Clinical Utility and Cost of Inpatient Transthoracic Echocardiography Following Acute Ischemic Stroke

Abstract

Background and Purpose:

It is unclear whether it is clinically necessary or cost-effective to routinely obtain a transthoracic echocardiogram (TTE) during inpatient admission for ischemic stroke.

Methods:

We assessed consecutive patients presenting with acute ischemic stroke at a comprehensive stroke center from 2015 to 2017 who underwent TTE. We assessed for findings on TTE that would warrant urgent intervention including cardiac thrombus, atrial myxoma, mitral stenosis, valve vegetation, valve dysfunction requiring surgery, and low ejection fraction. Subsequent changes in management included changes in anticoagulation, antibiotics, or valve surgery. We calculated in-hospital resource utilization and associated costs for inpatient TTE using individual direct cost details within a case-costing system.

Results:

Of 695 patients admitted with acute ischemic stroke, 516 (74%) had a TTE and were included in our analysis. TTE findings were potentially clinically significant in 30 patients (5.8%) and changed management in 17 patients (3.3%). Inpatient admission was prolonged to expedite TTE in 24 patients, while TTE occurred after discharge in 76 patients. After correcting for the cost of TTE, the mean difference in cost to prolong an admission for TTE was $555.52 (USD), or $16 832 per change in management.

Conclusions:

Given the low clinical utility of inpatient TTE after acute ischemic stroke and the costs associated with prolonging admission, discharge from hospital should not be delayed solely to obtain TTE.

Introduction

Secondary prevention of acute ischemic stroke is increasingly tailored to stroke etiology, which is often determined after a systematic series of investigations including transthoracic echocardiography (TTE). Previous studies report significant variability in the utility of TTE in this context, potentially owing to different definitions of clinically relevant findings.^1-7 Currently, there are no clear guidelines for the timing of cardiac investigations after ischemic stroke, particularly in relation to which tests should be performed prior to discharge from hospital.⁸ Also, the cost-effectiveness of TTE after stroke is unclear, as it has only been reported in a limited number of studies using computer modeling, and none that used real patients.^9-11 The aim of this study was to determine the value of TTE during admission for acute ischemic stroke. We examined the frequency of clinically relevant findings that might warrant urgent changes in management based on TTE in patients admitted with acute ischemic stroke. We also sought to estimate hospital costs associated with performing TTE during inpatient admission compared to deferring it until after hospital discharge, when early discharge is possible.

Methods

We conducted a retrospective cohort study and reviewed patients presenting from January 1, 2015 to December 31, 2017 with acute ischemic stroke within 12 hours of symptom onset to The Ottawa Hospital, a regional comprehensive stroke center serving a population of 1.2 million people with over 1000 annual admissions for ischemic stroke. Patients assessed in the emergency department as an acute “code stroke” were followed from their initial presentation to their eventual discharge and subsequent outpatient follow-up, when applicable. All patients underwent baseline computed tomography (CT) and CT angiography (CTA) on arrival except in the case of a known contraindication to contrast. Patients who received a transthoracic echocardiogram (TTE) were included in our study. The timing and extent of investigations were decided at the discretion of the treating physician.

The diagnosis of stroke was confirmed with CT or magnetic resonance imaging (MRI). Patients were excluded from the primary analysis if they had a diagnosis other than ischemic stroke, if the etiology of stroke could not be determined, or if they did not receive TTE within 6 months of presentation. The patient’s background characteristics, including age, sex, cardiovascular risk factors, general comorbidities, and medications were collected from electronic medical records. Stroke etiology was determined by the treating stroke neurologist using TOAST criteria at 6 months.¹² TTE was performed either during inpatient admission or after discharge in an outpatient setting. Discharge home was considered to have been delayed for the purposes of obtaining the TTE if this was documented by a physician either in progress notes or in the discharge summary.

Length of hospital admission and associated costs for each patient were provided by The Ottawa Hospital (TOH) Data Repositories. The TOH Data Repositories contain administrative data on patients, hospitalizations, outpatient, day care and emergency department visits, clinical documentation, interventions, and procedures for all patients seen at The Ottawa Hospital. Additionally, the TOH Data Repositories include human resource systems and financial information from the General Ledger and case costing data. Cost data were calculated in the context of Canada’s publicly funded health care system. We calculated hospital costs using The Ottawa Hospital’s case costing system^13,14 which links financial, clinical, and patient activity information that occurred during each patient encounter. The hospital costs consisted of direct costs that related to patient care (e.g., imaging, pharmacy, operating room costs, special care unit costs) and indirect costs associated with hospital overhead (e.g., information technology, financial services, plant operations). Total costs included the TTE as well as hospital costs. The cost of a TTE ($158.07) was obtained from the Ontario Schedule of Benefits: Physician Services Under The Health Insurance Act¹⁵ and confirmed by our case costing department.

TTE was performed using a standard protocol recommended by the American Society of Echocardiography.¹⁶ All patients 60 years of age or less received an agitated saline bubble study at rest and with Valsalva maneuver when possible. TTE reports were reviewed and the following findings were considered potentially clinically relevant as they would have warranted an urgent change in management: definite or possible left atrial (LA) or left ventricular (LV) thrombus, definite or possible myxoma or tumor, definite or possible valvular vegetation, moderate to severe mitral stenosis (grade 3+ or more), valve dysfunction requiring repair or replacement, and ejection fraction (EF) ≤ 20%. This definition was chosen after reviewing prior studies and reflecting on our own clinical practices^3-5; our final definition is similar to that of another published Canadian study.³ We deemed EF ≤ 20% significant as urgent optimization of cardiac function and/or other investigations may be warranted, and in our institution we often treat these patients with anticoagulation for secondary stroke prevention if this is felt to be the most likely stroke mechanism. We did not include findings that have been assessed in some prior studies but that do not usually result in an immediate change in management, including patent foramen ovale (PFO), mitral valve prolapse or regurgitation, mitral annular calcification, or aortic arch atheroma. We defined a change in medical management due to TTE as: starting or continuing IV anticoagulation, changing oral anticoagulation (e.g. starting de novo or switching from direct oral anticoagulant (DOAC) to warfarin), adding or continuing antibiotics, or surgery to repair or replace a cardiac valve. Transesophageal echocardiogram (TEE) was sometimes performed to verify TTE findings, but we did not consider a TEE itself (i.e. negative TEE) as a change in medical management.

We recorded the number of patients with potentially clinically relevant findings on TTE and the number of patients in whom subsequent changes in medical management occurred. We performed similar analysis on data from a subgroup of patients with atrial fibrillation that was known prior to admission. We calculated the total cost for all patients who received TTE after acute ischemic stroke, for those patients whose admission was prolonged to obtain TTE as an inpatient, and for those who were discharged and received TTE as an outpatient. Given the known skew associated with cost data, we reported both mean and median costs and used the Mann-Whitney U test to compare the cost differences. Cost data was calculated in Canadian Dollars (CAD) but converted and reported here in US Dollar (USD) equivalents using exchange rate 1 CAD = 0.76 USD (November 11, 2019). Due to the small number of patients in our final samples we did not perform regression analysis to adjust for confounding factors.

This study was approved by Ottawa Health Science Network Research Ethics Board. The data collected for this study is available for access to qualified researchers trained in human subject confidentiality protocols who are collaborating with the Ottawa Stroke Program.

Results

Of 2058 patients assessed for possible acute stroke, 695 patients had confirmed acute ischemic stroke with a documented etiology, and 516 (74%) had TTE as part of their management and were included in our study. Of these, 29 patients (5.6%) underwent TEE, usually following unremarkable TTE in the context of cryptogenic stroke. The mean age of the study population was 71 years, and there was a nearly equal distribution of males (52%) and females (48%). The majority of patients received acute treatment: 321 patients (62%) received tissue plasminogen activator (tPA) and 157 patients (30%) received endovascular therapy (EVT). Stroke etiology was determined to be cardioembolic in 202 patients (39%), large artery disease in 118 (23%), small vessel disease in 67 (13%), cryptogenic in 103 (20%), and another etiology in 26 (5%) (Table 1).

Table 1.

Baseline Characteristics of Patients With Acute Ischemic Stroke.

Characteristic	No. (%) with TTE (n = 516)
Age, mean +/- SD	71 +/- 14
Male sex	268 (52)
Known cardiac co-morbidities
Atrial fibrillation	118 (23)
Congestive heart failure	46 (9)
Cardiomyopathy	11 (2)
Severe coronary artery disease	112 (22)
Prosthetic valve	24 (5)
Congenital heart disease	6 (1)
Stroke etiology at 6 months
Large artery disease	118 (23)
Cardioembolic	202 (39)
Small vessel disease	67 (13)
Cryptogenic	103 (20)
Other	26 (5)
Antiplatelet use	205 (40)
Anticoagulant use
Warfarin	28 (5)
DOAC	34 (6)
Acute therapy
tPA	321 (62)
EVT	157 (30)

DOAC, Direct oral anticoagulant; EVT, endovascular therapy; SD, standard deviation; tPA, tissue plasminogen activator.

TTE findings were potentially clinically relevant in 30 patients (5.8%) (Table 2). The most common finding was definite or possible LA or LV thrombus, accounting for one third of potentially clinically relevant findings. TTE findings resulted in a change of medical management in 17 (3.3%) patients, or in 56.7% of those with potentially clinically significant findings on TTE (Table 3). The addition of IV anticoagulation or change in choice of oral anticoagulation accounted for 88% of management changes. We estimate that one urgent change in management occurs for every 30.3 patients who receive a TTE. As comparison, 157 patients (30.4%) received EVT for large vessel occlusion diagnosed using CTA, thus we estimate that one urgent change in management occurs for every 3.3 patients with acute ischemic stroke who receive CTA.

Table 2.

Summary of Potentially Clinically Relevant TTE Findings.

	All patients (n = 516)	Patients with known atrial fibrillation (n = 118)
Definite or possible LA or LV thrombus	10	1
Definite or possible myxoma or tumor	2	1
Definite or possible valvular vegetation	5	2
Moderate to severe mitral stenosis	2	1
Valve dysfunction requiring repair or replacement	2	0
Ejection fraction ≤ 20%	9	2

Table 3.

Summary of Changes to Medical Management due to TTE Findings.

	All patients (n = 516)	Patients with known atrial fibrillation (n = 118)
IV anticoagulation	7	0
Change in oral anticoagulation	8	0
Addition or continuation of antibiotics	0	0
Intervention to repair or replace cardiac valve	2	0

Of patients who received TTE after acute ischemic stroke, 118 were known for pre-existing atrial fibrillation. TTE findings were potentially clinically relevant in 7 (5.9%) patients with known atrial fibrillation (Table 2), though findings never resulted in a change of medical management (0%) (Table 3).

Cost data was available for 509 patients who received TTE after acute ischemic stroke (Table 4). There were 24 patients whose admission was prolonged to obtain inpatient TTE (median length of admission 3.5 days; inter quartile range [IQR] 2-5), while 76 patients received their TTEs after discharge (median length of admission 3.0 days; IQR 2-5). Patients with prolonged admission, on average, incurred an additional $555.52 per patient compared to those receiving TTE as an outpatient, though this difference was not statistically significant ($5 133.40 vs. $4 577.88; p = 0.15). Given that one urgent change in management occurs per 30.3 patients undergoing TTE, the cost per change in management associated with prolonging admission for TTE was approximately $16 832.

Table 4.

Total Health System Cost Following Acute Ischemic Stroke.*

	Number of patients	Mean age (SD)	Cardioembolic etiology (%)	Median length of admission (days, IQR)	Mean cost (SD)	Median cost (IQR)
All patients who received TTE	509	71.1 (14.1)	199 (39.0)	6.0 (3-12)	$13,347.92	$7,556.85
					(15,304.50)	(3,367.09, 17,646.14)
Patients with prolonged admission to obtain inpatient TTE	24	66.1 (15.3)	9 (37.5)	3.5 (2-5)	$5,133.40	$3,927.49
					(5,633.51)	(2,298.46, 4,775.72)
Patients who received TTE after discharge as an outpatient	76	69.9 (12.8)	22 (28.9)	3.0 (2-5)	$4,577.88	$2,615.13
					(5,072.92)	(1,677.85, 4,993.65)

IQR, inner quartile range; SD, standard deviation.

* Cost data include hospital and TTE costs and are reported in USD.

Of the 76 patients who were discharged from hospital prior to undergoing TTE, none were found to have had a cardioembolic stroke, and there were no clinically relevant findings or changes in management associated with TTE. However, 4 of these patients (5.2%) did have recurrent stroke prior to receiving their TTE; etiologies of recurrent stroke in these patients included giant cell arteritis, cryptogenic, and small vessel disease.

Discussion

The performance of TTE prior to discharge from hospital after acute ischemic stroke is considered routine in many centers, though our results suggest that its findings are infrequently clinically significant, rarely change management, and do not change management at all in patients with known atrial fibrillation. Previous studies reported clinically relevant findings on TTE in 3-37% of stroke patients, though nearly all studies report rates below 20%.^1-7 This variability is most likely explained by evolving definitions of clinically relevant findings and subsequent management based on current practices. For example, we chose to exclude PFO or left atrial enlargement as they do not immediately change management. However, we did include significant mitral stenosis as detection of valvular atrial fibrillation would change the preferred anticoagulation choice from DOAC to warfarin, which might not have been relevant in the pre-DOAC era.¹⁷ The majority of our management changes were related to anticoagulation, which could have had significant consequences if deferred. In our center an outpatient TTE routinely occurs within 1 week of discharge, thus other findings that could be relevant but that we did not deem urgent (e.g. aortic arch atheroma or PFO) would still be discovered relatively quickly.

In the case of patients with known atrial fibrillation and a prior echocardiogram, TTE after stroke does not appear to change management as findings are unlikely to alter the decision to anticoagulate. A small study performed in the pre-DOAC era similarly found that TTE was unlikely to change management in patients with atrial fibrillation.¹⁸ While intracardiac thrombus would be a finding of concern, there is limited evidence to suggest the superiority of one form of anticoagulation (warfarin, heparin or DOAC) over another in these cases.^19-22

Our cost analysis related to prolonged admission for the sake of expediting TTE is limited due to our small sample size, and thus we present a descriptive analysis without the benefit of regression analysis to adjust for confounding factors. However, our findings are of interest to a growing field of study pertaining to the utility of TTE in general, and in stroke specifically. A recent study investigating inpatient TTE after acute myocardial infarction reported that hospitals with higher rates of TTE had greater mean hospital costs and length of stay without significant differences in clinical outcomes.²³ A recent Canadian study reported that median length of hospital stay for stroke patients was 3 days longer for patients receiving echocardiography, suggesting that prolonging inpatient admission to expedite TTE is not unique to our center.⁷

There is limited data regarding the cost-effectiveness of TTE in secondary stroke prevention. Two prior American studies used computer modeling to complete a cost-effectiveness analysis of echocardiography after first ischemic stroke, and both found that TTE alone or in combination with other strategies was not cost-effective, though one found TEE to be cost-effective.^9,10 A British study using another modeling strategy found that TTE was cost-effective compared with TEE when a clinician deems it an appropriate test, though they emphasized that there were significant limitations to their economic analysis due to data limitations (e.g. unknown efficacy of treatment in reducing recurrent stroke).¹¹ Results from these studies could not be directly compared to our results due to differences in study design, as our study focused on the impact of inpatient TTE on health system costs as opposed to its overall cost-effectiveness. Future studies should investigate whether TTE is cost-effective in the real-world setting in all-comers.

Previous studies have attempted to determine a clinical decision rule to predict which patients are most likely to have relevant findings on TTE³; given our low number of events and subsequent management changes, we did not attempt to create a similar rule. Given the low yield of urgent TTE findings in our study, and the absence of cardioembolic stroke in patients discharged prior to TTE, it is likely safe to discharge most patients home to await TTE as an outpatient. Further study is required to examine the utility of TTE in all clinical contexts. Moreover, alternate methods of detecting cardiac thrombus are currently being explored,^24,25 and may eventually play a role in post-stroke care.

Limitations to the current study include that it was retrospective and based on a single center. The majority of our patients received tPA which could confound the rate of cardiac thrombus detection, and results could thus vary for patients admitted with subacute stroke or TIA who were not included in our current study. Our study likely overestimates the prevalence of significant TTE findings as patients with known alternate etiologies (e.g. carotid stenosis requiring intervention) would not have routinely undergone TTE and therefore would not have been included in our analysis. However, our rate of TTE post-stroke (74%) is consistent with recently published practices in another Canadian academic center, where 70% of stroke patients underwent TTE.²⁶ Moreover, our patients had a relatively high rate of cardioembolic etiology, possibly due to selection bias but also perhaps owing to our local practice of routinely obtaining at least 2 weeks of cardiac rhythm monitoring in patients without a known stroke etiology. We only captured patients with prolonged admission to expedite TTE if they had explicit documentation of delayed discharge home, thus we likely underestimated the number of such patients, including those whose transfer to another facility was delayed. Our results are focused on findings and management during inpatient admission and are therefore not generalizable to TTE performed after stroke in all contexts. Our cost data were limited to a low number of patients who had TTE as an outpatient, though this emphasizes that patients tend to receive TTE as an inpatient in our center.

In conclusion, our results suggest that TTE findings after acute ischemic stroke are infrequently clinically significant and rarely change management. Given increased costs associated with performing this investigation during admission, patient discharge from hospital should not be routinely delayed to expedite TTE.