key: cord-0791294-lqxmvcml
authors: Freno, Daniel R.; Shipe, Maren E.; Levack, Melissa M.; Shah, Ashish S.; Deppen, Stephen A.; O’Leary, Jared M.; Grogan, Eric L.
title: Modeling the Impact of Delaying TAVR for the Treatment of Aortic Stenosis in the Era of COVID-19
date: 2021-06-08
journal: JTCVS Open
DOI: 10.1016/j.xjon.2021.06.006
sha: 3c1c8ac539b256b114b411834df7bc68785815da
doc_id: 791294
cord_uid: lqxmvcml

Objective The aim of this study was to model the short term and 2-year overall survival for intermediate- and low-risk patients with severe symptomatic AS undergoing timely or delayed transcatheter aortic valve replacement during the 2019 novel coronavirus pandemic. Methods We developed a decision analysis model to evaluate two treatment strategies for both low-risk and intermediate-risk patients with aortic stenosis during the 2019 novel coronavirus pandemic. Results Prompt transcatheter aortic valve replacement resulted in improved 2-year overall survival when compared to delayed intervention for intermediate-risk patients (0.81 versus 0.67) and low-risk patients (0.95 vs 0.85), due to the risk of death or the need for urgent/emergent transcatheter aortic valve replacement in the waiting period. However, if the probability of acquiring the 2019 novel coronavirus is greater than 55% (intermediate risk patients) or 47% (low risk patients), delayed transcatheter aortic valve replacement is favorable to prompt intervention (0.66 vs 0.67, intermediate risk; 0.84 vs 0.85, low risk). Conclusions and Relevance Prompt transcatheter aortic valve replacement for both intermediate-risk and low-risk patients with symptomatic severe aortic stenosis results in improved 2-year survival when local healthcare system resources are not significantly constrained by the 2019 novel coronavirus.

without any of the previously stated characteristics, the recommendation was for either TAVR or 109 delay in TAVR with close clinical follow-up. 7 110

The risk of delaying the treatment of symptomatic AS must be balanced with the risk of 111 mortality due to COVID-19 infection. Early reports suggest that hospitalized patients, especially 112 those with significant comorbidities such as cardiovascular and respiratory disease are at higher 113 risk for complications including death from COVID-19 whether community or hospital-114 acquired. [8] [9] [10] [11] Additionally, it has been well established that patients older than 60 years are at 115 higher risk for complications and COVID-related mortality. 11-15 116

The purpose of this study was to compare the 2-year outcomes of delaying transfemoral 117 We developed a decision analysis model to evaluate two treatment strategies for AS during the 126 COVID-19 pandemic: prompt transfemoral TAVR or delayed transfemoral 127 TAVR after six months ( Figure 1 ). The decision tree details the initial choice (the decision node) 128 of proceeding promptly with TAVR or delaying TAVR and follows branch points to the ultimate 129 outcomes of death or 2-year overall survival (terminal nodes). The availability of hospital 130 resources can be a factor in the initial choice of delaying TAVR if local levels of COVID-19 131 infection are sufficiently high such that hospital beds and ventilators are unavailable. If the 132 operation is performed electively for either prompt or delayed TAVR, there are chance nodes for 133 operative mortality, perioperative COVID-19 infection, and mortality due to COVID-19. For the 134 delayed pathway there is a chance the patient will not undergo elective TAVR, but may 135 decompensate and require urgent or emergent TAVR or die due to either disease progression 136 during the interim or from contracting COVID-19 (see below). If the patient undergoes urgent or 137 emergent TAVR there are again chance nodes for operative mortality, perioperative COVID-19 138 infection, and mortality due to 

The COVID-19 parameters listed in Table 2 The 2-year overall survival (OS) for TAVR patients similar to our case scenarios was 200 established from the literature (Table 3) . [28] [29] If the patient underwent elective TAVR they had 201

improved OS compared to an urgent or emergent TAVR. 23 these COVID-19 variables, two-way sensitivity analysis was performed (Tables 2 and 3) Altering the probability of requiring urgent or emergent TAVR or dying before 242 undergoing TAVR did not change the outcome of favoring prompt TAVR. Prompt TAVR was 243 favored for a COVID-19 infection probability less than 55%; delayed TAVR was favored for a 244 COVID-19 infection probability greater than 55%.

Results of the two-way sensitivity analysis altering the probability of acquiring COVID-246 19 and the probability of mortality from an acquired COVID-19 infection are seen in figure 2 . 247

This figure demonstrates that for a wide range of probabilities of both acquiring COVID-19 or 248 dying from COVID-19, prompt TAVR is favored. Even if the probability of dying from an 249 acquired COVID-19 infection is greater than 50% and the probability of acquiring such infection 250 would have to be greater than 40% in order for delayed TAVR to be the favored strategy ( Figure  251 2). If the probability of undergoing urgent TAVR is less than or equal to 3% and the probability 252 of dying before undergoing TAVR is less than or equal to 1%, then delaying the procedure is 253 favored (Supplemental Figure 1) ; however, this scenario is clinically unlikely as the evidence 254

suggests that delaying TAVR even 3 months results in at least a 16% risk of needing an urgent 255 TAVR during that interval (Table 2) . 256 257 Sensitivity analyses: low risk 258

Altering the probability of requiring urgent or emergent TAVR or dying before 259 undergoing TAVR did not change the outcome of favoring prompt TAVR. Prompt TAVR was 260 favored for a COVID-19 infection probability less than 42%; delayed TAVR was favored for a 261 COVID-19 infection probability greater than 47%. 262

Two-way sensitivity analysis again demonstrates that for a wide range of probabilities of 263 acquiring COVID-19 and mortality from COVID-19, prompt TAVR is favored. If the 264 probability of COVID-19 mortality is greater than 50%, then the probability of perioperative 265 COVID-19 infection must be greater than 30%, in order for delayed TAVR to be favored ( Figure  266 3). If the probability of undergoing urgent TAVR is less than or equal to 3% and the probability 267 of dying before undergoing TAVR is less than 0.5%, then delaying the procedure is favored 268 (Supplemental Figure 2) ; again, this scenario is clinically unlikely as the evidence suggests that 269 delaying TAVR even 3 months results in at least a 16% risk of needing an urgent TAVR during 270 that interval (table 2) . Unites States has seen this degree of community prevalence to date in the pandemic. Examining 295 the communities with the highest burden of COVID-19 disease requiring the complete shutdown 296 of operative and procedural services reveals a prevalence threshold much lower than required in 297 our simulation for delayed TAVR to be preferred. This implies that as long as the healthcare 298 system in question has resources to offer TAVR, they should be doing so. younger patients with few comorbidities and a lower mortality rate of 10%, decision to delay 307 resection may be only preferred when infection prevalence exceeds 80%. It is unlikely that any 308 patient will fall into the predicted mortality range for a given incidence of COVID-19 which 309 means there are very few if any patient specific factors that should lead one to delay TAVR. 310

While this analysis was not designed to evaluate the decision making process for patients 311 undergoing surgical AVR it is interesting to not the similarities in the data between the two. 312

Two-year overall survival and in-hospital mortality are not statistically significantly different 313 between the two procedures. Therefore the only parameter likely to differ between the two groups would be risk of acquiring COVID-19 in the post-operative period, likely to be higher in 315 the surgical group owing to a higher percentage of patients requiring in-patient rehab or an 316 additional caregiver at home while recovering. This is accounted for in the two-way sensitivity 317 analysis described in figures 2 and 3, which would seem to suggest that prompt AVR is preferred 318 for almost all patients. 319

One limitation of this study is the paucity of literature available on COVID-19, which 320 resulted in estimating several model parameters from similar but non-identical clinical scenarios. 321

We addressed this by analyzing a range of values for the COVID-19 parameters in our sensitivity 322 analyses. Secondly, defining perioperative risk of acquiring COVID-19 is difficult as it is 323 becoming increasingly clear that individual behaviors and exposures weigh heavily on ones risk 324 of exposure. We addressed this by using the asymptomatic prevalence as our risk because it is a 325 good marker of the risk of coming into contact with someone in the community who 326 unknowingly has the disease and also because this number is readily available via local health 327 departments. Additionally, predicting the mortality rate for a patient who develops perioperative 328 COVID-19 after undergoing TAVR is handicapped by a complete available evidence. We 329 reference two case series detailing a post-operative mortality of 20% following a heterogenous 330 group of surgeries for a total of 75 patients. Lastly, another limitation of our study is our 331

inability to predict what the risk of COVID-19 transmission will be in 6 months. As the 332 pandemic has progressed, it has become increasingly clear that a variety of social and political 333 factors weigh heavily on the curve of transmission for a given community. Our model assumes 334 the institution of several well described public health mitigation efforts such as mask wearing 335

and social distancing which have demonstrated an ability to reduce transmission rates and local 336 community prevalence. It has become increasingly clear that the vast majority of transmissions of COVID-19 are occurring in the community and not within the hospital; therefore, it is a 338 reasonable assumption that delaying in-hospital procedures does not significantly reduce the risk 339 of acquiring COVID-19. Furthermore, as our two-way sensitivity analysis demonstrates, an 340

individual's risk of mortality from COVID-19 would have to be extremely high in order to 341 warrant delaying TAVR, even with a high community prevalence. 342

Resource utilization is a large element of medical decision making during a pandemic. In 343 the present analysis, we assumed that the treating center had adequate resources to proceed with 344 TAVR. As we have seen during COVID-19, some healthcare systems have become 345 overwhelmed and limitations in ICU beds, ventilators, personal protective equipment, a 346 dwindling blood product supply, and clinical staff which may preclude TAVR. Institutions 347 across the country have developed alternative staffing models to deal with surges in critically ill 348 coronavirus patients. These models often include physicians and nursing staff being reallocated 349 from one service arena to another. Which areas are negatively affected by staff being pulled will 350 vary from institution to institution and can potentially impact the ability to fully staff operating 351 rooms, cardiac catheterization labs, ICU's, or post-procedural step-down units. All these factors 352 must be taken into consideration when deciding upon whether a particular institution is resource 353 constrained enough that they cannot adequately care for TAVR patients. However, as the 354 prevalence of COVID-19 fluctuates in communities, or other infectious pandemics arise, this 355 model can be adapted to assist hospitals and surgeons to decide when to proceed with specific 356

severe AS during the COVID-19 pandemic resulted in an improved 2-year overall survival when 362 compared to delaying TAVR for a period as short as 3-6 months. This improved survival was 363 more pronounced for patients at intermediate risk but held true even for low-risk patients. As the 364 risk of perioperative COVID-19 increases above 55% (intermediate risk) and 47% (low risk) 365 delaying TAVR has an improved long-term survival; however, with these rates of COVID-19 366 infection, local hospitals would be overwhelmed and would have insufficient resources to 367 proceed with TAVR. According to our analysis, the only reason to delay TAVR would be 368 insufficient resources to care for these patients in the perioperative period. 

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Characteristics and Nombela-Franco 2-year overall survival data for low and intermediate risk patients based upon COVID-19 12 infection status and urgency of TAVR. Data is extrapolated using hazard ratio's for hospital 13 acquired pneumonia following TAVR. TAVR-transcatheter aortic valve replacement