Approximately 8% of individuals 80 years or older are affected by calcific aortic valve stenosis (AS), with the prevalence expected to grow in parallel to the aging population demographics [1]. Given the pathophysiological link between AS, aging, and cardiovascular risk factors, patients with AS often present at advanced ages suffering from multiple cardiac and non-cardiac comorbidities. In the past, one-third of patients were judged to be too old or comorbid to undergo surgical aortic valve replacement [2], and were therefore managed with palliative medical therapy. More recently, transcatheter aortic valve replacement (TAVR) has emerged as a less invasive option that was shown to be safe and superior to medical therapy for very high-risk older patients with severe symptomatic AS. The advent of TAVR has broadened the eligible patient population to include the oldest old who were previously not candidates. Even in nonagenarians, the procedural success rate has exceeded 95% and the 30-day and 1-year mortality rates have been estimated to be 5.5% and 23.0%, respectively [3]. However, despite these encouraging metrics, certain patients are evaluated and ultimately judged not to be good candidates for the TAVR procedure. The reasons may be multi-factorial owing to procedural considerations, comorbidities, and frailty. Few studies have systematically addressed the reasons for not proceeding with TAVR, and none have prospectively measured frailty using objective criteria as a key potential reason. Therefore, we sought to compare patients who proceeded with TAVR with those that did not to better understand the reasons cited by clinicians and patients for arriving at their decision and to determine the impact of these reasons on subsequent survival.

This study from the McGill Frailty Registry examined the factors influencing clinical decision making and ensuing survival among older AS patients who received TAVR, BAV, or conservative medical management. The lessons learned can be summarized as follows. First, TAVR was associated with a gain in projected survival of 2 months within the first year as compared to conservative medical management. Second, BAV was associated with a projected survival similar to TAVR for approximately 8 months, after which time survival (in the absence of definitive TAVR) declined precipitously. Third, the primary reason for not proceeding with TAVR was cited as either comorbidity or frailty, and these patients had the highest mortality rates. Lastly, when the primary reason for not proceeding was mild or unrelated symptoms, these patients had relatively low mortality rates during the first year of follow-up.

Previous studies have described reasons for not proceeding with TAVR [6‐8], however, these studies focused on comorbidities and symptoms and did not benefit from systematically-performed objective evaluations of frailty. This study further adds to the existing body of knowledge by connecting the various reasons for not proceeding with TAVR with projected survival. While comorbidity and frailty were associated with the lowest survival, deferral due to mild symptoms was associated with higher relative survival. Nevertheless, the 1-year mortality rate for mildly symptomatic patients was non-negligible, estimated at 15%, supporting the trend to perform aortic valve replacement sooner rather than later when AS is very severe – potentially even in asymptomatic patients [9].

An especially poor prognosis was observed when the cited reason for not proceeding with TAVR was comorbidities. Specific comorbidities found to be prevalent and influential for decision making were reduced LVEF, severe chronic kidney disease, and dementia; consistent with prior studies [10]. In a report from the STS/ACC TVT Registry, dialysis-dependent kidney disease was associated with a twofold increase in 1-year mortality rate up to 37% [11]. Other studies have reaffirmed the substantial increase in long-term and short-term risks [12, 13], including the procedural risk of contrast-induced acute kidney injury. In a meta-analysis, cirrhosis was also associated with a twofold increase in 1-year mortality [14]. In an analysis from the CoreValve Trial, oxygen-dependent lung disease was the comorbidity most strongly associated with 1-year mortality [15]. Overall, these data point to comorbidity profiles that may be equated with prohibitive risk or limited benefits to be expected from TAVR.

While frailty was commonly cited as a reason for choosing conservative medical management in our study and a previous study [16], frailty should not be equated with futility. It is important to note that one-half of TAVR patients manifest objective evidence of frailty at baseline, and that most still benefit from the procedure [17]. Those that typically do not benefit have severe frailty as defined by an EFT score of 5/5, advanced dementia, bedbound or non-mobile status, cachexia or severe sarcopenia, or disability for most basic activities of daily living. These risk factors, coupled with the aforementioned end-stage kidney, lung, and liver disease, have been grouped in the A-B-C-D-E mnemonic, which was put forth in the 2019 Canadian Cardiovascular Society TAVR Consensus Statement to guide decision making in potentially futile cases [18].

One of the strengths of this study is the use of the RMST to compare survival times in different subsets of patients who underwent or did not undergo TAVR. The RMST analysis yields results that are not only more intuitive to interpret, but are also more accurate for scenarios in which the hazard of an event changes over time [5, 19]. Cox proportional hazards analysis assumes that the hazard of an event is constant over the entire follow-up period, while logistic regression analysis assumes that the follow-up time period is constant and fixed for all patients; neither of which would have been ideal in this patient population. In the PARTNER B Trial, RMST was similarly used to demonstrate a gain in projected survival of 12.6 months within 5 years with TAVR as compared to conservative medical management [19].

BAV is used as a temporizing procedure to bridge the gap between TAVR and conservative medical management in challenging cases when patients suffer from severe comorbidities, frailty, or questionable symptoms. Epidemiologic and echocardiographic studies have shown the limited durability of the BAV procedure, with restenosis expected to occur at 6 months as evidenced by a mean aortic valve area progressing from 0.78 to 0.65 cm² [20]. Once restenosis occurs, the long-term survival approaches the natural history of severe AS patients [20‐22]; a finding which is supported by our data. Thus, our results and those of others suggest that patients should be reassessed at 6–8 months post-BAV to reconsider a more definitive procedure if clinically appropriate and in-line with the patient’s preferences.

Patients with severe AS referred for TAVR may never undergo the procedure based on concerns surrounding comorbidity, frailty, procedural feasibility and risks, and mild or unrelated symptoms. These concerns – elicited by clinicians or patients – should be thoroughly investigated and discussed using a shared-decision making approach [24]. A comprehensive treatment decision is one that follows from multi-disciplinary assessment, including objective assessment of frailty and disability, which informs the expected risks and benefits in an individualized fashion. Structured decision aid tools have been developed and validated to facilitate this process [25].