Author + information
- Magnus Settergren, MD, PhD∗ ( and )
- Rodney De Palma, MBBS, MSc
- Heart and Vascular Theme, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden
- ↵∗Address for correspondence:
Dr. Magnus Settergren, Heart and Vascular Theme, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Multiple valve disease is associated with increased morbidity and mortality and is an area where surgical options for treatment are associated with poor cardiovascular outcomes compared with isolated valve disease (1). In this context it is apposite to explore the potential role of transcatheter therapies in this patient category. Until now most of the research done in this field has been focusing on transcatheter aortic valve replacement (TAVR) and mitral regurgitation, showing that concomitant mitral regurgitation is an independent risk factor for increased mortality following TAVR (2). The prevalence and importance of concomitant mitral stenosis (MS) has, however, not been well documented and hitherto largely unknown.
The work by Joseph et al. (3) in this issue of JACC: Cardiovascular Interventions using the large U.S. transcatheter valve therapies (TVT) registry covering 4.8 years (2011 to 2015) sheds some contemporary light on this subject by evaluating the prevalence of MS in those undergoing TAVR. Their definition of severe MS, using echocardiographic and/or cardiac catheter hemodynamic data, follows accepted definitions. Thus, within the registry 11.6% of the TAVR cohort had concomitant MS and 2.7% were categorized as severe. The presence of severe aortic stenosis (AS) and MS portended a poor prognosis, whereas nonsevere MS was associated with no difference compared with isolated severe AS.
The classification and diagnosis of multiple (combined or multivalve) disease remains problematic. The spectrum encompasses a wide range of valve pathology (mixed single valve disease, combined stenotic lesions, combined regurgitant lesions, and combined mixed stenotic and regurgitant lesions). Of the possible combinations simultaneous AS and MS have been described in up to 17% of patients undergoing multiple valve open surgery (4).
The diagnosis is challenging not least because all the predominantly echocardiographic methodologies for exact quantification have only been validated in isolated valve disease and the combined valve pathologies can mutually interact to interfere with the traditional measurements. The effect of severe MS on AS can lead to low-flow low-gradient pathophysiology. Notably, because patients with severe MS have a high frequency of atrial fibrillation, the quantification of AS is rendered even more challenging. Conversely, the effect of severe AS on MS can lead to low-flow-low-gradient MS with a prolonged pressure half-time because of impaired left ventricular relaxation. As a consequence, methods that depend less on loading conditions, such as area assessment or direct 2- or 3-dimensional planimetry, are considered the most reliable parameters. Although in the presence of heavy calcification that precludes planimetry, there remains a clear place for right and left heart hemodynamic catheterization and additional biomarker or functional tests (5). Given the challenges in diagnosis there is a distinct possibility that the extent of combined severe AS and MS has been underestimated.
MS has 2 principal etiologies: rheumatic and degenerative. MS if caused by rheumatic disease is the first valve to succumb to inflammation and commissural fusion. Thus, the combination of rheumatic MS and either rheumatic or calcific AS typically leads to less hemodynamic stress on the left ventricle and aortic valve making ventricular hypertrophy and both aortic and mitral calcification less prominent. Degenerative MS, the most common cause in aging industrialized populations, results from progressive calcification from the leaflet base without commissural fusion and so leads to less critical stenosis.
From the TVT registry the exact disease etiology and diagnoses are not recorded and this shortcoming is acknowledged. The population, however, in the TVT registry likely represents a cohort with predominantly degenerative disease given the reported mean age of 82 years. A low rate of mitral valve intervention (1.4%) in the year following TAVR further supports this (3).
Linkage of procedures recorded in the TVT registry to 31,453 Medicaid and Medicare (U.S. public hospital) records revealed a higher mortality at 1 year with higher heart failure hospitalization, after adjustment for covariates and with small-moderate effect sizes compared with isolated aortic disease (3). This is not entirely surprising given that severe MS was treated conservatively initially and the effect sizes seen are similar to the poorer outcomes reported in those with concomitant severe mitral regurgitation (2). The identification of persistent pulmonary hypertension following TAVR may be important data that can be collected in future studies and would lend support to the second valve being the cause of the late adverse outcomes.
Double-valve surgery in combined degenerative stenotic disease is conventionally regarded the treatment of choice despite unimpressive results (an almost doubling of mortality according to the STS database) compared with isolated surgery (1). Therefore, a less invasive approach would be attractive. Until now percutaneous techniques have been limited to TAVR in combination with percutaneous mitral valve commissurotomy (6). This approach is unlikely to offer a practical solution to the current population of multivalve disease because they consist of an ever-decreasing number of rheumatic pathologies.
In degenerative MS, the presence of severe mitral annular calcification can act as an anchor for TAVR devices and has led to the development of valve-in-mitral annular calcification procedures. These data are, however, currently limited and early experiences have been associated with high complication rates (7,8). The advent of dedicated transcatheter mitral valve implantation technology via transapical or transseptal approaches may change that paradigm and make this disease entity a future therapeutic target (9).
Because of the general paucity of data on the management of mixed and multiple valve diseases, guideline groups have been unable to issue recommendations beyond the level of consensus (level C) and favor surgical solutions (10). The article by Joseph et al. (3) contributes important contemporary epidemiologic insights and opens the field for further research and development of an evidence-base in the transcatheter era. Moreover, the complexities of multivalve disease and the options of surgical and/or transcatheter procedures reinforce the continued central role of the heart team in decision-making.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Dr. Settergren serves as proctor for Abbott Vascular, Boston Scientific, and W.L. Gore; and is a consultant for NuHeart. Dr. De Palma has reported that he has no relationships relevant to the contents of this paper to disclose.
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