J. of Cardiovasc. Trans. Res. (2014) 7:375–386 DOI 10.1007/s12265-014-9561-9
Advances in Transcatheter Valve Therapies Daniel H. Steinberg & Mario Castillo-Sang & Eric R. Powers
Received: 20 February 2014 / Accepted: 25 March 2014 / Published online: 10 April 2014 # Springer Science+Business Media New York 2014
Abstract The surgical treatment for valvular heart disease is well established with excellent long-term outcomes in appropriately selected patients. For patients at elevated risk for surgical intervention, options have traditionally been limited to medical therapy with disappointing results. The advent of transcatheter techniques of valvular repair or replacement has revolutionized treatment options for these patients at significantly elevated risk for surgery. In both the aortic and mitral realms, landmark clinical trials and real-world registries have begun to define the roles of these therapies, and the development of multidisciplinary heart teams have helped optimize patient treatment pathways and outcomes. Transcatheter treatment of aortic stenosis and mitral regurgitation has emerged as an approved option for properly selected patients, and guidelines have evolved to include these therapies. Further procedural refinement, device development, and clinical trials will continue to evolve this field. Keywords Valvular heart disease . Transcatheter valve therapies . TAVR
Introduction Although initial attempts at surgical correction of valvular heart disease date back to the first half of the twentieth century [1–4], it was not until the development of cardiopulmonary bypass that surgical valve replacement became a realistic therapy. Since then, surgical valve replacement or repair
Associate Editor Angela Taylor oversaw the review of this article D. H. Steinberg : M. Castillo-Sang : E. R. Powers (*) Divisions of Cardiology and Cardiothoracic Surgery, Medical University of South Carolina, 25 Courtenay Drive, ART 7031 MSC 592, Charleston, SC 29425, USA e-mail: [email protected]
procedures have become the standard of care for patients with severe valvular stenosis or regurgitation. Each year, thousands of patients undergo valvular surgery in the USA alone, and the primary clinical/academic controversies focus on issues such as evolving surgical technique and optimal outcomes. Surgery is the standard of care for the overwhelming majority of patients with symptomatic, severe valvular heart disease. However, many patients, particularly those of advanced age, have comorbid conditions resulting in elevated or prohibitive surgical risk. With the lone exception of balloon mitral valvuloplasty (considered first-line therapy in appropriate patients), non-surgical options were traditionally quite limited, and medical therapy aimed at symptom relief remained the only viable treatment for patients who are not surgical candidates. Unfortunately, for patients at prohibitive surgical risk, medical therapy does little to alter the natural course of disease. The advent of transcatheter technologies has ushered in a new era in the treatment of valvular heart disease. With particular emphasis on patients at elevated risk for traditional open surgery, transcatheter therapies designed to treat aortic stenosis, pulmonic regurgitation, and mitral regurgitation have been developed, studied, and approved for their respective indications. This review will discuss concepts, controversies, and emerging issues pertinent to transcatheter therapy as part of the global management of patients with valvular heart disease. General Concepts of Transcatheter Therapy Two basic concepts underlying transcatheter therapy are optimal patient selection and expected therapeutic benefit. Transcatheter therapy offers a fundamentally less invasive (and ideally lower risk) option to surgical therapy, and it may offer the sole alternative to medical therapy, but whether that will provide an acceptable result (short and long-term) is of utmost importance.
376
J. of Cardiovasc. Trans. Res. (2014) 7:375–386
Transcatheter therapy also must focus on appropriate patient populations. In appropriately selected patients, surgical therapy represents the standard of care for the vast majority of valvular disease. However, comorbid conditions such as chronic lung disease, peripheral vascular or cerebrovascular disease, diabetes, renal insufficiency, and left ventricular dysfunction all affect a patient’s individual risk for surgery. These and other factors have become part of objective risk stratification tools, such as the Society of Thoracic Surgery (STS) or EuroSCORE, that aim to quantify risk and identify those that would likely not have an overall benefit from surgery. Other conditions, such as liver disease and frailty, or technical issues including porcelain aorta or a “hostile chest” due to prior radiation therapy are not included in traditional risk stratification, but they are often a part of the subjective evaluation of surgical risk stratification. For patients who are not suitable candidates for surgical treatment, some transcatheter therapies have already emerged as the new standard of care, while others still remain to be evaluated. Aortic Stenosis Aortic stenosis is the most common valvular pathology in the developed world. The natural history of aortic stenosis is well established. Once moderate disease is present (defined as a peak transvalvular jet velocity greater than 3.0 m per second (m/s), mean transvalvular gradient >25 mmHg, and valve area 4 m/s, mean gradient >40 mmHg, valve area 40 75 mm) [8]. As is the case with aortic stenosis, surgical aortic valve replacement is the standard of care in appropriately selected patients. Unfortunately, patients at elevated risk for surgical intervention may not have the same transcatheter options as do patients with aortic stenosis. Severe, primary aortic insufficiency is often associated with an enlarged aortic annulus and the absence of valvular or annular calcification. Annular enlargement poses problems based on currently available device sizes, but absence of calcification may pose a larger obstacle because the current TAVR devices rely on calcification to help anchor the devices. This is a particular issue for balloonexpandable devices, and it has implications for self-
380
expanding devices as well. Currently, primary aortic insufficiency is a contraindication for TAVR. It is entirely possible that next-generation devices may prove to be suitable for aortic insufficiency, but clinical trials will be necessary to demonstrate the utility of TAVR in patients with primary aortic insufficiency. Mitral Stenosis As a result of the decreasing incidence of rheumatic heart disease, the incidence and prevalence of mitral stenosis have decreased significantly in the developed world. Once the valve area decreases to about 2 cm2, a gradual progression is anticipated with the eventual development of symptoms. Similar to aortic stenosis, symptoms tend to correlate with survival as asymptomatic patients have a 10-year survival greater than 80 % while patients with limiting symptoms, and particularly those with pulmonary hypertension, have a median survival less than 3 years [51, 52]. Indications for therapy include moderatesevere mitral stenosis or mild stenosis with accompanying pulmonary hypertension in the presence of symptoms [53]. Surgical treatment for mitral stenosis includes the original closed commissurotomy procedures, open commissurotomy, and mitral valve replacement [1, 2, 8, 54]. Percutaneous mitral valvuloplasty (PTMV) was first introduced by Inoue and colleagues in 1984, and it is perhaps the most wellestablished structural heart disease therapy [55]. The most common technique involves transseptal access and inflation of a dedicated balloon (Inoue Balloon, Toray Medical, Japan) across the mitral valve (Fig. 3). In appropriately selected patients, PTMV has become the treatment of choice for mitral stenosis. Successful procedures are associated with a 80 % at 10+years following the procedure [8, 54, 56]. Patient selection is of primary importance to assure optimal results with PTMV. The evaluation is based on both valvular anatomy and physiology, focusing primarily on the thickness, mobility, and calcification of the leaflets and the subvalvular apparatus. These features together form the Wilkins score, graded from 4 to 16 (1–4 for each parameter, Fig. 4) [57]. Patients with scores of 8 or less are optimal candidates for PTMV provided they have no greater than moderate mitral regurgitation and there is no left atrial thrombus [54, 58]. The degree of commissural calcification has also been associated with inferior outcomes after PTMV [59]. Patients with high anatomic scores or with significant commissural calcification may still be candidates for PTMV, but the risk of complications, particularly severe mitral regurgitation, is higher [56, 60]. Surgical mitral valve replacement is recommended for those who are not suitable candidates for PTMV [8].
J. of Cardiovasc. Trans. Res. (2014) 7:375–386
Mitral Regurgitation The mitral apparatus is a complex structure consisting of the mitral valve leaflets, annulus, chordae, papillary muscles, and ventricular wall. An abnormality at any level may result in regurgitation of blood from the left ventricle to left atrium. Whether mitral regurgitation results from a primary valvular lesion (degenerative) or secondary to left ventricular disease (functional), it is an important contributor to cardiovascular morbidity and mortality. Indeed, severe mitral regurgitation is associated with increased mortality regardless of symptoms [61]. Extensive guidelines exist to help optimize the timing of surgery and outcomes in patients with severe mitral regurgitation [53]. However, treatment techniques for mitral regurgitation can be complex. From a technical perspective, it is important to understand a few fundamental concepts relating to surgical mitral valve replacement/repair in order to appreciate the issues relating to transcatheter therapy. Early attempts at surgical mitral valve replacement involved excision of the subvalvular apparatus, and postoperative left ventricular dysfunction was common; it was soon realized that preservation of the subvalvular apparatus during mitral valve replacement was important [62]. Suboptimal clinical results with valve replacement stimulated interest in mitral valve repair techniques, and Carpentier et al. eventually developed a series of repairs based on the anatomy of the mitral valve and the mechanism of regurgitation (Fig. 5) [63, 64]. These techniques potentially include modification of the leaflets, chords, or papillary muscles, but they almost invariably also include some form of annular modification. In fact, annular reinforcement is an independent predictor of freedom from recurrent mitral regurgitation and/or reoperation [65, 66]. For patients with degenerative disease, repair is often preferable to replacement, with mortality rate 2+ residual mitral regurgitation [70]. Of these 107 patients, 32 underwent subsequent mitral valve surgery up to 18 months postprocedure for reasons including failed initial implant (n=9), partial clip detachment (n=10), recurrent >2+ mitral regurgitation (n=10), atrial septal defect (n=2), or device malfunction (n=1). Importantly, surgical options were preserved in these patients, and 21 of the 25 patients in whom mitral valve repair was the original surgical plan (prior to MitraClip) underwent successful repair [71]. The EVEREST-II trial prospectively randomized patients with severe mitral regurgitation to percutaneous or surgical mitral valve repair (technique determined by the operating surgeon). In the 279 patients randomized, the primary effectiveness endpoint (freedom from death, surgery for valve dysfunction, and mitral regurgitation of 3–4+) at 1 year was less frequent in the MitraClip-treated group (55 % MitraClip vs. 73 % surgery, p=0.07). Rates for death were 6 and 6 %, and 3–4+ mitral regurgitation was present in 21 and 20 % in the percutaneous and surgical groups, respectively. Surgery
J. of Cardiovasc. Trans. Res. (2014) 7:375–386
for valve dysfunction was required more commonly in the MitraClip group at 1 year (20.4 % MitraClip vs. 2.2 % surgery, p
Advances in Transcatheter Valve Therapies Daniel H. Steinberg & Mario Castillo-Sang & Eric R. Powers
Received: 20 February 2014 / Accepted: 25 March 2014 / Published online: 10 April 2014 # Springer Science+Business Media New York 2014
Abstract The surgical treatment for valvular heart disease is well established with excellent long-term outcomes in appropriately selected patients. For patients at elevated risk for surgical intervention, options have traditionally been limited to medical therapy with disappointing results. The advent of transcatheter techniques of valvular repair or replacement has revolutionized treatment options for these patients at significantly elevated risk for surgery. In both the aortic and mitral realms, landmark clinical trials and real-world registries have begun to define the roles of these therapies, and the development of multidisciplinary heart teams have helped optimize patient treatment pathways and outcomes. Transcatheter treatment of aortic stenosis and mitral regurgitation has emerged as an approved option for properly selected patients, and guidelines have evolved to include these therapies. Further procedural refinement, device development, and clinical trials will continue to evolve this field. Keywords Valvular heart disease . Transcatheter valve therapies . TAVR
Introduction Although initial attempts at surgical correction of valvular heart disease date back to the first half of the twentieth century [1–4], it was not until the development of cardiopulmonary bypass that surgical valve replacement became a realistic therapy. Since then, surgical valve replacement or repair
Associate Editor Angela Taylor oversaw the review of this article D. H. Steinberg : M. Castillo-Sang : E. R. Powers (*) Divisions of Cardiology and Cardiothoracic Surgery, Medical University of South Carolina, 25 Courtenay Drive, ART 7031 MSC 592, Charleston, SC 29425, USA e-mail: [email protected]
procedures have become the standard of care for patients with severe valvular stenosis or regurgitation. Each year, thousands of patients undergo valvular surgery in the USA alone, and the primary clinical/academic controversies focus on issues such as evolving surgical technique and optimal outcomes. Surgery is the standard of care for the overwhelming majority of patients with symptomatic, severe valvular heart disease. However, many patients, particularly those of advanced age, have comorbid conditions resulting in elevated or prohibitive surgical risk. With the lone exception of balloon mitral valvuloplasty (considered first-line therapy in appropriate patients), non-surgical options were traditionally quite limited, and medical therapy aimed at symptom relief remained the only viable treatment for patients who are not surgical candidates. Unfortunately, for patients at prohibitive surgical risk, medical therapy does little to alter the natural course of disease. The advent of transcatheter technologies has ushered in a new era in the treatment of valvular heart disease. With particular emphasis on patients at elevated risk for traditional open surgery, transcatheter therapies designed to treat aortic stenosis, pulmonic regurgitation, and mitral regurgitation have been developed, studied, and approved for their respective indications. This review will discuss concepts, controversies, and emerging issues pertinent to transcatheter therapy as part of the global management of patients with valvular heart disease. General Concepts of Transcatheter Therapy Two basic concepts underlying transcatheter therapy are optimal patient selection and expected therapeutic benefit. Transcatheter therapy offers a fundamentally less invasive (and ideally lower risk) option to surgical therapy, and it may offer the sole alternative to medical therapy, but whether that will provide an acceptable result (short and long-term) is of utmost importance.
376
J. of Cardiovasc. Trans. Res. (2014) 7:375–386
Transcatheter therapy also must focus on appropriate patient populations. In appropriately selected patients, surgical therapy represents the standard of care for the vast majority of valvular disease. However, comorbid conditions such as chronic lung disease, peripheral vascular or cerebrovascular disease, diabetes, renal insufficiency, and left ventricular dysfunction all affect a patient’s individual risk for surgery. These and other factors have become part of objective risk stratification tools, such as the Society of Thoracic Surgery (STS) or EuroSCORE, that aim to quantify risk and identify those that would likely not have an overall benefit from surgery. Other conditions, such as liver disease and frailty, or technical issues including porcelain aorta or a “hostile chest” due to prior radiation therapy are not included in traditional risk stratification, but they are often a part of the subjective evaluation of surgical risk stratification. For patients who are not suitable candidates for surgical treatment, some transcatheter therapies have already emerged as the new standard of care, while others still remain to be evaluated. Aortic Stenosis Aortic stenosis is the most common valvular pathology in the developed world. The natural history of aortic stenosis is well established. Once moderate disease is present (defined as a peak transvalvular jet velocity greater than 3.0 m per second (m/s), mean transvalvular gradient >25 mmHg, and valve area 4 m/s, mean gradient >40 mmHg, valve area 40 75 mm) [8]. As is the case with aortic stenosis, surgical aortic valve replacement is the standard of care in appropriately selected patients. Unfortunately, patients at elevated risk for surgical intervention may not have the same transcatheter options as do patients with aortic stenosis. Severe, primary aortic insufficiency is often associated with an enlarged aortic annulus and the absence of valvular or annular calcification. Annular enlargement poses problems based on currently available device sizes, but absence of calcification may pose a larger obstacle because the current TAVR devices rely on calcification to help anchor the devices. This is a particular issue for balloonexpandable devices, and it has implications for self-
380
expanding devices as well. Currently, primary aortic insufficiency is a contraindication for TAVR. It is entirely possible that next-generation devices may prove to be suitable for aortic insufficiency, but clinical trials will be necessary to demonstrate the utility of TAVR in patients with primary aortic insufficiency. Mitral Stenosis As a result of the decreasing incidence of rheumatic heart disease, the incidence and prevalence of mitral stenosis have decreased significantly in the developed world. Once the valve area decreases to about 2 cm2, a gradual progression is anticipated with the eventual development of symptoms. Similar to aortic stenosis, symptoms tend to correlate with survival as asymptomatic patients have a 10-year survival greater than 80 % while patients with limiting symptoms, and particularly those with pulmonary hypertension, have a median survival less than 3 years [51, 52]. Indications for therapy include moderatesevere mitral stenosis or mild stenosis with accompanying pulmonary hypertension in the presence of symptoms [53]. Surgical treatment for mitral stenosis includes the original closed commissurotomy procedures, open commissurotomy, and mitral valve replacement [1, 2, 8, 54]. Percutaneous mitral valvuloplasty (PTMV) was first introduced by Inoue and colleagues in 1984, and it is perhaps the most wellestablished structural heart disease therapy [55]. The most common technique involves transseptal access and inflation of a dedicated balloon (Inoue Balloon, Toray Medical, Japan) across the mitral valve (Fig. 3). In appropriately selected patients, PTMV has become the treatment of choice for mitral stenosis. Successful procedures are associated with a 80 % at 10+years following the procedure [8, 54, 56]. Patient selection is of primary importance to assure optimal results with PTMV. The evaluation is based on both valvular anatomy and physiology, focusing primarily on the thickness, mobility, and calcification of the leaflets and the subvalvular apparatus. These features together form the Wilkins score, graded from 4 to 16 (1–4 for each parameter, Fig. 4) [57]. Patients with scores of 8 or less are optimal candidates for PTMV provided they have no greater than moderate mitral regurgitation and there is no left atrial thrombus [54, 58]. The degree of commissural calcification has also been associated with inferior outcomes after PTMV [59]. Patients with high anatomic scores or with significant commissural calcification may still be candidates for PTMV, but the risk of complications, particularly severe mitral regurgitation, is higher [56, 60]. Surgical mitral valve replacement is recommended for those who are not suitable candidates for PTMV [8].
J. of Cardiovasc. Trans. Res. (2014) 7:375–386
Mitral Regurgitation The mitral apparatus is a complex structure consisting of the mitral valve leaflets, annulus, chordae, papillary muscles, and ventricular wall. An abnormality at any level may result in regurgitation of blood from the left ventricle to left atrium. Whether mitral regurgitation results from a primary valvular lesion (degenerative) or secondary to left ventricular disease (functional), it is an important contributor to cardiovascular morbidity and mortality. Indeed, severe mitral regurgitation is associated with increased mortality regardless of symptoms [61]. Extensive guidelines exist to help optimize the timing of surgery and outcomes in patients with severe mitral regurgitation [53]. However, treatment techniques for mitral regurgitation can be complex. From a technical perspective, it is important to understand a few fundamental concepts relating to surgical mitral valve replacement/repair in order to appreciate the issues relating to transcatheter therapy. Early attempts at surgical mitral valve replacement involved excision of the subvalvular apparatus, and postoperative left ventricular dysfunction was common; it was soon realized that preservation of the subvalvular apparatus during mitral valve replacement was important [62]. Suboptimal clinical results with valve replacement stimulated interest in mitral valve repair techniques, and Carpentier et al. eventually developed a series of repairs based on the anatomy of the mitral valve and the mechanism of regurgitation (Fig. 5) [63, 64]. These techniques potentially include modification of the leaflets, chords, or papillary muscles, but they almost invariably also include some form of annular modification. In fact, annular reinforcement is an independent predictor of freedom from recurrent mitral regurgitation and/or reoperation [65, 66]. For patients with degenerative disease, repair is often preferable to replacement, with mortality rate 2+ residual mitral regurgitation [70]. Of these 107 patients, 32 underwent subsequent mitral valve surgery up to 18 months postprocedure for reasons including failed initial implant (n=9), partial clip detachment (n=10), recurrent >2+ mitral regurgitation (n=10), atrial septal defect (n=2), or device malfunction (n=1). Importantly, surgical options were preserved in these patients, and 21 of the 25 patients in whom mitral valve repair was the original surgical plan (prior to MitraClip) underwent successful repair [71]. The EVEREST-II trial prospectively randomized patients with severe mitral regurgitation to percutaneous or surgical mitral valve repair (technique determined by the operating surgeon). In the 279 patients randomized, the primary effectiveness endpoint (freedom from death, surgery for valve dysfunction, and mitral regurgitation of 3–4+) at 1 year was less frequent in the MitraClip-treated group (55 % MitraClip vs. 73 % surgery, p=0.07). Rates for death were 6 and 6 %, and 3–4+ mitral regurgitation was present in 21 and 20 % in the percutaneous and surgical groups, respectively. Surgery
J. of Cardiovasc. Trans. Res. (2014) 7:375–386
for valve dysfunction was required more commonly in the MitraClip group at 1 year (20.4 % MitraClip vs. 2.2 % surgery, p
