250 cases/year. Fellows will have the opportunity to work with highly qualified invasive cardiologists with ample experience in the field. The cases are varied and challenging, as our hospital serves both as primary facility for the local neighborhood, as well as a tertiary referral center for affiliated hospitals and health centers throughout the state of Massachusetts. Massachusetts General Hospital also attracts patients from across the United States and abroad. At the core of the Structural Heart Disease Interventional program, unique interventions will be available for the trainee including a variety of valvular and non-valvular procedures, as well as a wide selection of adult primary congenital heart defects and complex post-surgical residual defects of infancy (the table shown on the following page summarizes the principle structural heart disease diagnostic and interventional procedures). Dedicated clinical training skills in the selection, management and post-procedural care of these patients will be a fundamental aspect of the trainee’s experience and will be available both for in-patients and outpatients who visit our structural heart disease and adult congenital defects clinic. Furthermore, fellows will be encouraged to participate in formal didactic sessions, including weekly clinical catheterization conferences, morbidity and mortality conferences, journal clubs, combined surgical, pathological and congenital heart disease, and technical programs designed to enhance their knowledge and skills. The provision of an academically-based interventional program provides the environment and resources necessary to pursue complementary basic and/or clinical research in this field. Fellows will be encouraged to participate in the development of novel device therapies and designs, particularly in the areas of valve replacement and repair. Those interested in more in-depth investigation will have the option to work closely with senior mentors who act as principal investigators in ongoing projects. The institution provides a unique environment for the development of hybrid interventions that combine percutaneous endovascular strategies with simultaneous minimally invasive surgical techniques. Finally, a state-of-the-art animal research facility is available for the fellow to pursue translational research. To our knowledge, this constitutes one of the very first dedicated structural heart disease fellowship programs in the United States and worldwide. As with other emerging fields, we anticipate many future challenges. A consensus will be needed to further define the scope of this field and ultimately establish the necessary core curriculum, regulations and guidelines for optimal training and practice. Likewise, it will be necessary to obtain support from major medical organizations such as the American College of Cardiology, American Medical Association, and the Society of Cardiovascular Angiography and Interventions (SCAI). We are pleased to see the early interest shown by the SCAI, which established a Structural Heart Disease Council. The goals of this council are: to improve quality of care, strengthen advocacy efforts for the recognition of structural heart disease and its role in patient care and improved access to care, to increase opportunities for structural heart disease education, to enhance opportunities for mentoring and career development, and to foster relationships with other organizations.29 The council has already begun work on establishing objective performance criteria (OPCs) for many conditions including paravalvular leak devices and post-infarct ventricular septal defects, among others. We hope our experience will serve to help other similar emerging programs across the country and the world. The fellowship program at Massachusetts General Hospital reflects our commitment to patient care by providing expertise and training to dedicated, highly qualified physicians in the percutaneous treatment of adult congenital heart disease, and the establishment of the minimum standards necessary to prevent widespread indiscriminate use of these techniques. Acknowledgements. The authors wish to acknowledge the physicians, medical professionals, supportive medical industry, and most importantly, the patients and family members who have contributed in many ways to the evolution and the emergence of the new, exciting subspecialty of structural heart disease. _________________________ From the Department of Medicine, Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. The authors report no conflicts of interest regarding the content herein. Manuscript submitted May 29, 2009, provisional acceptance given June 8, 2009, final version accepted June 12, 2009. Address for correspondence: Igor F. Palacios, MD, Massachusetts General Hospital, 55 Fruit St., Suite GRB-800, Boston, MA 02114. E-mail: ipalacios@partners.org

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