Outcomes of Transcatheter Aortic Valve Replacement in Patients Treated With Systemic Steroids

Background. Chronic steroid therapy is associated with higher vascular complication rates in patients undergoing transcatheter aortic valve replacement (TAVR). The effect of corticosteroids on aortic annular complications has not been directly assessed in this population. Methods. A retrospective analysis of 1095 patients undergoing transfemoral TAVR was performed. Patients treated with chronic steroids at the time of the procedure (n = 99) were compared with those who received no steroids (n = 992). The primary outcome included a composite of aortic annular complications, defined as a combination of aortic annular rupture, aortic dissection/perforation, and left ventricular perforation. Results. The primary outcome was significantly higher in the steroid group (4.0% vs 0.5%; P<.01). This finding was primarily driven by higher rates of acute annular rupture in the steroid group (2.0% vs 0.2%; P=.04). Steroid use was associated with higher rates of intraoperative cardiac arrest (5.1% vs 1.5%; P=.03), device capture/retrieval (4.0% vs 0.8%; P=.01), and emergent conversion to open heart surgery (4.0% vs 0.6%; P<.01). There were no differences with respect to in-hospital mortality, stroke, myocardial infarction, need for permanent pacemaker, bleeding complications, minor vascular complications, hospital length of stay, hospital 30-day readmission, or 30-day echocardiographic findings. Additionally, within the steroid group, there were no significant differences between balloon-expandable vs self-expanding TAVR prostheses with respect to composite aortic annular complications. Conclusion. Chronic steroid therapy increases the risk of aortic annular complications in patients undergoing TAVR, with detrimental consequences including intraoperative cardiac arrest and conversion to open heart surgery. Steroid use should be considered in patient selection and determination of procedural technique for TAVR.

J INVASIVE CARDIOL 2022;34(1):E49-E54.

Key words: coronary perforation, corticosteroids, steroid therapy, transcatheter aortic valve replacement

Systemic corticosteroids are indicated in the treatment and management of various medical conditions. Previous reports have documented that chronic use of systemic corticosteroids may have an undesirable effect on several organ systems including the vasculature system, increasing the fragility of blood vessel walls and putting them at a higher risk of dissection, perforation, and rupture with invasive vascular procedures.^1-3 Increased rates of coronary perforation during percutaneous coronary intervention, for example, have been seen in patients who were treated with corticosteroids compared with those who were not on corticosteroids.¹

Over the last decade, transcatheter aortic valve replacement (TAVR) has become the treatment of choice for symptomatic severe aortic valve stenosis in prohibitive surgical risk patients. Additionally, over the last several years, TAVR has been established as an alternative to surgical aortic valve replacement (SAVR) in high, moderate, and most recently, low surgical risk patients.⁴ Because patients who undergo TAVR are often elderly with multiple comorbidities, it is not uncommon for these patients to have a medical illness that requires chronic corticosteroid therapy. Given that TAVR is an invasive vascular procedure, vascular complications are among the important clinical endpoints collected and reported. Notably, major vascular complications as reported by the Society of Thoracic Surgeons/American College of Cardiology (STS/ACC) Transcatheter Valve Therapy (TVT) registry include any aortic dissection, aortic rupture, annulus rupture, and left ventricular perforation.

Because major vascular complications are associated with higher mortality,⁵ patients at risk of such complications need to be identified and necessary precautions and preventive measures should be undertaken. Given the inconclusive and limited data on the association of corticosteroid use with vascular complications and more so with aortic annular complications during TAVR, we sought to analyze the impact of chronic steroid use on clinical outcomes in a large TAVR population.

Setting and design. This is a single-center, retrospective, observational study conducted at an 890-bed tertiary-care medical center (Hartford Hospital, Hartford, Connecticut). The study was approved by the local institutional review board and exempted from needing an informed consent.

Study population. From a cohort of 1600 TAVR procedures performed at our institution from 2012 to 2020, a total of 1095 consecutive, commercial patients treated with a transfemoral approach either with the balloon-expandable S3 or Ultra valve (Edwards Lifesciences) or the self-expanding Evolut valve (Evolut R and Evolut Pro; Medtronic) underwent retrospective analysis after applying exclusion criteria. Patients undergoing alternative non-femoral access, valve-in-valve cases, and patients with incomplete records submitted to the STS/ACC TVT registry were excluded to minimize procedural confounders. Final comparisons were made between 99 patients treated with oral corticosteroids vs 992 control patients who were not on oral corticosteroids at the time of TAVR. All reported outcomes conformed to the Valve Academic Research Consortium (VARC-2) definitions.⁶

Preprocedural evaluation. All patients underwent evaluation by a multidisciplinary valve committee with preprocedure review of catheterization, echocardiographic, and multislice computed tomography (CTA) data to document severity of aortic stenosis and suitability for TAVR. Baseline STS-predicted risk of 30-day mortality as well as incremental risk assessment based upon functional assessment, including frailty, severe pulmonary and hepatic disease, porcelain aorta, and hostile mediastinum were determined for all patients. Valve choice for each patient was made by the treating cardiothoracic surgeon and interventional cardiologist.

TAVR procedure. All TAVR procedures were performed in a hybrid catheterization laboratory using either conscious sedation or general anesthesia and with either transthoracic or transesophageal echocardiographic monitoring. Standard TAVR techniques for implantation of the S3, Ultra, Evolut R, and Evolut Pro valves were employed. Patients with a baseline aortic valve area <0.7 cm² underwent balloon aortic valvuloplasty prior to prosthesis insertion. Following initial valve deployment, postdilation was performed in all patients who demonstrated greater than mild aortic insufficiency measured by echocardiography or supravalvular aortography. Maximal balloon diameters for postdilation were determined by pre-TAVR CTA annular measurements, with a limit of 20% oversizing for S3/Ultra and the mean of the aortic annular diameter for Evolut.

Study outcomes. Baseline characteristics, including demographics, cardiovascular risk factors, comorbidities, prior cardiac history, pre-TAVR cardiac catheterization, echocardiographic and CTA data, STS score, and procedural characteristics, were compared between the steroid and non-steroid cohorts. Oral corticosteroids in the steroid-cohort included pre-TAVR use of prednisone, prednisolone, methylprednisolone, and dexamethasone. The primary outcome included a composite of aortic annular complications, defined as aortic annular rupture, aortic dissection/perforation, and left ventricular perforation. Secondary outcomes included in-hospital mortality, stroke, myocardial infarction, bleeding complications, cardiac arrest, minor vascular complications, emergent need for conversion to cardiac surgery, need for permanent pacemaker implantation, hospital length of stay and hospital readmission, and 30-day follow-up echocardiographic findings. Other than composite aortic annular complications, outcomes were defined as per VARC-2 and variables were as defined by the STS/ACC TVT registry data dictionary.^6,7

Statistical analysis. Categorical variables were analyzed using the Chi-square test or Fisher’s exact test. Continuous variables are expressed as mean ± standard deviation or median with interquartile range and were compared with a Student’s t-test or the Mann-Whitney U-test, respectively. Posthoc Bonferroni corrections were applied to adjust for multiple comparisons. Event rates were generated using the Kaplan-Meier method, and log-rank tests were used for group comparisons. All effects were considered significant at P<.05. The statistical analyses were performed with SPSS, version 21.0 (SPSS).

A total of 99 patients in the steroid cohort were compared with 992 patients in the non-steroid group. There were no significant differences between the 2 study cohorts with respect to baseline demographics, annular size, or valve type utilized (Table 1, Table 2, Table 3). Patients on steroids were more likely to have moderate and severe chronic lung disease and to require home oxygen than patients not on steroids. Additionally, there were no significant differences between the procedural technique between the 2 groups, other than the steroid group requiring a higher fluoroscopy dose area product than the non-steroid group (53,564 ± 82,575 vs 36,776 ± 49,445, respectively; P<.01) and Air kerma (949 ± 1016 vs 724.7 ± 736.1, respectively; P=.03).

Clinical outcomes. Primary and secondary procedural outcomes are listed in Table 4. The primary outcome of composite aortic annular complications was significantly higher in the steroid group than in the non-steroid group (4.0% vs 0.5%, respectively; P<.01). This finding was mainly driven by statistically higher rates of acute annular rupture (2.0% in the steroid group vs 0.2% in the non-steroid group; P=.04), with a trend in higher rates of left ventricular perforation (1.0% in the steroid group vs 0.0% in the non-steroid group; P=.09). In addition, the steroid group had higher rates of intraoperative cardiac arrest (5.1% vs 1.5%; P=.03), device capture or retrieval (4.0% vs 0.8%; P=.01), and need for emergent conversion to open heart surgery (4.0% vs 0.6%; P<.01) compared with the non-steroid group. There were no differences between the 2 groups with respect to in-hospital mortality, stroke, myocardial infarction, need for permanent pacemaker, bleeding complications, minor vascular complications, hospital length of stay, hospital 30-day readmission, or 30-day echocardiographic findings. Finally, within the steroid group, there were no significant differences between balloon-expandable vs self-expanding TAVR prostheses with respect to composite aortic annular complications (balloon expandable 1.0% vs self-expanding 0.4%; P=.46).

Prior studies on the incidence of TAVR aortic annular complications, defined as aortic root or annular dissection, perforation, and rupture, with or without cardiac tamponade, have reported a procedural incidence of 0.4%-2.3%.⁸ Factors associated with this complication include: (1) degree, location, and pattern of subannular calcification; (2) smaller body surface area; (3) type of transcatheter heart valve (eg, balloon-expandable vs self-expanding); (4) oversizing of balloon-expandable valves by >20%; and (5) aggressive postdilation.^8,9 The current study suggests that chronic steroid use should be added as an important additional etiology underlying this life-threatening adverse event.

Two previous studies have reported the potential impact of steroid use on TAVR outcomes. A single-center retrospective analysis found that corticosteroids were associated with higher rates of minor vascular complications in patients undergoing TAVR, without an increase in major vascular complications.² Notably, this study used VARC-2 criteria to define major vascular complications, which include aortic annular complications only as a subset of additional adverse events, including access-site vascular injury, distal embolization, and unplanned surgical or endovascular vascular repair. Similarly, in the Japanese OCEAN registry, more vascular complications were seen in steroid-treated patients, although this finding was primarily driven by access route complications requiring surgical cutdowns. Notably, aortic annular complications (termed “non-access route” by the authors) were not increased in patients on chronic steroid therapy.³ The size of the steroid groups in both of these studies was relatively small (25 and 67 patients, respectively), and therefore neither report may have had sufficient power to detect a statistically significant impact of steroid use on adverse aortic annular events.

Identification of steroid-use as a risk factor for aortic annular complications potentially should modify the preprocedural multidisciplinary evaluation of patients under consideration for TAVR. First, while valve oversizing relative to the annulus is typically used to minimize paravalvular aortic regurgitation and patient-prosthesis mismatch, current recommendations of maximal 20% oversizing for the S3/Ultra valve and 26%-31% for the Evolut series may need to be reduced in the steroid patient subgroup. Second, recommended limits on the maximal balloon size used to treat postimplant paravalvular aortic regurgitation (eg, maximal 20% oversizing for S3/Ultra and mean of the aortic annulus measured by CTA for Evolut) may need to be modified.  Finally, as TAVR has expanded to lower-risk populations, steroid use may need to be incorporated more prominently in the joint decision-making process of choosing SAVR rather than TAVR.

Study limitations. While our study is the largest to date to report on vascular complications in patients treated with chronic steroids undergoing TAVR, and the first to focus specifically on aortic annular complications, our findings are limited by an observational, retrospective design, where confounding factors may have affected outcomes. The steroid group had higher rates of severe chronic lung disease and home oxygen requirement, which may have been the reason behind their chronic steroid use. Furthermore, we were unable to obtain the degree, location, and pattern of annular and subannular calcification, and therefore cannot rule out those factors as confounding variables. The study was not powered to detect a significant difference in the primary outcome between balloon types seen in prior studies. Due to the low event rates, we were unable to perform a multivariable analysis.

Our study identifies chronic steroid therapy as a significant factor that increases the risk of aortic annular complications in patients undergoing TAVR, with detrimental consequences including acute aortic annular rupture, higher rates of device recapture or retrieval, cardiac arrest, and emergent conversion to open heart surgery. Multidisciplinary heart teams should consider steroid use in the preprocedure assessment of the suitability of SAVR vs TAVR, the degree of valve oversizing, and the limits of aggressive postimplant postdilation for both balloon-expandable and self-expanding bioprostheses.

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