Five years ago, we were asked to speculate on the changes that could be expected to occur in cardiovascular treatment between 2006 and 2011. In the current article, we retrospectively examine our predictions and describe the current status of cardiovascular medicine and surgery in 2011. As we predicted, this field has continued to build on earlier breakthroughs in interventional heart valve replacement, regenerative myocardial therapy, myocardial revascularization, and mechanical circulatory support. In addition, new percutaneous and surgical procedures to treat atrial fibrillation (AF) are revolutionizing the field of electrophysiology. Because cardiovascular medicine and surgery is such a broad topic, we will confine our article to these five areas, which have long been a special focus of physicians at the Texas Heart Institute.
Interventional Heart Valve Replacement
In 2006, we predicted that interventional heart valve replacement would become more widespread. At that time, clinical trials were already under way to evaluate percutaneous, catheter-based devices for aortic valve replacement. As of 2007, two transcatheter valves—the Edwards SAPIEN bovine valve (Edwards Lifesciences Corp., Irvine, CA) and the CoreValve® porcine valve (Medtronic, Minneapolis, MN)—were being used commercially in European heart centers. In the US, however, progress toward commercial approval has been much slower. In November 2011, the Edwards SAPIEN valve was approved by the Food and Drug Administration (FDA),1 becoming the first catheter-based valve replacement device to be commercially available in this country. The valve is mounted on a catheter and can be delivered via a transfemoral or transapical approach. It is approved for patients with severe aortic stenosis who are deemed to be at too high risk for conventional open heart surgery. Early results have shown better survival with the Edwards SAPIEN valve than with medical management in this high-risk population.2 Potential complications include vascular complications, strokes, and paravalvular leaks. With increasing operator experience and newer technology, however, these complications will become less prevalent.
The CoreValve is undergoing clinical trials in the US but is still regarded as an investigational device in this country. Several other catheter-based aortic valves are the focus of laboratory research. Competition in this field will lead to improvements and new innovation. Hopefully, approval for clinical use of other percutaneous valves will drive down the current prohibitive device cost. As valve delivery systems become smaller and implantation techniques are improved, there will be a high demand for a non-surgical means of replacing the aortic valve.
Meanwhile, surgical aortic valve replacement is still the gold standard, and new bioprosthetic and mechanical valve designs continue to evolve. Surgical aortic valve replacement can be performed with excellent early and long-term results, even in older and higher-risk patients.3 Minimally invasive approaches via an upper mini-sternotomy and a mini-thoracotomy are now technically feasible and have been adopted by many surgeons. Also, new sutureless valves have shown promise in early clinical trials. Data from ongoing and future clinical trials of any new valve device must be carefully scrutinized to determine the appropriate criteria for selecting the optimal device and best surgical or percutaneous approach for individual patients. Longer-term follow-up is required to evaluate the in vivo durability of new valve devices.
Regenerative Myocardial Therapy
Five years ago, we predicted that regenerative myocardial therapy would continue to reveal its promise for the treatment of patients with chronic heart failure. In 2011, the most successful form of regenerative myocardial therapy continues to be stem cell treatment, using adult progenitor cells obtained from the heart itself or from extracardiac tissues such as bone marrow, fat, or skeletal muscle.4 Stem cell therapy is being used to treat patients with acute myocardial infarction, myocardial ischemia without revascularization, ischemic cardiomyopathy, and, more recently, dilated cardiomyopathy. Various cell delivery methods are available, ranging from intracoronary infusion to intramyocardial injection (either during open heart surgery or via a catheter-based approach). After undergoing this treatment, selected patients have less angina and a greater capacity to exercise.5
Researchers are studying ways to further increase the clinical benefits of stem cell therapy. They are searching for a more potent cell type, as well as different cell sources. Most patients have been treated with cells obtained from their own tissue, but a newer approach involves the use of stem cells derived from a healthy young donor, which results in a more uniform, ‘off-the-shelf’ cell product. Although embryonic stem cells would be an even more promising source, their use is fraught with ethical problems and other complications that may not be resolved for some time. Therefore, cells with a pluripotent potential similar to that of embryonic stem cells have been artificially created. These cells, called induced pluripotent stem cells, are generated by genetically reprogramming adult somatic cells to express genes that endow cells with properties of embryonic stem cells.6 Despite the immense potential of this approach, safety concerns and regulatory issues must be addressed before these genetically modified cells can be used clinically.
Furthermore, innovative cell-labeling methods are being developed to monitor the fate of stem cells after they are delivered into the patient’s heart.7,8 Researchers hope to use these methods to devise strategies for improving the retention of cells after delivery. Gadonanotubes are showing promise as a revolutionary non-invasive means for tracking transplanted stem cells.9
In a unique mix of technology, investigators are testing the benefits of stem cell therapy in ventricular assist device (VAD) recipients; it is hoped that combined treatment will enhance recovery of left ventricular function in bridge-to-transplant or destination-therapy patients, allowing VAD removal.
One of the greatest current challenges is to translate cardiovascular breakthroughs at the basic science level into clinical practice. Completion of the Human Genome Project has led to the development of treatments for certain disorders involving single-gene mutations. To benefit the cardiovascular system, however, gene therapy must involve safe, efficient delivery methods. Recent cardiovascular gene therapy trials have been carried out with an excellent safety record,10 but the positive, clinically relevant effects of cardiovascular gene therapy have been minimal because of inefficient gene transfer. New innovations in gene delivery techniques are expected to lead to novel methods of treating cardiovascular disease.
In 2006, we predicted that expansion in the use of drug-eluting stents (DESs) would be a major breakthrough in cardiovascular medicine by 2011. We also predicted that the use of these stents would continue to have limited efficacy in patients with diffuse coronary disease and left main coronary artery lesions. Early randomized controlled trials had shown excellent results for DESs compared with bare metal stents in highly exclusive patient populations with lesions favorable to stenting.11,12 Therefore, by 2006, owing to favorable clinical trials and public demand for non-surgical revascularization, the use of DESs for percutaneous coronary interventions (PCIs) was expanding to include more complex ‘off-label’ coronary artery lesions. The rapid growth in PCIs and the reciprocal decline in surgical coronary artery bypass grafting (CABG) procedures led many observers to declare that PCI would soon eliminate the need for CABG.
Since 2006, several clinical trials have shown that CABG has a benefit over PCI in terms of mid- and long-term survival and freedom from complications, especially in patients with multi-vessel disease and diabetes mellitus.13–15 The Clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial16 compared medical treatment with PCI therapy and revealed no benefit for survival or for freedom from myocardial infarction in patients undergoing PCI. In 2011, the three-year data from the randomized controlled Synergy between PCI with taxus and cardiac surgery (SYNTAX) trial showed better survival and freedom from major adverse cardiac events in patients treated with CABG versus those undergoing PCI with a DES.17 The advantages of CABG were especially significant in patients with more complex three-vessel disease. Nevertheless, PCI continues to be the first-line therapy in most of these patients. Even though DESs have revolutionized cardiovascular medicine over the past decade and continue to benefit properly selected patients (i.e. non-diabetic patients with single- or double-vessel disease, large non-calcified vessels, and normal heart function, or patients with acute coronary syndrome), many patients are probably receiving stents inappropriately.18 New stent technologies are being studied in clinical trials, and biodegradable DESs have shown promise in early clinical trials.19
In addition, CABG has continued to evolve over the past decade. Despite the increasing ages and comorbidities of patients undergoing CABG, the actual hospital mortality for first-time CABG approaches only 1 %.15 The left internal mammary artery (LIMA) is known to have excellent long-term patency rates (>90 % in 15-year follow-up studies).20 The LIMA is used in 95 % of CABG procedures. Several studies continue to show that the use of bilateral internal mammary arteries improves survival and quality of life to an even greater extent than the use of one mammary artery alone.21,22 However, according to the Society of Thoracic Surgery database, only 4 % of CABG procedures use bilateral mammary artery conduits. In the near future, quality-of-care evaluations relying on evidence-based medicine, along with public reporting of these quality measures, will influence the practice of myocardial revascularization, including selection of medical management or PCI versus surgery; a minimally invasive approach versus a sternotomy; and an off-pump versus on-pump procedure. The same considerations will help determine which lesions to treat and which conduits to use.
During the past five years, the selective use of off-pump and less invasive techniques has been expanded by new technology and other innovations. Currently, robotic, offpump, totally endoscopic CABG is being performed efficaciously in highly selected patients by a small number of surgeons. New advances in proximal (PAS-Port®) and distal (C-Port®) anastomotic connectors (Cardica, Inc., Redwood City, CA) and improved stabilizers will allow wider use of these techniques.
Five years ago, only a handful of cardiovascular centers had ‘hybrid’ cardiac operating rooms consisting of full catheterization laboratory radiologic capabilities inside an operating room. Today, these specialized hybrid suites are commonplace. The concept of hybrid coronary revascularization involves combining minimally invasive CABG with PCI. This allows physicians to choose the best way to revascularize each lesion in a selected patient. Close collaboration between cardiologists and cardiac surgeons has prompted a growth in multidisciplinary teams formed to determine the best revascularization strategies on a local level (individual hospitals or practice groups), as well as on a global level (international cardiac surgical and cardiology societies involved in developing practice guidelines). Several residency programs are offering integrated programs intended to cross-train residents as ‘cardiovascular practitioners’ instead of cardiologists or cardiac surgeons.
Mechanical Circulatory Support for Replacement Therapy
Heart failure remains a large societal problem in the Western world. As baby boomers age, the number of patients who have severe heart failure is increasing. The high mortality rates for patients with stage D failure (defined by the American College of Cardiology and the American Heart Association) treated medically have not improved in the last 10 years. At this advanced stage, the only options are palliative measures or surgical management. In recent years, surgically implanted VADs have become available for long-term use and are now commonly implanted as a therapy for advanced heart failure. Studies have shown that whether they are implanted as a bridge to transplantation or as destination therapy, VADs clearly improve survival and quality of life in severely ill patients.23 Because of the growing heart failure population, further improvements are needed in VAD technology, patient selection criteria, and post-implant management. These improvements will help physicians determine what role assist devices should play in the management of chronic heart failure.
In 2006, we predicted that the advent of smaller, simpler mechanical circulatory support systems would redefine the treatment of heart failure. These predictions have been borne out. Worldwide, thousands of patients are now being supported by a VAD. Compared with earlier models, current pumps are much smaller, simpler, and more efficient, offering support as bridges to transplantation and as destination therapy.24,25 These newer pumps fit a wider range of patient sizes and are less invasive to implant than older systems. Because the new pumps have few moving parts, they are less susceptible to infection and failure. Additionally, they offer much greater patient comfort, allowing a relatively normal lifestyle. However, current pumps are all powered via percutaneous cables that lead from the pump to a battery pack. These cables can break and be a source of infection. In the next five years, we believe that transcutaneous energy transmission systems will be developed that will eliminate the problems associated with external cables.
The small VADs being used for bridging to transplantation and for destination therapy today are all rotary, continuous-flow pumps. In the US, only the HeartMate II® (Thoratec Corporation, Pleasanton, CA)26 is approved by the FDA for bridging to transplantation and for destination therapy. Other smaller VADs have been approved for destination therapy in Europe and are awaiting approval in the US. These systems include the HeartWare®—a very promising device.27 Researchers are developing a newer generation of devices that produce continuous flow via centrifugal force, and these pumps should prove even more effective. They will more easily allow for some pulsatile flow, which has been shown to be advantageous in patients undergoing support with these types of pumps. At this time, no good option exists for patients who also require right ventricular support, although devices are being developed for this purpose. The best solution in these cases would be a percutaneous device for right-sided cardiac support.
Since the 1960s, cardiac surgeons and biomedical engineers have been working to develop a total artificial heart (TAH) for the treatment of patients with severe biventricular failure and end-organ dysfunction. Because of the success of VAD technology, however, development of VADs has generally eclipsed that of TAHs. In the US, the only artificial heart being used clinically is the SynCardia temporary Total Artificial Heart (SynCardia Systems, Inc., Tucson, AZ),28 which was originally developed 30 years ago. This TAH now has a portable pneumatic driver that enables patients to be discharged from the hospital. At the Texas Heart Institute, we are developing artificial hearts composed of two continuous-flow pumps: one pump consists of MicroMed DeBakey VADs (MicroMed Cardiovascular, Inc., Houston, TX), and the other consists of HeartMate II VADs.29
As predicted, within the past five years researchers have also developed various short-term pumps that have significantly advanced the treatment of acute cardiac failure. These devices include the CentriMag® blood pump (Thoratec),30 the TandemHeart® transseptal ventricular assist system (CardiacAssist, Inc., Pittsburgh, PA),31 and the Impella® system (ABIOMED, Inc., Danvers, MA).32 Still needed, however, is a percutaneous device that can be inserted before patients become critically ill.
AF affects 4.5 million people worldwide. The past decade has seen an explosion of innovation in technology aimed at treating this arrhythmia. Nearly 20 % of all strokes are attributed to AF, and patients have a five-fold increased risk of stroke if they have AF. Medical management has focused on anticoagulation and heart rate or rhythm control. Electrophysiologists perform percutaneous catheter-based radio-frequency atrial ablation in selected patients, and success rates range from 30 to 80 %.33 Surgical atrial ablation creates linear transmural scars in the left atrium to disrupt the conduction of AF and isolate potential AF triggers from the rest of the atrium. Linear lesions are created with cryoablation endocardially or with radio-frequency or high-intensity focused ultrasound epicardially. Surgical atrial ablation for AF, using several types of energy sources to create atrial lesion sets, results in success rates of 70 to 90 %.34 Despite the advantages of surgical atrial ablation, a review of the Society of Thoracic Surgery database from 2004 to 2006 showed that only 38 % of AF patients undergoing heart surgery had surgical ablation performed simultaneously. According to this study, the rate of surgical ablations added to heart operations increased from 28 % in 2004 to 40.2 % in 2006.35 Since 2006, great strides have been made in educating surgeons and physicians about the benefits of treating AF during heart operations. New guidelines for following up patients and for reporting the results of clinical trials36 should more accurately identify proper strategies for AF surgery and catheter-based procedures. Less invasive operations and hybrid approaches involving surgical ablation, as well as catheter-based ablation and mapping procedures, are now being performed. Clinical trials are under way to determine the merits of these procedures.
Up to 90 % of blood clots that may cause strokes in AF patients develop in the left atrial appendage (LAA). Cardiac surgeons and cardiologists have become increasingly aware of the potential benefit of closing the LAA to prevent strokes in patients with AF.37 Surgical ligation can be performed endocardially with a double-running suture line, but purse-string closure and external staple closure may result in residual or recurrent communication with the LAA.38 AtriClip™ (AtriCure, Inc., West Chester, OH) is a device used to securely clamp the LAA epicardially and is gaining popularity due to its ease of application.39 Newer, less invasive surgical and percutaneous devices for LAA closure are currently undergoing clinical trials.40 The LARIAT™ suture delivery device (SentreHEART, Inc., Palo Alto, CA) uses magnets to couple an endocardial balloon (placed percutaneously) with a looped ligature (placed via pericardioscopy); the LARIAT is approved for clinical use and has shown promising early clinical utility.40
As of 2011, much ground remains for cardiovascular pioneers to explore, and many unsuspected pathways await our discovery. Extension of current knowledge, translation of that knowledge into the clinical arena, wider use of proven strategies, and wise allocation of established resources continue to be important goals. In Western countries, the aging population, with its increasing demand for medical services, remains a major focus of cardiovascular care. Physicians are seeking new ways to improve not only the length of life but also the quality of life, particularly in elderly patients. Whatever the future holds, new challenges and life-saving opportunities will continue to make the cardiovascular field an especially rewarding one.