Author + information
- Published online November 6, 2017.
- aCincinnati Children's Hospital Heart Institute, Cincinnati, Ohio
- bDepartment of Cardiology, Boston Children’s Hospital, Boston, Massachusetts
- cDepartment of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Gary D. Webb, Cincinnati Children's Hospital Heart Institute, 3333 Burnet Avenue, Cincinnati, Ohio 45229.
Unrepaired ostium secundum atrial septal defects (ASD) frequently present in adulthood, by which time many patients have functional tricuspid regurgitation (TR) related to right heart remodeling. ASD closure, whether surgical or percutaneous, is recommended for those with right heart enlargement in the absence of severe pulmonary vascular disease or other uncommon scenarios (1). In developed countries, the vast majority of patients are referred for percutaneous closure, given an innate preference for less invasive options and more rapid recovery. Surgery remains a reasonable alternative (2), and the risk of perioperative mortality or other severe adverse outcomes is not demonstrably inferior to percutaneous closure. In addition to those with anatomy unfavorable for percutaneous approaches, surgery may confer benefit for a subset of patients including those with substantial TR. Debate focuses on whether TR is likely to improve or resolve with ASD closure alone or whether tricuspid repair (or replacement) is required. Prior small studies have not been adequately powered to provide a definitive answer (3–5). As a consequence, arguments on the relative merits have remained largely dogmatic and anecdotal.
In this issue of JACC: Cardiovascular Interventions, Takaya et al. (6) help to address this void by presenting medium- to long-term outcomes of adults with ASD and concomitant functional TR who underwent percutaneous ASD closure between 2008 and 2014. They report a retrospective analysis of their extensive experience of 419 adults, 113 of who had moderate or severe TR, whereas the remainder had mild TR, followed for a median of 30 months. Compared to patients with mild TR, those with moderate or severe TR were older, more likely to have atrial fibrillation, and more symptomatic before closure. These patients had notable functional limitation. One-quarter had New York Heart Association functional class III symptoms. Nevertheless, patients with more severe TR experienced symptomatic improvement, right ventricular remodeling reflected in smaller right ventricular dimensions, lower B-type natriuretic peptide levels, and improvement in TR over time. TR improved to mild or better in a sizable majority (70%). Fewer than 1 in 10 experienced death or heart failure hospitalization during follow-up. This outcome is quite favorable in the context of the symptoms and comorbidities predating the procedure.
These results argue that percutaneous ASD closure is a reasonable option for patients with a clinical indication for closure of a hemodynamically important ASD who have coexisting moderate or severe functional TR. This argument is further buttressed by the lack of data supporting a direct clinical benefit to tricuspid valve intervention to address TR in a variety of other clinical scenarios. Comparison between the salient groups is clouded by extensive confounding by indication and patient-level complexity and comorbidity; the extent of confounding is indicated by the remarkably high mortality associated with tricuspid valve repair or replacement in other populations with TR. High absolute risk does not inherently constitute a contraindication to intervention. The converse is often true: sicker patients tend to gain more absolute benefit from interventions, because they have more to gain. However, even with beneficial intervention, sick patients tend to fare worse than patients who start out in a favorable position. The current finding that the presence of moderate or severe TR before ASD closure was associated with worse outcomes, therefore, in itself argues neither for nor against the adequacy of ASD closure. It admittedly stands to reason that residual severe TR should be independently disadvantageous for the long-term clinical course. But the attributable benefit to eliminating TR remains and likely will remain an open question, so we cannot argue that eliminating TR should be a priority with any degree of authority. No randomized trial will ever be performed to address this question. Overall, we believe the relatively widespread improvement in TR severity after percutaneous ASD closure observed in the current study provides adequate counterweight to the weak argument in favor of more aggressive surgical intervention to address the tricuspid valve issue.
This study epitomizes the contribution of straightforward, well-designed, observational, clinical research to clarify specific areas of clinical controversy. The investigators asked a simple question with appropriate methods, and the resulting findings are readily interpreted and directly applicable to practice. The value of continued longitudinal follow-up over a clinically relevant time period deserves special note. Data on acute complications and outcomes are, of course, indispensable. But for low-risk procedures, our concern is not whether the patient will gain benefit within a month or often even a year after an intervention, but whether there will be sustained improvement over time that outweighs an integrated analysis of the tangible and intangible costs (e.g., physical risks, short-term discomfort and anxiety, financial costs). Although there is usually some improvement in the severity of TR early after ASD closure, persistence of moderate or severe TR is common at 1 month or 6 months. TR, however, appears to continue to improve after 6 months with ongoing RV remodeling. Extended follow-up is challenging for a variety of reasons. Limited resources and logistical considerations make it unusual to have patients return for 4 visits, with or without imaging, within the first year after a procedure associated with low risk for medium-term complications such as percutaneous ASD closure. The challenge is accentuated for specialized procedures for which patients are referred specifically for the procedure and are then followed at a referring center. This may be an even greater obstacle in regionalized health systems where specific procedures are limited to a few centers. Such systems favor high volume and probably good short-term follow-up, but long-term care is likely to be at referring clinics. Long-term follow-up may be limited to administrative review. Although diagnostic codes for tricuspid regurgitation and hard outcomes such as hospitalization or death may be searchable, such coarse data cannot address many key clinical questions.
The question addressed by this paper has notable conceptual overlap with another situation frequently encountered in the care of patients with congenital heart disease, how best to address TR in those with previously repaired tetralogy of Fallot and severe pulmonary regurgitation. The value of tricuspid valve repair at the time of surgical pulmonary valve replacement (PVR) has long been a matter of debate, and the question has taken on increased importance with the advent of percutaneous PVR. Recent reports suggest that TR improves with percutaneous PVR alone, paralleling the current findings in patients with ASD (7–9). However, whereas TR may be due entirely to right ventricular dilation in many patients with tetralogy of Fallot, exceptions are common. Although both conceptually and based on the limited existing data, the current findings in patients with isolated ASD seem applicable across the spectrum of diagnoses that cause chronic right heart volume loading associated with distinctly functional TR, caution is warranted when considering populations with a higher prevalence of alternative (i.e., primary) mechanisms of TR, such as patients with additional congenital, post-operative, device-related, or structural disease of the tricuspid valve and right ventricle. What is true for ASD is even more acutely valid for such diagnoses: careful review of individual circumstances and personalized consideration remain fundamental to making the right decision for each patient.
Additional caveats apply beyond the critical importance of identifying the mechanism of TR. One is the importance of the larger clinical scenario. For example, surgery may be appealing in a young, otherwise well, patient with paroxysmal atrial fibrillation, severe right ventricular dilation, and torrential TR. Tricuspid repair and an atrial maze procedure in that context could be reasonable given the long event horizon and potential additive benefit of tricuspid repair and arrhythmia surgery. Another issue limiting inference is the potential for referral bias. We do not know who was referred for surgical closure. This could influence interpretation if a substantial number of patients with severe TR were selected for surgery by skilled clinicians who were able to identify those who would not improve with catheter ASD closure. Perhaps patients with very severe right ventricular dilation, for example, were preferentially referred for surgery. Thus, referring providers must still use judgment and consider surgery for patients who seem unlikely to improve with ASD closure alone. Alternatively, one could prepare the patient for a staged decision: percutaneous closure with reassessment in 1-2 years and possible tricuspid repair if there is an inadequate improvement in TR and symptoms. Despite these caveats, clinicians can be a bit more confident when referring patients with moderate right ventricular dilation and less than torrential TR for percutaneous ASD closure that there is likely to be adequate improvement in symptoms and TR severity without the need for surgery.
↵∗ 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.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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