A Comparison of Outcome in Patient With and Without Undergoing Cardiopulmonary Exercise Testing (CPET)

Introduction

Abdominal aortic aneurysm (AAA) is a life-threatening condition predominantly affecting men over the age of 65 with treatment usually indicated when it is more than 5.5 cm. ¹ The mortality risk after elective open AAA is approximately 3% in the UK though historically it has been higher. ¹ Therefore, it is of importance to assess the risk when identifying patients who may be suitable for an open AAA repair.

At present, there is no gold standard consensus of the choice of peri-operative investigations to assess patients suitable for open AAA repair. The recommendation from the Vascular Society guidelines and European Society of Vascular Surgery (ESVS) guidelines states that routine referral for Cardiopulmonary exercise testing (CPET) and cardiac work are not required prior to AAA repair . ² In patients with poor functional capacity, cardiac work up and optimisation is recommended prior to elective AAA repair . ² CPET is a preoperative risk stratification stool as it provides an objective measure of fitness and functional capacity. It helps evaluate several physiological variables of the circulatory, respiratory and metabolic systems under physiological stress.^3,4 It is a non-invasive assessment of the cardiorespiratory system and is considered the gold-standard method of measuring an individual’s aerobic capacity. ⁴ The test includes recording an exercise ECG, heart rate response to exercise, minute ventilation, and oxygen uptake per minute, and calculation of maximal oxygen consumption (VO2 max). ⁵ CPET has been used to help predict post-operative outcomes in patients with cardiorespiratory co-morbidities and help select patients for high-risk surgeries. However, despite the recommendation there has never been a trial or a report comparing CPET with non-physiological pre-operative testing in open aortic surgery.

The aim of our study is to investigate whether CPET perioperatively has value alongside non-physiological testing for patients undergoing elective open AAA repair.

Methods

This was a retrospective study looking at patients undergoing elective open AAA repair for infrarenal or juxtarenal aneurysms at 2 high volume major vascular centres between 2015-2019 (Queen Elizabeth Hospital and Birmingham Heartlands Hospital, Birmingham).

We followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines preparing the manuscript [STROBE - Strengthening the reporting of observational studies in epidemiology (strobe-statement.org)]. This was a retrospective study using prospectively collected data conducted within the clinical audit framework; no intervention was performed, and patients were not contacted outside their routine clinical care. The ethical approval was not required, and patient consent was not sought according to guidance from the UK Health Research Authority and UK Policy Framework for Health and Social Care Research (https://www.hra-decisiontools.org.uk). This was registered as an audit and approved at the Queen Elizabeth Hospital, part of University Hospitals Birmingham.

One vascular centre performed CPET as part of their routine peri-operative investigation along with anaesthetic assessment, echocardiogram, lung function tests and the other vascular centre did an anaesthetic review with other tests including echocardiogram and lung function tests. Patients were generally selected for open repair due to the presence of an infrarenal AAA usually more than 5.5 cm unless any adverse looking morphological features, younger age and if they were fit for surgery based on anaesthetic assessment in non-CPET centre and anaesthetic assessment in combination with a CPET assessment in the CPET centres. For suprarenal and complex AAA all the patients were referred to our local centre (CPET centre) for endovascular repair, this unit performing endovascular repairs for thoracoabdominal aneurysms. All patients were on appropriate best medical treatment for cardiovascular diease including antihypertensives, statins and aspirin (those patients on clopidogrel were changed to aspirin to allow the use of epidural catheters as per anaesthetic protocol).

Patients were identified from a prospective database of patients undergoing AAA repair. We excluded patient who underwent emergency surgery for symptomatic or ruptured AAA. Primary outcomes were mortality with other outcomes including length of stay at intensive care unit (ICU); total length of stay; post-operative complications including acute kidney injury (AKI).

Statistical analysis was performed using IBM SPSS software (Statistics 26.0 version). Continuous variables were presented as mean with standard deviation (SD), and categorical data were presented as proportions and percentages. Student’s t-test and Wilcoxon rank-sum test were used to compare continuous data as appropriate. Pearson’s chi-squared test and Fisher’s exact test were used to analyse categorical data. A P-value of <0.05 was considered significant.

Results

76 patients underwent elective infrarenal AAA surgery between the years of 2015 to 2019 in two different tertiary vascular centres. 38 patients had their surgeries performed in a CPET testing unit and 38 patients had their surgeries performed at non-CPET testing unit. Patient demographics is summarised in Table 1.

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Table 1.

Characteristics of Study Cohort in CPET Centre and Non-CPET Centre.

	CPET centre	Non-CPET centre
N	38	38
Mean age at operation, years	70.07 (47-81)	67.5 (56-81)
Gender (Men/Women)	36(94.7%)/2(5.3%)	35(92%)/3(8%)
Mean aneurysm size, cm	6.3	6.00
Graft (Tube/bifurcated)	18(47.4%)/20(52.6%)	17(45%)/21(55%)

In CPET unit 36 patients (94.7%) completed their CPET whilst 2 patients had CPET abandoned due to white coat induced hypertension. The mean VO2 max of patients that underwent CPET was 19.95 ± 3.65 mL Kg⁻¹ min⁻¹. Number of patients with VO2 max between 10-20 mL Kg⁻¹ min⁻¹ were 19 (52.78%). There were no patients in this cohort with a VO2 max <10 mL Kg⁻¹ min⁻¹. In both CPET and non-CPET centres patients had transthoracic echocardiogram (TTE) as part of their peri-operative assessment. The mean LVEF of patients was 63.58 ± 5.39%.

Sixty-nine patients underwent a midline incision for their repairs whilst 9 patients had a transverse abdominal incision with only 1 patient undergoing a retroperitoneal approach for repair. In the CPET group there were 30 infrarenal clamps whilst this was the same for the non-CPET groups. In the CPET group of the 8 patients there were 4 inter-renal clamps and 4 suprarenal clamps whilst in the non-CPET group of the 8 patients, 2 had inter-renal clamps and 6 suprarenal clamps. The mean operative time for patients in CPET centre was 3.24 ± 1.1 hours and the mean operative time for patients in non-CPET centre was 3.02 ± 0.5 hours. Independent t test performed shows that though the mean operative time in CPET centre was longer, this was not statistically significant (P = 0.13)

The mean duration of stay in ICU for patients in CPET centre was 2.5 ± 2.1 days; whilst the mean duration of stay in ICU for patients in non-CPET centre was 3.68 ± 4.1 days. This was statistically significant (P = 0.05). 6 patients in non-CPET centre had to stay in ICU for longer than 5 days. 4 of these patients required further respiratory support including non-invasive ventilation secondary to hospital acquired pneumonia (HAP). 1 patient in non-CPET centre stayed in ICU for 22 days as the patient had initially developed HAP and PE, the patient also developed abdominal compartment syndrome on day 7 and had to have emergency laparotomy; therefore, required further haemofiltration and cardiovascular pressor support. There were 2 patients in CPET centre that had to stay in ICU for longer than the average ICU stay duration (>5 days). 1 of the patients had a NSTEMI on day 3 and respiratory failure requiring further respiratory support and the other patient had acute limb ischaemia post-op and AKI requiring dialysis.

In CPET centre, the average length of stay at hospital was 6.97 ± 4.13 days. In non-CPET centre, the average length of stay at hospital was 10.78 ± 9.59 days and this was also statistically significant (P = 0.015).

In CPET centre, 37 patients (97.37%) were followed up 6 weeks and 1-year post-op as per trust guidelines. One patient in CPET centre died post-operatively on day 2 from the intra-operative bleed from aortic tear 0.5 cm above proximal anastomosis leading to profound hypovolaemic shock. Of the 37 patients that were followed up, 2 patients reported complications at 6-week follow-up of retrograde ejaculation. 35 patients (92.1%) reported no long-term complications at their 1-year post-op follow-up and were consequently discharged from the vascular service. Four patients developed HAP/Type 1 respiratory failure. One patient developed post-op limb ischaemia requiring fasciotomy and revascularization. One patient had an NSTEMI on day 3. Mortality rate in CPET centre is 2.63% (1/38).

In non-CPET centre, 36 patients (94.74%) were followed up at 6 weeks and 1-year post-op as per trust guidelines. There were 2 deaths in non-CPET centre cohort. One patient died from a possible large PE on the post-operative day 4, and one patient died from myocardial infarction (MI) on postoperative day 5. Both these patients suffered from sudden onset unwitnessed collapse and had no intra-operative complications or other predictive factors for sudden death. From the 36 patients that were eligible for follow-up, 4 patients developed post-operative ischaemic/discoloured foot requiring further embolectomy from common femoral artery (CFA) +/− jump graft to CFA. One patient developed rectus sheath haematoma post-operatively requiring embolization of the left inferior epigastric artery. One patient developed delayed ischaemic colitis. 1 patient had abdominal compartment syndrome requiring emergency laparotomy and suffered from acute bleeding from epiglottis during decannulation of tracheostomy, requiring input from ENT since. Five patients developed HAP post-operatively. Mortality rate in non-CPET centre is 5.26% (2/38). The difference in mortality rates between the 2 units was not statistically significant.

In CPET centre, 5 patients (13.16%) developed AKI within 72 hours post-operatively. 1 of those patients required dialysis. In non-CPET centre, 11 patients (28.95%) developed AKI within 72 hours post-operatively. 1 of the patients in non-CPET centre also required dialysis. All patients who developed AKI, recovered back to baseline.

Discussion

CPET has been considered a valuable perioperative risk stratification tool in cardiopulmonary surgery as it provides an objective measure of functional capacity and thereby helps predict post-operative outcomes.^3-5. However, there has not been much research in determining its value in vascular surgery. ⁶ The most important feature of this study is that this is the first study to directly compare the outcomes between performing CPET vs not performing CPET as part of a pragmatic perioperative investigations in patients undergoing elective open AAA repair.

This retrospective study highlights that CPET can be a valid prognostic indicator of post-operative outcomes. Our study showed that the mean duration of stay in ICU and total length of stay in hospital was significantly shorter in the CPET group (P = 0.05 and P = 0.015 respectively). The mean duration of stay in ICU for patients in the CPET group was 2.5 ± 2.13 days; whilst the mean duration of stay in ICU for patients in the non-CPET group was 3.68 ± 4.08 days. Mortality, number of patients developing AKI post-op, and requiring RBC transfusion were higher in non-CPET group (Table 2). The mortality rate in the CPET group (2.63%) is less than that of the national mortality (3%).

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Table 2.

Comparison of outcomes Between CPET Centre and Non-CPET Centre.

Outcome measured	CPET centre	Non-CPET centre	P
ICU length of stay (days ± SD)	2.5 ± 2.1	3.68 ± 4.1	0.05
Total length of stay (days ± SD)	6.97 ± 4.1	10.78 ± 9.6	0.015
Mortality (%)	2.6	5.3	0.56
Number of patients developing AKI post-op (%)	13.6	28.9	0.09

There are several theories behind how CPET can help predict post-operative outcome. One theory suggests that patients with a higher level of fitness function better with the prolonged increase in oxygen delivery induced by surgery without outpacing their anaerobic physiological parameters. ⁷ The other theory being that regular exercise creates a systemic effect similar to that of ischaemic preconditioning. Therefore, increasing the ischaemic conditions, it can help improve the patient’s ability to meet the demands with regards to oxygen delivery associated with surgery. ⁷

Several articles in current literature look at the role of CPET as a peri-operative risk stratification tool in major abdominal surgery. A recent systematic review looked at the efficacy of CPET in predicting risk of post-operative complications and mortality in comparison to other methods of risk stratification in patients undergoing non-cardiopulmonary surgery. It found that CPET variables outperform alternative perioperative risk stratification tools. ⁸ There are multiple studies looking at various cut-off values and thresholds for different CPET variables to help assess a patient’s functional capacity and predicting morbidity and mortality^9-11; however, there is no consensus in these cut-off values and there is lack of research in determining the gold standard CPET variable to be used and its cut-off value.

One of the main limitations of this study is that it is retrospective. Patients that were deemed unfit for undergoing elective open AAA repair are not included in the analysis. Hence, we are unable to determine the course of what had happened to patients that were not offered open AAA repair based on CPET results; whether they were offered EVAR or managed conservatively. Another limitation is that this is still a relatively small sample study thereby making sub-group analysis difficult. This allows for confounding factors such as the co-morbidities of patients in each centre that are not analysed. However, the aim of the study was not to look at any alternative or superior methods of selecting patients fit enough for elective open AAA repair. The aim was to directly compare the role of CPET vs non-physiological testing in patients undergoing elective open AAA repair.

This study indicates that CPET can be a useful adjunct in identifying patients at increased risk of adverse perioperative outcomes for patients undergoing elective open AAA repair. However, further research must be done in assessing and defining cut-off values for different CPET variables to help predict mortality and morbidity in these patients.