Stress Echocardiography Research Articles

The prognostic value of contrast stress echocardiography in a real-world population of symptomatic patients without known coronary artery disease

Abstract Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. In addition to diagnosis, non-invasive tests may also provide prognostic information useful in the risk stratification and management of CAD patients. Stress echocardiography (SE) is an accurate, non-invasive method for the detection of obstructive CAD. However, in real-world clinical practice the test performance may vary among different centres, depending on availability, local protocols, and operator expertise. Purpose To evaluate the prognostic value of contrast SE in a real-world population of symptomatic patients without known CAD. Methods This was a cohort follow-up study of patients without known CAD and symptoms of atypical chest pain, unexplained dyspnoea or palpitations who were referred to the echocardiography lab of a tertiary hospital for SE between January 2020 and December 2021. Patients with resting regional wall motion abnormalities were excluded. All patients underwent treadmill exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) if unable to exercise. Contrast agents were used in almost all patients (99%). The study population was followed-up for at least 2 years after SE by phone and/or electronic hospital records. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, acute coronary syndrome (ACS), or cardiac-related death. Results The study comprised 266 patients (mean age 58±12 years, 63% male) who underwent either ESE (58%) or DSE (42%). The patients' details are reported in Table 1. The most common indication for the exam was atypical chest pain, with a prevalence of 73%. SE exams were positive for inducible ischaemia in 14 (5%) patients. Symptoms during the exam were present in 3 (21%) patients with positive SE and 4 patients (2%) with negative SE (p=0.004). No serious complications (sustained ventricular tachycardia, myocardial infarction, or death) were recorded. During the follow-up (median 30, IQR 23–38 months), 264 patients (99%) were successfully contacted. Cardiac outcome occurred in 10 patients. Among 14 patients with positive SE, 8 underwent revascularization due to significant coronary artery stenosis. Among 250 patients with negative SE, 1 underwent revascularization due to significant coronary artery stenosis and 1 presented with ACS 13 months after the test (both patients underwent DSE). Negative predictive value was 99% over a median follow-up of 30 months, corresponding to an annualized event rate of 0.32% per year. A positive SE was significantly associated with cardiac outcome (log-rank test p<0.0001, Figure 1). Conclusion Contrast SE carries significant prognostic implications in symptomatic patients without known CAD. A positive test is strongly associated with the need for revascularization, while a normal test result has an excellent negative predictive value regarding cardiovascular morbidity and mortality.Figure 1

How to predict myocardial injury in patients with large ischaemic burden identified during stress echocardiography?

Abstract Background/Introduction Stress echocardiography (SE) is well established diagnostic tool in coronary artery disease (CAD) with broadly agreed consensus for the indications and protocols. There is, however, no clear non-invasive SE parameter in identifying high risk features in patients with large burden of inducible regional wall motion abnormalities (RWMA) that would require prompt treatment or urgent admission. Purpose To identify high risk features during SE associated with myocardial injury following a positive SE with large amount of RWMA. Methods All consecutive patients referred for SE from June 2019 to November 2022 to diagnose coronary artery disease were assessed for inducible RWMAs using a hybrid protocol (low dose Dobutamine and exercise on supine bike with 3 min increments of workload of 25W). Those with ≥4/17 segments of inducible RWMAs underwent measurement of Troponin level 1 hour after the test termination. Somatometric characteristics, risks factors, symptoms, haemodynamic pre- and during SE and results of subsequent coronary angiography were recorded. Results 631 patients were referred for assessment of CAD. 87 patients had ≥4/17 inducible RWMAs out of 152 patients with positive SE. 61/87 who had Troponin measurements were included in the analysis. Mean age was 65 ± 13 yo, 61% were male. There was high prevalence of known CAD (77%) and cardiovascular risks factors as hypertension (59%) and hyperlipidaemia (61%). The median exercise time was 9 minutes, 46% developed chest pain (CP), 49% - ECG changes, 39% - left ventricular (LV) dilatation and 74% - reduction in LVEF. Troponin was positive in 25/61 patients. Invasive coronary angiography confirmed clinical CAD in 51/61 patients. 5 patients had either normal angiogram or non-obstructive CAD, 5 patients were awaiting diagnostic test. The severity of CAD appears to be associated with magnitude of Troponin release (1 vessel disease - 16.5 ng/L, 2 vessels disease - 39.9 ng/L, 3 vessels disease – 58.2 ng/L). All patients (6/61) with higher troponin values (>90ng/L) had multivessel disease involving the left anterior descending (LAD) artery. Interestingly, 2/5 patients without CAD had elevated Troponin suggesting possible ongoing myopathic process. The only non-invasive SE parameters that were significantly related to troponin increase were recovery time (P=0.001) and exercise time (P<0.05) whereas symptoms, BP response and LVEF reduction showed a trend which did not achieve significance. Conclusions In patient with positive SE with large burden of inducible RWMAs prolonged recovery time and low threshold for ischaemia appear to be the most reliable characteristic to identify patients with potential myocardial injury and should be used as a triaging tool for admission or early invasive assessment.

Functional correlates of ischemic electrocardiographic changes during stress echocardiography. data form stress echo 2030 survey

Abstract Background/Introduction Cardiac stress tests are carried out in populations with a low probability of ischemic heart disease (IHD) much more frequently than in the past. Stress ECG remains a frequently used modality for the diagnosis of IHD in vast areas of the world with limited facilities. Purpose To assess the diagnostic value of stress ECG for diagnosing IHD using inducible regional wall motion abnormalities (RWMA) on stress echocardiography (SE) as the gold standard method of diagnosis. Methods The 12-lead ECG response was retrospectively analyzed in 4317 patients (age 64±13 years, 59.6% males) undergoing SE for chronic coronary syndromes who were prospectively recruited from 39 cardiac centers between March 2021 and February 2024. Exclusion criteria were left bundle branch block or pacemaker rhythm. ECG response was considered ischemic according to standard criteria (if ST-segment deviated >1.0 mm from baseline in ≥2 contiguous leads at 80 ms from J point) during an exercise (n=2980, 69.8%), dobutamine (n = 766, 18.0%), or vasodilator (n=519, 12.2%) SE. All patients underwent a comprehensive SE protocol with an assessment of wall motion score index (WMSI), B-lines (4-site simplified score), left ventricular contractile reserve (LVCR) based on force, coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending artery (LAD), and heart rate reserve (HRR). Results ECG changes occurred in 641 patients (14.8%, Group 1) for the overall studied population. Compared to patients without ECG changes (Group 2, n=3676, 85.2%), patients with ECG changes showed higher values of peak WMSI and lower values of CFVR and LVCR (see table).Amongst patients without inducible RWMA (n=3553), there were 392 (11%) patients with an ischemic ECG at stress (89% specificity). Of 764 patients with inducible RWMA during SE, 249 had an ischemic ECG trace (sensitivity 33%). In patients without inducible RWMA, those with ischemic ECG changes showed similar abnormal stress B-lines (23% vs. 21%, p=0.719), LVCR (61% vs. 63%, p=0.602), CFVR (31% vs 33%, p=0.607) and HRR (37% vs 41%, p=0.097) compared to those without ECG changes. Amongst patients with inducible RWMA and ECG changes, CFVR was significantly lower in patients with ECG changes (39.2% and 60.8%, respectively, p<0.001). Conclusions Simple standard stress ECG diagnostic value in the current era in populations with a low probability of IHD seems to be low. However, during SE, stress-induced ischemic ECG changes are associated with more extensive RWMA and blunted global LVCR, with reduced CFVR in the LAD. Therefore, analysis of ST segment changes during stress imaging studies can offer additional, significant information.

Regadenoson stress echocardiography: a road ahead

Abstract Introduction Drugs used in stress echocardiography (SE) have important limitations due to side effects and contraindications. Since its approval in 2008, Regadenoson has seen a significant increase in usage. This is largely attributed to its good safety profile and diagnostic accuracy, making it the preferred drug for stress tests in many European centers. However, despite its expanding use and major advantages, current guidelines don't place it as the first choice for SE, probably because the reported experience with this drug remains limited. The aim of the present study was to assess the safety and short-medium term prognosis of patients who underwent Regadenoson SE. Methods Retrospective observational study. Patients who underwent Regadenoson SE between 2017 and 2023 were included. Safety was assessed by monitoring immediate adverse effects following Regadenoson infusion and the need for using an antidote (Aminophylline). A positive test result was defined by the occurrence of any of the following: wall motion abnormalities, left ventricle dilatation, electrocardiographic changes or symptoms of ischemia. During the follow up, we registered the incidence of ischaemic events (admission for unstable angina, acute myocardial infarction (AMI) or cardiovascular (CV) death) and other CV events such as admission for heart failure (HF) and stroke. Additionally, we evaluated patients in both groups who underwent coronary angiography (by computerized tomography or coronary catheterization) during the follow up period. The groups with negative SE (NSE) and positive SE (PSE) were compared. Results The total number of patients was 344, with a median follow up of 29 months. Basal population characteristics and events by group (NSE and PSE) are shown in Figure 1. We needed to use the antidote in only one case, because of ventricular bigeminism, with no other major adverse effects reported. SE was positive in 37 (11%) patients. In this group, patients were more likely to present ischaemic events (16% vs. 3%, p<0.01) and admissions for HF (24% vs. 5%, p <0.01), compared to the NSE one. In those who underwent coronary angiography, revascularization was needed in 14 patients of the PSE group, and only in 7 of the NSE group (38% vs 2%, p < 0.05). The indications for these last cases were persistent angina in 5 patients (2 of them with history of coronary artery disease) and revascularization following an AMI in 2 patients. (Figure 2). Conclusions The probability of an ischaemic event after a negative Regadenoson SE remains very low, unlike positive studies. Regadenoson SE showed to be both safe in assessing ischemic cardiomyopathy and very useful for its prognostic value. These findings encourage its expanding use in the stress echo lab.

Accuracy of machine learning techniques to predict stress echocardiography results using clinical variables

Abstract Background Stress echocardiography (SE) is a diagnostic prognostic imaging modality for suspected coronary artery disease (CAD). Cardiovascular risk factors (CVRF) are used in the assessment of the probability of CAD. The link between the outcome of SE and patients’ variables including CVRF, current medication, and anthropometric variables has not been widely investigated.Objective: The aim of this study is to understand whether a machine learned algorithm can be used to predict significant CAD defined by inducible ischemia on SE in patients with suspected CAD based on anthropometrics, CVRF, and medication as variables. Methods A machine learning (ML) framework was generated to automate the prediction of inducible ischemia on stress echocardiography results. A mutual information-based feature selection methods (support vector machine (SVM) and random forest (RF) classifiers) were used to investigate the amount of information that each feature carried to define the positive outcome of SE.Data from 2201 patients were used to train and validate the framework. Patients mean age was 62 (SD 11) years. The data consists of anthropological data and classical CVRF, atrial fibrillation, prior diagnosis of CAD, stroke, obstructive airways disease, chronic inflammatory disease, chronic kidney disease (CKD>3) and prescribed medications at the time of the test. There were 394 positive and 1807 negative SE cases. Five-fold cross-validation was used to validate the performance of the framework. Results The feature selection methods showed that prescribed medications such as Weight, Diabetes, Antiplatelet drugs and ACE- inhibitor/ARB, were the features that shared the most information about the outcome of SE (sensitivity and specificity of 81% and 51% and 81% and 61% for SVM and RF, respectively) with the accuracy of 82%. Conclusion This study shows that ML can predict the outcome of SE based on only 4 clinical features. Further research correlating the clinical variable and SE result to cardiovascular outcome will improve the model’s clinical utility and facilitate patient selection for early treatment avoiding unnecessary downstream testing.

Negative long-term prognostic value of stress echocardiography in patients with incomplete revascularization after successful primary PCI

Abstract Background The role of stress echocardiography (SECHO) in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) has not been extensively documented. The Aim The aim of our study was to assess the negative long-term prognostic value of SECHO after successful pPCI and incomplete revascularization of non-culprit lesions. Methods Our study consisted of 194 patients (mean age 59±10years, male 136; 70.1%) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion other than treated vessel. Lesion severity of non-culprit coronary arteries was assessed by quantitative coronary angiography. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), chronotropic incompetence, heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were calculated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow up of the patients was 96 ± 32.5 months for the occurrence of all-cause mortality and non-fatal myocardial infarction (MI). Results Out of 194 patients, 38 (19.6%) had positive SECHO test, and 7 patients (3.6%) were lost to follow up so they were excluded from further analysis. During the follow-up period 29 out of 149 patients (18.8%) had an adverse event (20 deaths and 9 non-fatal MI). Negative predictive value of SECHO test was 81.2%. Median time from MI to SECHO test was 8 months. Using the Cox regression analysis, univariate predictors of adverse events were slow HRR (HR 3.750 [95% CI 1.620-8.679], p=0.002), Duke score (HR 0.866 [95% CI 0.755-0.994], p=0.040) and chronotropic incompetence (HR 0.310 [95% CI 0.107-0.895], p=0.030). In the multivariate analysis only the slow HRR remained an independent predictor of adverse events (HR 3.329 [95% CI 1.417-7.825], p=0.006). Using the Kaplan-Meier survival curve we see that the patients with slow HRR had much shorter event-free time (slow HRR 117.2 ± 13.4 months vs normal HRR test 139.4 ± 4.2 months, Log Rank 4.988, p=0.026). (Figure 1.) Conclusion SECHO test has excellent negative long-term prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI while patients with slow HRR have more pronounced risk for the occurrence of adverse events.Figure 1.Kaplan-Meier survival curve

Prognostic significance of coronary flow velocity reserve in patients with peripheral arterial disease

Abstract Background Patients with lower extremity peripheral arterial disease (PAD) have a higher risk of cardiovascular events. Stress echocardiography (SE) based on regional wall motion abnormality (RWMA) is imperfect for risk stratification in PAD, but it can be complemented with an assessment of coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending coronary artery. Purpose To assess the value of SE with RWMA and CFVR to predict survival in PAD. Methods In a retrospective analysis of prospectively acquired data in an observational, multicenter study, we recruited 359 patients (age 69±8 years, 240 [67%] males) with PAD referred for dipyridamole SE in 3 accredited laboratories. We assessed RWMA and CFVR (abnormal value <2.0). All patients were followed up for a median of 4.7 (interquartile range: 2.0 to 8.2 years). All-cause death was the outcome end-point. Results The positivity rate was 37/359 (10%) for RWMA and 159/359 (44%) for CFVR. During follow-up, 97 (27%) deaths were registered. At multivariable analysis, inducible RWMA and/or CFVR <2.0 (HR 2.58, 95% CI 1.65-4.04; p<0.0001), age ≥70 years, diabetes, dialysis treatment, and ejection fraction ≤50% were associated with decreased survival. The annual mortality was 7.4% in patients with RWMA and/or CFVR <2.0 and 2.7% in those with no RWMA and CFVR >2.0 (Figure, p<0.0001). Conclusion In patients with PAD, SE shows more than 4-fold higher prevalence of abnormal CFVR compared to RWMA. The prognostic value of CFVR outperforms RWMA, showing the importance of coronary microvascular dysfunction and diffuse, subcritical coronary atherosclerosis in determining the outcome.

Incremental role of Cardio-Ankle Vascular Index in predicting ischemic threshold in patients with suspected coronary artery disease

Abstract Background The Cardio-Ankle Vascular Index (CAVI) quantifies arterial stiffness and has emerged as a potential biomarker for cardiovascular disease and its associated risk factors. This study explores the prognostic utility of CAVI in predicting myocardial ischemia in patients with suspected coronary artery disease (CAD). Additionally, it examines the relationship between global longitudinal strain (GLS) and the wall motion score index (WMSI) during both rest and stress echocardiography. Methods We conducted a retrospective analysis of patients with suspected CAD who underwent CAVI measurement and stress echocardiography within a three-month window. Coronary angiography was utilized to evaluate anatomical stenosis (>50%). We used multivariate analysis to identify predictors of the ischemic threshold. Results In our cohort of 127 patients (average age 61.4 ± 9.1, 78% male), the prevalence of hypertension, dyslipidemia, and diabetes was 76%, 68% and 47% of patients, respectively. Prior coronary intervention and a history of myocardial infarction were showed significant prevalence at 33% and 9%, respectively. CAD distribution included absence in 15%, left main (LM) disease in 8%, proximal left anterior descending (LAD) artery disease in 38%, mid-to-distal LAD disease in 50%, left circumflex artery disease in 46%, and right coronary artery disease in 57%. A robust correlation between GLS and WMSI was observed both at rest and during peak stress (r=0.68 and r=0.57, p<0.001, respectively). High CAVI (≥8.5), resting GLS in the LAD(<-15.5%), and peak GLS during stress (<-15.3%) emerged as significant ischemic threshold predictors in multivariate analysis (AUC = 0.82, p<0.0001). Conclusion The correlation between WMSI and GLS provides valuable insights into cardiac mechanics. These findings underscore the clinical relevance of incorporating CAVI, GLS, and WMSI into routine assessments for patients with suspected CAD to enhance prognostic stratification.ROC for final predictive model

Double product derived from exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) in patients with a history of breast cancer and radiotherapy (RXT) exposure and MACE

Abstract Background Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts. Purpose We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population. Methods Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method. Results 696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=<0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=<0.01]. In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1). Conclusion DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.

Comprehensive stress echocardiography uncovers the heterogenity of phenotypes in non-ischemic heart failure with abnormal ejection fraction

Abstract Background Heart failure (HF) with abnormal left ventricular (LV) ejection fraction (EF) manifests in multiple phenotypes, each presenting distinct and potentially actionable therapeutic targets. This study aimed to assess the potential of the ABCDE+ stress echocardiography (SE) protocol in uncovering different phenotypes of non-ischemic HF. Methods With a retrospective analysis of prospectively acquired data, we identified 265 patients (mean age: 65.7±12.6 years; 154 males, 59.9%) with non-ischemic HF with EF<50% (mean =41.4±7.5) enrolled by 23 certified laboratories between 2021 and 2023. Ischemic origin was excluded based on data of angiography and medical history. ABCDE-SE was evaluated with exercise (n=98, 37.0%), dobutamine (n=50, 18.9%), or vasodilators (n=117, 44.1%). The protocol consisted of several steps: A assessed regional wall motion abnormality (RWMA); B evaluated number of B-lines; C measured left ventricular contractile reserve; Step D with coronary flow velocity reserve (CFVR) in the left anterior descending artery (LAD) was completed in 102 patients (38.5%); step E assessed heart rate reserve. Additionally, step F (evaluated in 188 patients at rest and 107 at peak stress) noted the presence of rest or stress-induced moderate-to-severe secondary mitral regurgitation. The SE response was graded on a scale from 0 (all steps normal) to 5 (all ABCDE+ steps abnormal). Results The mean ABCDE score was 1.5±1.2, ranging from 0 (n=59, 22.3%) to 5 (n=2, 0.8%) (see distribution of scores in Figure 1A). Abnormal results were observed in 21 subjects (7.9%) for A, 86 (32.5 %) for B, 147 (55.5%) for C, 42/102 (41.2%) for D, and 101 (38.1%) for E steps. Step F was abnormal in 22/188 (11.8%) at rest and in 16/107 (14.9%) at peak stress. The predominant "solitary phenotypes" (only one step abnormal) were impaired LV contractile function phenotype (step C in 47, 51.1%) followed by chronotropic insufficiency (step E in 17, 18.5%) and congestive phenotype (step B in 17, 18.5%) (see Figure 1B). The most frequent combined phenotype was BCE – congestive phenotype with impaired ventricular and heart rate reserves (28 [62.2%]). Notably, 38 patients (14.3%) demonstrated improved regional contractility, while 27 patients (10.2%) showed new regional wall motion abnormality (see Table). Conclusion Non-ischemic HF patients with abnormal EF exhibit a broad spectrum of phenotypes. Impaired left ventricular contractility, interstitial congestion, and chronotropic insufficiency are the most frequent abnormalities detected by ABCDE-SE. Up to one-quarter of such patients demonstrate normal SE results. This comprehensive approach paves the way for personalized, SE-guided therapy.

Pulmonary valve acceleration fraction as a novel echo parameter to evaluate systolic pulmonary artery pressure during exercise echocardiography

Abstract Background/Introduction Long-COVID is a disabling chronic condition. Some patients have features of exercise-induced pulmonary hypertension (PHT) but non-invasive assessment during exercise stress echo (SE) is often limited by absence of reliable jet of tricuspid regurgitation (TR). We aimed to investigate novel Doppler echo parameters elicited from right ventricular (RV) outflow tract to aid diagnosis of exercise induced PHT among patients referred to our centre with Long-COVID symptoms. Purpose We investigated the ratio of the pulmonary valve acceleration time (PV AccT) to RV ejection time (RV ET) to calculate the pulmonary acceleration fraction (PV AccT/RV ET), thereby adjusting to heart rate. To identify its utility to estimate pulmonary artery pressure (PASP) during SE we correlated the PV AccT/RV ET and the TR-estimated RV systolic pressure (RVSP) in patients referred for evaluation of exercise-induced PHT in Long-Covid patients. Methods We developed a dedicated Covid-19 SE protocol to assess RV and pulmonary hemodynamics. From November 2022 to February 2023 all consecutive patients with Long-COVID symptoms underwent supine bike exercise with 3-min increments of workload of 25W. We did not evaluate the inferior vena cava during exercise, therefore estimated pressures from maximal TR jet velocities only. Results We enrolled 93 consecutive patients. The mean age was 50.1 years, 42.9% were female. No patients had RV impairment or RVSP >40mmHg at baseline. The average exercise time was 12.4 minutes, only 33% achieved the sub-maximum target heart rate (THR), in 50/93 (53.7%) reasons for termination were recorded as shortness of breath. The pulmonary acceleration fraction could be recorded in every patient at rest and at stress, while 20/92 (21.7%) patients had insufficient spectral Doppler profile of TR to estimate RVSP. The PV acceleration fraction was correlated with the available RVSPs during exercise (Spearman’s ϱ -0.446 (95% CI -0.606- -0.251[p<0.0001]). ROC analysis indicated a pulmonary acceleration fraction ≤0.44 was associated with the maximum Youden index to discriminate an increase in RVSP >20mmHg during exercise (AUC =0.731 [p<0.001]) with a sensitivity and specificity of 70.0% and 80.0%. In logistic regression analysis, a PV acceleration fraction ≤0.44 was independently associated with an increase in RVSP>20mmHg during exercise independently of age, gender and baseline LVEF, LVEDV, TAPSE and baseline RVSP (p<0.001). Conclusions Significant proportion of Long-COVID patients are limited by symptoms and not able to achieve THR during exercise. PV Acc T/ PV ET correlates well to RVSP and can be used to estimate PA pressure. A threshold of 0.44 appears independently associated with a benchmark of PA systolic pressure increase of >20mmHg. Further studies needed to evaluate this new marker of pulmonary hypertension in other group of patients.

The application of supine bicycle exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Exposure to high altitude is likely to lead to acute mountain sickness (AMS). At present, there are no definite parameters that can accurately predict the occurrence of AMS. Objectives The purposes of this study are (1) to assess the relationship between stress echocardiographic parameters and AMS, (2) to identify the predictors of AMS at sea level by exercise stress echocardiography. Methods A total of 36 healthy adults were enrolled and underwent resting and exercise stress echocardiography on a supine bicycle at sea level. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and peak stage. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (sPAP), right ventricular (RV) dimension by 2D, right ventricular area at the end of diastole (RVAD), right ventricular area at the end of systolic (RVAS),RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI).Pulmonary vascular resistance (PVR) was calculated. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, and LV systolic and diastolic function between the two groups (P > 0.05). TRV, sPAP, and PVR were much higher at peak stage in AMS (+) group (P < 0.05). No significant differences were found in RV systolic function at rest and peak stage between the two groups. By multivariable logistic regression model, PVR and RVAD at peak stage were significantly associated with AMS occurrence (PVR-OR =1.962,95% CI: 0.689-0.973,p =0.002; RVAD-OR =1.962,95% CI: 0.638-0.967,p =0.005;). The cutoff value to predict AMS were 1.55 for PVR (AUC: 0.831) and 11.45 cm2 for RVAD (AUC: 0.802). Conclusions Supine bicycle exercise stress echocardiography is a useful and noninvasive technique to identify subjects susceptible to AMS. Subjects with higher PVR and RVAD at peak stage were associated with susceptibility to AMS.

Noninvasive identification of ANOCA endotypes by stepwise, multi-stress, multi-marker stress echocardiography

Abstract Background Angina with non-obstructive coronary artery disease (ANOCA) is increasingly recognized in clinical practice, but effective therapy is difficult due to the heterogenity of pathophysiological substrates: organic coronary microvascular dysfunction (CMD), functional (vasospastic) CMD, epicardial artery vasospasm, non-cardiac chest pain. Current guidelines recommend invasive coronary function testing with the inherent cost of catheterization time, radiation exposure, iodinated contrast effects and risks of invasive procedures. Objective To evaluate the feasibility of a step-wise, multi-marker, multi-stress assessment of ANOCA patients by stress echocardiography (SE). Methods In a prospective study design, we enrolled 54 ANOCA patients (age =54±14 years, 14 men, 25 %), without significant coronary artery disease (CAD) on invasive or noninvasive angiography. In all patients hyperventilation (HYPER) test (30 deep breaths/min for 5 min) was performed, followed by semi-supine exercise (EX) if negative. All patients underwent adenosine (ADO) test with coronary flow velocity reserve (CFVR) measurement in the mid-distal left anterior descending artery (LAD). Positivity criteria were a coronary flow velocity (CFV) decrease during HYPER despite the increase in the double product (DP) indicating functional CMD i.e. vasoconstriction); the presence of inducible regional wall motion abnormality (RWMA) with HYPER-EX (microvascular/epicardial spasm), and CFVR ≤2.0 with ADO hyperemia (organic CMD). Results Fifty one pts (94%) had normal increase in CFV at ADO: CFV rest 0.264±0.078 vs ADO 0.608±0.133, p<0.001, while 3pts (5%) showed decrease in CFV at ADO suggesting organic CMD. Double product (DP) increased during HYPER (rest 10061 ±2406 vs. HYPER 13580 ±3356, p<0.001). Twenty-nine pts (53%) showed a paradoxical vasoconstrictor response during HYPER despite the increase in DP (CFV decreased during HYPER: CFV rest 0.261±0.059 vs HYP 0.216±0.057, p<0.001). With HYPER-EX, RWMA was induced in 15 patients (27%), while 7 patients had also RWMA during HYPER. Conclusion In patients with ANOCA, a stepwise multi-marker (CFVR and RWMA) and multi-stress (ADO, HYPER and EX) SE identifies CMD phenotypes and actionable therapeutic targets. According to our results functional vasospastic CMD (paradoxical decrease of CFV with HYPER), is more frequent than organic CMD (reduced CFVR with ADO) in patients with ANOCA. Inducible RWMA with HYPER-EX indicate severe vasoconstrictor response.

High altitude exercise stress echocardiograph for identification of susceptibility to acute mountain sickness

Abstract Background Acute high-altitude exposure increases the risk of acute mountain disease (AMS) and high-altitude pulmonary edema. After the initial exposure to high altitude, mountain climbers are worried about whether they will develop AMS. At high altitudes, there are no accurate indicators to predict the near future occurrence of AMS. Objectives To investigate whether treadmill exercise stress echocardiography at high altitude can predict the occurrence of AMS, and to find out some powerful factors associated with the susceptibility to AMS. Methods 36 healthy lowlanders were taken by bus from sea level to an altitude of 3600 m the next morning, during which they rested overnight at an altitude of 2150 m. Treadmill exercise stress echocardiography was performed immediately upon arrival at 2150 m, and the 2018 Lake Louise Questionnaire Score was performed the next day when arrived at the altitude of 3600 m. Heart rate (HR) and blood pressure (BP) were monitored during stress echocardiography. Left ventricular (LV) ejection fraction and E/e’ were calculated at rest and immediately after exercise. Other right ventricular systolic function parameters and pulmonary artery pressure (PAP) were calculated at the same time, which included tricuspid regurgitation velocity (TRV), tricuspid annular peak systolic excursion (TAPSE), systolic PAP (SPAP), right ventricular (RV) dimension by 2D, RV fraction of area change (FAC), right ventricular outflow tract velocity time integral (RVOT VTI). Pulmonary vascular resistance (PVR) was calculated according to the formula: TRV/RVOT VTI*10+0.16. Mean PAP (mPAP) was calculated as the formula: sPAP*0.61+2. All subjects ascended to 3600m within 24 hours by bus. AMS was identified by 2018 Lake Louise Questionnaire Score. Univariable and multivariable logistic regression analysis assessed independent factors associated with AMS. Results At the altitude of 3600m, 13 of 36 subjects had AMS, which defined as AMS (+) group. And the rest was AMS (-) group. There were no significant differences in HR, BP, SO2 and LV systolic and diastolic function between the two groups (P > 0.05). No significant differences were noted at rest except for TV s' (P < 0.05). Immediately after exercise, TRV, TAPSE, SPAP, mPAP, PVR, and RV area at the end of systole were much higher in AMS (+) group (all P < 0.05). While FAC and TVs’/SPAP were much lower in AMS (+) group (P < 0.05). By multivariable logistic regression model, mPAP immediately after exercise was significantly correlated with AMS occurrence (OR =1.332, 95% CI: 0.669-0.993, P= 003). The cutoff value of mPAP to predict AMS was 32 mmHg (AUC: 0.831, specificity: 86.7%, sensitivity: 76.9%). Conclusions The mPAP immediately after exercise upon arrival at an altitude of 2150 m is a strong predictor of near future AMS, and treadmill exercise stress echocardiography is a simple and non-invasive tool to help mountain climbers avoid more severe mountain sickness.

The role of stress echocardiography in patients with congenital abnormalities of coronary arteries: two tertiary cardiac centres experience

Abstract Background Coronary anomalies (CA) include anomalous aortic origin of a coronary artery (AAOCA), anomalous coronary artery from the pulmonary artery and coronary fistulae. While outcome of natural history of anomalous left coronary artery from the pulmonary artery (ALCAPA) is poor, assessment of stress-induced ischaemia and/or arrhythmia are warranted for clinical decision making in AAOCA. Purpose The aim of this study was to establish the prevalence of ischaemia during exercise stress echocardiography (ESE) in patients with different congenital CA. Methods Patients with CA who had stress exercise echocardiography from two large tertiary cardiac centres were retrospectively recruited. Treadmill/bike exercise stress echo tests were performed and analysed according to ESC guidelines. Computed tomography (CT), magnetic resonance imaging (MRI), myocardial perfusion scintigraphy, positron emission tomography (PET) and invasive angiogram with intravascular ultrasound (IVUS) were used for CA morphology and myocardial perfusion assessment. Patients with sclerotic stenosis of >50% in any of the coronary arteries were excluded from this study. Results Total 59 patients, including 8 ALCAPA, 4 coronary fistula and 47 AAOCA (12 anomalous aortic origin of the left coronary artery (AAOLCA) and 35 anomalous aortic origin of the right coronary artery (AAORCA)) formed the study cohort. The mean age was 44±17 years. Cardiac symptoms at rest were present in 5 (63%) ALCAPA, 31 (66%) patients with with AAOCA, and none in patients with coronary fistula. Nine patients (7 ALCAPA, 1 coronary fistula and 1 AAOLCA) had undergone previous repair. Out of 47 patients with AAOCA patients, 31 (66%) had interarterial course of coronary arteries, and 8 (17%) had intramural course. A positive ESE presents in 2 (25%) ALCAPA, 1 (25%) coronary fistula patient and 1 (2%) AAOCA patient. Myocardial perfusion was assessed in 12 of 59 (20%) patients, of which 9 were AAOCA. Myocardial perfusion studies were negative in 11 patients with negative ESE tests, while only in one patient with AAOLCA myocardial perfusion defects were found on MRI and PET despite negative ESE. No major adverse cardiovascular events were observed during follow-up of patients with negative ESE. Following ESE, surgical repair of CA has been performed in 3 patients with AAORCA and in 2 patients with AAOLCA based on either symptoms attributable to anomalous coronary, evidence of myocardial ischaemia on myocardial perfusion assessment or high-risk anatomy.While 4 out of 5 repaired patients were symptomatic before repair, they became asymptomatic following repair. Conclusions Incidence of ischaemia on exercise stress echo is extremely low in AAOCA patients despite symptoms at rest and malignant anatomical features. Improving stress echo methodology by using myocardial perfusion assessment might shed a light on this discrepancy between ESE results and symptomatic status/high-risk anatomy.

The effect of exercise on RV-PC coupling in asymptomatic patients with significant primary mitral regurgitation

Abstract Background Right ventricular–pulmonary circulation (RV-PC coupling) serves as an index to evaluate RV function in relation to underlying RV afterload. Although impaired RV-PC coupling has been proposed as a predictor of adverse outcomes in heart failure (HF) patients with secondary mitral regurgitation (MR), there is limited data available for patients with primary MR. Purpose The objective of this study was to assess and compare alterations in RV-PC coupling during exercise with bicycle stress echocardiography in individuals with asymptomatic moderate to severe primary MR (MR group) and normal subjects (Control group). Μethods All patients and controls underwent stress echocardiography with a supine bicycle. RV systolic function was evaluated with TAPSE and S’. The non-invasively measured RV-PC coupling was evaluated by indexing TAPSE and S’ to right ventricular systolic pressure (RVSP) during baseline echocardiogram and peak workload stages of bicycle SE. Results Among the 48 patients in the MR group (mean age 53.5±15.16 years, 58.3% female), 39 patients had moderate MR(81.3%), 5 patients had moderate-to-severe MR(10.4%), and 4 patients had severe MR(8.3%). The duration of stress echocardiogram was significantly shorter in the MR group compared to control group (8.11±2.39 min vs 10.5±1.05 min, respectively; p<.001). Left Ventricular Ejection Fraction (LVEF) was within normal limits in both groups {70.7±11.9 % vs 72.6±12.1 %(p=NS} and the dimensions of left ventricular cavity (end-diastolic and end-systolic diameters) were significantly larger in the MR group compared to control group (49.25±5.21 mm vs 45.6±4.08mm (p .016) and 31.81±4.27mm vs 29.07±4.21mm (p .033) respectively}. TAPSE and RVSP increased from baseline to peak dose [23.48 ±3.05mm vs 29.94±3.48mm (p < .001), 8.54±4.56mmHg vs 43.79±5.27mmHg (p < .001), respectively]. There were no significant differences in TAPSE/RVSP and S’/RVSP between the two groups at rest. However, a significantly steady decrease was observed from baseline to peak dose (0.84±0.16 mm/mmHg vs 0.72±0.19mm/mmHg (p <.001) and 0.52±0.11 cm/sec/mmHg vs 0.50±0.15 cm/sec/mmHg (p .004), respectively). Conversely, these parameters did not exhibit a significant decrease in the control group. Finally, there was no significant correlation observed between the changes in the index TAPSE/RVSP , ratio E/E’ and systolic blood pressure. Conclusions RV-PC coupling decreases during exercise in asymptomatic patients with moderate to severe MR, independently of left ventricular dynamic changes. In contrast , there is no significant change in RV-PC coupling observed in the control group. Therefore, future studies should aim to evaluate the incremental role of this novel index not only in the assessment and evaluation of patients with MR but also as a potential prognostic marker.TAPSE/RVSP GraphTable of echocardiographic measurements

Moderate intensity exercise training ameliorates the heart failure with preserved ejection fraction phenotype in a preclinical model by improving cardiometabolic fitness

Abstract Introduction and Aim Exercise intolerance is a hallmark feature of patients with heart failure with preserved ejection fraction (HFpEF).While clinical evidence suggests potential benefits of exercise training in HFpEF, its mechanisms remain largely unknown.In this study, we used a translationally relevant murine model of cardiometabolic HFpEF(1) to assess whether moderate intensity continuous training(MICT) can ameliorate the HFpEF phenotype in mice and promote cardiometabolic health. Methods Twenty-five adult, male C57BL/6N were fed with the combination of high fat diet(HFD;D12492,Research diet)and L-NAME(0.5 g/L,in drinking water) for 15 weeks to elicit HFpEF as previously described(1).After the establishment of the HFpEF phenotype, mice were randomized in two groups:sedentary(SED,n= 10) and exercised(MICT,n=15)mice.MICT was carried out according to the protocol:running on 10-degree positive inclination treadmill for 8 consecutive weeks,5 times/week,60 minutes/day,at a speed gradually increasing from 0.1 to 0.2 m/sec on a weekly basis.Morphometry, echocardiography(TTE),isoproterenol-induced stress echocardiography(SE),time domain nuclear magnetic resonance, and treadmill exhaustion tests were performed at the beginning and end of MICT.Additionally, at the end of MICT blood and tissues were collected for proteomics analysis(Fig1).Non-trained male C57BL/6N mice(37w) were used as controls for the HFpEF mice. Results Before randomization, all HFpEF mice were similar in terms of phenotypic characteristics. Compared to SED mice, MICT induced a significantly decrease in body weight driven by a reduction of total fat mass with an increased in lean mass(Fig2A+B).Interestingly, MICT had no impact on skeletal muscle mass for all different muscle groups evaluated (extensor digitorum longus, soleus and tibialis anterior).Importantly, MICT led to a significant improvement in exercise capacity in HFpEF mice, as shown by increased running distance and time, surpassing even the running distance seen in non-HFpEF mice (SED:62.8±18.7,MICT:305.7±13.9,non-HFpEF mice: 129.72±15.2meters,p<0.001).Preclinical surrogate of HFpEF such as pulmonary congestion, evaluated by index lung weights, improved after aerobic training.Following MICT there was a marked improvement in diastolic dysfunction(measured by E/E’ratio) both at rest(SED:36.5±3.3,MICT:23.3±5.09,p<0.001) and after isoproterenol challenge(SED:42.6±15.1,MICT:26.09±3.75,p<0.001)(Fig2C).Moreover, the wet cardiac mass was lower in the MICT group(Fig2A), suggesting potential amelioration in cardiac hypertrophy following aerobic training. Conclusion Eight weeks of supervised MICT on treadmill improves functional status, exercise capacity, and diastolic function in a cardiometabolic HFpEF murine model.The most significant effects were seen on weight loss and fat mass reduction.Our findings suggest a beneficial impact of aerobic exercise in mitigating HFpEF by improving metabolic fitness in the preclinical HFpEF model.Fig1-Study DesignFig2-Characteristics SED vs MICT groups

Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) measurement in the detection of significant CAD in acute chest pain patients triaged using the No Objective Testing (NOT) rule

Abstract Background After rule-out of MI in ED chest pain patients, uncertainty exists with respect to which remaining patients would benefit from objective functional/anatomical testing to detect potential underlying CAD. Using proteomics, we experimentally identified IGFBP-3 as a biomarker to assist this risk stratification and applied its measurement to >3,000 ED patients from 3 separate studies. Methods An isolated rat heart perfusate model coupled to mass spectrometry identified markers of cardiac ischemia. Human cardiac ischemia was carried out using cardiac exercise stress testing (EST, n=12). Temporal changes in IGFBP-3 during experimental MI were determined in patients undergoing septal alcohol ablation (SAA, n=12) and arterio-venous gradients of IGFBP-3 were determined from cases of proscribed cardiac catheterisation (CC, n=14). The ability of IGFBP-3 to assist clinical assessment (ROC analyses, logistic regression, C-statistic, pathways analyses) and ED risk assessment by the No Objective Testing (NOT) rule was carried out on samples from 3 prospectively recruited studies (SPACE, NZ, n=766; APACE, CH, n=1,056; FAST-TRAC, USA, n=1,230). Results IGFBP-3 identified by MS was present in perfusates of ischemic hearts only (n=3). In human cardiac EST, a delta of IGFBP-3 (∆IGFBP-3) between 0-150minutes was seen in positive ischemic tests, but not in controls (n=6 per group, p=0.026). In SAA patients, peripheral IGFBP-3 levels did not change over 24 hours (n=12, p=0.573) whereas in CC patients, significant extraction gradients of IGFBP-3 were seen across the heart and liver (p=0.013, n=14). In ED chest pain patients identified by the NOT rule (n=1,708), ΔIGFBP-3 between presentation and +2 hours (∆ IGFBP-3) was an independent logistic model predictor of unstable angina (n=123) alongside age, sex, cholesterol and Hx of CAD/MI. At 90% specificity, ∆IGFBP-3 improved the sensitivity of the model from 31% to 43%, the PPV 20% to 25% and the NPV from 94% to 95% (p=0.020). IGFBP-3 made a small improvement in "low risk" NOT rule patient identification (29% to 30%), but made a larger improvement to the ROC curve based identification in NOT rule patients for the finding of stenosis >70% on angiography (n=101, AUC clinical model = 0.682; model plus ∆ IGFBP-3 = 0.725, p=0.044). Pathways analyses (that included hs-TnT) in angiography patients (n=224) revealed ∆IGFBP-3 generated a 28% relative increase in low risk case identification (n=46 to 59). Conclusions IGFBP-3 is identified as a novel potential biomarker of cardiac ischemia, that is taken up/degraded across the heart and appears less responsive to complete infarction (MI). 0-2 hour changes in IGFBP-3 (∆ IGFBP-3) in patients identified as eligible for ED based NOT rule inclusion show promise as a useful tool to identify those with significant CAD, evidenced by the diagnosis of unstable angina, positive EST results or findings of 70% occlusion on angiography.

Improving exercise cardiac reserve assessment using a novel cardiopulmonary and echocardiography testing protocol (CPET-ESE) based on individualised exercise intensity domains

Abstract Background Functional exercise stress echocardiography (ESE) is used to quantify changes in cardiac reserve and can improve early cardiac dysfunction diagnosis and follow-up.[1.2] Current ESE protocols do not account for individual variations in fitness and heart rate response, leading to difficulties in defining normal reference values.[2,3] Physiologically defined exercise intensity domains could be implemented as part of combined cardiopulmonary and ESE testing (CPET-ESE) to address this problem. Purpose We propose that using exercise intensity domains as part of CPET-ESE will result in cardiac reserve values not influenced by individual cardiorespiratory fitness or physical activity (PA) levels. We also hypothesise by matching work-rates and heart rates (HR), respectively, cardiac reserve will be higher in those exercising at the higher exercise intensity domain. Methods A total of 45 healthy adults (mean age 43.8 ± 14.2, range 18-65 y) underwent a CPET followed by a CPET-ESE consisting of two 6-minute stages: 1. Moderate intensity (MOD) at 90% of the work-rate at the gas exchange threshold (GET) and 2. High intensity (HIGH) at 40% of the difference between GET and peak. Global left ventricular and right ventricular free wall (LV and RV) longitudinal strain (Sl), RV fractional area change (RV-FAC), peak LV and RV TDI derived systolic (S’) and diastolic velocities (E’) were measured at each step, including rest. HIGH steps were matched 1-to-n with MOD steps from other participants based on work-rate and HR, respectively. Questionnaire derived PA was classified as low, moderate, and high active. Cardiorespiratory fitness was measured as peak oxygen uptake relative to body mass (mL·kg-1·min-1). Results After adjusting for age and sex, neither higher PA nor peak VO2 were associated with higher cardiac function parameters at either intensity (Table 1). Higher peak VO2 was associated with higher work-rate for HIGH only, while higher PA was associated with lower HR for MOD only (interaction term p<0.05). When paired by matching HR and work-rate, respectively, HIGH was associated with higher cardiac function parameters compared to MOD (all except for LV-S’ and RV-FAC when HR matched, Table 2), despite those matched from HIGH being older, less physically active and having lower peak VO2 (p<0.05 for all). Conclusions Current ESE protocols, which define submaximal exercise intensity using arbitrary work-rate or HR targets,[3] do not account for the complex differences in exercise response between healthy individuals. Cardiac function augmentation during exercise is likely a response to VO2 kinetics and this is not accurately described by either HR or work-rate alone. We derived normal reference values for cardiac reserve from implementing physiologically defined exercise intensity domains within the combined CPET-ESE testing frameworks. These values could be more appropriately used when comparing diverse clinical populations using CPET-ESE.

SMART-2D: a novel scoring system to predict non diagnostic exercise stress echocardiography in renal transplant candidates

Abstract Background Exercise stress echocardiography (ESE) is often used for pre-renal transplant risk stratification. Nearly 20% of ESE may be non-diagnostic, resulting in delays to transplant and increased healthcare cost. A simple, reliable tool for predicting non-diagnostic ESE may streamline assessment. Methods Retrospective analysis of 898 kidney transplant candidates between 2013-2020 who underwent exercise stress echocardiography for pre-transplant cardiovascular assessment was performed. The cohort was separated into a derivation and validation set. Multivariable logistic regression identified predictors of non-diagnostic ESE. Covariates associated with non-diagnostic ESE (p<0.10) on univariate analysis were included in the multivariable model. From this model, only variables with p<0.05 were included for score development. Model discrimination was assessed by area under the receiver operating curve (AUROC). Results Non-diagnostic ESE occurred in 17% (151/898). Predictors of non-diagnostic study formed the scoring system: 1 point for female sex, 2 points for BMI >40, 1 point for age >55, Heart Rate<55 4 points, <65 3 points and <75 2 points. LV Hypertrophy was assigned 2 points, Type 1 Diabetes 3 points and Type 2 diabetes 1 point, LV Dysfunction was assigned 2 points. This scoring system had excellent discriminative ability (derivation AUROC 0.80, validation AUROC 0.81). A score of 8 or more had a specificity of 97% and a positive likelihood ratio of 9.4 for non-diagnostic ESE. A score of <8 had a negative predictive value of 86%. Patients with Non-Diagnostic ESE had longer time to transplantation (695 vs 636 days), and more investigations performed (43.05% vs 17.94%, p<0.001) and less likely to receive a renal transplant (OR 0.47, p<0.001). Conclusion Non diagnostic ESE in pre-transplant assessment causes significant delays to patient care. A simple clinical scoring system may identify patients likely to have non-diagnostic ESE and can be utilised to identify patients who may benefit from alternative risk-stratification investigations.